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Robustness and stability of spin-glass ground states to perturbed interactions

Physical Review E 2023年第1期107卷 014126-014126页

作者： Vaibhav Mohanty Ard A. Louis Rudolf Peierls Centre for Theoretical Physics University of Oxford Oxford OX1 3NP United Kingdom MD-PhD Program and Program in Health Sciences and Technology Harvard Medical School Boston Massachusetts 02125 USA and Massachusetts Institute of Technology Cambridge Massachusetts 02139 USA

Across many problems in science and engineering, it is important to consider how much the output of a given system changes due to perturbations of the input. Here, we investigate the glassy phase of ±J spin glasses at zero temperature by calculating the robustness of the ground states to flips in the sign of single interactions. For random graphs and the Sherrington-Kirkpatrick model, we find relatively large sets of bond configurations that generate the same ground state. These sets can themselves be analyzed as subgraphs of the interaction domain, and we compute many of their topological properties. In particular, we find that the robustness, equivalent to the average degree, of these subgraphs is much higher than one would expect from a random model. Most notably, it scales in the same logarithmic way with the size of the subgraph as has been found in genotype-phenotype maps for RNA secondary structure folding, protein quaternary structure, gene regulatory networks, as well as for models for genetic programming. The similarity between these disparate systems suggests that this scaling may have a more universal origin.

关键词： Degree correlations Mutation Network structure Scaling laws of complex systems Real world networks Spin glasses

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An expandable chamber for safe brain retraction: new technologies in the field of transcranial endoscopic surgery

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2023年第4期24卷 326-335页

作者： Elena ROCA Anna GOBETTI Giovanna CORNACCHIA Oscar VIVALDI Barbara BUFFOLI Giorgio RAMORINO Head and Neck Department NeurosurgeryIstituto Ospedaliero Fondazione Poliambulanza25124 BresciaItaly Technology for Health PhD Program University of Brescia25124 BresciaItaly Materials Science and Technology at Department of Mechanical and Industrial Engineering University of Brescia25123 BresciaItaly Metallurgy at Department of Mechanical and Industrial Engineering University of Brescia25123 BresciaItaly Anatomy and Physiopathology Division Department of Clinical and Experimental SciencesUniversity of Brescia25123 BresciaItaly

Neurosurgery is a highly specialized field:it often involves surgical manipulation of noble structures and cerebral retraction is frequently necessary to reach deep-seated brain *** are still no reliable methods preventing possible retraction *** objective of this study was to design work chambers well suited for transcranial endoscopic surgery while providing safe retraction of the surrounding brain *** chamber is designed to be inserted close to the intracranial point of interest;once it is best placed it can be *** should guarantee an appreciable workspace similar to that of current neurosurgical *** experimental aspect of this study involved the use of a force sensor to evaluate the pressures exerted on the brain tissue during the retraction *** pterional craniotomy,pressure measurements were made during retraction with the use of a conventional metal spatula with different *** that,although the force values necessary for retraction and exerted on the spatula by the neurosurgeon are the same,the local pressure exerted on the parenchyma at the edge of the spatula at different inclinations varied greatly.A new method of cerebral retraction using a chamber retractor(CR)has been designed to avoid any type of complication due to spatula edge overpressures and to maintain acceptable pressure values exerted on the parenchyma.

关键词： Brain retraction Spatula Brain retractor design Brain retraction injury Retraction complication Transcranial endoscopic surgery

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Probabilistic genotype-phenotype maps reveal mutational robustness of RNA folding, spin glasses, and quantum circuits

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Physical Review Research 2025年第1期7卷 013118-013118页

作者： Anna Sappington Vaibhav Mohanty Department of Electrical Engineering and Computer Science Massachusetts Institute of Technology Cambridge Massachusetts 02139 USA Harvard-MIT Program in Health Sciences and Technology Harvard Medical School Boston Massachusetts 02115 USA and Massachusetts Institute of Technology Cambridge Massachusetts 02139 USA Harvard/MIT MD-PhD Program Harvard Medical School Boston Massachusetts 02115 USA and Massachusetts Institute of Technology Cambridge Massachusetts 02139 USA Department of Chemistry and Chemical Biology Harvard University Cambridge Massachusetts 02138 USA

