gebhart/patrepeval huggingface dataset:
Antiaggregatory activity in human platelets of potent antagonists of the P2Y1 receptor (2020)

Activation of the P2Y1 nucleotide receptor in platelets by ADP causes changes in shape and aggregation, mediated by activation of phospholipase C (PLC). Recently, MRS2500 (2-iodo-N6-methyl-(N)-methanocarba-2′-deoxyadenosine-3′,5′-bisphosphate) was introduced as a highly potent and selective antagonist for this receptor. We have studied the actions of MRS2500 in human platelets and compared these effects with the effects of two acyclic nucleotide analogues, a bisphosphate MRS2298 and a bisphosphonate derivative MRS2496, which act as P2Y1 receptor antagonists, although less potently than MRS2500. Improved synthetic methods for MRS2500 and MRS2496 were devised. The bisphosphonate is predicted to be more stable in general in biological systems than phosphate antagonists due to the non-hydrolyzable C–P bond. MRS2500 inhibited the ADP-induced aggregation of human platelets with an IC50 value of 0.95 nM. MRS2298 and MRS2496 also both inhibited the ADP-induced aggregation of human platelets with IC50 values of 62.8 nM and 1.5 μM, respectively. A similar order of potency was observed for the three antagonists in binding to the recombinant human P2Y1 receptor and in inhibition of ADP-induced shape change and ADP-induced rise in intracellular Ca2+. No substantial antagonism of the pathway linked to the inhibition of cyclic AMP was observed for the nucleotide derivatives, indicating no interaction of these three P2Y1 receptor antagonists with the proaggregatory P2Y12 receptor, which is also activated by ADP. Thus, all three of the bisphosphate derivatives are highly selective antagonists of the platelet P2Y1 receptor, and MRS2500 is the most potent such antagonist yet reported.
Multiresolution LOGISMOS graph search for automated choroidal layer segmentation of 3D macular OCT scans (2020)

The choroid is a vascular plexus located between the retina and the sclera, providing oxygen and nourishment to the outer layers of the retina. Thickness changes in the choroid are of importance in the pathophysiology of various ocular diseases such as glaucoma, age-related macular degeneration (AMD), and others. Our previous choroidal layer segmentation method of 3D macular optical coherence tomography (OCT) scans using choroidal vessel segmentation tended to segment thinner choroidal layers than ground truths, requiring long running time and much memory. To overcome these drawbacks, we introduce a new, fast, and memory-efficient multiresolution LOGISMOS (layered optimal graph image segmentation for multiple objects and surfaces) method. The key idea of the method is to consequently segment the choroidal layer in the higher resolution sub-OCT image volume constrained by the layer segmented in the lower resolution OCT image volume to reduce the size of columns for graph search. Generally, it outperformed our previous method and showed a similar performance to the inter-observer variability between 2 experts.
Acid Proteinase Secreted by Candida Tropicalis: Functional Analysis of Preproregion Cleavages in C. Tropicalis and Saccharomyces Cerevisiae (1996)

The 40 kDa secreted aspartyl proteinase (Sapt1) of Candida tropicalis is a pepsin-like enzyme encoded by the SAPT1 gene. According to the deduced amino acid sequence. Sapt1 has a putative preproregion of 60 amino acids preceding the mature enzyme. Maturation and processing of Sapt1 was analysed in C. tropicalis and Saccharomyces cerevisiae strains expressing wild-type or mutated forms of SAPT1. In S. cerevisiae, the glycosylated 46 kDa proenzyme was converted to the mature 40 kDa form of Sapt1 by KEX2-dependent proteolytic cleavage following the Lys59-Arg60 sequence. The replacement of Lys59-Arg60 by Lys59-Gly60 revealed that the precursor can be processed by an autocatalytic cleavage. This alternative processing pathway to produce mature Sapt1 is less efficient than the Kex2-mediated pathway. Finally, it was shown that in C. tropicalis and S. cerevisiae the removal of the proregion was a prerequisite for the secretion of Sapt1.
Consistent Modeling of Snapback Phenomenon Based on Conventional I-V Measurements (2018)

