gebhart/patrepeval huggingface dataset:
Strategic importance of networks for single specialty groups. (1987)

Increasing competition and the pressures of cutting costs are threatening the survival of single specialty groups. The author points out that these groups must be imaginative and innovative in developing networks with what may once have been economic enemies or they will die. A description of these some of these alternative health plans is included.
Comparative immunolocalization studies of collagenase 1 and collagenase 3 production in the rheumatoid lesion, and by human chondrocytes and synoviocytes in vitro (1998)

The degradation of fibrillar type II collagen is a major feature of cartilage destruction in rheumatoid arthritis (RA). Since collagenase 3 is produced by chondrocytes and preferentially degrades type II cartilage collagen, it seemed likely that this enzyme would have a prominent role in the destruction of rheumatoid joints. Using immunolocalization techniques, we have examined and compared the production and distributions of collagenase 1 and collagenase 3 in cells and tissues derived from rheumatoid knee arthroplasties. Primary cultures of chondrocytes stimulated with interleukin-1 beta showed that most of the cells produced collagenase 1, whereas only a minority (approximately 5-10%) produced collagenase 3; a few chondrocytes demonstrated the co-ordinate production of both enzymes. Primary cultures of rheumatoid synoviocytes produced collagenase 1, but not collagenase 3. Both enzymes were demonstrated in the rheumatoid lesion. Collagenase 1 was more commonly observed in both synovium and cartilage (22 of the 28 specimens), was especially prominent at cartilage erosion sites, and most of the positive specimens demonstrated extracellular enzyme. By contrast, collagenase 3 was observed less frequently (7/28 specimens) and was produced by relatively few chondrocytes and synovial cells, this usually being much less than that observed for chondrocytes of osteoarthritic cartilage. These observations suggest different regulatory mechanisms for the production of collagenases 1 and 3 in the rheumatoid lesion, and demonstrate that the distribution and production of collagenase 1 are far more prevalent than those for collagenase 3.
High‐affinity urokinase‐derived cyclic peptides inhibiting urokinase/urokinase receptor‐interaction: effects on tumor growth and spread (2002)

Urokinase-type plasminogen activator (uPA) binds with high affinity to its specific cell surface receptor (uPAR) (CD87) via a well-defined sequence within the N-terminal region of uPA (uPA(19-31)). Since this uPA/uPAR-interaction plays a significant role in tumor cell invasion and metastasis, it has become an attractive therapeutic target. Two small peptidic cyclic competitive antagonists of uPA/uPAR-interaction have been developed, based on the uPAR binding site in uPA: WX-360 (cyclo(21,29)[D-Cys21]-uPA(21-30)[S21C;H29C]) and its norleucine (Nle) derivative WX-360-Nle (cyclo(21,29)[D-Cys21]-uPA(21-30)[S21C;K23Nle;H29C]). These peptides display an only five to 10-fold lower affinity to uPAR as compared to the naturally occurring uPAR-ligand uPA. In this study, WX-360 and WX-360-Nle were tested in nude mice for their potency to inhibit tumor growth and intraperitoneal spread of lacZ-tagged human ovarian cancer cells. Intraperitoneal administration of either cyclic peptide (20 mg peptide/kg; 1x daily for 37 days) into the tumor-bearing nude mice resulted in a significant reduction of tumor weight and spread within the peritoneum as compared to the untreated control group. This is the first report demonstrating effective reduction of tumor growth and spread of human ovarian cancer cells in vivo by small synthetic uPA-derived cyclic peptides competitively interfering with uPA/uPAR-interaction. Thus, both WX-360 and WX-360-Nle are promising novel compounds to reduce dissemination of human ovarian carcinoma.
SubCM: a tool for improved visibility of software change in an industrial setting (2004)

Software configuration management is the discipline of managing large collections of software development artefacts from which software products are built. Software configuration management tools typically deal with artefacts at fine levels of granularity - such as individual source code files - and assist with coordination of changes to such artefacts. This paper describes a lightweight tool, designed to be used on top of a traditional file-based configuration management system. The add-on tool support enables users to flexibly define new hierarchical views of product structure, independent of the underlying artefact-repository structure. The tool extracts configuration and change data with respect to the user-defined hierarchy, leading to improved visibility of how individual subsystems have changed. The approach yields a range of new capabilities for build managers, and verification and validation teams. The paper includes a description of our experience using the tool in an organization that builds large embedded software systems.
Neurologic and Developmental Disability at Six Years of Age after Extremely Preterm Birth (2005)

