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5,921 results on '"Neale, P."'

1. Debias your Large Multi-Modal Model at Test-Time with Non-Contrastive Visual Attribute Steering

Author

Ratzlaff, Neale, Olson, Matthew Lyle, Hinck, Musashi, Aflalo, Estelle, Tseng, Shao-Yen, Lal, Vasudev, and Howard, Phillip

Subjects
Computer Science - Computer Vision and Pattern Recognition, Computer Science - Machine Learning
Abstract

Large Multi-Modal Models (LMMs) have demonstrated impressive capabilities as general-purpose chatbots that can engage in conversations about a provided input, such as an image. However, their responses are influenced by societal biases present in their training datasets, leading to undesirable differences in how the model responds when presented with images depicting people of different demographics. In this work, we propose a novel debiasing framework for LMMs that directly removes biased representations during text generation to decrease outputs related to protected attributes, or even representing them internally. Our proposed method is training-free; given a single image and a list of target attributes, we can ablate the corresponding representations with just one step of gradient descent on the image itself. Our experiments show that not only can we can minimize the propensity of LMMs to generate text related to protected attributes, but we can improve sentiment and even simply use synthetic data to inform the ablation while retaining language modeling capabilities on real data such as COCO or FACET. Furthermore, we find the resulting generations from a debiased LMM exhibit similar accuracy as a baseline biased model, showing that debiasing effects can be achieved without sacrificing model performance., Comment: 10 pages, 3 Figures, 3 Tables. arXiv admin note: text overlap with arXiv:2410.13976

Published
2024

2. Assessing methods for telluric removal on atmospheric retrievals of high-resolution optical exoplanetary transmission spectra

Author

Maguire, Cathal, Sedaghati, Elyar, Gibson, Neale P., Smette, Alain, and Pino, Lorenzo

Subjects
Astrophysics - Earth and Planetary Astrophysics, Astrophysics - Instrumentation and Methods for Astrophysics
Abstract

Recent advancements in ultra-stable ground-based high-resolution spectrographs have propelled ground-based astronomy to the forefront of exoplanet detection and characterisation. Retrieving accurate atmospheric parameters depends on accurate modelling and removal of the telluric contamination while preserving the faint underlying exoplanet signal. There exist many methods to model telluric contamination, whether directly modelling the Earth's transmission spectrum via radiative transfer modelling, or using a principal component analysis (PCA)-like reconstruction to fit the time-invariant features of a spectrum. We aimed to assess the efficacy of these various telluric removal methods in preserving the underlying exoplanetary spectra. We compared two of the most common telluric modelling and removal methods, molecfit and the PCA-like algorithm SysRem, using planetary transmission spectra injected into three high-resolution optical observations taken with ESPRESSO. These planetary signals were injected at orbital periods of P = 2 days and 12 days, resulting in differing changes in radial velocity during transit. We then retrieved various injected atmospheric model parameters in order to determine the efficacy of the telluric removal methods. For the close-in, high velocity injected signal, we found that SysRem performed better for species that are also present in the Earth's atmosphere across each of the datasets. As we moved to slower moving signals at larger orbital separations, for one of the three datasets, SysRem dampened the planetary H$_2$O signal. In contrast, the H$_2$O signal was preserved for the telluric modelling method, molecfit. However, this behaviour was not ubiquitous across all three of the injected datasets, with another dataset showing a more precise H$_2$O/Fe ratio when preprocessed with SysRem., Comment: 25 pages, 23 figures, appendices included. Accepted for publication in A&A

Published
2024

3. Debiasing Large Vision-Language Models by Ablating Protected Attribute Representations

Author

Ratzlaff, Neale, Olson, Matthew Lyle, Hinck, Musashi, Tseng, Shao-Yen, Lal, Vasudev, and Howard, Phillip

Subjects
Computer Science - Computer Vision and Pattern Recognition, Computer Science - Computation and Language, Computer Science - Machine Learning
Abstract

Large Vision Language Models (LVLMs) such as LLaVA have demonstrated impressive capabilities as general-purpose chatbots that can engage in conversations about a provided input image. However, their responses are influenced by societal biases present in their training datasets, leading to undesirable differences in how the model responds when presented with images depicting people of different demographics. In this work, we propose a novel debiasing framework for LVLMs by directly ablating biased attributes during text generation to avoid generating text related to protected attributes, or even representing them internally. Our method requires no training and a relatively small amount of representative biased outputs (~1000 samples). Our experiments show that not only can we can minimize the propensity of LVLMs to generate text related to protected attributes, but we can even use synthetic data to inform the ablation while retaining captioning performance on real data such as COCO. Furthermore, we find the resulting generations from a debiased LVLM exhibit similar accuracy as a baseline biased model, showing that debiasing effects can be achieved without sacrificing model performance., Comment: NeurIPS workshop on SafeGenAI, 10 pages, 2 figures

Published
2024

4. Hot Rocks Survey I : A shallow eclipse for LHS 1478 b

Author

August, Prune C., Buchhave, Lars A., Diamond-Lowe, Hannah, Mendonça, João M., Gressier, Amélie, Rathcke, Alexander D., Allen, Natalie H., Fortune, Mark, Jones, Kathryn D., Meier-Valdés, Erik A., Demory, Brice-Olivier, Espinoza, Nestor, Fisher, Chloe E., Gibson, Neale P., Heng, Kevin, Hoeijmakers, Jens, Hooton, Matthew J., Kitzmann, Daniel, and Prinoth, Bibiana

Subjects
Astrophysics - Earth and Planetary Astrophysics
Abstract

M dwarf systems offer a unique opportunity to study terrestrial exoplanetary atmospheres due to their smaller size and cooler temperatures. However, due to the extreme conditions these host stars impose, it is unclear whether their small, close-in rocky planets are able to retain any atmosphere at all. The Hot Rocks Survey aims to answer this question by targeting nine different M dwarf rocky planets spanning a range of planetary and stellar properties. LHS 1478 b orbits an M3-type star, has an equilibrium temperature of Teq = 585 K and experiences an instellation 21 times greater than that of Earth. We observe two secondary eclipses using photometric imaging at 15 um using the Mid-Infrared Instrument on the James Webb Space Telescope (JWST MIRI) to measure thermal emission from the dayside of the planet. We then compare these values to different atmospheric scenarios to evaluate potential heat transport and CO2 absorption signatures. We find a secondary eclipse depth of 146 +/- 56 ppm based on the first observation, while the second observation results in a non-detection due to significantly larger unexplained systematics. Based on the first observation alone, we can reject the null hypothesis of the dark (zero Bond albedo) no atmosphere bare rock model with a confidence level of 3.4 sigma. For an airless body with a Bond albedo of A=0.2, the significance decreases to 2.9 sigma. The secondary eclipse depth is consistent with the majority of atmospheric scenarios we considered, which all involve atmospheres which include different concentrations of CO2, and surface pressures from 0.1 to 10 bar. However, we stress that the two observations from our program do not yield consistent results, and more observations are needed to verify our findings. The Hot Rocks Survey serves as a relevant primer for future endeavors such as the Director's Discretionary Time (DDT) Rocky Worlds program., Comment: Submitted to A&A

Published
2024

5. Searching for Neutral Hydrogen Escape from the 120 Myr Old Sub-Neptune HIP94235b using HST

Author

Morrissey, Ava, Zhou, George, Huang, Chelsea X., Wright, Duncan, Auger, Caitlin, Rockcliffe, Keighley E., Newton, Elisabeth R., Rogers, James G., Gibson, Neale, Lowson, Nataliea, Mayorga, Laura C., and Wittenmyer, Robert A.

Subjects
Astrophysics - Earth and Planetary Astrophysics
Abstract

HIP94235 b, a 120 Myr old sub-Neptune, provides us the unique opportunity to study mass loss at a pivotal stage of the system's evolution: the end of a 100 million year (Myr) old phase of intense XUV irradiation. We present two observations of HIP94235 b using the Hubble Space Telescope's Space Telescope Imaging Spectrograph (HST/STIS) in the Ly-alpha wavelength region. We do not observe discernible differences across either the blue and red wings of the Ly-alpha line profile in and out of transit, and report no significant detection of outflowing neutral hydrogen around the planet. We constrain the rate of neutral hydrogen escaping HIP94235 b to an upper limit of 10^13 g/s, which remains consistent with energy-limited model predictions of 10^11 g/s. The Ly-alpha non-detection is likely due to the extremely short photoionization timescale of the neutral hydrogen escaping the planet's atmosphere. This timescale, approximately 15 minutes, is significantly shorter than that of any other planets with STIS observations. Through energy-limited mass loss models, we anticipate that HIP94235 b will transition into a super-Earth within a timescale of 1 Gyr., Comment: Accepted for publication in AJ

Published
2024

6. High-resolution atmospheric retrievals of WASP-76b transmission spectroscopy with ESPRESSO: Monitoring limb asymmetries across multiple transits

Author

Maguire, Cathal, Gibson, Neale P., Nugroho, Stevanus K., Fortune, Mark, Ramkumar, Swaetha, Gandhi, Siddharth, and de Mooij, Ernst

Subjects
Astrophysics - Earth and Planetary Astrophysics
Abstract

Direct atmospheric retrievals of exoplanets at high-resolution have recently allowed for a more detailed characterisation of their chemistry and dynamics from the ground. By monitoring the longitudinal distribution of species, as well as the varying vertical temperature structure and dynamics between the limbs of WASP-76b, across multiple transits, we aim to enhance our understanding of the 3D nature and chemical/dynamical evolution of such objects over the timescales of months/years. We present retrievals of three VLT/ESPRESSO observations of the ultra-hot Jupiter WASP-76b, including one not yet reported in the literature, from which we constrain the atmospheric abundances, vertical temperature structure, and atmospheric dynamics for both the leading and trailing limbs of the atmosphere separately, via novel rotational broadening kernels. We confirm the presence of VO recently reported in the atmosphere of WASP-76b. We find a uniform longitudinal distribution of Fe and Mg across the limbs of the atmosphere, for each of our transits, consistent with previous works as well as with stellar values. We constrain substellar Na/Fe and Cr/Fe ratios across each of our transits, consistent with previous studies of WASP-76b. Where constrained, V/Fe and VO/Fe ratios were also found to be broadly consistent between the limbs of the atmosphere for each of the transits, as well as with previous studies. However, for two of the transits, both V and VO were unconstrained in the leading limb, suggesting possible depletion due to recombination and condensation. The consistency of our constraints across multiple high-resolution observations, as well as with previous studies using varying modelling/retrieval frameworks and/or instruments, affirms the efficacy of high-resolution ground-based retrievals of exoplanetary atmospheres., Comment: Accepted for publication in Astronomy & Astrophysics. 23 pages, 16 figures (including appendix)

