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1. Associations between daily step count classifications and continuous glucose monitoring metrics in adults with type 1 diabetes: analysis of the Type 1 Diabetes Exercise Initiative (T1DEXI) cohort

Author

Turner, Lauren V., Marak, Martin Chase, Gal, Robin L., Calhoun, Peter, Li, Zoey, Jacobs, Peter G., Clements, Mark A., Martin, Corby K., Doyle, III, Francis J., Patton, Susana R., Castle, Jessica R., Gillingham, Melanie B., Beck, Roy W., Rickels, Michael R., and Riddell, Michael C.

Published
2024
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2. From isolated polyelectrolytes to star-like assemblies: The role of sequence heterogeneity on the statistical structure of the intrinsically disordered Neurofilament-low tail domain

Author

Kravikass, Mathar, Koren, Gil, Saleh, Omar A., and Beck, Roy

Subjects
Physics - Biological Physics, Condensed Matter - Soft Condensed Matter
Abstract

Intrinsically disordered proteins (IDPs) are a subset of proteins that lack stable secondary structure. Given their polymeric nature, previous mean-field approximations have been used to describe the statistical structure of IDPs. However, the amino-acid sequence heterogeneity and complex intermolecular interaction network have significantly impeded the ability to get proper approximations. One such case is the intrinsically disordered tail domain of Neurofilament low (NFLt), which comprises a 50 residue-long uncharged domain followed by a 96 residue-long negatively charged domain. Here, we measure two NFLt variants to identify the impact of the NFLt two main subdomains on its complex interactions and statistical structure. Using synchrotron small-angle x-ray scattering, we find that the uncharged domain of the NFLt induces attractive interactions that cause it to self-assemble into star-like polymer brushes. On the other hand, when the uncharged domain is truncated, the remaining charged N-terminal domains remain isolated in solution with typical polyelectrolyte characteristics. We further discuss how competing long- and short-ranged interactions within the polymer brushes dominate their ensemble structure, and, in turn, their implications on previously observed phenomena in NFL native and diseased states.

Published
2023
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3. Modulating Hierarchical Self-Assembly In Thermoresponsive Intrinsically Disordered Proteins Through High-Temperature Incubation Time

Author

Sethi, Vaishali, Cohen-Gerassi, Dana, Meir, Sagi, Ney, Max, Shmidov, Yulia, Koren, Gil, Adler-Abramovich, Lihi, Chilkoti, Ashutosh, and Beck, Roy

Subjects
Physics - Biological Physics, Condensed Matter - Soft Condensed Matter, Quantitative Biology - Biomolecules
Abstract

The cornerstone of structural biology is the unique relationship between protein sequence and the 3D structure at equilibrium. Although intrinsically disordered proteins (IDPs) do not fold into a specific 3D structure, breaking this paradigm, some IDPs exhibit large-scale organization, such as liquid-liquid phase separation. In such cases, the structural plasticity has the potential to form numerous self-assembled structures out of thermal equilibrium. Here, we report that high-temperature incubation time is a defining parameter for micro and nanoscale self-assembly of resilin-like IDPs. Interestingly, high-resolution scanning electron microscopy micrographs reveal that an extended incubation time leads to the formation of micron-size rods and ellipsoids that depend on the amino acid sequence. More surprisingly, a prolonged incubation time also induces amino acid composition-dependent formation of short-range nanoscale order, such as periodic lamellar nanostructures. We can correlate the lamellar structures to \b{eta}-sheet formation and demonstrate similarities between the observed nanoscopic structural arrangement and spider silk. We, therefore, suggest that regulating the period of high-temperature incubation, in the one-phase regime, can serve as a unique method of controlling the hierarchical self-assembly mechanism of structurally disordered proteins., Comment: 27pages, 8 figures

Published
2023

4. The Insulin-Only Bionic Pancreas Improves Glycemic Control in Non-Hispanic White and Minority Adults and Children With Type 1 Diabetes.

Author

Castellanos, Luz, Russell, Steven, Damiano, Edward, Beck, Roy, Shah, Viral, Bailey, Ryan, Calhoun, Peter, Bird, Keisha, and Mauras, Nelly

Subjects
Adult, Child, Humans, Bionics, Blood Glucose, Diabetes Mellitus, Type 1, Glycemic Control, Insulin, Pancreas, White People, Minority Groups, Artificial Organs
Abstract

OBJECTIVE: We evaluated the performance of the iLet bionic pancreas (BP) in non-Hispanic White individuals (here referred to as Whites) and in Black, Hispanic, and other individuals (here collectively referred to as Minorities). RESEARCH DESIGN AND METHODS: A multicenter, randomized controlled trial evaluated glycemic management with the BP versus standard of care (SC) in 161 adult and 165 pediatric participants with type 1 diabetes over 13 weeks. RESULTS: In Whites (n = 240), the mean baseline-adjusted difference in 13-week HbA1c between the BP and SC groups was -0.45% (95% CI -0.61 to -0.29 [-4.9 mmol/mol; -6.6 to -3.1]; P < 0.001), while this difference among Minorities (n = 84) was -0.53% (-0.83 to -0.24 [-6.0 mmol/mol; -9.2 to -2.8]; P < 0.001). In Whites, the mean baseline-adjusted difference in time in range between the BP and SC groups was 10% (95% CI 7-12; P < 0.001) and in Minorities was 14% (10-18; P < 0.001). CONCLUSIONS: The BP improves glycemic control in both Whites and Minorities and offers promise in decreasing health care disparities.

Published
2023

5. Intramolecular Structural Heterogeneity altered by Long-range Contacts in an Intrinsically Disordered Protein

Author

Koren, Gil, Meir, Sagi, Holschuh, Lennard, Mertens, Haydyn D. T., Ehm, Tamara, Yahalom, Nadav, Golombek, Adina, Schwartz, Tal, Svergun, Dmitri I., Saleh, Omar A., Dzubiella, Joachim, and Beck, Roy

Subjects
Physics - Biological Physics, Condensed Matter - Soft Condensed Matter
Abstract

Short-range interactions and long-range contacts drive the 3D folding of structured proteins. The proteins' structure has a direct impact on their biological function. However, nearly 40% of the eukaryotes proteome is composed of intrinsically disordered proteins (IDPs) and protein regions that fluctuate between ensembles of numerous conformations. Therefore, to understand their biological function, it is critical to depict how the structural ensemble statistics correlate to the IDPs' amino acid sequence. Here, using small-angle x-ray scattering (SAXS) and time-resolved F\"orster resonance energy transfer (trFRET), we study the intra-molecular structural heterogeneity of the neurofilament low intrinsically disordered tail domain (NFLt). Using theoretical results of polymer physics, we find that the Flory scaling exponent of NFLt sub-segments correlates linearly with their net charge, ranging from statistics of ideal to self-avoiding chains. Surprisingly, measuring the same segments in the context of the whole NFLt protein, we find that regardless of the peptide sequence, the segments' structural statistics are more expanded than when measured independently. Our findings show that while polymer physics can, to some level, relate the IDP's sequence to its ensemble conformations, long-range contacts between distant amino acids play a crucial role in determining intra-molecular structures. This emphasizes the necessity of advanced polymer theories to fully describe IDPs ensembles with the hope it will allow us to model their biological function.

Published
2022
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7. Trial of Hybrid Closed-Loop Control in Young Children with Type 1 Diabetes.

Author

Wadwa, R, Reed, Zachariah, Buckingham, Bruce, DeBoer, Mark, Ekhlaspour, Laya, Forlenza, Gregory, Schoelwer, Melissa, Lum, John, Kollman, Craig, Beck, Roy, and Breton, Marc

Subjects
Child, Child, Preschool, Humans, Blood Glucose, Blood Glucose Self-Monitoring, Diabetes Mellitus, Type 1, Glycated Hemoglobin, Hypoglycemic Agents, Insulin, Insulin Infusion Systems
Abstract

BACKGROUND: Closed-loop control systems of insulin delivery may improve glycemic outcomes in young children with type 1 diabetes. The efficacy and safety of initiating a closed-loop system virtually are unclear. METHODS: In this 13-week, multicenter trial, we randomly assigned, in a 2:1 ratio, children who were at least 2 years of age but younger than 6 years of age who had type 1 diabetes to receive treatment with a closed-loop system of insulin delivery or standard care that included either an insulin pump or multiple daily injections of insulin plus a continuous glucose monitor. The primary outcome was the percentage of time that the glucose level was in the target range of 70 to 180 mg per deciliter, as measured by continuous glucose monitoring. Secondary outcomes included the percentage of time that the glucose level was above 250 mg per deciliter or below 70 mg per deciliter, the mean glucose level, the glycated hemoglobin level, and safety outcomes. RESULTS: A total of 102 children underwent randomization (68 to the closed-loop group and 34 to the standard-care group); the glycated hemoglobin levels at baseline ranged from 5.2 to 11.5%. Initiation of the closed-loop system was virtual in 55 patients (81%). The mean (±SD) percentage of time that the glucose level was within the target range increased from 56.7±18.0% at baseline to 69.3±11.1% during the 13-week follow-up period in the closed-loop group and from 54.9±14.7% to 55.9±12.6% in the standard-care group (mean adjusted difference, 12.4 percentage points [equivalent to approximately 3 hours per day]; 95% confidence interval, 9.5 to 15.3; P

