gebhart/patrepeval huggingface dataset:
Time-resolved polarized fluorescence spectroscopy studies of plasminogen activator inhibitor type 1: conformational changes of the reactive center upon interactions with target proteases, vitronectin and heparin (1995)

Plasminogen activator inhibitor type 1 (PAI-1) is an important physiological inhibitor of the plasminogen activator system. To investigate the structure-functional aspects of this inhibitor, we have taken advantage of the lack of cysteine residues in the PAI-1 molecule and substituted Ser344 (P3) and Met347 (P1'), in the reactive center loop, with cysteines, thereby creating unique attachment sites for extrinsic fluorescent probe. Both cysteine mutants were purified and labeled with a sulfhydryl specific fluorophore, N-(4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacen yl-3-propionyl)-N- (iodoacetyl)ethylenediamine (BDYIA). The labeled mutants were found to reveal biochemical characteristics very similar to those of wild type PAI-1. Time-resolved fluorescence spectroscopy was used to examine orientational freedom of BDYIA in the reactive center loop of PAI-1. The orientational freedom of the probe was found to be greater in the latent form than in the active form of PAI-1, suggesting that the reactive center has a more relaxed conformation in the latent form than in the active form. Complex formation with target proteases, tissue type plasminogen activator (tPA) and urokinase type plasminogen activator (uPA), caused decreased orientational freedom of BDYIA in the P3 position, while the orientational freedom of BDYIA in position P1' increased to a level similar to that of BDYIA in reactive center-cleaved PAI-1. In contrast, complex formation with modified anhydro-uPA, which is unable to cleave its substrate, largely restricted the orientational freedom of BDYIA probe in the P1' position.(ABSTRACT TRUNCATED AT 250 WORDS)
Lymphoma Transformation (2001)

“When the cells in the blood are morphologically identical with those of the tumor, a genetic relationship between the blood changes and the organ changes is generally assumed. If (less frequently) the leukemic cells are of entirely different structure from those of the tumor, a relationship is less firmly established. In every instance the interpretation is difficult, and the diagnosis frequently in doubt.”
Glutathione S-Transferases (1974)

The purification of homogeneous glutathione S-transferases B and C from rat liver is described. Kinetic and physical properties of these enzymes are compared with those of homogeneous transferases A and E. The letter designations for the transferases are based on the reverse order of elution from carboxymethylcellulose, the purification step in which the transferases are separated from each other. Transferase B was purified on the basis of its ability to conjugate iodomethane with glutathione, whereas transferase C was purified on the basis of conjugation with 1,2-dichloro-4-nitrobenzene. Although each of the four enzymes can be identified by its reactivity with specific substrates, all of the enzymes are active to differing degrees in the conjugation of glutathione with p-nitrobenzyl chloride. Assay conditions for a variety of substrates are included. All four glutathione transferases have a molecular weight of 45,000 and are dissociable into subunits of approximately 25,000 daltons. Despite the similar physical properties and overlapping substrate specificities of these enzymes, only transferases A and C are immunologically related.
Effect of interleukin 12 on tumor induction by 3-methylcholanthrene. (1996)

Interleukin (IL)-12 has strong antitumor activity in transplantable tumor systems in the mouse. The present study was designed to determine whether tumor induction by 3-methylcholanthrene (3-MC), a carcinogenic hydrocarbon, can be inhibited by IL-12. BALB/cBy mice were injected subcutaneously with 25 micrograms or 100 micrograms of 3-MC and treated with 100 ng, 10 ng, or 1 ng of IL-12 for 5 days a week for 18 weeks, with a schedule of 3 weeks on and 1 week off. In mice injected with 25 micrograms of 3-MC, treatment with 100 ng of IL-12 delayed tumor appearance and reduced tumor incidence. Tumor appearance was also delayed in mice injected with 100 micrograms of 3-MC and treated with 100 ng of IL-12, but the final tumor incidence was the same as in non-IL-12-treated mice. In contrast to the characteristically round, hard, well-circumscribed, and protruding tumor induced by 3-MC, a percentage of tumors induced in IL-12-treated mice had atypical characteristics: flat, soft, and invasive. Atypical tumors had a longer latent period and were more frequently seen in mice injected with 100 micrograms of 3-MC and treated with 100 ng of IL-12. Interferon gamma, IL-10, and tumor necrosis factor could be induced throughout the treatment period by IL-12, indicating that repeated injections of IL-12 do not induce a state of tachyphylaxis. High production of interferon gamma by CD8 T cells and a TH2-->TH1 or TH0 shift in the cytokine secretion profile of CD4 T cells were also seen in the IL-12-treated mice. IL-12 provides a powerful new way to explore the defensive role of the immune system in tumorigenesis.
16S ribosomal DNA amplification for phylogenetic study (1991)