The snapback phenomenon is investigated with use of 2D-device simulations. It is found that the phenomenon is induced by three sequentially occurring mechanisms: 1. Impact ionization, 2. Potential increase, and 3. Bipolar effect. Further, it is demonstrated that this series of mechanisms can be successfully modeled with use of the compact model HiSIM\_HV by introducing an internal node within the substrate, which is solved in a consistent way. The node is verified to describe the new induced electrical balance correctly. It is demonstrated that the node potential change is the origin of the three involved mechanisms. The reason for the achieved simple but accurate modeling is mainly related to the potential-based modeling approach of HiSIM_HV adopted for the basic I - V modeling, which is influenced by the internal node potential as well.
Folding–function relationship of the most common cystic fibrosis–causing CFTR conductance mutants (2019)

Cystic fibrosis is caused by mutations in the <i>CFTR</i> gene, which are subdivided into six classes. Mutants of classes III and IV reach the cell surface but have limited function. Most class-III and class-IV mutants respond well to the recently approved potentiator VX-770, which opens the channel. We here revisited function and folding of some class-IV mutants and discovered that R347P is the only one that leads to major defects in folding. By this criterion and by its functional response to corrector drug VX-809, R347P qualifies also as a class-II mutation. Other class-IV mutants folded like wild-type CFTR and responded similarly to VX-809, demonstrating how function and folding are connected. Studies on both types of defects complement each other in understanding how compounds improve mutant CFTR function. This provides an attractive unbiased approach for characterizing mode of action of novel therapeutic compounds and helps address which drugs are efficacious for each cystic fibrosis disease variant.
Crown ethers as pre-organised exo-receptors in the divergent recognition of α,ω-diiodoperfluoroalkanes (2000)

Both the nitrogen atoms of Kryptofix® 2.2. 1 act as electron-donors to the iodine atoms of α,ω-diiodoperfluoroalkanes 2a,b giving rise to infinite 1D chains 3a,b as white crystalline solids which are stable in air at room temperature. The structural features of these non-covalent co-polymers have been studied using various techniques (IR, 1H NMR, 19F NMR, X-ray diffraction) and it has been established that when Kryptofix® 2.2. is halogen bonded to iodides 2, it adopts the same conformation as when in the pure form, namely the exo–exo topology. The co-existence of halogen-bonding and hydrogen-bonding in supramolecular architectures 3 suggests pre-organisation of the interacting partners as a new strategy in the rational design of divergent self-assembly processes.
Li2Sr4Al2Ta2N8O, a Nitridoalumotantalate with BCT‐Zeolite Type Structure (2011)

Abstract Li 2 Sr 4 Al 2 Ta 2 N 8 O was synthesized from Li 3 AlN 2 , Sr(NH 2 ) 2 , LiN 3 , and lithium metal as fluxing agent in weld shut tantalum crucibles. Single crystals were obtained as byproduct from reaction with the ampoule material. The crystal structure ( P 2 1 / n (no. 14), a = 9.4081(19), b = 10.012(2), c = 5.9832(12) Å, β = 93.44(3)°, Z = 2) was solved on the basis of single‐crystal X‐ray diffraction data. Li 2 Sr 4 Al 2 Ta 2 N 8 O is built up of vertex sharing AlN 4 and TaN 4 tetrahedra, forming a BCT‐zeolite type structure with Sr 2+ ions and molecular Li 2 O units incorporated into the voids. Lattice energy calculations (MAPLE) confirmed the electrostatic bonding interactions and the chemical composition.
Polyphenols Inhibit Candida albicans and Streptococcus mutans Biofilm Formation (2019)

<b>Background:</b> <i>Streptococcus mutans</i> (<i>S. mutans</i>) and <i>Candida albicans</i> (<i>C. albicans</i>) are two major contributors to dental caries. They have a symbiotic relationship, allowing them to create an enhanced biofilm. Our goal was to examine whether two natural polyphenols (Padma hepaten (PH) and a polyphenol extraction from green tea (PPFGT)) could inhibit the caries-inducing properties of <i>S. mutans</i> and <i>C. albicans</i>. <b>Methods:</b> Co-species biofilms of <i>S. mutans</i> and <i>C. albicans</i> were grown in the presence of PH and PPFGT. Biofilm formation was tested spectrophotometrically. Exopolysaccharides (EPS) secretion was quantified using confocal scanning laser microscopy. Biofilm development was also tested on orthodontic surfaces (Essix) to assess biofilm inhibition ability on such an orthodontic appliance. <b>Results:</b> PPFGT and PH dose-dependently inhibited biofilm formation without affecting the planktonic growth. We found a significant reduction in biofilm total biomass using 0.625 mg/mL PPFGT and 0.16 mg/mL PH. A concentration of 0.31 mg/mL PPFGT and 0.16 mg/mL PH inhibited the total cell growth by 54% and EPS secretion by 81%. A reduction in biofilm formation and EPS secretion was also observed on orthodontic PVC surfaces. <b>Conclusions:</b> The polyphenolic extractions PPFGT and PH have an inhibitory effect on <i>S. mutans</i> and <i>C. albicans</i> biofilm formation and EPS secretion.
Investigation of the count rate performance of the General Electric Advance positron emission tomograph (2002)

