gebhart/patrepeval huggingface dataset:
Deletions of chromosome 3p are frequent and early events in the pathogenesis of uterine cervical carcinoma. (1997)

To study the molecular abnormalities involved in the multistage development of cervical carcinoma (CC), we investigated the presence of oncogenic human papillomavirus (HPV) sequences, loss of heterozygosity (LOH), and microsatellite alterations at several genes/loci at 3p (3p14.2 at the FHIT gene, 3p14.3-21.1, 3p21, and 3p22-24.2), 9p21, RB and P53, and P53 gene point mutations in precisely microdissected archival tissues from 20 CCs and their accompanying precursor lesions (cervical intraepithelial neoplasia, CIN; n = 40) and normal epithelia (n = 20). In all HPV-positive cases (90% of CCs), HPV sequences were detected as the earliest appearing molecular change or simultaneously with other changes. LOH at any 3p region was found in 70% of CCs, and 3p14.2 (FHIT gene/FRA3B fragile site) (56%) and 3p21 (57%) were the most frequent 3p sites of loss. LOH at some 3p region was in the CIN I stage, and the 3p deletions in precursor CIN lesions were smaller than the 3p losses found in the associated invasive CC. LOH at the other regions studied and P53 gene mutations were less frequent and later events. Microsatellite alterations were detected in 35% of CCs, and identical abnormalities were detected in the associated precursor lesions. Although infection with oncogenic HPV strains is the earliest and most frequent molecular event, progressive deletions at one or more 3p regions (particularly at 3p14.2, and 3p21) are also frequent events occurring early in the pathogenesis of CC.
Her-2/neu expression in node-negative breast cancer: direct tissue quantitation by computerized image analysis and association of overexpression with increased risk of recurrent disease. (1993)

The HER-2/neu proto-oncogene (also known as c-erb B-2) is homologous with, but distinct from, the epidermal growth factor receptor. Amplification of this gene in node-positive breast cancers has been shown to correlate with both earlier relapse and shorter overall survival. In node-negative breast cancer patients, the subgroup for which accurate prognostic data could make a significant contribution to treatment decisions, the prognostic utility of HER-2/neu amplification and/or overexpression has been controversial. The purpose of this report is to address the issues surrounding this controversy and to evaluate the prognostic utility of overexpression in a carefully followed group of patients using appropriately characterized reagents and methods. In this report we present data from a study of HER-2/neu expression designed specifically to test whether or not overexpression is associated with an increased risk of recurrence in node-negative breast cancers. From a cohort of 704 women with node-negative breast cancer who experienced recurrent disease (relapsed cases) 105 were matched with 105 women with no recurrence (disease-free controls) after the equivalent follow-up period. Immunohistochemistry was used to assess HER-2/neu expression in archival tissue blocks from both relapsed cases and their matched disease-free controls. Importantly, a series of molecularly characterized breast cancer specimens were used to confirm that the antibody used was of sufficient sensitivity and specificity to identify those cancers overexpressing the HER-2/neu protein in this formalin-fixed, paraffin-embedded tissue cohort. In addition, a quantitative approach was developed to more accurately assess the amount of HER-2/neu protein identified by immunostaining tumor tissue. This was done using a purified HER-2/neu protein synthesized in a bacterial expression vector and protein lysates derived from a series of cell lines, engineered to express a defined range of HER-2/neu oncoprotein levels. By using cells with defined expression levels as calibration material, computerized image analysis of immunohistochemical staining could be used to determine the amount of oncoprotein product in these cell lines as well as in human breast cancer specimens. Quantitation of the amount of HER-2/neu protein product determined by computerized image analysis of immunohistochemical assays correlated very closely with quantitative analysis of a series of molecularly characterized breast cancer cell lines and breast cancer tissue specimens.(ABSTRACT TRUNCATED AT 400 WORDS)
Self-Attention Graph Pooling (2019)

