DNA Looping Kinetics Analyzed Using Diffusive Hidden Markov Model

Tethered particle experiments use light microscopy to measure the position of a micrometer-sized bead tethered to a microscope slide via a ~micrometer length polymer, in order to infer the behavior of the invisible polymer. Currently, this method is used to measure rate constants of DNA loop formation and breakdown mediated by repressor protein that binds to the DNA. We report a new technique for measuring these rates using a modified hidden Markov analysis that directly incorporates the diffusive motion of the bead, which is an inherent complication of tethered particle motion because it occurs on a time scale between the sampling frequency and the looping time. We compare looping lifetimes found with our method, which are consistent over a range of sampling frequencies, to those obtained via the traditional threshold-crossing analysis, which vary depending on how the raw data are filtered in the time domain. Our method does not involve such filtering, and so can detect short-lived looping events and sudden changes in looping behavior.Comment: 3 page pdf including 3 figures corrections: 2nd page, 1st column, values of diffusion coefficient, spring constant and the decay time were typed incorrectly. No conlcusions were affecte

B Cell Synovitis and Clinical Phenotypes in Rheumatoid Arthritis: Relationship to Disease Stages and Drug Exposure.

OBJECTIVE: To define the relationship of synovial B cells to clinical phenotypes at different stages of disease evolution and drug exposure in rheumatoid arthritis (RA). METHODS: Synovial biopsy specimens and demographic and clinical data were collected from 2 RA cohorts (n = 329), one of patients with untreated early RA (n = 165) and one of patients with established RA with an inadequate response to tumor necrosis factor inhibitors (TNFi-IR; n = 164). Synovial tissue was subjected to hematoxylin and eosin and immunohistochemical staining and semiquantitative assessment for the degree of synovitis (on a scale of 0-9) and of CD20+ B cell infiltrate (on a scale of 0-4). B cell scores were validated by digital image analysis and B cell lineage-specific transcript analysis (RNA-Seq) in the early RA (n = 91) and TNFi-IR (n = 127) cohorts. Semiquantitative CD20 scores were used to classify patients as B cell rich (≥2) or B cell poor (<2). RESULTS: Semiquantitative B cell scores correlated with digital image analysis quantitative measurements and B cell lineage-specific transcripts. B cell-rich synovitis was present in 35% of patients in the early RA cohort and 47.7% of patients in the TNFi-IR cohort (P = 0.025). B cell-rich patients showed higher levels of disease activity and seropositivity for rheumatoid factor and anti-citrullinated protein antibody in early RA but not in established RA, while significantly higher histologic synovitis scores in B cell-rich patients were demonstrated in both cohorts. CONCLUSION: We describe a robust semiquantitative histologic B cell score that closely replicates the quantification of B cells by digital or molecular analyses. Our findings indicate an ongoing B cell-rich synovitis, which does not seem to be captured by standard clinimetric assessment, in a larger proportion of patients with established RA than early RA

The phase of iron catalyst nanoparticles during carbon nanotube growth

We study the Fe-catalyzed chemical vapor deposition of carbon nanotubes by complementary in situ grazing-incidence X-ray diffraction, in situ X-ray reflectivity, and environmental transmission electron microscopy. We find that typical oxide supported Fe catalyst films form widely varying mixtures of bcc and fcc phased Fe nanoparticles upon reduction, which we ascribe to variations in minor commonly present carbon contamination levels. Depending on the as-formed phase composition, different growth modes occur upon hydrocarbon exposure: For γ-rich Fe nanoparticle distributions, metallic Fe is the active catalyst phase, implying that carbide formation is not a prerequisite for nanotube growth. For α-rich catalyst mixtures, Fe3C formation more readily occurs and constitutes part of the nanotube growth process. We propose that this behavior can be rationalized in terms of kinetically accessible pathways, which we discuss in the context of the bulk iron–carbon phase diagram with the inclusion of phase equilibrium lines for metastable Fe3C. Our results indicate that kinetic effects dominate the complex catalyst phase evolution during realistic CNT growth recipes.S.H. acknowledges funding from ERC grant InsituNANO (No. 279342). We acknowledge the European Synchrotron Radiation Facility (ESRF) for provision of synchrotron radiation facilities. We acknowledge the use of facilities within the LeRoy Eyring Center for Solid State Science at Arizona State University. C.T.W. and C.S.E. acknowledge funding from the EC project Technotubes. A.D.G. acknowledges funding from the Marshall Aid Commemoration Commission and the National Science Foundation. R.S.W. acknowledges funding from EPSRC (Doctoral training award) and B.C.B. acknowledges a Research Fellowship at Hughes Hall, Cambridge.This is the accepted manuscript. The final version is available from ACS at http://pubs.acs.org/doi/abs/10.1021/cm301402g