Recent studies of genotype-phenotype maps have reported universally enhanced phenotypic robustness to genotype mutations, a feature essential to evolution. Virtually all of these studies make a simplifying assumption that each genotype—represented as a sequence—maps deterministically to a single phenotype, such as a discrete structure. Here we introduce probabilistic genotype-phenotype (PrGP) maps, where each genotype maps to a vector of phenotype probabilities, as a more realistic and universal language for investigating robustness in a variety of physical, biological, and computational systems. We study three model systems to show that PrGP maps offer a generalized framework which can handle uncertainty emerging from various physical sources: (1) thermal fluctuation in RNA folding, (2) external field disorder in the spin-glass ground state search problem, and (3) superposition and entanglement in quantum circuits, which are realized experimentally on IBM quantum computers. In all three cases, we observe a biphasic robustness scaling which is enhanced relative to random expectation for more frequent phenotypes and approaches random expectation for less frequent phenotypes. We derive an analytical theory for the behavior of PrGP robustness, and we demonstrate that the theory is highly predictive of empirical robustness.

关键词： Quantum computers

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The Multifaceted Role of Bilirubin in Liver Disease:A Literature Review

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Journal of Clinical and Translational Hepatology 2024年第11期12卷 939-948页

作者： Mariana MRamírez-Mejía Stephany MCastillo-Castañeda Shreya CPal Xingshun Qi Nahum Méndez-Sánchez Plan of Combined Studies in Medicine(PECEM-MD/PhD) Faculty of MedicineNational Autonomous University of MexicoMexico CityMexico Liver Research Unit Medica Sur Clinic&FoundationMexico CityMexico Medical Dental and Health Sciences Master and Doctorate ProgramNational Autonomous University of MexicoMexico CityMexico Faculty of Medicine National Autonomous University of MexicoMexico CityMexico Department of Gastroenterology General Hospital of Northern Theater Command(formerly General Hospital of Shenyang Military Area)ShenyangLiaoningChina

Bilirubin,the primary breakdown product of hemoproteins,particularly hemoglobin,plays a key role in the diagnosis,prognosis,and monitoring of liver *** acute liver dis-eases,such as acute liver failure,drug-induced liver injury,and viral hepatitis,bilirubin serves as a biomarker reflecting the extent of hepatocyte loss and liver *** liver diseases,including alcohol-related liver disease,chronic hep-atitis C virus infection,metabolic dysfunction-associated fat-ty liver disease,and autoimmune liver diseases,are marked by persistent liver injury and *** levels in chronic liver diseases provide insight into liver function,disease severity,and *** a versatile biomarker,bilirubin offers valuable information on the pathophysiology of liver diseases and aids in guiding clinical decision-making regarding the treatment of liver diseases and their *** review aimed to explore the multifunctional role of bilirubin in liver diseases by analyzing its biological functions beyond its role as a biomarker of liver damage.

关键词： Bilirubin Liver failure Chronic liver failure Metabolic dysfunctionassociated fatty liver disease Hepatitis Acute-on-chronic liver failure

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Momordica charantia fruit extract with antioxidant capacity improves the expression of tyrosine-phosphorylated proteins in epididymal fluid of chronic stress rats

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Journal of Integrative Medicine 2022年第6期20卷 534-542页

作者： Supatcharee Arun Therachon Kamollerd Nareelak Tangsrisakda Sudtida Bunsueb Arada Chaiyamoon Alexander Tsang-Hsien Wu Sitthichai Iamsaard Department of Anatomy Faculty of MedicineKhon Kaen UniversityKhon Kaen 40002Thailand Research Institute for Human High Performance and Health Promotion(HHP&HP) Khon Kaen UniversityKhon Kaen 40002Thailand The PhD Program for Translational Medicine College of Medical Science and TechnologyTaipei Medical University and Academia SinicaTaipei 11031TaiwanChina Graduate Institute of Medical Sciences National Defense Medical CenterTaipei 114TaiwanChina