Advanced methods of applying deep learning to structured data such as graphs have been proposed in recent years. In particular, studies have focused on generalizing convolutional neural networks to graph data, which includes redefining the convolution and the downsampling (pooling) operations for graphs. The method of generalizing the convolution operation to graphs has been proven to improve performance and is widely used. However, the method of applying downsampling to graphs is still difficult to perform and has room for improvement. In this paper, we propose a graph pooling method based on self-attention. Self-attention using graph convolution allows our pooling method to consider both node features and graph topology. To ensure a fair comparison, the same training procedures and model architectures were used for the existing pooling methods and our method. The experimental results demonstrate that our method achieves superior graph classification performance on the benchmark datasets using a reasonable number of parameters.
Contributing Factors to Surgical Site Infections (2012)

Surgical site infections (SSIs) are the most common nosocomial infections. These complications lead to revision surgery, delayed wound healing, increased use of antibiotics, and increased length of hospital stay, all of which have a significant impact on patients and the cost of health care. Such intraoperative factors as proper skin preparation, adherence to sterile technique, surgical duration, and traffic in the operating room contribute more to SSIs than do patient-related risk factors such as diabetes mellitus, obesity, and preexisting colonization with methicillin-resistant Staphylococcus aureus. Surgeons have a responsibility to understand the current evidence regarding the factors that affect the rates of SSIs so as to provide the highest level of patient care.
Recombinant Human Bone Morphogenetic Protein-2 Binding and Incorporation in PLGA Microsphere Delivery Systems (1999)

The objective of this research was to determine the binding capacity and kinetics, and total incorporation of recombinant human bone morphogenetic protein-2 (rhBMP-2) in microspheres made from hydrophilic and hydrophobic poly(lactide-co-glycolide) (PLGA). Polymers were characterized by molecular weight, polydispersity, and acid number. Microspheres were produced via a water-in-oil-in-water double emulsion system and characterized for bulk density, size, specific surface area, and porosity. Protein concentrations were determined by reversed phase HPLC. Protein was loaded by soaking microspheres in a buffered solution, pH 4.5, of rhBMP-2, decanting excess liquid, and vacuum drying the wetted particles. Total loading and binding were determined by comparing protein concentration remaining to non-microsphere containing samples. Polymer acid number was the dominant polymer feature affecting the binding. Higher acid values correlated with increased rhBMP-2 binding. The amount of non-bound incorporated rhBMP-2 linearly correlated with the concentration of protein used in binding. High rhBMP-2 concentrations inhibit binding to PLGA microspheres. Binding was also inhibited by increased lactide content in the PLGA polymer. The polymer characteristics controlling rhBMP-2 binding to PLGA microspheres are acid value foremost followed by molecular weight and lactide/glycolide ratio. The total amount of rhBMP-2 incorporated depends on the bound amount and on the amount of free protein present.
Localization and Characterization of the Calsequestrin-binding Domain of Triadin 1 (2000)

Triadin is an integral membrane protein of the junctional sarcoplasmic reticulum that binds to the high capacity Ca(2+)-binding protein calsequestrin and anchors it to the ryanodine receptor. The lumenal domain of triadin contains multiple repeats of alternating lysine and glutamic acid residues, which have been defined as KEKE motifs and have been proposed to promote protein associations. Here we identified the specific residues of triadin responsible for binding to calsequestrin by mutational analysis of triadin 1, the major cardiac isoform. A series of deletional fusion proteins of triadin 1 was generated, and by using metabolically labeled calsequestrin in filter-overlay assays, the calsequestrin-binding domain of triadin 1 was localized to a single KEKE motif comprised of 25 amino acids. Alanine mutagenesis within this motif demonstrated that the critical amino acids of triadin binding to calsequestrin are the even-numbered residues Lys(210), Lys(212), Glu(214), Lys(216), Gly(218), Gln(220), Lys(222), and Lys(224). Replacement of the odd-numbered residues within this motif by alanine had no effect on calsequestrin binding to triadin. The results suggest a model in which residues 210-224 of triadin form a beta-strand, with the even-numbered residues in the strand interacting with charged residues of calsequestrin, stabilizing a "polar zipper" that links the two proteins together. This small, highly charged beta-strand of triadin may tether calsequestrin to the junctional face membrane, allowing calsequestrin to sequester Ca(2+) in the vicinity of the ryanodine receptor during Ca(2+) uptake and Ca(2+) release.
MicroRNA miR-29 Modulates Expression of Immunoinhibitory Molecule B7-H3: Potential Implications for Immune Based Therapy of Human Solid Tumors (2009)