Published
2023

8. Multicenter, Randomized Trial of a Bionic Pancreas in Type 1 Diabetes.

Author

Russell, Steven, Beck, Roy, Damiano, Edward, El-Khatib, Firas, Ruedy, Katrina, Balliro, Courtney, Li, Zoey, Calhoun, Peter, Wadwa, R, Buckingham, Bruce, Zhou, Keren, Daniels, Mark, Raskin, Philip, White, Perrin, Lynch, Jane, Pettus, Jeremy, Hirsch, Irl, Goland, Robin, Buse, John, Kruger, Davida, Mauras, Nelly, Muir, Andrew, McGill, Janet, Cogen, Fran, Weissberg-Benchell, Jill, Sherwood, Jordan, Castellanos, Luz, Hillard, Mallory, Tuffaha, Marwa, Putman, Melissa, Sands, Mollie, Forlenza, Gregory, Slover, Robert, Messer, Laurel, Cobry, Erin, Shah, Viral, Polsky, Sarit, Lal, Rayhan, Ekhlaspour, Laya, Hughes, Michael, Basina, Marina, Hatipoglu, Betul, Olansky, Leann, Bhangoo, Amrit, Forghani, Nikta, Kashmiri, Himala, Sutton, Francoise, Choudhary, Abha, Penn, Jimmy, Jafri, Rabab, Rayas, Maria, Escaname, Elia, Kerr, Catherine, Favela-Prezas, Ruby, Trikudanathan, Subbulaxmi, Williams, Kristen, Leibel, Natasha, Kirkman, M, Bergamo, Kate, Klein, Klara, Dostou, Jean, Machineni, Sriram, Young, Laura, Diner, Jamie, Bhan, Arti, Jones, J, Benson, Matthew, Bird, Keisha, Englert, Kimberly, Permuy, Joe, Cossen, Kristina, Felner, Eric, Salam, Maamoun, Silverstein, Julie, Adamson, Samantha, Cedeno, Andrea, Meighan, Seema, Dauber, Andrew, and Boeder, Schafer

Subjects
Adolescent, Adult, Aged, Bionics, Blood Glucose, Blood Glucose Self-Monitoring, Child, Diabetes Mellitus, Type 1, Glycated Hemoglobin, Humans, Hypoglycemic Agents, Insulin, Insulin Aspart, Insulin Infusion Systems, Insulin Lispro, Middle Aged, Young Adult
Abstract

BACKGROUND: Currently available semiautomated insulin-delivery systems require individualized insulin regimens for the initialization of therapy and meal doses based on carbohydrate counting for routine operation. In contrast, the bionic pancreas is initialized only on the basis of body weight, makes all dose decisions and delivers insulin autonomously, and uses meal announcements without carbohydrate counting. METHODS: In this 13-week, multicenter, randomized trial, we randomly assigned in a 2:1 ratio persons at least 6 years of age with type 1 diabetes either to receive bionic pancreas treatment with insulin aspart or insulin lispro or to receive standard care (defined as any insulin-delivery method with unblinded, real-time continuous glucose monitoring). The primary outcome was the glycated hemoglobin level at 13 weeks. The key secondary outcome was the percentage of time that the glucose level as assessed by continuous glucose monitoring was below 54 mg per deciliter; the prespecified noninferiority limit for this outcome was 1 percentage point. Safety was also assessed. RESULTS: A total of 219 participants 6 to 79 years of age were assigned to the bionic-pancreas group, and 107 to the standard-care group. The glycated hemoglobin level decreased from 7.9% to 7.3% in the bionic-pancreas group and did not change (was at 7.7% at both time points) in the standard-care group (mean adjusted difference at 13 weeks, -0.5 percentage points; 95% confidence interval [CI], -0.6 to -0.3; P

Published
2022

9. Complications, Visual Acuity, and Refractive Error 3 Years after Secondary Intraocular Lens Implantation for Pediatric Aphakia

Author

Freedman, Sharon F., Wallace, David K., Enyedi, Laura B., Prakalapakorn, Sasapin, Jones, Sarah K., Hug, Denise, Stahl, Erin D., Dent, Rebecca J., Kong, Lingkun, Wang, Serena, Gallerson, Bryan K., Hutchinson, Amy K., Lenhart, Phoebe, Brower, Judy, Morrison, David G., Ruark, Scott T., Mets-Halgrimson, Rebecca, Yoon, Hawke, Ralay-Ranaivo, Hantamalala, Hamidullah, Aaliyah, Areaux, Raymond, Anderson, Jill S., Holleschau, Ann M., Superstein, Rosanne, Belanger, Caroline, Fallaha, Nicole, Hamel, Patrick, Thibeault, Maryse, Tamkins, Susanna M., Chang, Ta, Park, Hee-Jung S., Trumler, Anya A., Liu, Xiaonong, Astle, William F., Sanders, Emi N., Traboulsi, Elias, Ghasia, Fatema, McOwen, Diana C., Gray, Michael E., Yang, Michael B., Bowman, Corey S., Galvin, Jennifer, Therriault, Margaret, Smith, Heather, Whitaker, Michele E., Orge, Faruk, Grigorian, Adriana P., Baird, Alicia M., Strominger, Mitchell B., Chen, Vicki, Klein, Shelley, Kemmer, Jacquelyn D., Neiman, Alexandra E., Mendoza, Myra N., Frohwein, Jill J., Bremer, Don, Cassady, Cybil, Golden, Richard, Jordan, Catherine, Rogers, David, Oravec, Sara A., Yanovitch, Tammy L., Lunsford, Keven, Nye, Christina, Shea, Caroline, Stillman, SueAnn M., LaRoche, G. Robert, Van Iderstine, Stephen C., Robertson, Elisa, Cruz, Oscar A., Ghadban, Rafif, Govreau, Dawn, Larson, Scott A., Longmuir, Susannah, Shan, Xiaoyan, Clarke, Michael P., Taylor, Kate, Powell, Christine, Hammond, Benjamin P., Gearinger, Matthew D., Czubinski, Andrea, Hendricks, Dorothy H., Jin, Jing, Salvin, Jonathan H., Fisher, Alicia, Lee, Katherine A., Brooks, Daniel, Schweinler, Bonita R., Sala, Nicholas A., Sala, Allyson M., Summers, Allison I., Karr, Daniel J., Wilson, Lorri B., Rauch, Paula K., O'Hara, Mary, Gandhi, Nandini, Hashmi, Tania, Colburn, Jeffrey, Dittman, Eileen, Whitfill, Charles R., Wheeler, Amy M., McCourt, Emily A., Singh, Jasleen, Welnick, Nanastasia, Azar, Nathalie F., Baker, Joseph, Droste, Patrick J., Peters, Robert J., Hilbrands, Jan, Pineles, Stacy L., Bernardo, Marianne J., Peterson, Edward, Peterson, Charla H., Kumar, Kartik, Melese, Ephrem, Lingua, Robert, Grijalva, Jeff, Crouch, Earl R., jr., Crouch, Earl R., III, Ventura, Gaylord, Anninger, William, Benson, Shawn L., Karp, Karen A., Smith, Jordana M., Brickman-Kelleher, Jill, Ticho, Benjamin H., Khammar, Alexander J., Clausius, Deborah A., Guo, Suquin, Suh, Donny, Chamberlain, Carolyn, Schloff, Susan, Madigan, William P., Burkman, Donna, Christiansen, Stephen P., Ramsey, Jean E., McConnell, Kate H., Friedman, Ilana, Rosado, Jose, Sauberan, Donald P., Hemberger, Jody C., Davis, Patricia L., Rudaitis, Indre, Lowery, Robert S., Cupit, Shawn, Bothun, Erick D., Mohney, Brian G., Wernimont, Suzanne M., Neilsen, Rebecca A., Herlihy, Erin P., Baran, Francine, Gladstone, Amy, Smith, Justin, Mellott, Mei, Kieser, Troy, Erzurum, S. Ayse, Colon, Beth, Shah, Birva, Quebbemann, Micaela, Beck, Roy W., Austin, Darrell S., Boyle, Nicole M., Conner, Courtney L., Chandler, Danielle L., Donahue, Quayleen, Fimbel, Brooke P., Robinson, Julianne L., Hercinovic, Amra, Hoepner, James E., Kaplon, Joseph D., Henderson, Robert J., Melia, B. Michele, Ortiz, Gillaine, Woodard, Victoria C., Stutz, Kathleen M., Sutherland, Desirae R., Wu, Rui, Everett, Donald F., Diener-West, Marie, Baker, John D., Davis, Barry, Phelps, Dale L., Poff, Stephen W., Saunders, Richard A., Tychsen, Lawrence, Bradfield, Yasmin S., Foster, Nicole C., Plager, David A., Salchow, Daniel J., Birch, Eileen E., Manny, Ruth E., Silver, Jayne L., Weise, Katherine K., Verderber, Lisa C., Repka, Michael X., Dean, Trevano W., Kraker, Raymond T., Li, Zhuokai, Yen, Kimberly G., de Alba Campomanes, Alejandra G., Young, Marielle P., Rahmani, Bahram, Haider, Kathryn M., Whitehead, George F., Lambert, Scott R., Kurup, Sudhi P., Kraus, Courtney L., Cotter, Susan A., Holmes, Jonathan M., Hatt, Sarah R., and Traboulsi, Elias I.

Published
2024
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13. Home OCT Imaging for Newly Diagnosed Neovascular Age-Related Macular Degeneration: A Feasibility Study

Author

Glassman, Adam R., Beck, Roy W., Baptista, Alyssa, Beaulieu, Wesley T., Calhoun, Claire T., Constantine, Sharon R., Dale, Brian B., Dupre, Simone S., Franklin, Crystal A., Galusic, Sandra, Huggins, Meagan, Hunter, Brenda L., Johnson, Paula A., Josic, Kristin, Kelly, Brittany, Liu, Danni, Maguire, Maureen G., Meadows, Britney, Melia, Michele, Preston, Carin M., Stockdale, Cynthia R., Zokruah, Alice, Sun, Jennifer K., Martin, Daniel F., Bhargava, Sangeeta, Barkmeier, Andrew J., Baskin, Darrell, Blodi, Barbra, Chew, Emily, Ferris, Frederick L., III, Jaffe, Glenn J., Jampol, Lee M., Jhaveri, Chirag D., MacCumber, Mathew, Maturi, Raj K., Solomon, Sharon D., Antoszyk, Andrew N., Lujan, Brandon, Slahi-Had, Hani, Lane, Richard Gary, Adams, Lydia, Rivera, Rachel R., Nakoski, Brenda, Weeks, Rhonda F., Braverman, Allan L., McDonald-Mueller, Lauren, Stuart, Maria A., Pulliam, Brook G., Boyd, Lynda K., Wehmeier, Jarrod, Schremp, Steve A., Googe, Joseph M., Oliver, Kristina, Walsh, Justin, Asher, Julie, Milstead, Katie, Wheeler, Jeff, Griffone, Hodge A., Blinder, Kevin J., Calhoun, Claire, Mein, Calvin E., Baskin, Darrell E., Vieyra, Gabriela, and Chica, Moises A.

