gebhart/patrepeval huggingface dataset:
Frequent monoallelic deletion of PTEN and its reciprocal associatioin with PIK3CA amplification in gastric carcinoma (2003)

Mutational alterations of PTEN and PIK3CA, which negatively and positively regulate PI3-kinase activity, respectively, have been observed in many types of human cancer. To explore the implication of PTEN and PIK3CA mutations in gastric tumorigenesis, we characterized the expression and mutation status of the genes in 126 gastric tissues and 15 cell lines. Expression of PTEN transcript was abnormally low in 5 of 15 (33%) cell lines and 20 of 55 (36%) primary carcinomas, whereas 0 of 71 noncancerous tissues including 16 benign tumors showed altered expression. Allelotyping analysis using an intragenic polymorphism (IVS4+109) revealed that 14 of 30 (47%) informative cases carried LOH of the gene, which is closely linked to low expression. The LOH rate was significantly higher in advanced tumors [12 of 19 (63%)] compared to early-stage tumors [2 of 11 (18%)] and more frequent in poorly differentiated tumors [9 of 13 (69%)] than well- or moderately differentiated tumors [5 of 17 (29%)]. Interestingly, however, none of the LOH tumors carried mutational disruption of the remaining allele, suggesting haploinsufficiency of PTEN in gastric tumorigenesis. Methylation studies revealed that PTEN pseudogene, but not PTEN, is methylated in cell lines and primary tumors, indicating that PTEN is not a target of epigenetic silencing in gastric cancers and that the pseudogene should be considered more carefully in methylation analysis of the PTEN promoter. Genomic amplification of PIK3CA was found in 9 of 15 (60%) cell lines and 20 of 55 (36.4%) primary tumors but in no noncancerous tissues. Furthermore, PIK3CA amplification was predominantly detected in tumors with no PTEN alterations, suggesting that mutations of PTEN and PIK3CA are mutually exclusive events in gastric tumorigenesis. Amplification of PIK3CA was strongly associated with increased expression of PIK3CA transcript and elevated levels of phospho-AKT. Collectively, our data reveal that 13 of 15 (87%) gastric cell lines and 31 of 55 (56%) primary carcinomas harbored either amplification of PIK3CA or abnormal reduction of PTEN. Mutually exclusive alterations of PTEN and PIK3CA also suggest that mutations of either gene could activate the PI3-kinase/AKT signaling pathway, which is directly linked to the malignant progression of gastric tumor cells.
Structure–Functions of HspB1 (Hsp27) (2011)

Human HspB1 (also denoted Hsp27) is a well-known member, together with alphaB-crystallin, of the small heat-shock (or stress) proteins (sHsps) (20–40 kDa). In this chapter, I describe procedures for testing the oligomeric and phosphorylation patterns of HspB1 as well as its interaction with specific partner/client polypeptides using tissue culture cells genetically modified to express different levels of this protein. The procedures have been developed in my laboratory and could be used in any well-established cellular laboratory. In addition, the different procedures presented here could be extended to test the nine other human sHsp members as well as sHsps from other species.
Formation of Active Derivatives of Glucoamylase I during the Digestion with Fungal Acid Protease and α-Mannosidase (1978)

Glucoamylase I (MW 90,000; N-terminal alanine) was selectively produced by a submerged culture of Aspergillus awamori var. kawachi as an enzyme having the ability to digest even raw starches, and was converted into a modified active glucoamylase decreasing in molecular weight during the digestion with the acid protease of the same mold strain. The modified glucoamylase (MW 83,000; N-terminal alanine plus isoleucine) was resembled to an intermediate type of glucoamylase I′, and exhibited hydrolysis curves for gelatinized potato starch and maltose in the same manner as that of glucoamylase I; but it did not digest raw starches and was not adsorbed onto cornstarch, and showed the lower hydrolysis limit of 80 percent for glycogen. The carbohydrate contents of glucoamylase I decreased 59 percent during the digestion with fungal α-mannosidase. The carbohydrate-split glucoamylase (MW 86,000; N-terminal alanine) was unstable at pH 9 or at 65°C in the same extent as glucoamylase I′, but was identical with glucoamylase I in the hydrolysis curves for various substrates, the digestibility for raw starches and the adsorbability onto cornstarch. Multiple forms of glucoamylase were observed when native glucoamylase I was degraded stepwisely with fungal acid protease and α-mannosidase.
Integrated Workflow Methodologies for Asset Teams (1998)

