gebhart/patrepeval huggingface dataset:
1791-P: The Threshold for Fasting Insulin Secretion Is Independent of the Beta-Cell Secretory Response to Glucose in Nondiabetic Humans (2020)

The transition from normal fasting glucose (NFG) and normal glucose tolerance (NGT) to type 2 diabetes is characterized by impaired fasting glucose (IFG) and impaired glucose tolerance (IGT). Graded Glucose Infusion (GGI) has been used to measure β-cell function in response to glucose and to extrapolate the β-cell threshold for insulin secretion. However, this assumes a linear relationship between fasting insulin secretion and the response to a GGI. This may not be the case in e.g., humans with IFG/NGT who have normal β-cell function despite IFG. As part of a series of experiments examining the pathogenesis of prediabetes, we examined the relationship of fasting insulin secretion with the subsequent β-cell response to GGI. To do so, we studied nondiabetic, weight-stable individuals (53 ± 2 yrs, BMI 27.5 ± 1.2 kg/m2). At the time of screening, subjects underwent a 75 g oral glucose tolerance test. On the study day, after an overnight fast, at 0700 (-120 min) a variable insulin infusion was used to maintain glucose at ∼80 mg/dL (until 0845). At 0900, GGI commenced (0-240 min total, starting at 1 mg/kg/min and doubling every 60 min). Insulin Secretion Rate (ISR) was estimated by deconvolution of frequently sampled peripheral C-peptide concentrations. The rate of change of ISR in response to increasing glucose concentrations was used to calculate β-cell responsivity to glucose and the set-point of insulin secretion. As expected, ISR rose throughout the study (0.07 ± 0.01, 0.21 ± 0.05, 0.30 ± 0.07, 0.55 ± 0.13, 0.94 ± 0.15 nmol/min; 0, 60, 120, 180, and 240 min respectively). The individual glucose threshold for insulin secretion (4.8 ± 0.1 mmol/l) was independent of β-cell function during the screening glucose tolerance test (R2 = 0.07, p = 0.67) and during the GGI (R2 = 0.06, p = 0.68). These data imply that the glucose threshold for insulin secretion is independent of β-cell function. Disclosure J.D. Kohlenberg: None. M.C. Laurenti: None. A.M. Egan: None. C. Dalla Man: Research Support; Self; Sanofi-Aventis Deutschland GmbH. R.A. Rizza: None. C. Cobelli: None. A. Vella: Advisory Panel; Self; vTv Therapeutics, Zealand Pharma A/S. Research Support; Self; Novo Nordisk A/S, Xeris Pharmaceuticals, Inc. Funding Endocrine Fellows Foundation; National Institutes of Health (R01DK78646, R01DK116231)
Stabilizing Agents for Drug Nanocrystals: Effect on Bioavailability (2016)

Drug nanocrystals are a versatile option for drug delivery purposes, and while the number of poorly soluble drug materials is all the time increasing, more research in this area is performed. Drug nanocrystals have a simple structure-a solid drug core is surrounded by a layer of stabilizing agent. However, despite the considerably simple structure, the selection of an appropriate stabilizer for a certain drug can be challenging. Mostly, the stabilizer selection is based purely on the requirement of physical stability, e.g., maintaining the nanosized particle size as long as possible after the formation of drug nanocrystals. However, it is also worth taking into account that stabilizer can affect the bioavailability in the final formulation via interactions with cells and cell layers. In addition, formation of nanocrystals is only one process step, and for the final formulation, more excipients are often added to the composition. The role of the stabilizers in the final formulation can be more than only stabilizing the nanocrystal particle size. A good example is the stabilizer's role as cryoprotectant during freeze drying. In this review, the stabilizing effect, role of stabilizers in final nanocrystalline formulations, challenges in reaching in vitro-in vivo correlation with nanocrystalline products, and stabilizers' effect on higher bioavailability are discussed.
A mathematical model for the freezing process in biological tissue (1988)