Among extremely preterm children, cognitive and neurologic impairment is common at school age. A comparison with their classroom peers indicates a level of impairment that is greater than is recognized with the use of standardized norms.
Comparison of Hi-C results using in-solution versus in-nucleus ligation (2015)

We conclude that in-nucleus ligation captures chromatin interactions more consistently over a wider range of distances, and significantly reduces both experimental noise and bias. In-nucleus ligation creates higher quality Hi-C libraries while simplifying the experimental procedure. We suggest that the entire range of 3C applications are likely to show similar benefits from in-nucleus ligation.
Bhasma : The ancient Indian nanomedicine (2014)

Ayurveda and other Indian system of medicine use metals, but their use is also amply described in Chinese and Egyptian civilization in 2500 B.C. Bhasma are unique ayurvedic metallic/minerals preparation, treated with herbal juice or decoction and exposed for Ayurveda, which are known in Indian subcontinent since 7(th) century A.D. and widely recommended for treatment of a variety of chronic ailments. Animal's derivative such as horns, shells, feathers, metallic, nonmetallic and herbals are normally administered as Bhasma. A Bhasma means an ash obtained through incineration; the starter material undergoes an elaborate process of purification and this process is followed by the reaction phase, which involves incorporation of some other minerals and/or herbal extract. There are various importance of Bhasma like maintaining optimum alkalinity for optimum health, neutralizing harmful acids that lead to illness; because Bhasma do not get metabolized so they don't produce any harmful metabolite, rather it breakdowns heavy metals in the body. Methods including for Bhasma preparation are parpati, rasayoga, sindora, etc., Bhasma which contain Fe, Cu, S or other manufacturing process plays a specific role in the final product(s). Particle size (1-2 μ) reduced significantly, which may facilitate absorption and assimilation of the drug into the body system. Standardization of Bhasma is utmost necessary to confirm its identity and to determine its quality, purity safety, effectiveness and acceptability of the product. But the most important challenges faced by these formulations are the lack of complete standardization by physiochemical parameters.
ATP-LipidsProtein Anchor and Energy Source in Two Dimensions (1996)

The ubiquitous function of ATP as energy equivalent in nature has resulted in a common folding pattern of ATP-binding proteins. Their binding pocket tolerates modifications of the adenine ring to some extend, whereas those of the triphosphate group strongly affect the binding affinity. In consequence, immobilized C8- and N6-modified ATP analogues are frequently used for affinity purification of ATPases or kinases. To combine this unique recognition principle with the fascinating properties of self-assembly, we have synthesized a novel class of hydrolyzable and nonhydrolyzable ATP-lipids where the nucleotides are covalently attached via C8- or N6-position of the adenine ring to a synthetic lipid. These ATP-lipids were characterized by various enzyme assays in micellar solution, resulting in ATPase and competition activities that are comparable to their free counterparts. The specific docking of actin as a model of an ATP-binding protein to ATP-lipid monolayers was followed by film balance technique and epifluorescence microscopy. Based on this specific interaction, actin-supported membranes were generated to study shape transitions of vesicular systems. Due to the coupling of actin to ATP-lipid bilayers drastic changes in the viscoelastic properties and shape transitions were observed by phase contrast microscopy. These results underline the properties of these novel ATP-lipids as protein anchor or energy source in two dimensions. They can be applied either to form phantom cells, actin-supported membranes or to orient and crystallize ATP-binding proteins at lipid interfaces.
Rationally Designed Redox-Sensitive Protein Hydrogels with Tunable Mechanical Properties (2016)