Published
2024
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9. How do wavelength correlations affect transmission spectra? Application of a new fast and flexible 2D Gaussian process framework to transiting exoplanet spectroscopy

Author

Fortune, Mark, Gibson, Neale P., Foreman-Mackey, Daniel, Evans-Soma, Thomas M., Maguire, Cathal, and Ramkumar, Swaetha

Subjects
Astrophysics - Earth and Planetary Astrophysics, Astrophysics - Instrumentation and Methods for Astrophysics
Abstract

The use of Gaussian processes (GPs) is a common approach to account for correlated noise in exoplanet time series, particularly for transmission and emission spectroscopy. This analysis has typically been performed for each wavelength channel separately, with the retrieved uncertainties in the transmission spectrum assumed to be independent. However, the presence of noise correlated in wavelength could cause these uncertainties to be correlated, which could significantly affect the results of atmospheric retrievals. We present a method that uses a GP to model noise correlated in both wavelength and time simultaneously for the full spectroscopic dataset while avoiding the use of a 'common-mode' correction. To make this analysis computationally tractable, we introduce a new fast and flexible GP method that can analyse 2D datasets when the input points lie on a (potentially non-uniform) 2D grid - in our case a time by wavelength grid - and the kernel function has a Kronecker product structure. This simultaneously fits all light curves and enables the retrieval of the covariance matrix of the transmission spectrum. By testing on synthetic datasets, we demonstrate that our new approach can reliably recover atmospheric features contaminated by noise correlated in time and wavelength. In contrast, fitting each spectroscopic light curve separately performed poorly when wavelength-correlated noise was present. It frequently underestimated the uncertainty of the scattering slope and overestimated the uncertainty in the strength of sharp absorption peaks in transmission spectra. Two archival VLT/FORS2 transit observations of WASP-31b were re-analysed, with our method strongly constraining the presence of wavelength-correlated noise in both datasets and recovering significantly different constraints on atmospheric features such as the scattering slope and strength of sodium and potassium features., Comment: Language revised version accepted for publication in Astronomy & Astrophysics. 35 pages, 18 figures (including appendix)

Published
2024
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10. Nightside clouds and disequilibrium chemistry on the hot Jupiter WASP-43b

Author

Bell, Taylor J., Crouzet, Nicolas, Cubillos, Patricio E., Kreidberg, Laura, Piette, Anjali A. A., Roman, Michael T., Barstow, Joanna K., Blecic, Jasmina, Carone, Ludmila, Coulombe, Louis-Philippe, Ducrot, Elsa, Hammond, Mark, Mendonça, João M., Moses, Julianne I., Parmentier, Vivien, Stevenson, Kevin B., Teinturier, Lucas, Zhang, Michael, Batalha, Natalie M., Bean, Jacob L., Benneke, Björn, Charnay, Benjamin, Chubb, Katy L., Demory, Brice-Olivier, Gao, Peter, Lee, Elspeth K. H., López-Morales, Mercedes, Morello, Giuseppe, Rauscher, Emily, Sing, David K., Tan, Xianyu, Venot, Olivia, Wakeford, Hannah R., Aggarwal, Keshav, Ahrer, Eva-Maria, Alam, Munazza K., Baeyens, Robin, Barrado, David, Caceres, Claudio, Carter, Aarynn L., Casewell, Sarah L., Challener, Ryan C., Crossfield, Ian J. M., Decin, Leen, Désert, Jean-Michel, Dobbs-Dixon, Ian, Dyrek, Achrène, Espinoza, Néstor, Feinstein, Adina D., Gibson, Neale P., Harrington, Joseph, Helling, Christiane, Hu, Renyu, Iro, Nicolas, Kempton, Eliza M. -R., Kendrew, Sarah, Komacek, Thaddeus D., Krick, Jessica, Lagage, Pierre-Olivier, Leconte, Jérémy, Lendl, Monika, Lewis, Neil T., Lothringer, Joshua D., Malsky, Isaac, Mancini, Luigi, Mansfield, Megan, Mayne, Nathan J., Mikal-Evans, Thomas, Molaverdikhani, Karan, Nikolov, Nikolay K., Nixon, Matthew C., Palle, Enric, de la Roche, Dominique J. M. Petit dit, Piaulet, Caroline, Powell, Diana, Rackham, Benjamin V., Schneider, Aaron D., Steinrueck, Maria E., Taylor, Jake, Welbanks, Luis, Yurchenko, Sergei N., Zhang, Xi, and Zieba, Sebastian

Subjects
Astrophysics - Earth and Planetary Astrophysics, Astrophysics - Instrumentation and Methods for Astrophysics
Abstract

Hot Jupiters are among the best-studied exoplanets, but it is still poorly understood how their chemical composition and cloud properties vary with longitude. Theoretical models predict that clouds may condense on the nightside and that molecular abundances can be driven out of equilibrium by zonal winds. Here we report a phase-resolved emission spectrum of the hot Jupiter WASP-43b measured from 5-12 $\mu$m with JWST's Mid-Infrared Instrument (MIRI). The spectra reveal a large day-night temperature contrast (with average brightness temperatures of 1524$\pm$35 and 863$\pm$23 Kelvin, respectively) and evidence for water absorption at all orbital phases. Comparisons with three-dimensional atmospheric models show that both the phase curve shape and emission spectra strongly suggest the presence of nightside clouds which become optically thick to thermal emission at pressures greater than ~100 mbar. The dayside is consistent with a cloudless atmosphere above the mid-infrared photosphere. Contrary to expectations from equilibrium chemistry but consistent with disequilibrium kinetics models, methane is not detected on the nightside (2$\sigma$ upper limit of 1-6 parts per million, depending on model assumptions)., Comment: 61 pages, 13 figures, 4 tables. This preprint has been submitted to and accepted in principle for publication in Nature Astronomy without significant changes

Published
2024

11. Association of leukemic molecular profile with efficacy of inotuzumab ozogamicin in adults with relapsed/refractory ALL.

Author

Zhao, Yaqi, Laird, A, Roberts, Kathryn, Yafawi, Rolla, Kantarjian, Hagop, DeAngelo, Daniel, Stelljes, Matthias, Liedtke, Michaela, Stock, Wendy, Gökbuget, Nicola, OBrien, Susan, Jabbour, Elias, Cassaday, Ryan, Loyd, Melanie, Olsen, Scott, Neale, Geoffrey, Liu, Xueli, Vandendries, Erik, Advani, Anjali, and Mullighan, Charles

Subjects
Humans, Inotuzumab Ozogamicin, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Adult, Female, Male, Middle Aged, Treatment Outcome, Aged, Recurrence, Antineoplastic Agents, Immunological, Young Adult, Drug Resistance, Neoplasm, Adolescent
Abstract

The phase 3 INO-VATE trial demonstrated higher rates of remission, measurable residual disease negativity, and improved overall survival for patients with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) who received inotuzumab ozogamicin (InO) vs standard-of-care chemotherapy (SC). Here, we examined associations between genomic alterations and the efficacy of InO. Of 326 randomized patients, 91 (InO, n = 43; SC, n = 48) had samples evaluable for genomic analysis. The spectrum of gene fusions and other genomic alterations observed was comparable with prior studies of adult ALL. Responses to InO were observed in all leukemic subtypes, genomic alterations, and risk groups. Significantly higher rates of complete remission (CR)/CR with incomplete count recovery were observed with InO vs SC in patients with BCR::ABL1-like ALL (85.7% [6/7] vs 0% [0/5]; P = .0076), with TP53 alterations (100% [5/5] vs 12.5% [1/8]; P = .0047), and in the high-risk BCR::ABL1- (BCR::ABL1-like, low-hypodiploid, KMT2A-rearranged) group (83.3% [10/12] vs 10.5% [2/19]; P < .0001). This retrospective, exploratory analysis of the INO-VATE trial demonstrated potential for benefit with InO for patients with R/R ALL across leukemic subtypes, including BCR::ABL1-like ALL, and for those bearing diverse genomic alterations. Further confirmation of the efficacy of InO in patients with R/R ALL exhibiting the BCR::ABL1-like subtype or harboring TP53 alterations is warranted. This trial was registered at www.ClinicalTrials.gov as #NCT01564784.

Published
2024

12. A genome sequence for the threatened whitebark pine.

Author

Neale, David, Zimin, Aleksey, Meltzer, Amy, Bhattarai, Akriti, Amee, Maurice, Figueroa Corona, Laura, Puiu, Daniela, Wright, Jessica, De La Torre, Amanda, McGuire, Patrick, Timp, Winston, Salzberg, Steven, Wegrzyn, Jill, and Allen, Brian

Subjects
Pinus albicaulis, annotation, conifer, genome assembly, gymnosperm, whitebark pine, Pinus, Molecular Sequence Annotation, Genome, Plant, Genomics, Endangered Species, High-Throughput Nucleotide Sequencing
Abstract

Whitebark pine (WBP, Pinus albicaulis) is a white pine of subalpine regions in the Western contiguous United States and Canada. WBP has become critically threatened throughout a significant part of its natural range due to mortality from the introduced fungal pathogen white pine blister rust (WPBR, Cronartium ribicola) and additional threats from mountain pine beetle (Dendroctonus ponderosae), wildfire, and maladaptation due to changing climate. Vast acreages of WBP have suffered nearly complete mortality. Genomic technologies can contribute to a faster, more cost-effective approach to the traditional practices of identifying disease-resistant, climate-adapted seed sources for restoration. With deep-coverage Illumina short reads of haploid megagametophyte tissue and Oxford Nanopore long reads of diploid needle tissue, followed by a hybrid, multistep assembly approach, we produced a final assembly containing 27.6 Gb of sequence in 92,740 contigs (N50 537,007 bp) and 34,716 scaffolds (N50 2.0 Gb). Approximately 87.2% (24.0 Gb) of total sequence was placed on the 12 WBP chromosomes. Annotation yielded 25,362 protein-coding genes, and over 77% of the genome was characterized as repeats. WBP has demonstrated the greatest variation in resistance to WPBR among the North American white pines. Candidate genes for quantitative resistance include disease resistance genes known as nucleotide-binding leucine-rich repeat receptors (NLRs). A combination of protein domain alignments and direct genome scanning was employed to fully describe the 3 subclasses of NLRs. Our high-quality reference sequence and annotation provide a marked improvement in NLR identification compared to previous assessments that leveraged de novo-assembled transcriptomes.