A mathematical model has been developed to study the process of freezing in biological organs. The model consists of a repetitive unit structure comprising a cylinder of tissue with an axial blood vessel (Krogh cylinder) and it is analysed by the methods of irreversible thermodynamics. The mathematical simulation of the freezing process in liver tissue compares remarkably well with experimental data on the structure of tissue frozen under controlled thermal conditions and the response of liver cells to changes in cooling rate. The study also supports the proposal that the damage mechanism responsible for the lack of success in attempts to preserve tissue in a frozen state, under conditions in which cells in suspension survive freezing, is direct mechanical damage caused by the formation of ice in the vascular system.
Expression of matrix factors in the process of neovascularization of intervertebral disc (2015)

&lt;sec&gt;&lt;title&gt;OBJECTIVE:&lt;/title&gt;&lt;p&gt; To investigate the effects of proteins products of endothelial cells (ECs) on the annulus fibrosus (AF) cell metabolism in an in vitro culture.&lt;/p&gt;&lt;/sec&gt;&lt;sec&gt;&lt;title&gt;METHODS:&lt;/title&gt;&lt;p&gt;Human AF cells were expanded in monolayer cultures and treated with proteins from the medium of cell line HMEC-1 (Human Microvascular Endothelial Cells) (125µg/ml). After 72h of treatment RNA was isolated from AF cells for analysis of gene expression and the culture medium was collected for protein expression analysis.&lt;/p&gt;&lt;/sec&gt;&lt;sec&gt;&lt;title&gt;RESULTS:&lt;/title&gt;&lt;p&gt; The qRT-PCR analysis demonstrated increased gene expression of matrix metalloproteinases (MMPs) in AF cells treated with protein products of endothelial cells compared with cells from control group of AF cells: MMP-1 243.10 times (p&lt;0.05), MMP-2 1.37 time (p&lt;0.05), MMP-3 39.83 times (p&lt;0.05) and MMP-13 5.70 times (p&lt;0.05). In contrast, tissue inhibitors of metalloproteinases (TIMPs) were suppressed; TIMP-2 (0.55 time) (p&lt;0.05) and TIMP-3 (0.60 time) (p&lt;0.05) in the exposed groups. The expression of aggrecan gene (0.83 time) (p&lt;0.05), an important extracellular matrix component, was also reduced. MMP-1 and MMP-3 detection was performed, confirming the results of PCR by Western Blot technique.&lt;/p&gt;&lt;/sec&gt;&lt;sec&gt;&lt;title&gt;CONCLUSIONS:&lt;/title&gt;&lt;p&gt; In this study, we observed that the proteins produced by ECs induced the MMPs expression and suppressed the TIMPs as well as the aggrecan in primary cells of the human intervertebral disc, targeting the development of potential treatments for intervertebral disc degeneration and associated discogenic pain.&lt;/p&gt;&lt;/sec&gt;
Local patch reconstruction framework for optic cup localization in glaucoma detection (2014)

Optic cup localization/segmentation has attracted much attention from medical imaging researchers, since it is the primary image component clinically used for identifying glaucoma, which is a leading cause of blindness. In this work, we present an optic cup localization framework based on local patch reconstruction, motivated by the great success achieved by reconstruction approaches in many computer vision applications recently. Two types of local patches, i.e. grids and superpixels are used to show the variety, generalization ability and robustness of the proposed framework. Tested on the ORIGA clinical dataset, which comprises of 325 fundus images from a population-based study, both implementations under the proposed frameworks achieved higher accuracy than the state-of-the-art techniques.
Bioinspired, nanoscale approaches in contemporary bioanalytics (2018)