Published
2024
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14. Order from disorder with intrinsically disordered peptide amphiphiles

Author

Jacoby, Guy, Asher, Merav Segal, Ehm, Tamara, Ionita, Inbal Abutbul, Shinar, Hila, Azoulay-Ginsburg, Salome, Danino, Dganit, Kozlov, Michael M., Amir, Roey J., and Beck, Roy

Subjects
Condensed Matter - Soft Condensed Matter, Condensed Matter - Mesoscale and Nanoscale Physics, Physics - Biological Physics, Physics - Chemical Physics
Abstract

Amphiphilic molecules and their self-assembled structures have long been the target of extensive research due to their potential applications in fields ranging from materials design to biomedical and cosmetic applications. Increasing demands for functional complexity have been met with challenges in biochemical engineering, driving researchers to innovate in the design of new amphiphiles. An emerging class of molecules, namely, peptide amphiphiles, combines key advantages and circumvents some of the disadvantages of conventional phospholipids and block-copolymers. Herein, we present new peptide amphiphiles comprised of an intrinsically disordered peptide conjugated to two variants of hydrophobic dendritic domains. These molecules termed intrinsically disordered peptide amphiphiles (IDPA), exhibit a sharp pH-induced micellar phase-transition from low-dispersity spheres to extremely elongated worm-like micelles. We present an experimental characterization of the transition and propose a theoretical model to describe the pH-response. We also present the potential of the shape transition to serve as a mechanism for the design of a cargo hold-and-release application. Such amphiphilic systems demonstrate the power of tailoring the interactions between disordered peptides for various stimuli-responsive biomedical applications., Comment: 27 pages, 4 figures, supplementary information file

Published
2021
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15. Intrinsically Disordered Proteins at the Nano-scale

Author

Ehm, Tamara, Shinar, Hila, Meir, Sagi, Sekhon, Amandeep, Sethi, Vaishali, Morgan, Ian L., Rahamim, Gil, Saleh, Omar A., and Beck, Roy

Subjects
Physics - Biological Physics, Condensed Matter - Mesoscale and Nanoscale Physics, Condensed Matter - Soft Condensed Matter, Quantitative Biology - Biomolecules, Quantitative Biology - Quantitative Methods
Abstract

The human proteome is enriched in proteins that do not fold into a stable 3D structure. These intrinsically disordered proteins (IDPs) spontaneously fluctuate between a large number of configurations in their native form. Remarkably, the disorder does not lead to dysfunction as with denatured folded proteins. In fact, unlike denatured proteins, recent evidences strongly suggest that multiple biological functions stem from such structural plasticity. Here, focusing on the nanoscopic length-scale, we review the latest advances in IDP research and discuss some of the future directions in this highly promising field., Comment: 15 pages, 5 figures

Published
2021
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17. Assessment of Baseline Ultrawidefield Fluorescein Angiographic Quantitative Leakage Parameters with Ultrawidefield Fundus Features and Clinical Parameters in Diabetic Retinopathy in Protocol AA

Author

Harara, Abla M., Palacios, Angela N., Berger, Brian B., Corak, Boris, Luong, Bianca, Jhaveri, Chirag D., Wilson, Daniela Mariel, Jonna, Gowtham, Gunderson, Ivana, Hosein, Kimberly, Reid, Ryan M., Chexal, Saradha, Moore, Tori, Seidu, Tina A., Gatavaski, Valerie, Ren, Yong, Stern, Bradley A., Benvenutti, Celia E., Oude-Reimerink, Dinah S., Shaheen, Jenny, Grybas, John, Vitale-Kuhn, Julianne, Staffne, Jessica L., Ventimiglia, Katie M., Allis, Megan, Monk, Mary K., Thomas, Marc E., Massu, Nicole M., Edwards, Paul Andrew, Troszak, Tracy A., Irons, Amber N., Rego, Brittany, Han, Dennis P., Dorsey, Eleanor, Nelson, Erika, Sheppard, Hannah, Beringer, Joseph R., Kim, Judy E., Keller, Kristy L., Packard, Krissa L., Altmann, Marriner L., Goldberg, Mara, Chen, Nickolas, Winter, Pat A., Bourgeois, Shay, Jacobo, Samantha, Moebius, Stephanie J., Connor, Thomas B., Barwick, Vicki, Williams, Vesper V., Wirostko, William J., Ghuman, A. Thomas, Leslie, Anita H., Sharma, Ashish G., Kiesel, Cheryl, Dyshanowitz, Danielle, Knips, Eileen, Wing, Glenn, Walker, Joseph P., Raskauskas, Paul A., Kiesel, Raymond K., Schlossman, Deborah K., Weimann, Elizabeth S., Sharuk, George S., Kwak, Hanna, Cavallerano, Jerry D., Rhee, Jae W., Sampani, Konstantina, Tran, Katie V., Bestourous, Leila, Miranda, Linette, Krigman, Michael N., Stockman, Margaret E., Arrigg, Paul G., Cavicchi, Robert W., Kirby, Rita K., Glynn, Shireen, Papaconstantinou, Steve L., Shah, Sabera T., Murtha, Timothy J., Carli, William, Finch, Autumn K., Gentile, Angella K., Price, Angela K., Murphy, Brittany A., Rowland, Beverly O., Fleming, Christina J., Mahr, Courtney, Shore, Carol A., Browning, David, McClain, Donna, Breglio, Erica, Lester, Gina M., Herby, Jenna T., Bratcher, Kayla A., Clark, Loraine M., Jackson, Lisa A., Watson, Lynn, McOwen, Michael D., Punjabi, Omar S., Bojaj, Swann J., Ennis, Sarah A., Fredenberg, Sherry L., Jones, Taylor S., Ragin, Teneisha A., Balasubramaniam, Uma M., Ornelas, Blanca, Rodriquez, Brenda, Edwards, Carla, Carns, Danielle R., Tonner, Eileen E., Woo, Kisung, Richine, Len, MacCumber, Mathew W., Merrill, Pauline Townsend, Kociborski, Sarah, Harless, Ashley M., Harris, Charlotte, White, Lorraine, Maturi, Raj K., Asher, Julie, Walsh, Justin, Wheeler, Jeff, Milstead, Katie, Oliver, Kristina, Lovelady, Lisa, Anderson, Nicholas G., Coppola, Patricia, Lince, Raul E., Shuler, R. Keith, Morris, Steve, Oelrich, Sarah M., Gardner, Brandon S., Moore, Bob, Cain, Dennis, Donohue, Deborah, Emmert, David, Adeyemo, Kemi, Levin, Lisa K., Frey, Mary, Rhoton, Nick, Bressler, Susan, Solomon, Sharon D., Ford, Amy L., Hughes, Ashley, Brewer, Alisha N., Booth, JoAnn T., Lunsford, Keven W., Ukleya, Lauren D., Burris, Russ, Kingsley, Ronald M., Almeida, Shannon R., Icks, Sonny, Shah, Vinay A., Bergman, Vanessa A., Castellarin, Alessandro A., Shook, Aimee H., Walker, Aimee, Pieramici, Dante J., Hong, Gina, Avery, Kelly, McKee, Kate M., Giust, Matthew, Munoz, Marco A., Fishbein, Sarah, Camp, Alecia B., Baker, Carl W., Baker, Jil D., Sedberry, Kylie S., Lambert, Lynnette F., Orr, Margaret J., Alcaraz, Sonya L., Kettler, Samantha, Caldwell, Tracey M., Miller, Abigail, Dorr, Christine M., Hampton, G. Robert, Brown, Jamin S., Barker, Jeffrey P., Rosenberg, Kevin I., Kwasniewski, Lynn M., Sienkiewycz, Laurie J., Spuches, Lisa, Manley, Michelle L., Robarge, Nicole E., DeSantis, Stefanie R., DeForge, Teresa M., Brucker, Alexander J., Kim, Benjamin J., Berger, Jim M., DuPont, Joan C., Drossner, Sheri, Freeman, Sara, Studebaker, Ashley, Payne, John F., Wells, John A., Spivey, Robbin, Ogbuewu, Tiffany N., Swinford, Tiffany R., Guillory, Adrienne, Hutson, Amy, Schefler, Amy C., Shah, Ankoor R., Almanza, Belinda A., Dives, Brenda, Richter, Beau A., Stoever, Cary A., Brown, David M., Foerster, Danee, Garcia, David, Rodriguez, Diana, Park, Daniel, Chen, Eric, Kegley, Eric N., Quellar, Elizabeth, Twining, Garret L., Koger-Grifaldo, Heather, Ortega, Ilsa, Carranza, Jolene, Major, James C., Williamson, Kimberly, Burt, Lindsay, Salinas, Luis R., Wolff, Lisa M., Benz, Matthew S., Estes, Maura A., James, Miranda F., Berry, Meredith, Vela, Melina, Landaverde, Nubia, Webb, Nina A., Fish, Richard H., Kim, Rosa Y., Yee, Rebecca, Karani, Sadia Y., Supapo, Stacy M., Dodel, Tamara L., McCoy, Tyneisha, Wong, Tien P., Sneed, Veronica A., Barnhart, Cassandra J., Cantrell, Debra, DuBose, Elizabeth L., Sharpe, Houston P., Ulrich, Jan Niklas, Bhansali, Kanika A., Esquejo, Rona Lyn, Garg, Seema, Grout, Sean, McKinney, Allen, Bobbitt, Brenda J., Wendel, Ceara L., Fagan, Damanda F., Andrews, Jacqueline, Holmes, Krystal Nikki, Seyez, Karen L., Williamson, Kimberly A., Moinfar, Nader, Walters, Paige N., Carlton, Steve, Rehling, Shannon M., Williams, Shana E., Reed, Tiara L., VandeVelde, Amber R., Yeager, Frank T., Fox, Gregory M., Batlle, Ivan R., Bruce, Kiersten, Pippin, Katherine, Ainley, Lexie R., Singh, Ravi S.J., Adamo, Ashley M., Guardado, Adrian, Patel, Apurva K., Puckett, Brian S., Hoerner, Christine, Ma, Colin, Clark, David J., Flato, Inessa M., Cohen, Joshua, Charpentier, Margaret E., Kopfer, Marcia, Peters, Mark A., Smith, Pualani, Tlucek, Paul S., Hobbs, Stephen, Ho, Stephanie L., Metzger, Ashley M., McCalla, Alesia K., Thompson, Amy, Ringrose, Christine, Sandler, Dallas R., Leder, Henry A., Belz, Jennifer L., Starr, JoAnn, Simmons, Jennifer L., Orr, Peggy R., Sotirakos, Peter, Singletary, Pamela V., Cain, Terri, Coffey, Teresa, Carter, Tiffany M., Robinson, Twyla J., Shah, Chirag P., Cammarata, Dominique, Kruger, Jennifer L., Colegrove, Lindsey, Graham, Margie, Gleason, Shane T., Noel, Bryan, Damron, Catherine, Holcomb, Diana M., Slade, Edward A., Van Arsdall, Jeanne, Bicknell, Lisa, Buck, Michelle, Stone, Thomas W., Farooq, Amina, Parsons, Brook, Singh, Harinderjit, Ivey, Ken, Foster, Lindsay Allison, Woodward, Michele, Ortiz, Siobhan O., Bailey, Thomas, Mynampati A, Bharani Krishna, White, Cheryl L., Hamdani, Ghulam Shabbir, Smith, Jazzmin N., Chalam, Kakarla V., Sambhav, Kumar, Babaria, Romesh, Grover, Sandeep, Carroll, Catherine, Chau, Felix Y., Lim, Jennifer I., Talasnik, Lauren A., Janowicz, Mark, Stankovic, Natasa, Berlatsky, Sarah L., Niec, Marcia, Sun, Jie, Johnson, Tametha, Ovando, Yesenia, Nakoski, Brenda, Mein, Calvin E., Wienecke, Christopher Sean, Castillo, Elaine, Baker, Jaynee, San Roman, Jonathan, Adams, Lydia, Kirschbaum, Lita, Chica, Moises A., Cloudt, Sara L., Moore, Tori R., Sabates, Felix N., Gallimore, Gary S., Chen, Yin C., Swann, Adrienne C., Cadwell, Deborah M., Diddie, Kenneth R., Boisvert, Taryn F., Tessau, Carrie D., Bowers, Jack, Nielsen, Jared S., Rostvold, Jay, Spillman, Jamie, Alliman, Kyle J., Boender, Lisa M., Johnson, Marilyn A., Parker, Marianne, Bix, Paula L., Ridgway, Spencer D., Woehl, Tami Jo, Stonewall, Whitney, Brown, Christopher M., Lema, Gareth M.C., Wiechelt, Luann, Yoganathan, Pradeepa, Boglione, Sandra L., Montesclaros, Chris A., Mangham, Cory, Karsaliya, Gopal, Le, Phillip V., Wong, Robert W., Godfrey, Anne Marie, Kuzmanovic, Aleksandra, Kirker, Andrew William, Harrison, Bryan, Forooghian, Farzin, Elvena, Garnet Louise, Hall, Laura J., Turhal, Bilgin, Brown, Ian, Kotei, Isaac A., Chen, Lina, Brent, Michael Henry, Moon, Michelle, Sutakovic, Olivera, Chang, Angela, Godfrey, Anne-Marie, Albiani, David, Maberley, David A.L., Navajas, Eduardo Vitor, Grant, Kelly, Tran, Khoi A., Jovanovic, Mira, Cao, Sijia, Wiens, Theresa, Kozbial, Andrzej, Orlin, Anton, Lenane, Courtney Nichole, Herder, Susan P., Kiss, Szilard, Reeves, Tom, Cruess, Alan F., Dean, Andrea, Hoskin-Mott, Ann, Morrison, Christine, Caldwell, Meggie D., Hynes, Mitzi, Gupta, R. Rishi, Durling, Stacey, MacDonnell, Trina, Beck, Roy W., Baptista, Alyssa, Beaulieu, Wesley T., Calhoun, Claire T., Constantine, Sharon R., Correia, Isabella, Dale, Brian B., Dupre, Simone S., Franklin, Crystal A., Galusic, Sandra, Huggins, Meagan, Hunter, Brenda L., Johnson, Paula A., Josic, Kristin, Kelly, Brittany, Maguire, Maureen G., Meadows, Britney, Stockdale, Cynthia R., Zokruah, Alice, Bhargava, Sangeeta, Barkmeier, Andrew J., Baskin, Darrell, Blodi, Barbra, Chew, Emily, Ferris, Frederick L., Jaffe, Glenn J., Bressler, Neil M., Lujan, Brandon, Tolls, Dorothy, Sheridan, Daniel, Pitoc, Cloyd M., Anne C Aquino, Lizzie, Salva, Claude Michael G., Lewis, Drew, Stainback, Jeffery, Makkena, Vijaya, Winter, Katrina, Mora, Adiel, Harrington, Chris, Vinh, Doc-Lap, Ehlers, Justis P., Yordi, Sari, Martin, Alison, Srivastava, Sunil K., and Sun, Jenifer K.

