gebhart/patrepeval huggingface dataset:
Genomic Landscape of Somatic Alterations in Esophageal Squamous Cell Carcinoma and Gastric Cancer (2016)

Gastric cancer and esophageal cancer are the second and sixth leading causes of cancer-related death worldwide. Multiple genomic alterations underlying gastric cancer and esophageal squamous cell carcinoma (ESCC) have been identified, but the full spectrum of genomic structural variations and mutations have yet to be uncovered. Here, we report the results of whole-genome sequencing of 30 samples comprising tumor and blood from 15 patients, four of whom presented with ESCC, seven with gastric cardia adenocarcinoma (GCA), and four with gastric noncardia adenocarcinoma. Analyses revealed that an A>C mutation was common in GCA, and in addition to the preferential nucleotide sequence of A located 5 prime to the mutation as noted in previous studies, we found enrichment of T in the 5 prime base. The A>C mutations in GCA suggested that oxidation of guanine may be a potential mechanism underlying cancer mutagenesis. Furthermore, we identified genes with mutations in gastric cancer and ESCC, including well-known cancer genes, TP53, JAK3, BRCA2, FGF2, FBXW7, MSH3, PTCH, NF1, ERBB2, and CHEK2, and potentially novel cancer-associated genes, KISS1R, AMH, MNX1, WNK2, and PRKRIR Finally, we identified recurrent chromosome alterations in at least 30% of tumors in genes, including MACROD2, FHIT, and PARK2 that were often intragenic deletions. These structural alterations were validated using the The Cancer Genome Atlas dataset. Our studies provide new insights into understanding the genomic landscape, genome instability, and mutation profile underlying gastric cancer and ESCC development. Cancer Res; 76(7); 1714-23. ©2016 AACR.
Extracellular Matrix Made by Bone Marrow Cells Facilitates Expansion of Marrow-Derived Mesenchymal Progenitor Cells and Prevents Their Differentiation Into Osteoblasts (2007)

The marrow ECM facilitates expansion of MCFUs in vitro while preserving their stem cell properties. We hypothesize that the ECM made by bone marrow cells plays an important role in the maintenance of MSC function.
Triazole: the Keystone in Glycosylated Molecular Architectures Constructed by a Click Reaction (2007)

The copper(I)-catalyzed modern version of the Huisgen-type azide-alkyne cycloaddition to give a 1,4-disubstituted 1,2,3-triazole unit is introduced as a powerful ligation method for glycoconjugation. Owing to its high chemoselectivity and tolerance of a variety of reaction conditions, this highly atom-economic and efficient coupling reaction is especially useful for the effective construction of complex glycosylated structures such as clusters, dendrimers, polymers, peptides, and macrocycles. In all cases the triazole ring plays a key role by locking into position the various parts of these molecular architectures. The examples reported and briefly discussed in this short review highlight the use of this reaction in carbohydrate chemistry and pave the way to further developments and applications.
Multi-resolution video representation for parallel disk arrays (1993)

In a multimedia storage system video is probably the most demanding data type because of its large data volume and strict timing requirements. Image compression and parallel I/O architecture have been proposed in the literature to address the storage problem associated with digital video. This paper takes a systems approach by integrating video compression with data layout algorithms on parallel disk arrays to support high-quality video rendition. Specifically, we propose to use a multiresolution video representation scheme based on Gaussian and Laplacian Pyramids, which allows the storage system to satisfy video access requests by transferring only the minimum amount of data that is absolutely necessary. We also develope a new array storage layout algorithm for the Laplacian pyramid coding scheme to support jitter-free video rendering at the level of disk subsystems. We report on the results of a simulation study on the effectiveness of the proposed integrated design. The result shows that under the assumed workload the multi-resolution scheme is significantly better than the conventional representation in terms of the I/O rate, average waiting time, and average physical data bandwidth requirement. Specifically, the Laplacian Pyramid representation costs three to four times less data traffic, , reduces the average waiting time to one-eighth of that of the conventional approach, and achieves a five to ten times better average I/O rate.
Computer simulation of topological defects around a colloidal particle or droplet dispersed in a nematic host (2001)

