gebhart/patrepeval huggingface dataset:
Initiation of Coagulation by Tissue Facto (1988)

Tissue factor (TF) is an integral membrane glycoprotein which functions as an initiator of coagulation. Furthermore, it is probably the principal biological initiator of this essential hemostatic process. This article reviews the studies which form the basis for these assertions. The work on TF is traced from the 19th century discovery of the thromboplastic activity of tissues to the recent purification of the protein from bovine and human tissues and the isolation cDNA clones coding from human TF. The features of TF structure and function which tailor it to the role of initiator of the coagulation cascade are considered. For example, cell-surface TF and factor VII, the plasma serine proteases zymogen, form a proteolytic complex without prior proteolysis of either component. In addition, a kinetic model for the molecular mechanism of TF-initiated clotting is reviewed. The factors which control the expression of TF procoagulant activity by cultured cells are examined in light of the hypothesized role of TF in normal hemostasis. Also, the potential pathological consequences of aberrant TF expression, i.e., thrombosis and hemorrhage, are explored.
Failures in Phase III: Causes and Consequences (2015)

Phase III randomized controlled trials (RCT) in oncology fail to lead to registration of new therapies more often than RCTs in other medical disciplines. Most RCTs are sponsored by the pharmaceutical industry, which reflects industry's increasing responsibility in cancer drug development. Many preclinical models are unreliable for evaluation of new anticancer agents, and stronger evidence of biologic effect should be required before a new agent enters the clinical development pathway. Whenever possible, early-phase clinical trials should include pharmacodynamic studies to demonstrate that new agents inhibit their molecular targets and demonstrate substantial antitumor activity at tolerated doses in an enriched population of patients. Here, we review recent RCTs and found that these conditions were not met for most of the targeted anticancer agents, which failed in recent RCTs. Many recent phase III RCTs were initiated without sufficient evidence of activity from early-phase clinical trials. Because patients treated within such trials can be harmed, they should not be undertaken. The bar should also be raised when making decisions to proceed from phase II to III and from phase III to marketing approval. Many approved agents showed only better progression-free survival than standard treatment in phase III trials and were not shown to improve survival or its quality. Introduction of value-based pricing of new anticancer agents would dissuade the continued development of agents with borderline activity in early-phase clinical trials. When collaborating with industry, oncologists should be more critical and better advocates for cancer patients.
Surface‐Energy Determinations of Tin Oxide‐Coated Soda–Lime–Silica Glass (1988)

The dispersive and polar surface‐energy components, as well as the total surface energy, of tin oxide coatings on soda–lime–silica glass were determined by the Owens–Wendt method. The total surface energy of tin oxide is greater than soda–lime–silica glass and, more importantly, exhibits significantly more‐dispersive and less‐polar character. These results indicate that tin oxide is significantly more covalent than soda–lime–silica glass. It is postulated that the more‐covalent tin oxide coatings increase the bond strength of organic coatings to soda–lime–silica glass. These effects improve the friction‐damage resistance of glass surfaces coated with metal oxides and organics, compared with glass surfaces coated with organics only.
Cloning and characterization of the Pseudomonas aeruginosa lasR gene, a transcriptional activator of elastase expression (1991)

We report the discovery of the lasR gene, which positively regulates elastase expression in Pseudomonas aeruginosa PAO1. The lasR gene was cloned by its ability to restore a positive elastase phenotype in strain PA103, a strain which possesses the elastase structural gene (lasB) but fails to synthesize the enzyme. Nucleotide sequence analysis revealed an open reading frame of 716 nucleotides encoding a protein of approximately 27 kDa. A labeled LasR protein of 27 kDa was detected in Escherichia coli by using a T7 RNA polymerase expression system. A chromosomal deletion mutant of the lasR gene was constructed in PAO1 by gene replacement. This mutant (PAO-R1) is devoid of elastolytic activity and elastase antigen. The deduced amino acid sequence of LasR is 27% homologous to the positive activator LuxR of Vibrio fischeri and the suspected activator 28K-UvrC of E. coli. Northern (RNA) analysis of total cellular RNA from PAO1, PAO-R1, and PAO-R1 containing the lasR gene on a multicopy plasmid (pMG1.7) revealed that a functional lasR gene is required for transcription of the elastase structural gene (lasB).
Simple delay monitor for droplet sorters (1991)