Objective:Although the protective effects of Momordica charantia L.(MC)extract on chemical-induced testicular damage have been studied,the preventive effects of MC extract on functional proteins in the epididymis under chronic stress have never been *** study investigated the protective effects of MC fruit extract on protein secretion,especially tyrosine-phosphorylated proteins,in the epididymis of rats exposed to chronic unpredictable stress(CUS).Methods:Total phenolic compounds(TPC),total flavonoid compounds(TFC)and antioxidant capacities of MC extract were *** male rats were divided into 4 groups:control group,CUS group,and 2groups of CUS that received different doses of MC extract(40 or 80 mg/kg).In treated groups,rats were given MC daily,followed by induction of CUS(1 stressor was randomly applied from a battery of 9 potential stressors)for 60 consecutive *** corticosterone and testosterone levels were analyzed after the end of *** of heat-shock protein 70(HSP-70)and tyrosine-phosphorylated proteins present in the fluid of the head and tail of the epididymis were quantified using Western ***:MC extract contained TPC of(19.005±0.270)mg gallic acid equivalents and TFC of(0.306±0.012)mg catechin equivalents per gram,and had 2,2-diphenyl-1-picrylhydrazyl antioxidant capacity of(4.985±0.086)mg trolox equivalents per gram,radical 50%inhibitory concentration of(2.011±0.008)mg/mL and ferric reducing antioxidant power of(23.697±0.819)μmol Fe(Ⅱ)per *** level in the epididymis was significantly increased,while the corticosterone level was significantly improved in groups treated with MC extract,compared to the CUS ***,an 80 mg/kg dose of MC extract prevented the impairments of HSP-70 and tyrosine-phosphorylated protein expressions in the luminal fluid of the epididymis of CUS ***:MC fruit extract had antioxidant activities and improved the functional proteins secreted from

关键词： Momordica charantia L. Antioxidant activity Epididymis Tyrosine-phosphorylated proteins Chronic unpredictable stress

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Hepatitis B surface antigen loss in chronic hepatitis B patients with low-viral-load

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Journal of Gastroenterology and Hepatology (Australia) 2024年第11期39卷 2327-2331页

作者： Jang, Tyng-Yuan Batsaikhan, Batbold Chen, Yo-Chia Dai, Chia-Yen PhD Program of Environmental and Occupational Medicine and Graduate Institute of Clinical Medicine Kaohsiung Medical University Kaohsiung Taiwan Department of Internal Medicine Kaohsiung Medical University Hospital Kaohsiung Medical University Kaohsiung Taiwan Department of Internal Medicine Pingtung Hospital Ministry of Health and Welfare Ping-Tung Taiwan Department of Internal Medicine Institute of Medical Sciences Mongolian National University of Medical Sciences Ulaanbaatar Mongolia Department of Biological Science and Technology National Pingtung University of Science and Technology Pingtung Taiwan College of Professional Studies National Pingtung University of Science and Technology Pingtung Taiwan Drug Development and Value Creation Research Center Kaohsiung Medical University Kaohsiung Taiwan

Background and Aim: Among low viral load (DNA of hepatitis B virus (HBV) was 10 IU/mL vs 2.3 log10 IU/mL;P = 0.003), and higher proportion of prior NAs-treated history. Logistic regression analysis revealed ... 详细信息

Background and Aim: Among low viral load (DNA of hepatitis B virus (HBV) was < 2000 IU/mL), the factor of the loss of hepatitis B surface antigen (HBsAg) remained elusive. Methods: The retrospective study recruited patients with chronic hepatitis B (CHB) who were negative low for hepatitis B e-antigen (HBeAg), had a low viral load, and experienced HBsAg loss during follow-up. CHB patients with low-viral load but without consequent HBsAg loss were also enrolled at the ratio of 1:4. The factors contributing to HBsAg loss were analyzed. Results: A total of 80 patients were recruited for the current study, with a mean age of 63.9 years and 61.3% being male. Among them, 62.5% patients (50/80) were treated with potent nucleoside/nucleotide analogues (NAs) during the follow-up period. Additionally, 12.5% patients (10/80) had a prior history of NAs treatment before enrolment. During the follow-up, HBsAg loss occurred in 17 patients (21.3%). Compared with patients without HBsAg loss, those with HBsAg loss were younger (57.9 years vs 65.5 years;P = 0.01), had lower HBV DNA levels (1.3 log₁₀ IU/mL vs 2.3 log₁₀ IU/mL;P = 0.003), and higher proportion of prior NAs-treated history. Logistic regression analysis revealed that the factors associated with factors associated with HBsAg loss were age < 60 years (OR/CI: 3.95/1.15–13.60, P = 0.03), prior NAs-treated history (OR/CI: 7.59/1.42–40.51, P = 0.01) and current NAs-treated (OR/CI: 0.19/0.05–0.71, P = 0.01). Conclusions: In the study, older age and prior NAs were positively associated with HBsAg loss, and current NAs was negatively associated with HBsAg loss. Additionally, some patients experienced HBsAg loss during the NAs therapy. © 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

