gebhart/patrepeval huggingface dataset:
Cytochrome c Oxidase Is Required for the Assembly/Stability of Respiratory Complex I in Mouse Fibroblasts (2006)

Cytochrome c oxidase (COX) biogenesis requires COX10, which encodes a protoheme:heme O farnesyl transferase that participates in the biosynthesis of heme a. We created COX10 knockout mouse cells that lacked cytochrome aa3, were respiratory deficient, had no detectable complex IV activity, and were unable to assemble COX. Unexpectedly, the levels of respiratory complex I were markedly reduced in COX10 knockout clones. Pharmacological inhibition of COX did not affect the levels of complex I, and transduction of knockout cells with lentivirus expressing wild-type or mutant COX10 (retaining residual activity) restored complex I to normal levels. Pulse-chase experiments could not detect newly assembled complex I, suggesting that either COX is required for assembly of complex I or the latter is quickly degraded. These results suggest that in rapidly dividing cells, complex IV is required for complex I assembly or stability.
Inhibition of DNA Transcription Using Cationic Mixed Monolayer Protected Gold Clusters (2001)

Efficient recognition of DNA is a prerequisite for the development of biological effectors, including transcription and translation regulators, transfection vectors, and DNA sensors. To provide an effective scaffold for multivalent interactions with DNA, we have fabricated mixed monolayer protected gold clusters (MMPCs) functionalized with tetraalkylammonium ligands that can interact with the DNA backbone via charge complementarity. Binding studies indicate that the MMPCs and DNA form a charge-neutralized, nonaggregated assembly. The interactions controlling these assemblies are highly efficient, completely inhibiting transcription by T7 RNA polymerase in vitro.
Missouri Child Support Guidelines (1992)

The Child Support Enforcement Amendments of 1984' and the Family Support Act of 1988, are designed to improve the adequacy, consistency, and collectability of child support awards. These two laws require states to develop specific guidelines providing a numerical formula for the determination of child support award amounts' and require that the guidelines be presumptive. Following the federal mandate, the Missouri Supreme Court enacted child support guidelines which have been mandatory since April 1, 1990.
Regulation of cytokine gene expression in T helper cell subsets. (1994)

We have examined the transcriptional regulation of the Th1-specific IL-2 gene and the Th2-specific IL-4 gene by transient transfection of promoter-chloramphenicol acetyl transferase (CAT) constructs into T cell clones and by electrophoretic mobility shift assays. Transfection of the Th2 clone D10.G4 with IL-4 promoter-CAT constructs demonstrated anti-CD3 inducible IL-4 promoter activity. In contrast, CAT constructs containing murine IL-2 promoter sequences were not inducible in D10.G4 cells. Transfection analyses in the Th1 clone D1.1 demonstrated inducible IL-2 promoter activity but no IL-4 promoter activity. Electrophoretic mobility shift assays using well-defined regulatory elements in the murine IL-2 gene promoter showed that anti-CD3 stimulation of Th2 clones failed to induce a characteristic increase in the ratio of p65-p50:p50-p50 NF-kappa B binding complexes in the nucleus that did occur in IL-2-producing clones. In addition, other protein complexes with NF-kappa B binding sequences were seen using lysates from Th1 and Th0 cells but not Th2 cells. Thus, expression of the promoter-CAT constructs directly correlates with endogenous IL-2 and IL-4 gene expression in Th1 and Th2 clones, confirming that the differential expression of IL-2 and IL-4 genes in these T cells is transcriptionally controlled. Furthermore, the lack of IL-2 transcription in activated Th2 cells is associated with the failure to generate required IL-2 gene promoter binding proteins, particularly NF-kappa B in the nucleus.
Double Suicide Gene (Cytosine Deaminase and Herpes Simplex Virus Thymidine Kinase) but Not Single Gene Transfer Allows Reliable Elimination of Tumor Cells In Vivo (1998)

