gebhart/patrepeval huggingface dataset:
A combination of factor Xa and phosphatidylcholine‐phosphatidylserine vesicles bypasses factor VIII in vivo (1988)

A combination of phosphatidylcholine-phosphatidylserine lipid vesicles (PCPS), as a source of coagulant active phospholipid, when infused with factor Xa bypasses factor VIII in vivo. To demonstrate this, a reproducible model of bleeding in haemophilic dogs was used. Control studies were performed in normal dogs. In initial studies, factor Xa/PCPS at a dose of 6.5 x 10(-12) and 4.0 x 10(-7) moles/kg respectively failed to correct the abnormal bleeding in the haemophilic animals and initiated a bleeding diathesis in the normal controls. Coagulation studies and immunoblotting demonstrated activation of protein C and an anticoagulant effect resulting from significant falls in the levels of factors V and VIII. Adjustment of the dose of factor Xa/PCPS to 2.6 x 10(-11) and 4.0 x 10(-8) moles/kg respectively produced an immediate haemostatic effect in both haemophilic and normal animals with bleeding stopping within 15-30 s. Despite this observation, protein C activation was again noted. It is concluded that the presence of coagulant active phospholipid and factor Xa in prothrombin complex concentrates may explain the observed factor VIII bypassing activity of these preparations and that the use of a controlled formulation of these two components may provide a more effective approach to the management of patients with factor VIII inhibitors.
Transforming Growth Factor-β Induces Platelet-Derived Growth Factor (PDGF) Messenger RNA and PDGF Secretion while Inhibiting Growth in Normal Human Mammary Epithelial Cells (1990)

Platelet-derived growth factor (PDGF) is a potent mitogen in human serum which specifically stimulates the proliferation of mesenchymal cells. We have now examined normal human mammary epithelial cells (HMEC) derived from reduction mammaplasties and grown in a serum-free defined medium. Medium conditioned by HMEC contained a PDGF-like activity that competed with [125I]PDGF for binding to PDGF receptors in normal human fibroblasts. When conditioned media were incubated with antiserum specific for either PDGF-A or PDGF-B, only PDGF-A antiserum was capable of inhibiting binding of conditioned media to PDGF receptors. Using an RNase protection assay, mRNA from normal HMEC was probed for both the PDGF-A and PDGF-B chains. Little or no PDGF-B was found in HMEC strains, while a strong signal was seen with the PDGF-A probe. When HMEC were grown in the presence of transforming growth factor-beta (TGF beta) for 48 h, inhibition of growth was observed in association with a 20- to 40-fold stimulation of PDGF-B mRNA and a 2-fold stimulation of PDGF-A mRNA. This mRNA induction was extremely rapid (within 1 h), and secreted PDGF activity was induced 2- to 3-fold. Two other HMEC growth inhibitors and differentiating agents, sodium butyrate and phorbol ester 12-O-tetradecanoylphorbol-13-acetate, had no effect on PDGF mRNA regulation. The current study suggests that PDGF gene induction is an extremely rapid and specific indicator of TGF beta function regardless of whether TGF beta is acting in a growth stimulatory or inhibitory manner. Any role of PDGF-B in TGF beta modulation of differentiation of normal or malignant mammary gland remains to be determined.
A phage integrase directs efficient site-specific integration in human cells (2000)

The integrase from the Streptomyces phage phiC31 carries out efficient recombination between the attP site in the phage genome and the attB site in the host bacterial chromosome. In this paper, we show that the enzyme also functions in human cells. A plasmid assay system was constructed that measured intramolecular integration of attP into attB. This assay was used to demonstrate that in the presence of the phiC31 integrase, precise unidirectional integration occurs with an efficiency of 100% in Escherichia coli and >50% in human cells. This assay system was also used to define the minimal sizes of attB and attP at 34 bp and 39 bp, respectively. Furthermore, precise and efficient intermolecular integration of an incoming plasmid bearing attP into an established Epstein-Barr virus plasmid bearing attB was documented in human cells. This work is a demonstration of efficient, site-specific, unidirectional integration in mammalian cells. These observations form the basis for site-specific integration strategies potentially useful in a broad range of genetic engineering applications.
Biodegradable polyhydroxyalkanoate implants for osteomyelitis therapy: in vitro antibiotic release (2001)