A series of 2D and 3D count rate measurements have been carried out on the Advance PET system. The measurements include: NEMA standard protocols; simultaneous imaging of two small vials containing [O-15] water and [F-18]; a cardiac insert placed in a water filled elliptical tank; two different head sized cylindrical tanks; and a Hoffman 3D phantom. The data were processed with and without dead time and scatter corrections. Plots were made of the total count rate, randoms, trues+scatter, scatter corrected trues, and noise equivalent count rate as a function of total activity in the machine and as the /spl mu/Ci/cc in the phantoms. The accuracy of deadtime corrections was also measured. In 2D mode, the NEMA standard protocol resulted in maximum 'trues' count rates of 540,000 cps in high sensitivity mode. In 3D mode the head sized cylindrical phantoms yielded a maximum trues rate of approximately 950,000 cps. Recovery of the water half-life was accurate with up to 50 mCi for the cardiac insert in 2D mode.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Prediction and validation of diffusion coefficients in a model drug delivery system using microsecond atomistic molecular dynamics simulation and vapour sorption analysis (2014)

Diffusion of small to medium sized molecules in polymeric medical device materials underlies a broad range of public health concerns related to unintended leaching from or uptake into implantable medical devices. However, obtaining accurate diffusion coefficients for such systems at physiological temperature represents a formidable challenge, both experimentally and computationally. While molecular dynamics simulation has been used to accurately predict the diffusion coefficients, D, of a handful of gases in various polymers, this success has not been extended to molecules larger than gases, e.g., condensable vapours, liquids, and drugs. We present atomistic molecular dynamics simulation predictions of diffusion in a model drug eluting system that represent a dramatic improvement in accuracy compared to previous simulation predictions for comparable systems. We find that, for simulations of insufficient duration, sub-diffusive dynamics can lead to dramatic over-prediction of D. We present useful metrics for monitoring the extent of sub-diffusive dynamics and explore how these metrics correlate to error in D. We also identify a relationship between diffusion and fast dynamics in our system, which may serve as a means to more rapidly predict diffusion in slowly diffusing systems. Our work provides important precedent and essential insights for utilizing atomistic molecular dynamics simulations to predict diffusion coefficients of small to medium sized molecules in condensed soft matter systems.
FIBER LENGTH DISTRIBUTION MEASUREMENT FOR LONG GLASS AND CARBON FIBER REINFORCED INJECTION MOLDED THERMOPLASTICS (2007)

Procedures for fiber length distribution (FLD) measurement of long fiber reinforced injection molded thermoplastics were refined for glass and carbon fibers. Techniques for sample selection, fiber separation, digitization and length measurement for both fiber types are described in detail. Quantitative FLD results are provided for glass and carbon reinforced polypropylene samples molded with a nominal original fiber length of 12.7 mm (1/2 in.) using equipment optimized for molding short fiber reinforced thermoplastics.
Sensitivity Analysis for Unmeasured Confounding in Medical Product Development and Evaluation Using Real World Evidence (2023)

