gebhart/patrepeval huggingface dataset:
BK Virus: A Clinical Review (2001)

We present a review of the clinically oriented literature about BK virus, a relative of JC virus, which is the etiologic agent of progressive multifocal leukoencephalopathy (PML). The kidney, lung, eye, liver, and brain have been proposed as sites of BK virus-associated disease, both primary and reactivated. BK virus has also been detected in tissue specimens from a variety of neoplasms. We believe that BK virus is most often permissively present in sites of disease in immunosuppressed patients, rather than being an etiologic agent that causes symptoms or pathologic findings. There is, however, strong evidence for BK virus-associated hemorrhagic cystitis and nephritis, especially in recipients of solid organ or bone marrow transplants. Now that BK virus can be identified by use of specific and sensitive techniques, careful evaluation of the clinical and pathologic presentations of patients with BK virus will allow us to form a clearer picture of viral-associated pathophysiology in many organ systems.
Vancomycin Derivatives That Inhibit Peptidoglycan Biosynthesis Without Binding d -Ala- d -Ala (1999)

Vancomycin is an important drug for the treatment of Gram-positive bacterial infections. Resistance to vancomycin has begun to appear, posing a serious public health threat. Vancomycin analogs containing modified carbohydrates are very active against resistant microorganisms. Results presented here show that these carbohydrate derivatives operate by a different mechanism than vancomycin; moreover, peptide binding is not required for activity. It is proposed that carbohydrate-modified vancomycin compounds are effective against resistant bacteria because they interact directly with bacterial proteins involved in the transglycosylation step of cell wall biosynthesis. These results suggest new strategies for designing glycopeptide antibiotics that overcome bacterial resistance.
Characteristics of a Cambered Circulation Control Airfoil Having Both Upper and Lower Surface Trailing Edge Slots (2004)

Abstract : A circulation control (CC) elliptic airfoil section with a thickness-to-chord ratio of 0.17 and 1- percent circular arc camber, was experimentally evaluated to determine its low speed aerodynamic characteristics. The model profile is that of a previously tested single upper surface trailing edge slot airfoil, modified to incorporate an additional blowing slot on the lower surface. The main objective of this initial test was to determine if the control range, that is the range of lift coefficient available at a given angle-of-attack and momentum coefficient, could be increased without compromising the performance previously obtained with the single slot version. Test results show that the control range is more than doubled and there is no impact on upper surface only blowing performance. The range of lift coefficient produced at alpha equals zero degrees, using a combination of upper and lower slot only blowing is C1 from +3.6 to -4.0. Blowing efficiency when using the lower slot was found to be higher than that obtained when using the upper slot. This finding was somewhat unexpected, since lower surface blowing is equivalent to using CC on a negatively cambered airfoil. Data was acquired using either only the upper or lower surface slot or with dual blowing, that is simultaneous upper and lower slot blowing.
Quantitation of Mr 46000 and Mr 300000 mannose 6-phosphate receptors in human cells and tissues. (1991)

A highly specific enzyme-linked immunosorbent assay for quantitation of the Mr 46000 Da and Mr 300000 Da mannose 6-phosphate receptors was developed. The assay allows to detect ng amounts of human mannose 6-phosphate receptors. Analysis of human cells and tissues revealed significant differences in their contents of the two mannose 6-phosphate receptors, normalized for total cell protein. The ratio of the two mannose 6-phosphate receptors also differed among cells and tissues, suggesting that their steady state concentrations are regulated independently.
Effects of Herpes Simplex Virus on Structure and Function of Nectin-1/HveC (2002)