We have constructed a simple device by which the optimal delay time between optical measurement of a cell and the application of the droplet charging pulse can be determined directly in a flow sorter. The device consists of a stainless steel chamber in which the sorted droplets are collected. In the collection chamber the collected droplets run through a capillary where a continuous fluorescence measurement is made. With a sample of fluorescent particles, the delay time is optimal when the measured fluorescence is maximal. The measuring volume is always filled with the last droplets sorted (about 3,000). With this device, the setting of the delay time can be done in a few seconds without the need for microscopical verification. The fluorescence in the collection chamber is excited and detected via optical fibers using about 10% of the light of the existing laser from the flow cytometer and an extra photomultiplier.
Development of Boronic Acid Grafted Random Copolymer Sensing Fluid for Continuous Glucose Monitoring (2008)

We have previously presented a microelectromechanical system (MEMS) based viscometric sensor for continuous glucose monitoring using protein Concanavalin A (Con A). To address its drawbacks, including immunotoxicity and instability issues, we have synthesized stable, biocompatible copolymers poly(acrylamide-ran-3-acrylamidophenylboronic acid) (PAA-ran-PAAPBA) for viscosity based glucose sensing. We found that PAA-ran-PAAPBA showed very high binding specificity to glucose. Several key factors such as polymer compositions, polymer molecular weights and polymer concentrations have been investigated to optimize viscometric responses. This polymer is able to detect glucose under physiological pH conditions in a reversible manner. Therefore, it has the potential to enable a highly reliable, continuous monitoring of glucose in subcutaneous tissue using the MEMS device.
Tumor cell traffic through the extracellular matrix is controlled by the membrane-anchored collagenase MT1-MMP (2004)

As cancer cells traverse collagen-rich extracellular matrix (ECM) barriers and intravasate, they adopt a fibroblast-like phenotype and engage undefined proteolytic cascades that mediate invasive activity. Herein, we find that fibroblasts and cancer cells express an indistinguishable pericellular collagenolytic activity that allows them to traverse the ECM. Using fibroblasts isolated from gene-targeted mice, a matrix metalloproteinase (MMP)-dependent activity is identified that drives invasion independently of plasminogen, the gelatinase A/TIMP-2 axis, gelatinase B, collagenase-3, collagenase-2, or stromelysin-1. In contrast, deleting or suppressing expression of the membrane-tethered MMP, MT1-MMP, in fibroblasts or tumor cells results in a loss of collagenolytic and invasive activity in vitro or in vivo. Thus, MT1-MMP serves as the major cell-associated proteinase necessary to confer normal or neoplastic cells with invasive activity.
Extensive homology exists between Marek disease herpesvirus and its vaccine virus, herpesvirus of turkeys. (1984)

Marek disease is a lymphomatous disease of chickens caused by infection of a herpesvirus, Marek disease virus (MDV). Marek disease is the only neoplastic disease for which a successful vaccine has been developed. The vaccine virus, herpesvirus of turkeys (HVT), is non-oncogenic in chickens. Despite the strong antigenic relationship between these viruses, previous studies showed that the two viral DNAs share little or no homology. Using less stringent hybridization conditions and methods that greatly improve the reassociation kinetics, we have reexamined the sequence homology between MDV and HVT DNA. We report here that HVT and MDV are far more closely related than previously reported. The homology between these two viral DNAs ranges between 70% and 80% at the nucleotide level and appears to extend over 90-95% of the respective genomes. Under the low stringency conditions used, MDV DNA fails to cross-hybridize with DNA from feline rhinotracheitis virus, an antigenically unrelated herpesvirus with a G-C content identical to that of MDV and HVT.
A simple spectrophotometric method for the quantification of residual haemoglobin in platelet concentrates (2004)