The genesis for this topical review stems from the interdisciplinary Biointerfaces International conference 2016 (BI 2016) in Zurich, Switzerland, wherein the need for advances in analytical tools was both expressed and addressed. Pushing the limits of detection for characterizing individual components, such as single proteins, single drug-delivery vehicles, or probing single living cells in a more natural environment, will contribute to the understanding of the complex biomolecular systems central to a number of applications including medical diagnostics, tissue engineering, and drug screening and delivery. Accordingly, the authors begin with an overview of single nanoparticle analytics highlighting two emerging techniques and how they compare with existing techniques. The first is based on single particle tracking of nanoparticles tethered to a mobile supported lipid bilayer, enabling the simultaneous characterization of both size and composition of individual nanoparticles. The second technique is based on probing variations in the ionic conduction across nanoscale apertures for detection of not only nanoparticles but also membrane-tethered proteins, thereby allowing a multiparameter characterization of individual nanoscopic objects, addressing their size, shape, charge, and dipole moment. Subsequently, the authors lead into an example of an area of application that stands to benefit from such advances in bioanalytics, namely, the development of biomimetic lipid- and polymer-based assemblies as stimuli-responsive artificial organelles and nanocarriers designed to optimize delivery of next generation high-molecular-weight biological drugs. This in turn motivates the need for additional advanced techniques for investigating the cellular response to drug delivery, and so the review returns again to bioanalytics, in this case single-cell analysis, while highlighting a technique capable of probing and manipulating the content of individual living cells via fluidic force microscopy. In presenting a concerted movement in the field of bioinspired bioanalytics, positioned in the context of drug delivery, while also noting the critical role of surface modifications, it is the authors’ aim to evaluate progress in the field of single component bioanalytics and to emphasize the impact of initiating and maintaining a fruitful dialogue among scientists, together with clinicians and industry, to guide future directions in this area and to steer innovation to successful translation.
Reproductive Biology of Picrorhiza kurroa – a Critically Endangered High Value Temperate Medicinal Plant (2011)

Picrorhiza kurroa Royle ex. Benth.(Family: Scrophulariaceae ), an important endangered temperate medicinal plant used as hepatic stimulant is a perennial herb propagated mostly by stolon segments. Chromosome number and its reproductive behaviour are reported for the first time. Meiosis is normal in the species with 2n=34 chromosomes. P. kurroa mostly prefers out-crossing as evinced by pollination experiments and floral architecture.
Are the current Indian growth charts really representative? Analysis of anthropometric assessment of school children in a South Indian district (2014)

This study shows that under and over-nutrition among school children is in almost equal proportions. There is an underestimation of obesity among children whenever an Indian or an International growth chart is used. Thus, this study brings out the need for a really representative growth chart.
Biosafety Studies of a Clinically Applicable Lentiviral Vector for the Gene Therapy of Artemis-SCID (2019)

Genetic deficiency of the nuclease DCLRE1C/Artemis causes radiosensitive severe combined immunodeficiency (RS-SCID) with lack of peripheral T and B cells and increased sensitivity to ionizing radiations. Gene therapy based on transplanting autologous gene-modified hematopoietic stem cells could significantly improve the health of patients with RS-SCID by correcting their immune system. A lentiviral vector expressing physiological levels of human ARTEMIS mRNA from an EF1a promoter without post-transcriptional regulation was developed as a safe clinically applicable candidate for RS-SCID gene therapy. The vector was purified in GMP-comparable conditions and was not toxic in vitro or in vivo. Long-term engraftment of vector-transduced hematopoietic cells was achieved in irradiated Artemis-deficient mice following primary and secondary transplantation (6 months each). Vector-treated mice displayed T and B lymphopoiesis and polyclonal T cells, had structured lymphoid tissues, and produced immunoglobulins. Benign signs of inflammation were noted following secondary transplants, likely a feature of the model. There was no evidence of transgene toxicity and no induction of hematopoietic malignancy. In vitro, the vector had low genotoxic potential on murine hematopoietic progenitor cells using an immortalization assay. Altogether, these preclinical data show safety and efficacy, and support further development of the vector for the gene therapy of RS-SCID. Genetic deficiency of the nuclease DCLRE1C/Artemis causes radiosensitive severe combined immunodeficiency (RS-SCID) with lack of peripheral T and B cells and increased sensitivity to ionizing radiations. Gene therapy based on transplanting autologous gene-modified hematopoietic stem cells could significantly improve the health of patients with RS-SCID by correcting their immune system. A lentiviral vector expressing physiological levels of human ARTEMIS mRNA from an EF1a promoter without post-transcriptional regulation was developed as a safe clinically applicable candidate for RS-SCID gene therapy. The vector was purified in GMP-comparable conditions and was not toxic in vitro or in vivo. Long-term engraftment of vector-transduced hematopoietic cells was achieved in irradiated Artemis-deficient mice following primary and secondary transplantation (6 months each). Vector-treated mice displayed T and B lymphopoiesis and polyclonal T cells, had structured lymphoid tissues, and produced immunoglobulins. Benign signs of inflammation were noted following secondary transplants, likely a feature of the model. There was no evidence of transgene toxicity and no induction of hematopoietic malignancy. In vitro, the vector had low genotoxic potential on murine hematopoietic progenitor cells using an immortalization assay. Altogether, these preclinical data show safety and efficacy, and support further development of the vector for the gene therapy of RS-SCID.
Nitrogen Implantation and In Situ HF Vapor Clean for Deep Submicrometer n-MOSFETs (2002)

