gebhart/patrepeval huggingface dataset:
166 The Role of Serine Proteases and their Inhibitors in Chronic Wounds (2008)

The role of proteases in chronic wounds has been the subject of many investigations in recent years. These studies have reported biochemical differences between chronic and acute wound fluids and have shown that elevated levels of proteases, in particular the matrix metalloproteinases are abundant in chronic wounds. While this has led to the hypothesis that the chronic wound environment is hostile and not conducive to wound repair, it is still unknown whether this is due to a direct or indirect defect in protease regulation or their inhibitors. We hypothesize that an excess of proteases, specifically the serine proteases present in chronic wounds, are primarily responsible for this hostile wound environment. These proteases degrade endogenous growth factors, reducing their efficacy and delaying healing. In this study, fluid and tissue from chronic and acute wounds were collected over a 24-hour period. Using ELISA, samples were assessed for protease activity (specifically elastase and typsin-like enzymes), their inhibitors and growth factors. Our results show that serine proteases, predominantly elastase, were significantly elevated in the chronic wound fluids. The serpins designed to control these proteases were not up-regulated when compared to the acute controls, resulting in excessive proteolytic activity. An increase in serine protease production without an increase in their serpins is thought to result in a reduction in growth factors, an effect, which was also observed in the chronic wound samples. This work indicates that there is an imbalance in the ratio of inhibitor to enzyme, due to an up regulation of protease production in chronic wounds. We also conclude that misregulation of serine proteases may be responsible for the observed excessive degradation of the extracellular matrix and growth factors in these chronic wounds.
Low dose compared to variable dose Warfarin and to Fondaparinux as prophylaxis for thromboembolism after elective hip or knee replacement surgery; a randomized, prospective study (2015)

ClinicalTrials.gov identifier # NCT00767559 FDA IND: 103,716.
Improving the Grading Accuracy of Astrocytic Neoplasms Noninvasively by Combining Timing Information with Cerebral Blood Flow: A Multi-TI Arterial Spin-Labeling MR Imaging Study (2016)

Multi-TI arterial spin-labeling imaging can evaluate perfusion dynamics by combining normalized bolus arrival time and normalized CBF values derived from multiple TIs. It is superior to single-TI arterial spin-labeling imaging and conventional MR imaging features when applied independently and can improve the diagnostic accuracy when combined with conventional MR imaging for grading astrocytomas.
Purification and characterization of a casein-kinase-II-type enzyme from Xenopus laevis ovary : biological effects on the meiotic cell division of full-grown oocyte (1988)

International audience
Daunomycin/d(TGGGGT): the first crystal structure of a drug bound to a G4-quadruplex DNA telomere (2002)

Telomeres occur as multiple repeats of guanine-rich segments at the 3' ends of chromosomes. Most of the telomeric region is double-helical, but a singlestranded overhang protrudes at the extreme 3' terminus, and the guanines in this region can associate strongly to form stacked G4 quadruplexes. There is intense current interest in designing intercalating drug molecules to act as inhibitors of the enzyme telomerase which protects tumor cells against telomere loss during replication. Despite this interest, little is presently known about quadruplex assemblies in vivo, and the only crystal structures which have been reported are for the uncomplexed G4-quadruplexes d(GGGGTTTTGGGG) and d(TGGGGT). We report the first structure determination of a crystal containing a drug molecule bound to a G4 quadruplex -the anti-cancer agent Daunomycin complexed with the telomeric sequence d(TGGGGT). The crystal is monoclinic, space group C2, with a = 53.078 , b = 47.239 , c = 31.914 , = 119.80. Intensity data were collected at SSRL to 1.17 resolution. The asymmetric unit contains four d(TGGGGT) strands in a G4 quadruplex stack, three daunomycin molecules, and three Na cations. The daunomycins are mutually coplanar, but they do not intercalate into the guanine core of the quadruplex. Instead, they make weak stacking interactions with guanines at one end of the quadruplex and stronger interactions with symmetry-related daunomycins from neighbouring asymmetric units. The aliphatic moieties of the daunomycins project into three of the four grooves spiraling around the G4 stack. The overall crystal architecture is highly asymmetric.
Resampling of SEM-EDS Element Maps to Assess the Length-Scale of Elemental Heterogeneity (2009)