The American Statistical Association Biopharmaceutical Section (ASA BIOP) scientific working group on real-world evidence (RWE) has been making continuous, extended efforts towards a goal of supporting and advancing regulatory science with respect to clinical studies intended to use real-world data for evidence generation for the purpose of medical product development and evaluation (i.e., RWE studies). In 2023, the working group published a manuscript delineating challenges and opportunities in constructing estimands for RWE studies following the framework in ICH E9(R1) guidance on estimand and sensitivity analysis. As a follow-up task, we describe the other issue, sensitivity analysis. Although the FDA's definition of RWE studies includes randomized trials using RWD as a primary source of evidence generation such as pragmatic trials, here we focus on non-randomized RWE studies and the issue of unmeasured confounding which is a major source of bias for most RWE studies. We review the availability and applicability of sensitivity analysis methods for different types of unmeasured confounding. We also provide some practical and regulatory considerations on using sensitivity analysis for such RWE studies. Then, we use a plasmode case study to demonstrate realistic ways to interpret sensitivity analysis results in supporting regulatory decision-making. We conclude with a brief discussion.
Task- and age-effects in functional neuroimaging studies of working memory – a quantitative meta-analysis (2010)

Introduction: Impairment of working memory is found in patients suffering from a variety of neuro-psychiatric disorders such as dementia, Parkinson's disease or schizophrenia. The neurobiological basis of this function and its socio-economically highly relevant impairment, however, are still largely unclear. While there is already a large number of functional imaging studies investigating the neural correlates of the working memory1, their results are often nonuniform and partly contradictory. To allow more generalisable inference about the involved brain regions as well as their age dependence we here report a coordinate-based meta-analysis on working memory studies.
Polysialic acid governs T-cell development by regulating progenitor access to the thymus (2009)

Although the polysialyltransferase ST8Sia IV is expressed in both primary and secondary human lymphoid organs, its product, polysialic acid (polySia), has been largely overlooked by immunologists. In contrast, polySia expression and function in the nervous system has been well characterized. In this context, polySia modulates cellular adhesion, migration, cytokine response, and contact-dependent differentiation. Provocatively, these same processes are vital components of immune development and function. We previously established that mouse multipotent hematopoietic progenitors use ST8Sia IV to express polySia on their cell surfaces. Here, we demonstrate that, relative to wild-type controls, ST8Sia IV(-/-) mice have a 30% reduction in total thymocytes and a concomitant deficiency in the earliest thymocyte precursors. T-cell progenitors originate in the bone marrow and are mobilized to the blood at regular intervals by unknown signals. We performed in vivo reconstitution experiments in which ST8Sia IV(-/-) progenitors competed with wild-type cells to repopulate depleted or deficient immune subsets. Progenitors lacking polySi exhibited a specific defect in T-cell development because of an inability to access the thymus. This phenotype probably reflects a decreased capacity of the ST8Sia IV(-/-) progenitors to escape from the bone marrow niche. Collectively, these results provide evidence that polySia is involved in hematopoietic development.
Lichtinduzierte modulare Ligation von konventionellen RAFT‐Polymeren (2012)

Ein nichtaktiviertes RAFT-Agens, das am Ende eines RAFT-Polymers gebunden ist, kann durch lichtinduzierte Diels-Alder-Reaktion unter milden Bedingungen und ohne Katalysator mit einem ortho-Chinodimethan (Photoenol) gekuppelt werden. Die Methode ist allgemein anwendbar und öffnet den Weg zur Konjugation vielfältiger RAFT-Polymere mit Photoenol-funktionalisierten (Makro)Molekülen (RAFT: reversible addition–fragmentation chain transfer). As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Cembranoid Synthesis Using Ketophosphonate - Aldehyde Crclization: Syntheses of Thunbergols and α- and β-Cembra-2,7,11-triene-4,6-diols (1989)

Cyclization of the ketophosphonate 18 was efficient and led to the thunbergols 3 and 4. Cyclization of the protected hydroxyphosphonate 28 was less efficient, but gave the cyclic ketone 29, a precursor of the cembratrienediols 1 and 2, with little racemization at C-1.
Novel Approach to Track the Lifecycle of Inflammation from Chemokine Expression to Inflammatory Proteins in Sweat Using Electrochemical Biosensor (2022)

Abstract Inflammatory biomarkers are modulated during the course of any infectious disease, and currently, there is no wearable technology that enables patient management through noninvasive monitoring of these markers. This work is the first demonstration of the discovery and quantification of interferon‐inducible protein (IP‐10) and tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL), two key prognostic markers of infection in human sweat. The levels of IP‐10 and TRAIL in sweat are quantified, validated, and confirmed using a standard reference method through preclinical human subject studies. Additionally, simultaneous and continuous detection of IP‐10, TRAIL, and C‐reactive protein (CRP), for infection monitoring in sweat using a wearable SWEATSENSER device is demonstrated. The SWEATSENSER is ultrasensitive with a limit of detection of 1 pg mL −1 (IP‐10 and TRAIL), 0.2 ng mL −1 (CRP) with a wide dynamic range. Bland–Altman analysis demonstrates good agreement between SWEATSENSER and standard reference methods through human subject studies. Serum to sweat relationship demonstrates the potential of the SWEATSENSER to track infection etiology.
Memristive technologies for data storage, computation, encryption, and radio-frequency communication (2022)