Introduction: Debates on Experience and Empiricism in Nineteenth Century France

The lasting effects of the debate over canon-formation during the 1980s affected the whole field of Humanities, which became increasingly engaged in interrogating the origin and function of the Western canon (Gorak 1991; Searle 1990). In philosophy, a great deal of criticism was, as a result, directed at the traditional narrative of seventeenth-and eighteenth-century philosophies—a critique informed by postcolonialism (Park 2013) as well as feminist historiography (Shapiro 2016). D. F. Norton (1981), L. Loeb (1981) and many others1 attempted to demonstrate the weaknesses of the tripartite division between rationalism, empiricism and critical philosophy.2 As time went on, symptoms of dissatisfaction with what has been called the “standard narrative” ( Vanzo 2013) and the “epistemological par-adigm” (Haakonssen 2004, 2006) only increased. Indeed, at present, a consensus has been reached that the narrative of the antagonism between “Continental rationalism” and “British empiricism”, and the consequent Aufhebung provided by “German critical philosophy,” has been unable to make sense of the complexity, variety and dynamics of early modern.Fil: Antoine-Mahut, Delphine. Ecole Normale Supérieure; FranciaFil: Manzo, Silvia Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones en Humanidades y Ciencias Sociales. Universidad Nacional de La Plata. Facultad de Humanidades y Ciencias de la Educación. Instituto de Investigaciones en Humanidades y Ciencias Sociales; Argentin

Association of the PHACTR1/EDN1 genetic locus with spontaneous coronary artery dissection

Background: Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of acute coronary syndromes (ACS) afflicting predominantly younger to middle-aged women. Observational studies have reported a high prevalence of extracoronary vascular anomalies, especially fibromuscular dysplasia (FMD) and a low prevalence of coincidental cases of atherosclerosis. PHACTR1/EDN1 is a genetic risk locus for several vascular diseases, including FMD and coronary artery disease, with the putative causal noncoding variant at the rs9349379 locus acting as a potential enhancer for the endothelin-1 (EDN1) gene. Objectives: This study sought to test the association between the rs9349379 genotype and SCAD. Methods: Results from case control studies from France, United Kingdom, United States, and Australia were analyzed to test the association with SCAD risk, including age at first event, pregnancy-associated SCAD (P-SCAD), and recurrent SCAD. Results: The previously reported risk allele for FMD (rs9349379-A) was associated with a higher risk of SCAD in all studies. In a meta-analysis of 1,055 SCAD patients and 7,190 controls, the odds ratio (OR) was 1.67 (95% confidence interval [CI]: 1.50 to 1.86) per copy of rs9349379-A. In a subset of 491 SCAD patients, the OR estimate was found to be higher for the association with SCAD in patients without FMD (OR: 1.89; 95% CI: 1.53 to 2.33) than in SCAD cases with FMD (OR: 1.60; 95% CI: 1.28 to 1.99). There was no effect of genotype on age at first event, P-SCAD, or recurrence. Conclusions: The first genetic risk factor for SCAD was identified in the largest study conducted to date for this condition. This genetic link may contribute to the clinical overlap between SCAD and FMD

Global disparities in surgeons’ workloads, academic engagement and rest periods: the on-calL shIft fOr geNEral SurgeonS (LIONESS) study

: The workload of general surgeons is multifaceted, encompassing not only surgical procedures but also a myriad of other responsibilities. From April to May 2023, we conducted a CHERRIES-compliant internet-based survey analyzing clinical practice, academic engagement, and post-on-call rest. The questionnaire featured six sections with 35 questions. Statistical analysis used Chi-square tests, ANOVA, and logistic regression (SPSS® v. 28). The survey received a total of 1.046 responses (65.4%). Over 78.0% of responders came from Europe, 65.1% came from a general surgery unit; 92.8% of European and 87.5% of North American respondents were involved in research, compared to 71.7% in Africa. Europe led in publishing research studies (6.6 ± 8.6 yearly). Teaching involvement was high in North America (100%) and Africa (91.7%). Surgeons reported an average of 6.7 ± 4.9 on-call shifts per month, with European and North American surgeons experiencing 6.5 ± 4.9 and 7.8 ± 4.1 on-calls monthly, respectively. African surgeons had the highest on-call frequency (8.7 ± 6.1). Post-on-call, only 35.1% of respondents received a day off. Europeans were most likely (40%) to have a day off, while African surgeons were least likely (6.7%). On the adjusted multivariable analysis HDI (Human Development Index) (aOR 1.993) hospital capacity &gt; 400 beds (aOR 2.423), working in a specialty surgery unit (aOR 2.087), and making the on-call in-house (aOR 5.446), significantly predicted the likelihood of having a day off after an on-call shift. Our study revealed critical insights into the disparities in workload, access to research, and professional opportunities for surgeons across different continents, underscored by the HDI

Rethinking place-making: aligning placeness factors with perceived urban design qualities (PUDQs) to improve the built environment in historical district