A set of oligonucleotide primers capable of initiating enzymatic amplification (polymerase chain reaction) on a phylogenetically and taxonomically wide range of bacteria is described along with methods for their use and examples. One pair of primers is capable of amplifying nearly full-length 16S ribosomal DNA (rDNA) from many bacterial genera; the additional primers are useful for various exceptional sequences. Methods for purification of amplified material, direct sequencing, cloning, sequencing, and transcription are outlined. An obligate intracellular parasite of bovine erythrocytes, Anaplasma marginale, is used as an example; its 16S rDNA was amplified, cloned, sequenced, and phylogenetically placed. Anaplasmas are related to the genera Rickettsia and Ehrlichia. In addition, 16S rDNAs from several species were readily amplified from material found in lyophilized ampoules from the American Type Culture Collection. By use of this method, the phylogenetic study of extremely fastidious or highly pathogenic bacterial species can be carried out without the need to culture them. In theory, any gene segment for which polymerase chain reaction primer design is possible can be derived from a readily obtainable lyophilized bacterial culture.
Battery Loss and Stress Mitigation in a Cascaded H-Bridge Multilevel Inverter for Vehicle Traction Applications by Filter Capacitors (2019)

In this paper, two types of filter capacitors of varying capacity were connected to the battery packs of a cascaded H-Bridge single-star multilevel vehicle traction inverter, and their influence on the battery losses has been analyzed. The battery and capacitor simulation models used are experimentally verified in a downscaled system. Different capacitor configurations were simulated for four-drive cycle scenarios to determine the potentials for the mitigation of current pulse stresses and battery loss reduction with respect to the added weight. By adding capacitors corresponding to a weight of 4% of the initial battery storage, the peak current is reduced by 5%-20%, depending on the operating point from dc to a few kilohertz, and the battery losses are reduced by 10%. In comparison, it is demonstrated that adding supercapacitors is more beneficial for lower output frequencies, while adding electrolytic capacitors is better for higher output frequencies. Furthermore, the low-order voltage harmonics of the dc-rails between the converter and battery were reduced by 10%-30% for frequencies above 9 kHz, which decreases the potential of electromagnetic disturbances. In addition, during cold battery temperatures, when it is very important to avoid heavy cyclings, the loss reduction using the capacitors was 2.5 times larger than for nominal temperature.
Agelastatin A: a novel inhibitor of osteopontin-mediated adhesion, invasion, and colony formation (2008)

Effective inhibitors of osteopontin (OPN)-mediated neoplastic transformation and metastasis are still lacking. (-)-Agelastatin A is a naturally occurring oroidin alkaloid with powerful antitumor effects that, in many cases, are superior to cisplatin in vitro. In this regard, past comparative assaying of the two agents against a range of human tumor cell lines has revealed that typically (-)-agelastatin A is 1.5 to 16 times more potent than cisplatin at inhibiting cell growth, its effects being most pronounced against human bladder, skin, colon, and breast carcinomas. In this study, we have investigated the effects of (-)-agelastatin A on OPN-mediated malignant transformation using mammary epithelial cell lines. Treatment with (-)-agelastatin A inhibited OPN protein expression and enhanced expression of the cellular OPN inhibitor, Tcf-4. (-)-Agelastatin A treatment also reduced beta-catenin protein expression and reduced anchorage-independent growth, adhesion, and invasion in R37 OPN pBK-CMV and C9 cell lines. Similar effects were observed in MDA-MB-231 and MDA-MB-435s human breast cancer cell lines exposed to (-)-agelastatin A. Suppression of Tcf-4 by RNA interference (short interfering RNA) induced malignant/invasive transformation in parental benign Rama 37 cells; significantly, these events were reversed by treatment with (-)-agelastatin A. Our study reveals, for the very first time, that (-)-agelastatin A down-regulates beta-catenin expression while simultaneously up-regulating Tcf-4 and that these combined effects cause repression of OPN and inhibition of OPN-mediated malignant cell invasion, adhesion, and colony formation in vitro. We have also shown that (-)-agelastatin A inhibits cancer cell proliferation by causing cells to accumulate in the G(2) phase of cell cycle.
Pathogenicity and Immunogenicity of a Vaccine Strain ofListeria monocytogenesThat Relies on a Suicide Plasmid To Supply an Essential Gene Product (2005)