Published
2024

13. Fine-mapping across diverse ancestries drives the discovery of putative causal variants underlying human complex traits and diseases

Author

Yuan, Kai, Longchamps, Ryan J., Pardiñas, Antonio F., Yu, Mingrui, Chen, Tzu-Ting, Lin, Shu-Chin, Chen, Yu, Lam, Max, Liu, Ruize, Xia, Yan, Guo, Zhenglin, Shi, Wenzhao, Shen, Chengguo, Daly, Mark J., Neale, Benjamin M., Feng, Yen-Chen A., Lin, Yen-Feng, Chen, Chia-Yen, O’Donovan, Michael C., Ge, Tian, and Huang, Hailiang

Published
2024
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15. Principled distillation of UK Biobank phenotype data reveals underlying structure in human variation

Author

Carey, Caitlin E., Shafee, Rebecca, Wedow, Robbee, Elliott, Amanda, Palmer, Duncan S., Compitello, John, Kanai, Masahiro, Abbott, Liam, Schultz, Patrick, Karczewski, Konrad J., Bryant, Samuel C., Cusick, Caroline M., Churchhouse, Claire, Howrigan, Daniel P., King, Daniel, Davey Smith, George, Neale, Benjamin M., Walters, Raymond K., and Robinson, Elise B.

Published
2024
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17. Gemini: A Family of Highly Capable Multimodal Models