Abstract Developing oil and gas fields in Southeast Asia profitably can be very challenging. This is partly due to the unique and difficult geological and geophysical problems associated with the Tertiary non-marine basins so prevalent in this part of the world. These problems stem from the discontinuous nature of these reservoirs, which make log correlation difficult and seismic mapping slow and untenable. In addition, reservoirs tend to be highly faulted, and characterized more often than not by poor seismic character. Numerous recompletions, relatively low per-well yields and fast drilling rates combine to pressure asset management teams to continually generate new well locations and update reserves. The workload is immense. These and other challenges have led to the recent emphasis on workflow planning as a means by which to reduce cycle time and increase integration. Effective workflow demands the need for integrated workstation software system This paper discusses workflow planning in Southeast Asia, its problems, some solutions and implications via the use of the GeoFrame* software platform.
Immunomodulation by LFA3TIP, an LFA-3/IgG1 fusion protein: cell line dependent glycosylation effects on pharmacokinetics and pharmacodynamic markers. (1995)

LFA3TIP, a fusion protein comprised of the first extracellular domain of LFA-3 fused to the hinge, CH2, and CH3 domains of human IgG1 inhibits responses of human and non-human primate T cells in vitro. In seeking to optimize the expression efficiency to prepare large quantities of LFA3TIP for primate studies, the protein was produced in both the CHO (Chinese hamster ovary) and murine NS-0 myeloma cell lines. Although LFA3TIP derived from these cell lines performs identically in vitro in CD2 receptor binding and T cell assays, examination of a pharmacodynamic marker-the reduction in CD2+ lymphocyte numbers-following the administration of equal doses of NS-0 or CHO derived LFA3TIP to baboons, suggested that the effect of the NS-0 derived material was less sustained. Pharmacokinetic analysis of the materials in baboons and mice shows that LFA3TIP produced by NS-0 cells is rapidly cleared from circulation relative to the product derived from CHO cells. The disparate clearance profiles correlate with distinct glycosylation patterns, with LFA3TIP derived from NS-0 cells being less extensively sialylated than that from CHO cells due in part to alpha-galactosyl capping of selected lactosamine moieties in the N-linked glycans of NS-0 derived LFA3TIP. Moreover, enzymatic desialylation of CHO derived LFA3TIP results in a glycoprotein with an evanescent serum profile when administered to mice and baboons. These results correlate the extent of N-acetylneuraminic acid capping with the clearance rates of LFA3TIP derived from the two distinct cell lines, and underscore the importance of evaluating glycosylation dependent PK parameters when choosing production cell lines for recombinant immunotherapeutics.
Preparation and characterization of murine monoclonal antibodies to swine lymphocyte antigens. (1988)

A panel of monoclonal antibodies (mAb) was developed by the fusion of Sp2/0 myeloma cells and spleen cells from mice immunized with peripheral blood mononuclear cells (PMNC) or T cells from NIH swine leucocyte antigen (SLA) inbred miniature swine. Twenty stable hybridoma clones were isolated that secreted mAb that reacted with swine PMNC, as determined by an enzyme-linked immunosorbent assay (ELISA). The binding profile to swine PMNC and the ability to fix complement of these mAb were investigated by flow cytometric analyses. The molecular weights of the antigens recognized by six of the mAb were determined by immunoprecipitation of 125I surface-labelled PMNC, followed by SDS-PAGE under reducing conditions. The most interesting mAb, 7-34-1 (IgG2a), precipitated a putative MHC class I molecule composed of a 50,000 MW heavy chain and a 12,000 MW light chain (beta 2m). This is the third SLA class I-reactive monoclonal antibody to be described for swine. Properties of the mAb described in this paper, mAb 7-34-1, are different from the two other SLA class I-specific mAb that have been described elsewhere in the literature (mAb 74-11-10 and mAb PT85). Monoclonal antibody 7-34-1 recognized class I antigens of SLA haplotypes a, c and d in an equivalent manner. This mAb should be especially useful as a general anti-SLA class I reagent for experiments on NIH miniature swine.
Neuroprotective and Neurotrophic Efficacy of Phytoestrogens in Cultured Hippocampal Neurons (2002)

