gebhart/patrepeval huggingface dataset:
Comparison of the genomic organization of Kirsten and Harvey sarcoma viruses (1978)

Current studies were undertaken to compare the genomes of Kirsten murine sarcoma virus (Ki-MuSV), Harvey murine sarcoma virus (Ha-MuSV), and the replication-defective endogenous rat virus to understand the function of these viral RNAs. Genome organization and sequence homology were studied by fingerprinting large RNase T1-resistant oligonucleotides and by cross-protecting homologous oligonucleotides against RNase A and T1 digestion with complementary DNA prepared from each of the other viral RNA. Ki-MuSV and Ha-MuSV were found to share an extensive series of rat-derived oligonucleotides begining ca. 1 kilobase (kb) from the 3' end and extending to within 1.5 kb of the 5'end of Ki-MuSV RNA. The total map distance covered in ca. 5.5 kb. The eight oligonucleotides covering the 1.5 kb at the 5' end of Ki-MuSV RNA were not found in Ha-MuSV RNA. Five out of these eight oligonucleotides, however, could be designated with certainty to be of rat virus origin. Since Ha-MuSV is 6.5 kb in size and Ki-MuSV is 8 kb in size, the major difference between them is the 1.5 kb from the replication-defective endogenous rat virus sequences at the 5' end of Ki-MuSV not present in Ha-MuSV. Consistent with the difference in the genome structure, these two sarcoma viral RNA'S yielded distinct major translation products in cell-free systems, I.E., A 50,000-dalton polypeptide (P50) from Ki-MuSV and a 22,000-dalton polypeptide (p22) from Ha-MuSV. These polypeptides may provide the necessary protein makers for identifying in vivo virus-coded proteins.
Primary structure determination of mono‐ and diacylglycerol lipase from Penicillium camembertii (1993)

The complete amino acid sequence of mono- and diacylglycerol lipase from Penicillium camembertii was determined. This lipase has a single polypeptide chain consisting of 276 amino acid residues with two disulfide linkages. The primary structure was revealed by sequencing the digests of the intact and S-pyridylethylated proteins by trypsin, endoproteinase Lys-C and V8 protease. The two-dimensional electrophoresis was also carried out to confirm the internal sequence. The catalytic triad of this lipase was Ser, Asp and His, and one potential N-glycosylation site was also revealed.
Comparison of tumor mutational burden (TMB) across tumor tissue and circulating tumor DNA (ctDNA). (2017)

e23028 Background: TMB is a potential biomarker for response to checkpoint blockade. Prior studies have associated tissue TMB with genomic instability and neoantigen binding sites for activated effector T cells. The goal of our study was to compare TMB in patients with paired next-generation sequencing (NGS) tests from tissue and ctDNA. Methods: Ninety-seven patients with NSCLC (N=53), breast cancer (N=34), and other solid tumors (N=10) with paired tissue (FoundationOne) and ctDNA (Guardant360, currently not clinically indicated for TMB) were examined retrospectively. Insufficient samples were eliminated (e.g., poor tissue quality or no mutations detected). TMB was compared using variants of unknown significance and synonymous mutations both with (N=74) and without potentially functional/driver variants (N=55). Results: Paired samples were compared using both continuous and binary TMB classifications (Table 1). TMB scores were significantly different using both comparisons (paired t-test, p&lt;0.05). In addition, correlation coefficients between the two assays were low (Pearson Correlation, r=0.24-0.33). No significant differences were found based on timeframe between biopsies. Conclusions: This study demonstrated a lack of concordance between TMB for tissue and ctDNA in paired samples. Potential reasons include differences in sequencing length (~0.79-1.1 million bp for tissue vs. 78,000-138,000 bp for ctDNA), mutation detection, and methods of determining TMB. Future studies are warranted to determine whether ctDNA TMB can predict response to immunotherapy. [Table: see text]
Troglitazone Inhibits Atherosclerosis in Apolipoprotein E–Knockout Mice (2001)

