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1. A Cross-national Study of Mathematics Achievement Via Three-level Multilevel Models

Author

Lee, Youjin and Lee, Youjin

Abstract

The present study explored the effects of the national and cultural contexts on students' mathematics achievement. The study also investigated the nature and magnitude of student-level (level 1), school-level (level 2), and country-level (level 3) factors that are associated with math achievement. The Program for International Student Assessment (PISA) 2018 datasets were used. The main predictors focusing on this study included university admission procedure and the country's culture of mindsets about intelligence at level 3, indicating extra-curricular activities at level 2, growth mindset, and resilience self-efficacy at level 1. Other than main predictors, various predictors including country's characteristics, school characteristics, school climate factors, students' demographic characteristics, and non-cognitive abilities were added in the analysis to examine the main predictors are statistically significant after controlling for other predictors. The findings of HLM analysis showed that mathematics achievement is associated with national and cultural contexts since the study found 31.30% of the total variation was accounted for level 3 in math achievement. Also, the significant findings of the study indicated that university admission procedure was significantly associated with country-mean math achievement while the country's culture of mindsets about intelligence was not at level 3. At level 2, providing extra-curricular activities in school was a significant predictor for math achievement. At level 1, a growth mindset and information and Communication Technology (ICT) usage were positively associated with math achievement. The other significant predictors for math achievement were found in the model. In addition, the study found that the compositional effect of ICT usage explained a significant amount of between schools and countries variance even after controlling for other predictors in the analysis. Moreover, the study found several counterintuitive asso

Published
2023

2. XYZeq: Spatially resolved single-cell RNA sequencing reveals expression heterogeneity in the tumor microenvironment.

Author

Lee, Youjin, Lee, Youjin, Bogdanoff, Derek, Wang, Yutong, Hartoularos, George C, Woo, Jonathan M, Mowery, Cody T, Nisonoff, Hunter M, Lee, David S, Sun, Yang, Lee, James, Mehdizadeh, Sadaf, Cantlon, Joshua, Shifrut, Eric, Ngyuen, David N, Roth, Theodore L, Song, Yun S, Marson, Alexander, Chow, Eric D, Ye, Chun Jimmie, Lee, Youjin, Lee, Youjin, Bogdanoff, Derek, Wang, Yutong, Hartoularos, George C, Woo, Jonathan M, Mowery, Cody T, Nisonoff, Hunter M, Lee, David S, Sun, Yang, Lee, James, Mehdizadeh, Sadaf, Cantlon, Joshua, Shifrut, Eric, Ngyuen, David N, Roth, Theodore L, Song, Yun S, Marson, Alexander, Chow, Eric D, and Ye, Chun Jimmie

Abstract

Single-cell RNA sequencing (scRNA-seq) of tissues has revealed remarkable heterogeneity of cell types and states but does not provide information on the spatial organization of cells. To better understand how individual cells function within an anatomical space, we developed XYZeq, a workflow that encodes spatial metadata into scRNA-seq libraries. We used XYZeq to profile mouse tumor models to capture spatially barcoded transcriptomes from tens of thousands of cells. Analyses of these data revealed the spatial distribution of distinct cell types and a cell migration-associated transcriptomic program in tumor-associated mesenchymal stem cells (MSCs). Furthermore, we identify localized expression of tumor suppressor genes by MSCs that vary with proximity to the tumor core. We demonstrate that XYZeq can be used to map the transcriptome and spatial localization of individual cells in situ to reveal how cell composition and cell states can be affected by location within complex pathological tissue.

Published
2021

3. XYZeq: Spatially resolved single-cell RNA sequencing reveals expression heterogeneity in the tumor microenvironment.

Author

Lee, Youjin, Lee, Youjin, Bogdanoff, Derek, Wang, Yutong, Hartoularos, George C, Woo, Jonathan M, Mowery, Cody T, Nisonoff, Hunter M, Lee, David S, Sun, Yang, Lee, James, Mehdizadeh, Sadaf, Cantlon, Joshua, Shifrut, Eric, Ngyuen, David N, Roth, Theodore L, Song, Yun S, Marson, Alexander, Chow, Eric D, Ye, Chun Jimmie, Lee, Youjin, Lee, Youjin, Bogdanoff, Derek, Wang, Yutong, Hartoularos, George C, Woo, Jonathan M, Mowery, Cody T, Nisonoff, Hunter M, Lee, David S, Sun, Yang, Lee, James, Mehdizadeh, Sadaf, Cantlon, Joshua, Shifrut, Eric, Ngyuen, David N, Roth, Theodore L, Song, Yun S, Marson, Alexander, Chow, Eric D, and Ye, Chun Jimmie

Abstract

Single-cell RNA sequencing (scRNA-seq) of tissues has revealed remarkable heterogeneity of cell types and states but does not provide information on the spatial organization of cells. To better understand how individual cells function within an anatomical space, we developed XYZeq, a workflow that encodes spatial metadata into scRNA-seq libraries. We used XYZeq to profile mouse tumor models to capture spatially barcoded transcriptomes from tens of thousands of cells. Analyses of these data revealed the spatial distribution of distinct cell types and a cell migration-associated transcriptomic program in tumor-associated mesenchymal stem cells (MSCs). Furthermore, we identify localized expression of tumor suppressor genes by MSCs that vary with proximity to the tumor core. We demonstrate that XYZeq can be used to map the transcriptome and spatial localization of individual cells in situ to reveal how cell composition and cell states can be affected by location within complex pathological tissue.

Published
2021

4. Efficient generation of isogenic primary human myeloid cells using CRISPR-Cas9 ribonucleoproteins.

Author

Hiatt, Joseph, Hiatt, Joseph, Cavero, Devin A, McGregor, Michael J, Zheng, Weihao, Budzik, Jonathan M, Roth, Theodore L, Haas, Kelsey M, Wu, David, Rathore, Ujjwal, Meyer-Franke, Anke, Bouzidi, Mohamed S, Shifrut, Eric, Lee, Youjin, Kumar, Vigneshwari Easwar, Dang, Eric V, Gordon, David E, Wojcechowskyj, Jason A, Hultquist, Judd F, Fontaine, Krystal A, Pillai, Satish K, Cox, Jeffery S, Ernst, Joel D, Krogan, Nevan J, Marson, Alexander, Hiatt, Joseph, Hiatt, Joseph, Cavero, Devin A, McGregor, Michael J, Zheng, Weihao, Budzik, Jonathan M, Roth, Theodore L, Haas, Kelsey M, Wu, David, Rathore, Ujjwal, Meyer-Franke, Anke, Bouzidi, Mohamed S, Shifrut, Eric, Lee, Youjin, Kumar, Vigneshwari Easwar, Dang, Eric V, Gordon, David E, Wojcechowskyj, Jason A, Hultquist, Judd F, Fontaine, Krystal A, Pillai, Satish K, Cox, Jeffery S, Ernst, Joel D, Krogan, Nevan J, and Marson, Alexander

Abstract

Genome engineering of primary human cells with CRISPR-Cas9 has revolutionized experimental and therapeutic approaches to cell biology, but human myeloid-lineage cells have remained largely genetically intractable. We present a method for the delivery of CRISPR-Cas9 ribonucleoprotein (RNP) complexes by nucleofection directly into CD14+ human monocytes purified from peripheral blood, leading to high rates of precise gene knockout. These cells can be efficiently differentiated into monocyte-derived macrophages or dendritic cells. This process yields genetically edited cells that retain transcript and protein markers of myeloid differentiation and phagocytic function. Genetic ablation of the restriction factor SAMHD1 increased HIV-1 infection >50-fold, demonstrating the power of this system for genotype-phenotype interrogation. This fast, flexible, and scalable platform can be used for genetic studies of human myeloid cells in immune signaling, inflammation, cancer immunology, host-pathogen interactions, and beyond, and could facilitate the development of myeloid cellular therapies.

Published
2021

5. Efficient generation of isogenic primary human myeloid cells using CRISPR-Cas9 ribonucleoproteins.

Author

Hiatt, Joseph, Hiatt, Joseph, Cavero, Devin A, McGregor, Michael J, Zheng, Weihao, Budzik, Jonathan M, Roth, Theodore L, Haas, Kelsey M, Wu, David, Rathore, Ujjwal, Meyer-Franke, Anke, Bouzidi, Mohamed S, Shifrut, Eric, Lee, Youjin, Kumar, Vigneshwari Easwar, Dang, Eric V, Gordon, David E, Wojcechowskyj, Jason A, Hultquist, Judd F, Fontaine, Krystal A, Pillai, Satish K, Cox, Jeffery S, Ernst, Joel D, Krogan, Nevan J, Marson, Alexander, Hiatt, Joseph, Hiatt, Joseph, Cavero, Devin A, McGregor, Michael J, Zheng, Weihao, Budzik, Jonathan M, Roth, Theodore L, Haas, Kelsey M, Wu, David, Rathore, Ujjwal, Meyer-Franke, Anke, Bouzidi, Mohamed S, Shifrut, Eric, Lee, Youjin, Kumar, Vigneshwari Easwar, Dang, Eric V, Gordon, David E, Wojcechowskyj, Jason A, Hultquist, Judd F, Fontaine, Krystal A, Pillai, Satish K, Cox, Jeffery S, Ernst, Joel D, Krogan, Nevan J, and Marson, Alexander

Abstract

Genome engineering of primary human cells with CRISPR-Cas9 has revolutionized experimental and therapeutic approaches to cell biology, but human myeloid-lineage cells have remained largely genetically intractable. We present a method for the delivery of CRISPR-Cas9 ribonucleoprotein (RNP) complexes by nucleofection directly into CD14+ human monocytes purified from peripheral blood, leading to high rates of precise gene knockout. These cells can be efficiently differentiated into monocyte-derived macrophages or dendritic cells. This process yields genetically edited cells that retain transcript and protein markers of myeloid differentiation and phagocytic function. Genetic ablation of the restriction factor SAMHD1 increased HIV-1 infection >50-fold, demonstrating the power of this system for genotype-phenotype interrogation. This fast, flexible, and scalable platform can be used for genetic studies of human myeloid cells in immune signaling, inflammation, cancer immunology, host-pathogen interactions, and beyond, and could facilitate the development of myeloid cellular therapies.

Published
2021

6. A Deep Neural Network for Simultaneous Estimation of b Jet Energy and Resolution

Author

Massachusetts Institute of Technology. Department of Physics, Massachusetts Institute of Technology. Department of Nuclear Science and Engineering, Massachusetts Institute of Technology. Laboratory for Nuclear Science, Lincoln Laboratory, Abercrombie, Daniel Robert, Allen, Benjamin E., Baty, Austin Alan, Bi, Ran, Brandt, Stephanie Akemi, Busza, Wit, Cali, Ivan Amos, D'Alfonso, Mariarosaria, Gomez-Ceballos, Guillelmo, Goncharov, Maxim, Harris, Philip Coleman, Hsu, David, Hu, Miao, Klute, Markus, Kovalskyi, Dmytro, Lee, Youjin, Luckey Jr, P David, Maier, Benedikt, Marini, Andrea Carlo, McGinn, Christopher Francis, Mironov, Camelia Maria, Narayanan, Sruthi Annapoorny, Niu, Xinmei, Paus, Christoph M. E., Rankin, Dylan Sheldon, Roland, Christof E, Roland, Gunther M, Shi, Zhenhua, Stephans, George S. F., Sumorok, Konstanty C, Tatar, Kaya, Velicanu, Dragos Alexandru, Wang, J., Wang, Tianwen, Wyslouch, Boleslaw, Massachusetts Institute of Technology. Department of Physics, Massachusetts Institute of Technology. Department of Nuclear Science and Engineering, Massachusetts Institute of Technology. Laboratory for Nuclear Science, Lincoln Laboratory, Abercrombie, Daniel Robert, Allen, Benjamin E., Baty, Austin Alan, Bi, Ran, Brandt, Stephanie Akemi, Busza, Wit, Cali, Ivan Amos, D'Alfonso, Mariarosaria, Gomez-Ceballos, Guillelmo, Goncharov, Maxim, Harris, Philip Coleman, Hsu, David, Hu, Miao, Klute, Markus, Kovalskyi, Dmytro, Lee, Youjin, Luckey Jr, P David, Maier, Benedikt, Marini, Andrea Carlo, McGinn, Christopher Francis, Mironov, Camelia Maria, Narayanan, Sruthi Annapoorny, Niu, Xinmei, Paus, Christoph M. E., Rankin, Dylan Sheldon, Roland, Christof E, Roland, Gunther M, Shi, Zhenhua, Stephans, George S. F., Sumorok, Konstanty C, Tatar, Kaya, Velicanu, Dragos Alexandru, Wang, J., Wang, Tianwen, and Wyslouch, Boleslaw

Abstract

We describe a method to obtain point and dispersion estimates for the energies of jets arising from b quarks produced in proton–proton collisions at an energy of √ s = 13 TeV at the CERN LHC. The algorithm is trained on a large sample of simulated b jets and validated on data recorded by the CMS detector in 2017 corresponding to an integrated luminosity of 41 fb⁻¹. A multivariate regression algorithm based on a deep feed-forward neural network employs jet composition and shape information, and the properties of reconstructed secondary vertices associated with the jet. The results of the algorithm are used to improve the sensitivity of analyses that make use of b jets in the final state, such as the observation of Higgs boson decay to b[overline b]. .

Published
2021

7. Evaluation of SARS-CoV-2 serology assays reveals a range of test performance.

Author

Whitman, Jeffrey D, Whitman, Jeffrey D, Hiatt, Joseph, Mowery, Cody T, Shy, Brian R, Yu, Ruby, Yamamoto, Tori N, Rathore, Ujjwal, Goldgof, Gregory M, Whitty, Caroline, Woo, Jonathan M, Gallman, Antonia E, Miller, Tyler E, Levine, Andrew G, Nguyen, David N, Bapat, Sagar P, Balcerek, Joanna, Bylsma, Sophia A, Lyons, Ana M, Li, Stacy, Wong, Allison Wai-Yi, Gillis-Buck, Eva Mae, Steinhart, Zachary B, Lee, Youjin, Apathy, Ryan, Lipke, Mitchell J, Smith, Jennifer Anne, Zheng, Tina, Boothby, Ian C, Isaza, Erin, Chan, Jackie, Acenas, Dante D, Lee, Jinwoo, Macrae, Trisha A, Kyaw, Than S, Wu, David, Ng, Dianna L, Gu, Wei, York, Vanessa A, Eskandarian, Haig Alexander, Callaway, Perri C, Warrier, Lakshmi, Moreno, Mary E, Levan, Justine, Torres, Leonel, Farrington, Lila A, Loudermilk, Rita P, Koshal, Kanishka, Zorn, Kelsey C, Garcia-Beltran, Wilfredo F, Yang, Diane, Astudillo, Michael G, Bernstein, Bradley E, Gelfand, Jeffrey A, Ryan, Edward T, Charles, Richelle C, Iafrate, A John, Lennerz, Jochen K, Miller, Steve, Chiu, Charles Y, Stramer, Susan L, Wilson, Michael R, Manglik, Aashish, Ye, Chun Jimmie, Krogan, Nevan J, Anderson, Mark S, Cyster, Jason G, Ernst, Joel D, Wu, Alan HB, Lynch, Kara L, Bern, Caryn, Hsu, Patrick D, Marson, Alexander, Whitman, Jeffrey D, Whitman, Jeffrey D, Hiatt, Joseph, Mowery, Cody T, Shy, Brian R, Yu, Ruby, Yamamoto, Tori N, Rathore, Ujjwal, Goldgof, Gregory M, Whitty, Caroline, Woo, Jonathan M, Gallman, Antonia E, Miller, Tyler E, Levine, Andrew G, Nguyen, David N, Bapat, Sagar P, Balcerek, Joanna, Bylsma, Sophia A, Lyons, Ana M, Li, Stacy, Wong, Allison Wai-Yi, Gillis-Buck, Eva Mae, Steinhart, Zachary B, Lee, Youjin, Apathy, Ryan, Lipke, Mitchell J, Smith, Jennifer Anne, Zheng, Tina, Boothby, Ian C, Isaza, Erin, Chan, Jackie, Acenas, Dante D, Lee, Jinwoo, Macrae, Trisha A, Kyaw, Than S, Wu, David, Ng, Dianna L, Gu, Wei, York, Vanessa A, Eskandarian, Haig Alexander, Callaway, Perri C, Warrier, Lakshmi, Moreno, Mary E, Levan, Justine, Torres, Leonel, Farrington, Lila A, Loudermilk, Rita P, Koshal, Kanishka, Zorn, Kelsey C, Garcia-Beltran, Wilfredo F, Yang, Diane, Astudillo, Michael G, Bernstein, Bradley E, Gelfand, Jeffrey A, Ryan, Edward T, Charles, Richelle C, Iafrate, A John, Lennerz, Jochen K, Miller, Steve, Chiu, Charles Y, Stramer, Susan L, Wilson, Michael R, Manglik, Aashish, Ye, Chun Jimmie, Krogan, Nevan J, Anderson, Mark S, Cyster, Jason G, Ernst, Joel D, Wu, Alan HB, Lynch, Kara L, Bern, Caryn, Hsu, Patrick D, and Marson, Alexander

Abstract

Appropriate use and interpretation of serological tests for assessments of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure, infection and potential immunity require accurate data on assay performance. We conducted a head-to-head evaluation of ten point-of-care-style lateral flow assays (LFAs) and two laboratory-based enzyme-linked immunosorbent assays to detect anti-SARS-CoV-2 IgM and IgG antibodies in 5-d time intervals from symptom onset and studied the specificity of each assay in pre-coronavirus disease 2019 specimens. The percent of seropositive individuals increased with time, peaking in the latest time interval tested (>20 d after symptom onset). Test specificity ranged from 84.3% to 100.0% and was predominantly affected by variability in IgM results. LFA specificity could be increased by considering weak bands as negative, but this decreased detection of antibodies (sensitivity) in a subset of SARS-CoV-2 real-time PCR-positive cases. Our results underline the importance of seropositivity threshold determination and reader training for reliable LFA deployment. Although there was no standout serological assay, four tests achieved more than 80% positivity at later time points tested and more than 95% specificity.