Published
2024
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18. Eight-Year Outcomes of Bilateral Lateral Rectus Recessions versus Unilateral Recession-Resection in Childhood Basic-Type Intermittent Exotropia

Author

Miller, Aaron M., Olvera, Maria N., Alexander, Monsey L., Curtin, Kathleen Mary, Dillon, Angela C., Gray, Carole L., Jackson, Jorie L., Qadir, Ximena V., Ramos, Cynthia R., Paysse, Evelyn A., Coats, David K., Yen, Kimberly G., Romany, Gihan, Homann, Melynda J., Kong, Lingkun, Law, Christine, Churchill, Sarah, MacSween, Lesley E., Hoover, Darren L., Huston, Pamela A., Racan, Pamela M., Soros, Kari E., Sala, Nicholas A., Sala, Nicholas Anthony, Johnson, Catherine, Sala, Allyson, Zeto, V. Lori, Donahue, Sean P., Wilkins, Carsyn Saige, Biernacki, Ronald J., Campbell, Megan K., Fraine, Lisa A., Ruark, Scott T., Crouch, Eric, Crouch, Earl R., Jr., Ventura, Gaylord G., Fritz, Carolina Andrea, Anderson, Jill S., Areaux, Raymond G., Jr, Holleschau, Ann M., Harder, Jessica Ann, May, Laura M., Merrill, Kim S., Schweigert, Anna I., Petersen, David B., Pickens, Tori S., McMurtrey, J. Ryan, Morrell, Beth A., Repka, Michael X., Liu, Xiaonong, Christoff, Alex, Silbert, David I., Modjesky, Heather, Woodall, Hayley L., Summers, Allison I., Kuo, Annie F., Wilson, Lorri B., Rauch, Paula, Lee, Jessy, Casey, Grant A., Narain, Srianna, Woodruff, Kevin, Ticho, Benjamin H., Clausius, Deborah A., Allen, Megan, Quebbemann, Micaela N., Shah, Birva K., Bothun, Erick D., Holmes, Jonathan M., Mohney, Brian G., Wernimont, Suzanne M., Czaplewski, Lindsay L., Eastman, Stacy L., Huisman, Jordan Joseph, Klaehn, Lindsay D., Kramer, Andrea M., Kroening, Rose M., Priebe, Debbie M., Wohlers, Moriah A., Jensen, Allison A., Flanagan, Maureen A., Tolbert, Tiffany Talia, Traboulsi, Elias, Ghasia, Fatema F., Meador, Angela M., McOwen, Diana Christine, Enyedi, Laura B., Jones, Sarah K., Kashyap, Namita, Loud, Rachel N., Waters, Amy L., Marsh, Justin D., Bond, Lezlie L., Ariss, Michelle M., Dent, Rebecca J., Phillips, Paul H., Lowery, Robert Scott, Haley, Wendy Jean, Brown, Shaina, Colon, Beth, Cupit, Shawn L., Holtorf, Hannah L., Sanders, Hayley Elizabeth, Bowsher, James D., Cheeseman, Edward W., Weas, Nikki M., Bradham, Carol U., Rahmani, Bahram, Ranaivo, Hantamalala Ralay, Cruz, Karla G., De Leon, Erika A., Klauer, Anthony Jeffrey, Tzanetakos, Vivian, McCoy Vrablec, Laura, Orge, Faruk H., Richards, Leslie, Baird, Alicia Marie, Glaser, Stephen R., Yost, Kasey L., Flores, Odalis R., Herlihy, Erin P., Taira, Alyssa, Alexander, Jessica, Gladstone, Amy, Kiens, Bridget Ann, Tews, Lyndsey A., Whitehead, George F., Shea, Caroline J., Stillman, SueAnn Marie, Nye, Christina N., Bartiss, Michael John, McGaw, Tennille F., Davis, Patricia L., Hulett, Katie R., Twite, Jacqueline, Bradfield, Yasmin S., Adler, Angela M., Anderson, Kristin A., Kraker, Raymond T., Beck, Roy W., Austin, Darrell S., Boyle, Nicole M., Chandler, Danielle L., Connelly, Patricia L., Conner, Courtney L., Donahue, Quayle, Fimbel, Brooke P., Henderson, Robert J., Hoepner, James E., Kaplon, Joseph D., Melia, B. Michele, Ortiz, Gillaine, Robinson, Julianne L., Stutz, Kathleen M., Sutherland, Desirae R., Toro, David O., Woodard, Victoria C., Wu, Rui, Cotter, Susan A., Birch, Eileen E., Christiansen, Stephen P., Hatt, Sarah R., Leske, David A., Melia, Michele, O’Hara, Mary, Pang, Yi, Romanchuck, Kenneth, Tamkins, Susanna M., Wallace, David K., Wheeler, David T., Bhatt, Amit, Chen, Angela M., Cheung, Nathan L., Cobb, Patricia, Colon, Beth J., Crouch, Eric R., Dean, Trevano W., Erzurum, S. Ayse, Esposito, Christina A., Fang, Caroline C., Gray, Michael E., Gunton, Kammi B., Hopkins, Kristine B., Jastrzembski, Benjamin G., Jenewein, Erin C., Jordan, Catherine O., Kraus, Courtney, Kurup, Sudhi P., Lazar, Elizabeth L., Li, Zhuokai, Lorenzana, Ingryd, McDowell, Paula S., Morrison, Ann M., Morrison, David G., Nylin, Elyse, Parker, Sue M., Patel, Reena, Plaumann, Maureen D., Pollack, Karen, Raghuram, Aparna, Retnasothie, Dashaini V., Roberts, Tawna L., Scheiman, Mitchell M., Shah, Veeral S., Superstein, Rosanne, Titelbaum, Jenna R., Vricella, Marilyn, Yamada, Tomohiko, Astle, William F., Christian, Melanie L., Everett, Donald F., Freedman, Sharon F., Good, William V., Lambert, Scott R., Lee, Katherine A., London, Richard, Manh, Vivian M., Manny, Ruth E., Pineles, Stacy L., Rogers, David L., Schweinler, Bonita R., Silver, Jayne L., Suh, Donny W., Verderber, Lisa C., Weise, Katherine K., Diener-West, Marie, Baker, John D., Davis, Barry, Higgins, Rosemary D., Poff, Stephen W., Saunders, Richard A., and Tychsen, Lawrence