关键词： HBeAg HBsAg HBV NAs viral load

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Incorporating Gender-Neutral Language in IRB Materials: Perceptions of IRB Professionals

Ethics and Human Research

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Ethics and Human Research 2025年第3期47卷 30-39页

作者： Nellis, Kevin L. Lichtman, Ronnie Birnbaum, Jeffrey Friedman, Stanley Zwicklbauer, Elise Executive director of Human Research Protections and Quality Assurance at the Research Foundation for the State University of New York (SUNY) Downstate Health Sciences University (DHSU) United States Midwife and Emeritus at the SUNY DHSU an adjunct at Lehman College of the City University of New York and a member of the SUNY DHSU IRB United States of pediatrics at SUNY DHSU and a principal investigator and executive director of Health & Education Alternatives for Teens (“HEAT”) and a former IRB member United States Retired distinguished teaching of physiology and pharmacology a former SUNY DHSU faculty member a former director of the MD/PhD program and former IRB vice chair United States Medical student at the SUNY DHSU College of Medicine United States

This study investigated the perceptions of institutional review board (IRB) professionals regarding the use of gender-neutral language in IRB guidance and informed consent documents, and whether respondents’ IRBs incorporated gender-neutral language in those documents. A survey was disseminated to a diverse group of IRB professionals whose emails were generated from a list received from the Office for Human Research Protections. Responses indicated substantial endorsement of gender-neutral language, although actual usage remains limited. The findings suggest that while the willingness to adopt inclusive language is high, barriers such as resource limitations and a lack of regulatory guidelines often impede its broader application. This study underscores the importance of developing explicit guidelines and resources to facilitate the adoption of gender-neutral language, enhancing inclusivity in research settings. © 2025 by The Hastings Center. All rights reserved.

关键词： gender-neutral language human research protection program (HRPP) inclusivity in research institutional review boards (IRBs) IRB consent form templates IRB forms IRB guidance language implementation survey study

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First Visit Characteristics Associated with Future Surgery in Intermittent Exotropia

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Journal of Binocular Vision and Ocular Motility 2022年第1期72卷 22-28页

作者： Nwanaji-Enwerem, Jamaji C. Gateman, Taylor Whitecross, Sarah Whitman, Mary C. MD/PhD Program Harvard Medical School Boston MA United States Division of Environmental Health Sciences School of Public Health University of California Berkeley CA United States Department of Ophthalmology Boston Children’s Hospital Boston MA United States Department of Ophthalmology Harvard Medical School Boston MA United States Department of Emergency Medicine Emory University School of Medicine Atlanta GA United States Gangarosa Department of Environmental Health Emory Rollins School of Public Health Atlanta GA United States

Purpose: Identify demographic and clinical characteristics at the first presentation associated with later having surgery for intermittent exotropia (IXT). Methods: Retrospective cohort study of 228 children with IXT and 5+ years of follow-up. Demographic and clinical data were extracted from medical records. A total 97 participants who underwent surgery during follow-up were compared to 131 participants who did not. Best subset regression was used to identify first visit variables associated with later having strabismus surgery. Surgery was then regressed on the selected variables using logistic models. Results: Age and control were the only first visit variables significantly associated with having surgery for IXT. Notably, neither angle of deviation nor stereopsis were associated with later surgery. In an adjusted logistic model, each one-month increase in age at presentation was associated with a 1% decrease in the odds of having surgery (OR = 0.991, 95% CI: 0.982–0.999, P = .04). Children with poor control at initial visit had almost five times greater odds of having surgery than those with good control (OR = 4.95, 95% CI: 2.31–10.98, P < .0001). Conclusions: Age and control of IXT are important factors at presentation associated with future surgical intervention for IXT. The magnitude of deviation and stereopsis was not significantly associated with future surgical treatment for IXT. © 2022 American Orthoptic Journal Inc.