Published
2020

8. Test performance evaluation of SARS-CoV-2 serological assays.

Author

Whitman, Jeffrey D, Whitman, Jeffrey D, Hiatt, Joseph, Mowery, Cody T, Shy, Brian R, Yu, Ruby, Yamamoto, Tori N, Rathore, Ujjwal, Goldgof, Gregory M, Whitty, Caroline, Woo, Jonathan M, Gallman, Antonia E, Miller, Tyler E, Levine, Andrew G, Nguyen, David N, Bapat, Sagar P, Balcerek, Joanna, Bylsma, Sophia A, Lyons, Ana M, Li, Stacy, Wong, Allison Wai-Yi, Gillis-Buck, Eva Mae, Steinhart, Zachary B, Lee, Youjin, Apathy, Ryan, Lipke, Mitchell J, Smith, Jennifer Anne, Zheng, Tina, Boothby, Ian C, Isaza, Erin, Chan, Jackie, Acenas, Dante D, Lee, Jinwoo, Macrae, Trisha A, Kyaw, Than S, Wu, David, Ng, Dianna L, Gu, Wei, York, Vanessa A, Eskandarian, Haig Alexander, Callaway, Perri C, Warrier, Lakshmi, Moreno, Mary E, Levan, Justine, Torres, Leonel, Farrington, Lila A, Loudermilk, Rita, Koshal, Kanishka, Zorn, Kelsey C, Garcia-Beltran, Wilfredo F, Yang, Diane, Astudillo, Michael G, Bernstein, Bradley E, Gelfand, Jeffrey A, Ryan, Edward T, Charles, Richelle C, Iafrate, A John, Lennerz, Jochen K, Miller, Steve, Chiu, Charles Y, Stramer, Susan L, Wilson, Michael R, Manglik, Aashish, Ye, Chun Jimmie, Krogan, Nevan J, Anderson, Mark S, Cyster, Jason G, Ernst, Joel D, Wu, Alan HB, Lynch, Kara L, Bern, Caryn, Hsu, Patrick D, Marson, Alexander, Whitman, Jeffrey D, Whitman, Jeffrey D, Hiatt, Joseph, Mowery, Cody T, Shy, Brian R, Yu, Ruby, Yamamoto, Tori N, Rathore, Ujjwal, Goldgof, Gregory M, Whitty, Caroline, Woo, Jonathan M, Gallman, Antonia E, Miller, Tyler E, Levine, Andrew G, Nguyen, David N, Bapat, Sagar P, Balcerek, Joanna, Bylsma, Sophia A, Lyons, Ana M, Li, Stacy, Wong, Allison Wai-Yi, Gillis-Buck, Eva Mae, Steinhart, Zachary B, Lee, Youjin, Apathy, Ryan, Lipke, Mitchell J, Smith, Jennifer Anne, Zheng, Tina, Boothby, Ian C, Isaza, Erin, Chan, Jackie, Acenas, Dante D, Lee, Jinwoo, Macrae, Trisha A, Kyaw, Than S, Wu, David, Ng, Dianna L, Gu, Wei, York, Vanessa A, Eskandarian, Haig Alexander, Callaway, Perri C, Warrier, Lakshmi, Moreno, Mary E, Levan, Justine, Torres, Leonel, Farrington, Lila A, Loudermilk, Rita, Koshal, Kanishka, Zorn, Kelsey C, Garcia-Beltran, Wilfredo F, Yang, Diane, Astudillo, Michael G, Bernstein, Bradley E, Gelfand, Jeffrey A, Ryan, Edward T, Charles, Richelle C, Iafrate, A John, Lennerz, Jochen K, Miller, Steve, Chiu, Charles Y, Stramer, Susan L, Wilson, Michael R, Manglik, Aashish, Ye, Chun Jimmie, Krogan, Nevan J, Anderson, Mark S, Cyster, Jason G, Ernst, Joel D, Wu, Alan HB, Lynch, Kara L, Bern, Caryn, Hsu, Patrick D, and Marson, Alexander

Abstract

Background:Serological tests are crucial tools for assessments of SARS-CoV-2 exposure, infection and potential immunity. Their appropriate use and interpretation require accurate assay performance data. Method:We conducted an evaluation of 10 lateral flow assays (LFAs) and two ELISAs to detect anti-SARS-CoV-2 antibodies. The specimen set comprised 128 plasma or serum samples from 79 symptomatic SARS-CoV-2 RT-PCR-positive individuals; 108 pre-COVID-19 negative controls; and 52 recent samples from individuals who underwent respiratory viral testing but were not diagnosed with Coronavirus Disease 2019 (COVID-19). Samples were blinded and LFA results were interpreted by two independent readers, using a standardized intensity scoring system. Results:Among specimens from SARS-CoV-2 RT-PCR-positive individuals, the percent seropositive increased with time interval, peaking at 81.8-100.0% in samples taken >20 days after symptom onset. Test specificity ranged from 84.3-100.0% in pre-COVID-19 specimens. Specificity was higher when weak LFA bands were considered negative, but this decreased sensitivity. IgM detection was more variable than IgG, and detection was highest when IgM and IgG results were combined. Agreement between ELISAs and LFAs ranged from 75.7-94.8%. No consistent cross-reactivity was observed. Conclusion:Our evaluation showed heterogeneous assay performance. Reader training is key to reliable LFA performance, and can be tailored for survey goals. Informed use of serology will require evaluations covering the full spectrum of SARS-CoV-2 infections, from asymptomatic and mild infection to severe disease, and later convalescence. Well-designed studies to elucidate the mechanisms and serological correlates of protective immunity will be crucial to guide rational clinical and public health policies.

Published
2020

9. Test performance evaluation of SARS-CoV-2 serological assays.

Author

Whitman, Jeffrey D, Whitman, Jeffrey D, Hiatt, Joseph, Mowery, Cody T, Shy, Brian R, Yu, Ruby, Yamamoto, Tori N, Rathore, Ujjwal, Goldgof, Gregory M, Whitty, Caroline, Woo, Jonathan M, Gallman, Antonia E, Miller, Tyler E, Levine, Andrew G, Nguyen, David N, Bapat, Sagar P, Balcerek, Joanna, Bylsma, Sophia A, Lyons, Ana M, Li, Stacy, Wong, Allison Wai-Yi, Gillis-Buck, Eva Mae, Steinhart, Zachary B, Lee, Youjin, Apathy, Ryan, Lipke, Mitchell J, Smith, Jennifer Anne, Zheng, Tina, Boothby, Ian C, Isaza, Erin, Chan, Jackie, Acenas, Dante D, Lee, Jinwoo, Macrae, Trisha A, Kyaw, Than S, Wu, David, Ng, Dianna L, Gu, Wei, York, Vanessa A, Eskandarian, Haig Alexander, Callaway, Perri C, Warrier, Lakshmi, Moreno, Mary E, Levan, Justine, Torres, Leonel, Farrington, Lila A, Loudermilk, Rita, Koshal, Kanishka, Zorn, Kelsey C, Garcia-Beltran, Wilfredo F, Yang, Diane, Astudillo, Michael G, Bernstein, Bradley E, Gelfand, Jeffrey A, Ryan, Edward T, Charles, Richelle C, Iafrate, A John, Lennerz, Jochen K, Miller, Steve, Chiu, Charles Y, Stramer, Susan L, Wilson, Michael R, Manglik, Aashish, Ye, Chun Jimmie, Krogan, Nevan J, Anderson, Mark S, Cyster, Jason G, Ernst, Joel D, Wu, Alan HB, Lynch, Kara L, Bern, Caryn, Hsu, Patrick D, Marson, Alexander, Whitman, Jeffrey D, Whitman, Jeffrey D, Hiatt, Joseph, Mowery, Cody T, Shy, Brian R, Yu, Ruby, Yamamoto, Tori N, Rathore, Ujjwal, Goldgof, Gregory M, Whitty, Caroline, Woo, Jonathan M, Gallman, Antonia E, Miller, Tyler E, Levine, Andrew G, Nguyen, David N, Bapat, Sagar P, Balcerek, Joanna, Bylsma, Sophia A, Lyons, Ana M, Li, Stacy, Wong, Allison Wai-Yi, Gillis-Buck, Eva Mae, Steinhart, Zachary B, Lee, Youjin, Apathy, Ryan, Lipke, Mitchell J, Smith, Jennifer Anne, Zheng, Tina, Boothby, Ian C, Isaza, Erin, Chan, Jackie, Acenas, Dante D, Lee, Jinwoo, Macrae, Trisha A, Kyaw, Than S, Wu, David, Ng, Dianna L, Gu, Wei, York, Vanessa A, Eskandarian, Haig Alexander, Callaway, Perri C, Warrier, Lakshmi, Moreno, Mary E, Levan, Justine, Torres, Leonel, Farrington, Lila A, Loudermilk, Rita, Koshal, Kanishka, Zorn, Kelsey C, Garcia-Beltran, Wilfredo F, Yang, Diane, Astudillo, Michael G, Bernstein, Bradley E, Gelfand, Jeffrey A, Ryan, Edward T, Charles, Richelle C, Iafrate, A John, Lennerz, Jochen K, Miller, Steve, Chiu, Charles Y, Stramer, Susan L, Wilson, Michael R, Manglik, Aashish, Ye, Chun Jimmie, Krogan, Nevan J, Anderson, Mark S, Cyster, Jason G, Ernst, Joel D, Wu, Alan HB, Lynch, Kara L, Bern, Caryn, Hsu, Patrick D, and Marson, Alexander

Abstract

Background:Serological tests are crucial tools for assessments of SARS-CoV-2 exposure, infection and potential immunity. Their appropriate use and interpretation require accurate assay performance data. Method:We conducted an evaluation of 10 lateral flow assays (LFAs) and two ELISAs to detect anti-SARS-CoV-2 antibodies. The specimen set comprised 128 plasma or serum samples from 79 symptomatic SARS-CoV-2 RT-PCR-positive individuals; 108 pre-COVID-19 negative controls; and 52 recent samples from individuals who underwent respiratory viral testing but were not diagnosed with Coronavirus Disease 2019 (COVID-19). Samples were blinded and LFA results were interpreted by two independent readers, using a standardized intensity scoring system. Results:Among specimens from SARS-CoV-2 RT-PCR-positive individuals, the percent seropositive increased with time interval, peaking at 81.8-100.0% in samples taken >20 days after symptom onset. Test specificity ranged from 84.3-100.0% in pre-COVID-19 specimens. Specificity was higher when weak LFA bands were considered negative, but this decreased sensitivity. IgM detection was more variable than IgG, and detection was highest when IgM and IgG results were combined. Agreement between ELISAs and LFAs ranged from 75.7-94.8%. No consistent cross-reactivity was observed. Conclusion:Our evaluation showed heterogeneous assay performance. Reader training is key to reliable LFA performance, and can be tailored for survey goals. Informed use of serology will require evaluations covering the full spectrum of SARS-CoV-2 infections, from asymptomatic and mild infection to severe disease, and later convalescence. Well-designed studies to elucidate the mechanisms and serological correlates of protective immunity will be crucial to guide rational clinical and public health policies.

Published
2020

10. Evaluation of SARS-CoV-2 serology assays reveals a range of test performance.

Author

Whitman, Jeffrey D, Whitman, Jeffrey D, Hiatt, Joseph, Mowery, Cody T, Shy, Brian R, Yu, Ruby, Yamamoto, Tori N, Rathore, Ujjwal, Goldgof, Gregory M, Whitty, Caroline, Woo, Jonathan M, Gallman, Antonia E, Miller, Tyler E, Levine, Andrew G, Nguyen, David N, Bapat, Sagar P, Balcerek, Joanna, Bylsma, Sophia A, Lyons, Ana M, Li, Stacy, Wong, Allison Wai-Yi, Gillis-Buck, Eva Mae, Steinhart, Zachary B, Lee, Youjin, Apathy, Ryan, Lipke, Mitchell J, Smith, Jennifer Anne, Zheng, Tina, Boothby, Ian C, Isaza, Erin, Chan, Jackie, Acenas, Dante D, Lee, Jinwoo, Macrae, Trisha A, Kyaw, Than S, Wu, David, Ng, Dianna L, Gu, Wei, York, Vanessa A, Eskandarian, Haig Alexander, Callaway, Perri C, Warrier, Lakshmi, Moreno, Mary E, Levan, Justine, Torres, Leonel, Farrington, Lila A, Loudermilk, Rita P, Koshal, Kanishka, Zorn, Kelsey C, Garcia-Beltran, Wilfredo F, Yang, Diane, Astudillo, Michael G, Bernstein, Bradley E, Gelfand, Jeffrey A, Ryan, Edward T, Charles, Richelle C, Iafrate, A John, Lennerz, Jochen K, Miller, Steve, Chiu, Charles Y, Stramer, Susan L, Wilson, Michael R, Manglik, Aashish, Ye, Chun Jimmie, Krogan, Nevan J, Anderson, Mark S, Cyster, Jason G, Ernst, Joel D, Wu, Alan HB, Lynch, Kara L, Bern, Caryn, Hsu, Patrick D, Marson, Alexander, Whitman, Jeffrey D, Whitman, Jeffrey D, Hiatt, Joseph, Mowery, Cody T, Shy, Brian R, Yu, Ruby, Yamamoto, Tori N, Rathore, Ujjwal, Goldgof, Gregory M, Whitty, Caroline, Woo, Jonathan M, Gallman, Antonia E, Miller, Tyler E, Levine, Andrew G, Nguyen, David N, Bapat, Sagar P, Balcerek, Joanna, Bylsma, Sophia A, Lyons, Ana M, Li, Stacy, Wong, Allison Wai-Yi, Gillis-Buck, Eva Mae, Steinhart, Zachary B, Lee, Youjin, Apathy, Ryan, Lipke, Mitchell J, Smith, Jennifer Anne, Zheng, Tina, Boothby, Ian C, Isaza, Erin, Chan, Jackie, Acenas, Dante D, Lee, Jinwoo, Macrae, Trisha A, Kyaw, Than S, Wu, David, Ng, Dianna L, Gu, Wei, York, Vanessa A, Eskandarian, Haig Alexander, Callaway, Perri C, Warrier, Lakshmi, Moreno, Mary E, Levan, Justine, Torres, Leonel, Farrington, Lila A, Loudermilk, Rita P, Koshal, Kanishka, Zorn, Kelsey C, Garcia-Beltran, Wilfredo F, Yang, Diane, Astudillo, Michael G, Bernstein, Bradley E, Gelfand, Jeffrey A, Ryan, Edward T, Charles, Richelle C, Iafrate, A John, Lennerz, Jochen K, Miller, Steve, Chiu, Charles Y, Stramer, Susan L, Wilson, Michael R, Manglik, Aashish, Ye, Chun Jimmie, Krogan, Nevan J, Anderson, Mark S, Cyster, Jason G, Ernst, Joel D, Wu, Alan HB, Lynch, Kara L, Bern, Caryn, Hsu, Patrick D, and Marson, Alexander

Abstract

Appropriate use and interpretation of serological tests for assessments of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure, infection and potential immunity require accurate data on assay performance. We conducted a head-to-head evaluation of ten point-of-care-style lateral flow assays (LFAs) and two laboratory-based enzyme-linked immunosorbent assays to detect anti-SARS-CoV-2 IgM and IgG antibodies in 5-d time intervals from symptom onset and studied the specificity of each assay in pre-coronavirus disease 2019 specimens. The percent of seropositive individuals increased with time, peaking in the latest time interval tested (>20 d after symptom onset). Test specificity ranged from 84.3% to 100.0% and was predominantly affected by variability in IgM results. LFA specificity could be increased by considering weak bands as negative, but this decreased detection of antibodies (sensitivity) in a subset of SARS-CoV-2 real-time PCR-positive cases. Our results underline the importance of seropositivity threshold determination and reader training for reliable LFA deployment. Although there was no standout serological assay, four tests achieved more than 80% positivity at later time points tested and more than 95% specificity.

Published
2020

11. A large CRISPR-induced bystander mutation causes immune dysregulation.

Author

Simeonov, Dimitre R, Simeonov, Dimitre R, Brandt, Alexander J, Chan, Alice Y, Cortez, Jessica T, Li, Zhongmei, Woo, Jonathan M, Lee, Youjin, Carvalho, Claudia MB, Indart, Alyssa C, Roth, Theodore L, Zou, James, May, Andrew P, Lupski, James R, Anderson, Mark S, Buaas, F William, Rokhsar, Daniel S, Marson, Alexander, Simeonov, Dimitre R, Simeonov, Dimitre R, Brandt, Alexander J, Chan, Alice Y, Cortez, Jessica T, Li, Zhongmei, Woo, Jonathan M, Lee, Youjin, Carvalho, Claudia MB, Indart, Alyssa C, Roth, Theodore L, Zou, James, May, Andrew P, Lupski, James R, Anderson, Mark S, Buaas, F William, Rokhsar, Daniel S, and Marson, Alexander

Abstract

A persistent concern with CRISPR-Cas9 gene editing has been the potential to generate mutations at off-target genomic sites. While CRISPR-engineering mice to delete a ~360 bp intronic enhancer, here we discovered a founder line that had marked immune dysregulation caused by a 24 kb tandem duplication of the sequence adjacent to the on-target deletion. Our results suggest unintended repair of on-target genomic cuts can cause pathogenic "bystander" mutations that escape detection by routine targeted genotyping assays.