Various random copolyesters of 3-hydroxybutyrate and 3-hydroxyvalerate (PHBV) and 3-hydroxybutyrate and 4-hydroxybutyrate P(3HB-4HB) were used in the construction of biodegradable, implantable rods for the local delivery of antibiotics (Sulperazone and Duocid) in chronic osteomyelitis therapy. Drug loading, type of active agent, and additional coating of the implant surface all have significant contributions to the in vitro release profile. The rate and duration of Sulperazone release from P(3HB-4HB) rods were controlled by the polymer/drug ratio (drug loading). The rate of drug dissolution was substantially higher than that of polymer degradation. Therefore, the release phenomenon was more dependent on drug dissolution rather than on polymer degradation or diffusion. Coating rods with the same type of polymer substantially reduced the initial burst effect observed with the uncoated rods, and significantly decreased the release rate so that the release kinetics became almost zero order. Antibiotic release from coated rods was sustained for over a period of 2 weeks at a constant rate, whereas uncoated rods released their contents in less than a week. Impregnation of Duocid into the hydrophobic polymer matrix yielded a rod with a smoother surface topography. The release from these rods was significantly higher than for rods loaded with Sulperazone and a zero order release could not be obtained with these samples.
Computationally-Guided Optimization of a Docking Hit to Yield Catechol Diethers as Potent Anti-HIV Agents (2011)

A 5-μM docking hit has been optimized to an extraordinarily potent (55 pM) non-nucleoside inhibitor of HIV reverse transcriptase. Use of free energy perturbation (FEP) calculations to predict relative free energies of binding aided the optimizations by identifying optimal substitution patterns for phenyl rings and a linker. The most potent resultant catechol diethers feature terminal uracil and cyanovinylphenyl groups. A halogen bond with Pro95 likely contributes to the extreme potency of compound 42. In addition, several examples are provided illustrating failures of attempted grafting of a substructure from a very active compound onto a seemingly related scaffold to improve its activity.
Exchanging the substrate specificities of pyruvate decarboxylase from Zymomonas mobilis and benzoylformate decarboxylase from Pseudomonas putida (2005)

Pyruvate decarboxylase from Zymomonas mobilis (PDC) and benzoylformate decarboxylase from Pseudomonas putida (BFD) are thiamine diphosphate-dependent enzymes that decarboxylate 2-keto acids. Although they share a common homotetrameric structure they have relatively low sequence similarity and different substrate spectra. PDC prefers short aliphatic substrates whereas BFD favours aromatic 2-keto acids. These preferences are also reflected in their carboligation reactions. PDC catalyses the conversion of benzaldehyde and acetaldehyde to (R)-phenylacetylcarbinol and predominantly (S)-acetoin, whereas (R)-benzoin and mainly (S)-2-hydroxypropiophenone are the products of BFD catalysis. Comparison of the X-ray structures of both enzymes identified two residues in each that were likely to be involved in determining substrate specificity. Site-directed mutagenesis was used to interchange these residues in both BFD and PDC. The substrate range and kinetic parameters for the decarboxylation reaction were studied for each variant. The most successful variants, PDCI472A and BFDA460I, catalysed the decarboxylation of benzoylformate and pyruvate, respectively, although both variants now preferred the long-chain aliphatic substrates, 2-ketopentanoic and 2-ketohexanoic acid. With respect to the carboligase activity, PDCI472A proved to be a real chimera between PDC and BFD whereas BFDA460I/F464I provided the most interesting result with an almost complete reversal of the stereochemistry of its 2-hydroxypropiophenone product.
Subunit Composition of Functional Nicotinic Receptors in Dopaminergic Neurons Investigated with Knock-Out Mice (2003)