Herpes simplex virus (HSV) entry requires the interaction between the envelope glycoprotein D (gD) and a cellular receptor such as nectin-1 (also named herpesvirus entry mediator C [HveC]) or HveA/HVEM. Nectin-1 is a cell adhesion molecule found at adherens junctions associated with the cytoplasmic actin-binding protein afadin. Nectin-1 can act as its own ligand in a homotypic interaction to bridge cells together. We used a cell aggregation assay to map an adhesive functional site on nectin-1 and identify the effects of gD binding and HSV early infection on nectin-1 function. Soluble forms of nectin-1 and anti-nectin-1 monoclonal antibodies were used to map a functional adhesive site within the first immunoglobulin-like domain (V domain) of nectin-1. This domain also contains the gD-binding site, which appeared to overlap the adhesive site. Thus, soluble forms of gD were able to prevent nectin-1-mediated cell aggregation and to disrupt cell clumps in an affinity-dependent manner. HSV also prevented nectin-1-mediated cell aggregation by occupying the receptor. Early in infection, nectin-1 was not downregulated from the cell surface. Rather, detection of nectin-1 changed gradually over a 30-min period of infection, as reflected by a decrease in the CK41 epitope and an increase in the CK35 epitope. The level of detection of virion gD on the cell surface increased within 5 min of infection in a receptor-dependent manner. These observations suggest that cell surface nectin-1 and gD may undergo conformational changes during HSV entry as part of an evolving interaction between the viral envelope and the cell plasma membrane.
Evaluation of the Digital Rectal Examination as a Screening Test for Prostate Cancer (1998)

For PSA values of 0-3.9 ng/mL, the positive predictive value and sensitivity of DRE, tumor volume, and tumor grade were strongly dependent on PSA level. DRE has a poor performance in low PSA ranges.
Inactivation of a common epitope responsible for the induction of antibody-dependent enhancement of HIV (1998)

A variety of mutations within the primary C'-ADE domain inhibit binding of enhancing human MAb as well as blocking the association of gp120 and gp41. A conservative W596Y mutation blocks binding of all enhancing human MAb with retention of gp120-gp41 association. These data are important to the design of vaccines in which the primary enhancing epitope is disarmed to prevent the subsequent induction of an amnestic response that could lead to viral enhancement of infection. The retention of the gp120-gp41 association is postulated to yield an immunogen similar to natural infection for both subunit and genetic vaccines.
Feasibility of surface activated bonding for ultra-fine pitch interconnection-a new concept of bump-less direct bonding for system level packaging (2002)

In the present study a method of ultra-high density interconnection, the surface activation (SAB) method is introduced. Also for the next generation of packaging, which might bridge to global interconnection on chip, a concept of bump-less bonding is proposed. The bumpless bonding will be especially suitable and inevitable for ultra-high density interconnection when it will convert the range of /spl mu/m size. For such bonding requires at the same time, combinations of a ultra-thin chip and a flexible substrate. The surface activated bonding method enables the metals and non-metallic materials to be bonded at room temperature only by contact. Some fundamental experiments and preliminary results of examination of the feasibility of the method for Cu and Cu direct bonding are presented.
RNase H-dependent PCR (rhPCR): improved specificity and single nucleotide polymorphism detection using blocked cleavable primers (2011)

rhPCR eliminates the formation of primer dimers and markedly improves the specificity of PCR with respect to off-target amplification. These advantages of the assay should find utility in challenging qPCR applications such as genotyping, high level multiplex assays and rare allele detection.
Capacitative calcium entry in parotid acinar cells (1989)

The intracellular Ca2+ indicator, fura-2, was used to monitor changes in cytosolic [Ca2+] in parotid acinar cells. When parotid cells were incubated in a medium containing low [Ca2+], and [Ca2+] was restored to the physiological range, there was a small increase in cytosolic [Ca2+]. If, however, the cells were first activated by a muscarinic agonist, and receptor activation was terminated before the addition of Ca2+ by the addition of a pharmacological excess of the muscarinic-receptor antagonist atropine, the initial increase in cytosolic [Ca2+] was faster and transiently larger than in the control cells which had not been previously stimulated. This suggested that a stimulation of Ca2+ entry occurred owing to the prior emptying of the agonist-regulated intracellular Ca2+ pool. This extra Ca2+ influx seen in pool-depleted cells persisted even when the interval between the addition of atropine and Ca2+ was increased from 1 to 20 min. Also, when the pool was allowed to refill by adding atropine in the presence of extracellular Ca2+, and Ca2+ was then sequentially removed and restored, the rise in cytosolic [Ca2+] after the addition of extracellular Ca2+ was not rapid, and resembled the increase seen in unstimulated cells. These results indicate that, when the agonist-sensitive Ca2+ pool is emptied by an agonist, Ca2+ influx across the plasma membrane is increased. This influx of Ca2+ occurs independently of the concentrations of inositol phosphates and probably of any second messengers linked directly to receptor activation. It appears rather to be a consequence of the empty state of the Ca2+ pool. Further, we suggest that, whenever the agonist-sensitive Ca2+ pool is emptied by agonist activation, the plasma-membrane permeability to Ca2+ will be increased, and this may account, at least in part, for the phenomenon of receptor-activated Ca2+ entry.
Unexpected interaction between beta-adrenergic blockade and heart rate variability before and after myocardial infarction. A longitudinal study in dogs at high and low risk for sudden death. (1994)