Published
2019

12. A large CRISPR-induced bystander mutation causes immune dysregulation.

Author

Simeonov, Dimitre R, Simeonov, Dimitre R, Brandt, Alexander J, Chan, Alice Y, Cortez, Jessica T, Li, Zhongmei, Woo, Jonathan M, Lee, Youjin, Carvalho, Claudia MB, Indart, Alyssa C, Roth, Theodore L, Zou, James, May, Andrew P, Lupski, James R, Anderson, Mark S, Buaas, F William, Rokhsar, Daniel S, Marson, Alexander, Simeonov, Dimitre R, Simeonov, Dimitre R, Brandt, Alexander J, Chan, Alice Y, Cortez, Jessica T, Li, Zhongmei, Woo, Jonathan M, Lee, Youjin, Carvalho, Claudia MB, Indart, Alyssa C, Roth, Theodore L, Zou, James, May, Andrew P, Lupski, James R, Anderson, Mark S, Buaas, F William, Rokhsar, Daniel S, and Marson, Alexander

Abstract

A persistent concern with CRISPR-Cas9 gene editing has been the potential to generate mutations at off-target genomic sites. While CRISPR-engineering mice to delete a ~360 bp intronic enhancer, here we discovered a founder line that had marked immune dysregulation caused by a 24 kb tandem duplication of the sequence adjacent to the on-target deletion. Our results suggest unintended repair of on-target genomic cuts can cause pathogenic "bystander" mutations that escape detection by routine targeted genotyping assays.

Published
2019

13. Search for long-lived particles decaying into displaced jets in proton-proton collisions at √s = 13 TeV

Author

Massachusetts Institute of Technology. Department of Physics, Massachusetts Institute of Technology. Laboratory for Nuclear Science, Abercrombie, Daniel Robert, Allen, Brandon Leigh, Azzolini, Virginia, Bi, Ran, Brandt, Stephanie Akemi, Busza, Wit, Cali, Ivan Amos, D'Alfonso, Mariarosaria, Demiragli, Zeynep, Gomez-Ceballos, Guillelmo, Goncharov, Maxim, Harris, Philip Coleman, Hsu, Dylan George, Hu, Miao, Iiyama, Yutaro, Innocenti, Gian Michele, Klute, Markus, Kovalskyi, Dmytro, Lee, Youjin, Luckey Jr, P David, Maier, Benedikt, Marini, Andrea Carlo, McGinn, Christopher Francis, Mironov, Camelia Maria, Narayanan, Sruthi A., Niu, Xinmei, Paus, Christoph M. E., Terry, David Rankin, Roland, Christof E, Roland, Gunther M, Shi, Zhaozhong, Stephans, George S. F., Sumorok, Konstanty C, Tatar, Kaya, Velicanu, Dragos Alexandru, Wang, Jianchun, Wang, Tianwen, Wyslouch, Boleslaw, Massachusetts Institute of Technology. Department of Physics, Massachusetts Institute of Technology. Laboratory for Nuclear Science, Abercrombie, Daniel Robert, Allen, Brandon Leigh, Azzolini, Virginia, Bi, Ran, Brandt, Stephanie Akemi, Busza, Wit, Cali, Ivan Amos, D'Alfonso, Mariarosaria, Demiragli, Zeynep, Gomez-Ceballos, Guillelmo, Goncharov, Maxim, Harris, Philip Coleman, Hsu, Dylan George, Hu, Miao, Iiyama, Yutaro, Innocenti, Gian Michele, Klute, Markus, Kovalskyi, Dmytro, Lee, Youjin, Luckey Jr, P David, Maier, Benedikt, Marini, Andrea Carlo, McGinn, Christopher Francis, Mironov, Camelia Maria, Narayanan, Sruthi A., Niu, Xinmei, Paus, Christoph M. E., Terry, David Rankin, Roland, Christof E, Roland, Gunther M, Shi, Zhaozhong, Stephans, George S. F., Sumorok, Konstanty C, Tatar, Kaya, Velicanu, Dragos Alexandru, Wang, Jianchun, Wang, Tianwen, and Wyslouch, Boleslaw

Abstract

A search for long-lived particles decaying into jets is presented. Data were collected with the CMS detector at the LHC from proton-proton collisions at a center-of-mass energy of 13 TeV in 2016, corresponding to an integrated luminosity of 35.9 fb⁻¹. The search examines the distinctive topology of displaced tracks and secondary vertices. The selected events are found to be consistent with standard model predictions. For a simplified model in which long-lived neutral particles are pair produced and decay to two jets, pair production cross sections larger than 0.2 fb are excluded at 95% confidence level for a long-lived particle mass larger than 1000 GeV and proper decay lengths between 3 and 130 mm. Several supersymmetry models with gauge-mediated supersymmetry breaking or R-parity violation, where pair-produced long-lived gluinos or top squarks decay to several final-state topologies containing displaced jets, are also tested. For these models, in the mass ranges above 200 GeV, gluino masses up to 2300–2400 GeV and top squark masses up to 1350–1600 GeV are excluded for proper decay lengths approximately between 10 and 100 mm. These are the most restrictive limits to date on these models.

Published
2019

14. Search for dark matter produced in association with a single top quark or a top quark pair in proton-proton collisions at √s =13 TeV

Author

Massachusetts Institute of Technology. Department of Physics, Massachusetts Institute of Technology. Laboratory for Nuclear Science, Massachusetts Institute of Technology. Department of Nuclear Science and Engineering, Massachusetts Institute of Technology. Department of Mechanical Engineering, Abercrombie, Daniel Robert, Allen, Brandon Leigh, Azzolini, Virginia, Baty, Austin Alan, Bauer, Gerry P, Bi, Ran, Brandt, Stephanie Akemi, Busza, Wit, Cali, Ivan Amos, D'Alfonso, Mariarosaria, Demiragli, Zeynep, Gomez-Ceballos, Guillelmo, Goncharov, Maxim, Harris, Philip Coleman, Hsu, Dylan George, Hu, Miao, Iiyama, Yutaro, Innocenti, Gian Michele, Klute, Markus, Kovalskyi, Dmytro, Lee, Youjin, Luckey Jr, P David, Maier, Benedikt, Marini, Andrea Carlo, McGinn, Christopher Francis, Mironov, Camelia Maria, Narayanan, S., Niu, Xinmei, Paus, Christoph M. E., Roland, Christof E, Roland, Gunther M, Shi, Zhaozhong, Stephans, George S. F., Sumorok, Konstanty C, Tatar, Kaya, Velicanu, Dragos Alexandru, Wang, Jing, Wang, Taiwei, Wyslouch, Boleslaw, Massachusetts Institute of Technology. Department of Physics, Massachusetts Institute of Technology. Laboratory for Nuclear Science, Massachusetts Institute of Technology. Department of Nuclear Science and Engineering, Massachusetts Institute of Technology. Department of Mechanical Engineering, Abercrombie, Daniel Robert, Allen, Brandon Leigh, Azzolini, Virginia, Baty, Austin Alan, Bauer, Gerry P, Bi, Ran, Brandt, Stephanie Akemi, Busza, Wit, Cali, Ivan Amos, D'Alfonso, Mariarosaria, Demiragli, Zeynep, Gomez-Ceballos, Guillelmo, Goncharov, Maxim, Harris, Philip Coleman, Hsu, Dylan George, Hu, Miao, Iiyama, Yutaro, Innocenti, Gian Michele, Klute, Markus, Kovalskyi, Dmytro, Lee, Youjin, Luckey Jr, P David, Maier, Benedikt, Marini, Andrea Carlo, McGinn, Christopher Francis, Mironov, Camelia Maria, Narayanan, S., Niu, Xinmei, Paus, Christoph M. E., Roland, Christof E, Roland, Gunther M, Shi, Zhaozhong, Stephans, George S. F., Sumorok, Konstanty C, Tatar, Kaya, Velicanu, Dragos Alexandru, Wang, Jing, Wang, Taiwei, and Wyslouch, Boleslaw

Abstract

A search for dark matter produced in association with top quarks in proton-proton collisions at a center-of-mass energy of 13 TeV is presented. The data set used corresponds to an integrated luminosity of 35.9 fb⁻¹ recorded with the CMS detector at the LHC. Whereas previous searches for neutral scalar or pseudoscalar mediators considered dark matter production in association with a top quark pair only, this analysis also includes production modes with a single top quark. The results are derived from the combination of multiple selection categories that are defined to target either the single top quark or the top quark pair signature. No significant deviations with respect to the standard model predictions are observed. The results are interpreted in the context of a simplified model in which a scalar or pseudoscalar mediator particle couples to a top quark and subsequently decays into dark matter particles. Scalar and pseudoscalar mediator particles with masses below 290 and 300 GeV, respectively, are excluded at 95% confidence level, assuming a dark matter particle mass of 1 GeV and mediator couplings to fermions and dark matter particles equal to unity. Keywords: Dark matter; Hadron-Hadron scattering (experiments); Top physics

Published
2019

15. Search for beyond the standard model Higgs bosons decaying into a bb‾ pair in pp collisions at √s=13 TeV

Author

Massachusetts Institute of Technology. Department of Physics, Massachusetts Institute of Technology. Laboratory for Nuclear Science, Massachusetts Institute of Technology. Department of Nuclear Science and Engineering, Lincoln Laboratory, Massachusetts Institute of Technology. Department of Mechanical Engineering, Abercrombie, Daniel Robert, Allen, Benjamin E., Azzolini, Virginia, Barbieri, Richard Alexander, Baty, Austin Alan, Bauer, Gerry P, Bi, Ran, Brandt, Stephanie Akemi, Busza, Wit, Cali, Ivan Amos, D'Alfonso, Mariarosaria, Demiragli, Zeynep, Gomez-Ceballos, Guillelmo, Goncharov, Maxim, Harris, Philip Coleman, Hsu, Dylan George, Hu, Miao, Iiyama, Yutaro, Innocenti, Gian Michele, Klute, Markus, Kovalskyi, Dmytro, Lee, Youjin, Levin, Andrew (Andrew Michael), Luckey Jr, P David, Maier, Benedikt, Marini, Andrea Carlo, McGinn, Christopher Francis, Mironov, Camelia Maria, Narayanan, Sruthi A., Niu, Xinmei, Paus, Christoph M. E., Roland, Christof E, Roland, Gunther M, Stephans, George S. F., Sumorok, Konstanty C, Tatar, Kaya, Velicanu, Dragos Alexandru, Wang, Jing, Wang, Taiwei, Wyslouch, Boleslaw, Shi, Zhaozhong, CMS Collaboration, Massachusetts Institute of Technology. Department of Physics, Massachusetts Institute of Technology. Laboratory for Nuclear Science, Massachusetts Institute of Technology. Department of Nuclear Science and Engineering, Lincoln Laboratory, Massachusetts Institute of Technology. Department of Mechanical Engineering, Abercrombie, Daniel Robert, Allen, Benjamin E., Azzolini, Virginia, Barbieri, Richard Alexander, Baty, Austin Alan, Bauer, Gerry P, Bi, Ran, Brandt, Stephanie Akemi, Busza, Wit, Cali, Ivan Amos, D'Alfonso, Mariarosaria, Demiragli, Zeynep, Gomez-Ceballos, Guillelmo, Goncharov, Maxim, Harris, Philip Coleman, Hsu, Dylan George, Hu, Miao, Iiyama, Yutaro, Innocenti, Gian Michele, Klute, Markus, Kovalskyi, Dmytro, Lee, Youjin, Levin, Andrew (Andrew Michael), Luckey Jr, P David, Maier, Benedikt, Marini, Andrea Carlo, McGinn, Christopher Francis, Mironov, Camelia Maria, Narayanan, Sruthi A., Niu, Xinmei, Paus, Christoph M. E., Roland, Christof E, Roland, Gunther M, Stephans, George S. F., Sumorok, Konstanty C, Tatar, Kaya, Velicanu, Dragos Alexandru, Wang, Jing, Wang, Taiwei, Wyslouch, Boleslaw, Shi, Zhaozhong, and CMS Collaboration

Abstract

A search for Higgs bosons that decay into a bottom quark-antiquark pair and are accompanied by at least one additional bottom quark is performed with the CMS detector. The data analyzed were recorded in proton-proton collisions at a centre-of-mass energy of s√=13 TeV at the LHC, corresponding to an integrated luminosity of 35.7 fb⁻¹. The final state considered in this analysis is particularly sensitive to signatures of a Higgs sector beyond the standard model, as predicted in the generic class of two Higgs doublet models (2HDMs). No signal above the standard model background expectation is observed. Stringent upper limits on the cross section times branching fraction are set for Higgs bosons with masses up to 1300 GeV. The results are interpreted within several MSSM and 2HDM scenarios. Keywords: Beyond Standard Model; Hadron-Hadron scattering (experiments); Higgs physics

Published
2019

16. Performance of the CMS muon detector and muon reconstruction with proton-proton collisions at √s = 13 TeV

Author

Massachusetts Institute of Technology. Department of Physics, Massachusetts Institute of Technology. Department of Nuclear Science and Engineering, Massachusetts Institute of Technology. Laboratory for Nuclear Science, Massachusetts Institute of Technology. Department of Mechanical Engineering, Abercrombie, Daniel Robert, Allen, Brandon Leigh, Azzolini, Virginia, Barbieri, Richard Alexander, Baty, Austin Alan, Bauer, Gerry P, Bi, Ran, Brandt, Stephanie Akemi, Busza, Wit, Cali, Ivan Amos, D'Alfonso, Mariarosaria, Demiragli, Zeynep, Gomez-Ceballos, Guillelmo, Goncharov, Maxim, Harris, Philip Coleman, Hsu, Dylan George, Hu, Miao, Iiyama, Yutaro, Innocenti, Gian Michele, Klute, Markus, Kovalskyi, Dmytro, Lee, Youjin, Levine, Alan M, Luckey Jr, P David, Maier, Benedikt, Marini, Andrea Carlo, McGinn, Christopher Francis, Mironov, Camelia Maria, Narayanan, S., Niu, Xinmei, Paus, Christoph M. E., Roland, Christof E, Roland, Gunther M, Salfeld-Nebgen, Jakob Maxillian Henry, Stephans, George S. F., Sumorok, Konstanty C, Tatar, Kaya, Velicanu, Dragos Alexandru, Wang, Jing, Wang, Taiwei, Wyslouch, Boleslaw, Massachusetts Institute of Technology. Department of Physics, Massachusetts Institute of Technology. Department of Nuclear Science and Engineering, Massachusetts Institute of Technology. Laboratory for Nuclear Science, Massachusetts Institute of Technology. Department of Mechanical Engineering, Abercrombie, Daniel Robert, Allen, Brandon Leigh, Azzolini, Virginia, Barbieri, Richard Alexander, Baty, Austin Alan, Bauer, Gerry P, Bi, Ran, Brandt, Stephanie Akemi, Busza, Wit, Cali, Ivan Amos, D'Alfonso, Mariarosaria, Demiragli, Zeynep, Gomez-Ceballos, Guillelmo, Goncharov, Maxim, Harris, Philip Coleman, Hsu, Dylan George, Hu, Miao, Iiyama, Yutaro, Innocenti, Gian Michele, Klute, Markus, Kovalskyi, Dmytro, Lee, Youjin, Levine, Alan M, Luckey Jr, P David, Maier, Benedikt, Marini, Andrea Carlo, McGinn, Christopher Francis, Mironov, Camelia Maria, Narayanan, S., Niu, Xinmei, Paus, Christoph M. E., Roland, Christof E, Roland, Gunther M, Salfeld-Nebgen, Jakob Maxillian Henry, Stephans, George S. F., Sumorok, Konstanty C, Tatar, Kaya, Velicanu, Dragos Alexandru, Wang, Jing, Wang, Taiwei, and Wyslouch, Boleslaw

Abstract

The CMS muon detector system, muon reconstruction software, and high-level trigger underwent significant changes in 2013-2014 in preparation for running at higher LHC collision energy and instantaneous luminosity. The performance of the modified system is studied using proton-proton collision data at center-of-mass energy √s = 13 TeV, collected at the LHC in 2015 and 2016. The measured performance parameters, including spatial resolution, efficiency, and timing, are found to meet all design specifications and are well reproduced by simulation. Despite the more challenging running conditions, the modified muon system is found to perform as well as, and in many aspects better than, previously. We dedicate this paper to the memory of Prof. Alberto Benvenuti, whose work was fundamental for the CMS muon detector.

Published
2019

17. Time reconstruction and performance of the CMS electromagnetic calorimeter

Author

Massachusetts Institute of Technology. Department of Physics, Massachusetts Institute of Technology. Laboratory for Nuclear Science, Massachusetts Institute of Technology. Department of Nuclear Science and Engineering, Alver, Burak Han, Bauer, Gerry P, Bendavid, Joshua L., Busza, Wit, Butz, Erik M., Cali, Ivan Amos, Chan, M., D'Enterria, David, Everaerts, Pieter Bruno Bart, Gomez-Ceballos, Guillelmo, Hahn, Kristian Allan, Harris, Philip Coleman, Jaditz, Stephen Hunter, Kim, Y., Klute, Markus, Lee, Youjin, Li, W., Loizides, Constantinos, Ma, T., Miller, M., Paus, Christoph M. E., Roland, Christof E, Roland, Gunther M, Rudolph, Matthew Scott, Stephans, George S. F., Sumorok, Konstanty C, Sung, K., Vaurynovich, Siarhei S., Wenger, Edward Allen, Wyslouch, Boleslaw, Xie, Si, Yilmaz, Yetkin, Yoon, A. S., Nahn, Steven, Massachusetts Institute of Technology. Department of Physics, Massachusetts Institute of Technology. Laboratory for Nuclear Science, Massachusetts Institute of Technology. Department of Nuclear Science and Engineering, Alver, Burak Han, Bauer, Gerry P, Bendavid, Joshua L., Busza, Wit, Butz, Erik M., Cali, Ivan Amos, Chan, M., D'Enterria, David, Everaerts, Pieter Bruno Bart, Gomez-Ceballos, Guillelmo, Hahn, Kristian Allan, Harris, Philip Coleman, Jaditz, Stephen Hunter, Kim, Y., Klute, Markus, Lee, Youjin, Li, W., Loizides, Constantinos, Ma, T., Miller, M., Paus, Christoph M. E., Roland, Christof E, Roland, Gunther M, Rudolph, Matthew Scott, Stephans, George S. F., Sumorok, Konstanty C, Sung, K., Vaurynovich, Siarhei S., Wenger, Edward Allen, Wyslouch, Boleslaw, Xie, Si, Yilmaz, Yetkin, Yoon, A. S., and Nahn, Steven

Abstract

The resolution and the linearity of time measurements made with the CMS electromagnetic calorimeter are studied with samples of data from test beam electrons, cosmic rays, and beam-produced muons. The resulting time resolution measured by lead tungstate crystals is better than 100 ps for energy deposits larger than 10 GeV. Crystal-to-crystal synchronization with a precision of 500 ps is performed using muons produced with the first LHC beams in 2008.