Memristive devices, which combine a resistor with memory functions such that voltage pulses can change their resistance (and hence their memory state) in a nonvolatile manner, are beginning to be implemented in integrated circuits for memory applications. However, memristive devices could have applications in many other technologies, such as non-von Neumann in-memory computing in crossbar arrays, random number generation for data security, and radio-frequency switches for mobile communications. Progress toward the integration of memristive devices in commercial solid-state electronic circuits and other potential applications will depend on performance and reliability challenges that still need to be addressed, as described here.
Pleiotropic effects of polysaccharide capsule loss on selected biological properties of Streptococcus suis. (2010)

In this study, an unencapsulated Streptococcus suis mutant was used to investigate the pleiotropic effects resulting from capsule loss. The capsule deficient mutant of S. suis acquired a biofilm-positive phenotype, which was associated with significantly increased cell surface hydrophobicity. Cell-associated fibrinogen-binding and chymotrypsin-like activities were decreased in the unencapsulated mutant. The mutant did not differ significantly from the encapsulated parent strain for minimal inhibitory concentrations to penicillin G, ampicillin, and tetracycline. However, while the encapsulated strain was highly resistant to the bactericidal action of penicillin G and ampicillin, the unencapsulated mutant was approximately 60-fold more sensitive. Compared with the parent strain, the unencapsulated mutant induced a much higher inflammatory response in monocyte-derived macrophages resulting in an increased secretion of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, and IL-8. The capsule appears to hinder important adhesins or hydrophobic molecules that mediate biofilm formation, as well as cell wall components capable of stimulating immune cells.
Automatic Detection of Sentence and Clause Units using Local Syntactic Dependency (2007)

For robust detection of sentence and clause units in spontaneous speech such as lectures and meetings, we propose a novel cascaded chunking strategy which incorporates syntactic and semantic information. Application of general syntactic parsing is difficult for spontaneous speech having ill-formed sentences and disfluencies, especially for erroneous transcripts generated by ASR systems. Therefore, we focus on the local syntactic dependency of adjacent words and phrases, and train binary classifiers based on SVM (support vector machines) for this purpose. An experimental evaluation using spontaneous talks of the CSJ (Corpus of Spontaneous Japanese) demonstrates that the proposed dependency analysis can be robustly performed and is effective for clause/sentence unit detection in ASR outputs.
A near-optimal stochastic gradient method for decentralized non-convex finite-sum optimization. (2020)

This paper describes a $near$-$optimal$ stochastic first-order gradient method for decentralized finite-sum minimization of smooth non-convex functions. Specifically, we propose GT-SARAH that employs a local SARAH-type variance reduction and global gradient tracking to address the stochastic and decentralized nature of the problem. Considering a total number of $N$ cost functions, equally divided over a directed network of $n$ nodes, we show that GT-SARAH finds an $\epsilon$-accurate first-order stationary point in ${\mathcal{O}(N^{1/2}\epsilon^{-1})}$ gradient computations across all nodes, independent of the network topology, when ${n\leq\mathcal{O}(N^{1/2}(1-\lambda)^{3})}$, where ${(1-\lambda)}$ is the spectral gap of the network weight matrix. In this regime, GT-SARAH is thus, to the best our knowledge, the first decentralized method that achieves the algorithmic lower bound for this class of problems. Moreover, GT-SARAH achieves a $non$-$asymptotic$ $linear$ $speedup$, in that, the total number of gradient computations at each node is reduced by a factor of $1/n$ compared to the near-optimal algorithms for this problem class that process all data at a single node. We also establish the convergence rate of GT-SARAH in other regimes, in terms of the relative sizes of the number of nodes $n$, total number of functions $N$, and the network spectral gap $(1-\lambda)$. Over infinite time horizon, we establish the almost sure and mean-squared convergence of GT-SARAH to a first-order stationary point.