gebhart/patrepeval huggingface dataset:
Temperature-Induced Switching of Enzyme Activity with Smart Polymer−Enzyme Conjugates (2003)

A method for thermally induced switching of enzyme activity has been developed, based on the site-directed conjugation of end-reactive temperature-responsive polymers to a unique cysteine (Cys) residue positioned near the enzyme active site. The reversible temperature-induced collapse of N,N-dimethylacrylamide (DMA)/N-4-phenylazo-phenylacrylamide (AZAAm) copolymers (DMAAm) has been used as a molecular switch to control the catalytic activity of endoglucanase 12A (EG 12A). The polymer was conjugated to the EG 12A site-directed mutant N55C, directly adjacent to the cellulose binding cleft, and to the S25C mutant, where the conjugation site is more distant. The N55C conjugate displayed a larger activity shutoff efficiency in the collapsed polymer state than the S25C conjugate. Increasing the polymer molecular weight was also shown to increase the shutoff efficiency of the switch. Related to these effects of conjugation site and polymer size, the switching efficiency was found to be strongly dependent on substrate size. With a small substrate, o-nitrophenyl-beta-d-cellobioside (ONPC), there was minimal blocking of enzyme activity when the polymer was in the expanded state. With a large substrate, hydroxyethyl cellulose (HEC), there was a large reduction of enzyme activity in the polymer expanded state, even with relatively small polymer chains, and a further reduction when the polymer was collapsed. Similar general trends for the interactive effects of conjugation site, polymer size, and substrate size were observed for immobilized conjugates. Kinetic studies demonstrated that the switching activity was due to the blocking of substrate association by the collapsed polymers. These investigations provide mechanistic insight that can be utilized to design molecular switches for a variety of stimuli-responsive polymer-protein conjugates.
A Fast and Accurate Dependency Parser using Neural Networks (2014)

Almost all current dependency parsers classify based on millions of sparse indicator features. Not only do these features generalize poorly, but the cost of feature computation restricts parsing speed significantly. In this work, we propose a novel way of learning a neural network classifier for use in a greedy, transition-based dependency parser. Because this classifier learns and uses just a small number of dense features, it can work very fast, while achieving an about 2% improvement in unlabeled and labeled attachment scores on both English and Chinese datasets. Concretely, our parser is able to parse more than 1000 sentences per second at 92.2% unlabeled attachment score on the English Penn Treebank.
Oligodeoxynucleotide Modifications Determine the Magnitude of B Cell Stimulation by CpG Motifs (1996)

We have recently reported that oligodeoxynucleotides (ODN) that contain a CpG dinucleotide flanked by two purines on the 5'-side and two pyrimidines on the 3'-side induce potent B cell proliferation and differentiation. The present study investigates the role of the ODN backbone in determining the magnitude of the lymphocyte stimulation. Phosphorothioate ODN were approximately 2 logs more potent than the same sequence with a phosphodiester backbone. Chimeric ODN in which the 5'- and 3'-ends were modified with nuclease-resistant internucleotide linkages induced widely varying degrees of immune activation depending on the modification. Phosphorodithioate linkages were by far the most potent and induced B cell activation at nanomolar concentrations, approximately 1 log lower than required for the next most potent modification, phosphorothioate. Methylphosphorothioate terminal linkages were slightly more potent than phosphodiester, which were in turn slightly more potent than terminal methylphosphonate-modified ODN.
The Bacterial Histone-like Protein HU Specifically Recognizes Similar Structures in All Nucleic Acids (2002)

HU, a major component of the bacterial nucleoid, shares properties with histones, high mobility group proteins (HMGs), and other eukaryotic proteins. HU, which participates in many major pathways of the bacterial cell, binds without sequence specificity to duplex DNA but recognizes with high affinity DNA repair intermediates. Here we demonstrate that HU binds to double-stranded DNA, double-stranded RNA, and linear DNA-RNA duplexes with a similar low affinity. In contrast to this nonspecific binding to total cellular RNA and to supercoiled DNA, HU specifically recognizes defined structures common to both DNA and RNA. In particular HU binds specifically to nicked or gapped DNA-RNA hybrids and to composite RNA molecules such as DsrA, a small non-coding RNA. HU, which modulates DNA architecture, may play additional key functions in the bacterial machinery via its RNA binding capacity. The simple, straightforward structure of its binding domain with two highly flexible beta-ribbon arms and an alpha-helical platform is an alternative model for the elaborate binding domains of the eukaryotic proteins that display dual DNA- and RNA-specific binding capacities.
In vivo studies on the relationship between intestinal iron (Fe3+) absorption, hypoxia and erythropoiesis in the mouse (1988)