We use molecular dynamics to study the ordering of a nematic liquid crystal around a spherical particle or droplet. Homeotropic boundary conditions and strong anchoring create a hedgehog (radial point defect) director configuration on the particle surface and in its vicinity; this topological defect is canceled by nearby defect structures in the surrounding liquid crystal, so as to give a uniform director field at large distances. We observe three defect structures for different particle sizes: a quadrupolar one with a ring defect surrounding the particle in the equatorial plane; a dipolar one with a satellite defect at the north or south pole; and a transitional, nonequatorial, ring defect. These observations are broadly consistent with the predictions of the simplest elastic theory. By studying density and order-parameter maps, we are able to examine behavior near the particle surface, and in the disclination core region, where the elastic theory is inapplicable. Despite the relatively small scale of the inhomogeneities in our systems, the simple theory gives reasonably accurate predictions of the variation of defect position with particle size.
Up-regulation of Akt3 in Estrogen Receptor-deficient Breast Cancers and Androgen-independent Prostate Cancer Lines (1999)

We measured the insulin-stimulated amount of Akt1, Akt2, and Akt3 enzymatic activities in four breast cancer cell lines and three prostate cancer cell lines. In the estrogen receptor-deficient breast cancer cells and the androgen-insensitive prostate cells, the amount of Akt3 enzymatic activity was approximately 20-60-fold higher than in the cells that were estrogen- or androgen-responsive. In contrast, the levels of Akt1 and -2 were not increased in these cells. The increase in Akt3 enzyme activity correlated with an increase in both Akt3 mRNA and protein. In a prostate cancer cell line lacking the tumor suppressor PTEN (a lipid and protein phosphatase), the basal enzymatic activity of Akt3 was constitutively elevated and represented the major active Akt in these cells. Finally, reverse transcription-PCR was used to examine the Akt3 expression in 27 primary breast carcinomas. The expression levels of Akt3 were significantly higher in the estrogen receptor-negative tumors in comparison to the estrogen receptor-positive tumors. To see if the increase in Akt3 could be due to chromosomal abnormalities, the Akt3 gene was assigned to human chromosome 1q44 by fluorescence in situ hybridization and radiation hybrid cell panel analyses. These results indicate that Akt3 may contribute to the more aggressive clinical phenotype of the estrogen receptor-negative breast cancers and androgen-insensitive prostate carcinomas.
One Polypeptide with Two Aminoacyl-tRNA Synthetase Activities (2000)

The genome sequences of certain archaea do not contain recognizable cysteinyl-transfer RNA (tRNA) synthetases, which are essential for messenger RNA-encoded protein synthesis. However, a single cysteinyl-tRNA synthetase activity was detected and purified from one such organism, Methanococcus jannaschii. The amino-terminal sequence of this protein corresponded to the predicted sequence of prolyl-tRNA synthetase. Biochemical and genetic analyses indicated that this archaeal form of prolyl-tRNA synthetase can synthesize both cysteinyl-tRNA(Cys) and prolyl-tRNA(Pro). The ability of one enzyme to provide two aminoacyl-tRNAs for protein synthesis raises questions about concepts of substrate specificity in protein synthesis and may provide insights into the evolutionary origins of this process.
Yellow luminescence and related deep levels in unintentionally doped GaN films (1999)

The deep level energy distribution associated with the well-known ``yellow luminescence'' in GaN is studied by means of two complementary deep level techniques: photoluminescence and surface photovoltage spectroscopy. The combined experimental results show that the yellow luminescence is due to capture of conduction band electrons, or electrons from shallow donors (with a maximum depth on the order of the thermal energy) by a deep acceptor level with a broad energy distribution, centered at \ensuremath{\sim}2.2 eV below the conduction band edge. In addition, the results show that the density of yellow luminescence related states possesses a significant surface component.
Alveolar Macrophage–mediated Killing of Pneumocystis carinii f. sp. muris Involves Molecular Recognition by the Dectin-1 β-Glucan Receptor (2003)