关键词： Exotropia intermittent exotropia natural history strabismus strabismus surgery

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Probabilistic Genotype-Phenotype Maps Reveal Mutational Robustness of RNA Folding, Spin Glasses, and Quantum Circuits

arXiv

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arXiv 2023年

作者： Sappington, Anna Mohanty, Vaibhav Department of Electrical Engineering and Computer Science Massachusetts Institute of Technology CambridgeMA02139 United States Program for Health Sciences and Technology Harvard Medical School BostonMA02115 United States Massachusetts Institute of Technology CambridgeMA02139 United States Harvard/MIT MD-PhD Program Harvard Medical School BostonMA02115 United States Department of Chemistry and Chemical Biology Harvard University CambridgeMA02138 United States

Recent studies of genotype-phenotype (GP) maps have reported universally enhanced phenotypic robustness to genotype mutations, a feature essential to evolution. Virtually all of these studies make a simplifying assumption that each genotype—represented as a sequence—maps deterministically to a single phenotype, such as a discrete structure. Here, we introduce probabilistic genotype-phenotype (PrGP) maps, where each genotype maps to a vector of phenotype probabilities, as a more realistic and universal language for investigating robustness in a variety of physical, biological, and computational systems. We study three model systems to show that PrGP maps offer a generalized framework which can handle uncertainty emerging from various physical sources: (1) thermal fluctuation in RNA folding, (2) external field disorder in spin glass ground state finding, and (3) superposition and entanglement in quantum circuits, which are realized experimentally on IBM quantum computers. In all three cases, we observe a novel biphasic robustness scaling which is enhanced relative to random expectation for more frequent phenotypes and approaches random expectation for less frequent phenotypes. We derive an analytical theory for the behavior of PrGP robustness, and we demonstrate that the theory is highly predictive of empirical robustness. © 2023, CC BY.

关键词： Quantum computers

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Structural Basis for p19 Targeting by Anti–IL-23 Biologics: Correlations with Short- and Long-Term Efficacy in Psoriasis

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JID Innovations 2024年第2期4卷 100261-100261页

作者： Daniele, Stefano G. Eldirany, Sherif A. Damiani, Giovanni Ho, Minh Bunick, Christopher G. MD-PhD Program Yale School of Medicine New Haven CT United States Department of Dermatology University of Connecticut Health Center Farmington CT United States Italian Center of Precision Medicine and Chronic Inflammation Milan Italy Department of Biomedical Surgical and Dental Sciences University of Milan Milan Italy Graduate Program (PhD) in Pharmacological Sciences Department of Pharmaceutical and Pharmacological Sciences University of Padua Padua Italy Department of Dermatology Yale School of Medicine New Haven CT United States Program in Translational Biomedicine Yale School of Medicine New Haven CT United States

IL-23 is central to psoriasis pathogenesis. Biologics targeting IL-23 are important therapies against psoriasis. IL-23 inhibitors risankizumab, tildrakizumab, and guselkumab bind the IL-23 p19 subunit, whereas ustekinumab binds p40;however, the structural composition of the IL-23–binding epitopes and how these molecular properties relate to clinical efficacy are not known. Utilizing epitope data derived from hydrogen-deuterium exchange or crystallographic experiments, we mapped inhibitor epitope locations, hydrophobicity, and surface charge onto the IL-23 surface. Molecular properties of each inhibitor epitope, including solvent-accessible surface area, were correlated to binding affinity, kinetic values, and clinical efficacy scores for plaque psoriasis through linear regression analysis. Each IL-23 inhibitor binds an epitope with a unique size, composition, and location except for a 10-residue overlap region outside of the IL-23 receptor epitope. We observed strong correlations between epitope surface area and K_D and k_off but not k_on. Epitope surface area, K_D, and k_off were further associated with short-term (10–16 weeks) and long-term (44–60 weeks) clinical efficacy according to PASI-90 responses, with risankizumab demonstrating highest efficacy among IL-23 biologics. In contrast, k_on, epitope hydrophobicity, polarity, and charge content did not correlate with efficacy. These data exemplify how molecular principles of medications within a therapeutic class can explain their differential clinical responses. © 2024 The Authors

关键词： Guselkumab Inflammatory skin disease epitope Risankizumab Tildrakizumab Ustekinumab

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