Atherosclerotic coronary heart disease is a common complication of the insulin resistance syndrome that can occur with or without diabetes mellitus. Thiazolidinediones (TZDs), which are insulin-sensitizing antidiabetic agents, can modulate the development of atherosclerosis not only by changing the systemic metabolic conditions associated with insulin resistance but also by exerting direct effects on vascular wall cells that express peroxisome proliferator-activated receptor-gamma (PPAR-gamma), a nuclear receptor for TZDs. Here we show that troglitazone, a TZD, significantly inhibited fatty streak lesion formation in apolipoprotein E-knockout mice fed a high-fat diet (en face aortic surface lesion areas were 6.9+/-2.5% vs 12.7+/-4.7%, P<0.05; cross-sectional lesion areas were 191 974+/-102 911 micrometer(2) vs 351 738+/-175 597 micrometer(2), P<0.05; n=10). Troglitazone attenuated hyperinsulinemic hyperglycemia and increased high density lipoprotein cholesterol levels. In the aorta, troglitazone markedly increased the mRNA levels of CD36, a scavenger receptor for oxidized low density lipoprotein, presumably by upregulating its expression, at least in part, in the macrophage foam cells. These results indicate that troglitazone potently inhibits fatty streak lesion formation by modulating both metabolic extracellular environments and arterial wall cell functions.
Effect of whey protein to modulate immune response in children with atopic asthma (2006)

These results suggest a modest impact of whey protein supplementation on the cytokine response in atopic asthma. Supplementation for longer periods, or with more potent whey-based supplements, currently under development, may prove more beneficial.
CD200-expressing human basal cell carcinoma cells initiate tumor growth (2013)

Smoothened antagonists directly target the genetic basis of human basal cell carcinoma (BCC), the most common of all cancers. These drugs inhibit BCC growth, but they are not curative. Although BCC cells are monomorphic, immunofluorescence microscopy reveals a complex hierarchical pattern of growth with inward differentiation along hair follicle lineages. Most BCC cells express the transcription factor KLF4 and are committed to terminal differentiation. A small CD200(+) CD45(-) BCC subpopulation that represents 1.63 ± 1.11% of all BCC cells resides in small clusters at the tumor periphery. By using reproducible in vivo xenograft growth assays, we determined that tumor initiating cell frequencies approximate one per 1.5 million unsorted BCC cells. The CD200(+) CD45(-) BCC subpopulation recreated BCC tumor growth in vivo with typical histological architecture and expression of sonic hedgehog-regulated genes. Reproducible in vivo BCC growth was achieved with as few as 10,000 CD200(+) CD45(-) cells, representing ~1,500-fold enrichment. CD200(-) CD45(-) BCC cells were unable to form tumors. These findings establish a platform to study the effects of Smoothened antagonists on BCC tumor initiating cell and also suggest that currently available anti-CD200 therapy be considered, either as monotherapy or an adjunct to Smoothened antagonists, in the treatment of inoperable BCC.
l-Ascorbic Acid Potentiates Endothelial Nitric Oxide Synthesis via a Chemical Stabilization of Tetrahydrobiopterin (2001)

Ascorbic acid has been shown to stimulate endothelial nitric oxide (NO) synthesis in a time- and concentration-dependent fashion without affecting NO synthase (NOS) expression or l-arginine uptake. The present study investigates if the underlying mechanism is related to the NOS cofactor tetrahydrobiopterin. Pretreatment of human umbilical vein endothelial cells with ascorbate (1 microm to 1 mm, 24 h) led to an up to 3-fold increase of intracellular tetrahydrobiopterin levels that was concentration-dependent and saturable at 100 microm. Accordingly, the effect of ascorbic acid on Ca(2+)-dependent formation of citrulline (co-product of NO) and cGMP (product of the NO-activated soluble guanylate cyclase) was abolished when intracellular tetrahydrobiopterin levels were increased by coincubation of endothelial cells with sepiapterin (0.001-100 microm, 24 h). In contrast, ascorbic acid did not modify the pterin affinity of endothelial NOS, which was measured in assays with purified tetrahydrobiopterin-free enzyme. The ascorbate-induced increase of endothelial tetrahydrobiopterin was not due to an enhanced synthesis of the compound. Neither the mRNA expression of the rate-limiting enzyme in tetrahydrobiopterin biosynthesis, GTP cyclohydrolase I, nor the activities of either GTP cyclohydrolase I or 6-pyruvoyl-tetrahydropterin synthase, the second enzyme in the de novo synthesis pathway, were altered by ascorbate. Our data demonstrate that ascorbic acid leads to a chemical stabilization of tetrahydrobiopterin. This was evident as an increase in the half-life of tetrahydrobiopterin in aqueous solution. Furthermore, the increase of tetrahydrobiopterin levels in intact endothelial cells coincubated with cytokines and ascorbate was associated with a decrease of more oxidized biopterin derivatives (7,8-dihydrobiopterin and biopterin) in cells and cell supernatants. The present study suggests that saturated ascorbic acid levels in endothelial cells are necessary to protect tetrahydrobiopterin from oxidation and to provide optimal conditions for cellular NO synthesis.
Strategies to Enhance Implantation and Survival of Stem Cells After Their Injection in Ischemic Neural Tissue (2017)