Protein hydrogels are an important class of materials for applications in biotechnology and medicine. The fine-tuning of their sequence, molecular weight, and stereochemistry offers unique opportunities to engineer biofunctionality, biocompatibility, and biodegradability into these materials. Here we report a new family of redox-sensitive protein hydrogels with controllable mechanical properties composed of recombinant silk-elastin-like protein polymers (SELPs). The SELPs were designed and synthesized with different ratios of silk-to-elastin blocks that incorporated periodic cysteine residues. The cysteine-containing SELPs were thermally responsive in solution and rapidly formed hydrogels at body temperature under physiologically relevant, mild oxidative conditions. Upon addition of a low concentration of hydrogen peroxide at 0.05% (w/v), gelation occurred within minutes for the SELPs with a protein concentration of approximately 4% (w/v). The gelation time and mechanical properties of the hydrogels were dependent on the ratio of silk to elastin. These polymer designs also significantly affected redox-sensitive release of a highly polar model drug from the hydrogels in vitro. Furthermore, oxidative gelation was performed at other physiologically relevant temperatures, and this resulted in hydrogels with tunable mechanical properties, thus, providing a secondary level of control over hydrogel stiffness. These newly developed injectable SELP hydrogels with redox-sensitive features and tunable mechanical properties may be potentially useful as biomaterials with broad applications in controlled drug delivery and tissue engineering.
Data-driven brain MRI segmentation supported on edge confidence and a priori tissue information (2005)

Brain magnetic resonance imaging segmentation is accomplished in this work by applying nonparametric density estimation, using the mean shift algorithm in the joint spatial-range domain. The quality of the class boundaries is improved by including an edge confidence map, that represents the confidence of truly being in the presence of a border between adjacent regions; an adjacency graph is then constructed with the labeled regions, and analyzed and pruned to merge adjacent regions. In order to assign image regions to a cerebral tissue type, a spatial normalization between image data and standard probability maps is carried out, so that for each structure a maximum a posteriori probability criterion is applied. The method was applied to synthetic and real images, keeping all parameters constant throughout the process for each type of data. The combination of region segmentation and edge detection proved to be a robust technique, as adequate clusters were automatically identified, regardless of the noise level and bias. In a comparison with reference segmentations, average Tanimoto indexes of 0.90-0.99 were obtained for synthetic data and of 0.59-0.99 for real data, considering gray matter, white matter, and background.
Contribution to the mode of action of univalent gold. (1991)

Au+ binds to the collagen structure and, therefore, the authors studied the kinetics of the interaction between sodium gold thiosulphate (SGTS) and C1q complement subcomponent, the structure of is partially collagenous. The kinetics was evaluated densitometrically and compared with that of collagen and SGTS. On the basis of those results, the effect of SGTS upon collagen type-II-induced arthritis (CIA) was investigated in Wistar rats. SGTS (20 mg per kg of body weight weekly) was administered i.m. starting i) with the first immunization dose, ii) with the second immunization dose, and iii) after the onset of arthritis. Regardless of the timing of drug administration the manifestation of arthritis was decreased, but the decrease was more expressed in the first two groups. It was concluded that SGTS administration is capable of inhibiting CIA, provided that the drug is applied sufficiently early. Since formation of antibodies to type-II collagen remained unaffected, it is feasible that the mode of action of gold complexes is based mainly on blocking the activation of complement system.
Effect of W Film Stress on W-Gate MOS Characteristics (1989)

The fixed oxide charge density ( N f ) of W-gate MOS capacitors has been investigated as a function of both annealing temperature and stress of the W film. It is found that N f greatly increases upon 1000°C annealing when the total stress, which is defined as the product of the W film stress before 1000°C annealing and thickness of the W film, is more than 1.4×10 5 dyne/cm (compressive). The interface state density ( D it ) also increases with increase in N f . For the samples whose N f is large, etch pits are revealed on the Si surface by Secco etching. There is a linear correlation between the etch pit density and the N f value. It is supposed that the increases of N f and D it are due to Si defects formed at the SiO 2 /Si interface by the large stress of the W film.
Estimating Total Nephron Number in the Adult Kidney Using the Physical Disector/Fractionator Combination (2012)