The Harboe spectrophotometric method is convenient, safe, accurate and reproducible, and outperforms the TMB and PLHP methods for quantification of residual Hb in PC.
UPPAAL 4.0 (2006)

UPPAAL 4.0 is the result of over two and a half years of development and contains many new features, additions to the modeling language, performance improvements, enhancements and polish to the easy to use graphical user interface, and is accompanied by several open source libraries. The tool and libraries are available free of charge for academic, educational and evaluation purposes from http://www.uppaal.com/. We describe three of the new features: user defined functions, priorities and symmetry reduction
Human Truncated Tau Induces Mature Neurofibrillary Pathology in a Mouse Model of Human Tauopathy (2016)

Alzheimer's disease (AD) represents the most common neurodegenerative disorder. Several animal models have been developed in order to test pathophysiological mechanisms of the disease and to predict effects of pharmacological interventions. Here we examine the molecular and behavioral features of R3m/4 transgenic mice expressing human non-mutated truncated tau protein (3R tau, aa151-391) that were previously used for efficacy testing of passive tau vaccine. The mouse model reliably recapitulated crucial histopathological features of human AD, such as pre-tangles, neurofibrillary tangles, and neuropil threads. The pathology was predominantly located in the brain stem. Transgenic mice developed mature sarkosyl insoluble tau complexes consisting of mouse endogenous and human truncated and hyperphosphorylated forms of tau protein. The histopathological and biochemical features were accompanied by significant sensorimotor impairment and reduced lifespan. The sensorimotor impairment was monitored by a highly sensitive, fully-automated tool that allowed us to assess early deficit in gait and locomotion. We suggest that the novel transgenic mouse model can serve as a valuable tool for analysis of the therapeutic efficacy of tau vaccines for AD therapy.
Characterization of receptors for alpha-melanocyte-stimulating hormone on human melanoma cells. (1989)

Receptors for alpha-melanocyte-stimulating hormone (alpha-MSH) on human malignant melanoma cell lines were investigated with a specific binding assay and characterized with structural analogues of alpha-MSH and adrenocorticotropic hormone and by photoaffinity cross-linking of the hormone-receptor complex. Specific binding of high-performance liquid chromatography-purified, monoiodinated alpha-MSH in the presence of 1 mM 1,10-phenanthroline as protease inhibitor was highest after a 2-h incubation at 37 degrees C. The nonspecific binding was less than 20% and dissociation of the ligand-receptor complex was relatively slow. Ten out of 12 human cell lines showed specific binding sites for alpha-MSH with Kp values ranging from 0.195 to 2.87 nM and the sites/cell being approximately 400 to approximately 1600. Virtually identical results were obtained in an assay where the cells remained attached to the culture dishes during the entire experiment. The study of hormone analogues with the D10 cell line showed that oxidized alpha-MSH had an approximately 40-fold lower affinity than alpha-MSH whereas [Nle4,D-Phe7]-alpha-MSH displayed a threefold and the adrenocorticotropic hormone fragments (1-17) and (1-24) a 20- and 8-fold higher affinity. Cross-linking of the alpha-MSH-receptor complex of three cell lines using monoiodinated [Nle4,D-Phe7,Trp(2-nitro-4-azidophenylsulfenyl)9]-alpha-MSH as photoaffinity label revealed a major Mr 45,000 protein band on sodium dodecyl sulfate-polyacrylamide gels, analogous to the MSH receptor of mouse B16 melanoma cells.
Tissue expression and enzymologic characterization of human prostate specific membrane antigen and its rat and pig orthologs (2007)