Published
2019

18. Search for dark matter in proton-proton collisions at 8 TeV with missing transverse momentum and vector boson tagged jets

Author

Massachusetts Institute of Technology. Department of Physics, Massachusetts Institute of Technology. Laboratory for Nuclear Science, Abercrombie, Daniel Robert, Allen, Brandon Leigh, Apyan, Aram, Barbieri, Richard Alexander, Baty, Austin Alan, Bi, Ran, Bierwagen, Katharina, Brandt, Stephanie Akemi, Busza, Wit, Cali, Ivan Amos, Demiragli, Zeynep, Di Matteo, Leonardo, Gomez-Ceballos, Guillelmo, Goncharov, Maxim, Hsu, Dylan George, Iiyama, Yutaro, Innocenti, Gian Michele, Klute, Markus, Kovalskyi, Dmytro, Krajczar, Krisztian F., Lai, Yue Shi, Lee, Youjin, Levin, A., Luckey Jr, P David, Marini, Andrea Carlo, McGinn, Christopher Francis, Mironov, Camelia Maria, Narayanan, S., Niu, Xinmei, Paus, Christoph M. E., Roland, Christof E, Roland, Gunther M, Salfeld-Nebgen, Jakob Maxillian Henry, Stephans, George S. F., Sumorok, Konstanty C, Tatar, Kaya, Varma, Mukund Madhav, Velicanu, Dragos Alexandru, Veverka, Jan, Wang, Jing, Wang, Ta-Wei, Wyslouch, Boleslaw, Yang, Ming, Wyslouch, Victoria, Massachusetts Institute of Technology. Department of Physics, Massachusetts Institute of Technology. Laboratory for Nuclear Science, Abercrombie, Daniel Robert, Allen, Brandon Leigh, Apyan, Aram, Barbieri, Richard Alexander, Baty, Austin Alan, Bi, Ran, Bierwagen, Katharina, Brandt, Stephanie Akemi, Busza, Wit, Cali, Ivan Amos, Demiragli, Zeynep, Di Matteo, Leonardo, Gomez-Ceballos, Guillelmo, Goncharov, Maxim, Hsu, Dylan George, Iiyama, Yutaro, Innocenti, Gian Michele, Klute, Markus, Kovalskyi, Dmytro, Krajczar, Krisztian F., Lai, Yue Shi, Lee, Youjin, Levin, A., Luckey Jr, P David, Marini, Andrea Carlo, McGinn, Christopher Francis, Mironov, Camelia Maria, Narayanan, S., Niu, Xinmei, Paus, Christoph M. E., Roland, Christof E, Roland, Gunther M, Salfeld-Nebgen, Jakob Maxillian Henry, Stephans, George S. F., Sumorok, Konstanty C, Tatar, Kaya, Varma, Mukund Madhav, Velicanu, Dragos Alexandru, Veverka, Jan, Wang, Jing, Wang, Ta-Wei, Wyslouch, Boleslaw, Yang, Ming, and Wyslouch, Victoria

Abstract

A search is presented for an excess of events with large missing transverse momentum in association with at least one highly energetic jet, in a data sample of proton-proton collisions at a centre-of-mass energy of 8 TeV. The data correspond to an integrated luminosity of 19.7 fb⁻¹ collected by the CMS experiment at the LHC. The results are interpreted using a set of simplified models for the production of dark matter via a scalar, pseudoscalar, vector, or axial vector mediator. Additional sensitivity is achieved by tagging events consistent with the jets originating from a hadronically decaying vector boson. This search uses jet substructure techniques to identify hadronically decaying vector bosons in both Lorentz-boosted and resolved scenarios. This analysis yields improvements of 80% in terms of excluded signal cross sections with respect to the previous CMS analysis using the same data set. No significant excess with respect to the standard model expectation is observed and limits are placed on the parameter space of the simplified models. Mediator masses between 80 and 400 GeV in the scalar and pseudoscalar models, and up to 1.5 TeV in the vector and axial vector models, are excluded.[Figure not available: see fulltext.] Keywords: Dark matter; Hadron-Hadron scattering (experiments)

Published
2019

19. Measurement of the muon stopping power in lead tungstate

Author

Massachusetts Institute of Technology. Department of Physics, Massachusetts Institute of Technology. Department of Nuclear Science and Engineering, Massachusetts Institute of Technology. Laboratory for Nuclear Science, Alver, Burak Han, Bauer, Gerry P, Bendavid, Joshua L., Busza, Wit, Butz, Erik M., Cali, Ivan Amos, Chan, M., D'Enterria, David, Everaerts, Pieter Bruno Bart, Gomez-Ceballos, Guillelmo, Hahn, Kristian Allan, Harris, Philip Coleman, Jaditz, Stephen Hunter, Kim, Y., Klute, Markus, Lee, Youjin, Li, W., Loizides, Constantinos, Miller, M., Paus, Christoph M. E., Roland, Christof E, Roland, Gunther M, Rudolph, Matthew Scott, Stephans, George S. F., Sumorok, Konstanty C, Sung, K., Vaurynovich, Siarhei S., Wenger, Edward Allen, Wyslouch, Boleslaw, Xie, S., Yilmaz, Yetkin, Yoon, A.S., CMS Collaboration, Ma. T., Nahn, Steven, Massachusetts Institute of Technology. Department of Physics, Massachusetts Institute of Technology. Department of Nuclear Science and Engineering, Massachusetts Institute of Technology. Laboratory for Nuclear Science, Alver, Burak Han, Bauer, Gerry P, Bendavid, Joshua L., Busza, Wit, Butz, Erik M., Cali, Ivan Amos, Chan, M., D'Enterria, David, Everaerts, Pieter Bruno Bart, Gomez-Ceballos, Guillelmo, Hahn, Kristian Allan, Harris, Philip Coleman, Jaditz, Stephen Hunter, Kim, Y., Klute, Markus, Lee, Youjin, Li, W., Loizides, Constantinos, Miller, M., Paus, Christoph M. E., Roland, Christof E, Roland, Gunther M, Rudolph, Matthew Scott, Stephans, George S. F., Sumorok, Konstanty C, Sung, K., Vaurynovich, Siarhei S., Wenger, Edward Allen, Wyslouch, Boleslaw, Xie, S., Yilmaz, Yetkin, Yoon, A.S., CMS Collaboration, Ma. T., and Nahn, Steven

Abstract

A large sample of cosmic ray events collected by the CMS detector is exploited to measure the specific energy loss of muons in the lead tungstate (PbWO₄) of the electromagnetic calorimeter. The measurement spans a momentum range from 5 GeV/c to 1 TeV/c. The results are consistent with the expectations over the entire range. The calorimeter energy scale, set with 120 GeV/c electrons, is validated down to the sub-GeV region using energy deposits, of order 100 MeV, associated with low-momentum muons. The muon critical energy in PbWO₄ is measured to be 160⁺⁵₋₆±8 GeV, in agreement with expectations. This is the first experimental determination of muon critical energy.

Published
2019

20. Effect of Thermal Fluctuations on the Radiative Rate in Core/Shell Quantum Dots.

Author

Balan, Arunima D, Balan, Arunima D, Eshet, Hagai, Olshansky, Jacob H, Lee, Youjin V, Rabani, Eran, Alivisatos, A Paul, Balan, Arunima D, Balan, Arunima D, Eshet, Hagai, Olshansky, Jacob H, Lee, Youjin V, Rabani, Eran, and Alivisatos, A Paul

Abstract

The effect of lattice fluctuations and electronic excitations on the radiative rate is demonstrated in CdSe/CdS core/shell spherical quantum dots (QDs). Using a combination of time-resolved photoluminescence spectroscopy and atomistic simulations, we show that lattice fluctuations can change the radiative rate over the temperature range from 78 to 300 K. We posit that the presence of the core/shell interface plays a significant role in dictating this behavior. We show that the other major factor that underpins the change in radiative rate with temperature is the presence of higher energy states corresponding to electron excitation into the shell. These effects should be present in other core/shell samples and should also affect other excited state rates, such as the rate of Auger recombination or the rate of charge transfer.

Published
2017

21. Temperature-Dependent Hole Transfer from Photoexcited Quantum Dots to Molecular Species: Evidence for Trap-Mediated Transfer.

Author

Olshansky, Jacob H, Olshansky, Jacob H, Balan, Arunima D, Ding, Tina X, Fu, Xiao, Lee, Youjin V, Alivisatos, A Paul, Olshansky, Jacob H, Olshansky, Jacob H, Balan, Arunima D, Ding, Tina X, Fu, Xiao, Lee, Youjin V, and Alivisatos, A Paul

Abstract

The effect of temperature on the rate of hole transfer from photoexcited quantum dots (QDs) is investigated by measuring the driving force dependence of the charge transfer rate for different sized QDs across a range of temperatures from 78 to 300 K. Spherical CdSe/CdS core/shell QDs were used with a series of ferrocene-derived molecular hole acceptors with an 800 meV range in electrochemical potential. Time-resolved photoluminescence measurements and photoluminescence quantum yield measurements in an integrating sphere were both performed from 78 to 300 K to obtain temperature-dependent rates for a series of driving forces as dictated by the nature of the molecular acceptor. For both QD sizes studied and all ligands, the Arrhenius plot of hole transfer exhibited an activated (linear) regime at higher temperatures and a temperature-independent regime at low temperatures. The extracted activation energies in the high-temperature regime were consistent across all ligands for a given QD size. This observation is not consistent with direct charge transfer from the QD valence band to the ferrocene acceptor. Instead, a model in which charge transfer is mediated by a shallow and reversible trap more accurately fits the experimental results. Implications for this observed trap-mediated transfer are discussed including as a strategy to more efficiently extract charge from QDs.

Published
2017

22. Search for dark matter and unparticles produced in association with a Z boson in proton-proton collisions at √s = 8 TeV