Innate immune mechanisms against Pneumocystis carinii, a frequent cause of pneumonia in immunocompromised individuals, are not well understood. Using both real time polymerase chain reaction as a measure of organism viability and fluorescent deconvolution microscopy, we show that nonopsonic phagocytosis of P. carinii by alveolar macrophages is mediated by the Dectin-1 beta-glucan receptor and that the subsequent generation of hydrogen peroxide is involved in alveolar macrophage-mediated killing of P. carinii. The macrophage Dectin-1 beta-glucan receptor colocalized with the P. carinii cyst wall. However, blockage of Dectin-1 with high concentrations of anti-Dectin-1 antibody inhibited binding and concomitant killing of P. carinii by alveolar macrophages. Furthermore, RAW 264.7 macrophages overexpressing Dectin-1 bound P. carinii at a higher level than control RAW cells. In the presence of Dectin-1 blockage, killing of opsonized P. carinii could be restored through FcgammaRII/III receptors. Opsonized P. carinii could also be efficiently killed in the presence of FcgammaRII/III receptor blockage through Dectin-1-mediated phagocytosis. We further show that Dectin-1 is required for P. carinii-induced macrophage inflammatory protein 2 production by alveolar macrophages. Taken together, these results show that nonopsonic phagocytosis and subsequent killing of P. carinii by alveolar macrophages is dependent upon recognition by the Dectin-1 beta-glucan receptor.
Variations in optical absorption spectra of adult and fetal haemoglobins and its effect on pulse oximetry (1989)

One of the concerns clinicians have relates to the interpretation of noninvasive pulse oximeters in newborns since at birth high levels of fetal hemoglobin (HbF) is present in the blood. Accurate in vivo studies of pulse oximeters in infants with predominantly HbF cannot be easily performed. Therefore, the objective of this in vitro study was to determine whether the presence of high levels of HbF in the blood can significantly affect the accuracy of noninvasive pulse oximeters. It is evident from our results that there is no perceptible difference in the 650-1000 nm wavelength region, which is commonly used in pulse oximetry, between the optical absorption spectra of hemolyzed whole adult and fetal blood. Our observations are in good agreement with in vivo studies published by other investigators showing considerable correlations between SpO2 measured by a pulse oximeter and SaO2 values analyzed in vitro by an IL 282 CO-Oximeter.
An overview of pain management: the clinical efficacy and value of treatment. (2013)

Appropriate treatment of pain requires an understanding of the characteristics of pain, including the severity and the nature of the pain-for example, acute versus chronic pain or nociceptive versus neuropathic pain. Appropriate treatment requires an understanding of the efficacies of the available agents in different pain models, and their adverse events, to best match them to the type of pain. While numerous classes of drugs are used to treat pain, 3 categories in particular-acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), and opioids-are most often used for the treatment of pain, along with adjuvants (eg, muscle relaxants, anticonvulsants). Each of these drugs is associated with different adverse events and with varying degrees of efficacy. In general, acetaminophen is the least potent, while NSAIDs and opioids offer stronger analgesic effects. At the same time, acetaminophen use can cause acute liver failure, and NSAIDs are associated with serious complications impacting the gastrointestinal, cardiovascular, and renal systems. Opioids can cause cognitive deficiency, motor impairment, and respiratory depression, among other problems; they also represent a significant addiction risk in certain groups of patients. This article reviews the safety and efficacy of NSAIDs relative to other therapeutic agents in the treatment of 4 common types of pain, summarizes clinical treatment guidelines in these types of pain, and compares the relative roles of NSAIDs, acetaminophen, and opioids in treating pain.
Identification of a Graft Versus Host Disease-Associated Human Minor Histocompatibility Antigen (1995)

Minor histocompatibility antigen disparities between human leukocyte antigen (HLA)-matched bone marrow donors and recipients are a major risk factor for graft versus host disease (GVHD). An HLA-A2.1-restricted cytotoxic T cell clone that recognized the minor histocompatibility antigen HA-2 was previously isolated from a patient with severe GVHD after HLA-identical bone marrow transplantation. The HLA-A2.1-bound peptide representing HA-2 has now been identified. This peptide appears to originate from a member of the non-filament-forming class I myosin family. Because HA-2 has a phenotype frequency of 95 percent in the HLA-A2.1-positive population, it is a candidate for immunotherapeutic intervention in bone marrow transplantation.
Zinc ion availability--the determinant of efficacy in zinc lozenge treatment of common colds (1997)