Suicide genes such as cytosine deaminase (CD) and herpes simplex virus thymidine kinase (TK) encode products that convert nontoxic substances (prodrugs) into toxic metabolites. Suicide gene transfer is currently being used in cancer therapy or can be used as a safety modality. To analyze the reliability of suicide genes as a safety modality for a vaccination study with viable cytokine/B7 gene-modified tumor cells, the individual and combined efficacy of the two suicide genes was compared for in vitro and in vivo cell killing of a murine mammary adenocarcinoma cell line (TS/A). To adapt the system to an in vivo gene delivery situation, bulk cultures cotransfected with the CD and TK gene were used instead of selected clones. In vitro, both CD and TK conferred sensitivity to the respective prodrug but the combined cytotoxic effects of both gene products were always superior. For in vivo analysis BALB/c mice were injected subcutaneously with CD- and TK-modified TS/A cells, treated with prodrugs, and tumor size was evaluated for a period of 100 days. In the in vivo situation the combination of both enzyme/prodrug systems was again most effective. The highest single concentration of 5-FC (500 mg/kg) or GCV (100 mg/kg) was not able to fully protect the animals from developing tumors, whereas a combination of 5-FC (250 mg/kg) and GCV (50 mg/kg) resulted in complete tumor eradication. In nude mice treated in the same way, most CD/TK tumors could not be eliminated. Furthermore, BALB/c mice cured of TS/A-CD/TK tumors developed a systemic tumor immunity against challenge with parental TS/A cells. These findings indicate that reliable tumor elimination by the suicide genes depends on T cells. The cooperative effect of both suicide genes was confirmed in vitro with the human renal cell carcinoma line RCC26. We conclude that TK and CD together, but neither gene alone, act as a safety mechanism for the elimination of tumor cells in a reliable fashion and suggest that a rapid and quantitative antigen release by effective TK- and CD-mediated tumor destruction is necessary for T cell immunity to develop.
ARISE: A Phase 3 randomized trial of erenumab for episodic migraine (2018)

Background Calcitonin gene-related peptide plays an important role in migraine pathophysiology. Erenumab, a human monoclonal antibody that inhibits the calcitonin gene-related peptide receptor, is being evaluated for migraine prevention. Methods In this randomized, double-blind, placebo-controlled, phase 3 study, 577 adults with episodic migraine were randomized to placebo or 70 mg erenumab; 570 patients were included in efficacy analyses. Primary endpoint was change in monthly migraine days. Secondary endpoints were ≥50% reduction in monthly migraine days, change in acute migraine-specific medication treatment days, and ≥5-point reduction in Physical Impairment and Impact on Everyday Activities domain scores measured by the Migraine Physical Function Impact Diary. All endpoints assessed change from baseline at month 3. Results Patients receiving erenumab experienced -2.9 days change in monthly migraine days, compared with -1.8 days for placebo, least-squares mean (95% CI) treatment difference of -1.0 (-1.6, -0.5) ( p < 0.001). A ≥ 50% reduction in monthly migraine days was achieved by 39.7% (erenumab) and 29.5% (placebo) of patients (OR:1.59 (95% CI: 1.12, 2.27) ( p = 0.010). Migraine-specific medication treatment days were reduced by -1.2 (erenumab) and -0.6 (placebo) days, a treatment difference of -0.6 (-1.0, -0.2) ( p = 0.002). The ≥5-point reduction rates in Migraine Physical Function Impact Diary - Physical Impairment were 33.0% and 27.1% (OR:1.33 (0.92, 1.90) ( p = 0.13) and in Migraine Physical Function Impact Diary - Everyday Activities were 40.4% and 35.8% (OR:1.22 (0.87, 1.71) ( p = 0.26). Safety and adverse event profiles of erenumab were similar to placebo. Most frequent adverse events were upper respiratory tract infection, injection site pain, and nasopharyngitis. Conclusions As a preventive treatment of episodic migraine, erenumab at a dosage of 70 mg monthly significantly reduced migraine frequency and acute migraine-specific medication use. (Funded by Amgen). Trial registration ClinicalTrials.gov, NCT02483585.
Central Pressure: Variability and Impact of Cardiovascular Risk Factors (2008)

