gebhart/patrepeval huggingface dataset:
Basic fibroblast growth factor and transforming growth factor beta‐1: Synergistic mediators of angiogenesis in vitro (1993)

We investigated the relative roles of basic fibroblast growth factor (bFGF) and transforming growth factor beta-1 (TGF-b) on bovine aortic endothelial cell mitogenesis and morphogenesis using two-dimensional Petri dish cultures and a three-dimensional hydrated collagen gel. bFGF alone stimulated endothelial cell proliferation with an EC50 of 0.5 ng/ml. At bFGF levels greater than 2.5 ng/ml, morphologic alterations in confluent monolayers predominated; cells changed from a cobblestone morphology to an elongated cell pattern and showed enhanced migration into a denuded area of a Petri dish. In the three-dimensional model, exposure of endothelial cell monolayers to high bFGF levels stimulated minor cell migration directly under the monolayer but no invasion into the gel matrix. In combination with bFGF, heparin potentiated morphogenic changes, but not mitogenesis. bFGF modification of the antiproliferative effect of TGF-b in confluent cultures was evidenced by induction of endothelial cell sprouting in response to 0.5 ng/ml TGF-b and 10-20 ng/ml bFGF in two-dimensional cultures. On collagen gels, endothelial cells migrated into the deep layers of the gel in a dose-dependent manner: invasion was maximal at 0.3-0.7 ng/ml TGF-b with decreased invasion at higher concentrations. The optimal collagen concentration that supported cell invasion was 0.075% collagen with the number of invading cells decreasing with increasing collagen gel density. By scanning electron microscopy, invading endothelial cells assumed a fibroblast-like appearance with slender cell extensions. We concluded that bFGF and TGF-b had independent effects on endothelial cell morphology and mitogenesis in culture. In combination at specific doses, these agents stimulated sprouting in the two-dimensional model and cell invasion in a collagen gel model. Morphogenic changes may be the primary event in determining angiogenesis.
Restoration of normal growth control and membrane antigen composition in malignant cells by N,N-dimethylformamide. (1984)

The effects of the differentiation agent, N,N-dimethylformamide (DMF), on malignant AKR-MCA cells were studied. The properties of DMF-treated AKR-MCA cells were compared to those of the normal parental AKR-2B mouse embryo fibroblasts. AKR-MCA cells grown in 1% DMF were found to be more similar to their normal counterparts than to untreated AKR-MCA cells by several criteria. These criteria included the loss of the transformed morphology, a 2-fold reduction of doubling time, a 10-fold reduction of saturation density, and the complete loss of the ability to grow with anchorage independence. The expression of high-molecular-weight membrane antigens (Mr 110,000 to 450,000), which was found to be greatly reduced in AKR-MCA cells in comparison to normal AKR-2B cells, was restored by treatment of AKR-MCA cells with DMF. The expression of a low-molecular-weight AKR-MCA cell-associated membrane antigen, on the other hand was found to be suppressed. Studies on the mitogenic response of these cells indicated that AKR-MCA and AKR-2B cells may be regulated by different types of growth control. Growth-arrested AKR-MCA cells did not respond to epidermal growth factor, but responded to nutrient replenishment. AKR-2B cells, on the other hand, responded to epidermal growth factor, but did not respond to nutrient replenishment. Treatment of AKR-MCA cells with DMF restored their ability to respond to epidermal growth factor, while their ability to respond to nutrient replenishment was lost. The results of this study indicated that DMF treatment induced the normalization of malignant AKR-MCA cells with regard to membrane antigen composition and growth control properties.
Comparison of approaches for determining end-members in hyperspectral data (2002)

A very useful analysis approach for hyperspectral data has been linear unmixing which is a projection into a coordinate system where the coordinates are the constituent or end member spectra of the scene. The most useful technique is to determine the spectra from the image. Once these spectra are found, the image cube can be "unmixed" into fractional abundances of each material in each pixel. Several autonomous methods, ORASIS, the first real time autonomous algorithm; N-FINDR, an algorithm that determines end members by inflating a simplex, and Iterative Error Analysis (LEA) which finds end members by iterative unmixing are compared in this paper. Computer implementations of the three autonomous algorithms are evaluated using hyperspectral AVIRIS data of Cuprite, Nevada. The fractional abundance maps produced by the three algorithms are compared to a mineral map made by the USGS based upon an AVIRIS scene, and the end member spectra are compared to library spectra.
Eradication ofPropionibacterium acnesby its endogenic porphyrins after illumination with high intensity blue light (2003)