Author

Massachusetts Institute of Technology. Department of Nuclear Science and Engineering, Massachusetts Institute of Technology. Department of Physics, Massachusetts Institute of Technology. Laboratory for Nuclear Science, Apyan, Aram, Barbieri, Richard Alexander, Baty, Austin Alan, Bierwagen, Katharina, Brandt, Stephanie Akemi, Busza, Wit, Cali, Ivan Amos, Demiragli, Zeynep, Di Matteo, Leonardo, Gomez-Ceballos, Guillelmo, Goncharov, Maxim, Gulhan, Doga Can, Iiyama, Yutaro, Innocenti, Gian Michele, Klute, Markus, Kovalskyi, Dmytro, Lai, Yue Shi, Lee, Youjin, Levin, Andrew Michael, Luckey Jr, P David, Marini, Andrea Carlo, McGinn, Christopher Francis, Mironov, Camelia Maria, Narayanan, Siddharth Madhavan, Niu, Xinmei, Paus, Christoph M. E., Ralph, Duncan Kelley, Roland, Christof E, Roland, Gunther M, Salfeld-Nebgen, Jakob Maxillian Henry, Stephans, George S. F., Sumorok, Konstanty C, Varma, Mukund Madhav, Velicanu, Dragos Alexandru, Veverka, Jan, Wang, Jing, Wang, Ta-Wei, Wyslouch, Boleslaw, Yang, Ming, Wyslouch, Victoria, Khachatryan, V., Sirunyan, A. M., Tumasyan, A., Adam, W., Asilar, E., Bergauer, T., Brandstetter, J., Brondolin, E., Dragicevic, M., Erö, J., Flechl, M., Friedl, M., Frühwirth, R., Ghete, V. M., Hartl, C., Hörmann, N., Hrubec, J., Jeitler, M., Knünz, V., König, A., Krammer, M., Krätschmer, I., Liko, D., Matsushita, T., Mikulec, I., Rabady, D., Rahbaran, B., Rohringer, H., Schieck, J., Schöfbeck, R., Strauss, J., Treberer-Treberspurg, W., Waltenberger, W., Wulz, C.-E., Mossolov, V., Shumeiko, N., Suarez Gonzalez, J., Alderweireldt, S., Cornelis, T., De Wolf, E. A., Janssen, X., Knutsson, A., Lauwers, J., Luyckx, S., Van De Klundert, M., Van Haevermaet, H., Van Mechelen, P., Van Remortel, N., Van Spilbeeck, A., Abu Zeid, S., Blekman, F., D’Hondt, J., Daci, N., De Bruyn, I., Deroover, K., Heracleous, N., Keaveney, J., Lowette, S., Moreels, L., Olbrechts, A., Python, Q., Strom, D., Tavernier, S., Van Doninck, W., Van Mulders, P., Van Onsem, G. P., Van Parijs, I., Barria, P., Brun, H., Caillol, C., Clerbaux, B., De Lentdecker, G., Fasanella, G., Favart, L., Grebenyuk, A., Karapostoli, G., Lenzi, T., Léonard, A., Maerschalk, T., Marinov, A., Perniè, L., Randle-conde, A., Seva, T., Vander Velde, C., Vanlaer, P., Yonamine, R., Zenoni, F., Zhang, F., Beernaert, K., Benucci, L., Cimmino, A., Crucy, S., Dobur, D., Fagot, A., Garcia, G., Gul, M., Mccartin, J., Ocampo Rios, A. A., Poyraz, D., Ryckbosch, D., Salva, S., Sigamani, M., Tytgat, M., Van Driessche, W., Yazgan, E., Zaganidis, N., Basegmez, S., Beluffi, C., Bondu, O., Brochet, S., Bruno, G., Caudron, A., Ceard, L., Da Silveira, G. G., Delaere, C., Favart, D., Forthomme, L., Giammanco, A., Hollar, J., Jafari, A., Jez, P., Komm, M., Lemaitre, V., Mertens, A., Musich, M., Nuttens, C., Perrini, L., Pin, A., Piotrzkowski, K., Popov, A., Quertenmont, L., Selvaggi, M., Vidal Marono, M., Beliy, N., Hammad, G. H., Aldá Júnior, W. L., Alves, F. L., Alves, G. A., Brito, L., Correa Martins Junior, M., Hamer, M., Hensel, C., Mora Herrera, C., Moraes, A., Pol, M. E., Rebello Teles, P., Belchior Batista Das Chagas, E., Carvalho, W., Chinellato, J., Custódio, A., Da Costa, E. M., De Jesus Damiao, D., De Oliveira Martins, C., Fonseca De Souza, S., Huertas Guativa, L. M., Malbouisson, H., Matos Figueiredo, D., Mundim, L., Nogima, H., Prado Da Silva, W. L., Santoro, A., Sznajder, A., Tonelli Manganote, E. J., Vilela Pereira, A., Ahuja, S., Bernardes, C. A., De Souza Santos, A., Dogra, S., Tomei, Fernandez Perez T. R., Gregores, E. M., Mercadante, P. G., Moon, C. S., Novaes, S. F., Padula, Sandra S., Romero Abad, D., Ruiz Vargas, J. C., Aleksandrov, A., Hadjiiska, R., Iaydjiev, P., Rodozov, M., Stoykova, S., Sultanov, G., Vutova, M., Dimitrov, A., Glushkov, I., Litov, L., Pavlov, B., Petkov, P., Ahmad, M., Bian, J. G., Chen, G. M., Chen, H. S., Chen, M., Cheng, T., Du, R., Jiang, C. H., Plestina, R., Romeo, F., Shaheen, S. M., Spiezia, A., Tao, J., Wang, C., Wang, Z., Zhang, H., Asawatangtrakuldee, C., Ban, Y., Li, Q., Liu, S., Mao, Y., Qian, S. J., Wang, D., Xu, Z., Avila, C., Cabrera, A., Chaparro Sierra, L. F., Florez, C., Gomez, J. P., Gomez Moreno, B., Sanabria, J. C., Godinovic, N., Lelas, D., Puljak, I., Ribeiro Cipriano, P. M., Antunovic, Z., Kovac, M., Brigljevic, V., Kadija, K., Luetic, J., Micanovic, S., Sudic, L., Attikis, A., Mavromanolakis, G., Mousa, J., Nicolaou, C., Ptochos, F., Razis, P. A., Rykaczewski, H., Bodlak, M., Finger, M., Assran, Y., Elgammal, S., Ellithi Kamel, A., Mahmoud, M. A., Mohammed, Y., Calpas, B., Kadastik, M., Murumaa, M., Raidal, M., Tiko, A., Veelken, C., Eerola, P., Pekkanen, J., Voutilainen, M., Härkönen, J., Karimäki, V., Kinnunen, R., Lampén, T., Lassila-Perini, K., Lehti, S., Lindén, T., Luukka, P., Mäenpää, T., Peltola, T., Tuominen, E., Tuominiemi, J., Tuovinen, E., Wendland, L., Talvitie, J., Tuuva, T., Besancon, M., Couderc, F., Dejardin, M., Denegri, D., Fabbro, B., Faure, J. L., Favaro, C., Ferri, F., Ganjour, S., Givernaud, A., Gras, P., Hamel de Monchenault, G., Jarry, P., Locci, E., Machet, M., Malcles, J., Rander, J., Rosowsky, A., Titov, M., Zghiche, A., Antropov, I., Baffioni, S., Beaudette, F., Busson, P., Cadamuro, L., Chapon, E., Charlot, C., Dahms, T., Davignon, O., Filipovic, N., Granier de Cassagnac, R., Jo, M., Lisniak, S., Mastrolorenzo, L., Miné, P., Naranjo, I. N., Nguyen, M., Ochando, C., Ortona, G., Paganini, P., Pigard, P., Regnard, S., Salerno, R., Sauvan, Sirois, Y., Strebler, T., Yilmaz, Y., Zabi, A., Agram, J.-L., Andrea, J., Aubin, A., Bloch, D., Brom, J.-M., Buttignol, M., Chabert, E. C., Chanon, N., Collard, C., Conte, E., Coubez, X., Fontaine, J.-C., Gelé, D., Goerlach, U., Goetzmann, C., Le Bihan, A.-C., Merlin, J. A., Skovpen, K., Van Hove, P., Gadrat, S., Beauceron, S., Bernet, C., Boudoul, G., Bouvier, E., Carrillo Montoya, C. A., Chierici, R., Contardo, D., Courbon, B., Depasse, P., El Mamouni, H., Fan, J., Fay, J., Gascon, S., Gouzevitch, M., Ille, B., Lagarde, F., Laktineh, I. B., Lethuillier, M., Mirabito, L., Pequegnot, A. L., Perries, S., Ruiz Alvarez, J. D., Sabes, D., Sgandurra, L., Sordini, V., Vander Donckt, M., Verdier, P., Viret, S., Toriashvili, T., Tsamalaidze, Z., Autermann, C., Beranek, S., Edelhoff, M., Feld, L., Heister, A., Kiesel, M. K., Klein, K., Lipinski, M., Ostapchuk, A., Preuten, M., Raupach, F., Schael, S., Schulte, J. F., Verlage, T., Weber, H., Wittmer, B., Zhukov, V., Ata, M., Brodski, M., Dietz-Laursonn, E., Duchardt, D., Endres, M., Erdmann, M., Erdweg, S., Esch, T., Fischer, R., Güth, A., Hebbeker, T., Heidemann, C., Hoepfner, K., Knutzen, S., Kreuzer, P., Merschmeyer, M., Meyer, A., Millet, P., Olschewski, M., Padeken, K., Papacz, P., Pook, T., Radziej, M., Reithler, H., Rieger, M., Scheuch, F., Sonnenschein, L., Teyssier, D., Thüer, S., Cherepanov, V., Erdogan, Y., Flügge, G., Geenen, H., Geisler, M., Hoehle, F., Kargoll, B., Kress, T., Kuessel, Y., Künsken, A., Lingemann, J., Nehrkorn, A., Nowack, A., Nugent, I. M., Pistone, C., Pooth, O., Stahl, A., Aldaya Martin, M., Asin, I., Bartosik, N., Behnke, O., Behrens, U., Bell, A. J., Borras, K., Burgmeier, A., Campbell, A., Choudhury, S., Costanza, F., Diez Pardos, C., Dolinska, G., Dooling, S., Dorland, T., Eckerlin, G., Eckstein, D., Eichhorn, T., Flucke, G., Gallo, E., Garay Garcia, J., Geiser, A., Gizhko, A., Gunnellini, P., Hauk, J., Hempel, M., Jung, H., Kalogeropoulos, A., Karacheban, O., Kasemann, M., Katsas, P., Kieseler, J., Kleinwort, C., Korol, I., Lange, W., Leonard, J., Lipka, K., Lobanov, A., Lohmann, W., Mankel, R., Marfin, I., Melzer-Pellmann, I.-A., Meyer, A. B., Mittag, G., Mnich, J., Mussgiller, A., Naumann-Emme, S., Nayak, A., Ntomari, E., Perrey, H., Pitzl, D., Placakyte, R., Raspereza, A., Roland, B., Sahin, M. Ö., Saxena, P., Schoerner-Sadenius, T., Schröder, M., Seitz, C., Spannagel, S., Trippkewitz, K. D., Walsh, R., Wissing, C., Blobel, V., Centis Vignali, M., Draeger, A. R., Erfle, J., Garutti, E., Goebel, K., Gonzalez, D., Görner, M., Haller, J., Hoffmann, M., Höing, R. S., Junkes, A., Klanner, R., Kogler, R., Kovalchuk, N., Lapsien, T., Lenz, T., Marchesini, I., Marconi, D., Meyer, M., Nowatschin, D., Ott, J., Pantaleo, F., Peiffer, T., Perieanu, A., Pietsch, N., Poehlsen, J., Rathjens, D., Sander, C., Scharf, C., Schettler, H., Schleper, P., Schlieckau, E., Schmidt, A., Schwandt, J., Sola, V., Stadie, H., Steinbrück, G., Tholen, H., Troendle, D., Usai, E., Vanelderen, L., Vanhoefer, A., Vormwald, B., Akbiyik, M., Barth, C., Baus, C., Berger, J., Böser, C., Butz, E., Chwalek, T., Colombo, F., De Boer, W., Descroix, A., Dierlamm, A., Fink, S., Frensch, F., Friese, R., Giffels, M., Gilbert, A., Haitz, D., Hartmann, F., Heindl, S. M., Husemann, U., Katkov, I., Kornmayer, A., Lobelle Pardo, P., Maier, B., Mildner, H., Mozer, M. U., Müller, T., Müller, Th., Plagge, M., Quast, G., Rabbertz, K., Röcker, S., Roscher, F., Sieber, G., Simonis, H. J., Stober, F. M., Ulrich, R., Wagner-Kuhr, J., Wayand, S., Weber, M., Weiler, T., Wöhrmann, C., Wolf, R., Anagnostou, G., Daskalakis, G., Geralis, T., Giakoumopoulou, V. A., Kyriakis, A., Loukas, D., Psallidas, A., Topsis-Giotis, I., Agapitos, A., Kesisoglou, S., Panagiotou, A., Saoulidou, N., Tziaferi, E., Evangelou, I., Flouris, G., Foudas, C., Kokkas, P., Loukas, N., Manthos, N., Papadopoulos, I., Paradas, E., Strologas, J., Bencze, G., Hajdu, C., Hazi, A., Hidas, P., Horvath, D., Sikler, F., Veszpremi, V., Vesztergombi, G., Zsigmond, A. J., Beni, N., Czellar, S., Karancsi, J., Molnar, J., Szillasi, Z., Bartók, M., Makovec, A., Raics, P., Trocsanyi, Z. L., Ujvari, B., Mal, P., Mandal, K., Sahoo, D. K., Sahoo, N., Swain, S. K., Bansal, S., Beri, S. B., Bhatnagar, V., Chawla, R., Gupta, R., Bhawandeep, U., Kalsi, A. K., Kaur, A., Kaur, M., Kumar, R., Mehta, A., Mittal, M., Singh, J. B., Walia, G., Kumar, Ashok, Bhardwaj, A., Choudhary, B. C., Garg, R. B., Kumar, A., Malhotra, S., Naimuddin, M., Nishu, N., Ranjan, K., Sharma, R., Sharma, V., Bhattacharya, S., Chatterjee, K., Dey, S., Dutta, S., Jain, Sa., Majumdar, N., Modak, A., Mondal, K., Mukherjee, S., Mukhopadhyay, S., Roy, A., Roy, D., Roy Chowdhury, S., Sarkar, S., Sharan, M., Abdulsalam, A., Chudasama, R., Dutta, D., Jha, V., Kumar, V., Mohanty, A. K., Pant, L. M., Shukla, P., Topkar, A., Aziz, T., Banerjee, S., Bhowmik, S., Chatterjee, R. M., Dewanjee, R. K., Dugad, S., Ganguly, S., Ghosh, S., Guchait, M., Gurtu, A., Kole, G., Kumar, S., Mahakud, B., Maity, M., Majumder, G., Mazumdar, K., Mitra, S., Mohanty, G. B., Parida, B., Sarkar, T., Sur, N., Sutar, B., Wickramage, N., Chauhan, S., Dube, S., Kothekar, K., Sharma, S., Bakhshiansohi, H., Behnamian, H., Etesami, S. M., Fahim, A., Goldouzian, R., Khakzad, M., Mohammadi Najafabadi, M., Naseri, M., Paktinat Mehdiabadi, S., Rezaei Hosseinabadi, F., Safarzadeh, B., Zeinali, M., Felcini, M., Grunewald, M., Abbrescia, M., Calabria, C., Caputo, C., Colaleo, A., Creanza, D., Cristella, L., De Filippis, N., De Palma, M., Fiore, L., Iaselli, G., Maggi, G., Maggi, M., Miniello, G., My, S., Nuzzo, S., Pompili, A., Pugliese, G., Radogna, R., Ranieri, A., Selvaggi, G., Silvestris, L., Venditti, R., Verwilligen, P., Abbiendi, G., Battilana, C., Benvenuti, A. C., Bonacorsi, D., Braibant-Giacomelli, S., Brigliadori, L., Campanini, R., Capiluppi, P., Castro, A., Cavallo, F. R., Chhibra, S. S., Codispoti, G., Cuffiani, M., Dallavalle, G. M., Fabbri, F., Fanfani, A., Fasanella, D., Giacomelli, P., Grandi, C., Guiducci, L., Marcellini, S., Masetti, G., Montanari, A., Navarria, F. L., Perrotta, A., Rossi, A. M., Rovelli, T., Siroli, G. P., Tosi, N., Travaglini, R., Cappello, G., Chiorboli, M., Costa, S., Di Mattia, A., Giordano, F., Potenza, R., Tricomi, A., Tuve, C., Barbagli, G., Ciulli, V., Civinini, C., D’Alessandro, R., Focardi, E., Gonzi, S., Gori, V., Lenzi, P., Meschini, M., Paoletti, S., Sguazzoni, G., Tropiano, A., Viliani, L., Benussi, L., Bianco, S., Piccolo, D., Primavera, F., Calvelli, V., Ferro, F., Lo Vetere, M., Monge, M. R., Robutti, E., Tosi, S., Brianza, L., Dinardo, M. E., Fiorendi, S., Gennai, S., Gerosa, R., Ghezzi, A., Govoni, P., Malvezzi, S., Manzoni, R. A., Marzocchi, B., Moroni, L., Paganoni, M., Pedrini, D., Ragazzi, S., Redaelli, N., Tabarelli de Fatis, T., Buontempo, S., Cavallo, N., Di Guida, S., Esposito, M., Fabozzi, F., Iorio, A. O. M., Lanza, G., Lista, L., Meola, S., Merola, M., Paolucci, P., Sciacca, C., Thyssen, F., Azzi, P., Bacchetta, N., Benato, L., Bisello, D., Boletti, A., Branca, A., Carlin, R., Checchia, P., Dall’Osso, M., Dorigo, T., Dosselli, U., Gasparini, F., Gasparini, U., Gozzelino, A., Kanishchev, K., Lacaprara, S., Margoni, M., Meneguzzo, A. T., Passaseo, M., Pazzini, J., Pozzobon, N., Ronchese, P., Simonetto, F., Torassa, E., Tosi, M., Zanetti, M., Zotto, P., Zucchetta, A., Zumerle, G., Braghieri, A., Magnani, A., Montagna, P., Ratti, S. P., Re, V., Riccardi, C., Salvini, P., Vai, I., Vitulo, P., Alunni Solestizi, L., Bilei, G. M., Ciangottini, D., Fanò, L., Lariccia, P., Mantovani, G., Menichelli, M., Saha, A., Santocchia, A., Androsov, K., Azzurri, P., Bagliesi, G., Bernardini, J., Boccali, T., Castaldi, R., Ciocci, M. A., Dell’Orso, R., Donato, S., Massachusetts Institute of Technology. Department of Nuclear Science and Engineering, Massachusetts Institute of Technology. Department of Physics, Massachusetts Institute of Technology. Laboratory for Nuclear Science, Apyan, Aram, Barbieri, Richard Alexander, Baty, Austin Alan, Bierwagen, Katharina, Brandt, Stephanie Akemi, Busza, Wit, Cali, Ivan Amos, Demiragli, Zeynep, Di Matteo, Leonardo, Gomez-Ceballos, Guillelmo, Goncharov, Maxim, Gulhan, Doga Can, Iiyama, Yutaro, Innocenti, Gian Michele, Klute, Markus, Kovalskyi, Dmytro, Lai, Yue Shi, Lee, Youjin, Levin, Andrew Michael, Luckey Jr, P David, Marini, Andrea Carlo, McGinn, Christopher Francis, Mironov, Camelia Maria, Narayanan, Siddharth Madhavan, Niu, Xinmei, Paus, Christoph M. E., Ralph, Duncan Kelley, Roland, Christof E, Roland, Gunther M, Salfeld-Nebgen, Jakob Maxillian Henry, Stephans, George S. F., Sumorok, Konstanty C, Varma, Mukund Madhav, Velicanu, Dragos Alexandru, Veverka, Jan, Wang, Jing, Wang, Ta-Wei, Wyslouch, Boleslaw, Yang, Ming, Wyslouch, Victoria, Khachatryan, V., Sirunyan, A. M., Tumasyan, A., Adam, W., Asilar, E., Bergauer, T., Brandstetter, J., Brondolin, E., Dragicevic, M., Erö, J., Flechl, M., Friedl, M., Frühwirth, R., Ghete, V. M., Hartl, C., Hörmann, N., Hrubec, J., Jeitler, M., Knünz, V., König, A., Krammer, M., Krätschmer, I., Liko, D., Matsushita, T., Mikulec, I., Rabady, D., Rahbaran, B., Rohringer, H., Schieck, J., Schöfbeck, R., Strauss, J., Treberer-Treberspurg, W., Waltenberger, W., Wulz, C.-E., Mossolov, V., Shumeiko, N., Suarez Gonzalez, J., Alderweireldt, S., Cornelis, T., De Wolf, E. A., Janssen, X., Knutsson, A., Lauwers, J., Luyckx, S., Van De Klundert, M., Van Haevermaet, H., Van Mechelen, P., Van Remortel, N., Van Spilbeeck, A., Abu Zeid, S., Blekman, F., D’Hondt, J., Daci, N., De Bruyn, I., Deroover, K., Heracleous, N., Keaveney, J., Lowette, S., Moreels, L., Olbrechts, A., Python, Q., Strom, D., Tavernier, S., Van Doninck, W., Van Mulders, P., Van Onsem, G. P., Van Parijs, I., Barria, P., Brun, H., Caillol, C., Clerbaux, B., De Lentdecker, G., Fasanella, G., Favart, L., Grebenyuk, A., Karapostoli, G., Lenzi, T., Léonard, A., Maerschalk, T., Marinov, A., Perniè, L., Randle-conde, A., Seva, T., Vander Velde, C., Vanlaer, P., Yonamine, R., Zenoni, F., Zhang, F., Beernaert, K., Benucci, L., Cimmino, A., Crucy, S., Dobur, D., Fagot, A., Garcia, G., Gul, M., Mccartin, J., Ocampo Rios, A. A., Poyraz, D., Ryckbosch, D., Salva, S., Sigamani, M., Tytgat, M., Van Driessche, W., Yazgan, E., Zaganidis, N., Basegmez, S., Beluffi, C., Bondu, O., Brochet, S., Bruno, G., Caudron, A., Ceard, L., Da Silveira, G. G., Delaere, C., Favart, D., Forthomme, L., Giammanco, A., Hollar, J., Jafari, A., Jez, P., Komm, M., Lemaitre, V., Mertens, A., Musich, M., Nuttens, C., Perrini, L., Pin, A., Piotrzkowski, K., Popov, A., Quertenmont, L., Selvaggi, M., Vidal Marono, M., Beliy, N., Hammad, G. H., Aldá Júnior, W. L., Alves, F. L., Alves, G. A., Brito, L., Correa Martins Junior, M., Hamer, M., Hensel, C., Mora Herrera, C., Moraes, A., Pol, M. E., Rebello Teles, P., Belchior Batista Das Chagas, E., Carvalho, W., Chinellato, J., Custódio, A., Da Costa, E. M., De Jesus Damiao, D., De Oliveira Martins, C., Fonseca De Souza, S., Huertas Guativa, L. M., Malbouisson, H., Matos Figueiredo, D., Mundim, L., Nogima, H., Prado Da Silva, W. L., Santoro, A., Sznajder, A., Tonelli Manganote, E. J., Vilela Pereira, A., Ahuja, S., Bernardes, C. A., De Souza Santos, A., Dogra, S., Tomei, Fernandez Perez T. R., Gregores, E. M., Mercadante, P. G., Moon, C. S., Novaes, S. F., Padula, Sandra S., Romero Abad, D., Ruiz Vargas, J. C., Aleksandrov, A., Hadjiiska, R., Iaydjiev, P., Rodozov, M., Stoykova, S., Sultanov, G., Vutova, M., Dimitrov, A., Glushkov, I., Litov, L., Pavlov, B., Petkov, P., Ahmad, M., Bian, J. G., Chen, G. M., Chen, H. S., Chen, M., Cheng, T., Du, R., Jiang, C. H., Plestina, R., Romeo, F., Shaheen, S. M., Spiezia, A., Tao, J., Wang, C., Wang, Z., Zhang, H., Asawatangtrakuldee, C., Ban, Y., Li, Q., Liu, S., Mao, Y., Qian, S. J., Wang, D., Xu, Z., Avila, C., Cabrera, A., Chaparro Sierra, L. F., Florez, C., Gomez, J. P., Gomez Moreno, B., Sanabria, J. C., Godinovic, N., Lelas, D., Puljak, I., Ribeiro Cipriano, P. M., Antunovic, Z., Kovac, M., Brigljevic, V., Kadija, K., Luetic, J., Micanovic, S., Sudic, L., Attikis, A., Mavromanolakis, G., Mousa, J., Nicolaou, C., Ptochos, F., Razis, P. A., Rykaczewski, H., Bodlak, M., Finger, M., Assran, Y., Elgammal, S., Ellithi Kamel, A., Mahmoud, M. A., Mohammed, Y., Calpas, B., Kadastik, M., Murumaa, M., Raidal, M., Tiko, A., Veelken, C., Eerola, P., Pekkanen, J., Voutilainen, M., Härkönen, J., Karimäki, V., Kinnunen, R., Lampén, T., Lassila-Perini, K., Lehti, S., Lindén, T., Luukka, P., Mäenpää, T., Peltola, T., Tuominen, E., Tuominiemi, J., Tuovinen, E., Wendland, L., Talvitie, J., Tuuva, T., Besancon, M., Couderc, F., Dejardin, M., Denegri, D., Fabbro, B., Faure, J. L., Favaro, C., Ferri, F., Ganjour, S., Givernaud, A., Gras, P., Hamel de Monchenault, G., Jarry, P., Locci, E., Machet, M., Malcles, J., Rander, J., Rosowsky, A., Titov, M., Zghiche, A., Antropov, I., Baffioni, S., Beaudette, F., Busson, P., Cadamuro, L., Chapon, E., Charlot, C., Dahms, T., Davignon, O., Filipovic, N., Granier de Cassagnac, R., Jo, M., Lisniak, S., Mastrolorenzo, L., Miné, P., Naranjo, I. N., Nguyen, M., Ochando, C., Ortona, G., Paganini, P., Pigard, P., Regnard, S., Salerno, R., Sauvan, Sirois, Y., Strebler, T., Yilmaz, Y., Zabi, A., Agram, J.-L., Andrea, J., Aubin, A., Bloch, D., Brom, J.-M., Buttignol, M., Chabert, E. C., Chanon, N., Collard, C., Conte, E., Coubez, X., Fontaine, J.-C., Gelé, D., Goerlach, U., Goetzmann, C., Le Bihan, A.-C., Merlin, J. A., Skovpen, K., Van Hove, P., Gadrat, S., Beauceron, S., Bernet, C., Boudoul, G., Bouvier, E., Carrillo Montoya, C. A., Chierici, R., Contardo, D., Courbon, B., Depasse, P., El Mamouni, H., Fan, J., Fay, J., Gascon, S., Gouzevitch, M., Ille, B., Lagarde, F., Laktineh, I. B., Lethuillier, M., Mirabito, L., Pequegnot, A. L., Perries, S., Ruiz Alvarez, J. D., Sabes, D., Sgandurra, L., Sordini, V., Vander Donckt, M., Verdier, P., Viret, S., Toriashvili, T., Tsamalaidze, Z., Autermann, C., Beranek, S., Edelhoff, M., Feld, L., Heister, A., Kiesel, M. K., Klein, K., Lipinski, M., Ostapchuk, A., Preuten, M., Raupach, F., Schael, S., Schulte, J. F., Verlage, T., Weber, H., Wittmer, B., Zhukov, V., Ata, M., Brodski, M., Dietz-Laursonn, E., Duchardt, D., Endres, M., Erdmann, M., Erdweg, S., Esch, T., Fischer, R., Güth, A., Hebbeker, T., Heidemann, C., Hoepfner, K., Knutzen, S., Kreuzer, P., Merschmeyer, M., Meyer, A., Millet, P., Olschewski, M., Padeken, K., Papacz, P., Pook, T., Radziej, M., Reithler, H., Rieger, M., Scheuch, F., Sonnenschein, L., Teyssier, D., Thüer, S., Cherepanov, V., Erdogan, Y., Flügge, G., Geenen, H., Geisler, M., Hoehle, F., Kargoll, B., Kress, T., Kuessel, Y., Künsken, A., Lingemann, J., Nehrkorn, A., Nowack, A., Nugent, I. M., Pistone, C., Pooth, O., Stahl, A., Aldaya Martin, M., Asin, I., Bartosik, N., Behnke, O., Behrens, U., Bell, A. J., Borras, K., Burgmeier, A., Campbell, A., Choudhury, S., Costanza, F., Diez Pardos, C., Dolinska, G., Dooling, S., Dorland, T., Eckerlin, G., Eckstein, D., Eichhorn, T., Flucke, G., Gallo, E., Garay Garcia, J., Geiser, A., Gizhko, A., Gunnellini, P., Hauk, J., Hempel, M., Jung, H., Kalogeropoulos, A., Karacheban, O., Kasemann, M., Katsas, P., Kieseler, J., Kleinwort, C., Korol, I., Lange, W., Leonard, J., Lipka, K., Lobanov, A., Lohmann, W., Mankel, R., Marfin, I., Melzer-Pellmann, I.-A., Meyer, A. B., Mittag, G., Mnich, J., Mussgiller, A., Naumann-Emme, S., Nayak, A., Ntomari, E., Perrey, H., Pitzl, D., Placakyte, R., Raspereza, A., Roland, B., Sahin, M. Ö., Saxena, P., Schoerner-Sadenius, T., Schröder, M., Seitz, C., Spannagel, S., Trippkewitz, K. D., Walsh, R., Wissing, C., Blobel, V., Centis Vignali, M., Draeger, A. R., Erfle, J., Garutti, E., Goebel, K., Gonzalez, D., Görner, M., Haller, J., Hoffmann, M., Höing, R. S., Junkes, A., Klanner, R., Kogler, R., Kovalchuk, N., Lapsien, T., Lenz, T., Marchesini, I., Marconi, D., Meyer, M., Nowatschin, D., Ott, J., Pantaleo, F., Peiffer, T., Perieanu, A., Pietsch, N., Poehlsen, J., Rathjens, D., Sander, C., Scharf, C., Schettler, H., Schleper, P., Schlieckau, E., Schmidt, A., Schwandt, J., Sola, V., Stadie, H., Steinbrück, G., Tholen, H., Troendle, D., Usai, E., Vanelderen, L., Vanhoefer, A., Vormwald, B., Akbiyik, M., Barth, C., Baus, C., Berger, J., Böser, C., Butz, E., Chwalek, T., Colombo, F., De Boer, W., Descroix, A., Dierlamm, A., Fink, S., Frensch, F., Friese, R., Giffels, M., Gilbert, A., Haitz, D., Hartmann, F., Heindl, S. M., Husemann, U., Katkov, I., Kornmayer, A., Lobelle Pardo, P., Maier, B., Mildner, H., Mozer, M. U., Müller, T., Müller, Th., Plagge, M., Quast, G., Rabbertz, K., Röcker, S., Roscher, F., Sieber, G., Simonis, H. J., Stober, F. M., Ulrich, R., Wagner-Kuhr, J., Wayand, S., Weber, M., Weiler, T., Wöhrmann, C., Wolf, R., Anagnostou, G., Daskalakis, G., Geralis, T., Giakoumopoulou, V. A., Kyriakis, A., Loukas, D., Psallidas, A., Topsis-Giotis, I., Agapitos, A., Kesisoglou, S., Panagiotou, A., Saoulidou, N., Tziaferi, E., Evangelou, I., Flouris, G., Foudas, C., Kokkas, P., Loukas, N., Manthos, N., Papadopoulos, I., Paradas, E., Strologas, J., Bencze, G., Hajdu, C., Hazi, A., Hidas, P., Horvath, D., Sikler, F., Veszpremi, V., Vesztergombi, G., Zsigmond, A. J., Beni, N., Czellar, S., Karancsi, J., Molnar, J., Szillasi, Z., Bartók, M., Makovec, A., Raics, P., Trocsanyi, Z. L., Ujvari, B., Mal, P., Mandal, K., Sahoo, D. K., Sahoo, N., Swain, S. K., Bansal, S., Beri, S. B., Bhatnagar, V., Chawla, R., Gupta, R., Bhawandeep, U., Kalsi, A. K., Kaur, A., Kaur, M., Kumar, R., Mehta, A., Mittal, M., Singh, J. B., Walia, G., Kumar, Ashok, Bhardwaj, A., Choudhary, B. C., Garg, R. B., Kumar, A., Malhotra, S., Naimuddin, M., Nishu, N., Ranjan, K., Sharma, R., Sharma, V., Bhattacharya, S., Chatterjee, K., Dey, S., Dutta, S., Jain, Sa., Majumdar, N., Modak, A., Mondal, K., Mukherjee, S., Mukhopadhyay, S., Roy, A., Roy, D., Roy Chowdhury, S., Sarkar, S., Sharan, M., Abdulsalam, A., Chudasama, R., Dutta, D., Jha, V., Kumar, V., Mohanty, A. K., Pant, L. M., Shukla, P., Topkar, A., Aziz, T., Banerjee, S., Bhowmik, S., Chatterjee, R. M., Dewanjee, R. K., Dugad, S., Ganguly, S., Ghosh, S., Guchait, M., Gurtu, A., Kole, G., Kumar, S., Mahakud, B., Maity, M., Majumder, G., Mazumdar, K., Mitra, S., Mohanty, G. B., Parida, B., Sarkar, T., Sur, N., Sutar, B., Wickramage, N., Chauhan, S., Dube, S., Kothekar, K., Sharma, S., Bakhshiansohi, H., Behnamian, H., Etesami, S. M., Fahim, A., Goldouzian, R., Khakzad, M., Mohammadi Najafabadi, M., Naseri, M., Paktinat Mehdiabadi, S., Rezaei Hosseinabadi, F., Safarzadeh, B., Zeinali, M., Felcini, M., Grunewald, M., Abbrescia, M., Calabria, C., Caputo, C., Colaleo, A., Creanza, D., Cristella, L., De Filippis, N., De Palma, M., Fiore, L., Iaselli, G., Maggi, G., Maggi, M., Miniello, G., My, S., Nuzzo, S., Pompili, A., Pugliese, G., Radogna, R., Ranieri, A., Selvaggi, G., Silvestris, L., Venditti, R., Verwilligen, P., Abbiendi, G., Battilana, C., Benvenuti, A. C., Bonacorsi, D., Braibant-Giacomelli, S., Brigliadori, L., Campanini, R., Capiluppi, P., Castro, A., Cavallo, F. R., Chhibra, S. S., Codispoti, G., Cuffiani, M., Dallavalle, G. M., Fabbri, F., Fanfani, A., Fasanella, D., Giacomelli, P., Grandi, C., Guiducci, L., Marcellini, S., Masetti, G., Montanari, A., Navarria, F. L., Perrotta, A., Rossi, A. M., Rovelli, T., Siroli, G. P., Tosi, N., Travaglini, R., Cappello, G., Chiorboli, M., Costa, S., Di Mattia, A., Giordano, F., Potenza, R., Tricomi, A., Tuve, C., Barbagli, G., Ciulli, V., Civinini, C., D’Alessandro, R., Focardi, E., Gonzi, S., Gori, V., Lenzi, P., Meschini, M., Paoletti, S., Sguazzoni, G., Tropiano, A., Viliani, L., Benussi, L., Bianco, S., Piccolo, D., Primavera, F., Calvelli, V., Ferro, F., Lo Vetere, M., Monge, M. R., Robutti, E., Tosi, S., Brianza, L., Dinardo, M. E., Fiorendi, S., Gennai, S., Gerosa, R., Ghezzi, A., Govoni, P., Malvezzi, S., Manzoni, R. A., Marzocchi, B., Moroni, L., Paganoni, M., Pedrini, D., Ragazzi, S., Redaelli, N., Tabarelli de Fatis, T., Buontempo, S., Cavallo, N., Di Guida, S., Esposito, M., Fabozzi, F., Iorio, A. O. M., Lanza, G., Lista, L., Meola, S., Merola, M., Paolucci, P., Sciacca, C., Thyssen, F., Azzi, P., Bacchetta, N., Benato, L., Bisello, D., Boletti, A., Branca, A., Carlin, R., Checchia, P., Dall’Osso, M., Dorigo, T., Dosselli, U., Gasparini, F., Gasparini, U., Gozzelino, A., Kanishchev, K., Lacaprara, S., Margoni, M., Meneguzzo, A. T., Passaseo, M., Pazzini, J., Pozzobon, N., Ronchese, P., Simonetto, F., Torassa, E., Tosi, M., Zanetti, M., Zotto, P., Zucchetta, A., Zumerle, G., Braghieri, A., Magnani, A., Montagna, P., Ratti, S. P., Re, V., Riccardi, C., Salvini, P., Vai, I., Vitulo, P., Alunni Solestizi, L., Bilei, G. M., Ciangottini, D., Fanò, L., Lariccia, P., Mantovani, G., Menichelli, M., Saha, A., Santocchia, A., Androsov, K., Azzurri, P., Bagliesi, G., Bernardini, J., Boccali, T., Castaldi, R., Ciocci, M. A., Dell’Orso, R., and Donato, S.