The rat and pig orthologs of GCPII seem to be suitable to approximate human GCPII in enzymologic studies. However, the diffuse expression pattern of GCPII in animal and human tissues could be a caveat for the potential utilization of GCPII-targeted anticancer drugs. Furthermore, variations in GCPII tissue distribution among the species studied should be considered when using rat or pig as models for antineoplastic drug discovery.
Fractal image coding: a review (1993)

An approach to image coding based on a fractal theory of iterated contractive transformations defined piecewise is described. The main characteristics of this approach are that it relies on the assumption that image redundancy can be efficiently captured and exploited through piecewise self-transformability on a block-wise basis, and it approximates an original image by a fractal image, obtained from a finite number of iterations of an image transformation called a fractal code. This approach is referred to as fractal block coding. The general coding-decoding system is based on the construction, for an image to be encoded, of a fractal code-a contractive image transformation for which the original image is an approximate fixed point-which, when applied iteratively on any initial image of the decoder, produces a sequence of images which converges to a fractal approximation of the original. The design of a system for the encoding of monochrome digital images at rates below 1 b/pixel is described. Ideas and extensions from the work of other researchers are presented.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Production and characterisation of a monoclonal antibody to a cell-surface, glucomannoprotein constituent of Candida albicans and other pathogenic Candida species (1988)

A murine monoclonal antibody (MAB AF-1) class IgM was raised to a soluble glucomannoprotein extract (GMP) of Candida albicans. Agglutination and indirect immunofluorescence assays with purified MAB showed that AF-1 was directed against a cell-surface epitope shared by C. albicans serotypes A and B, C. tropicalis, C. guilliermondii and C. viswanathii, but not by C. krusei, C. parapsilosis, C. kefyr (pseudotropicalis) and T. glabrata. Treatment with heat, protease or periodate-treated GMP and with other cell-wall extracts of C. albicans provided evidence that the epitope recognised by MAB AF-1 is carried by the polysaccharide moiety of cell-surface glucomannoprotein molecule(s).
Significance of T helper 17 immunity in transplantation (2011)

Th17 immunity is now beginning to be appreciated as a set of responses mediated not only by CD4 Th17 cells but a variety of immune cells and a plethora of cytokines that collaborate to mediate immune disorders, including transplant rejection. Development and contribution of de-novo autoimmunity to chronic rejection is increasingly appreciated. The developmental plasticity of Tregs and Th17 cells is a major hurdle to Treg-based cellular therapies for transplantation. Several biologics targeting Th17 immunity are under evaluation for autoimmune disease. It remains to be determined whether these can be used in transplantation to improve outcomes.
The effect of oxygen on the growth and physiology of Porphyromonas gingivalis (2004)

Oxygen constitutes a constant challenge for the survival of strict anaerobes in the oral environment. The aim of this study was to investigate the effect of oxygen on the physiology and growth of Porphyromonas gingivalis in a continuous culture system when grown under conditions of hemin limitation and excess. Results showed that, when grown in the presence of hemin at 0.5 mg/l, P. gingivalis could tolerate low levels of oxygen, being able to reach steady-state when 6% oxygen was present in the incoming gas mixture. When the hemin concentration was increased to 5 mg/l, the culture tolerated 10% oxygen. Anaerobically-grown cells were coccoid in shape, whereas those grown in the presence of oxygen were bacillary. Acetate was the predominant end-product in cultures grown in the presence of oxygen or in cultures hemin-limited. Despite some changes in the activity of Arg- and Lys-gingipain, most of the proteolytic activity was retained in the presence of oxygen. Activity of each of the three anti-oxidant enzymes tested (NADH oxidase, NADH peroxidase and SOD) was detected under all conditions and usually increased under oxygenated environments. Higher activities were also seen in the hemin-limited cultures. These results show some of the changes that occur in the physiology of P. gingivalis as a result of oxidative stress and confirm that hemin has a protective effect on the growth of the microorganism in the presence of oxygen.
PolyMOF Nanoparticles: Dual Roles of a Multivalent polyMOF Ligand in Size Control and Surface Functionalization (2019)