Propionibacterium acnes is a Gram-positive, microaerophilic bacterium that causes skin wounds. It is known to naturally produce high amounts of intracellular porphyrins. The results of the present study confirm that the investigated strain of P. acnes is capable of producing endogenic porphyrins with no need for any trigger molecules. Extracts from growing cultures have demonstrated emission peaks around 612 nm when excited at 405 nm, which are characteristic for porphyrins. Endogenic porphyrins were determined and quantified after their extraction from the bacterial cells by fluorescence intensity and by elution retention time on high-performance liquid chromatography (HPLC). The porphyrins produced by P. acnes are mostly coproporphyrin, as shown by the HPLC elution patterns. Addition of delta-aminolevulinic acid (ALA) enhanced intracellular porphyrin synthesis and higher amounts of coproporphyrin have been found. Eradication of P. acnes by its endogenic porphyrins was examined after illumination with intense blue light at 407-420 nm. The viability of 24 h cultures grown anaerobically in liquid medium was reduced by less than two orders of magnitude when illuminated once with a light dose of 75 J cm(-2). Better photodynamic effects were obtained when cultures were illuminated twice or three times consecutively with a light dose of 75 J cm(-2) and an interval of 24 h between illuminations. The viability of the culture under these conditions decreased by four orders of magnitude after two illuminations and by five orders of magnitude after three illuminations. When ALA-triggered cultures were illuminated with intense blue light at a light dose of 75 J cm(-2) the viability of the treated cultures decreased by seven orders of magnitude. This decrease in viability can occur even after a single exposure of illumination for the indicated light intensity. X-ray microanalysis and transmission electron microscopy revealed structural damages to membranes in the illuminated P. acnes. Illumination of the endogenous coproporphyrin with blue light (407-420 nm) apparently plays a major role in P. acnes photoinactivation. A treatment protocol with a series of several illuminations or illumination after application of ALA may be suitable for curing acne. Treatment by both pathways may overcome the resistance of P. acnes to antibiotic treatment.
CDK5RAP3 Is a Novel Repressor of p14ARF in Hepatocellular Carcinoma Cells (2012)

CDK5 regulatory subunit associated protein 3 (CDK5RAP3) is a novel activator of PAK4 and processes important prometastatic function in hepatocarcinogenesis. However, it remains unclear if there are other mechanisms by which CDK5RAP3 promotes HCC metastasis. Here, we showed that in CDK5RAP3 stable knockdown SMMC-7721 HCC cells, p14 ARF tumor suppressor was upregulated at protein and mRNA levels, and ectopic expression of CDK5RAP3 was found to repress the transcription of p14 ARF . Using chromatin immunoprecipitation assay, we demonstrated that CDK5RAP3 bound to p14 ARF promoter in vivo. Furthermore, knockdown of p14 ARF in CDK5RAP3 stable knockdown HCC cells reversed the suppression of HCC cell invasiveness mediated by knockdown of CDK5RAP3. Taken together, our findings provide the new evidence that overexpression of CDK5RAP3 promotes HCC metastasis via downregulation of p14 ARF .
Coronavirus Disease 2019 (COVID-19) Complicated by Acute Respiratory Distress Syndrome: An Internist’s Perspective (2020)

A pandemic outbreak of a novel coronavirus disease (COVID-19) that began in Wuhan, China, in December 2019 has spread rapidly to multiple countries. In the United States, the first confirmed case was reported on January 20, 2020, and since then, the number of cases is rising exponentially on a daily basis. We report a case of COVID-19 infection that presented with symptoms suggestive of pneumonia. Due to the major backlog with an immense number of pending tests, it took 48 hours for the result to come back positive, while the patient went into acute respiratory distress syndrome. We provide an internist's perspective of the difficulties encountered in terms of the available management options, as the patient progressively deteriorated on the regular medical floor prompting transfer to the intensive care unit.
Chaperone‐like activity of synucleins (2000)

