gebhart/patrepeval huggingface dataset:
Inhibition of Glioblastoma Growth in a Highly Invasive Nude Mouse Model Can Be Achieved by Targeting Epidermal Growth Factor Receptor but not Vascular Endothelial Growth Factor Receptor-2 (2008)

Abstract Purpose: Major shortcomings of traditional mouse models based on xenografted human glioblastoma cell lines are that tumor cells do not invade and that genetic alterations, such as amplification of the epidermal growth factor receptor (EGFR) gene, are not maintained. Such models are thus of limited value for preclinical studies. We established a highly invasive model to evaluate the effect of antibodies against EGFR (cetuximab) and vascular endothelial growth factor receptor-2 (antibody DC101). Experimental Design: After short-term culture, glioblastoma spheroids were implanted into the brains of nude mice. Animals were treated either i.c. with cetuximab or i.p. with DC101. Tumor burden was determined histologically using image analysis of 36 different landmark points on serial brain sections. Results: Invasive xenografts were obtained from nine different glioblastomas. Three of seven cases treated with cetuximab responded with significant tumor growth inhibition, whereas four did not. All responsive tumors were derived from glioblastomas exhibiting EGFR amplification and expression of the truncated EGFRvIII variant, which were maintained in the xenografts. All nonresponsive tumors lacked EGFR amplification and EGFRvIII expression. The proportion of apoptotic cells was increased, whereas proliferation and invasion were decreased in responsive tumors. None of four xenograft cases treated with DC101 responded to treatment, and the diffusely invading tumors grew independent of angiogenesis. Conclusions: Inhibition of glioblastoma growth and invasion can be achieved using i.c. delivery of an anti-EGFR antibody, but tumor response depends on the presence of amplified and/or mutated EGFR. Antiangiogenic treatment with DC101 is not effective against diffusely invading tumors.
In vivo IgA coating of anaerobic bacteria in human faeces. (1996)

The bacterial flora in the human colon, although extremely diverse, has a relatively stable composition and non-infectious anaerobic bacteria are dominant. The flora forms a pool of numerous different antigens separated from mucosal immunocompetent cells by just a single layer of epithelial cells. Despite this thin barrier, however, the colonic mucosa is physiologically only mildly inflamed. This study looked at the mucosal humoral immune response against faecal anaerobes. By flow cytometric analysis the in vivo immunoglobulin coating of anaerobic bacteria in faecal samples of 22 healthy human volunteers was determined. In a previous study flow cytometric analysis of faecal bacteria has been found to be a very sensitive method to detect immunoglobulins on faecal bacteria. This technique showed that in vivo many bacteria are coated with IgA (24-74%) and less with IgG and IgM. The presence of many bacteria coated with IgA implies that IgA coating does not result in permanent removal of the species from the colon. The absence of immunoglobulin coating suggests that there is immunological unresponsiveness for anaerobic bacterial antigens. It is concluded that both immunological unresponsiveness and preferential coating with IgA are responsible for the relative absence of colonic mucosal inflammation.
Intrinsic Cardiac Neurons (1991)

Intrinsic Cardiac Neurons. Physiological evidence indicates that afferent neurons, local circuit neurons, as well as efferent sympathetic and efferent parasympathetic neurons, are located in the mammalian intrinsic cardiac nervous system. Complex interneuronal interactions can occur between these neurons, as well as between such neurons and other intrathoracic and central nervous system neurons. A variety of neurochemicals have been proposed to be involved in such interneuronal interactions. Thus the electrophysiologic properties and synaptology of intrinsic cardiac neurons may be more varied than has been appreciated accounting, at least in part, for the variety of neuronal responses that in situ intrinsic cardiac neurons are capable of displaying. The various interactions that occur between intrinsic cardiac neurons and other intrathoracic neurons, as well as between neurons in all intrathoracic ganglia and the central nervous system, will have to be characterized in order to clarify the role of the autonomic nervous system regulating the heart throughout each cardiac cycle.
FcγRIIIB Gene Duplication: Evidence for Presence and Expression of Three Distinct FcγRIIIB Genes in NA(1+,2+)SH(+) Individuals (1998)