Author

Gemini Team, Anil, Rohan, Borgeaud, Sebastian, Alayrac, Jean-Baptiste, Yu, Jiahui, Soricut, Radu, Schalkwyk, Johan, Dai, Andrew M., Hauth, Anja, Millican, Katie, Silver, David, Johnson, Melvin, Antonoglou, Ioannis, Schrittwieser, Julian, Glaese, Amelia, Chen, Jilin, Pitler, Emily, Lillicrap, Timothy, Lazaridou, Angeliki, Firat, Orhan, Molloy, James, Isard, Michael, Barham, Paul R., Hennigan, Tom, Lee, Benjamin, Viola, Fabio, Reynolds, Malcolm, Xu, Yuanzhong, Doherty, Ryan, Collins, Eli, Meyer, Clemens, Rutherford, Eliza, Moreira, Erica, Ayoub, Kareem, Goel, Megha, Krawczyk, Jack, Du, Cosmo, Chi, Ed, Cheng, Heng-Tze, Ni, Eric, Shah, Purvi, Kane, Patrick, Chan, Betty, Faruqui, Manaal, Severyn, Aliaksei, Lin, Hanzhao, Li, YaGuang, Cheng, Yong, Ittycheriah, Abe, Mahdieh, Mahdis, Chen, Mia, Sun, Pei, Tran, Dustin, Bagri, Sumit, Lakshminarayanan, Balaji, Liu, Jeremiah, Orban, Andras, Güra, Fabian, Zhou, Hao, Song, Xinying, Boffy, Aurelien, Ganapathy, Harish, Zheng, Steven, Choe, HyunJeong, Weisz, Ágoston, Zhu, Tao, Lu, Yifeng, Gopal, Siddharth, Kahn, Jarrod, Kula, Maciej, Pitman, Jeff, Shah, Rushin, Taropa, Emanuel, Merey, Majd Al, Baeuml, Martin, Chen, Zhifeng, Shafey, Laurent El, Zhang, Yujing, Sercinoglu, Olcan, Tucker, George, Piqueras, Enrique, Krikun, Maxim, Barr, Iain, Savinov, Nikolay, Danihelka, Ivo, Roelofs, Becca, White, Anaïs, Andreassen, Anders, von Glehn, Tamara, Yagati, Lakshman, Kazemi, Mehran, Gonzalez, Lucas, Khalman, Misha, Sygnowski, Jakub, Frechette, Alexandre, Smith, Charlotte, Culp, Laura, Proleev, Lev, Luan, Yi, Chen, Xi, Lottes, James, Schucher, Nathan, Lebron, Federico, Rrustemi, Alban, Clay, Natalie, Crone, Phil, Kocisky, Tomas, Zhao, Jeffrey, Perz, Bartek, Yu, Dian, Howard, Heidi, Bloniarz, Adam, Rae, Jack W., Lu, Han, Sifre, Laurent, Maggioni, Marcello, Alcober, Fred, Garrette, Dan, Barnes, Megan, Thakoor, Shantanu, Austin, Jacob, Barth-Maron, Gabriel, Wong, William, Joshi, Rishabh, Chaabouni, Rahma, Fatiha, Deeni, Ahuja, Arun, Tomar, Gaurav Singh, Senter, Evan, Chadwick, Martin, Kornakov, Ilya, Attaluri, Nithya, Iturrate, Iñaki, Liu, Ruibo, Li, Yunxuan, Cogan, Sarah, Chen, Jeremy, Jia, Chao, Gu, Chenjie, Zhang, Qiao, Grimstad, Jordan, Hartman, Ale Jakse, Garcia, Xavier, Pillai, Thanumalayan Sankaranarayana, Devlin, Jacob, Laskin, Michael, Casas, Diego de Las, Valter, Dasha, Tao, Connie, Blanco, Lorenzo, Badia, Adrià Puigdomènech, Reitter, David, Chen, Mianna, Brennan, Jenny, Rivera, Clara, Brin, Sergey, Iqbal, Shariq, Surita, Gabriela, Labanowski, Jane, Rao, Abhi, Winkler, Stephanie, Parisotto, Emilio, Gu, Yiming, Olszewska, Kate, Addanki, Ravi, Miech, Antoine, Louis, Annie, Teplyashin, Denis, Brown, Geoff, Catt, Elliot, Balaguer, Jan, Xiang, Jackie, Wang, Pidong, Ashwood, Zoe, Briukhov, Anton, Webson, Albert, Ganapathy, Sanjay, Sanghavi, Smit, Kannan, Ajay, Chang, Ming-Wei, Stjerngren, Axel, Djolonga, Josip, Sun, Yuting, Bapna, Ankur, Aitchison, Matthew, Pejman, Pedram, Michalewski, Henryk, Yu, Tianhe, Wang, Cindy, Love, Juliette, Ahn, Junwhan, Bloxwich, Dawn, Han, Kehang, Humphreys, Peter, Sellam, Thibault, Bradbury, James, Godbole, Varun, Samangooei, Sina, Damoc, Bogdan, Kaskasoli, Alex, Arnold, Sébastien M. R., Vasudevan, Vijay, Agrawal, Shubham, Riesa, Jason, Lepikhin, Dmitry, Tanburn, Richard, Srinivasan, Srivatsan, Lim, Hyeontaek, Hodkinson, Sarah, Shyam, Pranav, Ferret, Johan, Hand, Steven, Garg, Ankush, Paine, Tom Le, Li, Jian, Li, Yujia, Giang, Minh, Neitz, Alexander, Abbas, Zaheer, York, Sarah, Reid, Machel, Cole, Elizabeth, Chowdhery, Aakanksha, Das, Dipanjan, Rogozińska, Dominika, Nikolaev, Vitaliy, Sprechmann, Pablo, Nado, Zachary, Zilka, Lukas, Prost, Flavien, He, Luheng, Monteiro, Marianne, Mishra, Gaurav, Welty, Chris, Newlan, Josh, Jia, Dawei, Allamanis, Miltiadis, Hu, Clara Huiyi, de Liedekerke, Raoul, Gilmer, Justin, Saroufim, Carl, Rijhwani, Shruti, Hou, Shaobo, Shrivastava, Disha, Baddepudi, Anirudh, Goldin, Alex, Ozturel, Adnan, Cassirer, Albin, Xu, Yunhan, Sohn, Daniel, Sachan, Devendra, Amplayo, Reinald Kim, Swanson, Craig, Petrova, Dessie, Narayan, Shashi, Guez, Arthur, Brahma, Siddhartha, Landon, Jessica, Patel, Miteyan, Zhao, Ruizhe, Villela, Kevin, Wang, Luyu, Jia, Wenhao, Rahtz, Matthew, Giménez, Mai, Yeung, Legg, Keeling, James, Georgiev, Petko, Mincu, Diana, Wu, Boxi, Haykal, Salem, Saputro, Rachel, Vodrahalli, Kiran, Qin, James, Cankara, Zeynep, Sharma, Abhanshu, Fernando, Nick, Hawkins, Will, Neyshabur, Behnam, Kim, Solomon, Hutter, Adrian, Agrawal, Priyanka, Castro-Ros, Alex, Driessche, George van den, Wang, Tao, Yang, Fan, Chang, Shuo-yiin, Komarek, Paul, McIlroy, Ross, Lučić, Mario, Zhang, Guodong, Farhan, Wael, Sharman, Michael, Natsev, Paul, Michel, Paul, Bansal, Yamini, Qiao, Siyuan, Cao, Kris, Shakeri, Siamak, Butterfield, Christina, Chung, Justin, Rubenstein, Paul Kishan, Agrawal, Shivani, Mensch, Arthur, Soparkar, Kedar, Lenc, Karel, Chung, Timothy, Pope, Aedan, Maggiore, Loren, Kay, Jackie, Jhakra, Priya, Wang, Shibo, Maynez, Joshua, Phuong, Mary, Tobin, Taylor, Tacchetti, Andrea, Trebacz, Maja, Robinson, Kevin, Katariya, Yash, Riedel, Sebastian, Bailey, Paige, Xiao, Kefan, Ghelani, Nimesh, Aroyo, Lora, Slone, Ambrose, Houlsby, Neil, Xiong, Xuehan, Yang, Zhen, Gribovskaya, Elena, Adler, Jonas, Wirth, Mateo, Lee, Lisa, Li, Music, Kagohara, Thais, Pavagadhi, Jay, Bridgers, Sophie, Bortsova, Anna, Ghemawat, Sanjay, Ahmed, Zafarali, Liu, Tianqi, Powell, Richard, Bolina, Vijay, Iinuma, Mariko, Zablotskaia, Polina, Besley, James, Chung, Da-Woon, Dozat, Timothy, Comanescu, Ramona, Si, Xiance, Greer, Jeremy, Su, Guolong, Polacek, Martin, Kaufman, Raphaël Lopez, Tokumine, Simon, Hu, Hexiang, Buchatskaya, Elena, Miao, Yingjie, Elhawaty, Mohamed, Siddhant, Aditya, Tomasev, Nenad, Xing, Jinwei, Greer, Christina, Miller, Helen, Ashraf, Shereen, Roy, Aurko, Zhang, Zizhao, Ma, Ada, Filos, Angelos, Besta, Milos, Blevins, Rory, Klimenko, Ted, Yeh, Chih-Kuan, Changpinyo, Soravit, Mu, Jiaqi, Chang, Oscar, Pajarskas, Mantas, Muir, Carrie, Cohen, Vered, Lan, Charline Le, Haridasan, Krishna, Marathe, Amit, Hansen, Steven, Douglas, Sholto, Samuel, Rajkumar, Wang, Mingqiu, Austin, Sophia, Lan, Chang, Jiang, Jiepu, Chiu, 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Yang, Eichenbaum, Ali, Brovelli, Thomas, Potluri, Sahitya, Lahoti, Preethi, Baetu, Cip, Ghorbani, Ali, Chen, Charles, Crawford, Andy, Pal, Shalini, Sridhar, Mukund, Gurita, Petru, Mujika, Asier, Petrovski, Igor, Cedoz, Pierre-Louis, Li, Chenmei, Chen, Shiyuan, Santo, Niccolò Dal, Goyal, Siddharth, Punjabi, Jitesh, Kappaganthu, Karthik, Kwak, Chester, LV, Pallavi, Velury, Sarmishta, Choudhury, Himadri, Hall, Jamie, Shah, Premal, Figueira, Ricardo, Thomas, Matt, Lu, Minjie, Zhou, Ting, Kumar, Chintu, Jurdi, Thomas, Chikkerur, Sharat, Ma, Yenai, Yu, Adams, Kwak, Soo, Ähdel, Victor, Rajayogam, Sujeevan, Choma, Travis, Liu, Fei, Barua, Aditya, Ji, Colin, Park, Ji Ho, Hellendoorn, Vincent, Bailey, Alex, Bilal, Taylan, Zhou, Huanjie, Khatir, Mehrdad, Sutton, Charles, Rzadkowski, Wojciech, Macintosh, Fiona, Shagin, Konstantin, Medina, Paul, Liang, Chen, Zhou, Jinjing, Shah, Pararth, Bi, Yingying, Dankovics, Attila, Banga, Shipra, Lehmann, Sabine, Bredesen, Marissa, Lin, Zifan, Hoffmann, John Eric, Lai, Jonathan, Chung, Raynald, Yang, Kai, Balani, Nihal, Bražinskas, Arthur, Sozanschi, Andrei, Hayes, Matthew, Alcalde, Héctor Fernández, Makarov, Peter, Chen, Will, Stella, Antonio, Snijders, Liselotte, Mandl, Michael, Kärrman, Ante, Nowak, Paweł, Wu, Xinyi, Dyck, Alex, Vaidyanathan, Krishnan, R, Raghavender, Mallet, Jessica, Rudominer, Mitch, Johnston, Eric, Mittal, Sushil, Udathu, Akhil, Christensen, Janara, Verma, Vishal, Irving, Zach, Santucci, Andreas, Elsayed, Gamaleldin, Davoodi, Elnaz, Georgiev, Marin, Tenney, Ian, Hua, Nan, Cideron, Geoffrey, Leurent, Edouard, Alnahlawi, Mahmoud, Georgescu, Ionut, Wei, Nan, Zheng, Ivy, Scandinaro, Dylan, Jiang, Heinrich, Snoek, Jasper, Sundararajan, Mukund, Wang, Xuezhi, Ontiveros, Zack, Karo, Itay, Cole, Jeremy, Rajashekhar, Vinu, Tumeh, Lara, Ben-David, Eyal, Jain, Rishub, Uesato, Jonathan, Datta, Romina, Bunyan, Oskar, Wu, Shimu, Zhang, John, Stanczyk, Piotr, Zhang, Ye, Steiner, David, Naskar, Subhajit, Azzam, Michael, Johnson, Matthew, Paszke, Adam, Chiu, Chung-Cheng, Elias, Jaume Sanchez, Mohiuddin, Afroz, Muhammad, Faizan, Miao, Jin, Lee, Andrew, Vieillard, Nino, Park, Jane, Zhang, Jiageng, Stanway, Jeff, Garmon, Drew, Karmarkar, Abhijit, Dong, Zhe, Lee, Jong, Kumar, Aviral, Zhou, Luowei, Evens, Jonathan, Isaac, William, Irving, Geoffrey, Loper, Edward, Fink, Michael, Arkatkar, Isha, Chen, Nanxin, Shafran, Izhak, Petrychenko, Ivan, Chen, Zhe, Jia, Johnson, Levskaya, Anselm, Zhu, Zhenkai, Grabowski, Peter, Mao, Yu, Magni, Alberto, Yao, Kaisheng, Snaider, Javier, Casagrande, Norman, Palmer, Evan, Suganthan, Paul, Castaño, Alfonso, Giannoumis, Irene, Kim, Wooyeol, Rybiński, Mikołaj, Sreevatsa, Ashwin, Prendki, Jennifer, Soergel, David, Goedeckemeyer, Adrian, Gierke, Willi, Jafari, Mohsen, Gaba, Meenu, Wiesner, Jeremy, Wright, Diana Gage, Wei, Yawen, Vashisht, Harsha, Kulizhskaya, Yana, Hoover, Jay, Le, Maigo, Li, Lu, Iwuanyanwu, Chimezie, Liu, Lu, Ramirez, Kevin, Khorlin, Andrey, Cui, Albert, LIN, Tian, Wu, Marcus, Aguilar, Ricardo, Pallo, Keith, Chakladar, Abhishek, Perng, Ginger, Abellan, Elena Allica, Zhang, Mingyang, Dasgupta, Ishita, Kushman, Nate, Penchev, Ivo, Repina, Alena, Wu, Xihui, van der Weide, Tom, Ponnapalli, Priya, Kaplan, Caroline, Simsa, Jiri, Li, Shuangfeng, Dousse, Olivier, Piper, Jeff, Ie, Nathan, Pasumarthi, Rama, Lintz, Nathan, Vijayakumar, Anitha, Andor, Daniel, Valenzuela, Pedro, Lui, Minnie, Paduraru, Cosmin, Peng, Daiyi, Lee, Katherine, Zhang, Shuyuan, Greene, Somer, Nguyen, Duc Dung, Kurylowicz, Paula, Hardin, Cassidy, Dixon, Lucas, Janzer, Lili, Choo, Kiam, Feng, Ziqiang, Zhang, Biao, Singhal, Achintya, Du, Dayou, McKinnon, Dan, Antropova, Natasha, Bolukbasi, Tolga, Keller, Orgad, Reid, David, Finchelstein, Daniel, Raad, Maria Abi, Crocker, Remi, Hawkins, Peter, Dadashi, Robert, Gaffney, Colin, Franko, Ken, Bulanova, Anna, Leblond, Rémi, Chung, Shirley, Askham, Harry, Cobo, Luis C., Xu, Kelvin, Fischer, Felix, Xu, Jun, Sorokin, Christina, Alberti, Chris, Lin, Chu-Cheng, Evans, Colin, Dimitriev, Alek, Forbes, Hannah, Banarse, Dylan, Tung, Zora, Omernick, Mark, Bishop, Colton, Sterneck, Rachel, Jain, Rohan, Xia, Jiawei, Amid, Ehsan, Piccinno, Francesco, Wang, Xingyu, Banzal, Praseem, Mankowitz, Daniel J., Polozov, Alex, Krakovna, Victoria, Brown, Sasha, Bateni, MohammadHossein, Duan, Dennis, Firoiu, Vlad, Thotakuri, Meghana, Natan, Tom, Geist, Matthieu, Girgin, Ser tan, Li, Hui, Ye, Jiayu, Roval, Ofir, Tojo, Reiko, Kwong, Michael, Lee-Thorp, James, Yew, Christopher, Sinopalnikov, Danila, Ramos, Sabela, Mellor, John, Sharma, Abhishek, Wu, Kathy, Miller, David, Sonnerat, Nicolas, Vnukov, Denis, Greig, Rory, Beattie, Jennifer, Caveness, Emily, Bai, Libin, Eisenschlos, Julian, Korchemniy, Alex, Tsai, Tomy, Jasarevic, Mimi, Kong, Weize, Dao, Phuong, Zheng, Zeyu, Liu, Frederick, Zhu, Rui, Teh, Tian Huey, Sanmiya, Jason, Gladchenko, Evgeny, Trdin, Nejc, Toyama, Daniel, Rosen, Evan, Tavakkol, Sasan, Xue, Linting, Elkind, Chen, Woodman, Oliver, Carpenter, John, Papamakarios, George, Kemp, Rupert, Kafle, Sushant, Grunina, Tanya, Sinha, Rishika, Talbert, Alice, Wu, Diane, Owusu-Afriyie, Denese, Thornton, Chloe, Pont-Tuset, Jordi, Narayana, Pradyumna, Li, Jing, Fatehi, Saaber, Wieting, John, Ajmeri, Omar, Uria, Benigno, Ko, Yeongil, Knight, Laura, Héliou, Amélie, Niu, Ning, Gu, Shane, Pang, Chenxi, Li, Yeqing, Levine, Nir, Stolovich, Ariel, Santamaria-Fernandez, Rebeca, Goenka, Sonam, Yustalim, Wenny, Strudel, Robin, Elqursh, Ali, Deck, Charlie, Lee, Hyo, Li, Zonglin, Levin, Kyle, Hoffmann, Raphael, Holtmann-Rice, Dan, Bachem, Olivier, Arora, Sho, Koh, Christy, Yeganeh, Soheil Hassas, Põder, Siim, Tariq, Mukarram, Sun, Yanhua, Ionita, Lucian, Seyedhosseini, Mojtaba, Tafti, Pouya, Liu, Zhiyu, Gulati, Anmol, Liu, Jasmine, Ye, Xinyu, Chrzaszcz, Bart, Wang, Lily, Sethi, Nikhil, Li, Tianrun, Brown, Ben, Singh, Shreya, Fan, Wei, Parisi, Aaron, Stanton, Joe, Koverkathu, Vinod, Choquette-Choo, Christopher A., Li, Yunjie, Lu, TJ, Shroff, Prakash, Varadarajan, Mani, Bahargam, Sanaz, Willoughby, Rob, Gaddy, David, Desjardins, Guillaume, Cornero, Marco, Robenek, Brona, Mittal, Bhavishya, Albrecht, Ben, Shenoy, Ashish, Moiseev, Fedor, Jacobsson, Henrik, Ghaffarkhah, Alireza, Rivière, Morgane, Walton, Alanna, Crepy, Clément, Parrish, Alicia, Zhou, Zongwei, Farabet, Clement, Radebaugh, Carey, Srinivasan, Praveen, van der Salm, Claudia, Fidjeland, Andreas, Scellato, Salvatore, Latorre-Chimoto, Eri, Klimczak-Plucińska, Hanna, Bridson, David, de Cesare, Dario, Hudson, Tom, Mendolicchio, Piermaria, Walker, Lexi, Morris, Alex, Mauger, Matthew, Guseynov, Alexey, Reid, Alison, Odoom, Seth, Loher, Lucia, Cotruta, Victor, Yenugula, Madhavi, Grewe, Dominik, Petrushkina, Anastasia, Duerig, Tom, Sanchez, Antonio, Yadlowsky, Steve, Shen, Amy, Globerson, Amir, Webb, Lynette, Dua, Sahil, Li, Dong, Bhupatiraju, Surya, Hurt, Dan, Qureshi, Haroon, Agarwal, Ananth, Shani, Tomer, Eyal, Matan, Khare, Anuj, Belle, Shreyas Rammohan, Wang, Lei, Tekur, Chetan, Kale, Mihir Sanjay, Wei, Jinliang, Sang, Ruoxin, Saeta, Brennan, Liechty, Tyler, Sun, Yi, Zhao, Yao, Lee, Stephan, Nayak, Pandu, Fritz, Doug, Vuyyuru, Manish Reddy, Aslanides, John, Vyas, Nidhi, Wicke, Martin, Ma, Xiao, Eltyshev, Evgenii, Martin, Nina, Cate, Hardie, Manyika, James, Amiri, Keyvan, Kim, Yelin, Xiong, Xi, Kang, Kai, Luisier, Florian, Tripuraneni, Nilesh, Madras, David, Guo, Mandy, Waters, Austin, Wang, Oliver, Ainslie, Joshua, Baldridge, Jason, Zhang, Han, Pruthi, Garima, Bauer, Jakob, Yang, Feng, Mansour, Riham, Gelman, Jason, Xu, Yang, Polovets, George, Liu, Ji, Cai, Honglong, Chen, Warren, Sheng, XiangHai, Xue, Emily, Ozair, Sherjil, Angermueller, Christof, Li, Xiaowei, Sinha, Anoop, Wang, Weiren, Wiesinger, Julia, Koukoumidis, Emmanouil, Tian, Yuan, Iyer, Anand, Gurumurthy, Madhu, Goldenson, Mark, Shah, Parashar, Blake, MK, Yu, Hongkun, Urbanowicz, Anthony, Palomaki, Jennimaria, Fernando, Chrisantha, Durden, Ken, Mehta, Harsh, Momchev, Nikola, Rahimtoroghi, Elahe, Georgaki, Maria, Raul, Amit, Ruder, Sebastian, Redshaw, Morgan, Lee, Jinhyuk, Zhou, Denny, Jalan, Komal, Li, Dinghua, Hechtman, Blake, Schuh, Parker, Nasr, Milad, Milan, Kieran, Mikulik, Vladimir, Franco, Juliana, Green, Tim, Nguyen, Nam, Kelley, Joe, Mahendru, Aroma, Hu, Andrea, Howland, Joshua, Vargas, Ben, Hui, Jeffrey, Bansal, Kshitij, Rao, Vikram, Ghiya, Rakesh, Wang, Emma, Ye, Ke, Sarr, Jean Michel, Preston, Melanie Moranski, Elish, Madeleine, Li, Steve, Kaku, Aakash, Gupta, Jigar, Pasupat, Ice, Juan, Da-Cheng, Someswar, Milan, M., Tejvi, Chen, Xinyun, Amini, Aida, Fabrikant, Alex, Chu, Eric, Dong, Xuanyi, Muthal, Amruta, Buthpitiya, Senaka, Jauhari, Sarthak, Khandelwal, Urvashi, Hitron, Ayal, Ren, Jie, Rinaldi, Larissa, Drath, Shahar, Dabush, Avigail, Jiang, Nan-Jiang, Godhia, Harshal, Sachs, Uli, Chen, Anthony, Fan, Yicheng, Taitelbaum, Hagai, Noga, Hila, Dai, Zhuyun, Wang, James, Hamer, Jenny, Ferng, Chun-Sung, Elkind, Chenel, Atias, Aviel, Lee, Paulina, Listík, Vít, Carlen, Mathias, van de Kerkhof, Jan, Pikus, Marcin, Zaher, Krunoslav, Müller, Paul, Zykova, Sasha, Stefanec, Richard, Gatsko, Vitaly, Hirnschall, Christoph, Sethi, Ashwin, Xu, Xingyu Federico, Ahuja, Chetan, Tsai, Beth, Stefanoiu, Anca, Feng, Bo, Dhandhania, Keshav, Katyal, Manish, Gupta, Akshay, Parulekar, Atharva, Pitta, Divya, Zhao, Jing, Bhatia, Vivaan, Bhavnani, Yashodha, Alhadlaq, Omar, Li, Xiaolin, Danenberg, Peter, Tu, Dennis, Pine, Alex, Filippova, Vera, Ghosh, Abhipso, Limonchik, Ben, Urala, Bhargava, Lanka, Chaitanya Krishna, Clive, Derik, Li, Edward, Wu, Hao, Hongtongsak, Kevin, Li, Ianna, Thakkar, Kalind, Omarov, Kuanysh, Majmundar, Kushal, Alverson, Michael, Kucharski, Michael, Patel, Mohak, Jain, Mudit, Zabelin, Maksim, Pelagatti, Paolo, Kohli, Rohan, Kumar, Saurabh, Kim, Joseph, Sankar, Swetha, Shah, Vineet, Ramachandruni, Lakshmi, Zeng, Xiangkai, Bariach, Ben, Weidinger, Laura, Vu, Tu, Andreev, Alek, He, Antoine, Hui, Kevin, Kashem, Sheleem, Subramanya, Amar, Hsiao, Sissie, Hassabis, Demis, Kavukcuoglu, Koray, Sadovsky, Adam, Le, Quoc, Strohman, Trevor, Wu, Yonghui, Petrov, Slav, Dean, Jeffrey, and Vinyals, Oriol