Nicotinic acetylcholine receptors (nAChRs) expressed by dopaminergic (DA) neurons have long been considered as potential therapeutic targets for the treatment of several neuropsychiatric diseases, including nicotine and cocaine addiction or Parkinson's disease. However, DA neurons express mRNAs coding for most, if not all, neuronal nAChR subunits, and the subunit composition of functional nAChRs has been difficult to establish. Immunoprecipitation experiments performed on mouse striatal extracts allowed us to identify three main types of heteromeric nAChRs (alpha4beta2*, alpha6beta2*, and alpha4alpha6beta2*) in DA terminal fields. The functional relevance of these subtypes was then examined by studying nicotine-induced DA release in striatal synaptosomes and recording ACh-elicited currents in DA neurons fromalpha4, alpha6, alpha4alpha6, and beta2 knock-out mice. Our results establish that alpha6beta2* nAChRs are functional and sensitive to alpha-conotoxin MII inhibition. These receptors are mainly located on DA terminals and consistently do not contribute to DA release induced by systemic nicotine administration, as evidenced by in vivo microdialysis. In contrast, (nonalpha6)alpha4beta2* nAChRs represent the majority of functional heteromeric nAChRs on DA neuronal soma. Thus, whereas a combination of alpha6beta2* and alpha4beta2* nAChRs may mediate the endogenous cholinergic modulation of DA release at the terminal level, somato-dendritic (nonalpha6)alpha4beta2* nAChRs most likely contribute to nicotine reinforcement.
Overview of monoclonal B‐cell lymphocytosis (2007)

Monoclonal B-cell lymphocytosis (MBL) has been the subject of more intensive investigation for the last 10 years. The increased presence of MBL in unaffected, first-degree relatives with familial chronic lymphocytic leukaemia (CLL) suggest that it is surrogate marker for early disease. In normal population studies, MBL is found to be increased in ageing subjects. Consensus criteria for the diagnosis of MBL have been proposed. The differential diagnosis has been further clarified and the prevalence of MBL is most prominent in the elderly. The aetiology of MBL is unknown but probably involves immune mechanism of senescence or altered response. Environmental health studies suggest that exposure to certain toxins may lead to MBL but further work is needed. MBL is a precursor to CLL but may also regress, remain stable or progress to clinical CLL.
Molecular markers and determinants of prostate cancer metastasis (2001)

Although intensely studied, the molecular and biochemical determinants of prostate cancer development and progression remain ill-defined. Moreover, current markers and methodologies cannot distinguish between a tumor that will remain indolent and not impinge on patient survival, versus a tumor with aggressive traits culminating in metastatic spread and death. Once prostate cancer is confirmed the most significant threat to a patient's survival and quality of life involves tumor metastasis. Radical surgery notwithstanding, prostate cancer accounts for 10% of all cancer-related deaths primarily arising through development of metastasis. Metastasis markers demonstrating an acceptable level of reliability are an obvious necessity if disproportionate and costly treatment is to be avoided and a reasonably accurate determination of clinical prognosis and measure of successful response to treatment is to be made. Therapeutic strategies that specifically inhibit metastatic spread are not presently possible and may not become available in the immediate future. This is because, while localized tumorigenesis has been relatively amenable to detection, analysis and treatment, metastasis remains a relatively undefined, complex and underexplored area of prostate cancer research. New findings in the field such subclasses of genes called metastasis suppressors and cancer progression suppressors, have opened up exciting avenues of investigation. We review current methodological approaches, model experimental systems and genes presently known or having potential involvement in human prostate cancer metastasis.
<title>Inhibition and regression of tumors in hamster DMBA model following laser microvascular targeting</title> (1998)

Vascular targeting is a recent approach to cancer therapy that aims at damaging tumor vasculature to induce tumor cell hypoxia and subsequent cell death. Squamous cell cancer arises in the superficial mucosal and cutaneous epithelial layers, and tumor microvasculature therefore may be particularly well suited for targeting by selective photothermolysis. An initial evaluation of the effect of selective eradication of microvasculature on tumor development was undertaken here using the chemically-induced hamster cheek pouch model and a 585 nm pulsed dye laser. In a first group of 6 hamsters, progression of premalignant mucosal lesions was compared between control and laser treatment groups, and laser-induced regression of established tumors was evaluated. In a second group of 12 hamsters, the number of laser treatments required to produce complete regression of tumors of the buccal mucosa was determined. The effect of the laser on tumors appearing on the skin in these animals was also investigated. These experiments showed that laser treatment inhibited tumor development and caused complete regression of established tumors 10 mm<SUP>3</SUP> or smaller. Photothermal microvascular targeting may be useful in treating dyplasia and early tumors of the upper aerodigestive tract and skin, with fewer adverse sequelae than existing modalities.
Discovery of Inhibitors of Cell Adhesion Molecule Expression in Human Endothelial Cells. 1. Selective Inhibition of ICAM-1 and E-Selectin Expression (2001)