Recently, a new alloantigen on IgG Fc receptor type IIIb (Fc gamma RIIIb), SH, was described (Bux et al, Blood 89:1027, 1997). We identified three healthy individuals whose neutrophils reacted positively with the SH antiserum. The neutrophil antigen (NA) phenotype of all three donors was NA(1+,2+). Analysis of genomic DNA showed that the three donors were positive for the described SH-encoding mutation in the NA2-Fc gamma RIIIB gene, 266C-->A. However, NA(1,2) genotyping and nucleotide sequencing of an NA2-specific fragment amplified from the genomic DNA fragment showed that these individuals carried three Fc gamma RIIIB genes, namely, NA1-Fc gamma RIIIB, NA2-Fc gamma RIIIB, and SH-Fc gamma RIIIB, encoding NA1-Fc gamma RIIIb, NA2-Fc gamma RIIIb, and SH-Fc gamma RIIIb, respectively. Southern blot analysis confirmed these findings. Furthermore, all three transcripts were isolated from neutrophil mRNA. To investigate whether the presence of three Fc gamma RIIIB genes resulted in a higher membrane expression of Fc gamma RIIIb, we measured the reactivity of neutrophils from NA(1+,2+)SH(+) individuals with a panel of CD16 monoclonal antibodies (MoAbs) in comparison with neutrophils from NA(1+,2+)SH(-) controls. Reactivity of four different anti-pan-Fc gamma RIII MoAbs and NA2-specific MoAb GRM1 was higher with SH(+) neutrophils compared with controls, whereas that of NA1-specific MoAbs was similar, which is in concordance with the results from the genomic analysis. We observed that reactivity with NA2-specific CD16 MoAb PEN1 was sixfold higher in SH(+) individuals compared with controls. Apparently, the 60Ala-->Asp substitution in SH-Fc gamma RIIIb influences the epitope recognized by PEN1. In conclusion, we identified three NA(1+,2+)SH(+) individuals carrying three Fc gamma RIIIB genes and observed a clear gene-dosage effect on the level of expression of neutrophil Fc gamma RIIIb.
Laser Scanning Microscopy Applied to Studies of the Cell Cycle. (1997)

Abstract Non-confocal Laser Scanning Microscopy (LSCM) was developed to allow applying the tenents of flow cytometery to specimens attached to a microscope slide (1). Areas of the slide are scanned, fluorescently labled cells are automatically segmented, and a list of features for each cell is calculated and stored in a list mode data file. Figure 1 shows a block diagram of the LSCM. A collimated laser beam scans in the y direction, and values from photomultiplier and photodiode detectors are digitized to.25 micron resolution. The automated stage advances in.5 micron steps in the x direction. When cascading memory banks are filled, the “image” is segmented. Figure 2 shows contours drawn as part of the segmentation process. The innermost contour is drawn around pixels that exceed a predetermined threshold, and is used to define events. Other contours are used to define integration areas, background calculation and correction, and integrating nuclear vs. peripheral fluorescence areas.
Medicinal Chemistry, Metabolic Profiling and Drug Target Discovery: A Role for Metabolic Profiling in Reverse Pharmacology and Chemical Genetics (2005)

Comprehensive analysis of the metabolome can contribute to mechanism of action studies for small molecules discovered in phenotypic screens. Examples are presented in this overview of the rapidly developing field of "metabolic profiling." These examples include the use of NMR in gene function analysis, GC-based studies on the identification of metabolic pathways affected by PPAR-gamma agonists, applications of Fourier-transform MS and the use of stable isotope-based metabolic profiling (SIDMAP) to investigate metabolic adaptive changes induced by effective anticancer agents.
Cutaneous malignant melanoma and atypical moles associated with a constitutional rearrangement of chromosomes 5 and 9 (1993)

Hereditary cutaneous malignant melanoma (HCMM) with or without atypical moles has been described in several large kindreds worldwide. Despite numerous studies of these kindreds, the gene or genes responsible for this disorder has not yet been identified. Cytogenetic and molecular studies of melanoma tumor tissue and cell lines suggest that a gene involved in the pathogenesis of malignant melanoma lies on chromosome 9p. We describe a woman with atypical moles and multiple primary melanomas, who lacks a family history of HCMM, and, has a de novo constitutional unbalanced reciprocal translocation involving the short arms of chromosomes 5 and 9 with a cytogenetically visible deletion of 5p or 9p: [46,XX,-5,-9, +der(5)t(5;9) (p13.3 or 14.2;p13.3 or 21.2), +der(9)t(5;9)]. This finding supports the hypothesis that a gene predisposing to HCMM lies on the short arm of chromosome 9.
Gene expression profiling detects gene amplification and differentiates tumor types in breast cancer. (2003)