Published
2024
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19. Machine-learning Iterative Calculation of Entropy for Physical Systems

Author

Nir, Amit, Sela, Eran, Beck, Roy, and Bar-Sinai, Yohai

Subjects
Condensed Matter - Statistical Mechanics, Condensed Matter - Disordered Systems and Neural Networks, Condensed Matter - Soft Condensed Matter
Abstract

Characterizing the entropy of a system is a crucial, and often computationally costly, step in understanding its thermodynamics. It plays a key role in the study of phase transitions, pattern formation, protein folding and more. Current methods for entropy estimation suffer either from a high computational cost, lack of generality or inaccuracy, and inability to treat complex, strongly interacting systems. In this paper, we present a novel method, termed MICE, for calculating the entropy by iteratively dividing the system into smaller subsystems and estimating the mutual information between each pair of halves. The estimation is performed with a recently proposed machine learning algorithm which works with arbitrary network architectures that can be chosen to fit the structure and symmetries of the system at hand. We show that our method can calculate the entropy of various systems, both thermal and athermal, with state-of-the-art accuracy. Specifically, we study various classical spin systems, and identify the jamming point of a bidisperse mixture of soft disks. Lastly, we suggest that besides its role in estimating the entropy, the mutual information itself can provide an insightful diagnostic tool in the study of physical systems., Comment: 8 pages, 4 figures + Supplementary information: 10 pages, 6 figures

Published
2020
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20. Glassy dynamics and memory effects in an intrinsically disordered protein construct

Author

Morgan, Ian L., Avinery, Ram, Rahamim, Gil, Beck, Roy, and Saleh, Omar A.

Subjects
Condensed Matter - Soft Condensed Matter, Physics - Biological Physics
Abstract

Glassy, nonexponential relaxations in globular proteins are typically attributed to conformational behaviors that are missing from intrinsically disordered proteins. Yet, we show that single molecules of a disordered-protein construct display two signatures of glassy dynamics, logarithmic relaxations and a Kovacs memory effect, in response to changes in applied tension. We attribute this to the presence of multiple independent local structures in the chain, which we corroborate with a model that correctly predicts the force dependence of the relaxation. The mechanism established here likely applies to other disordered proteins., Comment: 6 pages, 3 figures, accepted for publication in Physical Review Letters

Published
2020
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21. Super-resolution SAXS based on PSF engineering and sub-pixel detector translations

Author

Gutman, Benjamin, Mrejen, Michael, Shabat, Gil, Avinery, Ram, Shkolnisky, Yoel, and Beck, Roy

Subjects
Physics - Instrumentation and Detectors, Condensed Matter - Mesoscale and Nanoscale Physics, Physics - Applied Physics
Abstract

Small-angle X-ray scattering (SAXS) technique enables convenient nanoscopic characterization for various systems and conditions. Nonetheless, lab-based SAXS systems intrinsically suffer from insufficient x-ray flux and limited angular resolution. Here, we develop a two-step reconstruction methodology to enhance the angular resolution for given experimental conditions. Using minute hardware additions, we show that translating the x-ray detector in subpixel steps and modifying the incoming beam shape results in a set of 2D scattering images which is sufficient for super-resolution SAXS reconstruction. The technique is verified experimentally to show above 25\% increase in resolution. Such advantages have a direct impact on the ability to resolve faster and finer nanoscopic structures and can be implemented in most existing SAXS apparatuses., Comment: submitted to Journal of Applied Crystallography on Feb, 16th 2020

Published
2020
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23. C-peptide and metabolic outcomes in trials of disease modifying therapy in new-onset type 1 diabetes: an individual participant meta-analysis

Author

Greenbaum, Carla, Krisher, Jeffrey, Skyler, Jay, Wherrett, Diane, Hannelius, Ulf, Lindqvist, Anton, Nowak, Christoph, Bebu, Ionut, Braffett, Barbara, Napolitano, Antonella, Jan Mohamed, Salim, Weir, Gordon, Nepom, Gerald, Beck, Roy, Richard, Claudia, Hedrick, Joseph, Ludvigsson, Johnny, Von Herrath, Matthias, Leon, Francisco, Ramos, Eleanor, Narendran, Parth, Gitelman, Stephen, Dabelea, Dana, Andrews, Rob, Haller, Michael, Jensen, Elizabeth, Harold, Kevan, Dutz, Jan, Taylor, Peter N, Collins, Kimberly S, Lam, Anna, Karpen, Stephen R, Greeno, Brianna, Walker, Frank, Lozano, Alejandro, Atabakhsh, Elnaz, Ahmed, Simi T, Marinac, Marjana, Latres, Esther, Senior, Peter A, Rigby, Mark, Gottlieb, Peter A, and Dayan, Colin M

Published
2023
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24. Extended Use of the Control-IQ Closed-Loop Control System in Children With Type 1 Diabetes.

Author

Kanapka, Lauren, Wadwa, R, Breton, Marc, Ruedy, Katrina, Ekhlaspour, Laya, Forlenza, Gregory, Cengiz, Eda, Schoelwer, Melissa, Jost, Emily, Carria, Lori, Emory, Emma, Hsu, Liana, Weinzimer, Stuart, DeBoer, Mark, Buckingham, Bruce, Oliveri, Mary, Kollman, Craig, Dokken, Betsy, Cherñavvsky, Daniel, and Beck, Roy

Subjects
Adolescent, Blood Glucose, Child, Diabetes Mellitus, Type 1, Humans, Hypoglycemia, Hypoglycemic Agents, Insulin, Insulin Infusion Systems
Abstract

OBJECTIVE: To further evaluate the safety and efficacy of the Control-IQ closed-loop control (CLC) system in children with type 1 diabetes. RESEARCH DESIGN AND METHODS: After a 16-week randomized clinical trial (RCT) comparing CLC with sensor-augmented pump (SAP) therapy in 101 children 6-13 years old with type 1 diabetes, 22 participants in the SAP group initiated use of the CLC system (referred to as SAP-CLC cohort), and 78 participants in the CLC group continued use of CLC (CLC-CLC cohort) for 12 weeks. RESULTS: In the SAP-CLC cohort, mean percentage of time in range 70-180 mg/dL (TIR) increased from 55 ± 13% using SAP during the RCT to 65 ± 10% using CLC (P < 0.001), with 36% of the cohort achieving TIR >70% plus time

Published
2021

25. Delayed nucleation in lipid particles

Author

Jacoby, Guy, Portnaya, Irina, Danino, Dganit, Diamant, Haim, and Beck, Roy

Subjects
Condensed Matter - Soft Condensed Matter
Abstract

Metastable states in first-order phase-transitions have been traditionally described by classical nucleation theory (CNT). However, recently an increasing number of systems displaying such a transition have not been successfully modelled by CNT. The delayed crystallization of phospholipids upon super-cooling is an interesting case, since the extended timescales allow access into the dynamics. Herein, we demonstrate the controllable behavior of the long-lived metastable liquid-crystalline phase of dilauroyl-phosphatidylethanolamine (DLPE), arranged in multi-lamellar vesicles, and the ensuing cooperative transition to the crystalline state. Experimentally, we find that the delay in crystallization is a bulk phenomenon, which is tunable and can be manipulated to span two orders of magnitude in time by changing the quenching temperature, solution salinity, or adding a secondary phospholipid. Our results reveal the robust persistence of the metastability, and showcase the apparent deviation from CNT. This distinctive suppression of the transition may be explained by the resistance of the multi-lamellar vesicle to deformations caused by nucleated crystalline domains. Since phospholipids are used as a platform for drug-delivery, a programmable design of cargo hold and release can be of great benefit.

Published
2019
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26. Nanoparticle mobility over a surface as a probe for weak transient disordered peptide-peptide interactions

Author

Chakraborty, Indrani, Rahamim, Gil, Avinery, Ram, Roichman, Yael, and Beck, Roy

Subjects
Physics - Biological Physics, Condensed Matter - Soft Condensed Matter
Abstract

Weak interactions form the core basis of a vast number of biological processes, in particular, those involving intrinsically disordered proteins. Here, we establish a new technique capable of probing these weak interactions between synthetic unfolded polypeptides using a convenient yet efficient, quantitative method based on single particle tracking of peptide-coated gold nanoparticles over peptide-coated surfaces. We demonstrate that our technique is sensitive enough to observe the influence of a single amino acid mutation on the transient peptide-peptide interactions. Furthermore, the effects of buffer salinity, expected to alter weak electrostatic interactions, are also readily detected and examined in detail. The method presented here has the potential to evaluate in a high throughput manner, weak interactions for a wide range of disordered proteins, polypeptides, and other biomolecules.

Published
2019
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27. Glycemic Outcomes of Use of CLC Versus PLGS in Type 1 Diabetes: A Randomized Controlled Trial.