B7-H3, a surface immunomodulatory glycoprotein, inhibits natural killer cells and T cells. The monoclonal antibody (mAb) 8H9 is specific for 4Ig-B7-H3, the long and principal form of B7-H3. Early results from radioimmunotherapy using 8H9 have shown promise in patients with metastatic solid tumors to the central nervous system. Whereas B7-H3 transcript was ubiquitously expressed in a wide spectrum of human solid tumors as well as human normal tissues, B7-H3 protein was preferentially expressed only in tumor tissues. By quantitative reverse transcription-PCR, all three isoforms of microRNA miR-29 (a, b, and c) were highly expressed in normal tissues. However, they were down-regulated in a broad spectrum of solid tumors, including neuroblastoma, sarcomas, brain tumors, and tumor cell lines. B7-H3 protein expression was inversely correlated with miR-29 levels in both cell lines and tumor tissues tested. Using luciferase reporter assay, miR-29a was shown to directly target B7-H3 3' untranslated region, and knock-in and knockdown of miR-29a led to down-regulation and up-regulation, respectively, of B7-H3 protein expression. The ability of miR-29 to control B7-H3 protein expression has implications in immune escape by solid tumors. Differential modulation of this key immunoinhibitory molecule in tumor versus normal tissues may advance both cell-mediated immunotherapy and antibody-based targeted strategies using the B7-H3-specific mAb 8H9.
Generation and biochemical characterization of glycoPEGylated factor VIIa derivatives (2008)

Prophylaxis with 2-4 times weekly dosing of factor (F)VIII or FIX is established as an efficacious and safe treatment in haemophilia. Although prophylaxis is not readily available for the inhibitor patient, recent studies have demonstrated a reduction in bleeding episodes in inhibitor patients treated with daily infusions of FVIIa. In order to develop a treatment option comparable to prophylaxis with FVIII or FIX we looked to PEGylation which is an established method for prolonging the circulatory half-life of proteins. However, due to the numerous interactions of FVIIa with the cell surface, TF, FIX and FX there are limited options for unspecific chemical modification of FVIIa without loss of activity. Consequently, we explored the GlycoPEGylationtrade mark technology for selective PEGylation of the two N-glycans in the FVIIa light chain and protease domain to generate seven specifically modified derivatives with PEG groups ranging from 2 to 40 kDa. These derivatives were evaluated in vitro for their ability to interact with small synthetic substrates as well as key molecules relevant to function in the coagulation pathway. The results demonstrate that modification of FVIIa using glycoPEGylation has only a very limited effect on the hydrolysis S-2288 and FX activation. However, the modification does to some extend alter the ability of FVIIa to interact with TF and more importantly, reduces the rate of ATIII inhibition by up to 50% which could allow for an extended active half-life in circulation.
THE BIOCHEMISTRY OF P-GLYCOPROTEIN-MEDIATED MULTIDRUG RESISTANCE (1989)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More
Lysosomal Acid Lipase Deficiency: Correction of Lipid Storage by Adenovirus-Mediated Gene Transfer in Mice (2002)

Lysosomal acid lipase (LAL) is the essential enzyme for hydrolysis of triglycerides (TGs) and cholesteryl esters (CEs) in lysosomes. Its deficiency produces two human phenotypes: Wolman disease (WD) and cholesteryl ester storage disease (CESD). The LAL null (lal(-/-)) mouse mimicks aspects of human WD and CESD. The potential for gene therapy of LAL deficiency was tested with first-generation adenoviral vectors containing human LAL cDNA (Ad-hLAL) by intravenous injection into lal(-/-) mice. Compared with phosphate-buffered saline-injected controls, the mice receiving Ad-hLAL had increased hepatic LAL activity, decreased hepatomegaly, and normalization of histopathology. hLAL protein and mRNA were detected by immunohistochemical staining and in situ hybridization in hepatic parenchymal and sinusoid lining cells, splenic sinusoidal cells, lung macrophages, and adrenal cortical cells. Mice showed TG reductions in liver, spleen, and small intestine of 68, 54, and 50%, respectively, and cholesterol reductions of 55, 52, and 34%, respectively, at 20 days postinjection. These studies provide the basis for the use of gene therapy, in the form of gene transfer via intravenously administered adenovirus, to correct deficiency states, such as WD and CESD, and histopathology of a variety of tissues.
Amplification of Inflammation in Emphysema and its Association with Latent Adenoviral Infection (2001)