Global gene expression analysis using microarrays has been used to characterize the molecular profile of tumors. Gene expression variability at the mRNA level can be caused by a number of different events, including novel signaling, downstream activation of transcription enhancers or silencers, somatic mutation, and genetic amplification or deletion. Genomic amplifications are commonly observed in cancer and often include known oncogenes. The tyrosine kinase-type cell surface receptor, ERBB2, is an oncogene located on chromosome 17q21.1 that is amplified in 10-40% of breast tumors. We report for the first time that phenylethanolamine N-methyltransferase (PNMT), proteasome subunit, beta type 3 (PSMB3), ribosomal protein L19 (RPL19), and nuclear receptor subfamily 1, group D, member 1 (NR1D1) are coexpressed with ERBB2 in 34 breast cancer biopsies and also mapped within the same chromosomal location as the ERBB2 gene. Consistent with previous reports, we also observed that the steroidogenic acute regulatory protein-related gene, MLN64, and growth factor receptor bound protein 7 were coexpressed with ERBB2. Coexpression and colocalization of PNMT and MLN64 with ERBB2 suggested that the amplification of ERBB2 includes the chromosomal region harboring these genes. This hypothesis was validated in a subset of 12 biopsies. Gene amplification of ERBB2, PNMT, and MLN64 significantly correlated with increased mRNA gene expression (P < 0.05). These results suggest that gene expression profiling of breast biopsies may become a valuable method for adequately characterizing and choosing treatment modality for patients with breast cancer.
Antihemophilic Factor: Separation of an Active Fragment Following Dissociation by Salts or Detergents (1972)

Summary Dissociation of canine antihemophilic factor (factor VIII, molecular weight &gt;2 × 106) by salts and detergents was studied with the use of agarose gel chromatography. The dissociated fragments retained antihemophilic factor activity. Partial dissociation occurred in 1 M or 2 M KCl, 1 M KBr, 0.25% sodium desoxycholate and 0.1% Triton X-100, but essentially no dissociation was observed in 3 M KC1. A high degree of dissociation occurred in 0.25 M CaCl2. Removal of Ca2+ before chromatographic fractionation of the preparation resulted in complete reversal of the dissociation. However, upon separation of an active, dissociated fraction from the very high molecular weight components by gel chromatography in 0.25 M CaCl2, followed by removal of Ca2+ from the fraction, no tendency toward reaggregation was seen. The apparent molecular weight of the dissociated fragment, determined by gel chromatography, is about 25,000. It is proposed that antihemophilic factor activity is associated with a molecule, of relatively low molecular weight, which in plasma or partially purified fractions is bound by electrostatic and hydrophobic bonds to a high molecular weight carrier. The activities of both dissociated and undissociated preparations were neutralized by an antibody to human antihemophilic factor. In contrast to the behavior of undissociated antihemophilic factor, the activity of the dissociated preparation was not affected by incubation with a dilute, highly purified thrombin preparation.
Kalafungin. II. Chemical transformations and the absolute configuration. (1976)

The properties of number of kalafungin derivatives and analogues are consistent with the proposed structure. The absolute stereochemistry of the three active centers was determined to be RRR by optical rotatory dispersion comparisons.
Melatonin ameliorated okadaic-acid induced Alzheimer-like lesions. (2004)

Our results suggest multiple protective functions of Mel against a series of pathological lesions known to culminate in AD, including abnormal phosphorylation of cytoskeletal proteins, microtubule disassembly and mitochondrion-initiated cell toxicity.
Non-Invasive Vagus Nerve Stimulation (nVNS) for Acute Treatment of Migraine: An Open-Label Pilot Study (S40.004) (2013)

OBJECTIVE: Assessment of a novel, non-invasive, portable VNS device for acute treatment of migraine.
[Clinical analysis of 50 cases of pulmonary complications associated with Tsutsugamushi disease]. (2002)

Pulmonary complications were common in tsutsugamushi disease. The prognosis was good if diagnosed and treated properly at an early stage.
The Second-Site Mutation in the Herpes Simplex Virus Recombinants Lacking the γ 1 34.5 Genes Precludes Shutoff of Protein Synthesis by Blocking the Phosphorylation of eIF-2α (1998)