Author

Brown, Sue, Beck, Roy, Raghinaru, Dan, Buckingham, Bruce, Laffel, Lori, Wadwa, R, Kudva, Yogish, Levy, Carol, Pinsker, Jordan, Dassau, Eyal, Doyle, Francis, Ambler-Osborn, Louise, Anderson, Stacey, Church, Mei, Ekhlaspour, Laya, Forlenza, Gregory, Levister, Camilla, Simha, Vinaya, Breton, Marc, Kollman, Craig, Lum, John, and Kovatchev, Boris

Subjects
Adolescent, Adult, Aged, Blood Glucose, Blood Glucose Self-Monitoring, Diabetes Mellitus, Type 1, Female, Humans, Hypoglycemia, Injections, Subcutaneous, Insulin, Insulin Infusion Systems, Intention to Treat Analysis, Male, Middle Aged, Prognosis, Treatment Outcome, United States, Young Adult
Abstract

OBJECTIVE: Limited information is available about glycemic outcomes with a closed-loop control (CLC) system compared with a predictive low-glucose suspend (PLGS) system. RESEARCH DESIGN AND METHODS: After 6 months of use of a CLC system in a randomized trial, 109 participants with type 1 diabetes (age range, 14-72 years; mean HbA1c, 7.1% [54 mmol/mol]) were randomly assigned to CLC (N = 54, Control-IQ) or PLGS (N = 55, Basal-IQ) groups for 3 months. The primary outcome was continuous glucose monitor (CGM)-measured time in range (TIR) for 70-180 mg/dL. Baseline CGM metrics were computed from the last 3 months of the preceding study. RESULTS: All 109 participants completed the study. Mean ± SD TIR was 71.1 ± 11.2% at baseline and 67.6 ± 12.6% using intention-to-treat analysis (69.1 ± 12.2% using per-protocol analysis excluding periods of study-wide suspension of device use) over 13 weeks on CLC vs. 70.0 ± 13.6% and 60.4 ± 17.1% on PLGS (difference = 5.9%; 95% CI 3.6%, 8.3%; P < 0.001). Time >180 mg/dL was lower in the CLC group than PLGS group (difference = -6.0%; 95% CI -8.4%, -3.7%; P < 0.001) while time

Published
2020

28. Randomized Controlled Trial of Mobile Closed-Loop Control.

Author

Kovatchev, Boris, Anderson, Stacey, Raghinaru, Dan, Kudva, Yogish, Laffel, Lori, Levy, Carol, Pinsker, Jordan, Wadwa, R, Buckingham, Bruce, Doyle, Francis, Brown, Sue, Church, Mei, Dadlani, Vikash, Dassau, Eyal, Ekhlaspour, Laya, Forlenza, Gregory, Isganaitis, Elvira, Lam, David, Lum, John, and Beck, Roy

Subjects
Adolescent, Adult, Aged, Biosensing Techniques, Blood Glucose, Blood Glucose Self-Monitoring, Diabetes Mellitus, Type 1, Female, Humans, Hypoglycemic Agents, Insulin, Insulin Infusion Systems, Insulin, Regular, Human, Male, Middle Aged, Mobile Applications, Pancreas, Artificial, Telemedicine, United States, Young Adult
Abstract

OBJECTIVE: Assess the efficacy of inControl AP, a mobile closed-loop control (CLC) system. RESEARCH DESIGN AND METHODS: This protocol, NCT02985866, is a 3-month parallel-group, multicenter, randomized unblinded trial designed to compare mobile CLC with sensor-augmented pump (SAP) therapy. Eligibility criteria were type 1 diabetes for at least 1 year, use of insulin pumps for at least 6 months, age ≥14 years, and baseline HbA1c

Published
2020

29. Continuous glucose monitoring and metrics for clinical trials: an international consensus statement

Author

Battelino, Tadej, Alexander, Charles M, Amiel, Stephanie A, Arreaza-Rubin, Guillermo, Beck, Roy W, Bergenstal, Richard M, Buckingham, Bruce A, Carroll, James, Ceriello, Antonio, Chow, Elaine, Choudhary, Pratik, Close, Kelly, Danne, Thomas, Dutta, Sanjoy, Gabbay, Robert, Garg, Satish, Heverly, Julie, Hirsch, Irl B, Kader, Tina, Kenney, Julia, Kovatchev, Boris, Laffel, Lori, Maahs, David, Mathieu, Chantal, Mauricio, Dídac, Nimri, Revital, Nishimura, Rimei, Scharf, Mauro, Del Prato, Stefano, Renard, Eric, Rosenstock, Julio, Saboo, Banshi, Ueki, Kohjiro, Umpierrez, Guillermo E, Weinzimer, Stuart A, and Phillip, Moshe

Published
2023
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30. Cambridge hybrid closed-loop algorithm in children and adolescents with type 1 diabetes: a multicentre 6-month randomised controlled trial

Author

Hovorka, R, Acerini, C L, Thankamony, A, Allen, J M, Boughton, C K, Dovc, K, Dunger, D B, Ware, J, Musolino, G, Tauschmann, M, Wilinska, M E, Hayes, J F, Hartnell, S, Slegtenhorst, S, Ruan, Y, Haydock, M, Mangat, J, Denvir, L, Kanthagnany, SK, Law, J, Randell, T, Sachdev, P, Saxton, M, Coupe, A, Stafford, S, Ball, A, Keeton, R, Cresswell, R, Crate, L, Cripps, H, Fazackerley, H, Looby, L, Navarra, H, Saddington, C, Smith, V, Verhoeven, V, Bratt, S, Khan, N, Moyes, L, Sandhu, K, West, C, Wadwa, R P, Alonso, G, Forlenza, G, Slover, R, Towers, L, Berget, C, Coakley, A, Escobar, E, Jost, E, Lange, S, Messer, L, Thivener, K, Campbell, F M, Yong, J, Metcalfe, E, Allen, M, Ambler, S, Waheed, S, Exall, J, Tulip, J, Buckingham, B A, Ekhlaspour, L, Maahs, D, Norlander, L, Jacobson, T, Twon, M, Weir, C, Leverenz, B, Keller, J, Davis, N, Kumaran, A, Trevelyan, N, Dewar, H, Price, G, Crouch, G, Ensom, R, Haskell, L, Lueddeke, LM, Mauras, N, Benson, M, Bird, K, Englert, K, Permuy, J, Ponthieux, K, Marrero-Hernandez, J, DiMeglio, L A, Ismail, H, Jolivette, H, Sanchez, J, Woerner, S, Kirchner, M, Mullen, M, Tebbe, M, Besser, R EJ, Basu, S, London, R, Makaya, T, Ryan, F, Megson, C, Bowen-Morris, J, Haest, J, Law, R, Stamford, I, Ghatak, A, Deakin, M, Phelan, K, Thornborough, K, Shakeshaft, J, Weinzimer, S A, Cengiz, E, Sherr, J L, Van Name, M, Weyman, K, Carria, L, Steffen, A, Zgorski, M, Sibayan, J, Beck, R W, Borgman, S, Davis, J, Rusnak, J, Hellman, A, Cheng, P, Kanapka, L, Kollman, C, McCarthy, C, Chalasani, S, Hood, K K, Hanes, S, Viana, J, Lanning, M, Fox, D S, Arreaza-Rubin, G, Eggerman, T, Green, N, Janicek, R, Gabrielson, D, Belle, S H, Castle, J, Green, J, Legault, L, Willi, S M, Wysham, C, Ware, Julia, Boughton, Charlotte K, Allen, Janet M, Wilinska, Malgorzata E, Tauschmann, Martin, Denvir, Louise, Thankamony, Ajay, Campbell, Fiona M, Wadwa, R Paul, Buckingham, Bruce A, Davis, Nikki, DiMeglio, Linda A, Mauras, Nelly, Besser, Rachel E J, Ghatak, Atrayee, Weinzimer, Stuart A, Hood, Korey K, Fox, D Steven, Kanapka, Lauren, Kollman, Craig, Sibayan, Judy, Beck, Roy W, and Hovorka, Roman

Published
2022
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31. Universal and accessible entropy estimation using a compression algorithm

Author

Avinery, Ram, Kornreich, Micha, and Beck, Roy

Subjects
Condensed Matter - Statistical Mechanics, Condensed Matter - Soft Condensed Matter, Physics - Biological Physics, Physics - Computational Physics
Abstract

Entropy and free-energy estimation are key in thermodynamic characterization of simulated systems ranging from spin models through polymers, colloids, protein structure, and drug-design. Current techniques suffer from being model specific, requiring abundant computation resources and simulation at conditions far from the studied realization. Here, we present a universal scheme to calculate entropy using lossless compression algorithms and validate it on simulated systems of increasing complexity. Our results show accurate entropy values compared to benchmark calculations while being computationally effective. In molecular-dynamics simulations of protein folding, we exhibit unmatched detection capability of the folded states by measuring previously undetectable entropy fluctuations along the simulation timeline. Such entropy evaluation opens a new window onto the dynamics of complex systems and allows efficient free-energy calculations.

Published
2017
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32. Continuous Glucose Monitoring Prediction of Gestational Diabetes Mellitus and Perinatal Complications.

Author

Li, Zoey, Beck, Roy, Durnwald, Celeste, Carlson, Anders, Norton, Elizabeth, Bergenstal, Richard, Johnson, Mary, Dunnigan, Sean, Banfield, Matthew, Krumwiede, Katie, Sibayan, Judy, and Calhoun, Peter

Subjects
*CONTINUOUS glucose monitoring, *GESTATIONAL diabetes, *GLUCOSE tolerance tests, *PREDICTION models, *GESTATIONAL age
Abstract

Objective: To assess the performance of continuous glucose monitoring (CGM)-measured glycemic metrics in predicting development of gestational diabetes mellitus (GDM) and select perinatal complications. Research Methods: In a prospective observational study, CGM data were collected from 760 pregnant females throughout gestation after study enrollment. GDM was diagnosed using the oral glucose tolerance test (OGTT) at 24–34 weeks of gestation. Predictive models were built using logistic and elastic net regression. Predictive performance was assessed by the area under the receiver-operating characteristic (AUROC) curve. Results: The AUROCs of using second trimester percent time >140 mg/dL (TA140) and week 13–14 TA140 in predicting GDM were 0.81 and 0.74, respectively. The AUROCs for predicting large-for-gestational-age (LGA) births and hypertensive disorders of pregnancy (HDP) using second trimester TA140 were both 0.58. When matching the specificity of OGTT, a model using TA140 in weeks 13–14 achieved similar sensitivity to OGTT in predicting HDP (13% vs. 10%, respectively) and LGA (6% for both methods). Elastic net also demonstrated similar AUROC and diagnostic performance with no meaningful improvement by using multiple predictors. Conclusion: CGM-measured hyperglycemic metrics such as TA140 predicted GDM with high AUROCs as early as 13–14 weeks of gestation. These metrics were also similar statistically to the OGTT at 24–34 weeks in predicting perinatal complications, although sensitivity was low for both. CGM could potentially be used as an early screening tool for elevated hyperglycemia during gestation, which could be used in addition to or instead of the OGTT. [ABSTRACT FROM AUTHOR]

Published
2024
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33. Continuous Glucose Monitoring-Derived Differences in Pregnancies With and Without Adverse Perinatal Outcomes.