The depression in HR variability produced by myocardial infarction has a clearly different temporal recovery pattern between low- and high-risk animals. After myocardial infarction, beta-adrenergic blockade does not alter HR variability, thus preserving its predictive value. Before myocardial infarction, however, beta-blockade increases HR variability only in the animals destined to be at low risk for lethal arrhythmias after the infarction. The recovery pattern of HR variability after myocardial infarction may contribute to the early recognition of individuals at high risk for sudden death.
The Oral Antidiabetic Pioglitazone Protects from Neurodegeneration and Amyotrophic Lateral Sclerosis-Like Symptoms in Superoxide Dismutase-G93A Transgenic Mice (2005)

Amyotrophic lateral sclerosis (ALS) represents a fatal neurodegenerative disorder characterized by progressive death of the upper and lower motor neurons. Because accompanying inflammation may interact with and promote neurodegeneration, anti-inflammatory treatment strategies are being evaluated. Because peroxisome proliferator-activated receptor gamma (PPARgamma) agonists act as potent anti-inflammatory drugs, we tested whether superoxide dismutase (SOD1)-G93A transgenic mice, a mouse model of ALS, benefit from oral treatment with the PPARgamma agonist pioglitazone (Pio). Pio-treated transgenic mice revealed improved muscle strength and body weight, exhibited a delayed disease onset, and survived significantly longer than nontreated SOD1-G93A mice. Quantification of motor neurons of the spinal cord at day 90 revealed complete neuroprotection by Pio, whereas nontreated SOD1-G93A mice had lost 30% of motor neurons. This was paralleled by preservation of the median fiber diameter of the quadriceps muscle, indicating not only morphological but also functional protection of motor neurons by Pio. Activated microglia were significantly reduced at sites of neurodegeneration in Pio-treated SOD1-G93A mice, as were the protein levels of cyclooxygenase 2 and inducible nitric oxide synthase. Interestingly, mRNA levels of the suppressor of cytokine signaling 1 and 3 genes were increased by Pio, whereas both the mRNA and protein levels of endogenous mouse SOD1 and of transgenic human SOD1 remained unaffected.
Systems analysis of human T helper17 cell differentiation uncovers distinct time-regulated transcriptional modules (2021)

T helper (Th) 17 cells protect from infections and are pathogenic in autoimmunity. While human Th17 cell differentiation has been defined, the global and stepwise transcriptional changes accompanying this process remain uncharacterized. Herein, by performing transcriptome analysis of human Th17 cells, we uncovered three time-regulated modules: early, involving exclusively "signaling pathways" genes; late, characterized by response to infections; and persistent, involving effector immune functions. To assign them an inflammatory or regulatory potential, we compared Th17 cells differentiated in presence or absence of interleukin (IL)-1β, respectively. Most inflammatory genes belong to the persistent module, whereas regulatory genes are lately or persistently induced. Among inflammatory genes, we identified the effector molecules IL17A, IL17F, IL26, IL6, interferon (IFN)G, IFNK, LTA, IL1A, platelet-derived growth factor (PDGF) A and the transcriptional regulators homeodomain-only protein homeobox (HOPX) and sex-determining-region-Y-box (SOX)2, whose expression was independently validated. This study provides an integrative representation of the stepwise human Th17 differentiation program and offers new perspectives toward therapeutic targeting of Th17-related autoimmune diseases.
Abnormal Alpha-Cell Function in Diabetes (1970)