The effect of hypoxia and changes in erythropoiesis on the absorption of 59Fe3+ from in situ tied-off duodenal segments was studied in the mouse. Hypoxia led to an increase in mucosal uptake within 6 h, whilst mucosal transfer was unaffected for about 20 h, suggesting independent regulation of these two processes. Hypoxia (3 d) stimulated erythropoiesis and resulted in a 2-3-fold increase in the total mucosal uptake of 59Fe. Conversely, hyperoxia (100% O2) caused a decrease in reticulocyte counts and the total mucosal uptake. The changes in the transfer of 59Fe from the mucosa to the body were more marked than changes in uptake in both hypoxia and hyperoxia. Mice subjected to subtotal nephrectomy showed a normal increase in the total mucosal uptake of 59Fe3+ following hypoxic exposure, despite the absence of any changes in the reticulocyte count. Obliteration of the erythroid tissue of animals by splenectomy and 89Sr treatment was accompanied by a marked decrease in the transfer of 59Fe from mucosa to the carcass. However, exposure of splenectomized 89Sr-treated mice to hypoxia resulted in an increase in the total mucosal uptake and carcass transfer of 59Fe, without any change in erythropoiesis. These results indicate that hypoxia enhances mucosal iron uptake by a mechanism which is independent of stimulated erythropoiesis, but that changes in the rate of erythropoiesis have an additional effect, particularly on the transfer phase of iron absorption.
A Novel Fluorogenic Coumarin Substrate for Monitoring Acid Phosphatase Activity at Low pH Environment (2008)

This article described the synthesis and application of 6-chloro-8-fluoro-4-methylumbelliferone phosphate (CF-MUP) in analyzing acid phosphatase activity. Compared to the existing MUP, the new coumarin phosphate, CF-MUP, demonstrateed much higher sensitivity and was more robust for detecting the activity of acid phosphatase than the classic substrate 4-methylumbelliferone phosphate (MUP). The product of enzyme reaction, 6-chloro-8-fluoro-4-methylumbelliferone (CF-MU) possesses strong fluorescence at approximately 450 nm with low pKa (4.7), high fluorescence quantum yield and pH independence in the physiological pH range. This new fluorescence dye, CF-MU, is a convenient tool for assays with buffer pH between 4.5 and 8.
The Nitration of α- and β-Acylnaphthalenes (1995)

The nitration of a- and ß- acylnaphthalenes with copper(II) nitrate in acetic anhydride or nitric acid/acetic acid mixtures gives high yields of the corresponding mononitro compounds. The assignment of constitution to these products is made on the basis of extensive 1H n.m.r. chemicl shift and coupling constant data. In the case of a- acylnaphthalenes, with the notable exception of a- pivalonaphthone, nitration occurs in the a-positions of the unsubstituted ring to give mixtures of 5- and 8-nitro compounds. a- Pivalonaphthone gives appreciable amounts of the 4-nitro compound and also of the 8-nitro compound. This result indicates that the pivaloyl group does not shield the 8-position sterically to any significant extent and is effectively electronically neutral, unlike the other acyl substituents , in allowing attack at the a-position (position 4) of the acylated ring. This result is ascribable to the lack of coplanarity of the pivaloyl group with the naphthalene system. All of the ß- acylnaphthalenes gave mixtures of 4-, 5- and 8-nitro derivatives in proportions that did not vary significantly with the nature of the acyl group.
An 80-kilodalton antigen from Histoplasma capsulatum that has homology to heat shock protein 70 induces cell-mediated immune responses and protection in mice (1992)