Metal-organic framework nanoparticles (MOF NPs) have emerged as an important class of materials that display significantly enhanced performance in many applications compared to bulk MOF materials; their synthesis, however, commonly involves a tedious sequence that controls particle size and surface properties in separate steps. Now, a simple strategy to access functional MOF NPs in one pot is reported that uses a polyMOF ligand possessing a polymer block for surface functionalization and a coordination block with tunable multivalency for size control. This strategy produces uniform polyMOF-5 NPs with sizes down to 20 nm, displaying exceptional structural and colloidal stability upon exposure to ambient conditions. A detailed time-dependent study revealed that the polyMOF NPs were formed following an aggregation-confined crystallization mechanism. Generality was demonstrated through the synthesis of well-defined polyUiO-66 NPs.
Angiotensin II Activates RhoA in Cardiac Myocytes (1998)

The organization of actin into striated fibers (myofibrils) is one of the major features of cardiac hypertrophy. However, its signal transduction mechanism is not well understood. Although Rho-family small G proteins have been implicated in actin organization in many cell types, it is not fully elucidated whether Rho mediates the organization of actin fibers by hypertrophic stimuli in cardiac myocytes. Therefore, we examined (1) whether Rho is activated by the hypertrophic stimulus, angiotensin II (Ang II), and (2) whether Rho mediates the Ang II-induced organization of actin fibers in cultured neonatal rat cardiac myocytes. Treatment of myocytes with Ang II caused a rapid formation of both striated (mature myofibrils) and nonstriated (premyofibrils) actin fibers within 30 minutes, as determined by phalloidin stainings of the polymerized actin and troponin T stainings. Immunoblot analyses and immunostainings have indicated that cardiac myocytes express RhoA, but RhoB is undetectable. In the control state, RhoA was observed predominantly in the cytosolic fraction, but it was translocated in part to the particulate fraction in response to Ang II, consistent with activation of RhoA by Ang II. Incubation of myocytes with exoenzyme C3 for 48 hours completely ADP-ribosylated Rho in vivo. The C3 treatment abolished formation of premyofibrils induced by Ang II, suggesting that Ang II causes premyofibril formation via a Rho-dependent mechanism. The Ang II-induced mature myofibril formation was only partly abolished by C3. Expression of constitutively active RhoA (V14RhoA) caused the formation of premyofibrils but not mature myofibrils. The C3 treatment inhibited Ang II-induced atrial natriuretic factor induction, whereas it had no effect on c-fos induction. These results indicate that RhoA is activated by Ang II and mediates the Ang II-induced formation of premyofibrils and induction of a subset of genes. Distinct signaling mechanisms seem to be responsible for striated mature myofibril formation by Ang II.
Genetic Restriction of AIDS Pathogenesis by an SDF-1 Chemokine Gene Variant (1998)

Stromal-derived factor (SDF-1) is the principal ligand for CXCR4, a coreceptor with CD4 for T lymphocyte cell line-tropic human immunodeficiency virus-type 1 (HIV-1). A common polymorphism, SDF1-3'A, was identified in an evolutionarily conserved segment of the 3' untranslated region of the SDF-1 structural gene transcript. In the homozygous state, SDF1-3'A/3'A delays the onset of acquired immunodeficiency syndrome (AIDS), according to a genetic association analysis of 2857 patients enrolled in five AIDS cohort studies. The recessive protective effect of SDF1-3'A was increasingly pronounced in individuals infected with HIV-1 for longer periods, was twice as strong as the dominant genetic restriction of AIDS conferred by CCR5 and CCR2 chemokine receptor variants in these populations, and was complementary with these mutations in delaying the onset of AIDS.
Correctable visual impairment in stroke rehabilitation patients (2000)

stroke professionals need to enquire about patients' spectacles and assess their condition. Patients with reduced visual acuity in the absence of significant non-refractive disease should be referred to an optometrist: in this series 14% of patients had visual impairment which benefited from refractive correction.