Extended abstract of a paper presented at Microscopy and Microanalysis 2009 in Richmond, Virginia, USA, July 26 – July 30, 2009
Extracellular Vesicle Proteins Associated with Systemic Vascular Events Correlate with Heart Failure: An Observational Study in a Dyspnoea Cohort (2016)

Extracellular vesicle levels of CD14, SerpinG1 and SerpinF2 are associated with the occurrence of heart failure in subjects suspected for acute heart failure, suggesting common underlying pathophysiological mechanisms for heart failure and vascular events.
The case for normothermic machine perfusion in liver transplantation (2017)

In recent years, there has been growing interest in normothermic machine perfusion (NMP) as a preservation method in liver transplantation. In most countries, because of a donor organ shortage, an unacceptable number of patients die while awaiting transplantation. In an attempt to increase the number of donor organs available, transplant teams are implanting a greater number of high-risk livers, including those from donation after circulatory death, older donors, and donors with steatosis. NMP maintains the liver ex vivo on a circuit by providing oxygen and nutrition at 37°C. This permits extended preservation times, the ability to perform liver viability assessment, and the potential for liver-directed therapeutic interventions during preservation. It is hoped that this technology may facilitate the enhanced preservation of marginal livers with improved posttransplant outcomes by reducing ischemia/reperfusion injury. Clinical trials have demonstrated its short-term superiority over cold storage in terms of early biochemical liver function, and it is anticipated that it may result in increased organ utilization, helping to reduce the number of wait-list deaths. However, further studies are required to demonstrate longer-term efficacy and the impact on biliary complications as well as further knowledge to exploit and maximize the potential of this exciting new technology. Liver Transplantation 24 269-275 2018 AASLD.
Interaction Between the Cathode Active Material and the Carbon Conductive Agent in High-Voltage Cathode System that is Concerned with the Gas Evolution (2015)

The interfacial reactions that contributed to the gas formation between carbon conductive agents and the electrolyte at the positive electrode in high-voltage batteries, potentials over 4.5 V, have been investigated. The amount of gas generated was quantified for various conductive agents: acetylene black (AB), furnace black (FB), specially customized AB, and graphite (GR). The experiments revealed that in the high-voltage system, the specific gas evolution was induced by both the cathode active material and the conductive agent. The high-voltage properties of the carbon conductive agents, such as the anion intercalation and self-discharging properties, were evaluated for each carbon electrode. The results implied the existence of a local battery composed of the conductive agent and LNi0.5Mn1.5O4. This redox couple appears to play a key role in the gas evolution, which was sensitive to crystallinity, surface area and metallic impurities of conductive agents.
[Clinical case of the month. A male with 46,XX karyotype]. (1998)

The XX males represent a rare expression of the Klinefelter syndrome associated with hypergonadotropic hypogonadism. Generally the patients are of small stature with normal secondary sexual male features but with small testes and constant sterility. The plasma concentrations of FSH and LH are very high in accordance with the decrease of the testicular function. From the genetic point of view, the XX males may be divided in 3 groups: 1) in 80% of cases, the XX males bear the SRY gene and exhibit a XY translation during the paternal meiosis with the presence of the SRY gene on one of the X chromosomes as a marker of the male differentiation; 2) in 10% of cases, the males are (SRY-)XX; the abnormal development is then due to other genes than the TDF, which, when mutated, can induce sexual male differentiation. The remaining 10% of cases are due to chromosomal mosaïcism with more XX than XY.
Safety and Efficacy of Long-term Treatment With Ozanimod: An Oral S1P Receptor Modulator, in Moderate to Severe Ulcerative Colitis - TOUCHSTONE Extension 2-Year Follow-up (2017)