In cells infected with the herpes simplex virus 1 (HSV-1) recombinant R3616 lacking both copies of the gamma134.5 gene, the double-stranded protein kinase R (PKR) is activated, eIF-2alpha is phosphorylated, and protein synthesis is shut off. Although PKR is also activated in cells infected with the wild-type virus, the product of the gamma134.5 gene, infected-cell protein 34.5 (ICP34.5), binds protein phosphatase 1alpha and redirects it to dephosphorylate eIF-2alpha, thus enabling sustained protein synthesis. Serial passage in human cells of a mutant lacking the gamma134.5 gene yields second-site, compensatory mutants lacking various domains of the alpha47 gene situated next to the US11 gene (I. Mohr and Y. Gluzman, EMBO J. 15:4759-4766, 1996). We report the construction of two recombinant viruses: R5103, lacking the gamma134. 5, US8, -9, -10, and -11, and alpha47 (US12) genes; and R5104, derived from R5103 and carrying a chimeric DNA fragment containing the US10 gene and the promoter of the alpha47 gene fused to the coding domain of the US11 gene. R5104 exhibited a protein synthesis profile similar to that of wild-type virus, whereas protein synthesis was shut off in cells infected with R5103 virus. Studies on the wild-type parent and mutant viruses showed the following: (i) PKR was activated in cells infected with parent or mutant virus but not in mock-infected cells, consistent with earlier studies; (ii) lysates of R3616, R5103, and R5104 virus-infected cells lacked the phosphatase activity specific for eIF-2alpha characteristic of wild-type virus-infected cells; and (iii) lysates of R3616 and R5103, which lacked the second-site compensatory mutation, contained an activity which phosphorylated eIF-2alpha in vitro, whereas lysates of mock-infected cells or cells infected with HSV-1(F) or R5104 did not phosphorylate eIF-2alpha. We conclude that in contrast to wild-type virus-infected cells, which preclude the shutoff of protein synthesis by causing rapid dephosphorylation of eIF-2alpha, in cells infected with gamma134.5(-) virus carrying the compensatory mutation, eIF-2alpha is not phosphorylated. The activity made apparent by the second-site mutation may represent a more ancient mechanism evolved to preclude the shutoff of protein synthesis.
Relative anti-caries efficacy of 1100, 1700, 2200, and 2800 ppm fluoride ion in a sodium fluoride dentifrice over 1 year (2001)

There is limited evidence from clinical trials on the dose response of sodium fluoride dentifrices at concentrations above 1100 ppm fluoride ion, with respect to caries efficacy. This randomized, double-blind study examined the anti-caries effectiveness of sodium fluoride dentifrices containing 1700 ppm, 2200 ppm and 2800 ppm fluoride ion relative to an 1100 ppm fluoride ion control. A population of 5439 elementary schoolchildren, aged 6-15 years, was recruited from an urban central Ohio area with a low fluoride content water supply (<0.3 ppm). Subjects were examined by visual-tactile and radiographic examination at baseline and after 1, 2, and 3 years of using the sodium fluoride dentifrices. Subjects were stratified according to gender, age and baseline DMFS scores derived from the visual-tactile baseline examination and randomly assigned to one of four treatment groups: 0.243% sodium fluoride (1100 ppm fluoride ion), 0.376% sodium fluoride (1700 ppm fluoride ion), 0.486% sodium fluoride (2200 ppm fluoride ion), and 0.619% sodium fluoride (2800 ppm fluoride ion). All products were formulated with the same fluoride compatible silica abrasive. Results after 1 year provided evidence of a positive sodium fluoride dose response. Compared to the 1100 ppm fluoride treatment group, the 1700 ppm fluoride treatment group had an 11.0% reduction in DMFS that was not statistically significant, while the 2200 ppm and 2800 ppm fluoride treatment groups showed statistically significant (P<0.05) reductions of 18.6% and 20.4%, respectively. The reductions in caries delivered by the higher fluoride dentifrices were present across all tooth surface types, but were most pronounced for occlusal surfaces. Results at years 2 and 3 were confounded by a concurrent fluoride rinse program, which involved portions of the study population. While the trends for the higher fluoride dentifrices observed at year 1 remained at years 2 and 3, the difference observed between treatments were substantially less and failed to reach statistical significance (P<0.05). Collectively, the data demonstrate that the 2200 ppm and the 2800 ppm fluoride treatments delivered statistically significantly greater caries efficacy than the 1100 ppm fluoride treatment. This large-scale clinical trial provides evidence of a positive statistically significant dose relationship between dental caries and sodium fluoride in a dentifrice at levels above 1100 ppm fluoride at year 1.
TNF Regulates Chemokine Induction Essential for Cell Recruitment, Granuloma Formation, and Clearance of Mycobacterial Infection (2002)