A critical early event in the inflammatory cascade is the induced expression of cell adhesion molecules on the lumenal surface of vascular endothelial cells. These adhesion molecules include E-selectin, ICAM-1, and VCAM-1, which serve to recruit circulating leukocytes to the site of the inflammation. These adhesive interactions allow the leukocytes to firmly adhere to and cross the vascular endothelium and migrate to the site of tissue injury. Pharmaceutical agents which would prevent the induced expression of one or more of the cell adhesion molecules on the endothelium might be expected to provide a novel mechanism to attenuate the inflammatory responses associated with chronic inflammatory diseases. A thieno[2,3-d]pyrimidine, A-155918, was identified from a whole-cell high-throughput assay for compounds which inhibited the tumor necrosis factor-alpha (TNFalpha)-induced expression of E-selectin, ICAM-1, or VCAM-1 on human vascular endothelial cells. Traditional medicinal chemistry methods were applied to this low-micromolar inhibitor, resulting in the 2,4-disubstituted thieno[2,3-c]pyridine A-205804, a potent and selective lead inhibitor of E-selectin and ICAM-1 expression (IC(50) = 20 and 25 nM, respectively). The relative position of the nitrogen atom in the thienopyridine isomer was shown to be critical for activity, as was a small amide 2-substituent.
Scalable Recognition with a Vocabulary Tree (2006)

A recognition scheme that scales efficiently to a large number of objects is presented. The efficiency and quality is exhibited in a live demonstration that recognizes CD-covers from a database of 40000 images of popular music CD’s. The scheme builds upon popular techniques of indexing descriptors extracted from local regions, and is robust to background clutter and occlusion. The local region descriptors are hierarchically quantized in a vocabulary tree. The vocabulary tree allows a larger and more discriminatory vocabulary to be used efficiently, which we show experimentally leads to a dramatic improvement in retrieval quality. The most significant property of the scheme is that the tree directly defines the quantization. The quantization and the indexing are therefore fully integrated, essentially being one and the same. The recognition quality is evaluated through retrieval on a database with ground truth, showing the power of the vocabulary tree approach, going as high as 1 million images.
Influences on High-Voltage Electro Pulse Boring in Granite (2018)

As the exploration and drilling of oil, natural gas and geothermal wells are expanding continuously, research into high-efficiency rock drilling technology is imperative. High-voltage electro pulse boring (EPB) has the advantages of high rock breaking efficiency and good wall quality, and is a new and efficient potential method of rock breaking. The design of electrode drill bits and the selection of drilling process parameters are the main obstacles restricting the commercialization of EPB. Accordingly, it is necessary to determine the influences on high-voltage EPB. In this study, based on the equivalent circuit of high-voltage electro pulse breakdown, a mathematical model of high-voltage electro pulse discharge in rock is established. Meanwhile, a numerical simulation model of high-voltage EPB of hard granite is established based on a coaxial cylindrical electrode structure, which is often used for electrode drill bits. The simulation analysis software Comsol Multiphysics (Comsol Multiphysics®5.3a, COMSOL Co., Ltd., Stockholm, Sweden) is used to study the influences of granite composition, electrode spacing and electrode shape on the high-voltage EPB process. In addition, the influences of electrical parameters on high-voltage EPB are calculated according to a model of high-voltage electro pulse discharge in rock. Finally, it is demonstrated that high-voltage EPB is influenced by granite composition, electrical parameters, electrode spacing, and electrode shape, and the relationships between these factors are obtained. This study is of guiding significance for improving rock breaking efficiency, reducing energy loss, designing electrode drill bits and selecting drilling process parameters.
Correction of the Mutation Responsible for Sickle Cell Anemia by an RNA-DNA Oligonucleotide (1996)

A chimeric oligonucleotide composed of DNA and modified RNA residues was used to direct correction of the mutation in the hemoglobin betaS allele. After introduction of the chimeric molecule into lymphoblastoid cells homozygous for the betaS mutation, there was a detectable level of gene conversion of the mutant allele to the normal sequence. The efficient and specific conversion directed by chimeric molecules may hold promise as a therapeutic method for the treatment of genetic diseases.
Activation of nasal cilia in immotile cilia syndrome. (1979)