High post-transplantation cell mortality is the main limitation of various approaches that are aimed at improving regeneration of injured neural tissue by an injection of neural stem cells (NSCs) and mesenchymal stromal cells (MStroCs) in and/or around the lesion. Therefore, it is of paramount importance to identify efficient ways to increase cell transplant viability. We have previously proposed the "evolutionary stem cell paradigm," which explains the association between stem cell anaerobic/microaerophilic metabolic set-up and stem cell self-renewal and inhibition of differentiation. Applying these principles, we have identified the main critical point in the collection and preparation of these cells for experimental therapy: exposure of the cells to atmospheric O<sub>2</sub>, that is, to oxygen concentrations that are several times higher than the physiologically relevant ones. In this way, the primitive anaerobic cells become either inactivated or adapted, through commitment and differentiation, to highly aerobic conditions (20%-21% O<sub>2</sub> in atmospheric air). This inadvertently compromises the cells' survival once they are transplanted into normal tissue, especially in the hypoxic/anoxic/ischemic environment, which is typical of central nervous system (CNS) lesions. In addition to the findings suggesting that stem cells can shift to glycolysis and can proliferate in anoxia, recent studies also propose that stem cells may be able to proliferate in completely anaerobic or ischemic conditions by relying on anaerobic mitochondrial respiration. In this systematic review, we propose strategies to enhance the survival of NSCs and MStroCs that are implanted in hypoxic/ischemic neural tissue by harnessing their anaerobic nature and maintaining as well as enhancing their anaerobic properties via appropriate ex vivo conditioning.
Correlation between Reduced Daptomycin Susceptibility and Vancomycin Resistance in Vancomycin-Intermediate Staphylococcus aureus (2006)

We present here findings of a strong positive correlation between reduced daptomycin susceptibility and vancomycin resistance in vancomycin-intermediate Staphylococcus aureus (VISA). This correlation is related to cell wall thickening, suggesting that, similar to the case with vancomycin resistance in VISA, the physical barrier of a thickened cell wall may contribute to daptomycin resistance in S. aureus.
SARs stimulate but do not confer position independent gene expression (1994)

Two minimal scaffold-associated regions (SARs) from Drosophila were tested in stably transformed cells for their effects on the expression of reporter genes. The expression of genes bounded by two SARs is consistently stimulated by about 20- to 40-fold, if the average of a pool of cell transformants is analyzed. However, analysis of individual, stable cell transformants demonstrates that flanking SAR elements do not confer position-independent expression on the reporter gene and that the extent of position-dependent variegation is similarly large with or without the flanking SAR elements. The SAR stimulation of expression is observed in stable but not in transiently transfected cell lines. The Drosophila scs and scs' boundary elements, which do not bind to the nuclear matrix in vitro, are only about one-tenth as active as SARs in stimulating expression in stable transformants. Interestingly, the SAR stimulatory effect can be blocked by a fragment containing CpG islands (approximately 70% GC), if positioned between the SAR and the enhancer. In contrast, when inserted in the same position, control fragments, such as the scs/scs' elements, do not interfere with SAR function.
Effective Gene Transfer to Human Melanomas via Integrin-Targeted Adenoviral Vectors (2002)