Nephron number has emerged as a useful parameter for assessing the roles of specific genes and feto-maternal environmental factors in kidney development. Nephron number is also of clinical interest due to increasing evidence suggesting that low nephron number is associated with increased risk for developing chronic adult disease, including cardiovascular and renal disease. The physical disector/fractionator combination is considered the gold standard method for estimating total nephron number in kidneys. Here we describe the use of this method to estimate total nephron number in mouse and rat kidneys, and variations to the method required to estimate nephron number in larger species, including human.
Laboratory and Flight Performance of the Mars Pathfinder (15,1/6) Convolutionally Encoded Telemetry Link (1997)

Compatibility between the Mars Pathflnder spacecraft-generated (15,1/6) convolutional code and the DSN Block III maximum-likelihood convolutional decoder has been demonstrated in the laboratory at all spacecraft data rates. Laboratory tests of the (15,1/6) code (unconcatenated) have found it to be superior to that of the (7,1/2) convolutional code. At 20 bps, the performance gain of the (15,1/6) code over that of the (7,1/2) code is 1.5 dB, and at 1185 to 11,060 bps the performance gain is over 2 dB at a threshold of 5£ 10 i3 bit-error rate. In addition, the Mars Pathflnder project has successfully completed a test campaign to measure the in-∞ight performance of the (15,1/6) convolutional code concatenated with the Reed{Solomon code. It has been found to match the laboratory tests performed prior to launch.
Development of volume-stable adipose tissue constructs using polycaprolactone-based polyurethane scaffolds and fibrin hydrogels (2013)

Adipose tissue engineering aims at the restoration of soft tissue defects and the correction of contour deformities. It is therefore crucial to provide functional adipose tissue implants with appropriate volume stability. Here, we investigate two different fibrin formulations, alone or in combination with biodegradable polyurethane (PU) scaffolds as additional support structures, with regard to their suitability to generate volume-stable adipose tissue constructs. Human adipose-derived stem cells (ASCs) were incorporated in a commercially available fibrin sealant as well as a stable fibrin hydrogel previously developed by our group. The composite constructs made from the commercially available fibrin and porous poly(ε-caprolactone)-based polyurethane scaffolds exhibited increased volume stability as compared to fibrin gels alone; however, only constructs using the stable fibrin gels completely maintained their size and weight for 21 days. Adipogenesis of ASCs was not impaired by the additional PU scaffold. After induction with a common hormonal cocktail, for constructs with either fibrin formulation, strong adipogenic differentiation of ASCs was observed after 21 days in vitro. Furthermore, upregulation of adipogenic marker genes was demonstrated at mRNA (PPARγ, C/EBPα, GLUT4 and aP2; qRT-PCR) and protein (leptin; ELISA) levels. Stable fibrin/PU constructs were further evaluated in a pilot in vivo study, resulting in areas of well-vascularized adipose tissue within the implants after only 5 weeks. Copyright © 2013 John Wiley & Sons, Ltd.
The Complexity of the His Bundle: Understanding Its Anatomy and Physiology through the Lens of the Past and the Present (2016)

In this paper, we describe the anatomy and physiology of the His bundle and describe the mechanisms by which permanent His-bundle pacing can be accomplished.
Pan-Cancer Analysis of TCGA Data Revealed Promising Reference Genes for qPCR Normalization (2019)