Nasal biopsy specimens were obtained from 5 normal subjects and from 7 patients with immotile cilia syndrome. Of the latter, 3 had Kartagener's syndrome, one had Kartagener's forme fruste, and 3 had bronchiectasis and sinusitis. An in vitro motility test was used to assess ciliary movement. Exogenous adenosine triphosphate and adenosine triphosphatase activated the immotile cilia to levels equal to or slightly greater than the spontaneous activity seen in normal subjects. Absence of dynein arms on ciliary peripheral microtubule doublets was a consistent finding in the patients' specimens and is suggested to be the basic defect in this syndrome that is responsible for immotility and absence of mucociliary clearance.
Streptococcal hyaluronic acid: proposed mechanisms of degradation and loss of synthesis during stationary phase (1983)

Streptococcal hyaluronic acid was found to distribute into two discrete sizes. Cellular hyaluronic acid from strain D181 had an average molecular weight of 10 X 10(6), whereas the average molecular weight of extracellular hyaluronic acid from the same strain was 2 X 10(6). Cellular streptococcal hyaluronic acid was purified to homogeneity. Proteases were unable to cleave the purified cellular polymer, indicating that a peptide was not involved in cross-linking five extracellular hyaluronate polymers to form a cell-bound complex. Lipids apparently are not part of the cellular hyaluronic acid because phosphorus and glycerol were not detected by radioisotopic techniques, and denaturing conditions did not change the size of the polymer. Membranes obtained from various strains of group A and C streptococci cleaved the cellular form of the hyaluronate polymer demonstrating the presence of a membrane-bound hyaluronidase-like activity. By contrast, this activity was not found in the extracellular products of the strains studied. Furthermore, membranes derived from streptococci at the stationary phase of growth no longer had the capacity to synthesize hyaluronic acid. The loss of this property appeared to be due to changes in the structure of the membrane.
REAL TIME IMPLEMENTATION OF A BLIND BEAMFORMER FOR SUBBAND SPEECH ENHANCEMENT USING KURTOSIS MAXIMIZATION (2006)

This paper presents a real time implementation of a blind beamformer for subband speech enhancement. The beamformer adaptivelymaximizes the statistical kurtosis measure of the beamformer’soutput signal. Speech carries high kurtosis and noiseoften exhibit lower kurtosis. Hence, maximization of the outputsignal’s kurtosis enhances speech, in general. The implementationis carried out on a novel framework for real time audio processingin MATLAB and uses low latency ASIO sound cards.The implementation is evaluated using recorded signals and thespeech is enhanced approximately 10 dB by the proposed approachwith perceptually low speech distortion.
Launching the germline in Caenorhabditis elegans: regulation of gene expression in early germ cells (1999)

One hundred years after Weismann's seminal observations, the mechanisms that distinguish the germline from the soma still remain poorly understood. This review describes recent studies in Caenorhabditis elegans, which suggest that germ cells utilize unique mechanisms to regulate gene expression. In particular, mechanisms that repress the production of mRNAs appear to be essential to maintain germ cell fate and viability.
Preliminary study on antiamnestic mechanism of ginsenoside Rg1 and Rb1. (1990)

The effect of ginsenoside Rg1 and Rb1 on memory in mice and rats were studied using one trial avoidance learning method. The results showed that Rg1 and Rb1 improved acquisition, consolidation and retrieval of memory improved by amnestic agents. For the elucidation of the antiamnestic mechanism of Rg1 and Rb1, HPLC-ECD, isotope labelling technique, radioligand binding assay, RIA and oxygen radical generating systems were employed in experiments. Rg1 and Rb1 were shown to increase protein bisynthesis of brain and ACTH level of plasma and decrease 5-HT level or slow down the 5-HT turnover rate in rats. No specific binding of Rg1 and Rb1 to alpha 1, alpha 2 and beta-adrenoceptors, or to DA, 5-HT, GABA and M-cholinergic receptors was detectable. However, 5 days after ip Rg1 and Rb1, higher Bmas values were obtained for the brain membranes from treated mice than those from control mice. In the mean time, Rg1 and Rb1 did not lower and might even increase the contents of acetylcholine in the brain. Besides, Rb1 could antagonize lipid peroxidation in the brain. Besides, Rb1 could antagonize lipid peroxidation and scavenge oxygen free radicals as well as increase catalase and GSH-PX activities. Clearly, these data may serve as the basis for the elucidation of the antiamnestic mechanism of Rg1 and Rb1.