Introduction: Ozanimod, an oral, once-daily immunomodulator that selectively targets S1P1R and S1P5R, has demonstrated clinical efficacy in ulcerative colitis (UC) for induction and maintenance therapy in the TOUCHSTONE trial [1]. The objective of the open-label extension (OLE) of the TOUCH-STONE trial is to evaluate the long-term efficacy and safety of daily 1 mg ozanimod in patients with moderate to severe UC who had initially participated in the TOUCHSTONE trial for up to 32 weeks. Methods: A total of 197 patients were randomized (1:1:1) and treated with daily ozanimod 0.5 mg (n=65), 1 mg (n=67), or placebo (n=65) in the TOUCHSTONE trial. Of the initial 197, 170 (86%) entered the OLE and received daily ozanimod 1 mg. As of the data cut-off in March 2017, 100 (58.8%) had efficacy evaluations reported through Week 92; of these 100 patients, 94 (55.3%) had received ozanimod 1 mg/day in the OLE for ≥2 years. Efficacy data are reported as observed through Week 92 and safety includes all events through the data cut-off of March 2017. Results: At OLE entry, the partial Mayo Score (pMS) for patients on placebo, ozanimod 0.5 mg, and 1.0 mg was 4.6, 4.5, and 3.3 respectively, which improved significantly by OLE Week 8 (-2.3, -1.9 and -1.1), with the greatest improvement reported in patients who had received placebo or ozanimod 0.5 mg in the TOUCHSTONE trial. At the OLE Week 92 visit, 91/100 (91.0%) had little or no active disease based on the physician global assessment (PGA 0 or 1), 97/100 (97.0%) had little or no blood in their stools (rectal bleeding subscore [RBS] 0 or 1), 86/100 (86.0%) had no blood in the stools (RBS 0). Adverse events (AEs) and serious AEs were reported in 85 (50.0%) and 20 (11.1%) of patients respectively. The most common AEs (>2.0%) during OLE were UC flare, anaemia, nausea, upper respiratory tract infection, nasopharyngitis, back pain, arthralgia, headache, transaminase elevation, and hypertension. The only serious AEs in ≥2 patients were anaemia and UC flare. Transaminase level >3x upper limit of normal (ULN) occurred in 5 (2.9%) patients in the OLE. All elevations were asymptomatic,<5xULN, transient, and resolving while receiving continued treatment. Conclusion: Long-term treatment with ozanimod continues to be safe and well tolerated with good compliance and evidence of durable efficacy.
Detection and identification of phytopathogenic Xanthomonas strains by amplification of DNA sequences related to the hrp genes of Xanthomonas campestris pv. vesicatoria (1994)

Three pairs of oligonucleotide primers specific for different regions of the hrp gene (hypersensitive reaction and pathogenicity) cluster of Xanthomonas campestris pv. vesicatoria were designed and tested for amplification of DNA isolated from a large number of different bacteria. DNA sequences related to the hrp genes were successfully amplified from X. fragariae and from 28 pathovars of X. campestris. No DNA amplification occurred with genomic DNA from phytopathogenic strains of X. campestris pv. secalis, X. campestris pv. translucens, and X. albilineans or from nonpathogenic opportunistic xanthomonads and phytopathogenic strains of the genera Acidovorax, Agrobacterium, Clavibacter, Erwinia, Pseudomonas, and Xylella. The DNA from those bacteria also failed to hybridize to hrp-specific fragments in Southern blot analysis. DNA fragments amplified with a particular primer pair were of identical size from each of the different phytopathogenic xanthomonads. However, restriction analysis of these fragments by using frequently cutting endonucleases revealed variation in the pattern for these hrp-related fragments amplified from the different Xanthomonas strains. The restriction patterns generated for the different fragments allowed distinction of the strains representing a pathovar or species of phytopathogenic xanthomonads. We believe that DNA amplification with hrp-specific oligonucleotide primers is a highly sensitive and specific method that can be applied for detection and identification of phytopathogenic xanthomonads.
Balancing accuracy and interpretability of machine learning approaches for radiation treatment outcomes modeling (2019)

Radiation outcomes prediction (ROP) plays an important role in personalized prescription and adaptive radiotherapy. A clinical decision may not only depend on an accurate radiation outcomes' prediction, but also needs to be made based on an informed understanding of the relationship among patients' characteristics, radiation response and treatment plans. As more patients' biophysical information become available, machine learning (ML) techniques will have a great potential for improving ROP. Creating explainable ML methods is an ultimate task for clinical practice but remains a challenging one. Towards complete explainability, the interpretability of ML approaches needs to be first explored. Hence, this review focuses on the application of ML techniques for clinical adoption in radiation oncology by balancing accuracy with interpretability of the predictive model of interest. An ML algorithm can be generally classified into an interpretable (IP) or non-interpretable (NIP) ("black box") technique. While the former may provide a clearer explanation to aid clinical decision-making, its prediction performance is generally outperformed by the latter. Therefore, great efforts and resources have been dedicated towards balancing the accuracy and the interpretability of ML approaches in ROP, but more still needs to be done. In this review, current progress to increase the accuracy for IP ML approaches is introduced, and major trends to improve the interpretability and alleviate the "black box" stigma of ML in radiation outcomes modeling are summarized. Efforts to integrate IP and NIP ML approaches to produce predictive models with higher accuracy and interpretability for ROP are also discussed.
Supplementary Video1 from Whole-body PET Imaging of T-cell Response to Glioblastoma (2023)