Subjects
Computer Science - Computation and Language, Computer Science - Artificial Intelligence, Computer Science - Computer Vision and Pattern Recognition
Abstract

This report introduces a new family of multimodal models, Gemini, that exhibit remarkable capabilities across image, audio, video, and text understanding. The Gemini family consists of Ultra, Pro, and Nano sizes, suitable for applications ranging from complex reasoning tasks to on-device memory-constrained use-cases. Evaluation on a broad range of benchmarks shows that our most-capable Gemini Ultra model advances the state of the art in 30 of 32 of these benchmarks - notably being the first model to achieve human-expert performance on the well-studied exam benchmark MMLU, and improving the state of the art in every one of the 20 multimodal benchmarks we examined. We believe that the new capabilities of the Gemini family in cross-modal reasoning and language understanding will enable a wide variety of use cases. We discuss our approach toward post-training and deploying Gemini models responsibly to users through services including Gemini, Gemini Advanced, Google AI Studio, and Cloud Vertex AI.

Published
2023

18. Chromatin binding by HORMAD proteins regulates meiotic recombination initiation

Author

Milano, Carolyn R, Ur, Sarah N, Gu, Yajie, Zhang, Jessie, Allison, Rachal, Brown, George, Neale, Matthew J, Tromer, Eelco C, Corbett, Kevin D, and Hochwagen, Andreas

Subjects
Biochemistry and Cell Biology, Biological Sciences, Genetics, Underpinning research, 1.1 Normal biological development and functioning, Generic health relevance, Meiosis, Nucleosomes, Cryoelectron Microscopy, Phylogeny, Saccharomyces cerevisiae, DNA, Nuclear Proteins, Saccharomyces cerevisiae Proteins, Budding Yeast, Chromatin, Chromosome Segregation, HORMA, Information and Computing Sciences, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

The meiotic chromosome axis coordinates chromosome organization and interhomolog recombination in meiotic prophase and is essential for fertility. In S. cerevisiae, the HORMAD protein Hop1 mediates the enrichment of axis proteins at nucleosome-rich islands through a central chromatin-binding region (CBR). Here, we use cryoelectron microscopy to show that the Hop1 CBR directly recognizes bent nucleosomal DNA through a composite interface in its PHD and winged helix-turn-helix domains. Targeted disruption of the Hop1 CBR-nucleosome interface causes a localized reduction of axis protein binding and meiotic DNA double-strand breaks (DSBs) in axis islands and leads to defects in chromosome synapsis. Synthetic effects with mutants of the Hop1 regulator Pch2 suggest that nucleosome binding delays a conformational switch in Hop1 from a DSB-promoting, Pch2-inaccessible state to a DSB-inactive, Pch2-accessible state to regulate the extent of meiotic DSB formation. Phylogenetic analyses of meiotic HORMADs reveal an ancient origin of the CBR, suggesting that the mechanisms we uncover are broadly conserved.

Published
2024

19. Associations of plasma neurofilament light chain with cognition and neuroimaging measures in community-dwelling early old age men

Author

Tang, Rongxiang, Buchholz, Erik, Dale, Anders M, Rissman, Robert A, Fennema-Notestine, Christine, Gillespie, Nathan A, Hagler, Donald J, Lyons, Michael J, Neale, Michael C, Panizzon, Matthew S, Puckett, Olivia K, Reynolds, Chandra A, Franz, Carol E, Kremen, William S, and Elman, Jeremy A

Subjects
Biomedical and Clinical Sciences, Health Sciences, Brain Disorders, Mental Health, Health Disparities, Prevention, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Aging, Neurodegenerative, Dementia, Acquired Cognitive Impairment, Basic Behavioral and Social Science, Clinical Research, Neurosciences, Alzheimer's Disease, Behavioral and Social Science, Mind and Body, 4.1 Discovery and preclinical testing of markers and technologies, Neurological, Mental health, Humans, Male, Neurofilament Proteins, Aged, Middle Aged, Independent Living, Cross-Sectional Studies, Cognitive Dysfunction, Neuroimaging, Cognition, Biomarkers, Neuropsychological Tests, Magnetic Resonance Imaging, Brain, White Matter, Neurofilament light chain, White matter hyperintensity, Processing speed, Neurodegeneration, Blood-based biomarkers, Medical and Health Sciences, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundPlasma neurofilament light chain (NfL) is a promising biomarker of neurodegeneration with potential clinical utility in monitoring the progression of neurodegenerative diseases. However, the cross-sectional associations of plasma NfL with measures of cognition and brain have been inconsistent in community-dwelling populations.MethodsWe examined these associations in a large community-dwelling sample of early old age men (N = 969, mean age = 67.57 years, range = 61-73 years), who are either cognitively unimpaired (CU) or with mild cognitive impairment (MCI). Specifically, we investigated five cognitive domains (executive function, episodic memory, verbal fluency, processing speed, visual-spatial ability), as well as neuroimaging measures of gray and white matter.ResultsAfter adjusting for age, health status, and young adult general cognitive ability, plasma NfL level was only significantly associated with processing speed and white matter hyperintensity (WMH) volume, but not with other cognitive or neuroimaging measures. The association with processing speed was driven by individuals with MCI, as it was not detected in CU individuals.ConclusionsThese results suggest that in early old age men without dementia, plasma NfL does not appear to be sensitive to cross-sectional individual differences in most domains of cognition or neuroimaging measures of gray and white matter. The revealed plasma NfL associations were limited to WMH for all participants and processing speed only within the MCI cohort. Importantly, considering cognitive status in community-based samples will better inform the interpretation of the relationships of plasma NfL with cognition and brain and may help resolve mixed findings in the literature.