An extract of the cell wall and cell membrane from Histoplasma capsulatum yeast cells was assayed by Western blot (immunoblot) for reactivity with two monoclonal antibodies to heat shock protein 70. Four bands with molecular masses of 80, 66, 54, and 32 kDa bound both antibodies. The 80-kDa protein was isolated, analyzed for homology to heat shock protein 70, and tested for antigenicity and immunogenicity in C57BL/6 mice. The 80-kDa protein reacted with monoclonal antibody to heat shock protein 70. Sera from mice immunized with the antigen recognized H. capsulatum heat shock protein 70. Moreover, the amino-terminal sequence of the 80-kDa protein revealed substantial homology with heat shock protein 70 from several species. The 80-kDa protein induced delayed-type hypersensitivity responses in mice immunized with either viable yeast cells or antigen. Splenocytes from mice immunized with yeast cells or with antigen responded in vitro to the 80-kDa antigen. Immunization of mice with the antigen enhanced host resistance against a sublethal inoculum of H. capsulatum yeast cells, but it did not reduce the mortality of mice given a lethal challenge of yeast cells. Thus, this antigen manifests homology with members of the heat shock protein 70 family. Furthermore, the 80-kDa protein elicits cellular immune responses to H. capsulatum, and it mediates protective immunity.
Ki-67 Staining Is a Strong Predictor of Distant Metastasis and Mortality for Men With Prostate Cancer Treated With Radiotherapy Plus Androgen Deprivation: Radiation Therapy Oncology Group Trial 92–02 (2004)

Ki67-SI was the most significant determinant of DM and CSD and was also associated with OD. The Ki67-SI should be considered for the stratification of patients in future trials.
Anti-Inflammatory Drug Therapy Alters β-Amyloid Processing and Deposition in an Animal Model of Alzheimer's Disease (2003)

Alzheimer's disease (AD) is characterized by a microglial-mediated inflammatory response elicited by extensive amyloid deposition in the brain. Nonsteroidal anti-inflammatory drug (NSAID) treatment reduces AD risk, slows disease progression, and reduces microglial activation; however, the basis of these effects is unknown. We report that treatment of 11-month-old Tg2576 mice overexpressing human amyloid precursor protein (APP) with the NSAID ibuprofen for 16 weeks resulted in the dramatic and selective reduction of SDS-soluble beta-amyloid (Abeta)42, whereas it had smaller effects on SDS-soluble Abeta40 levels. Ibuprofen treatment resulted in 60% reduction of amyloid plaque load in the cortex of these animals. In vitro studies using APP-expressing 293 cells showed that ibuprofen directly affected APP processing, specifically reducing the production of Abeta42. Ibuprofen treatment resulted in a significant reduction in microglial activation in the Tg2576 mice, as measured by CD45 and CD11b expression. NSAIDs activate the nuclear hormone receptor peroxisome proliferator-activated receptor gamma (PPARgamma); however, a potent agonist of this receptor, pioglitazone, only modestly reduced SDS-soluble Abeta levels and did not affect amyloid plaque burden or microglia activation, indicating that PPARgamma activation is not involved in the Abeta lowering effect of NSAIDs. These data show that chronic NSAID treatment can reduce brain Abeta levels, amyloid plaque burden, and microglial activation in an animal model of Alzheimer's disease.
Functional characterization of a Ca2+‐activated non‐selective cation channel in human atrial cardiomyocytes (2004)

Cardiac arrhythmias, which occur in a wide variety of conditions where intracellular calcium is increased, have been attributed to the activation of a transient inward current (Iti). Iti is the result of three different [Ca]i-sensitive currents: the Na(+)-Ca2+ exchange current, a Ca(2+)-activated chloride current and a Ca(2+)-activated non-selective cationic current. Using the cell-free configuration of the patch-clamp technique, we have characterized the properties of a Ca(2+)-activated non-selective cation channel (NSC(Ca)) in freshly dissociated human atrial cardiomyocytes. In excised inside-out patches, the channel presented a linear I-V relationship with a conductance of 19 +/- 0.4 pS. It discriminated poorly among monovalent cations (Na+ and K+) and was slightly permeable to Ca2+ ions. The channel's open probability was increased by depolarization and a rise in internal calcium, for which the Kd for [Ca2+]i was 20.8 microM. Channel activity was reduced in the presence of 0.5 mM ATP or 10 microM glibenclamide on the cytoplasmic side to 22.1 +/- 16.8 and 28.5 +/- 8.6%, respectively, of control. It was also inhibited by 0.1 mM flufenamic acid. The channel shares several properties with TRPM4b and TRPM5, two members of the 'TRP melastatin' subfamily. In conclusion, the NSC(Ca) channel is a serious candidate to support the delayed after-depolarizations observed in [Ca2+] overload and thus may be implicated in the genesis of arrhythmias.
Investigation of Mesa Dielectric Waveguides (2001)