Abstract

A search for evidence of particle dark matter (DM) and unparticle production at the LHC has been performed using events containing two charged leptons, consistent with the decay of a Z boson, and large missing transverse momentum. This study is based on data collected with the CMS detector corresponding to an integrated luminosity of 19.7 fb[superscript −1] of pp collisions at the LHC at a center-of-mass energy of 8 TeV. No significant excess of events is observed above the number expected from the standard model contributions. The results are interpreted in terms of 90% confidence level limits on the DM-nucleon scattering cross section, as a function of the DM particle mass, for both spin-dependent and spin-independent scenarios. Limits are set on the effective cutoff scale Λ, and on the annihilation rate for DM particles, assuming that their branching fraction to quarks is 100%. Additionally, the most stringent 95% confidence level limits to date on the unparticle model parameters are obtained.

Published
2017

23. Effect of Thermal Fluctuations on the Radiative Rate in Core/Shell Quantum Dots.

Author

Balan, Arunima D, Balan, Arunima D, Eshet, Hagai, Olshansky, Jacob H, Lee, Youjin V, Rabani, Eran, Alivisatos, A Paul, Balan, Arunima D, Balan, Arunima D, Eshet, Hagai, Olshansky, Jacob H, Lee, Youjin V, Rabani, Eran, and Alivisatos, A Paul

Abstract

The effect of lattice fluctuations and electronic excitations on the radiative rate is demonstrated in CdSe/CdS core/shell spherical quantum dots (QDs). Using a combination of time-resolved photoluminescence spectroscopy and atomistic simulations, we show that lattice fluctuations can change the radiative rate over the temperature range from 78 to 300 K. We posit that the presence of the core/shell interface plays a significant role in dictating this behavior. We show that the other major factor that underpins the change in radiative rate with temperature is the presence of higher energy states corresponding to electron excitation into the shell. These effects should be present in other core/shell samples and should also affect other excited state rates, such as the rate of Auger recombination or the rate of charge transfer.

Published
2017

24. Temperature-Dependent Hole Transfer from Photoexcited Quantum Dots to Molecular Species: Evidence for Trap-Mediated Transfer.

Author

Olshansky, Jacob H, Olshansky, Jacob H, Balan, Arunima D, Ding, Tina X, Fu, Xiao, Lee, Youjin V, Alivisatos, A Paul, Olshansky, Jacob H, Olshansky, Jacob H, Balan, Arunima D, Ding, Tina X, Fu, Xiao, Lee, Youjin V, and Alivisatos, A Paul

Abstract

The effect of temperature on the rate of hole transfer from photoexcited quantum dots (QDs) is investigated by measuring the driving force dependence of the charge transfer rate for different sized QDs across a range of temperatures from 78 to 300 K. Spherical CdSe/CdS core/shell QDs were used with a series of ferrocene-derived molecular hole acceptors with an 800 meV range in electrochemical potential. Time-resolved photoluminescence measurements and photoluminescence quantum yield measurements in an integrating sphere were both performed from 78 to 300 K to obtain temperature-dependent rates for a series of driving forces as dictated by the nature of the molecular acceptor. For both QD sizes studied and all ligands, the Arrhenius plot of hole transfer exhibited an activated (linear) regime at higher temperatures and a temperature-independent regime at low temperatures. The extracted activation energies in the high-temperature regime were consistent across all ligands for a given QD size. This observation is not consistent with direct charge transfer from the QD valence band to the ferrocene acceptor. Instead, a model in which charge transfer is mediated by a shallow and reversible trap more accurately fits the experimental results. Implications for this observed trap-mediated transfer are discussed including as a strategy to more efficiently extract charge from QDs.