This is a re-analysis of reports from 1984 to 1992 of double-blind, placebo-controlled, clinical trials of zinc lozenges in the treatment of common colds. This re-analysis was performed to test the hypothesis that major variations in daily zinc ion availability (ZIA) between chemically different lozenge formulations caused differing results in these clinical trials. Solution chemistry computations determined the bioavailability of Zn2+ ions at physiological pH from the lozenges used in these clinical trails. ZIA was derived from Fick's laws of diffusion in a bio-electric field. Lozenges that released Zn2+ ions at physiological pH (positive ZIAs) shortened colds. Lozenges that released negatively charged zinc species at physiological pH (negative ZIAs) lengthened colds. Lozenges having a zero ZIA had no effect on common colds. Lozenges with ZIA = 100 shortened colds by 7 days while ZIA = -55 lozenges lengthened colds by 4.4 days. A linear dose-response relationship exists between ZIAs of zinc lozenges and changes in duration of common colds. It is concluded that: prospective efficacy of zinc lozenges can be predicted based upon readily determined ZIA factors and ZIAs; chemically different zinc lozenge formulations having greatly different ZIAs resulted in greatly differing results in clinical trials; mast cell granule-derived Zn2+ ions are the foundation of the primary immune system; and high ZIA zinc acetate lozenges are beneficial for common colds.
Sustained expression of the pim-1 kinase is specifically induced in myeloid cells by cytokines whose receptors are structurally related. (1992)

We have examined the effects of myeloid growth factors on expression of the pim-1 kinase protein in human and murine myeloid cells. pim-1 protein was identified in K562 cells by immunoblotting as a 33 kDa protein. In the human factor-dependent myeloid leukemia cell line M07E, pim-1 protein was induced by interleukin 3 (IL-3) or granulocyte-macrophage colony-stimulating factor (GM-CSF), with maximum expression by 4 h. Expression continued for the duration of growth factor exposure, but declined rapidly when cytokines were removed. GM-CSF induced pim-1 protein in a dose-dependent manner, with expression being proportional to the proliferative effect of the cytokine. To examine the specificity of pim-1 protein induction, we compared pim-1 protein levels in myeloid cells which demonstrated different GM-CSF response phenotypes. We also examined the effects on pim-1 protein expression of different growth factors which induced similar response phenotypes. GM-CSF induced pim-1 protein in several myeloid cell lines, most of which demonstrated a proliferative response, but did not induce pim-1 protein expression in neutrophils or monocytic cells. In contrast, the murine cell line Mac-11 expressed pim-1 message in response to IL-3 and GM-CSF, but not in response to bryostatin or M-CSF, which were equivalent mitogens. In human U937 myeloid cells sustained expression of pim-1 protein was induced by GM-CSF, G-CSF and IL-6, but not by bryostatin. Expression of the pim-1 kinase protein in response to myeloid cytokines depends on both the nature of the growth factor and the response phenotype. The pim-1 kinase may be an important intermediate in transmembrane signaling or response phenotype induced by IL-3, GM-CSF and other cytokines whose receptors are structurally similar. Its constitutive expression in some myeloid leukemia cell lines suggests activation of signal cascades utilized by myeloid growth factors.
Functional Characterization of the Opitz Syndrome Gene Product (Midin): Evidence for Homodimerization and Association With Microtubules Throughout the Cell Cycle (1999)

Opitz syndrome (OS) is a multiple congenital anomaly manifested by abnormal closure of midline structures. The gene responsible for the X-linked form of this disease, MID1, encodes a protein (midin) that contains a RING, two B-boxes, a coiled-coil (the so-called tripartite motif) and an RFP-like domain. The tripartite motif is characteristic of a family of proteins, named the B-box family, involved in cell proliferation and development. Since the subcellular compartmentalization and the ability to form multiprotein structures both appear to be crucial for the function of this family of proteins, we have studied these properties on the wild-type and mutated forms of midin. We found that endogenous midin is associated with microtubules throughout the cell cycle, co-localizing with cytoplasmic fibres in interphase and with the mitotic spindle and midbodies during mitosis and cytokinesis. Immunoprecipitation experiments demonstrated the ability of the tripartite motif to mediate midin homodimerization, consistent with the evidence, obtained by gel filtration analysis, that midin exists in the form of large protein complexes. Functional characterization of altered forms of midin, resulting from mutations found in OS patients, revealed that association with microtubules is compromised, while the ability to homodimerize and form multiprotein complexes is retained. We suggest that midin is involved in the formation of multiprotein structures acting as anchor points to microtubules and that impaired association with these cytoskeletal structures causes OS developmental defects.
Chemical Conjugation of Heterologous Proteins on the Surface of Cowpea Mosaic Virus (2004)