This work describes a high performance and reliable deep submicrometer n-channel metal oxide semiconductor field effect transistor (n-MOSFET) with ultrathin gate oxide prepared by combining nitrogen gate electrode implantation and native-oxide-free in situ HF vapor preoxidation cleaning. The results herein reveal that the performance and reliability, including the leakage current of the ultrathin gate oxide, charge-to-breakdown, drain current, transconductance, charge pumping current, stress induced leakage current, and hot carrier reliability of n-MOSFETs are all significantly improved. The enhanced reliability and performance are attributed to the native-oxide-free process, smooth interface, and reduced incorporation of As in the gate oxide which results from HF vapor cleaning and nitrogen implantation. © 2001 The Electrochemical Society. All rights reserved.
Document Spanners for Extracting Incomplete Information (2018)

Rule-based information extraction has lately received a fair amount of attention from the database community, with several languages appearing in the last few years. Although information extraction systems are intended to deal with semistructured data, all language proposals introduced so far are designed to output relations, thus making them incapable of handling incomplete information. To remedy the situation, we propose to extend information extraction languages with the ability to use mappings, thus allowing us to work with documents which have missing or optional parts. Using this approach, we simplify the semantics of regex formulas and extraction rules, two previously defined methods for extracting information. We extend them with the ability to handle incomplete data, and study how they compare in terms of expressive power. We also study computational properties of these languages, focusing on the query enumeration problem, as well as satisfiability and containment.
The Multilayer In-Place Learning Network for the Development of General Invariances and Multi-Task Learning (2007)

Currently, there is a lack of general-purpose in-place learning engines that incrementally learn multiple tasks, to develop "soft" multi-task-shared invariances in the intermediate internal representation while a developmental robot interacts with its environment. Computationally, biologically inspired in-place learning provides unusually efficient learning algorithms whose simplicity, low computational complexity, and generality are set apart from typical conventional learning algorithms. We present in this paper the multiple-layer in-place learning network (MILN) for this ambitious goal. As a key requirement for autonomous mental development, the network enables both unsupervised and supervised learning to occur concurrently, depending on whether motor supervision signals are available or not at the motor end (the last layer) during the agent's interactions with the environment. We present principles based on which MILN automatically develops invariant neurons in different layers and why such invariant neuronal clusters are important for learning later tasks in open-ended development.
Antibody screening at reduced pH enables preferential selection of potently neutralizing antibodies targeting SARS‐CoV‐2 (2021)

Antiviral monoclonal antibody (mAb) discovery enables the development of antibody-based antiviral therapeutics. Traditional antiviral mAb discovery relies on affinity between antibody and a viral antigen to discover potent neutralizing antibodies, but these approaches are inefficient because many high affinity mAbs have no neutralizing activity. We sought to determine whether screening for anti-SARS-CoV-2 mAbs at reduced pH could provide more efficient neutralizing antibody discovery. We mined the antibody response of a convalescent COVID-19 patient at both physiological pH (7.4) and reduced pH (4.5), revealing that SARS-CoV-2 neutralizing antibodies were preferentially enriched in pH 4.5 yeast display sorts. Structural analysis revealed that a potent new antibody called LP5 targets the SARS-CoV-2 N-terminal domain supersite via a unique binding recognition mode. Our data combine with evidence from prior studies to support antibody screening at pH 4.5 to accelerate antiviral neutralizing antibody discovery.
Understanding Our Drugs and Our Diseases (2006)