Epidemiological data from retrospective and case-control studies have indicated that estrogen replacement therapy (ERT) can decrease the risk of developing Alzheimer's disease. In addition, ERT has been found to promote cellular correlates of memory and to promote neuronal survival both in vivo and in vitro. Phytoestrogens have been proposed as potential alternatives to ERT. To determine whether phytoestrogens exert estrogen agonist effect in neural tissue, investigations of neuroprotective and neurotrophic efficacy of phytoestrogens were conducted. Six phytoestrogens, genistein, genistin, daidzein, daidzin, formononetin, and equol, were tested for their neuroprotective efficacy against two toxic insults, glutamate excitotoxicity and beta-amyloid(25-35). Neuronal membrane damage was quantitatively measured by lactate dehydrogenase (LDH) release, and neuronal mitochondrial viability was determined by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromid (MTT) assay. Results of these studies demonstrated that all phytoestrogens induced a modest but significant reduction in LDH release following exposure to glutamate and beta-amyloid(25-35). In contrast, none of phytoestrogens induced a significant increase in reduced MTT levels, which occurred in the presence of a full estrogen agonist, 17beta-estradiol. Analysis of the neurotrophic potential of genistein and daidzein, two phytoestrogens that exerted a significant reduction in LDH release, demonstrated that neither of these molecules promoted hippocampal neuron process outgrowth. Results of these analyses indicate that although phytoestrogens exert a neuroprotective effect at the plasma membrane, they do not sustain neuron mitochondrial viability nor do they induce cellular correlates of memory as neurite outgrowth and synaptogenesis are putative mechanisms of memory. Data derived from these investigations would predict that phytoestrogens could exert some neuroprotective effects analogous to that of antioxidants, but that these molecules are not functional equivalents to endogenously active 17beta-estradiol or to estrogen replacement formulations and, therefore, would raise the concern that they may not reduce the risk of Alzheimer's disease or sustain memory function in postmenopausal women.
ABC Transporters and Azole Susceptibility in Laboratory Strains of the Wheat Pathogen Mycosphaerella graminicola (2002)

Laboratory strains of Mycosphaerella graminicola with decreased susceptibilities to the azole antifungal agent cyproconazole showed a multidrug resistance phenotype by exhibiting cross-resistance to an unrelated chemical, cycloheximide or rhodamine 6G, or both. Decreased azole susceptibility was found to be associated with either decreased or increased levels of accumulation of cyproconazole. No specific relationship could be observed between azole susceptibility and the expression of ATP-binding cassette (ABC) transporter genes MgAtr1 to MgAtr5 and the sterol P450 14alpha-demethylase gene, CYP51. ABC transporter MgAtr1 was identified as a determinant in azole susceptibility since heterologous expression of the protein reduced the azole susceptibility of Saccharomyces cerevisiae and disruption of MgAtr1 in one specific M. graminicola laboratory strain with constitutive MgAtr1 overexpression restored the level of susceptibility to cyproconazole to wild-type levels. However, the level of accumulation in the mutant with an MgAtr1 disruption did not revert to the wild-type level. We propose that variations in azole susceptibility in laboratory strains of M. graminicola are mediated by multiple mechanisms.
(B1) Candida and Mycotic Infections (2006)

Oral candidiasis (OC) is the most common mucosal manifestation of HIV infection. This workshop examined OC and other mycoses associated with HIV infection. Historically, blood CD4 cell numbers were the primary prognosticator for the development of OC. However, a study that statistically evaluated the predictive role of HIV viral load vs. CD4 cell counts revealed viral load to be a stronger predictor for OC. The role of biofilms and antifungal resistance in recalcitrant OC is unclear at present. In general, micro-organisms including yeasts in biofilms are more resistant to antifungals than their planktonic counterparts. When the remaining organisms are eliminated, the few resistant organisms may not be problematic, because they are present in low numbers. Unusual exotic mycoses in HIV-infected patients are more common in patients from the developing than the developed world. These infections may be recurrent and recalcitrant to therapy, be present in multiple and uncommon sites, increase with the progression of HIV disease, and may play a role similar to that of the more common mycoses. Typing and subtyping of yeasts are probably not critical to the clinical management of candidiasis caused by Candida albicans and non-albicans strains, including C. dubliniensis, because it is responsive to antifungal therapy. C. glabrata is probably the only exception. The presence of oral thrush in infants younger than 6 months of age is associated with an increased post-natal transmission risk of HIV infection. Thus, perinatal retroviral therapy should be combined with the treatment of oral thrush to prevent the post-natal acquisition of HIV.
CYCLINACS: NOVEL FAST-CYCLING ACCELERATORS FOR HADRONTHERAPY (2007)