This study examines the hypothesis that the cigarette smoke-induced inflammatory process is amplified in severe emphysema and explores the association of this response with latent adenoviral infection. Lung tissue from patients with similar smoking histories and either no (n = 7), mild (n = 7), or severe emphysema (n = 7) was obtained by lung resection. Numbers of polymorphonuclear cells (PMN), macrophages, B cells, CD4, CD8 lymphocytes, and eosinophils present in tissue and airspaces and of epithelial cells expressing adenoviral E1A protein were determined using quantitative techniques. Severe emphysema was associated with an absolute increase in the total number of inflammatory cells in the lung tissue and airspaces. The computed tomography (CT) determined extent of lung destruction was related to the number of cells/m(2) surface area by R(2) values that ranged from 0.858 (CD8 cells) to 0.483 (B cells) in the tissue and 0.630 (CD4 cells) to 0.198 (B cells) in the airspaces. These changes were associated with a 5- to 40-fold increase in the number of alveolar epithelial cells expressing adenoviral E1A protein in mild and severe disease, respectively. We conclude that cigarette smoke-induced lung inflammation is amplified in severe emphysema and that latent expression of the adenoviral E1A protein expressed by alveolar epithelial cells influenced this amplification process.
On-Column Ion-Exchange Preconcentration of Inorganic Anions in Open Tubular Capillary Electrochromatography with Elution Using Transient-Isotachophoretic Gradients. 3. Implementation and Method Development (2002)

A solid-phase extraction method based on an ion-exchange retention mechanism has been used for in-line preconcentration of inorganic anions prior to their separation by capillary electrophoresis (CE). A single capillary containing a preconcentration and a separation zone has been used in a commercial CE instrument without instrumental modification. Analyte anions were retained on a preconcentration zone comprising an adsorbed layer of cationic latex particles, while separation was achieved in a separation zone comprising fused silica modified by adsorption of a cationic polymer. Elution of the adsorbed analytes was achieved using an eluotropic gradient formed by a transient isotachophoretic boundary between a fluoride electrolyte and a naphthalenedisulfonate electrolyte. Optimization of the electrolyte concentrations, sample injection times, and back-flushing times allowed the successful separation of sub-ppb levels of inorganic anions using a 100-min injection at 2 bar pressure, introducing over 40 capillary volumes of sample. A method based on a 10-min injection allowed a 100-fold increase in sensitivity over conventional hydrodynamic injection for Br-, I-, NO3-, CrO4(2-), and MoO4(2-) with a total analysis time of 25 min. Detection limits were dependent on the injection time but were in the range 2.2-11.6 ppb for a 10-min injection time. This approach was used to determine NO3- in Antarctic ice cores where the analysis could be performed using a sample volume 100 times less than that used for ion chromatography.
Chirp reduction of directly modulated semiconductor lasers at 10 Gb/s by strong CW light injection (1994)

The influence of strong light injection on the reduction of the dynamical linewidth broadening of directly current-modulated semiconductor lasers at high bit rates is theoretically investigated and experimentally verified for 10 Gb/s NRZ pseudorandom modulation with a large current swing of 40 mA pp. Significant chirp reduction and single-mode operation are observed for bulk DFB, quantum well DFB lasers at 10 Gb/s and a weakly coupled bulk DFB laser at 8 Gb/s, so that an improvement of the transmission performance using standard monomode fibers in the 1.55 /spl mu/m low-loss wavelength region can be achieved for all these laser types, where dispersion otherwise causes severe penalties for long-haul transmission. The properties of injection-locked bulk DFB and quantum well DFB lasers with respect to high bit rate modulation have been systematically studied by the use of the rate equation formalism. A dynamically stable locking range of more than 30 GHz under modulation has been found for both laser types with injection ratios higher than 0.5.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Cytokine disturbances in systemic lupus erythematosus (2011)