Published
2017

25. Discovery of stimulation-responsive immune enhancers with CRISPR activation.

Author

Simeonov, Dimitre R, Simeonov, Dimitre R, Gowen, Benjamin G, Boontanrart, Mandy, Roth, Theodore L, Gagnon, John D, Mumbach, Maxwell R, Satpathy, Ansuman T, Lee, Youjin, Bray, Nicolas L, Chan, Alice Y, Lituiev, Dmytro S, Nguyen, Michelle L, Gate, Rachel E, Subramaniam, Meena, Li, Zhongmei, Woo, Jonathan M, Mitros, Therese, Ray, Graham J, Curie, Gemma L, Naddaf, Nicki, Chu, Julia S, Ma, Hong, Boyer, Eric, Van Gool, Frederic, Huang, Hailiang, Liu, Ruize, Tobin, Victoria R, Schumann, Kathrin, Daly, Mark J, Farh, Kyle K, Ansel, K Mark, Ye, Chun J, Greenleaf, William J, Anderson, Mark S, Bluestone, Jeffrey A, Chang, Howard Y, Corn, Jacob E, Marson, Alexander, Simeonov, Dimitre R, Simeonov, Dimitre R, Gowen, Benjamin G, Boontanrart, Mandy, Roth, Theodore L, Gagnon, John D, Mumbach, Maxwell R, Satpathy, Ansuman T, Lee, Youjin, Bray, Nicolas L, Chan, Alice Y, Lituiev, Dmytro S, Nguyen, Michelle L, Gate, Rachel E, Subramaniam, Meena, Li, Zhongmei, Woo, Jonathan M, Mitros, Therese, Ray, Graham J, Curie, Gemma L, Naddaf, Nicki, Chu, Julia S, Ma, Hong, Boyer, Eric, Van Gool, Frederic, Huang, Hailiang, Liu, Ruize, Tobin, Victoria R, Schumann, Kathrin, Daly, Mark J, Farh, Kyle K, Ansel, K Mark, Ye, Chun J, Greenleaf, William J, Anderson, Mark S, Bluestone, Jeffrey A, Chang, Howard Y, Corn, Jacob E, and Marson, Alexander

Abstract

The majority of genetic variants associated with common human diseases map to enhancers, non-coding elements that shape cell-type-specific transcriptional programs and responses to extracellular cues. Systematic mapping of functional enhancers and their biological contexts is required to understand the mechanisms by which variation in non-coding genetic sequences contributes to disease. Functional enhancers can be mapped by genomic sequence disruption, but this approach is limited to the subset of enhancers that are necessary in the particular cellular context being studied. We hypothesized that recruitment of a strong transcriptional activator to an enhancer would be sufficient to drive target gene expression, even if that enhancer was not currently active in the assayed cells. Here we describe a discovery platform that can identify stimulus-responsive enhancers for a target gene independent of stimulus exposure. We used tiled CRISPR activation (CRISPRa) to synthetically recruit a transcriptional activator to sites across large genomic regions (more than 100 kilobases) surrounding two key autoimmunity risk loci, CD69 and IL2RA. We identified several CRISPRa-responsive elements with chromatin features of stimulus-responsive enhancers, including an IL2RA enhancer that harbours an autoimmunity risk variant. Using engineered mouse models, we found that sequence perturbation of the disease-associated Il2ra enhancer did not entirely block Il2ra expression, but rather delayed the timing of gene activation in response to specific extracellular signals. Enhancer deletion skewed polarization of naive T cells towards a pro-inflammatory T helper (TH17) cell state and away from a regulatory T cell state. This integrated approach identifies functional enhancers and reveals how non-coding variation associated with human immune dysfunction alters context-specific gene programs.

Published
2017

26. Search for Supersymmetry in the Vector-Boson Fusion Topology in Proton-Proton Collisions √s = 8TeV

Author

Massachusetts Institute of Technology. Department of Physics, Massachusetts Institute of Technology. Laboratory for Nuclear Science, Apyan, Aram, Barbieri, Richard Alexander, Baty, Austin Alan, Bierwagen, Katharina, Brandt, Stephanie Akemi, Busza, Wit, Cali, Ivan Amos, Demiragli, Zeynep, Di Matteo, Leonardo, Gomez-Ceballos, Guillelmo, Goncharov, Maxim, Gulhan, Doga Can, Iiyama, Yutaro, Innocenti, Gian Michele, Klute, Markus, Kovalskyi, Dmytro, Lai, Yue Shi, Lee, Youjin, Levin, Amy Elizabeth, Luckey Jr, P David, McGinn, Christopher Francis, Mironov, Camelia Maria, Niu, Xinmei, Paus, Christoph M. E., Ralph, Duncan Kelley, Roland, Christof E, Roland, Gunther M, Salfeld-Nebgen, Jakob Maxillian Henry, Stephans, George S. F., Sumorok, Konstanty C, Varma, Mukund Madhav, Velicanu, Dragos Alexandru, Veverka, Jan, Wang, Jing, Wang, Ta-Wei, Wyslouch, Boleslaw, Yang, Ming, Wyslouch, Victoria, Massachusetts Institute of Technology. Department of Physics, Massachusetts Institute of Technology. Laboratory for Nuclear Science, Apyan, Aram, Barbieri, Richard Alexander, Baty, Austin Alan, Bierwagen, Katharina, Brandt, Stephanie Akemi, Busza, Wit, Cali, Ivan Amos, Demiragli, Zeynep, Di Matteo, Leonardo, Gomez-Ceballos, Guillelmo, Goncharov, Maxim, Gulhan, Doga Can, Iiyama, Yutaro, Innocenti, Gian Michele, Klute, Markus, Kovalskyi, Dmytro, Lai, Yue Shi, Lee, Youjin, Levin, Amy Elizabeth, Luckey Jr, P David, McGinn, Christopher Francis, Mironov, Camelia Maria, Niu, Xinmei, Paus, Christoph M. E., Ralph, Duncan Kelley, Roland, Christof E, Roland, Gunther M, Salfeld-Nebgen, Jakob Maxillian Henry, Stephans, George S. F., Sumorok, Konstanty C, Varma, Mukund Madhav, Velicanu, Dragos Alexandru, Veverka, Jan, Wang, Jing, Wang, Ta-Wei, Wyslouch, Boleslaw, Yang, Ming, and Wyslouch, Victoria

Published
2017

27. Single-Cell Genomics Unveils Critical Regulators of Th17 Cell Pathogenicity

Author

Institute for Medical Engineering and Science, Massachusetts Institute of Technology. Department of Biology, Massachusetts Institute of Technology. Department of Chemistry, Regev, Aviv, Shalek, Alexander K, Gaublomme, Jellert T., Yosef, Nir, Lee, Youjin, Gertner, Rona S., Yang, Li V., Wu, Chuan, Pandolfi, Pier Paolo, Mak, Tak, Satija, Rahul, Kuchroo, Vijay K., Park, Hongkun, Institute for Medical Engineering and Science, Massachusetts Institute of Technology. Department of Biology, Massachusetts Institute of Technology. Department of Chemistry, Regev, Aviv, Shalek, Alexander K, Gaublomme, Jellert T., Yosef, Nir, Lee, Youjin, Gertner, Rona S., Yang, Li V., Wu, Chuan, Pandolfi, Pier Paolo, Mak, Tak, Satija, Rahul, Kuchroo, Vijay K., and Park, Hongkun

Abstract

Extensive cellular heterogeneity exists within specific immune-cell subtypes classified as a single lineage, but its molecular underpinnings are rarely characterized at a genomic scale. Here, we use single-cell RNA-seq to investigate the molecular mechanisms governing heterogeneity and pathogenicity of Th17 cells isolated from the central nervous system (CNS) and lymph nodes (LN) at the peak of autoimmune encephalomyelitis (EAE) or differentiated in vitro under either pathogenic or non-pathogenic polarization conditions. Computational analysis relates a spectrum of cellular states in vivo to in vitro differentiated Th17 cells, and unveils genes governing pathogenicity and disease susceptibility. Using knockout mice, we validate four new genes: Gpr65, Plzp, Toso and Cd5l (in a companion paper). Cellular heterogeneity thus informs Th17 function in autoimmunity, and can identify targets for selective suppression of pathogenic Th17 cells while potentially sparing non-pathogenic tissue-protective ones, National Institutes of Health (U.S.) (Grant P50 HG006193), National Cancer Institute (U.S.) (David H. Koch Institute for Integrative Cancer Research at MIT. Grant P30-CA14051), Klarman Cell Observatory

Published
2016

29. YouJin Lee, cello

Author

Lee, YouJin; Kim, Soojin, Ball State University. School of Music, Lee, YouJin; Kim, Soojin, and Ball State University. School of Music

Abstract

With Soojin Kim, piano.; This recital is presented in partial fulfillment of the requirements for the Artist Diploma in music performance.; Includes a list of upcoming BSU School of Music events (for April 2015)., Series LXIX, Number 243., This archival material has been provided for educational purposes. Ball State University Libraries recognizes that some historic items may include offensive content. Our statement regarding objectionable content is available at: https://dmr.bsu.edu/digital/about

Published
2015

31. Altered cofactor regulation with disease-associated p97/VCP mutations.

Author

Zhang, Xiaoyi, Zhang, Xiaoyi, Gui, Lin, Zhang, Xiaoyan, Bulfer, Stacie L, Sanghez, Valentina, Wong, Daniel E, Lee, YouJin, Lehmann, Lynn, Lee, James Siho, Shih, Pei-Yin, Lin, Henry J, Iacovino, Michelina, Weihl, Conrad C, Arkin, Michelle R, Wang, Yanzhuang, Chou, Tsui-Fen, Zhang, Xiaoyi, Zhang, Xiaoyi, Gui, Lin, Zhang, Xiaoyan, Bulfer, Stacie L, Sanghez, Valentina, Wong, Daniel E, Lee, YouJin, Lehmann, Lynn, Lee, James Siho, Shih, Pei-Yin, Lin, Henry J, Iacovino, Michelina, Weihl, Conrad C, Arkin, Michelle R, Wang, Yanzhuang, and Chou, Tsui-Fen

Abstract

Dominant mutations in p97/VCP (valosin-containing protein) cause a rare multisystem degenerative disease with varied phenotypes that include inclusion body myopathy, Paget's disease of bone, frontotemporal dementia, and amyotrophic lateral sclerosis. p97 disease mutants have altered N-domain conformations, elevated ATPase activity, and altered cofactor association. We have now discovered a previously unidentified disease-relevant functional property of p97 by identifying how the cofactors p37 and p47 regulate p97 ATPase activity. We define p37 as, to our knowledge, the first known p97-activating cofactor, which enhances the catalytic efficiency (kcat/Km) of p97 by 11-fold. Whereas both p37 and p47 decrease the Km of ATP in p97, p37 increases the kcat of p97. In contrast, regulation by p47 is biphasic, with decreased kcat at low levels but increased kcat at higher levels. By deleting a region of p47 that lacks homology to p37 (amino acids 69-92), we changed p47 from an inhibitory cofactor to an activating cofactor, similar to p37. Our data suggest that cofactors regulate p97 ATPase activity by binding to the N domain. Induced conformation changes affect ADP/ATP binding at the D1 domain, which in turn controls ATPase cycling. Most importantly, we found that the D2 domain of disease mutants failed to be activated by p37 or p47. Our results show that cofactors play a critical role in controlling p97 ATPase activity, and suggest that lack of cofactor-regulated communication may contribute to p97-associated disease pathogenesis.

Published
2015

32. YouJin Lee, cello

Author

Lee, YouJin; Kim, Soojin, Ball State University. School of Music, Lee, YouJin; Kim, Soojin, and Ball State University. School of Music

Abstract

With Soojin Kim, piano.; This recital is presented in partial fulfillment of the requirements for the Artist Diploma in music performance.; Includes a list of upcoming BSU School of Music events (for April 2015)., Series LXIX, Number 243., This archival material has been provided for educational purposes. Ball State University Libraries recognizes that some historic items may include offensive content. Our statement regarding objectionable content is available at: https://dmr.bsu.edu/digital/about

Published
2015

33. Moon-Sook Park, soprano

Author

Park, Moon-Sook; Kim, Soojin; Lee, YouJin, Ball State University. School of Music, Park, Moon-Sook; Kim, Soojin; Lee, YouJin, and Ball State University. School of Music

Abstract

With Soojin Kim, piano, Youjin Lee, cello.; Includes biographical information about educator & vocalist Moon-Sook Park.; Includes a list of upcoming BSU School of Music events (for September 2014-October 2014)., Series LXIX, Number 21., This archival material has been provided for educational purposes. Ball State University Libraries recognizes that some historic items may include offensive content. Our statement regarding objectionable content is available at: https://dmr.bsu.edu/digital/about

Published
2014

34. SooJin Lee, soprano

Author

Lee, Soojin; Hwang, Hyunyoung; Madsen, Kirsten; Rouch, Robert; Lee, YouJin, Ball State University. School of Music, Lee, Soojin; Hwang, Hyunyoung; Madsen, Kirsten; Rouch, Robert; Lee, YouJin, and Ball State University. School of Music

Abstract

With Hyunyoung Hwang, piano, Kirsten Madsen, oboe, Robert Rouch, harpsichord, You Jin Lee, cello.; This recital is presented in partial fulfillment of the requirements for the Artist Diploma in Music Performance., Series LXVIII, Number 263., This archival material has been provided for educational purposes. Ball State University Libraries recognizes that some historic items may include offensive content. Our statement regarding objectionable content is available at: https://dmr.bsu.edu/digital/about

Published
2014

35. General recital hour

Author

McGee, Angela; Graham, Anna Marie; Luzadder, Samantha; Aichinger, Skylar; Bischoff, Ryan; Johns, Nicholas; Moore, Evan; Wells, Philipp; Chapman, Cory; Dunbar, Alex; Lee, Soojin; Rouch, Robert; Madsen, Kirsten; Lee, YouJin, Ball State University. School of Music, McGee, Angela; Graham, Anna Marie; Luzadder, Samantha; Aichinger, Skylar; Bischoff, Ryan; Johns, Nicholas; Moore, Evan; Wells, Philipp; Chapman, Cory; Dunbar, Alex; Lee, Soojin; Rouch, Robert; Madsen, Kirsten; Lee, YouJin, and Ball State University. School of Music

Abstract

With Angela McGee, harp, Anna Marie Graham, marimba, Samantha Luzadder, marimba, Skylar Aichinger, tuba, Ryan Bischoff, percussion, Nicholas Johns, percussion, Evan Moore, percussion, Philipp Wells, percussion, Cory Chapman, percussion, Alex Dunbar, percussion, Soojin Lee, soprano, Robert Rouch, harpsichord, Kirsten Madsen, oboe, Youjin Lee, cello.; Includes a list of upcoming BSU School of Music events (for Apr. 2014)., Series LXVIII, Number 210., This archival material has been provided for educational purposes. Ball State University Libraries recognizes that some historic items may include offensive content. Our statement regarding objectionable content is available at: https://dmr.bsu.edu/digital/about

Published
2014

36. YouJin Lee, cello

Author

Lee, YouJin; Kim, Soojin, Ball State University. School of Music, Lee, YouJin; Kim, Soojin, and Ball State University. School of Music

Abstract

With Soojin Kim, piano.; This recital is presented in partial fulfillment of the requirements for the Artist Diploma in music performance.; Includes a list of upcoming BSU School of Music events (for November 2014)., Series LXIX, Number 68., This archival material has been provided for educational purposes. Ball State University Libraries recognizes that some historic items may include offensive content. Our statement regarding objectionable content is available at: https://dmr.bsu.edu/digital/about

Published
2014

37. General recital hour

Author

McGee, Angela; Graham, Anna Marie; Luzadder, Samantha; Aichinger, Skylar; Bischoff, Ryan; Johns, Nicholas; Moore, Evan; Wells, Philipp; Chapman, Cory; Dunbar, Alex; Lee, Soojin; Rouch, Robert; Madsen, Kirsten; Lee, YouJin, Ball State University. School of Music, McGee, Angela; Graham, Anna Marie; Luzadder, Samantha; Aichinger, Skylar; Bischoff, Ryan; Johns, Nicholas; Moore, Evan; Wells, Philipp; Chapman, Cory; Dunbar, Alex; Lee, Soojin; Rouch, Robert; Madsen, Kirsten; Lee, YouJin, and Ball State University. School of Music

Abstract

With Angela McGee, harp, Anna Marie Graham, marimba, Samantha Luzadder, marimba, Skylar Aichinger, tuba, Ryan Bischoff, percussion, Nicholas Johns, percussion, Evan Moore, percussion, Philipp Wells, percussion, Cory Chapman, percussion, Alex Dunbar, percussion, Soojin Lee, soprano, Robert Rouch, harpsichord, Kirsten Madsen, oboe, Youjin Lee, cello.; Includes a list of upcoming BSU School of Music events (for Apr. 2014)., Series LXVIII, Number 210., This archival material has been provided for educational purposes. Ball State University Libraries recognizes that some historic items may include offensive content. Our statement regarding objectionable content is available at: https://dmr.bsu.edu/digital/about

Published
2014

38. YouJin Lee, cello

Author

Lee, YouJin; Kim, Soojin, Ball State University. School of Music, Lee, YouJin; Kim, Soojin, and Ball State University. School of Music

Abstract

With Soojin Kim, piano.; This recital is presented in partial fulfillment of the requirements for the Artist Diploma in music performance.; Includes a list of upcoming BSU School of Music events (for November 2014)., Series LXIX, Number 68., This archival material has been provided for educational purposes. Ball State University Libraries recognizes that some historic items may include offensive content. Our statement regarding objectionable content is available at: https://dmr.bsu.edu/digital/about

Published
2014

39. Moon-Sook Park, soprano

Author

Park, Moon-Sook; Kim, Soojin; Lee, YouJin, Ball State University. School of Music, Park, Moon-Sook; Kim, Soojin; Lee, YouJin, and Ball State University. School of Music

Abstract

With Soojin Kim, piano, Youjin Lee, cello.; Includes biographical information about educator & vocalist Moon-Sook Park.; Includes a list of upcoming BSU School of Music events (for September 2014-October 2014)., Series LXIX, Number 21., This archival material has been provided for educational purposes. Ball State University Libraries recognizes that some historic items may include offensive content. Our statement regarding objectionable content is available at: https://dmr.bsu.edu/digital/about

Published
2014

40. SooJin Lee, soprano

Author

Lee, Soojin; Hwang, Hyunyoung; Madsen, Kirsten; Rouch, Robert; Lee, YouJin, Ball State University. School of Music, Lee, Soojin; Hwang, Hyunyoung; Madsen, Kirsten; Rouch, Robert; Lee, YouJin, and Ball State University. School of Music

Abstract

With Hyunyoung Hwang, piano, Kirsten Madsen, oboe, Robert Rouch, harpsichord, You Jin Lee, cello.; This recital is presented in partial fulfillment of the requirements for the Artist Diploma in Music Performance., Series LXVIII, Number 263., This archival material has been provided for educational purposes. Ball State University Libraries recognizes that some historic items may include offensive content. Our statement regarding objectionable content is available at: https://dmr.bsu.edu/digital/about