Listeria monocytogenes is a bacterial pathogen that elicits a strong cellular immune response and thus has potential use as a vaccine vector. An attenuated strain, L. monocytogenes dal dat, produced by deletion of two genes (dal and dat) used for d-alanine synthesis, induces cytotoxic T lymphocytes and protective immunity in mice following infection in the presence of d-alanine. In order to obviate the dependence of L. monocytogenes dal dat on supplemental d-alanine yet retain its attenuation and immunogenicity, we explored mechanisms to allow transient endogenous synthesis of the amino acid. Here, we report on a derivative strain, L. monocytogenes dal dat/pRRR, that expresses a dal gene and synthesizes d-alanine under highly selective conditions. We constructed the suicide plasmid pRRR carrying a dal gene surrounded by two res1 sites and a resolvase gene, tnpR, which acts at the res1 sites. The resolvase gene is regulated by a promoter activated upon exposure to host cell cytosol. L. monocytogenes dal dat/pRRR was thus able to grow in liquid culture and to infect host cells without d-alanine supplementation. However, after infection of these cells, resolvase-mediated excision of the dal gene resulted in strong down-regulation of racemase expression. As a result, this system allowed only transient growth of L. monocytogenes dal dat/pRRR in infected cells and survival in animals for only 2 to 3 days. Nevertheless, mice immunized with L. monocytogenes dal dat/pRRR generated listeriolysin O-specific effector and memory CD8(+) T cells and were protected against lethal challenge by wild-type Listeria. This vector may be an attractive vaccine candidate for the induction of protective cellular immune responses.
Fragment-Based Discovery of New Highly Substituted 1H-Pyrrolo[2,3-b]- and 3H-Imidazolo[4,5-b]-Pyridines as Focal Adhesion Kinase Inhibitors (2013)

Focal adhesion kinase (FAK) is considered as an attractive target for oncology, and small-molecule inhibitors are reported to be in clinical testing. In a surface plasmon resonance (SPR)-mediated fragment screening campaign, we discovered bicyclic scaffolds like 1H-pyrazolo[3,4-d]pyrimidines binding to the hinge region of FAK. By an accelerated knowledge-based fragment growing approach, essential pharmacophores were added. The establishment of highly substituted unprecedented 1H-pyrrolo[2,3-b]pyridine derivatizations provided compounds with submicromolar cellular FAK inhibition potential. The combination of substituents on the bicyclic templates and the nature of the core structure itself have a significant impact on the compounds FAK selectivity. Structural analysis revealed that the appropriately substituted pyrrolo[2,3-b]pyridine induced a rare helical DFG-loop conformation. The discovered synthetic route to introduce three different substituents independently paves the way for versatile applications of the 7-azaindole core.
Control Growth Factor Release Using a Self-Assembled [polycation∶heparin] Complex (2010)

The importance of growth factors has been recognized for over five decades; however their utilization in medicine has yet to be fully realized. This is because free growth factors have short half-lives in plasma, making direct injection inefficient. Many growth factors are anchored and protected by sulfated glycosaminoglycans in the body. We set out to explore the use of heparin, a well-characterized sulfated glycosaminoglycan, for the controlled release of fibroblast growth factor-2 (FGF-2). Heparin binds a multitude of growth factors and maintains their bioactivity for an extended period of time. We used a biocompatible polycation to precipitate out the [heparin:FGF-2] complex from neutral buffer to form a release matrix. We can control the release rate of FGF-2 from the resultant matrix by altering the molecular weight of the polycation. The FGF-2 released from the delivery complex maintained its bioactivity and initiated cellular responses that were at least as potent as fresh bolus FGF-2 and fresh heparin stabilized FGF-2. This new delivery platform is not limited to FGF-2 but applicable to the large family of heparin-binding growth factors.
Principle of equivalence between scanning and conventional optical imaging systems (1977)