Author

Durnwald, Celeste, Beck, Roy W., Zoey Li, Norton, Elizabeth, Bergenstal, Richard, Johnson, Mary, Sean Dunnigan, Banfield, Matthew, Krumwiede, Katie, Sibayan, Judy, Calhoun, Peter, and Carlson, Anders L.

Subjects
*BLOOD sugar monitors, *CONTINUOUS glucose monitoring, *FETAL growth disorders, *GESTATIONAL diabetes, *GESTATIONAL age
Abstract

OBJECTIVE: To evaluate whether continuous glucose monitoring (CGM)-derived glycemic patterns observed throughout pregnancy were associated with adverse perinatal outcomes, specifically fetal growth disorders and hypertensive disorders of pregnancy (HDP). METHODS: We conducted a prospective observational study of individuals with viable singleton pregnancies and screening hemoglobin A1c levels less than 6.5%. Those with preexisting diabetes were excluded. Enrollment occurred at the earliest gestational age before 17 weeks. Participants wore blinded continuous glucose monitors consecutively as willing until delivery. Those with at least 14 days of CGM data were included in analysis. Rates of large-for-gestational-age (LGA) neonates, small-for-gestational age (SGA) neonates, and HDP were assessed. Continuous glucose monitoring-derived glycemic metrics were calculated, including mean glucose level and percent time above and below thresholds. Two-sample t tests were used to compare glycemic metrics between participants with and without adverse perinatal outcomes. RESULTS: Of 937 participants enrolled, 760 met inclusion criteria. Those delivering LGA neonates or who were diagnosed with HDP had higher mean glucose levels (10269 vs 10068, P5.01 and 10368 vs 9968, P,.001) and spent more time above 120 mg/dL (median 16% vs 12%, P5.006, and 16% vs 12%, P,.001, respectively) and above 140 mg/dL (median 3.9% vs 2.8%, P5.006, and 3.5% vs 2.8%, P,.001, respectively) throughout gestation than those without these outcomes. These findings were present regardless of gestational diabetes mellitus status. Participants with SGA neonates had lower mean glucose levels (9767 vs 10168, P5.01) and spent less time above 140 mg/dL (median 1.6% vs 2.3%, P5.01) and more time below 63 mg/dL (median 3.0% vs 2.3%, P5.02) than those without SGA neonates. CONCLUSION: Individuals with LGA neonates or HDP exhibit a slightly higher mean glucose levels and spend more time hyperglycemic in early pregnancy than those who do not experience these outcomes. [ABSTRACT FROM AUTHOR]

Published
2024
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34. TNF-α inhibitors for type 1 diabetes: exploring the path to a pivotal clinical trial.

Author

Bazile, Cassandra, Abdel Malik, Magdy M., Ackeifi, Courtney, Anderson, Randy L., Beck, Roy W., Donath, Marc Y., Dutta, Sanjoy, Hedrick, Joseph A., Karpen, Stephen R., Kay, Thomas W. H., Marder, Thomas, Marinac, Marjana, McVean, Jennifer, Meyer, Robert, Pettus, Jeremy, Quattrin, Teresa, Verstegen, Ruud H. J., Vieth, Joshua A., and Latres, Esther

Subjects
TYPE 1 diabetes, TUMOR necrosis factors, YOUNG adults, TREND setters, INSULIN pumps
Abstract

Type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of insulin-producing β-cells in the pancreas. This destruction leads to chronic hyperglycemia, necessitating lifelong insulin therapy to manage blood glucose levels. Typically diagnosed in children and young adults, T1D can, however, occur at any age. Ongoing research aims to uncover the precise mechanisms underlying T1D and to develop potential interventions. These include efforts to modulate the immune system, regenerate β-cells, and create advanced insulin delivery systems. Emerging therapies, such as closed-loop insulin pumps, stem cell-derived β-cell replacement and disease-modifying therapies (DMTs), offer hope for improving the quality of life for individuals with T1D and potentially moving towards a cure. Currently, there are no disease-modifying therapies approved for stage 3 T1D. Preserving β-cell function in stage 3 T1D is associated with better clinical outcomes, including lower HbA1c and decreased risk of hypoglycemia, neuropathy, and retinopathy. Tumor Necrosis Factor alpha (TNF-α) inhibitors have demonstrated efficacy at preserving β-cell function by measurement of C-peptide in two clinical trials in people with stage 3 T1D. However, TNF-α inhibitors have yet to be evaluated in a pivotal trial for T1D. To address the promising clinical findings of TNF-α inhibitors in T1D, Breakthrough T1D convened a panel of key opinion leaders (KOLs) in the field. The workshop aimed to outline an optimal clinical path for moving TNF-α inhibitors to a pivotal clinical trial in T1D. Here, we summarize the evidence for the beneficial use of TNF-α inhibitors in T1D and considerations for strategies collectively identified to advance TNF-α inhibitors beyond phase 2 clinical studies for stage 3 T1D. [ABSTRACT FROM AUTHOR]

Published
2024
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35. A Randomized Comparison of Postprandial Glucose Excursion Using Inhaled Insulin Versus Rapid-Acting Analog Insulin in Adults With Type 1 Diabetes Using Multiple Daily Injections of Insulin or Automated Insulin Delivery.

Author

Hirsch, Irl B., Beck, Roy W., Marak, Martin Chase, Calhoun, Peter, Mottalib, Adham, Salhin, Amna, Manessis, Anastasios, Coviello, Andrea D., Bhargava, Anuj, Thorsell, Ashley, Atakov Castillo, Astrid, Bode, Bruce W., Levister, Camilla, Levy, Carol J., Donahue, Cassandra, Cordero, Christian, Beatson, Christie, Langel, Christine R., Jacobson, Christopher, and Kurek, Corey

Subjects
*INSULIN derivatives, *TYPE 1 diabetes, *BLOOD sugar, *INSULIN therapy, *INSULIN
Abstract

OBJECTIVE: To compare postprandial glucose excursions following a bolus with inhaled technosphere insulin (TI) or subcutaneous rapid-acting analog (RAA) insulin. RESEARCH DESIGN AND METHODS: A meal challenge was completed by 122 adults with type 1 diabetes who were using multiple daily injections (MDI), a nonautomated pump, or automated insulin delivery (AID) and who were randomized to bolus with their usual RAA insulin (n = 61) or TI (n = 61). RESULTS: The primary outcome, the treatment group difference in area under the curve for glucose >180 mg/dL over 2 h, was less with TI versus RAA (adjusted difference −12 mg/dL, 95% CI −22 to −2, P = 0.02). With TI, the glucose excursion was smaller (P = 0.01), peak glucose lower (P = 0.01), and time to peak glucose shorter (P = 0.006). Blood glucose <70 mg/dL occurred in one participant in each group. CONCLUSIONS: Postmeal glucose excursion was smaller with TI than with RAA insulin in a cohort that included both AID and MDI users. [ABSTRACT FROM AUTHOR]

Published
2024
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36. Effect of Impaired Awareness of Hypoglycemia on Glucose Decline During and After Exercise in the T1DEXI Study.

Author

Kamimoto, Jorge L Jo, Li, Zoey, Gal, Robin L, Castle, Jessica R, Doyle, Francis J, Jacobs, Peter G, Martin, Corby K, Beck, Roy W, Calhoun, Peter, Riddell, Michael C, and Rickels, Michael R

Subjects
CONTINUOUS glucose monitoring, TYPE 1 diabetes, GLYCOSYLATED hemoglobin, HYPOGLYCEMIA, INSULIN
Abstract

Context Adults with type 1 diabetes (T1D) face the necessity of balancing the benefits of exercise with the potential hazards of hypoglycemia. Objective This work aimed to assess whether impaired awareness of hypoglycemia (IAH) affects exercise-associated hypoglycemia in adults with T1D. Methods We compared continuous glucose monitoring (CGM)-measured glucose during exercise and for 24 hours following exercise from 95 adults with T1D and IAH (Clarke score ≥4 or ≥1 severe hypoglycemic event within the past year) to 95 "aware" adults (Clarke score ≤2 and no severe hypoglycemic event within the past year) matched on sex, age, insulin delivery modality, and glycated hemoglobin A1c. A total of 4236 exercise sessions, and 1794 exercise days and 839 sedentary days, defined as 24 hours following exercise or a day without exercise, respectively, were available for analysis. Results Participants with IAH exhibited a nonsignificant trend toward greater decline in glucose during exercise compared to "aware" (−21 ± 44 vs −19 ± 43 mg/dL [−1.17 ± 2.44 vs −1.05 ± 2.39 mmol/L], adjusted group difference of −4.2 [95% CI, −8.4 to 0.05] mg/dL [−0.23 95% CI, −.47 to 0.003 mmol/L]; P =.051). Individuals with IAH had a higher proportion of days with hypoglycemic events below 70 mg/dL [3.89 mmol/L] (≥15 minutes <70 mg/dL [<3.89 mmol/L]) both on exercise days (51% vs 43%; P =.006) and sedentary days (48% vs 30%; P =.001). The increased odds of experiencing a hypoglycemic event below 70 mg/dL (<3.89 mmol/L) for individuals with IAH compared to "aware" did not differ significantly between exercise and sedentary days (interaction P =.36). Conclusion Individuals with IAH have a higher underlying risk of hypoglycemia than "aware" individuals. Exercise does not appear to differentially increase risk for hypoglycemia during the activity, or in the subsequent 24 hours for IAH compared to aware individuals with T1D. [ABSTRACT FROM AUTHOR]