Analysis of mouse genetic models of human disease-associated traits has provided important insight into the pathogenesis of human disease. As one example, analysis of a murine genetic model of osteoporosis demonstrated that genetic variation within the 15-lipoxygenase (Alox15) gene affected peak bone mass, and that treatment with inhibitors of this enzyme improved bone mass and quality in rodent models. However, the method that has been used to analyze mouse genetic models is very time consuming, inefficient, and costly. To overcome these limitations, a computational method for analysis of mouse genetic models was developed that markedly accelerates the pace of genetic discovery. It was used to identify a genetic factor affecting the rate of metabolism of warfarin, an anticoagulant that is commonly used to treat clotting disorders. Computational analysis of a murine genetic model of narcotic drug withdrawal suggested a potential new approach for treatment of narcotic drug addiction. Thus, the results derived from computational mouse genetic analysis can suggest new treatment strategies, and can provide new information about currently available medicines.
Identification of new protein-coding genes with a potential role in the virulence of the plant pathogen Xanthomonas euvesicatoria (2017)

The discovery and re-annotation of numerous genes in the genome of Xe shows that also a well-annotated genome can be improved. Additionally, our proteogenomic analyses validates "hypothetical" proteins and will improve annotation of Xanthomonadaceae genomes, providing a solid basis for further studies.
Comments on 'Rapid pulsed microwave propagation' (and reply) (1992)

For the original article see ibid., vol.1, no.12, p.374-5 (1991). The commenter attempts to refute the claim by the authors of the above-titled paper that their measurements reveal microwaves propagating faster than the velocity of light. The authors defend their observations.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Mathematical foundations for quantifying shape, shading, and cast shadows in realist master drawings and paintings (2006)

The problem of inferring the two-dimensional location of an illuminant in an image, such as a digital photograph, has been studied as part of general scene analysis. One application area for analytical techniques and algorithms to this end is forensic image analysis, particularly in the detection of tampering and composites. For instance, if algorithms applied to two figures or two sections of an image reveal that these regions were captured under different lighting directions, it is highly likely that these regions were captured separately and later digitally integrated into the composite image, that is, the photograph was tampered. Recently some of these techniques have been applied to the study of realist master paintings and drawings in order to answer questions about the studio working methods of artists. We reveiw several sources of visual information about the location of the illuminant, stressing those most relevant to problems in the analysis of art, specifically paintings and drawings. We then present the foundations for a Bayesian method for integrating estimates from different sources, and then explore the application of such methods to the problem of inferring the location of the illuminant in realist paintings.
X-ray diffraction characterization of stress and crystallographic texture in thin film media (1993)

X-ray diffraction was used to measure the stress and the in-plane crystallographic texture of Co alloy films on grooved substrates. The preference for the c-axis to lie parallel to the groove direction was quantified. A small in-plane stress was measured which displayed an anisotropy between the two directions. The magnitude of this stress appears to be large enough (according to a simple calculation) to contribute to observed coercive anisotropies. The techniques used for extracting the in-plane crystallographic texture and the value of the in-plane stress from the X-ray measurements are discussed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Effect of Aging Heat‐Treatment on Mechanical Properties of AD730™ Superalloy (2014)

cited By 6; Conference of 8th International Symposium on Superalloy 718 and Derivatives 2014 ; Conference Date: 28 September 2014 Through 1 October 2014; Conference Code:110234
Comparison of electrophysiologic data across diverse cardiac geometries (2003)

The authors describe a method for generating one three-dimensional heart surface from digitized serial sections of a number of hearts. This allows a composite surface to be generated from the contours of successive slices of the hearts used in the laboratory. The electrophysiologic data gathered from all hearts can then be mapped onto the generated three-dimensional surface, allowing, for instance, the computation of average values of the measured variable at predetermined points on the standard surface. Thus by using the same geometric surface comparisons between different studies are made possible.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>