Published
2024

20. Continuing benefits of the Montreal Protocol and protection of the stratospheric ozone layer for human health and the environment

Author

Madronich, S., Bernhard, G. H., Neale, P. J., Heikkilä, A., Andersen, M. P. Sulbæk, Andrady, A. L., Aucamp, P. J., Bais, A. F., Banaszak, A. T., Barnes, P. J., Bornman, J. F., Bruckman, L. S., Busquets, R., Chiodo, G., Häder, D.-P., Hanson, M. L., Hylander, S., Jansen, M. A. K., Lingham, G., Lucas, R. M., Calderon, R. Mackenzie, Olsen, C., Ossola, R., Pandey, K. K., Petropavlovskikh, I., Revell, L. E., Rhodes, L. E., Robinson, S. A., Robson, T. M., Rose, K. C., Schikowski, T., Solomon, K. R., Sulzberger, B., Wallington, T. J., Wang, Q.-W., Wängberg, S.-Å., White, C. C., Wilson, S. R., Zhu, L., and Neale, R. E.

Published
2024
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21. Plastics in the environment in the context of UV radiation, climate change and the Montreal Protocol: UNEP Environmental Effects Assessment Panel, Update 2023

Author

Jansen, Marcel A. K., Andrady, Anthony L., Bornman, Janet F., Aucamp, Pieter J., Bais, Alkiviadis F., Banaszak, Anastazia T., Barnes, Paul W., Bernhard, Germar H., Bruckman, Laura S., Busquets, Rosa, Häder, Donat-P., Hanson, Mark L., Heikkilä, Anu M., Hylander, Samuel, Lucas, Robyn M., Mackenzie, Roy, Madronich, Sasha, Neale, Patrick J., Neale, Rachel E., Olsen, Catherine M., Ossola, Rachele, Pandey, Krishna K., Petropavlovskikh, Irina, Revell, Laura E., Robinson, Sharon A., Robson, T. Matthew, Rose, Kevin C., Solomon, Keith R., Andersen, Mads P. Sulbæk, Sulzberger, Barbara, Wallington, Timothy J., Wang, Qing-Wei, Wängberg, Sten-Åke, White, Christopher C., Young, Antony R., Zepp, Richard G., and Zhu, Liping

Published
2024
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25. Diagnostic utility of DNA methylation analysis in genetically unsolved pediatric epilepsies and CHD2 episignature refinement

Author

LaFlamme, Christy W., Rastin, Cassandra, Sengupta, Soham, Pennington, Helen E., Russ-Hall, Sophie J., Schneider, Amy L., Bonkowski, Emily S., Almanza Fuerte, Edith P., Allan, Talia J., Zalusky, Miranda Perez-Galey, Goffena, Joy, Gibson, Sophia B., Nyaga, Denis M., Lieffering, Nico, Hebbar, Malavika, Walker, Emily V., Darnell, Daniel, Olsen, Scott R., Kolekar, Pandurang, Djekidel, Mohamed Nadhir, Rosikiewicz, Wojciech, McConkey, Haley, Kerkhof, Jennifer, Levy, Michael A., Relator, Raissa, Lev, Dorit, Lerman-Sagie, Tally, Park, Kristen L., Alders, Marielle, Cappuccio, Gerarda, Chatron, Nicolas, Demain, Leigh, Genevieve, David, Lesca, Gaetan, Roscioli, Tony, Sanlaville, Damien, Tedder, Matthew L., Gupta, Sachin, Jones, Elizabeth A., Weisz-Hubshman, Monika, Ketkar, Shamika, Dai, Hongzheng, Worley, Kim C., Rosenfeld, Jill A., Chao, Hsiao-Tuan, Neale, Geoffrey, Carvill, Gemma L., Wang, Zhaoming, Berkovic, Samuel F., Sadleir, Lynette G., Miller, Danny E., Scheffer, Ingrid E., Sadikovic, Bekim, and Mefford, Heather C.

Published
2024
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29. A unified framework for estimating country-specific cumulative incidence for 18 diseases stratified by polygenic risk

Author

Jermy, Bradley, Läll, Kristi, Wolford, Brooke N., Wang, Ying, Zguro, Kristina, Cheng, Yipeng, Kanai, Masahiro, Kanoni, Stavroula, Yang, Zhiyu, Hartonen, Tuomo, Monti, Remo, Wanner, Julian, Youssef, Omar, Lippert, Christoph, van Heel, David, Okada, Yukinori, McCartney, Daniel L., Hayward, Caroline, Marioni, Riccardo E., Furini, Simone, Renieri, Alessandra, Martin, Alicia R., Neale, Benjamin M., Hveem, Kristian, Mägi, Reedik, Palotie, Aarno, Heyne, Henrike, Mars, Nina, Ganna, Andrea, and Ripatti, Samuli

Published
2024
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31. Author Correction: Membrane lipids drive formation of KRAS4b-RAF1 RBDCRD nanoclusters on the membrane

Author

Shrestha, Rebika, Carpenter, Timothy S., Van, Que N., Agamasu, Constance, Tonelli, Marco, Aydin, Fikret, Chen, De, Gulten, Gulcin, Glosli, James N., López, Cesar A., Oppelstrup, Tomas, Neale, Chris, Gnanakaran, Sandrasegaram, Gillette, William K., Ingólfsson, Helgi I., Lightstone, Felice C., Stephen, Andrew G., Streitz, Frederick H., Nissley, Dwight V., and Turbyville, Thomas J.

Published
2024
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32. Membrane lipids drive formation of KRAS4b-RAF1 RBDCRD nanoclusters on the membrane

Author

Shrestha, Rebika, Carpenter, Timothy S., Van, Que N., Agamasu, Constance, Tonelli, Marco, Aydin, Fikret, Chen, De, Gulten, Gulcin, Glosli, James N., López, Cesar A., Oppelstrup, Tomas, Neale, Chris, Gnanakaran, Sandrasegaram, Gillette, William K., Ingólfsson, Helgi I., Lightstone, Felice C., Stephen, Andrew G., Streitz, Frederick H., Nissley, Dwight V., and Turbyville, Thomas J.

Published
2024
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36. The genetics of spatiotemporal variation in cortical thickness in youth

Author

J. Eric Schmitt, Aaron Alexander-Bloch, Jakob Seidlitz, Armin Raznahan, and Michael C. Neale

Subjects
Biology (General), QH301-705.5
Abstract

Abstract Prior studies have shown strong genetic effects on cortical thickness (CT), structural covariance, and neurodevelopmental trajectories in childhood and adolescence. However, the importance of genetic factors on the induction of spatiotemporal variation during neurodevelopment remains poorly understood. Here, we explore the genetics of maturational coupling by examining 308 MRI-derived regional CT measures in a longitudinal sample of 677 twins and family members. We find dynamic inter-regional genetic covariation in youth, with the emergence of regional subnetworks in late childhood and early adolescence. Three critical neurodevelopmental epochs in genetically-mediated maturational coupling were identified, with dramatic network strengthening near eleven years of age. These changes are associated with statistically-significant (empirical p-value

Published
2024
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37. Analysis of optimization models under different approaches to deal with uncertainty regarding pre-disaster planning in food bank supply chains

Author

Adrian Fernando Rivera-Morales, Neale Ricardo Smith, Angel Ruiz, and Leopoldo Eduardo Cárdenas-Barrón

Subjects
demand uncertainty, cardinality-constraints, optimization models, humanitarian logistics, minimize unmet demand, equity, Industrial engineering. Management engineering, T55.4-60.8, Social Sciences, Commerce, HF1-6182, Business, HF5001-6182
Abstract

Purpose: Pre-positioning is a crucial choice in pre-disaster humanitarian logistics planning that consists of deciding in advance how much aid and where should it be located to enable effective and prompt operations in the case of an emergency. To support managers making such decisions, we propose four mathematical formulations that, considering the uncertainty on the demand to satisfy, seek to optimize aid prepositioning (before the event) and further distribution (after the event) in order to minimize unmet demand (MUD). The purpose of this paper is to evaluate and compare the performance of these formulations on a real case to discuss when and why should each approach be applied. Design/methodology/approach: The two first formulations adopt the cardinality-constrained (CC) approach to handle uncertainty. These formulations differ in their objective functions, the first formulation’s objective seeks to MUD, whilst the second incorporates equity in the way that demand is satisfied. The two remaining formulations are scenario-based (SB) and as in the previous two formulations, seek to MUD with and without equity considerations, respectively. Findings: Applying our formulations to a case study, we compare the differences between the solutions produced by the proposed formulations and the solutions that would have been produced without uncertainty (perfect information) to have a better understanding of their performance and their behavior. A discussion of the strengths and weaknesses of each model is provided to help managers choose the model that best suits their needs. Originality/value: The formulations are applied to a case study where a food bank is faced with the arrival of a hurricane in Mexico. As far as our knowledge, it is the first work in literature to deal with humanitarian logistics under a cardinality-constrained approach.