The effect of large carbohydrate or protein meals upon plasma glucagon was compared in 14 nondiabetic and 24 diabetic patients. In nondiabetic subjects carbohydrate suppressed mean glucagon concentration from 126 ± 15 μμg (S.E.M.) to 90 ± 11 μμg (S.E.M.) per milliliter. In adult-type and juvenile-type diabetes, however, glucagon did not fall despite marked hyperglycemia. In nondiabetic subjects protein increased mean glucagon from 121 ± 11 (S.E.M.) to a peak of 203 ± 18 μμg (S.E.M.) per milliliter. In diabetes of both types protein induced a similar rise in glucagon despite fasting plasma glucose levels averaging above 215 mg per 100 ml. In nondiabetic subjects made hyperglycemic by glucose infusion, protein ingestion failed to stimulate glucagon. In normal persons glucagon falls after carbohydrate and rises after protein, unless hyperglycemia is induced. In diabetic patients glucagon is not suppressed by carbohydrate and rises normally after protein despite hyperglycemia. Inappropriate hyperglucagonemia appears to be a common feature of human diabetes that must exaggerate the metabolic consequences of insulin lack and unfavorably influence diabetic control.
Active Tumor Targeting of Nanomaterials Using Folic Acid, Transferrin and Integrin Receptors (2011)

Folic acid, transferrin and integrin alpha v beta 3 (αvβ3) receptors are overexpressed in various cancer cell lines. Ligands having high affinity for these receptors are often conjugated to nanocarriers to facilitate the tumor localization of therapeutic agents. In this review the use of these ligands for targeted delivery using liposomes, dendrimers and (N-(2-hydroxypropyl) methacrylamide) (HPMA) copolymers is discussed. Emphasis is placed on discussing drug delivery systems that have been optimized for in-vitro binding as well as in-vivo pharmacokinetics. Our aim is to understand the various factors influencing the targeting ability of nanocarriers.
Fast Ptychographic Reconstruction for Sparse Binary Ptychography Data. (2022)

4D STEM has flourished in recent years as hardware developments in fast-pixelated detectors have caught up with the theory [1].The high sensitivity and fast readout-speed of modern pixelated detectors means that low dose 4D STEM can be performed by allowing reduced probe dwell times.Combined with the high dose efficiency 4D STEM techniques such as ptychography this has opened up new areas of materials science to 4D STEM imaging.In particular a strong focus has developed on dose efficient method of imaging highly beam sensitive materials including, battery materials, zeolites and biological samples [2,3,4].It has previously been demonstrated by O'Leary et al. that high quality ptychographic reconstructions can be obtained from sparse binary CBED patterns such that within individual diffraction patterns electron events recorded by the detector do not overlap and cumulative doses as low as 1000eÅ -2 [3].It was demonstrated that despite the very low bit-depth in the diffraction information that high quality reconstructions could be obtained by single side band reconstruction.
Widely Tunable, Nondegenerate Three-Wave Mixing Microwave Device Operating near the Quantum Limit (2012)

We present the first experimental realization of a widely frequency tunable, nondegenerate three-wave mixing device for quantum signals at gigahertz frequency. It is based on a new superconducting building block consisting of a ring of four Josephson junctions shunted by a cross of four linear inductances. The phase configuration of the ring remains unique over a wide range of magnetic fluxes threading the loop. It is thus possible to vary the inductance of the ring with flux while retaining a strong, dissipation-free, and noiseless nonlinearity. The device has been operated in amplifier mode, and its noise performance has been evaluated by using the noise spectrum emitted by a voltage-biased tunnel junction at finite frequency as a test signal. The unprecedented accuracy with which the crossover between zero-point fluctuations and shot noise has been measured provides an upper bound for the noise and dissipation intrinsic to the device.
IL-11 inhibits Clostridium difficile toxin A enterotoxicity in rat ileum (1997)