&lt;p&gt;Zr-89 DFO-OX40 mAb PET Vaccinated, day 5&lt;/p&gt;
AN IMPROVED SYNTHESIS OF FLUORENONE METHYLNITRONE (1979)

(1979). AN IMPROVED SYNTHESIS OF FLUORENONE METHYLNITRONE. Organic Preparations and Procedures International: Vol. 11, No. 2, pp. 95-96.
<title>Design of optical systems which transform one bundle of incoherent light into another</title> (1993)

A new method of design of optical systems are presented in this paper. This method is a generalization of one recently developed at Instituto de Energia Solar (I.E.S.) of Univ. Polit. de Madrid. The method referenced has been used on the design of non-imaging concentrators for finite and infinite source. Outstanding results at the 3D performance have been achieved. The method now presented has also been used in the concentrators design, getting the same results as former's. The aim of this method is the design of two surfaces optically active (lens, two mirror or lens-mirror combination) to transform one incoherent radiation of light arriving at the system's aperture into a different radiation at the system's outlet. A computer program has been built for the method application, and some examples have been included.
CuH-Catalyzed Regio- and Enantioselective Hydrocarboxylation of Allenes: Towards Carboxylic Acids with Acyclic Quaternary Centers (2021)

We report a method to prepare α-chiral carboxylic acid derivatives, including those bearing all-carbon quaternary centers, through an enantioselective CuH-catalyzed hydrocarboxylation of allenes with a commercially available fluoroformate. A broad range of heterocycles and functional groups on the allenes were tolerated in this protocol, giving enantioenriched α-quaternary and tertiary carboxylic acid derivatives in good yields with exclusive branched regioselectivity. The synthetic utility of this approach was further demonstrated by derivatization of the products to afford biologically important compounds, including the antiplatelet drug indobufen.
Ring Finger Protein 213 Assembles into a Sensor for ISGylated Proteins with Antimicrobial Activity (2021)

ABSTRACT ISG15 is an interferon-stimulated, ubiquitin-like protein that can conjugate to substrate proteins (ISGylation) to counteract microbial infection, but the underlying mechanisms remain elusive. Here, we used a viral-like particle trapping technology to identify ISG15-binding proteins and discovered Ring Finger Protein 213 (RNF213) as an ISG15 interactor and cellular sensor of ISGylated proteins. RNF213 is a poorly-characterized, interferon-induced megaprotein that is frequently mutated in Moyamoya disease, a rare cerebrovascular disorder. We found that interferon induces ISGylation and oligomerization of RNF213 on lipid droplets, where it acts as a sensor for ISGylated proteins. We showed that RNF213 has broad antimicrobial activity in vitro and in vivo, counteracting infection with Listeria monocytogenes, herpes simplex virus 1 (HSV-1), human respiratory syncytial virus (RSV) and coxsackievirus B3 (CVB3), and we observed a striking co-localization of RNF213 with intracellular bacteria. Together, our findings provide novel molecular insights into the ISGylation pathway and reveal RNF213 as a key antimicrobial effector.
De novodominantASXL3mutations alter H2A deubiquitination and transcription in Bainbridge–Ropers syndrome (2015)