Published
2024
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38. Exploring the X-Factor: Generation X Public School Principals and Assistant Principals Experience Leading a Multigenerational Workforce

Author

Katreca N. Reed Neale

Abstract

There is a shortage of literature containing the principal's voice and articulation of her or his journey through leadership. This exploratory research extends the understanding of the nature and meaning of the lived experiences of the Generation X cohort within the context of school principals and assistant principals leading in 21st century schools. This qualitative hermeneutic phenomenological study explored Generation X school principals' and assistant principals' experiences leading a multigenerational workforce. A multigenerational workforce is defined as comprising of employees from five different generations: Traditionalists, Baby Boomers, Generation X, Millennials, and Generation Z. The researcher sought to explore (a) what aspects of Generation X school principal and assistant principal education, training, or development helped them prepare as a school leader; (b) how Generation X school principals and assistant principals describe and enact their leadership style(s) to lead a multigenerational workforce; and (c) how societal context has influenced Generation X principal and assistant principal leadership (i.e., Global Pandemic, social and emotional health concerns). Three global themes emerged from semi-structured interviews with 15 Generation X school principals and assistant principals in a public school district: Identity, Flexibility and Adaptability, and Social Awareness. The findings indicate (a) participant identity for these participants is multifaceted and informed by culture and social interactions, (b) Generation X leaders are flexible and adaptable, and (c) Generation X leaders utilize social awareness and societal context to foster equitable and inclusive learning environments. This research highlights the experiences of an often overlooked generation to help these Generation X leaders reflect on the ways their adolescent experiences influence the way they currently lead a multigenerational workforce. [The dissertation citations contained here are published with the permission of ProQuest LLC. Further reproduction is prohibited without permission. Copies of dissertations may be obtained by Telephone (800) 1-800-521-0600. Web page: http://www.proquest.com/en-US/products/dissertations/individuals.shtml.]

Published
2024

39. Disparities in Suicidal Behaviors and Mental Health Issues among Gender Minority College Students

Author

Justin Watts, Carly Scarton, Neale R. Chumbler, Elizabeth With, Tamara Knapp-Grosz, and Sara Ousby

Abstract

Mental health issues are prominent among gender minorities; however, research examining these issues among college campuses is limited, and has often overlooked individuals who identify outside of transgender or cisgender identities. Our findings indicated that transgender participants reported the highest rates and frequencies of non-suicidal self injury, suicidal thoughts, and suicide attempt compared to cisgender peers; followed closely by gender-expansive participants. Gender minority participants reported higher rates of family distress and social anxiety.

Published
2024
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40. High-resolution emission spectroscopy retrievals of MASCARA-1b with CRIRES+: Strong detections of CO, H$_2$O and Fe emission lines and a C$/$O consistent with solar

Author

Ramkumar, Swaetha, Gibson, Neale P., Nugroho, Stevanus K., Maguire, Cathal, and Fortune, Mark

Subjects
Astrophysics - Earth and Planetary Astrophysics
Abstract

The characterization of exoplanet atmospheres has proven to be successful using high-resolution spectroscopy. Phase curve observations of hot/ultra-hot Jupiters can reveal their compositions and thermal structures, thereby allowing the detection of molecules and atoms in the planetary atmosphere using the cross-correlation technique. We present pre-eclipse observations of the ultra-hot Jupiter, MASCARA-1b, observed with the recently upgraded CRIRES+ high-resolution infrared spectrograph at the VLT. We report a detection of $\rm Fe$ ($\approx$8.3$\sigma$) in the K-band and confirm previous detections of $\rm CO$ (>15$\sigma$) and $\rm H_2O$ (>10$\sigma$) in the day-side atmosphere of MASCARA-1b. Using a Bayesian inference framework, we retrieve the abundances of the detected species and constrain planetary orbital velocities, $T$-$P$ profiles, and the carbon-to-oxygen ratio ($\rm C/O$). A free retrieval results in an elevated $\rm CO$ abundance ($\log_{10}$($\chi_{\rm{{}^{12}CO}}$) = $-2.85^{+0.57}_{-0.69}$), leading to a super-solar $\rm C/O$ ratio. More realistically, allowing for vertically-varying chemistry in the atmosphere by incorporating a chemical-equilibrium model results in a $\rm C/O$ of $0.68^{+0.12}_{-0.22}$ and a metallicity of $[\rm M/H] = 0.62^{+0.28}_{-0.55}$, both consistent with solar values. Finally, we also report a slight offset of the $\rm Fe$ feature in both K$_{\rm p}$ and v$_{\rm sys}$ that could be a signature of atmospheric dynamics. Due to the 3D structure of exoplanet atmospheres and the exclusion of time/phase dependence in our 1D forward models, further follow-up observations and analysis are required to confirm or refute this result., Comment: 21 pages, 18 figures, 4 tables, accepted for publication in Monthly Notices of the Royal Astronomical Society

Published
2023
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41. ExoGemS Detection of a Metal Hydride in an Exoplanet Atmosphere

Author

Flagg, Laura, Turner, Jake D., Deibert, Emily, Ridden-Harper, Andrew, de Mooij, Ernst, MacDonald, Ryan J., Jayawardhana, Ray, Gibson, Neale, Langeveld, Adam, and Sing, David

Subjects
Astrophysics - Earth and Planetary Astrophysics
Abstract

Exoplanet atmosphere studies are often enriched by synergies with brown dwarf analogs. However, many key molecules commonly seen in brown dwarfs have yet to be confirmed in exoplanet atmospheres. An important example is chromium hydride (CrH), which is often used to probe atmospheric temperatures and classify brown dwarfs into spectral types. Recently, tentative evidence for CrH was reported in the low-resolution transmission spectrum of the hot Jupiter WASP-31b. Here, we present high spectral resolution observations of WASP-31b's transmission spectrum from GRACES/Gemini North and UVES/VLT. We detect CrH at 5.6$\sigma$ confidence, representing the first metal hydride detection in an exoplanet atmosphere at high spectral resolution. Our findings constitute a critical step in understanding the role of metal hydrides in exoplanet atmospheres., Comment: accepted to ApJL

Published
2023

42. Investigation of a Human Case of Francisella tularensis Infection, United Kingdom, 2023

Author

Ameeka Thompson, Tim Brooks, Catherine Houlihan, Tommy Rampling, Helen Umpleby, Kayleigh Hansford, Jolyon Medlock, Alexander Vaux, Julie Logan, Andrew Frost, Sue Neale, Stephen Wyllie, Kirsty Dodgson, Dominic Haigh, Isra Halim, Raqib Huq, Michael Riste, and N. Claire Gordon

Subjects
Francisella tularensis, zoonoses, tularemia, bacteria, bacterial zoonoses, United Kingdom, Medicine, Infectious and parasitic diseases, RC109-216
Abstract

Tularemia, caused by Francisella tularensis, is not known to occur in the United Kingdom. We report a case of tularemia diagnosed in July 2023 in a UK patient with no travel in the 6 weeks before symptom onset. We describe the subsequent multiagency investigation into possible routes of acquisition.

Published
2024
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44. Retrieval survey of metals in six ultra-hot Jupiters: Trends in chemistry, rain-out, ionisation and atmospheric dynamics

Author

Gandhi, Siddharth, Kesseli, Aurora, Zhang, Yapeng, Louca, Amy, Snellen, Ignas, Brogi, Matteo, Miguel, Yamila, Casasayas-Barris, Núria, Pelletier, Stefan, Landman, Rico, Maguire, Cathal, and Gibson, Neale P.

Subjects
Astrophysics - Earth and Planetary Astrophysics
Abstract

Ground-based high-resolution spectroscopy (HRS) has detected numerous chemical species and atmospheric dynamics in exoplanets, most notably ultra-hot Jupiters (UHJs). However, quantitative estimates on abundances have been challenging but are essential for accurate comparative characterisation and to determine formation scenarios. In this work we retrieve the atmospheres of six UHJs (WASP-76~b, MASCARA-4~b, MASCARA-2~b, WASP-121~b, HAT-P-70~b and WASP-189~b) with ESPRESSO and HARPS-N/HARPS observations, exploring trends in eleven neutral species and dynamics. While Fe abundances agree well with stellar values, Mg, Ni, Cr, Mn and V show more variation, highlighting the difficulty in using a single species as a proxy for metallicity. We find that Ca, Na, Ti and TiO are under-abundant, potentially due to ionisation and/or night-side rain-out. Our retrievals also show that relative abundances between species are more robust, consistent with previous works. We perform spatially- and phase-resolved retrievals for WASP-76~b and WASP-121~b given their high signal-to-noise observations, and find the chemical abundances in each of the terminator regions are broadly consistent. We additionally constrain dynamics for our sample through Doppler shifts and broadening of the planetary signals during the primary eclipse, with median blue shifts between $\sim$0.9-9.0~km/s due to day-night winds. Furthermore, we constrain spectroscopic masses for MASCARA-2~b and HAT-P-70~b consistent with their known upper limits, but we note that these may be biased due to degeneracies. This work highlights the importance of future HRS studies to further probe differences and trends between exoplanets., Comment: 26 pages, 11 figures, 5 tables, published in AJ

Published
2023
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45. A spectroscopic thermometer: individual vibrational band spectroscopy with the example of OH in the atmosphere of WASP-33b

Author

Wright, Sam O. M., Nugroho, Stevanus K., Brogi, Matteo, Gibson, Neale P., de Mooij, Ernst J. W., Waldmann, Ingo, Tennyson, Jonathan, Kawahara, Hajime, Kuzuhara, Masayuki, Hirano, Teruyuki, Kotani, Takayuki, Kawashima, Yui, Masuda, Kento, Birkby, Jayne L., Watson, Chris A., Tamura, Motohide, Zwintz, Konstanze, Harakawa, Hiroki, Kudo, Tomoyuki, Hodapp, Klaus, Jacobson, Shane, Konishi, Mihoko, Kurokawa, Takashi, Nishikawa, Jun, Omiya, Masashi, Serizawa, Takuma, Ueda, Akitoshi, Vievard, Sébastien, and Yurchenko, Sergei N.