The utility of recombinant adenoviral vectors (Adv) for gene therapy is limited by their low transduction efficiency and lack of specificity for target cells. The low transduction efficiency is often recognized as due to deficiency of the primary adenoviral receptor, the coxsackievirus-adenovirus receptor (CAR). In this paper, studies of CAR levels on human melanoma cell lines confirmed that low transduction efficiency was closely related to deficiency of the adenoviral receptor. To achieve CAR-independent gene transfer via Adv, we modified viral tropism via genetic alteration of the adenovirus type 5 (Ad5) fiber protein. Insertion of an Arg-Gly-Asp (RGD)-containing peptide in the HI loop of the fiber knob domain allowed the virus to use an alternative receptor, the integrin receptor, during the cell entry process. With this modified vector (Adv-F/RGD) transduction was increased 5- to 96-fold relative to a vector containing wild-type fiber (Adv-F/wt) in five human melanoma cells expressing integrins of the alpha(v)beta(3), alpha(v)beta(5) class, which are recognized by the RGD peptide motif. In contrast, no significant difference in transduction efficiency between Adv-F/RGD and Adv-F/wt was observed in 293 cells, which show high-level expression of CAR. In this study, we attempted to apply Adv-F/RGD for gene therapy for malignant melanoma. At the same multiplicity of infection, melanoma cells infected with Adv-F/RGD carrying human interleukin 2 (AxCAhIL2-F/RGD) produced a higher level of cytokine than cells infected with AxCAhIL2-F/wt. Treatment by intratumoral injection of AxCAhIL2-F/RGD was more effective than intratumoral injection of AxCAhIL2-F/wt in regressing tumors in a melanoma xenograft model. These data suggest that integrin-targeted adenoviral vectors may be a powerful tool in gene therapy for CAR-deficient melanomas.
BBX32, an Arabidopsis B-Box Protein, Functions in Light Signaling by Suppressing HY5-Regulated Gene Expression and Interacting with STH2/BBX21 (2011)

A B-box zinc finger protein, B-BOX32 (BBX32), was identified as playing a role in determining hypocotyl length during a large-scale functional genomics study in Arabidopsis (Arabidopsis thaliana). Further analysis revealed that seedlings overexpressing BBX32 display elongated hypocotyls in red, far-red, and blue light, along with reduced cotyledon expansion in red light. Through comparative analysis of mutant and overexpression line phenotypes, including global expression profiling and growth curve studies, we demonstrate that BBX32 acts antagonistically to ELONGATED HYPOCOTYL5 (HY5). We further show that BBX32 interacts with SALT TOLERANCE HOMOLOG2/BBX21, another B-box protein previously shown to interact with HY5. Based on these data, we propose that BBX32 functions downstream of multiple photoreceptors as a modulator of light responses. As such, BBX32 potentially has a native role in mediating gene repression to maintain dark adaptation.
Pentraxin 3, a Sensitive Early Marker of Hemodialysis-Induced Inflammation (2012)

PTX-3 stands out as a rapid and sensitive marker of hemodialysis-induced inflammation. Membrane flux and hemodiafiltration did not alter the inflammatory response.
Association of Alzheimer's Disease Onset With Ginkgo Biloba and Other Symptomatic Cognitive Treatments in a Population of Women Aged 75 Years and Older From the EPIDOS Study (2003)

These results suggest that C4A treatment may reduce the risk of developing Alzheimer's dementia in elderly women. The potential preventive effect of C4A treatments, including EGb 761, requires further examination. To establish a causal relationship, these findings have to be confirmed with prospective studies.
N-terminal Domains Elicit Formation of Functional Pmel17 Amyloid Fibrils (2009)