Mesa dielectric waveguides fabricated by ion-beam sputtering Al2O3 and SiO2 on an etched Silicon substrate are investigated. This structure supports a single stable mode at 1540 nm, and demonstrated losses of 0.2-0.7 dB/cm.
Adaptive Beamforming Using a Microphone Array for Hands-Free Telephony (1999)

This thesis describes the design and implementation of a 4-channel microphone array that is an adaptive beamformer used for hands-free telephony in a noisy environment. The microphone signals are amplified, then sent to an A/D converter. The microprocessor board takes the data from the 4 channels and utilizes digital signal processing to determine the direction-of-arrival of the sources and create an output which `steers&amp;apos; the microphone array to the desired look direction while trying to minimize the energy of interference sources and noise. All of the processing for this thesis will be done on a computer using MATLAB. The MUSIC algorithm
Transduction of Murine Bone Marrow Cells With an MDR1 Vector Enables Ex Vivo Stem Cell Expansion, but These Expanded Grafts Cause a Myeloproliferative Syndrome in Transplanted Mice (1998)

Attempts to expand repopulating hematopoietic cells ex vivo have yielded only modest amplification in stem cell numbers. We now report that expression of an exogenous human multi-drug resistance 1 (MDR1) gene enables dramatic ex vivo stem cell expansion in the presence of early acting hematopoietic cytokines. Bone marrow cells were transduced with retroviral vectors expressing either the MDR1 gene or a variant of human dihydrofolate reductase (DHFR), and then expanded for 12 days in the presence of interleukin-3 (IL-3), IL-6, and stem cell factor. When these cells were injected into nonirradiated mice, high levels of long-term engraftment were only seen with MDR1-transduced grafts. To verify that expansion of MDR1-transduced repopulating cells had occurred, competitive repopulation assays were performed using MDR1 expanded grafts. These experiments showed progressive expansion of MDR1-transduced repopulating cells over the expansion period, with a 13-fold overall increase in stem cells after 12 days. In all of the experiments, mice transplanted with expanded MDR1-transduced stem cells developed a myeloproliferative disorder characterized by high peripheral white blood cell counts and splenomegaly. These results show that MDR1-transduced stem cells can be expanded in vitro using hematopoietic cytokines without any drug selection, but enforced stem cell self-renewal divisions can have adverse consequences.
Cold Promoted Activation of Factor VII (1972)

Summary The cold promoted shortening of the thrombotest times induced by incubation of plasma with prekallikrein activators for 20 hours at 0° C is due to activation of factor VII. No change was recorded for the other coagulation factors. The activation was strong, as the presence of 1 per cent cold activated factor VII reduced the thrombotest time of factor VII deficient plasma from 115 to 38.7 seconds. The activation of factor X by the cold activated factor VII occurred in the course of seconds, in the presence of calcium and thromboplastin. Cold promoted activation of factor VII also implied reduced cephalin time, probably via traces of thrombin inducing intrinsic factor X activator activity during the clotting test. Generation of cold promoted activator activity (CPA) was independent of coagulation factors V, VIII, IX, X, XI, and calcium, but factor XII was a prerequisite. Of factor VII even traces were sufficient for the generation of CPA. The activation of the kallikrein system, that occurs in parallel with the cold promoted activation of factor VII, occurred both in factor VII deficient plasma and in ordinary control plasma. In the reaction sequence, the activation of factor VII therefore is less likely to be the first step, it possibly is a result of activation of the kallikrein system.
Roles of Aurora Kinases in Mitosis and Tumorigenesis (2007)

Aurora kinases, which have been implicated in several vital events in mitosis, represent a protein kinase family highly conserved during evolution. The activity of Aurora kinases is delicately regulated, mainly by phosphorylation and degradation. Deregulation of Aurora kinase activity can result in mitotic abnormality and genetic instability, leading to defects in centrosome function, spindle assembly, chromosome alignment, and cytokinesis. Both the expression level and the kinase activity of Aurora kinases are found to be up-regulated in many human cancers, indicating that these kinases might serve as useful targets for the development of anticancer drugs. This review focuses on recent progress on the roles of Aurora kinases in mitosis and tumorigenesis.
INTRAVENOUS POLYETHYLENE GLYCOL SUCCESSFULLY TREATS SEVERE ACCELERATION-INDUCED BRAIN INJURY IN RATS AS ASSESSED BY MAGNETIC RESONANCE IMAGING (2009)