A cyclinac is a high-gradient linac which, driven by a large-current cyclotron, produces the low hadron currents needed for tumour treatments.. For about 15 years TERA has been developing high-frequencies (3 GHz) and thus high-gradient structures. This paper introduces these novel fast-cycling accelerators, illustrates their advantages with respect to cyclotrons and synchrotrons - in particular for the treatment of moving organs - and describes two applications: IDRA for protontherapy and CABOTO for carbon ion therapy.
[Serum glutathione S-transferase in bromobenzene-induced acute hepato-toxicity in mice]. (2001)

The activity of serum glutathione S-transferase (GST) was tested in bromobenzene-induced acute hepatotoxicity in mice. The data showed that a lot of small local necrosis in liver biopsy was observed and serum GST activity was increased after 2 h of treatment with bromobenzene (150 mg/kg i.p.) in mice. Serum alanine transaminase (ALT) activity was also gradually enhanced after 8 hours of treatment. The most obvious changes were at 16 hours of bromobenzene treatment, and serum GST activity was firstly restored to normal level after 24 hours of treatment. There were good positive correlations between serum GST, ALT, as well as serum GST and the changes on liver biopsy. Evaluating analysis of the diagnosis test showed that the sensitivity, specificity and accuracy was 89%, 75% and 82% in serum GST test, and 39%, 92% and 64% in serum ALT test respectively. The ROC work curve also demonstrated that serum GST was more sensitive and specific than serum ALT.
Transition metal‐mediated glycoxidation accelerates cross‐linking of β‐amyloid peptide (2000)

beta-Amyloid deposits, hallmarks of Alzheimer's disease, contain both sugar-derived 'advanced glycation end products' (AGEs) and copper and iron ions. Our in vitro experiments using synthetic beta-amyloid peptide and glucose or fructose show that formation of covalently cross-linked high-molecular-mass beta-amyloid peptide oligomers is accelerated by micromolar amounts of copper (Cu+, Cu2+) and iron (Fe2+, Fe3+) ions. Formation of these covalent AGE cross-links can be inhibited by capping agents of amino groups, redox-inactive metal chelators and antioxidants, suggesting that these drugs may be able to slow down the formation of insoluble beta-amyloid deposits in vivo and possibly the progression of Alzheimer's disease.
Biological effects of low level laser therapy. (2014)

The use of low level laser to reduce pain, inflammation and edema, to promote wound, deeper tissues and nerves healing, and to prevent tissue damage has been known for almost forty years since the invention of lasers. This review will cover some of the proposed cellular mechanisms responsible for the effect of visible light on mammalian cells, including cytochrome c oxidase (with absorption peaks in the Near Infrared (NIR)). Mitochondria are thought to be a likely site for the initial effects of light, leading to increased ATP production, modulation of reactive oxygen species, and induction of transcription factors. These effects in turn lead to increased cell proliferation and migration (particularly by fibroblasts).
Traffic Incident Detection Using Multiple-Kernel Support Vector Machine (2012)

This paper presents applications of the multiple-kernel learning support vector machine (MKL-SVM) in traffic incident detection. The standard SVM was applied in traffic incident detection and achieved good results. However, the results depended greatly on the kernel function and parameters, and choosing the appropriate ones for the SVM was a procedure of trial and error. Unlike the SVM, the MKL-SVM used a convex combination of basic kernel functions instead of a single basic kernel function to construct an adaptive SVM model. This adaptive model could improve average performance in traffic incident detection just by randomly selecting the kernel function and parameters. As a result, the MKL-SVM avoided the burden of choosing the appropriate kernel function and parameters. The SVM ensemble algorithm trained many individual SVM classifiers to construct the classifier ensemble and then used this classifier ensemble to detect traffic incidents. Consequently, training occurred many times. Compared with the SVM ensemble algorithm, the training time cost of the MKL-SVM was much lower because training occurred only once. Extensive experiments were performed to evaluate the performance of three algorithms: standard SVM, SVM ensemble, and MKL-SVM. The experimental results showed that the performance of the MKL-SVM was much better than that of the standard SVM and slightly better than the SVM ensemble. More important, the performance of the MKL-SVM was stable.
Antibody-Independent, CD4 + T-Cell-Dependent Protection against Pneumococcal Colonization Elicited by Intranasal Immunization with Purified Pneumococcal Proteins (2007)