Quantitative PCR (qPCR) remains the most widely used technique for gene expression evaluation. Obtaining reliable data using this method requires reference genes (RGs) with stable mRNA level under experimental conditions. This issue is especially crucial in cancer studies because each tumor has a unique molecular portrait. The Cancer Genome Atlas (TCGA) project provides RNA-Seq data for thousands of samples corresponding to dozens of cancers and presents the basis for assessment of the suitability of genes as reference ones for qPCR data normalization. Using TCGA RNA-Seq data and previously developed CrossHub tool, we evaluated mRNA level of 32 traditionally used RGs in 12 cancer types, including those of lung, breast, prostate, kidney, and colon. We developed an 11-component scoring system for the assessment of gene expression stability. Among the 32 genes, <i>PUM1</i> was one of the most stably expressed in the majority of examined cancers, whereas <i>GAPDH</i>, which is widely used as a RG, showed significant mRNA level alterations in more than a half of cases. For each of 12 cancer types, we suggested a pair of genes that are the most suitable for use as reference ones. These genes are characterized by high expression stability and absence of correlation between their mRNA levels. Next, the scoring system was expanded with several features of a gene: mutation rate, number of transcript isoforms and pseudogenes, participation in cancer-related processes on the basis of Gene Ontology, and mentions in PubMed-indexed articles. All the genes covered by RNA-Seq data in TCGA were analyzed using the expanded scoring system that allowed us to reveal novel promising RGs for each examined cancer type and identify several "universal" pan-cancer RG candidates, including <i>SF3A1, CIAO1</i>, and <i>SFRS4</i>. The choice of RGs is the basis for precise gene expression evaluation by qPCR. Here, we suggested optimal pairs of traditionally used RGs for 12 cancer types and identified novel promising RGs that demonstrate high expression stability and other features of reliable and convenient RGs (high expression level, low mutation rate, non-involvement in cancer-related processes, single transcript isoform, and absence of pseudogenes).
A 2 GHz fractional-N digital PLL with 1b noise shaping ΔΣ TDC (2011)

A 2 GHz fractional-N digital PLL with a single delay cell, noise shaping ΔΣ TDC is implemented in a 0.13µm CMOS. With a simple structure of Δ modulator followed by a charge pump integrator, a wide range TDC input is converted to ΔΣ modulated bit stream. The implemented TDC consumes 1 mA, and the DPLL shows the in-band phase noise of −107 dBc at 500 kHz offset.
Multi-step multi-sensor hider-seeker games (2009)

We study a multi-step hider-seeker game where the hider is moving on a graph and, in each step, the seeker is able to search c subsets of the graph nodes. We model this game as a zero-sum Bayesian game, which can be solved in weakly polynomial time in the players ’ action spaces. The seeker’s action space is exponential in c, and both players’ action spaces are exponential in the game horizon. To manage this intractability, we use a column/constraint generation approach for both players. This approach requires an oracle to determine best responses for each player. However, we show that computing a best response for the seeker is NPhard, even for a single-step game when c is part of the input, and that computing a best response is NPhard for both players for the multi-step game, even if c =1. An integer programming formulation of the best response for the hider is practical for moderate horizons, but computing an exact seeker best response is impractical due to the exponential dependence on both c and the horizon. We therefore develop an approximate best response oracle with bounded suboptimality for the seeker. We prove performance bounds on the strategy that results when column/constraint generation with approximate best responses converges, and we measure the performance of our algorithm in simulations. In our experimental results, column/constraint generation converges to near-minimax strategies for both players fairly quickly. 1
Repurposing Quinacrine against Ebola Virus Infection <i>In Vivo</i> (2019)

Quinacrine hydrochloride is a small-molecule, orally bioavailable drug that has been used clinically as an antimalarial and for many other applications. A machine learning model trained on Ebola virus (EBOV) screening data identified quinacrine as a potent (nanomolar) <i>in vitro</i> inhibitor. In the current study, quinacrine 25 mg/kg was shown to protect 70% of mice (statistically significant) from a lethal challenge with mouse-adapted EBOV with once-daily intraperitoneal dosing for 8 days.
Biocatalytic Asymmetric Synthesis of Chiral Amines from Ketones Applied to Sitagliptin Manufacture (2010)

Pharmaceutical synthesis can benefit greatly from the selectivity gains associated with enzymatic catalysis. Here, we report an efficient biocatalytic process to replace a recently implemented rhodium-catalyzed asymmetric enamine hydrogenation for the large-scale manufacture of the antidiabetic compound sitagliptin. Starting from an enzyme that had the catalytic machinery to perform the desired chemistry but lacked any activity toward the prositagliptin ketone, we applied a substrate walking, modeling, and mutation approach to create a transaminase with marginal activity for the synthesis of the chiral amine; this variant was then further engineered via directed evolution for practical application in a manufacturing setting. The resultant biocatalysts showed broad applicability toward the synthesis of chiral amines that previously were accessible only via resolution. This work underscores the maturation of biocatalysis to enable efficient, economical, and environmentally benign processes for the manufacture of pharmaceuticals.