Synucleins are a family of small proteins that are predominantly expressed in neurons. The functions of the synucleins are not entirely understood, but they have been implicated in the pathogenesis of several neurodegenerative diseases. Our data show that α‐, β‐ or γ‐synuclein suppresses the aggregation of thermally denatured alcohol dehydrogenase and chemically denatured insulin. The A53T but not the A30P mutant α‐synuclein was able to inhibit the aggregation of insulin and the chaperone‐like activity of α‐synuclein was lost upon removal of its C‐terminal residues 98–140. These results demonstrate that synucleins with the exception of the A30P mutant possess chaperone‐like activity.
MALT lymphoma and extranodal diffuse large B-cell lymphoma are targeted by aberrant somatic hypermutation (2006)

Recently, a novel mechanism introducing genetic instability, termed aberrant somatic hypermutation (ASHM), has been described in diffuse large B-cell lymphoma. To further investigate whether ASHM also occurs in mucosa-associated lymphoid tissue type (MALT) lymphoma, we studied the mutation profile of PIM1, PAX5, RhoH/TTF, and c-MYC in 17 MALT lymphomas and 17 extranodal diffuse large B-cell lymphomas (DLBCLs) still exhibiting a low-grade MALT lymphoma component (transformed MALT lymphoma). Mutations in one or more genes were detected in 13 (76.5%) of 17 cases of MALT lymphomas and in all of 17 (100%) cases of extranodal DLBCL. A total of 100 sequence variants were found in 30 of 34 cases, 28 in the MALT lymphomas and 72 in extranodal DLBCL. Further, in PIM1 and c-MYC some of the mutations were found to affect coding exons, leading to amino acid exchanges, thus potentially altering gene function. Expression levels of activation-induced cytidine deaminase (AID), an enzyme essential for somatic hypermutation (SHM), was associated with the mutational load. These data indicate that aberrant SHM is associated with extranodal DLBCL and MALT lymphoma, likewise. By mutating regulatory and coding sequences of the targeted genes, ASHM may represent a major contributor to their pathogenesis.
Nuclear RNA Export Pathways (2000)

One of the most profound differences between prokaryotes and eukaryotes is that only the latter segregate RNA synthesis and protein synthesis into distinct cellular compartments, i.e., into the nucleus and cytoplasm, respectively. This segregation offers opportunities for the regulation of both gene expression and RNA posttranscriptional processing that are not available to prokaryotes. However, it also means that eukaryotic cells must continuously transport large numbers of macromolecules between the nucleus and the cytoplasm in order that these can fulfill their appointed role in the life of the cell. In this review, I will describe the mechanisms used by the cell to move different classes of cellular RNA from their nuclear site of synthesis to the cytoplasm, where the majority then participate in the process of protein synthesis. While my primary focus will be on the insights that have been gleaned from the study of nuclear RNA export in vertebrate cells, I will also refer to studies with the yeast Saccharomyces cerevisiae which, because of its genetic malleability, has proven to be a valuable system for the identification of critical components of the nucleocytoplasmic transport machinery. More comprehensive overviews of nucleocytoplasmic transport, particularly of protein import, are provided by several excellent recent reviews in this area (21, 42, 50, 70).
Genetic Risk Prediction — Are We There Yet? (2009)

A major goal of the Human Genome Project was to facilitate the identification of inherited genetic variants that increase or decrease the risk of complex diseases. The completion of the International HapMap Project and the development of new methods for genotyping individual DNA samples at 500,000 or more loci have led to a wave of discoveries through genomewide association studies. These analyses have identified common genetic variants that are associated with the risk of more than 40 diseases and human phenotypes. Several companies have begun offering direct-to-consumer testing that uses the same single-nucleotide polymorphism chips that are used in genomewide . . .
Amplification of fgfr4 gene in human breast and gynecological cancers (1993)