Subjects
Astrophysics - Earth and Planetary Astrophysics
Abstract

Individual vibrational band spectroscopy presents an opportunity to examine exoplanet atmospheres in detail by distinguishing where the vibrational state populations of molecules differ from the current assumption of a Boltzmann distribution. Here, retrieving vibrational bands of OH in exoplanet atmospheres is explored using the hot Jupiter WASP-33b as an example. We simulate low-resolution spectroscopic data for observations with the JWST's NIRSpec instrument and use high resolution observational data obtained from the Subaru InfraRed Doppler instrument (IRD). Vibrational band-specific OH cross section sets are constructed and used in retrievals on the (simulated) low and (real) high resolution data. Low resolution observations are simulated for two WASP-33b emission scenarios: under the assumption of local thermal equilibrium (LTE) and a toy non-LTE model for vibrational excitation of selected bands. We show that mixing ratios for individual bands can be retrieved with sufficient precision to allow the vibrational population distributions of the forward models to be reconstructed. A simple fit for the Boltzmann distribution in the LTE case shows that the vibrational temperature is recoverable in this manner. For high resolution, cross-correlation applications, we apply the individual vibrational band analysis to an IRD spectrum of WASP-33b, applying an 'un-peeling' technique. Individual detection significances for the two strongest bands are shown to be in line with Boltzmann distributed vibrational state populations consistent with the effective temperature of the WASP-33b atmosphere reported previously. We show the viability of this approach for analysing the individual vibrational state populations behind observed and simulated spectra including reconstructing state population distributions., Comment: Submitted for publication in AJ

Published
2023
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46. High-resolution Emission Spectroscopy of the Ultrahot Jupiter KELT-9b: Little Variation in Day- and Nightside Emission Line Contrasts

Author

Ridden-Harper, Andrew, de Mooij, Ernst, Jayawardhana, Ray, Gibson, Neale, Karjalainen, Raine, and Karjalainen, Marie

Subjects
Astrophysics - Earth and Planetary Astrophysics
Abstract

The transmission spectrum of the ultrahot Jupiter KELT-9b ($T_{eq}$ $\sim$ 4000 K) exhibits absorption by several metal species. We searched for atomic and molecular lines in its emission spectrum by observing partial phase curves with the CARMENES spectrograph ($R$ $\sim$ 80,000 $-$ 95,000). We find evidence for emission by Si I in the atmosphere of KELT-9b for the first time. Additionally we find evidence for emission by Mg I and Ca II, which were previously detected in transmission, and confirmed earlier detections of Fe I emission. Conversely, we find no evidence for dayside emission from Al I, Ca I, Cr I, FeH, Fe II, K I, Li I, Mg II, Na I, OH, Ti I, TiO, V I, V II, VO, and Y I. By employing likelihood mapping, we find indications of there being little variation in emission line contrast between the day- and nightsides $-$suggesting that KELT-9b may harbor iron emission on its nightside. Our results demonstrate that high-resolution ground-based emission spectroscopy can provide valuable insights into exoplanet atmospheres., Comment: Accepted for publication in AJ

Published
2023
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47. A guidance for the enrichment of micropollutants from wastewater by solid-phase extraction before bioanalytical assessment

Author

Tobias Schulze, Peta A. Neale, Jörg Ahlheim, Liza-Marie Beckers, Maria König, Janet Krüger, Margit Petre, Aleksandra Piotrowska, Rita Schlichting, Susanne Schmidt, Martin Krauss, and Beate I. Escher

Subjects
Standardization, Wastewater, Solid-phase extraction, Micropollutants, Chemical analysis, Bioassays, Environmental sciences, GE1-350, Environmental law, K3581-3598
Abstract

Abstract Background Wastewater can contain a complex mixture of organic micropollutants, with both chemical analysis and effect-based methods needed to identify relevant micropollutants and detect mixture effects. Solid-phase extraction (SPE) is commonly used to enrich micropollutants prior to analysis. While the recovery and stability of individual micropollutants by SPE has been well studied, few studies have optimized SPE for effect-based methods. The aim of the current study was to develop and evaluate two standard operating procedures (SOPs) for the enrichment of micropollutants in preparation for chemical analysis and bioanalysis, one covering a broad range of chemicals and the other selective for estrogenic chemicals. Results Pristine surface water spiked with > 600 micropollutants was used to develop a generic extraction method for micropollutants with a wide range of physiochemical properties, while water spiked with estrogenic chemicals was used to identify a selective extraction method. Three different SPE sorbents were tested, with recoveries of individual chemicals and effect in assays indicative of mutagenicity, estrogenic activity, and fish embryo toxicity assessed. The sorbent HRX at pH 7 was selected for the generic extraction method as it showed the best recovery of both individual chemicals and effect in the bioassays. The sorbent HLB at pH 3 showed optimal recovery of estrogenic chemicals and estrogenic activity. The two optimal SPE methods were applied to spiked and unspiked wastewater effluents, with the concentrations of detected chemicals and observed effects similar to those of previous studies. The long-term storage of both extracts and SPE cartridges for estrogens and estrogenic activity after extraction with the HRX and HLB methods were evaluated, with estrogenic effectiveness close to 100% after 112 days when HLB was used. Conclusions HRX is recommended for generic extraction, while HLB is optimal for the selective extraction of estrogenic micropollutants. However, if a laboratory only wants to use a single SPE sorbent, HLB can be used for both generic and selective extraction as it yielded similar chemical and effect recovery as HRX for a wide range of micropollutants. This paper is supplemented by the final SOP that includes a variant for generic extraction and one for the extraction of estrogenic chemicals.

Published
2024
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48. Diagnostic utility of DNA methylation analysis in genetically unsolved pediatric epilepsies and CHD2 episignature refinement

Author

Christy W. LaFlamme, Cassandra Rastin, Soham Sengupta, Helen E. Pennington, Sophie J. Russ-Hall, Amy L. Schneider, Emily S. Bonkowski, Edith P. Almanza Fuerte, Talia J. Allan, Miranda Perez-Galey Zalusky, Joy Goffena, Sophia B. Gibson, Denis M. Nyaga, Nico Lieffering, Malavika Hebbar, Emily V. Walker, Daniel Darnell, Scott R. Olsen, Pandurang Kolekar, Mohamed Nadhir Djekidel, Wojciech Rosikiewicz, Haley McConkey, Jennifer Kerkhof, Michael A. Levy, Raissa Relator, Dorit Lev, Tally Lerman-Sagie, Kristen L. Park, Marielle Alders, Gerarda Cappuccio, Nicolas Chatron, Leigh Demain, David Genevieve, Gaetan Lesca, Tony Roscioli, Damien Sanlaville, Matthew L. Tedder, Sachin Gupta, Elizabeth A. Jones, Monika Weisz-Hubshman, Shamika Ketkar, Hongzheng Dai, Kim C. Worley, Jill A. Rosenfeld, Hsiao-Tuan Chao, Undiagnosed Diseases Network, Geoffrey Neale, Gemma L. Carvill, University of Washington Center for Rare Disease Research, Zhaoming Wang, Samuel F. Berkovic, Lynette G. Sadleir, Danny E. Miller, Ingrid E. Scheffer, Bekim Sadikovic, and Heather C. Mefford

Subjects
Science
Abstract

Abstract Sequence-based genetic testing identifies causative variants in ~ 50% of individuals with developmental and epileptic encephalopathies (DEEs). Aberrant changes in DNA methylation are implicated in various neurodevelopmental disorders but remain unstudied in DEEs. We interrogate the diagnostic utility of genome-wide DNA methylation array analysis on peripheral blood samples from 582 individuals with genetically unsolved DEEs. We identify rare differentially methylated regions (DMRs) and explanatory episignatures to uncover causative and candidate genetic etiologies in 12 individuals. Using long-read sequencing, we identify DNA variants underlying rare DMRs, including one balanced translocation, three CG-rich repeat expansions, and four copy number variants. We also identify pathogenic variants associated with episignatures. Finally, we refine the CHD2 episignature using an 850 K methylation array and bisulfite sequencing to investigate potential insights into CHD2 pathophysiology. Our study demonstrates the diagnostic yield of genome-wide DNA methylation analysis to identify causal and candidate variants as 2% (12/582) for unsolved DEE cases.

Published
2024
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49. Inhibition of topoisomerase 2 catalytic activity impacts the integrity of heterochromatin and repetitive DNA and leads to interlinks between clustered repeats

Author

Michalis Amoiridis, John Verigos, Karen Meaburn, William H. Gittens, Tao Ye, Matthew J. Neale, and Evi Soutoglou

Subjects
Science
Abstract

Abstract DNA replication and transcription generate DNA supercoiling, which can cause topological stress and intertwining of daughter chromatin fibers, posing challenges to the completion of DNA replication and chromosome segregation. Type II topoisomerases (Top2s) are enzymes that relieve DNA supercoiling and decatenate braided sister chromatids. How Top2 complexes deal with the topological challenges in different chromatin contexts, and whether all chromosomal contexts are subjected equally to torsional stress and require Top2 activity is unknown. Here we show that catalytic inhibition of the Top2 complex in interphase has a profound effect on the stability of heterochromatin and repetitive DNA elements. Mechanistically, we find that catalytically inactive Top2 is trapped around heterochromatin leading to DNA breaks and unresolved catenates, which necessitate the recruitment of the structure specific endonuclease, Ercc1-XPF, in an SLX4- and SUMO-dependent manner. Our data are consistent with a model in which Top2 complex resolves not only catenates between sister chromatids but also inter-chromosomal catenates between clustered repetitive elements.

Published
2024
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50. Exploring freshwater stream bacterial communities as indicators of land use intensity

Author

Syrie Hermans, Anju Gautam, Gillian D. Lewis, Martin Neale, Hannah L. Buckley, Bradley S. Case, and Gavin Lear

Subjects
Environmental sciences, GE1-350, Microbiology, QR1-502
Abstract

Abstract Background Stream ecosystems comprise complex interactions among biological communities and their physicochemical surroundings, contributing to their overall ecological health. Despite this, many monitoring programs ignore changes in the bacterial communities that are the base of food webs in streams, often focusing on stream physicochemical assessments or macroinvertebrate community diversity instead. We used 16S rRNA gene sequencing to assess bacterial community compositions within 600 New Zealand stream biofilm samples from 204 sites within a 6-week period (February–March 2010). Sites were either dominated by indigenous forests, exotic plantation forests, horticulture, or pastoral grasslands in the upstream catchment. We sought to predict each site’s catchment land use and environmental conditions based on the composition of the stream bacterial communities. Results Random forest modelling allowed us to use bacterial community composition to predict upstream catchment land use with 65% accuracy; urban sites were correctly assigned 90% of the time. Despite the variation inherent when sampling across a ~ 1000-km distance, bacterial community data could correctly differentiate undisturbed sites, grouped by their dominant environmental properties, with 75% accuracy. The positive correlations between actual values and those predicted by the models built using the stream biofilm bacterial data ranged from weak (average log N concentration in the stream water, R2 = 0.02) to strong (annual mean air temperature, R2 = 0.69). Conclusions Freshwater bacterial community data provide useful insights into land use impacts on stream ecosystems; they may be used as an additional measure to screen stream catchment attributes.

Published
2024
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