ABSTRACT Immunity to pneumococcal colonization in mice by exposure to live or killed pneumococci has been shown to be antibody independent but dependent on CD4 + T cells. Here we show that intranasal immunization with pneumococcal proteins (pneumococcal surface protein C, adhesin A, and a pneumolysoid) can elicit a similar mechanism of protection. Colonization could be significantly reduced in mice congenitally deficient in immunoglobulins after intranasal immunization with this mixture of proteins; conversely, the depletion of CD4 + T cells in immunized wild-type mice at the time of challenge eliminated the protection afforded by immunization. Overall, our results show that intranasal immunization with a mixture of pneumococcal proteins protects against colonization in an antibody-independent, CD4 + T-cell-dependent manner.
Label-Free Imaging of Female Genital Tract Melanocytic Lesions With Pump-Probe Microscopy: A Promising Diagnostic Tool (2017)

Pump-probe microscopy provides unique information regarding the biochemical composition of genital tract melanocytic lesions, which can be used to improve the diagnosis and staging of vulvar melanomas.
cDNA to chick lumican (corneal keratan sulfate proteoglycan) reveals homology to the small interstitial proteoglycan gene family and expression in muscle and intestine. (1992)

A 1.9-kb cDNA clone to chick lumican (keratan sulfate proteoglycan) was isolated by screening an expressing vector library made from chick corneal RNA with antiserum to chick corneal lumican. The cDNA clone contained an open reading frame coding for a 343-amino acid protein, Mr = 38,640. Structural features of the deduced sequence include: a 18-amino acid signal peptide, cysteine residues at the N- and C-terminal regions, and a central leucine-rich region (comprising 62% of the protein) containing nine repeats of the sequence LXXLXLXXNXL/I, where X represents any amino acid. Lumican contains three variations of this sequence that are tandemly linked to form a unit and three units tandemly linked to form the leucine-rich region. The sequential arrangement of these repeats and their spacing suggest that this region arose by duplication. The deduced sequence shows five potential N-linked glycosylation sites, four of which are in the leucine-rich region. These sites are also potential keratan sulfate attachment sites. The cDNA clone to lumican hybridizes to a 2.0-kb mRNA found in tissues other than cornea, predominantly muscle and intestine. Radiolabeling and immunoprecipitation studies show that lumican core protein is also synthesized by these tissues. The primary structure of lumican is similar to fibromodulin, decorin, and biglycan, which indicates it belongs to the small interstitial proteoglycan gene family. The expression of lumican in tissues other than cornea indicates a broader role for lumican besides contributing to corneal transparency.
Reversal of Visual Neglect in Parkinson's Disease by Treatment with Picotesla Range Magnetic Fields (1993)

Visual neglect and impairment in perceptual motor or visuospatial tasks are among the most frequently encountered abnormalities in neuropsychological testing of patients with Parkinson's disease, being present in up to 90% of patients. It has been proposed that neglect reflects an attentional-arousal deficit induced by lesions that interrupt a cortical-limbic-reticular loop. Recently, we have reported that application of extracranial magnetic fields (MF) in the picoTesla range was efficacious in reducing the severity of the motor disability of Parkinsonism as well as improving some of the cognitive abnormalities associated with the disease such as visuoperceptive deficits. We now present a 61 year old fully medicated Parkinsonian patient in whom rapid reversal of left visual neglect as well as improvement in visuoconstructional (drawing) performance was noted immediately after a single external application of MF. We propose that this effect was related to enhancement of directed attention through a mechanism involving an interaction between the pineal gland, which is considered a "magnetosensor," and the reticular formation which mediates arousal and attention. This report demonstrates the efficacy of extremely weak MF in reversing some of the cognitive abnormalities in Parkinsonism, notably neglect and visuoperceptive deficits, which contribute significantly to impairment of the patient's daily living activities.