Genetic economy leads to symmetric distributions of chemically identical subunits in icosaherdal and helical viruses. Modification of the subunit genes of a variety of viruses has permitted the display of polypeptides on both the infectious virions and virus particles made in expression systems. Icosahedral chimeric particles of this type often display novel properties resulting in high local concentrations of the insert. Here we report an extension of this concept in which entire proteins were chemically cross-linked to lysine and cysteine residues genetically engineered on the coat protein of icosahedral Cowpea mosaic virus particles. Three exogenous proteins, the LRR domain of internalin B, the T4 lysozyme, and the Intron 8 gene product of the of the HER2 tyrosine kinase receptor were derivatized with appropriate bifunctional cross-linkers and conjugated to the virus capsid. Characterization of these particles demonstrated that (1) virtually 100% occupancy of the 60 sites was achieved; (2) biological activity (either enzyme or binding specificity) of the attached protein was preserved; (3) in one case (LRR-internalin B) the attached protein conformed with the icosahedral symmetry to the extent that a reconstruction of the derivatized particles displayed added density with a shape consistent with the X-ray structure of the attached protein. Strategies demonstrated here allow virus particle targeting to specific cell types and the use of an icosahedral virus as a platform for structure determination of small proteins at moderate resolution.
Isolation and characterization of homogeneous heat-labile enterotoxins with high specific activity from Escherichia coli cultures (1979)

The heat-labile enterotoxin (LT) has been isolated in homogeneous form with high specific activity from three sources: cell-free supernatant, NaCl extract, and whole-cell lysates of an enterotoxigenic Escherichia coli strain. In vitro immunological assays were used in lieu of tedious and highly variable bioassays to recognize fractions with activity. This revealed that the major portion of the LT remained adherent to columns containing agarose, from which it could be eluted quantitatively in practically homogeneous form by galactose. Isolated LT has remarkable similarities to the cholera enterotoxin (choleragen) in both subunit structure and amino acid composition, although there are also notable differences in these two enterotoxins, which are related immunologically and by mode of action. Unlike choleragen, in which the A region is totally nicked, E. coli LT, depending on its source, is activated by proteolytic processing. The activity of LT is equivalent to that of choleragen in bioassays on adrenal cells, in rabbit skin, and in rabbit ileal loops, especially when, depending on the source of material, the LT has been activated by treatment with trypsin. The whole-cell lysate is the richest source of LT.
Transient Gene Expression in Intact and Organized Rice Tissues. (1990)

Regulated gene expression of chimeric genes has been studied extensively in electroporated protoplasts. The applicability of these assays is limited, however, because protoplasts are not always physiologically identical to the cells from which they are derived. We have developed a procedure to electroporate DNA into intact and organized leaf structures of rice. Optimization of the new gene delivery system mainly involved eliminating explant-released nucleases, prolonging the DNA/explant incubation time, and expanding the pulse time. Using a [beta]-glucuronidase gene under the control of constitutive promoters, we demonstrated that all cell types within a leaf base were susceptible to electroporation-mediated DNA uptake. Although the technique was initially developed for leaf bases of young etiolated rice seedlings, we proved that it was equally applicable both to other monocotyledons, including wheat, maize, and barley, and to other explants, such as etiolated and green sheath and lamina tissues from rice. Transient gene expression assays with electroporated leaf bases showed that the promoter from a pea light-harvesting chlorophyll a/b-binding protein gene displayed both light- and chloroplast-dependent expression in rice, and that the promoter from the Arabidopsis S-adenosylmethionine synthetase gene was, as in transgenic Arabidopsis and tobacco, preferentially expressed in cells surrounding the vascular bundles.