De novo truncating mutations in Additional sex combs-like 3 (ASXL3) have been identified in individuals with Bainbridge-Ropers syndrome (BRS), characterized by failure to thrive, global developmental delay, feeding problems, hypotonia, dysmorphic features, profound speech delays and intellectual disability. We identified three novel de novo heterozygous truncating variants distributed across ASXL3, outside the original cluster of ASXL3 mutations previously described for BRS. Primary skin fibroblasts established from a BRS patient were used to investigate the functional impact of pathogenic variants. ASXL3 mRNA transcripts from the mutated allele are prone to nonsense-mediated decay, and expression of ASXL3 is reduced. We found that ASXL3 interacts with BAP1, a hydrolase that removes mono-ubiquitin from histone H2A lysine 119 (H2AK119Ub1) as a component of the Polycomb repressive deubiquitination (PR-DUB) complex. A significant increase in H2AK119Ub1 was observed in ASXL3 patient fibroblasts, highlighting an important functional role for ASXL3 in PR-DUB mediated deubiquitination. Transcriptomes of ASXL3 patient and control fibroblasts were compared to investigate the impact of chromatin changes on transcriptional regulation. Out of 564 significantly differentially expressed genes (DEGs) in ASXL3 patient fibroblasts, 52% were upregulated and 48% downregulated. DEGs were enriched in molecular processes impacting transcriptional regulation, development and proliferation, consistent with the features of BRS. This is the first single gene disorder linked to defects in deubiquitination of H2AK119Ub1 and suggests an important role for dynamic regulation of H2A mono-ubiquitination in transcriptional regulation and the pathophysiology of BRS.
Free Energy Calculations to Estimate Ligand-Binding Affinities in Structure-Based Drug Design (2014)

Post-genomic era has led to the discovery of several new targets posing challenges for structure-based drug design efforts to identify lead compounds. Multiple computational methodologies exist to predict the high ranking hit/lead compounds. Among them, free energy methods provide the most accurate estimate of predicted binding affinity. Pathway-based Free Energy Perturbation (FEP), Thermodynamic Integration (TI) and Slow Growth (SG) as well as less rigorous end-point methods such as Linear interaction energy (LIE), Molecular Mechanics-Poisson Boltzmann./Generalized Born Surface Area (MM-PBSA/GBSA) and λ-dynamics have been applied to a variety of biologically relevant problems. The recent advances in free energy methods and their applications including the prediction of protein-ligand binding affinity for some of the important drug targets have been elaborated. Results using a recently developed Quantum Mechanics (QM)/Molecular Mechanics (MM) based Free Energy Perturbation (FEP) method, which has the potential to provide a very accurate estimation of binding affinities to date has been discussed. A case study for the optimization of inhibitors for the fructose 1,6- bisphosphatase inhibitors has been described.
Slip Gain Estimation for Indirect Field Controlled Drives Using Stator Transient Signals (2006)

Field oriented control of induction machines is a well-established technology, widely used in applications where high-bandwidth torque control of AC machines is needed. A key parameter in the implementation of the indirect field orientation (IFO) method is the slip gain, the inverse of the rotor time constant, which is used for estimation of the rotor flux angle. A method for estimating the slip gain using the transient response of the system is presented in this paper. The method uses the transient response of the stator voltage or stator flux immediately following a change in the torque command. Estimation of the slip gain using this method does not have a significant dependence on any machine or system parameter and it can be easily integrated into standard drives
Granulomatosis With Angiitis and the Expunging of a Medical Eponym (2018)

1Rosalind Franklin University Medical School, Chicago, IL, USA. 2Division of Gastroenterology, Hepatology and Nutrition, University of Miami Miller School of Medicine, Miami, FL, USA. 3Internal Medicine Residency, Advocate Lutheran General Hospital, Park Ridge, 60068, IL, USA. Correspondence: E.D.E. (email: [email protected])
Deconstructing and reconstructing turn‐taking in caregiver‐infant interactions: a platform for embodied models of early cooperation (2022)

Despite recent advances in AI, building systems that can engage in natural and realistic cooperative interactions with human partners remains a challenge. In this article, we argue that as a precursor to modelling sophisticated cooperation in adults, it's useful to build a model of how cooperation develops in infants. We present a simple initial model of infant cooperation, embodied in BabyX - a hyperrealistic virtual simulation of an 18-month-old infant that can interact with human partners in real time. Our focus in this paper is on cooperative behaviours in the nonverbal domain. The framework for our model of these behaviours is a cognitive model of events and event processing. We detail how cognitive and motor mechanisms in BabyX lead to rudimentary cooperation manifested in nonverbal turn-taking. We introduce a novel empirical paradigm for testing BabyX's model of cooperation, by comparing her interactions with users with 'real' interactions between human infants and their caregivers, which we observed in a detailed empirical study. In this study, we find nonverbal turn-taking in human infant-caregiver interactions, consistent with our BabyX model. This initial model provides the foundation for a comprehensive, and developmentally consistent, model of human cooperation.