The principle of equivalence between the imaging properties of scanning and conventional imaging systems has been proven in the past by assuming scalar sources of radiation and isotropic media. We prove here its general validity for optical systems with vector, electromagnetic sources of radiation and any optically nonactive media.
Risk factors for low birth weight in Sanaa city Yemen. (2002)

Low birth weight (LBW) represents the third leading cause of death in children in Yemen and is the most significant predictor of death health growth and development. The aim of this study was to estimate the birth weight distribution and prevalence of low birth weights in Sanaa City of Yemen and to determine some of the contributing risk factors. A descriptive cross-sectional design was used to study women who delivered in the four main hospitals in Sanaa City during the study period. Respondents were 2256 mothers ranging in age from 14-45 years with a mean age of 29.55 years. The mean age at the time of marriage was 22.38 years. Anthropometric measurements and interviews were used to determine the risk factors. The birth weights and anthropometric measurements of all babies born alive to mothers interviewed in the four hospitals during the period were collected. Post-delivery weight and other measurements of respondents were also collected. The data collected were entered into a computer using Statistical Package for Social Science (SPSS). The mean birth weight of the newborns in the study was 2812 g. Twenty-two percent of the newborns weighed between 700 and 2499 g. About 39% of respondents had urinary tract infection while 29% suffered from anemia and 10% had bleeding during pregnancy. All anthropometric measurements were significantly associated with LBW. Mothers who were younger in age at their first delivery had low post-delivery weight and bled during pregnancy were more likely to have LBW babies. There is a need for national prospective research project to study the low birth weight problem at the national level. There is also a need to discourage teenage pregnancies and to encourage utilization of mother and child health services and treat concomitant illnesses during pregnancy. (authors)
A Geometric Approach to Hyper-Redundant Manipulator Obstacle Avoidance (1992)

The term hyper-redundant refers to redundant manipulators with a very large or infinite number of degrees of freedom. These manipulators are analogous in morphology to snakes, elephant trunks, and tentacles. While a variety of obstacle avoidance algorithms for nonredundant and mildly redundant manipulators exist, little analysis has been performed for hyper-redundant robots. This paper presents a strictly geometric algorithm for hyper-redundant manipulator obstacle avoidance which relies on the use of “tunnels” in the obstacle-filled workspace. Methods of differential geometry are used to formulate equations which guarantee that sections of the manipulator are confined to the tunnels, and therefore avoid obstacles. A general formulation is presented with an example to illustrate this approach.
Sequence-independent inhibition of RNA transcription by DNA dumbbells and other decoys (1997)

DNA dumbbells are stable, short segments of double-stranded DNA with closed nucleotide loops on each end, conferring resistance to exonucleases. Dumbbells may be designed to interact with transcription factors in a sequence-specific manner. The internal based paired sequence of DNA dumbbells in this study contains the X-box, a positive regulatory motif found in all MHC class II DRA promoters. In electrophoretic mobility shift assays (EMSAs), dumbbells and other oligonucleotides ('decoys') with the core X-box sequence were found to compete with the native strand for binding to X-box binding proteins (including RFX1). However, only the X-box dumbbell was capable of forming detectable complexes with such proteins using EMSA. In a model cell system, dumbbells were tested for their ability to block RFX1VP16 activation of a plasmid containing multiple repeats of the X-box linked to the CAT gene. While it appeared that dumbbells could block this activation, the effect was non-specific. This and further evidence suggests an inhibition of transcription, most likely via an interaction with the general transcriptional machinery.
PANCREAS PRESERVATION WITH UNIVERSITY OF WISCONSIN AND CELSIOR SOLUTIONS: A SINGLE-CENTER, PROSPECTIVE, RANDOMIZED PILOT STUDY (2004)