Published
2024
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41. Doses of medial rectus muscle recessions for divergence insufficiency-type esotropia

Author

Miller, Aaron M., primary, Holmes, Jonathan M., additional, Wu, Rui, additional, Kraker, Raymond T., additional, Crouch, Eric R., additional, Lee, Katherine A., additional, Del Monte, Monte A., additional, Marsh, Justin D., additional, Kraus, Courtney L., additional, Wallace, David K., additional, Colburn, Jeffrey D., additional, Kemp, Pavlina S., additional, Cotter, Susan A., additional, Beck, Roy W., additional, Alvarez, Gillaine, additional, Austin, Darrell S., additional, Boyle, Nicole M., additional, Chandler, Danielle L., additional, Connelly, Patricia L., additional, Conner, Courtney L., additional, Dean, Trevano W., additional, Donahue, Quayleen, additional, Fimbel, Brooke P., additional, Henderson, Robert J., additional, Hercinovic, Amra, additional, Hoepner, James E., additional, Kaplon, Joseph D., additional, Li, Zhuokai, additional, Melia, B. Michele, additional, Robinson, Julianne L., additional, Shah, Jennifer A., additional, Toro, David O., additional, Jenewein, Erin C., additional, Felius, Joost, additional, Collins, Megan E., additional, Leske, David A., additional, Astle, William F., additional, Birch, Eileen E., additional, Chen, Angela M., additional, Christian, Melanie L., additional, Christiansen, Stephen P., additional, Crouch, Earl R., additional, Donahue, Sean P., additional, Enyedi, Laura B., additional, Erzurum, S. Ayse, additional, Everett, Donald F., additional, Freedman, Sharon F., additional, Good, William V., additional, Lambert, Scott R., additional, London, Richard, additional, Manh, Vivian M., additional, Manny, Ruth E., additional, Morrison, David G., additional, Pineles, Stacy L., additional, Ranaivo, Hantamalala Ralay, additional, Repka, Michael X., additional, Ruark, Scott T., additional, Schweinler, Bonita R., additional, Silver, Jayne L., additional, Summers, Allison I., additional, Verderber, Lisa C., additional, and Weise, Katherine K., additional

Published
2024
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42. Cost-Effectiveness of Closed-Loop Automated Insulin Delivery Using the Cambridge Hybrid Algorithm in Children and Adolescents with Type 1 Diabetes: Results from a Multicenter 6-Month Randomized Trial

Author

Fox, D. Steven, primary, Ware, Julia, additional, Boughton, Charlotte K, additional, Allen, Janet M., additional, Wilinska, Malgorzata E, additional, Tauschmann, Martin, additional, Denvir, Louise, additional, Thankamony, Ajay, additional, Campbell, Fiona, additional, Wadwa, R. Paul, additional, Buckingham, Bruce A., additional, Davis, Nikki, additional, DiMeglio, Linda A., additional, Mauras, Nelly, additional, Besser, Rachel E. J., additional, Ghatak, Atrayee, additional, Weinzimer, Stuart A., additional, Kanapka, Lauren, additional, Kollman, Craig, additional, Sibayan, Judy, additional, Beck, Roy W., additional, Hood, Korey K., additional, and Hovorka, Roman, additional

Published
2024
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46. Phosphorylation-induced mechanical regulation of intrinsically disordered neurofilament protein assemblies

Author

Malka-Gibor, Eti, Kornreich, Micha, Laser-Azogui, Adi, Doron, Ofer, Zingerman-Koladko, Irena, Medalia, Ohad, and Beck, Roy

Subjects
Physics - Biological Physics
Abstract

The biological function of protein assemblies was conventionally equated with a unique three-dimensional protein structure and protein-specific interactions. However, in the past 20 years it was found that some assemblies contain long flexible regions that adopt multiple structural conformations. These include neurofilament (NF) proteins that constitute the stress-responsive supportive network of neurons. Herein, we show that NF networks macroscopic properties are tuned by enzymatic regulation of the charge found on the flexible protein regions. The results reveal an enzymatic (phosphorylation) regulation of macroscopic properties such as orientation, stress-response and expansion in flexible protein assemblies. Together with a model explaining the attractive electrostatic interactions induced by enzymatically added charges, we demonstrate that phosphorylation-regulation is far richer and versatile than previously considered., Comment: 9 pages, 5 figures

Published
2016
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47. Neurofilaments function as shock absorbers: compression response arising from disordered proteins

Author

Kornreich, Micha, Malka-Gibor, Eti, Zuker, Ben, Laser-Azogui, Adi, and Beck, Roy

Subjects
Condensed Matter - Soft Condensed Matter
Abstract

What can cells gain by using disordered, rather than folded, proteins in the architecture of their skeleton? Disordered proteins take multiple co-existing conformations, and often contain segments which act as random-walk-shaped polymers. Using X-ray scattering we measure the compression response of disordered protein hydrogels, which are the main stress-responsive component of neuron cells. We find that at high compression their mechanics are dominated by gas-like steric and ionic repulsions. At low compression, specific attractive interactions dominate. This is demonstrated by the considerable hydrogel expansion induced by the truncation of critical short protein segments. Accordingly, the floppy disordered proteins form a weakly cross-bridged hydrogel, and act as shock absorbers that sustain large deformations without failure., Comment: 5 pages, 3 figures

Published
2016
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49. REPLACE-BG: A Randomized Trial Comparing Continuous Glucose Monitoring With and Without Routine Blood Glucose Monitoring in Adults With Well-Controlled Type 1 Diabetes

Author

Aleppo, Grazia, Ruedy, Katrina J, Riddlesworth, Tonya D, Kruger, Davida F, Peters, Anne L, Hirsch, Irl, Bergenstal, Richard M, Toschi, Elena, Ahmann, Andrew J, Shah, Viral N, Rickels, Michael R, Bode, Bruce W, Philis-Tsimikas, Athena, Pop-Busui, Rodica, Rodriguez, Henry, Eyth, Emily, Bhargava, Anuj, Kollman, Craig, and Beck, Roy W

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Clinical Research, Diabetes, Pediatric, Prevention, Clinical Trials and Supportive Activities, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Metabolic and endocrine, Adult, Aged, Blood Glucose, Blood Glucose Self-Monitoring, Diabetes Mellitus, Type 1, Female, Glycated Hemoglobin, Humans, Insulin Infusion Systems, Male, Middle Aged, Socioeconomic Factors, Young Adult, REPLACE-BG Study Group, Medical and Health Sciences, Endocrinology & Metabolism, Biomedical and clinical sciences, Health sciences
Abstract

ObjectiveTo determine whether the use of continuous glucose monitoring (CGM) without confirmatory blood glucose monitoring (BGM) measurements is as safe and effective as using CGM adjunctive to BGM in adults with well-controlled type 1 diabetes (T1D).Research design and methodsA randomized noninferiority clinical trial was conducted at 14 sites in the T1D Exchange Clinic Network. Participants were ≥18 years of age (mean 44 ± 14 years), had T1D for ≥1 year (mean duration 24 ± 12 years), used an insulin pump, and had an HbA1c ≤9.0% (≤75 mmol/mL) (mean 7.0 ± 0.7% [53 ± 7.7 mmol/mol]); prestudy, 47% were CGM users. Participants were randomly assigned 2:1 to the CGM-only (n = 149) or CGM+BGM (n = 77) group. The primary outcome was time in range (70-180 mg/dL) over the 26-week trial, with a prespecified noninferiority limit of 7.5%.ResultsCGM use averaged 6.7 ± 0.5 and 6.8 ± 0.4 days/week in the CGM-only and CGM+BGM groups, respectively, over the 26-week trial. BGM tests per day (including the two required daily for CGM calibration) averaged 2.8 ± 0.9 and 5.4 ± 1.4 in the two groups, respectively (P < 0.001). Mean time in 70-180 mg/dL was 63 ± 13% at both baseline and 26 weeks in the CGM-only group and 65 ± 13% and 65 ± 11% in the CGM+BGM group (adjusted difference 0%; one-sided 95% CI -2%). No severe hypoglycemic events occurred in the CGM-only group, and one occurred in the CGM+BGM group.ConclusionsUse of CGM without regular use of confirmatory BGM is as safe and effective as using CGM with BGM in adults with well-controlled T1D at low risk for severe hypoglycemia.

Published
2017

50. Evaluation of Pump Discontinuation and Associated Factors in the T1D Exchange Clinic Registry.

Author

Wong, Jenise C, Boyle, Claire, DiMeglio, Linda A, Mastrandrea, Lucy D, Abel, Kimber-Lee, Cengiz, Eda, Cemeroglu, Pinar A, Aleppo, Grazia, Largay, Joseph F, Foster, Nicole C, Beck, Roy W, Adi, Saleh, and T1D Exchange Clinic Network

Subjects
T1D Exchange Clinic Network, Humans, Diabetes Mellitus, Type 1, Insulin Infusion Systems, Registries, Longitudinal Studies, Patient Compliance, Adolescent, Adult, Child, Child, Preschool, Female, Male, Young Adult, Glycated Hemoglobin, T1D Exchange, adult, children, continuous subcutaneous insulin infusion, discontinuation factors, pump use, Clinical Research, Pediatric Research Initiative, Pediatric, Diabetes, Autoimmune Disease, 6.1 Pharmaceuticals, 7.1 Individual care needs, Evaluation of treatments and therapeutic interventions, Management of diseases and conditions, Nutrition and Dietetics
Abstract

BackgroundThe objectives of this study were to examine factors associated with insulin pump discontinuation among children and adults followed longitudinally for 1 year in the multicenter T1D Exchange clinic registry, and to provide participant-reported reasons for stopping pump therapy.MethodsWe longitudinally followed 8935 participants of all ages using an insulin pump at the time of registry enrollment. Logistic regressions were used to identify demographic and clinical factors associated with pump discontinuation. Pump discontinuation was self-reported by participants on a first annual follow-up survey.ResultsThe overall frequency of pump discontinuation was 3%. Discontinuation was higher in adolescents (4%) and young adults (4%) than in younger children (3%) or older adults (1%). In multivariate analysis of children between 6 and

Published
2017

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