A single intravenous dose of PEG dramatically limits sequelae of severe acceleration-induced brain injury--in this case, assessed by cytotoxic edema on DW-MRI--by intervening at the primary injury level of neuronal membrane disruption. This outcome is unprecedented, as no prior treatments for DAI have demonstrated similar efficacy. DAI treatment with intravenous PEG may have future clinical relevance and warrants further investigation.
17β-Estradiol Replacement Reverses Age-Related Lung Disease in Estrogen-Deficient C57BL/6J Mice (2013)

The role that estrogens play in the aging lung is poorly understood. Remodeling of the aging lung with thickening of the alveolar walls and reduction in the number of peripheral airways is well recognized. The present study was designed to address whether estrogen deficiency would affect age-associated changes in the lungs of female C57BL/6J mice. Lungs isolated from old mice (24 months old, estrogen-deficient) demonstrated decreased lung volume and decreased alveolar surface area. There was no difference in alveolar number in the lungs of old and young mice (6 months old, estrogen-replete). Estrogen replacement restored lung volume, alveolar surface area, and alveolar wall thickness to that of a young mouse. Estrogen receptor-α (ERα) protein expression increased without a change in ERβ protein expression in the lung tissue isolated from old mice. In the lungs of old mice, the number of apoptotic cells was increased as well as the activation of matrix metalloproteinase-2 and ERK. Young mice had the highest serum 17β-estradiol levels that decreased with age. Our data suggest that in the aging female mouse lung, estrogen deficiency and an increase of ERα expression lead to the development of an emphysematous phenotype. Estrogen replacement partially prevents these age-associated changes in the lung architecture by restoration of interalveolar septa. Understanding the role of estrogens in the remodeling of the lung during aging may facilitate interventions and therapies for aging-related lung disease in women.
Simvastatin reduces melanoma progression in a murine model (2013)

Statins are a class of drugs that inhibit the rate-limiting step in the cholesterol biosynthetic pathway and show an anticancer effect, probably through the inhibition of cell proliferation. To date, the exact mechanism of cancer cell growth arrest induced by statins is not known. We report that simvastatin is able to induce apoptosis in melanoma cells but not in normal cells and also able to contrast the growth of tumor in an experimental melanoma murine model. We observed a delay in the tumor development in almost the 50% of the simvastatin administered animals and a strong reduction of the tumor volume with a differences of ~150% compared to the controls. Also the survival rate was significantly higher in mice that received the drug with a survival increase of ~130% compared to the controls. The tumor growth reduction in mice was supported by the results of cell migration assay, confirming that simvastatin clearly reduced cell migration. Moreover, simvastatin induced a strong downregulation of NonO gene expression, an important growth factor involved in the splicing regulation. This result could explain the decrease of melanoma cells proliferation, suggesting a possible action mechanism. The results derived from our experiments may sustain the many reports on the anticancer inhibitory property of statins and encourage new studies on this drug for a possible use in therapy, probably in combination with conventional chemotherapy.
The deduced sequence of the novel protransglutaminase E (TGase3) of human and mouse (1993)

At least three transglutaminases are involved in terminal differentiation events in the epidermis and its derivatives, such as the hair follicle, presumably in cross-linking structural proteins and in the formation of the cornified cell envelope. Of these, only the transglutaminase 3 is a proenzyme, requiring activation by proteolytic cleavage, and is the least understood. Using oligonucleotides designed from the amino acid sequences of peptides of the guinea pig enzyme, we amplified mRNA and deduced the complete amino acid sequences of the mouse and human protransglutaminase 3 enzymes. Both proteins contain 692 amino acids of molecular mass about 77 kDa. Following expression in yeast, the proenzymes encoded by the full-length cDNA clones are active enzymes and can be further activated 15-fold on treatment with dispase. Although these proteins share 38-53% identity to other members of the transglutaminase family, surprisingly, the mouse, human, and guinea pig enzymes have not been highly conserved and show only 50-75% identity to each other. Much of the sequence variation occurs in the vicinity of the proteolytic activation site which lies at the most flexible and hydrophilic region of the molecule and is flanked by a sequence of 12 residues that are absent from other transglutaminases. We suggest that cleavage of this exposed flexible hinge region promotes a conformational change in the protein to a more compact form, resulting in activation of the enzyme. Expression of mouse and human protransglutaminase 3 mRNAs is regulated by calcium, as for other late differentiation products of the epidermis, suggesting that this enzyme is responsible for the later stages of cell envelope formation in the epidermis and hair follicle.