Published
2014

41. M13-templated magnetic nanoparticles for targeted in vivo imaging of prostate cancer

Author

Massachusetts Institute of Technology. Department of Biological Engineering, Massachusetts Institute of Technology. Department of Materials Science and Engineering, Koch Institute for Integrative Cancer Research at MIT, Ghosh, Debadyuti, Lee, Youjin, Kohli, Aditya G., Yun, Dong Soo, Belcher, Angela M., Thomas, Stephanie, Kelly, Kimberly A., Belcher, Angela M, Massachusetts Institute of Technology. Department of Biological Engineering, Massachusetts Institute of Technology. Department of Materials Science and Engineering, Koch Institute for Integrative Cancer Research at MIT, Ghosh, Debadyuti, Lee, Youjin, Kohli, Aditya G., Yun, Dong Soo, Belcher, Angela M., Thomas, Stephanie, Kelly, Kimberly A., and Belcher, Angela M

Abstract

Molecular imaging allows clinicians to visualize the progression of tumours and obtain relevant information for patient diagnosis and treatment1. Owing to their intrinsic optical, electrical and magnetic properties, nanoparticles are promising contrast agents for imaging dynamic molecular and cellular processes such as protein–protein interactions, enzyme activity or gene expression2. Until now, nanoparticles have been engineered with targeting ligands such as antibodies and peptides to improve tumour specificity and uptake. However, excessive loading of ligands can reduce the targeting capabilities of the ligand3, 4, 5 and reduce the ability of the nanoparticle to bind to a finite number of receptors on cells6. Increasing the number of nanoparticles delivered to cells by each targeting molecule would lead to higher signal-to-noise ratios and would improve image contrast. Here, we show that M13 filamentous bacteriophage can be used as a scaffold to display targeting ligands and multiple nanoparticles for magnetic resonance imaging of cancer cells and tumours in mice. Monodisperse iron oxide magnetic nanoparticles assemble along the M13 coat, and its distal end is engineered to display a peptide that targets SPARC glycoprotein, which is overexpressed in various cancers. Compared with nanoparticles that are directly functionalized with targeting peptides, our approach improves contrast because each SPARC-targeting molecule delivers a large number of nanoparticles into the cells. Moreover, the targeting ligand and nanoparticles could be easily exchanged for others, making this platform attractive for in vivo high-throughput screening and molecular detection., National Institutes of Health (U.S.) (NIH Center for Cancer Nanotechnology Excellence U54-CA151884), National Institutes of Health (U.S.) (NIH NCI RO1 CA137071)

Published
2014

42. Virus-templated Au and Au–Pt core–shell nanowires and their electrocatalytic activities for fuel cell applications

Author

Massachusetts Institute of Technology. Department of Biological Engineering, Massachusetts Institute of Technology. Department of Materials Science and Engineering, Massachusetts Institute of Technology. Department of Mechanical Engineering, Lee, Youjin, Kim, Junhyung, Yun, Dong Soo, Nam, Yoon Sung, Shao-Horn, Yang, Belcher, Angela M., Massachusetts Institute of Technology. Department of Biological Engineering, Massachusetts Institute of Technology. Department of Materials Science and Engineering, Massachusetts Institute of Technology. Department of Mechanical Engineering, Lee, Youjin, Kim, Junhyung, Yun, Dong Soo, Nam, Yoon Sung, Shao-Horn, Yang, and Belcher, Angela M.

Abstract

A facile synthetic route was developed to make Au nanowires (NWs) from surfactant-mediated bio-mineralization of a genetically engineered M13 phage with specific Au binding peptides. From the selective interaction between Au binding M13 phage and Au ions in aqueous solution, Au NWs with uniform diameter were synthesized at room temperature with yields greater than 98% without the need for size selection. The diameters of Au NWs were controlled from 10 nm to 50 nm. The Au NWs were found to be active for electrocatalytic oxidation of CO molecules for all sizes, where the activity was highly dependent on the surface facets of Au NWs. This low-temperature high yield method of preparing Au NWs was further extended to the synthesis of Au–Pt core–shell NWs with controlled coverage of Pt shell layers. Electro-catalytic studies of ethanol oxidation with different Pt loading showed enhanced activity relative to a commercial supported Pt catalyst, indicative of the dual functionality of Pt for the ethanol oxidation and Au for the anti-poisoning component of Pt. These new one-dimensional noble metal NWs with controlled compositions could facilitate the design of new alloy materials with tunable properties., United States. Army Research Office (Institute for Collaborative Biotechnologies, grant W911NF-09-0001), National Science Foundation (U.S.) (MRSEC Program, award no. DMR–0819762), Samsung (Firm) (Samsung Foundation of Culture, Samsung Scholarship)

Published
2014

43. Dynamic regulatory network controlling TH17 cell differentiation

Author

move to dc.description.sponsorship, Massachusetts Institute of Technology. Department of Biology, Regev, Aviv, Lu, Diana, Yosef, Nir, Shalek, Alex K., Gaublomme, Jellert T., Jin, Hulin, Lee, Youjin, Awasthi, Amit, Wu, Chuan, Karwacz, Katarzyna, Xiao, Sheng, Jorgolli, Marsela, Gennert, David, Satija, Rahul, Shakya, Arvind, Trombetta, John J., Pillai, Meenu R., Ratcliffe, Peter J., Coleman, Mathew L., Bix, Mark, Tantin, Dean, Park, Hongkun, Kuchroo, Vijay K., move to dc.description.sponsorship, Massachusetts Institute of Technology. Department of Biology, Regev, Aviv, Lu, Diana, Yosef, Nir, Shalek, Alex K., Gaublomme, Jellert T., Jin, Hulin, Lee, Youjin, Awasthi, Amit, Wu, Chuan, Karwacz, Katarzyna, Xiao, Sheng, Jorgolli, Marsela, Gennert, David, Satija, Rahul, Shakya, Arvind, Trombetta, John J., Pillai, Meenu R., Ratcliffe, Peter J., Coleman, Mathew L., Bix, Mark, Tantin, Dean, Park, Hongkun, and Kuchroo, Vijay K.

Abstract

Despite their importance, the molecular circuits that control the differentiation of naive T cells remain largely unknown. Recent studies that reconstructed regulatory networks in mammalian cells have focused on short-term responses and relied on perturbation-based approaches that cannot be readily applied to primary T cells. Here we combine transcriptional profiling at high temporal resolution, novel computational algorithms, and innovative nanowire-based perturbation tools to systematically derive and experimentally validate a model of the dynamic regulatory network that controls the differentiation of mouse T[subscript H]17 cells, a proinflammatory T-cell subset that has been implicated in the pathogenesis of multiple autoimmune diseases. The T[subscript H]17 transcriptional network consists of two self-reinforcing, but mutually antagonistic, modules, with 12 novel regulators, the coupled action of which may be essential for maintaining the balance between T[subscript H]17 and other CD4[superscript +] T-cell subsets. Our study identifies and validates 39 regulatory factors, embeds them within a comprehensive temporal network and reveals its organizational principles; it also highlights novel drug targets for controlling T[subscript H]17 cell differentiation., National Human Genome Research Institute (U.S.) (1P50HG006193-01), National Institutes of Health (U.S.). Pioneer Award (DP1OD003958-01), Howard Hughes Medical Institute, Klarman Cell Observatory

Published
2013

44. Dynamic regulatory network controlling TH17 cell differentiation

Author

Massachusetts Institute of Technology. Department of Biology, Regev, Aviv, Lu, Diana, Yosef, Nir, Shalek, Alex K., Gaublomme, Jellert T., Jin, Hulin, Lee, Youjin, Awasthi, Amit, Wu, Chuan, Karwacz, Katarzyna, Xiao, Sheng, Jorgolli, Marsela, Gennert, David, Satija, Rahul, Shakya, Arvind, Trombetta, John J., Pillai, Meenu R., Ratcliffe, Peter J., Coleman, Mathew L., Bix, Mark, Tantin, Dean, Park, Hongkun, Kuchroo, Vijay K., Massachusetts Institute of Technology. Department of Biology, Regev, Aviv, Lu, Diana, Yosef, Nir, Shalek, Alex K., Gaublomme, Jellert T., Jin, Hulin, Lee, Youjin, Awasthi, Amit, Wu, Chuan, Karwacz, Katarzyna, Xiao, Sheng, Jorgolli, Marsela, Gennert, David, Satija, Rahul, Shakya, Arvind, Trombetta, John J., Pillai, Meenu R., Ratcliffe, Peter J., Coleman, Mathew L., Bix, Mark, Tantin, Dean, Park, Hongkun, and Kuchroo, Vijay K.

Abstract

Despite their importance, the molecular circuits that control the differentiation of naive T cells remain largely unknown. Recent studies that reconstructed regulatory networks in mammalian cells have focused on short-term responses and relied on perturbation-based approaches that cannot be readily applied to primary T cells. Here we combine transcriptional profiling at high temporal resolution, novel computational algorithms, and innovative nanowire-based perturbation tools to systematically derive and experimentally validate a model of the dynamic regulatory network that controls the differentiation of mouse T[subscript H]17 cells, a proinflammatory T-cell subset that has been implicated in the pathogenesis of multiple autoimmune diseases. The T[subscript H]17 transcriptional network consists of two self-reinforcing, but mutually antagonistic, modules, with 12 novel regulators, the coupled action of which may be essential for maintaining the balance between T[subscript H]17 and other CD4[superscript +] T-cell subsets. Our study identifies and validates 39 regulatory factors, embeds them within a comprehensive temporal network and reveals its organizational principles; it also highlights novel drug targets for controlling T[subscript H]17 cell differentiation., National Human Genome Research Institute (U.S.) (1P50HG006193-01), National Institutes of Health (U.S.). Pioneer Award (DP1OD003958-01), Howard Hughes Medical Institute, Klarman Cell Observatory

Published
2013

45. Fabrication of 1-dimensional nanowires from genetically modified M13 phage through surfactant-mediated hybridization and the applications in medical diagnosis, energy devices, and catalysis

Author

Angela M. Belcher., Massachusetts Institute of Technology. Dept. of Materials Science and Engineering., Lee, Youjin, Angela M. Belcher., Massachusetts Institute of Technology. Dept. of Materials Science and Engineering., and Lee, Youjin

Abstract

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Materials Science and Engineering, 2010., Vita., Includes bibliographical references., Biological building blocks served as excellent templates for the preparation of various nano-materials due to their beneficial interactions at the molecular level. The bio-mineralization of genetically engineered M13 bacteriophage resulted in one-dimensional nanowires having outstanding properties in diverse applications. As a bridge between the chemical synthesis of nanostructures and the bio-mineralization of M13 phage, surfactant molecules were introduced to the biological systems. The specific affinity of M13 phage with Au-binding peptides was strong enough to attract Au ions despite the existence of surfactant molecules. Consequently, the surfactant-mediated bio-mineralization of M13 phage enabled us to precisely control the morphologies and structures in nanometer scale. The Au-binding M13 phage could also integrate other noble metals (Ag/Pt/Pd) to prepare homogeneous Au-based noble metal alloy nanowires in structures and compositions, and their electrochemical properties upon the systematic changes in compositions were investigated. Especially for the Au-Pt system, the catalytic activity study on the two distinct structures, the alloy and the core/shell, provided us important factors to design new catalysts with optimized activities., by Youjin Lee., Ph.D.

Published
2010

46. Fabrication of 1-dimensional nanowires from genetically modified M13 phage through surfactant-mediated hybridization and the applications in medical diagnosis, energy devices, and catalysis

Author

Angela M. Belcher., Massachusetts Institute of Technology. Dept. of Materials Science and Engineering., Lee, Youjin, Angela M. Belcher., Massachusetts Institute of Technology. Dept. of Materials Science and Engineering., and Lee, Youjin

Abstract

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Materials Science and Engineering, 2010., Vita., Includes bibliographical references., Biological building blocks served as excellent templates for the preparation of various nano-materials due to their beneficial interactions at the molecular level. The bio-mineralization of genetically engineered M13 bacteriophage resulted in one-dimensional nanowires having outstanding properties in diverse applications. As a bridge between the chemical synthesis of nanostructures and the bio-mineralization of M13 phage, surfactant molecules were introduced to the biological systems. The specific affinity of M13 phage with Au-binding peptides was strong enough to attract Au ions despite the existence of surfactant molecules. Consequently, the surfactant-mediated bio-mineralization of M13 phage enabled us to precisely control the morphologies and structures in nanometer scale. The Au-binding M13 phage could also integrate other noble metals (Ag/Pt/Pd) to prepare homogeneous Au-based noble metal alloy nanowires in structures and compositions, and their electrochemical properties upon the systematic changes in compositions were investigated. Especially for the Au-Pt system, the catalytic activity study on the two distinct structures, the alloy and the core/shell, provided us important factors to design new catalysts with optimized activities., by Youjin Lee., Ph.D.

Published
2010

47. Fabrication of 1-dimensional nanowires from genetically modified M13 phage through surfactant-mediated hybridization and the applications in medical diagnosis, energy devices, and catalysis

Author

Angela M. Belcher., Massachusetts Institute of Technology. Dept. of Materials Science and Engineering., Lee, Youjin, Angela M. Belcher., Massachusetts Institute of Technology. Dept. of Materials Science and Engineering., and Lee, Youjin

Abstract

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Materials Science and Engineering, 2010., Vita., Includes bibliographical references., Biological building blocks served as excellent templates for the preparation of various nano-materials due to their beneficial interactions at the molecular level. The bio-mineralization of genetically engineered M13 bacteriophage resulted in one-dimensional nanowires having outstanding properties in diverse applications. As a bridge between the chemical synthesis of nanostructures and the bio-mineralization of M13 phage, surfactant molecules were introduced to the biological systems. The specific affinity of M13 phage with Au-binding peptides was strong enough to attract Au ions despite the existence of surfactant molecules. Consequently, the surfactant-mediated bio-mineralization of M13 phage enabled us to precisely control the morphologies and structures in nanometer scale. The Au-binding M13 phage could also integrate other noble metals (Ag/Pt/Pd) to prepare homogeneous Au-based noble metal alloy nanowires in structures and compositions, and their electrochemical properties upon the systematic changes in compositions were investigated. Especially for the Au-Pt system, the catalytic activity study on the two distinct structures, the alloy and the core/shell, provided us important factors to design new catalysts with optimized activities., by Youjin Lee., Ph.D.

Published
2010

48. Fabrication of 1-dimensional nanowires from genetically modified M13 phage through surfactant-mediated hybridization and the applications in medical diagnosis, energy devices, and catalysis

Author

Angela M. Belcher., Massachusetts Institute of Technology. Dept. of Materials Science and Engineering., Lee, Youjin, Angela M. Belcher., Massachusetts Institute of Technology. Dept. of Materials Science and Engineering., and Lee, Youjin

Abstract

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Materials Science and Engineering, 2010., Vita., Includes bibliographical references., Biological building blocks served as excellent templates for the preparation of various nano-materials due to their beneficial interactions at the molecular level. The bio-mineralization of genetically engineered M13 bacteriophage resulted in one-dimensional nanowires having outstanding properties in diverse applications. As a bridge between the chemical synthesis of nanostructures and the bio-mineralization of M13 phage, surfactant molecules were introduced to the biological systems. The specific affinity of M13 phage with Au-binding peptides was strong enough to attract Au ions despite the existence of surfactant molecules. Consequently, the surfactant-mediated bio-mineralization of M13 phage enabled us to precisely control the morphologies and structures in nanometer scale. The Au-binding M13 phage could also integrate other noble metals (Ag/Pt/Pd) to prepare homogeneous Au-based noble metal alloy nanowires in structures and compositions, and their electrochemical properties upon the systematic changes in compositions were investigated. Especially for the Au-Pt system, the catalytic activity study on the two distinct structures, the alloy and the core/shell, provided us important factors to design new catalysts with optimized activities., by Youjin Lee., Ph.D.

Published
2010

49. Transcriptional signature of human pro-inflammatory TH17 cells identifies reduced IL10 gene expression in multiple sclerosis

Author

Hu, Dan, Notarbartolo, Samuele, Croonenborghs, Tom, Patel, Bonny, Cialic, Ron, Yang, Tun-Hsiang, Aschenbrenner, Dominik, Andersson, Karin M., Gattorno, Marco, Pham, Minh, Kivisakk, Pia, Pierre, Isabelle V., Lee, Youjin, Kiani, Karun, Bokarewa, Maria, Tjon, Emily, Pochet, Nathalie, Sallusto, Federica, Kuchroo, Vijay K., Weiner, Howard L., Hu, Dan, Notarbartolo, Samuele, Croonenborghs, Tom, Patel, Bonny, Cialic, Ron, Yang, Tun-Hsiang, Aschenbrenner, Dominik, Andersson, Karin M., Gattorno, Marco, Pham, Minh, Kivisakk, Pia, Pierre, Isabelle V., Lee, Youjin, Kiani, Karun, Bokarewa, Maria, Tjon, Emily, Pochet, Nathalie, Sallusto, Federica, Kuchroo, Vijay K., and Weiner, Howard L.

Abstract

We have previously reported the molecular signature of murine pathogenic TH17 cells that induce experimental autoimmune encephalomyelitis (EAE) in animals. Here we show that human peripheral blood IFN-γ+IL-17+ (TH1/17) and IFN-γ−IL-17+ (TH17) CD4+ T cells display distinct transcriptional profiles in high-throughput transcription analyses. Compared to TH17 cells, TH1/17 cells have gene signatures with marked similarity to mouse pathogenic TH17 cells. Assessing 15 representative signature genes in patients with multiple sclerosis, we find that TH1/17 cells have elevated expression of CXCR3 and reduced expression of IFNG, CCL3, CLL4, GZMB, and IL10 compared to healthy controls. Moreover, higher expression of IL10 in TH17 cells is found in clinically stable vs. active patients. Our results define the molecular signature of human pro-inflammatory TH17 cells, which can be used to both identify pathogenic TH17 cells and to measure the effect of treatment on TH17 cells in human autoimmune diseases.

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