Host immunity to mycobacterial infection is dependent on the activation of T lymphocytes and their recruitment with monocytes to form granulomas. These discrete foci of activated macrophages and lymphocytes provide a microenvironment for containing the infection. The cytokine, TNF, is essential for the formation and maintenance of granulomas, but the mechanisms by which TNF regulates these processes are unclear. We have compared the responses of TNF-deficient (TNF(-/-)) and wild-type C57BL/6 mice to infection with Mycobacterium smegmatis, a potent inducer of TNF, and virulent Mycobacterium tuberculosis to delineate the TNF-dependent and -independent components of the process. The initial clearance of M. smegmatis was TNF independent, but TNF was required for the early expression of mRNA encoding C-C and C-X-C chemokines and the initial recruitment of CD11b(+) macrophages and CD4(+) T cells to the liver during the second week of infection. Late chemokine expression and cell recruitment developed in TNF(-/-) mice associated with enhanced Th1-like T cell responses and mycobacterial clearance, but recruited leukocytes did not form tight granulomas. Infection of TNF(-/-) mice with M. tuberculosis also resulted in an initial delay in chemokine induction and cellular recruitment to the liver. Subsequently, increased mRNA expression was evident in TNF(-/-) mice, but the loosely associated lymphocytes and macrophages failed to form granulomas and prevent progressive infection. Therefore, TNF orchestrates early induction of chemokines and initial leukocyte recruitment, but has an additional role in the aggregation of leukocytes into functional granulomas capable of controlling virulent mycobacterial infection.
Efficacy of the Herpes Simplex Virus 2 (HSV-2) Glycoprotein D/AS04 Vaccine against Genital HSV-2 and HSV-1 Infection and Disease in the Cotton Rat Sigmodon hispidus Model (2015)

In spite of the high health burden of genital herpes, there is still no effective intervention against the disease. The significant gap in knowledge on genital herpes pathogenesis has been further highlighted by the recent failure of GSK HSV-2 vaccine Simplirix (gD/AS04) to protect humans against HSV-2 and the surprising finding that the vaccine protected against HSV-1 genital herpes instead. In this study, we report that gD/AS04 has higher efficacy against HSV-1 compared to HSV-2 genital herpes in the novel DMPA-synchronized cotton rat model of HSV-1 and HSV-2 infection. The findings help explain the results of the Simplirix trial.
Properties of Silicon Nanoparticles:  A Molecular Dynamics Study (1996)

Constant energy molecular dynamics simulations of silicon cluster growth have been conducted for clusters up to 480 atoms using the Stillinger−Weber empirical interatomic potential. It is found that the interior atoms of the 480-atom clusters, at the temperatures used, show bulklike characteristics. The cluster binding energy has been fit to an expression that separates the surface and bulk contributions to the energy over wide temperatures and size ranges. The average surface energy of an atom was found to be independent of cluster size and of a magnitude relative to the bulk, such that all cluster sizes were stable under the conditions studied here (600 < T < 2000 K). The photon density of states is similar to bulk silicon and does not show a strong cluster size dependence. Atomic self-diffusion coefficients have been calculated and compare quite well with experimental data on self-diffusion coefficient measurements of silicon surfaces.
The Cell's Cookbook For Iron–Sulfur Clusters: Recipes For Fool's Gold? (2004)

The right ingredients: Novel biosynthetic pathways for iron–sulfur clusters (see figure) are being unraveled rapidly in the model organism Saccharomyces cerevisiae. This hot research field provides new insights into the assembly of iron–sulfur proteins as well as into the origin of life, mitochondrial evolution, and iron-storage diseases.
Diagnosis of Noncultivatable Gastroenteritis Viruses, the Human Caliciviruses (2001)

Gastroenteritis is one of the most common illnesses of humans, and many different viruses have been causally associated with this disease. Of those enteric viruses that have been established as etiologic agents of gastroenteritis, only the human caliciviruses cannot be cultivated in vitro. The cloning of Norwalk virus and subsequently of other human caliciviruses has led to the development of several new diagnostic assays. Antigen detection enzyme immunoassays (EIAs) using polyclonal hyperimmune animal sera and antibody detection EIAs using recombinant virus-like particles have supplanted the use of human-derived reagents, but the use of these assays has been restricted to research laboratories. Reverse transcription-PCR assays for the detection of human caliciviruses are more widely available, and these assays have been used to identify virus in clinical specimens as well as in food, water, and other environmental samples. The application of these newer assays has significantly increased the recognition of the importance of human caliciviruses as causes of sporadic and outbreak-associated gastroenteritis.