Pmel17 is a transmembrane protein that mediates the early steps in the formation of melanosomes, the subcellular organelles of melanocytes in which melanin pigments are synthesized and stored. In melanosome precursor organelles, proteolytic fragments of Pmel17 form insoluble, amyloid-like fibrils upon which melanins are deposited during melanosome maturation. The mechanism(s) by which Pmel17 becomes competent to form amyloid are not fully understood. To better understand how amyloid formation is regulated, we have defined the domains within Pmel17 that promote fibril formation in vitro. Using purified recombinant fragments of Pmel17, we show that two regions, an N-terminal domain of unknown structure and a downstream domain with homology to a polycystic kidney disease-1 repeat, efficiently form amyloid in vitro. Analyses of fibrils formed in melanocytes confirm that the polycystic kidney disease-1 domain forms at least part of the physiological amyloid core. Interestingly, this same domain is also required for the intracellular trafficking of Pmel17 to multivesicular compartments within which fibrils begin to form. Although a domain of imperfect repeats (RPT) is required for fibril formation in vivo and is a component of fibrils in melanosomes, RPT is not necessary for fibril formation in vitro and in isolation is unable to adopt an amyloid fold in a physiologically relevant time frame. These data define the structural core of Pmel17 amyloid, imply that the RPT domain plays a regulatory role in timing amyloid conversion, and suggest that fibril formation might be physically linked with multivesicular body sorting.
Novel, Broad-Spectrum Anticonvulsants Containing a Sulfamide Group: Advancement of N -((Benzo[ b ]thien-3-yl)methyl)sulfamide (JNJ-26990990) into Human Clinical Studies (2009)

In seeking broad-spectrum anticonvulsants to treat epilepsy and other neurological disorders, we synthesized and tested a group of sulfamide derivatives (4a-k, 5), which led to the clinical development of 4a (JNJ-26990990). This compound exhibited excellent anticonvulsant activity in rodents against audiogenic, electrically induced, and chemically induced seizures, with very weak inhibition of human carbonic anhydrase-II (IC(50) = 110 microM). The pharmacological profile for 4a supports its potential in the treatment of multiple forms of epilepsy, including pharmacoresistant variants. Mechanistically, 4a inhibited voltage-gated Na(+) channels and N-type Ca(2+) channels but was not effective as a K(+) channel opener. The pharmacokinetics and metabolic properties of 4a are discussed.
Cyclic AMP-specific PDE4 Phosphodiesterases as Critical Components of Cyclic AMP Signaling (2003)

In the five decades that have elapsed since the identification of the second messenger cAMP, most of the components involved in this signaling pathway have been identified, and many of their functions are understood at the molecular and atomic levels. Yet an unexpected and often disconcerting outcome of this progress is the realization that apparently identical cAMP signals induce divergent physiological responses. Countless reports indicate that G protein-coupled receptors (GPCRs)1 that activate the cAMP pathway have distinct and often opposing effects on cell replication/differentiation.
Melanoma metastasis is associated with enhanced expression of the syntenin gene (2004)

Primary cutaneous melanomas and melanoma metastases were examined for differential gene expression using subtractive suppression hybridization in a search for any genes associated with metastasis. Generating a subtracted library of candidate genes up-regulated in melanoma metastases, this library contained 8 different cDNAs, among them a cDNA fragment of the syntenin gene which was overexpressed in further independent melanoma resection specimens on cDNA Southern blots when compared to acquired melanocytic nevi from which melanomas are known to arise. Upon immunohistochemistry, the syntenin protein expression was detected in the cytoplasm of primary cutaneous melanomas and melanoma metastases. Melanoma metastases exhibited higher proportions of tumour cells positive for syntenin immunostaining in comparison to acquired melanocytic nevi or non-metastasizing primary melanomas which was statistically significant. In addition to melanoma, gastric cancer tissues exhibited a higher syntenin mRNA expression on a matched tumour/normal cDNA array than their normal counterparts which was statistically significant. Altogether, we here first describe the detection of the syntenin protein in resection specimens of melanocytic lesions. We conclude that melanoma metastasis is associated with increased expression of the syntenin gene which may participate in signal transduction and cell adhesion via the multifunctional protein-binding properties of its tandem PDZ domains.
앱(app)을 통해 보여지는 아트 아카이브의 정보 구조 분석 -미술 정보 가이드 앱을 중심으로- (2013)

As recent usage of the smartphone increases, being helped by the application is increasing quickly. Other than searches from the portal sites, using search application has made. The rapid development of mobile markets has changed the pattern of people`s time usage. Use of smartphone`s quick search has also changed the leisure time. Art information applications for smartphone users have made things easier for people to display and encounter with culture news. In addition, these archived data can be shared easily through the applications. This paper will examine more through the information structures of the top 3 popular downloaded applications. Study will be focused on the literature and case studies and will look through the archive of concept art and type. The case studies will compare and contrast the structures of each applications and compare the structure of changes made depends on the context.