Within the range of cold ischemia time reported in this study, UW and Celsior solutions have similar safety profiles for pancreas preservation.
Evaluation of Intravenous Magnesium Sulfate for the Treatment of Hydrofluoric Acid Burns (1994)

Hydrofluoric acid exposures to the skin can produce severe, progressive burns. Medical treatment of these burns is aimed at neutralizing the free fluoride ion, which is felt to be responsible for burn progression. Both calcium and magnesium will form complexes with free fluoride and have been used as topical or intradermal treatments in the past. This study evaluated the efficacy of intravenous magnesium sulfate for the treatment of hydrofluoric acid burns and compared this treatment to controls and burns treated with intradermal calcium gluconate in a rabbit model. Both treatments demonstrated a reduction in burn area over time, wound depth, healing time and final scar area compared to controls. The intravenous magnesium treatment showed trends toward improved outcome compared to the intradermal calcium treatment in all parameters evaluated, but these differences did not reach statistical significance. This investigation found intravenous magnesium to be an effective method for treating hydrofluoric acid burns. Intravenous magnesium may have significant utility for treating hydrofluoric acid burns that are not amenable to current therapies.
Inflammatory Cortical Demyelination in Early Multiple Sclerosis (2011)

In this cohort of patients with early-stage multiple sclerosis, cortical demyelinating lesions were frequent, inflammatory, and strongly associated with meningeal inflammation. (Funded by the National Multiple Sclerosis Society and the National Institutes of Health.).
Comparative biosynthesis, covalent post-translational modifications and efficiency of prosegment cleavage of the prohormone convertases PC1 and PC2: glycosylation, sulphation and identification of the intracellular site of prosegment cleavage of PC1 and PC2 (1993)

We present herein the pulse-chase analysis of the biosynthesis of the prohormone convertases PC1 and PC2 in the endocrine GH4C1 cells infected with vaccinia virus recombinants expressing these convertases. Characterization of the pulse-labelled enzymes demonstrated that pro-PC1 (88 kDa) is cleaved into PC1 (83 kDa) and pro-PC2 (75 kDa) into PC2 (68 kDa). Secretion of glycosylated and sulphated PC1 (84 kDa) occurs about 30 min after the onset of biosynthesis, whereas glycosylated and sulphated PC2 (68 kDa) is detected in the medium after between 1 and 2 h. Furthermore, in the case of pro-PC2 only, we observed that a fraction of this precursor escapes glycosylation. A small proportion (about 5%) of the intracellular glycosylated pro-PC2 (75 kDa) is sulphated, and it is this glycosylated and sulphated precursor that is cleaved into the secretable 68 kDa form of PC2. Major differences in the carbohydrate structures of PC1 and PC2 are demonstrated by the resistance of the secreted PC1 to endoglycosidase H digestion and sensitivity of the secreted PC2 to this enzyme. Inhibition of N-glycosylation with tunicamycin caused a dramatic intracellular degradation of these convertases within the endoplasmic reticulum, with the net effect of a reduction in the available activity of PC1 and PC2. These results emphasize the importance of N-glycosylation in the folding and stability of PC1 and PC2. Pulse-labelling experiments in uninfected mouse beta TC3 and rat Rin m5F insulinoma cells, which endogenously synthesize PC2, showed that, as in infected GH4C1 cells, pro-PC2 predominates intracellularly. In order to define the site of prosegment cleavage, pulse-chase analysis was performed at low temperature (15 degrees C) or after treatment of GH4C1 cells with either brefeldin A or carbonyl cyanide m-chlorophenylhydrazone. These results demonstrated that the onset of the conversions of pro-PC1 into PC1 and non-glycosylated pro-PC2 into PC2 (65 kDa) occur in a pre-Golgi compartment, presumably within the endoplasmic reticulum. In contrast, pulse labelling in the presence of Na(2)35SO4 demonstrated that the processing of glycosylated and sulphated pro-PC2 occurs within the Golgi apparatus. In order to test the possibility that zymogen processing is performed by furin, we co-expressed this convertase with either pro-PC1 or pro-PC2. The data demonstrated the inability of furin to cleave either proenzyme.