Pulse pressure varies throughout the arterial tree, resulting in a gradient between central and peripheral pressure. Factors such as age, heart rate, and height influence this gradient. However, the relative impact of cardiovascular risk factors and atheromatous disease on central pressure and the normal variation in central pressure in healthy individuals are unclear. Seated peripheral (brachial) and central (aortic) blood pressures were assessed, and the ratio between aortic and brachial pulse pressure (pulse pressure ratio, ie, 1/amplification) was calculated in healthy individuals, diabetic subjects, patients with cardiovascular disease, and in individuals with only 1 of the following: hypertension, hypercholesterolemia, or smoking. The age range was 18 to 101 years, and data from 10 613 individuals were analyzed. Compared with healthy individuals, pulse pressure ratio was significantly increased (ie, central systolic pressure was relatively higher) in individuals with risk factors or disease (P<0.01 for all of the comparisons). Although aging was associated with an increased pulse pressure ratio, there was still an average+/-SD difference between brachial and aortic systolic pressure of 11+/-4 and 8+/-3 mm Hg for men and women aged >80 years, respectively. Finally, stratifying individuals by brachial pressure revealed considerable overlap in aortic pressure, such that >70% of individuals with high-normal brachial pressure had similar aortic pressures as those with stage 1 hypertension. These data demonstrate that cardiovascular risk factors affect the pulse pressure ratio, and that central pressure cannot be reliably inferred from peripheral pressure. However, assessment of central pressure may improve the identification and management of patients with elevated cardiovascular risk.
Native, industrial and fossil chitins (1999)

Countless living organisms continuously synthesize and degrade chitin enzymatically, for nutritional, morphogenetic and defensive or aggressive purposes. Chemically modified chitins are important in the light of their biochemical significance in medicine and crop protection; their environmentally friendly behaviour permits industrial exploitation of the huge chitinous biomasses generated by fishing activities and biotechnology. Chitin is promptly metabolized in sediments, and fossil chitin is not frequently encountered.
Identifying 5-methylcytosine and related modifications in DNA genomes (1998)

Intense interest in the biological roles of DNA methylation, particularly in eukaryotes, has produced at least eight different methods for identifying 5-methylcytosine and related modifications in DNA genomes. However, the utility of each method depends not only on its simplicity but on its specificity, resolution, sensitivity and potential artifacts. Since these parameters affect the interpretation of data, they should be considered in any application. Therefore, we have outlined the principles and applications of each method, quantitatively evaluated their specificity,resolution and sensitivity, identified potential artifacts and suggested solutions, and discussed a paradox in the distribution of m5C in mammalian genomes that illustrates how methodological limitations can affect interpretation of data. Hopefully, the information and analysis provided here will guide new investigators entering this exciting field.
A Non–D2-Receptor-Binding Drug for the Treatment of Schizophrenia (2020)

In this 4-week trial involving patients with an acute exacerbation of schizophrenia, SEP-363856, a non-D2-receptor-binding antipsychotic drug, resulted in a greater reduction from baseline in the PANSS total score than placebo. Longer and larger trials are necessary to confirm the effects and side effects of SEP-363856, as well as its efficacy relative to existing drug treatments for patients with schizophrenia. (Funded by Sunovion Pharmaceuticals; ClinicalTrials.gov number, NCT02969382.).
On the hybridization in some archimedean carbon clusters (1987)

Hybridization, bond, and deviation angles as well as strain energies in Archimedean carbon clusters C24, C48, C60, and C120 are calculated within the iterated maximum overlap approximation.
Studies on solid dispersions of nifedipine (1992)

Nifedipine-Polyethylene glycol solid dispersions were prepared by melting or fusion method in order to improve nifedipine solubility in the aqueous body fluids. The dissolution rate of the drug was markedly increased in these solid dispersion systems. The increase in dissolution was a function of the ratio of drug to polyethylene glycol used and the molecular weight of polyethylene glycol. The dissolution rate was compared with a 10% w/w physical mixture of drug with polyethylene glycol.The physical state of nifedipine after fusion was determined by X-ray crystallography on the pure drug and on the solidified melts. The X-ray diffraction studies indicated that nifedipine in the solid dispersion which was obtained by sudden cooling of the melt, was in the thermodynamically unstable metastable form. It was established that the slow cooling of the melt as well as powdering of solid dispersion resulted in the emergence of crystallinity.The effect of aging on nifedipine-polyethylene glycol 6000 solid dispersions has been investigated. After storage at room temperature for six months, solid dispersions showed no change in the dissolution rate and the X-ray diffraction pattern showed slight enhancement in crystallinity.
An Application of Reversible-Jump MCMC to Multivariate Spherical Gaussian Mixtures (1997)