The pathogenesis of systemic lupus erythematosus (SLE) is complex, and the resulting disease manifestations are heterogeneous. Cytokine dysregulation is pervasive, and their protein and gene expression profiles may serve as markers of disease activity and severity. Importantly, biologic agents that target specific cytokines may represent novel therapies for SLE. Four cytokines (IL-6, TNFα, IFNα, and BLyS) are being evaluated as therapeutic targets in SLE. The present review will examine the roles of each of these cytokines in murine and human SLE, and will summarize results from clinical trials of agents that target these cytokines.
Monoclonal antibodies to Fc receptors for IgG on human mononuclear phagocytes. Antibody characterization and induction of superoxide production in a monocyte cell line. (1986)

We have utilized monoclonal antibodies against the two IgG Fc receptors (p40 and p72) of U937 cells to stimulate the release of superoxide. The monoclonal antibody (mAb) specific for p40 (IV3) has been described elsewhere. A murine IgG1 mAb specific for the high affinity p72 Fc receptor (designated mAb FcR32 or simply mAb 32) bound to the same p72 precipitated by Sepharose-human IgG as shown by preclearing experiments and by identical isoelectric focussing patterns. Binding of mAb 32 to p72 was independent of the Fc region of the antibody since Fab' fragments of mAb 32 affinity adsorbed p72. The binding of both mAb 32 and human IgG1 to the intact U937 cell was not reciprocally inhibitory, indicating that mAb 32 does not interfere with the ligand binding site of p72. mAb 32 bound to human monocytes, U937, and HL60 cells, but not to granulocytes or lymphocytes. U937 cells cultured in gamma-interferon and 1,25-dihydroxycholecalciferol generated superoxide when incubated with mAb 32 or IV3 followed by cross-linking with F(ab')2 anti-murine Ig. Incubation with mAb 32 or IV3 alone or with 3 of 5 other anti-U937 mAbs cross-linked with anti-murine Ig did not result in superoxide generation. Immune complex-mediated superoxide production was inhibited 80% by IgG, but not by mAb 32 or IV3.
Porcine coronary arteries with regenerated endothelium have a reduced endothelium-dependent responsiveness to aggregating platelets and serotonin. (1987)

To test the ability of regenerated endothelium to evoke endothelium-dependent relaxations, male Yorkshire pigs underwent balloon endothelial denudation of the proximal left anterior descending coronary artery. Endothelium-dependent responses were examined in vitro, in rings of coronary segments taken from the denuded area or from the proximal left circumflex coronary artery. The experiments were performed 8 days or 4 weeks after the denudation. Endothelial regrowth was confirmed by histologic examination 8 days after the denudation and by demonstrating the presence of endothelium-dependent relaxations to bradykinin; at that time aggregating platelets evoked normal endothelium-dependent responses. However, 4 weeks after the denudation, the relaxations to aggregating platelets were markedly depressed although continuous endothelial lining was present, and the endothelium-dependent responses to bradykinin, adenosine diphosphate, the Ca2+-ionophore A23187, platelet activating factor, and thrombin were unaltered. Four weeks after denudation, endothelium-dependent relaxations to serotonin were depressed. Higher concentration of serotonin induced endothelium-dependent contractions in quiescent rings with regenerated endothelium, suggesting that regenerated endothelial cells may produce endothelium-derived constricting factor(s) and release less endothelium-derived relaxing factor(s) when exposed to the monoamine. The endothelium-dependent relaxation to serotonin was not reduced by the S2-serotonergic antagonist ketanserin but prevented by the combined S1- and S2-serotonergic blocker methiothepin. The platelet-induced relaxation was due to released serotonin and adenine nucleotides in control left circumflex coronary arteries, but in left anterior descending coronary artery with regenerated endothelium, it was due solely to the latter. The platelet-induced contractions were due to activation of receptors on the smooth muscle cells. Four weeks after denudation, regenerated endothelial cells were morphologically different from native cells; they were elongated and cuboidal, and the number of the cells had increased twofold. At this state, eccentric myointimal thickening was present in the previously denuded portion. These experiments indicate that the protective role of endothelial cells against the vasoconstriction induced by aggregating platelets is depressed in the chronic regenerated state. A lack of responsiveness to serotonin appears to be the cause for the endothelial dysfunction.
High Vaginal Concentrations of Atopobium vaginae and Gardnerella vaginalis in Women Undergoing Preterm Labor (2009)

III.