We have investigated gene amplification of fibroblast growth factor receptor-4 (FGFR4) gene in 30 primary breast tumor samples and 15 gynecological tumor samples. Ten percent of the breast tumors showed 2- to 4-fold amplification. Amplification was found more frequently in estrogen- and progesterone-receptor-positive tumors and in tumors with high lymph-node involvement. Breast tumor samples were also analyzed for the amplification of fgfr3 and erbB2 genes and the chromosome 11q13 located genes hst1/int2/bcl1/sea. erbB2 gene was amplified 2- to 13-fold in 13% of the cases, but no amplification of int2/hst1/bcl1/sea amplicon was found. Gynecological tumors were also analyzed for the amplification of fgfr4 and fgfr3 genes and for int2 and hst1 oncogenes. Eleven of the 15 gynecological tumors were ovarian neoplasms including 2 benign tumors; the remainder comprised 1 ovarian metastasis of breast cancer; 1 endometrial cancer; 1 uterine leiomyosarcoma and 1 carcinosarcoma of the fallopian tube. In gynecological tumors, fgfr4 gene was found to be amplified in 2 ovarian tumors. Amplification of hst1 was found in 1 benign ovarian tumor. Thus, the fgfr4 gene may be involved in breast and ovarian tumorigenesis.
Refined atomic model of wheat serine carboxypeptidase II at 2.2-.ANG. resolution (1992)

The crystal structure of the homodimeric serine carboxypeptidase II from wheat (CPDW-II, M(r) 120K) has been determined and fully refined at 2.2-A resolution to a standard crystallographic R factor of 16.9% using synchrotron data collected at the Brookhaven National Laboratory. The model has an rms deviation from ideal bond lengths of 0.018 A and from bond angles of 2.8 degrees. The model supports the general conclusions of an earlier study at 3.5-A resolution and will form the basis for investigation into substrate binding and mechanistic studies. The enzyme has an alpha + beta fold, consisting of a central 11-stranded beta-sheet with a total of 15 helices on either side. The enzyme, like other serine proteinases, contains a "catalytic triad" Ser146-His397-Asp338 and a presumed "oxyanion hole" consisting of the backbone amides of Tyr147 and Gly53. The carboxylate of Asp338 and imidazole of His397 are not coplanar in contrast to the other serine proteinases. A comparison of the active site features of the three families of serine proteinases suggests that the "catalytic triad" should actually be regarded as two diads, a His-Asp diad and a His-Ser diad, and that the relative orientation of one diad with respect to the other is not particularly important. Four active site residues (52, 53, 65, and 146) have unfavorable backbone conformations but have well-defined electron density, suggesting that there is some strain in the active site region. The binding of the free amino acid arginine has been analyzed by difference Fourier methods, locating the binding site for the C-terminal carboxylate of the leaving group. The carboxylate makes hydrogen bonds to Glu145, Asn51, and the amide of Gly52. The carboxylate of Glu145 also makes a hydrogen bond with that of Glu65, suggesting that one or both may be protonated. Thus, the loss of peptidase activity at pH > 7 may in part be due to deprotonation of Glu145. The active site does not reveal exposed peptide amides and carbonyl oxygen atoms that could interact with substrate in an extended beta-sheet fashion. The fold of the polypeptide backbone is completely different than that of trypsin or subtilisin, suggesting that this is a third example of convergent molecular evolution to a common enzymatic activity. Furthermore, it is suggested that the active site sequence motif "G-X-S-X-G/A", often considered the hallmark of serine peptidase or esterase activity, is fortuitous and not the result of divergent evolution.(ABSTRACT TRUNCATED AT 400 WORDS)
THERAPEUTIC CRITERIA IN RHEUMATOID ARTHRITIS (1949)

This report summarizes recommendations for uniform therapeutic criteria in rheumatoid arthritis. The need for such criteria arose from the recognition of the confusing language and standards found in the many therapeutic reports on this disease. In an effort to develop common standards for the evaluation of therapy in this condition, the Committee for Therapeutic Criteria of the New York Rheumatism Association was formed in 1945. A number of previous attempts had been made to establish some order in this subject.<sup>1</sup> One of the chief difficulties which confronted us was the varied language used in the body and conclusions of articles on therapy which did not lend themselves to any accurate appraisal. For example, in presenting their conclusions, writers reporting results employed such terms as excellent, good, improved, greatly improved, moderately improved, objectively improved and so on. Even investigators using the same methods of therapy have reported their results in
Expression of the glycosylphosphatidylinositol-linked complement-inhibiting protein CD59 antigen in insect cells using a baculovirus vector (1993)