Applications of Gaussian mixture models occur frequently in the fields of statistics and artificial neural networks. One of the key issues arising from any mixture model application is how to estimate the optimum number of mixture components. This paper extends the Reversible-Jump Markov Chain Monte Carlo (MCMC) algorithm to the case of multivariate spherical Gaussian mixtures using a hierarchical prior model. Using this method the number of mixture components is no longer fixed but becomes a parameter of the model which we shall estimate. The Reversible-Jump MCMC algorithm is capable of moving between parameter subspaces which correspond to models with different numbers of mixture components. As a result a sample from the full joint distribution of all unknown model parameters is generated. The technique is then demonstrated on a simulated example and a well known vowel dataset.
Abstract data views: an interface specification concept to enhance design for reuse (1995)

The abstract data view (ADV) design model was originally created to specify clearly and formally the separation of the user interface from the application component of a software system, and to provide a systematic design method that is independent of specific application environments. Such a method should lead to a high degree of reuse of designs for both interface and application components. The material presented, extends the concept of ADV's to encompass the general specification of interfaces between application components in the same or different computing environments. This approach to specifying interfaces clearly separates application components from each other, since they do not need to know how they are used, or how they obtain services from other application components. Thus, application components called abstract data objects (ADOs), are designed to minimize knowledge of the environment in which they are used and should be more amenable to reuse.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Sphingosine 1-phosphate induces alpha-smooth muscle actin expression in lung fibroblasts via Rho-kinase. (2005)

Transformation of fibroblasts into myofibroblasts is an important phenomenon that contributes to airway remodeling in bronchial asthma. Although several articles have recently indicated that a bioactive lysosphingolipid sphingosine 1-phosphate (S1P) plays roles in the pathogenesis of bronchial asthma, the role of S1P in the remodeling process is poorly understood. In the present study, we examined the effects of S1P on alpha-smooth muscle actin (SMA) expression and the morphology in lung fibroblasts. S1P stimulated the expression of alpha-SMA in a human lung fibroblast cell line WI38 that expresses EDG/S1P receptors. These processes were inhibited by Y-27632, but not by pertussis toxin. These results suggest that S1P induces a phenotypic change of lung fibroblasts via Rho-kinase that may lead to airway remodeling.
Fruit extract of Emblica officinalis ameliorates hyperthyroidism and hepatic lipid peroxidation in mice. (2003)

The ethanolic extract from the fruits of Emblica officinalis Gaertn (Euphorbiaceae) was investigated to evaluate its possible ameliorating effects, on the L-thyroxine (L-T4) induced hyperthyroidism and on hepatic lipid peroxidation in mice. While an increase in serum T3 (triiodothyronine) and T4 (thyroxine) concentrations, and in a thyroid dependent parameter, hepatic glucose 6-phospatase (glu-6-pase) activity was observed in L-T4 (0.5 mg/kg/d) treated animals, simultaneous oral administration of the plant extract at a dose of 250 mg/kg/d (p.o.) for 30 days in hyperthyroid mice reduced T3 and T4 concentrations by 64 and 70% respectively as compared to a standard antithyroid drug, propyl thiouracil (PTU) that decreased the levels of the thyroid hormones by 59 and 40% respectively. The plant extract also maintained nearly normal value of glu-6-pase activity in hyperthyroid mice. The plant extract also decreased hepatic lipid peroxidation (LPO) and increased the superoxide dismutase (SOD) and catalase (CAT) activities in hyperthyroid mice, exhibiting its hepatoprotective nature. Our findings suggest that the test material may potentially ameliorate the hyperthyroidism with an additional hepatoprotective benefit.
Activity-Based Protein Profiling of Protein Tyrosine Phosphatases (2009)