Interleukin-11 (IL-11) is a stromal cell-derived cytokine with several biological activities against hematopoietic cells. Recent results indicated that IL-11 reduced mucosal damage in animal models of colitis. This study aimed to explore the action of recombinant human IL-11 (rhIL-11) on the intestinal effects of Clostridium difficile toxin A, an inflammatory enterotoxin, and cholera toxin, a noninflammatory enterotoxin in rat ileum. We administered rhIL-11 subcutaneously to rats before injection of toxin A into ileal loops and measured fluid secretion, epithelial permeability to mannitol, histopathological damage, and release of rat mast cell protease II (RMCP II) from intestinal mast cells and of tumor necrosis factor-alpha (TNF-alpha) and macrophage inflammatory protein-2 (MIP-2) from lamina propria macrophages. rhIL-11 (50-1,000 micrograms/kg) inhibited toxin A but not cholera toxin-mediated secretion and permeability in a dose-dependent fashion and reduced toxin A-induced epithelial cell damage. Rats treated with rhIL-11 also showed reduced RMCP II, TNF-alpha, and MIP-2 release in response to toxin A. Exposure of rat peripheral monocytes in vitro to rhIL-11 (1 microgram/ml) inhibited lipopolysaccharide and toxin A-mediated increases in TNF-alpha mRNA and protein levels. We conclude that rhIL-11 blocks the intestinal effects of C. difficile toxin A, possibly by inhibiting release of inflammatory mediators from mucosal mast cells and intestinal macrophages.
Epidemiology of Heart Failure (2013)

Heart failure (HF) has been singled out as an epidemic and is a staggering clinical and public health problem, associated with significant mortality, morbidity, and healthcare expenditures, particularly among those aged ≥ 65 years. The case mix of HF is changing over time with a growing proportion of cases presenting with preserved ejection fraction for which there is no specific treatment. Despite progress in reducing HF-related mortality, hospitalizations for HF remain frequent and rates of readmissions continue to rise. To prevent hospitalizations, a comprehensive characterization of predictors of readmission in patients with HF is imperative and must integrate the impact of multimorbidity related to coexisting conditions. New models of patient-centered care that draw on community-based resources to support HF patients with complex coexisting conditions are needed to decrease hospitalizations.
Structure‐Aided Optimization of Kinase Inhibitors Derived from Alsterpaullone (2005)

In order to perform computer-aided design of novel alsterpaullone derivatives, the vicinity of the entrance to the ATP-binding site was scanned for areas that could be useful as anchoring points for additional protein-ligand interactions. Based on the alignment of alsterpaullone in a CDK1/cyclin B homology model, substituents were attached to the 2-position of the parent scaffold to enable contacts within the identified areas. Synthesis of the designed structures revealed three derivatives (3-5) with kinase-inhibitory activity similar to alsterpaullone. The novel 2-cyanoethylalsterpaullone (7) proved to be the most potent paullone described so far, exhibiting inhibitory concentrations for CDK1/ cyclin B and GSK-3beta in the picomolar range.
Rearrangements of desmosomal and cytoskeletal proteins during the transition from epithelial to fibroblastoid organization in cultured rat bladder carcinoma cells. (1989)

Changes of cell morphology and the state of differentiation are known to play important roles in embryogenesis as well as in carcinogenesis. Examples of particularly profound changes are the conversions of epithelial to mesenchymal cells; i.e., the dissociation of some or all polygonal, polar epithelial cells and their transformation into elongate, fibroblastoid cells of high motility. As an in vitro model system for such changes in cell morphology, we have used cell cultures of the rat bladder carcinoma-derived cell line NBT-II which, on exposure to inducing medium containing a commercial serum substitute (Ultroser G), show an extensive change in their organization (epithelial-mesenchymal transition): the junctions between the epithelial cells are split, the epithelial cell organization is lost, and the resulting individual cells become motile and assume a spindle-like fibroblastoid appearance. Using immunofluorescence microscopy and biochemical protein characterization techniques, we show that this change is accompanied by a redistribution of desmosomal plaque proteins (desmoplakins, desmoglein, plakoglobin) and by a reorganization of the cytokeratin and the actin-fodrin filament systems. Moreover, intermediate-sized filaments of the vimentin type are formed in the fibroblastoid cells. We demonstrate that the modulation of desmosomal proteins, specifically an increase in soluble desmoplakins, is a relatively early event in cell dissociation and in epithelial-mesenchymal transition. In this process, a latent period of 5 h upon addition of inducing medium precedes the removal of these desmosomal components from the plasma membrane. The transition, which is reversible, is dependent on continued protein synthesis and phosphorylation but not on the presence of the inducing medium beyond the initial 2-h period. We discuss the value of this experimental system as a physiologically relevant approach for studying the regulation of the assembly and disassembly of desmosomes and other intercellular adhesion structures, and as a model of the conversion of cells from one state of differentiation into another.