CD59 antigen (CD59) is a glycosylphosphatidylinositol (GPI)-linked membrane glycoprotein which protects human cells from complement-mediated lysis. Here we report the expression of functionally active CD59 in Spodoptera frugiperda insect cells using a baculovirus vector. Recombinant CD59 was expressed abundantly on the surface of the insect cells and protected the cells from lysis by human complement. The protein was released from the cell surface by treatment with phosphatidylinositol-specific phospholipase C, indicating that it was attached to the insect cell membrane via a GPI anchor. The cells also secreted CD59 into the culture medium. Recombinant CD59 was affinity-purified from spent culture medium and from detergent extract of transfected cells. Protein purified from both sources produced multiple bands on SDS/PAGE, all of a lower apparent molecular mass than the human erythrocyte protein. However, N-terminal protein sequencing and deglycosylation studies confirmed that signals for leader peptide cleavage and N-linked glycosylation had been recognized in the insect cells, suggesting that the differences in apparent molecular mass between the native and recombinant proteins were attributable to the extent of glycosylation. Protein derived from both sources was, in part, GPI-anchored as demonstrated by phase-partition studies and incorporation into cells membranes. Incorporated recombinant protein rendered erythrocytes resistant to complement lysis.
Requirement of ArcA for Redox Regulation in Escherichia coli under Microaerobic but Not Anaerobic or Aerobic Conditions (2002)

In Escherichia coli, the two-component regulatory ArcAB system functions as a major control system for the regulation of expression of genes encoding enzymes involved in both aerobic and anaerobic catabolic pathways. Previously, we have described the physiological response of wild-type E. coli to changes in oxygen availability through the complete range from anaerobiosis to full aerobiosis (S. Alexeeva, B. de Kort, G. Sawers, K. J. Hellingwerf, and M. J. Teixeira de Mattos, J. Bacteriol. 182:4934-4940, 2000, and S. Alexeeva, K. J. Hellingwerf, and M. J. Teixeira de Mattos, J. Bacteriol. 184:1402-1406, 2002). Here, we address the question of the contribution of the ArcAB-dependent transcriptional regulation to this response. Wild-type E. coli and a mutant lacking the ArcA regulator were grown in glucose-limited chemostat cultures at controlled levels of oxygen availability ranging from full aerobiosis to complete anaerobiosis. A flux analysis of the distribution of catabolic fluxes over parallel pathways was carried out, and the intracellular redox state (as reflected by the NADH/NAD ratio) was monitored for all steady states. Deletion of ArcA neither significantly altered the in vivo activity of the pyruvate dehydrogenase complex and pyruvate formate lyase nor significantly affected catabolism under fully aerobic and fully anaerobic conditions. In contrast, profound effects of the absence of ArcA were seen under conditions of oxygen-restricted growth: increased respiration, an altered electron flux distribution over the cytochrome o- and d-terminal oxidases, and a significant change in the intracellular redox state were observed. Thus, the ArcA regulator was found to exert major control on flux distribution, and it is concluded that the ArcAB system should be considered a microaerobic redox regulator.
Mechanism of Activation of the GM‐CSF, IL‐3, and IL‐5 Family of Receptors (1998)

The process of ligand binding leading to receptor activation is an ordered and sequential one. High-affinity binding of GM-CSF, interleukin 3 (IL-3), and IL-5 to their receptors induces a number of key events at the cell surface and within the cytoplasm that are necessary for receptor activation. These include receptor oligomerization, activation of tyrosine kinase activity, phosphorylation of the receptor, and the recruitment of SH2 (src-homology) and PTB (phosphotyrosine binding) domain proteins to the receptor. Such a sequence of events represents a recurrent theme among cytokine, growth factor, and hormone receptors; however, a number of very recent and interesting findings have identified unique features in this receptor system in terms of: A) how GM-CSF/IL-3/IL-5 bind, oligomerize, and activate their cognate receptors; B) how multiple biological responses such as proliferation, survival, and differentiation can be transduced from activated GM-CSF, IL-3, or IL-5 receptors, and C) how the presence of novel phosphotyrosine-independent signaling motifs within a specific cytoplasmic domain of betaC may be important for mediating survival and differentiation by these cytokines. This review does not attempt to be all-encompassing but rather to focus on the most recent and significant discoveries that distinguish the GM-CSF/IL-3/IL-5 receptor subfamily from other cytokine receptors.