The ability to accurately monitor the dynamics involved with the activity and state of a specific protein population in a complex biological system represents one of the major technological challenges in studying systems biology. Over the past several years a number of groups have attempted to spearhead this new frontier of systems biology by developing enzyme family-specific activity-based chemical probes linked to appropriate reporter groups that by nature only target and subsequently tag the active form of these enzymes. In this work, we will highlight the methods used to characterize activity-based probes as to their utility in biological contexts. Specifically, we will address activity-based protein profiling of the protein tyrosine phosphatases, a highly conserved enzyme family responsible for the phospho-tyrosine hydrolysis reaction, a ubiquitous reaction that is absolutely essential to the regulation of a myriad of cellular processes.
Neuron-Binding Human Monoclonal Antibodies Support Central Nervous System Neurite Extension (2004)

Two human IgMs (sHIgM12 and sHIgM42) were identified that supported in vitro central nervous system (CNS) neurite extension equal to the potent neurite stimulatory molecule laminin. Both IgMs bound to multiple cell types in unfixed CNS tissue and to the surface of neurons in culture. Both monoclonal antibodies (mAbs) overrode the inhibitory effect of CNS mouse myelin on granule cell neurite extension. Neither mAb bound to the surface of mature oligodendrocytes or strictly colocalized with myelin proteins. Sialidase treatment eliminated the neuronal surface binding of both mAbs, whereas blocking sphingolipid synthesis with Fumonisin B1 or removing GPI-linked proteins with PIPLC did not. When used as substrates for mixed neuron/glia aggregates, sHIgM12 and sHIgM42 supported robust neurite extension while astrocytes remained in the aggregates. In contrast, laminin supported astrocyte migration and spreading. Human mAbs that support neurite extension are novel factors that may be of use in encouraging axon repair following injury while minimizing glial cell infiltration. Both human mAbs were isolated from individuals with monoclonal gammopathy. Each individual has carried high mAb titers in circulation for years without detriment. sHIgM12 and sHIgM42 are therefore unlikely to be systemically pathogenic.
Evaluation of a modified culture medium for Borrelia burgdorferi sensu lato (2007)

The aim of the present study was to assess the possible use of a modified medium, prepared in the laboratory using the constituents of Barbour-Stonner-Kelly (BSK) medium and medium 199 as base, for the culture of Borrelia strains, comparing the growth of individual strains in this medium and in the BSK-H medium, and the protein profile and antigenic characteristics of Borrelia proteins expressed in these media. A qualitative evaluation of growth of Borrelia species was made with acceptable results (morphology and motility), but during a quantitative evaluation using the three main genospecies of Borrelia, the better results were obtained with a B. burgdorferi sensu stricto strain. The modified medium did not enable the growth of a B. afzelii strain. The protein profile and antigenic characteristic of the expressed proteins in the modified medium were studied with satisfactory results. These results suggest the modified medium as an alternative for the cultivation of Borrelia strains, with some limitations, in poorly-resourced laboratories.
Synthesis of Microporous Silica Templated by Gelatin (2004)

Abstract Gelatin, a low cost biopolymer was successfully used as a porogen to form microporous silica in the presence of formic acid as a cosolvent.
Cytotoxic T Lymphocyte (CTL) Responses to Human Cytomegalovirus pp65, IE1‐Exon4, gB, pp150, and pp28 in Healthy Individuals: Reevaluation of Prevalence of IE1‐Specific CTLs (2000)

The prevalence of human cytomegalovirus (HCMV) pp65-, pp150-, IE1-exon4-, gB- and pp28-specific cytotoxic T lymphocyte (CTL) responses was compared among 34 healthy individuals, grouped by neutralizing antibody titers. Moderately and highly seropositive donors showed predominantly pp65- and IE1-exon4-specific CTL responses (92% and 76% of the donors, respectively), with similar precursor frequencies in the 2 donors tested. In addition, highly seropositive and a few moderately seropositive donors showed CTL responses to gB and pp150 (33% and 30% of the donors, respectively). No individual recognized pp28 as a target in the CTL assay. Phenotypic analysis revealed a mixed effector population of CD4+ and CD8+ (1 donor) or only CD8+ cells for pp65-specific effectors (2 donors). IE1-exon4- and pp150-specific effectors were CD8+ (2 donors and 1 donor, respectively), whereas gB-specific CTLs were CD4+ (1 donor). These data may help to design a cellular immunity-based vaccine effective against HCMV diseases.