Understanding the concept of place is critically important for urban design and place-making practice, and this research attempted to investigate the pathways by which perceived urban design qualities (PUDQs) influence placeness factors in the Chinese context. Twelve hypotheses were developed and combined in a structural equation model for validation. The Tanhualin historical district in Wuhan, China was selected for the analysis. As a result, place attachment was verified as a critical bridge factor that mediated the influence of PUDQs on place satisfaction. Among the five selected PUDQs, walkability and space quality were revealed as the most influential factors associated with place attachment and place satisfaction. Accessibility was actually indirectly beneficial to place-making via the mediation of walkability. Corresponding implications and strategies were discussed to maintain the sense of place for historic districts

On the "Mockness" of Mock Juries: Real versus Mock Juries as Conversational Forms

This paper is an analysis of real versus simulated, or "mock", juries. It is specifically focused on similarities and differences between the two forms of group-based deliberation with respect to the content and organization of deliberative talk. Via analysis of transcript from six deliberations-two real and four mock-the value of mock juries as an investigative tool is assessed based not on the relationship between "input" variables, such as the nature of the case, the sociodemographic or sociometric nature of the jurors themselves, or wording of the juries' decision rules, and the "output" variable of the jury's decision, but rather based on the internal nature of jurors' discourse. This is a radically different focus from traditional studies comprising mock juries, one enabled by use of real deliberations for comparative evaluation

Justiça Global: Por que não jurisdições estatais em disputas financeiras transnacionais?

The article brings the debate about Global Justice to the centre stage of the Sovereign Debt Restructuring (SDRs) field. The judicial system that intervenes in sovereign debt conflicts was not on the agenda of the last reform processes activated in this field. In the NML Capital vs. Argentina (NML) trial, judges from different instances and different jurisdictions issued declarations of the same dimensions related to the same object of litigation. The article makes a comparative analysis of the argumentative strategies that judges used at the time of justifying their positions in order to show the tensions in which they incurred. It is explained that: a) these tensions are the result of agents –the judges– that must take decisions in a context of crossroads where the expected option in accordance with usual legal practices would undermine their own position in the field of sovereign debt market; b) these crossroads are rooted in the structural limits of the judicial system in which these agents operate. Contrary to what official statements postulate, it is argued that these limits conspire against the possibility that state courts provide Justice in transnational disputes, in which they must judge another equally sovereign State.Este artigo coloca o debate sobre Justiça Global no centro do campo da Reestruturação da Dívida Soberana (REDS). O sistema de justiça que intervém nos conflitos da dívida soberana não fazia parte da agenda dos últimos processos de reforma ativados neste campo. No litigio NML Capital vs. Argentina (NML), juízes de diferentes instâncias e diferentes jurisdições pronunciaram-se sobre as mesmas dimensões do mesmo objeto litigioso. Este artigo traz uma análise comparativa das estratégias argumentativas que estes juízes utilizaram para justificar suas posições e para mostrar as tensões em que incorreram. Explica-se então que: 1) essas tensões são o resultado de agentes –os juízes– que devem tomar decisões no contexto da encruzilhadas em que a opção esperada de acordo com as práticas legais habituais minaria sua própria posição no campo de mercado de dívida soberana; 2) essas encruzilhadas têm suas raízes nos limites estruturais do sistema de justiça, na qual que esses agentes operam. Contra o que postulam os discursos hegemônicos neste campo, argumenta-se que estes limites conspiram contra a possibilidade dos tribunais estatais de brindar soluções Justas em disputas que devem julgar a outro Estado igualmente soberano e que excede-os em sua escala.Fil: Manzo, Alejandro Gabriel. Universidad Nacional de Córdoba. Centro de Investigaciones Jurídicas y Sociales. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones Jurídicas y Sociales; Argentin

From Attractio and Impulsus to Motion of Liberty : Rarefaction and Condensation, Nature and Violence, in Cardano, Francis Bacon, Glisson and Hale

There was a particular way of understanding and explaining changes in matter's quantity whose first exposition can be traced back to the Renaissance in Girolamo Cardano's classification of the natural motions of the universe, particu- larly in the motions of impulsus (impenetrability) and attractio (abhorrence of a vacuum). Cardano's exposition was read attentively by Francis Bacon, whose idea of "motion of liberty" both modified and retained elements of the Cardanian view. The Baconian treatment of the motion of liberty made its way well into the seven- teenth century in the works of Francis Glisson and Matthew Hale, who draw heavily on it to provide their own account of rarefaction and condensation. The aim of this essay is to reconstruct the history of the accounts of the processes of rarefaction and condensation held by these authors in order to examine the ramifications of the Cardanian approach in the seventeenth century. This history will not only provide us with new instruments for understanding the intellectual relationship between the Renaissance and the early modern period but also improve our understanding of the transformation of the world picture across the emergence of early modern science.Fil: Manzo, Silvia. Universidad Nacional de La Plata. Facultad de Humanidades y Ciencias de la Educación. Instituto de Investigaciones en Humanidades y Ciencias Sociales (UNLP-CONICET); Argentina