gebhart/patrepeval huggingface dataset:
A stimulatory GDP/GTP exchange protein for smg p21 is active on the post-translationally processed form of c-Ki-ras p21 and rhoA p21. (1991)

We have purified a stimulatory GDP/GTP exchange protein for smg p21A and -B, ras p21-like small GTP-binding proteins (G proteins), cloned its cDNA, and named it GDP dissociation stimulator (smg p21 GDS). We show here that smg p21 GDS is active not only on smg p21A and -B but also on c-Ki-ras p21 and rhoA p21, all of which are post-translationally processed. Furthermore, we show that smg p21 GDS is inactive on the post-translationally unprocessed form of these proteins and on the post-translationally unprocessed form of c-Ha-ras p21 and smg p25A. All of the small G proteins recognized by smg p21 GDS have a cDNA-predicted C-terminal "CAAX" motif (where C is cysteine, A is an aliphatic amino acid, and X is any amino acid) and a polybasic region upstream of this motif. These results suggest that smg p21 GDS is at least active on a group of small G proteins having these unique C-terminal structures. Moreover, they suggest that the C-terminal post-translational processing of these small G proteins, by farnesylation or geranylgeranylation of the C-terminal cysteine residue, removal of amino acids in positions denoted "AAX", and carboxyl methylation of the exposed cysteine residue, is important for the smg p21 GDS action.
Mechanism of Assembly of the Outer Membrane of Salmonella typhimurium (1972)

Abstract The cell envelope of Salmonella typhimurium has been separated into cytoplasmic and outer membrane fractions of relatively high purity by a new method based on isopycnic sucrose density gradient centrifugation of the total membrane fraction obtained by lysis of lysozyme-EDTA spheroplasts. The outer membrane fraction contained approximately 60% of the protein of the total membranes, 50% of the phospholipid, and 90% of the lipopolysaccharide. The cytoplasmic and outer membrane fractions differed markedly in over-all protein composition as determined by polyacrylamide gel electrophoresis in sodium dodecyl sulfate as well as in specific enzyme activities. Total cytochromes, DPNH oxidase, succinate dehydrogenase, d-lactate dehydrogenase, and Enzyme II of the α-methylglucoside phosphotransferase system were recovered essentially exclusively in cytoplasmic membrane; the specific activities of these in the outer membrane were 1 to 5% of the values obtained for cytoplasmic membrane fractions. In contrast, a phospholipase activity tentatively identified as a mixture of phospholipase A and lysophospholipase, appeared to be localized primarily in the outer membrane. UDP-sugar hydrolase, ribonuclease I and endonuclease I activities were associated with both membrane fractions. Preliminary analysis of the phospholipid composition of the isolated fractions also showed significant quantitative differences in the relative distribution of the major glycerophosphatides. The ratios of phosphatidylglycerol to phosphatidylethanolamine and of cardiolipin to phosphatidylethanolamine in the outer membrane were approximately one-half and one-quarter those of the cytoplasmic membrane.
Discovering Medical Knowledge Using Visual Analytics (2015)

Due to advanced technologies, the amount of biomedical data has been increasing drastically. Such large data sets might be obtained from hospitals, medical practices or laboratories and can be used to discover unknown knowledge and to find and reflect hypotheses. Based on this fact, knowledge discovery systems can support experts to make further decisions, explore the data or to predict future events. To analyze and communicate such a vast amount of information to the user, advanced techniques such as knowledge discovery and information visualization are necessary. Visual analytics combines these fields and supports users to integrate domain knowledge into the knowledge discovery process. This article gives a state-of-the-art overview on visual analytics reseach with a focus on the biomedical domain, systems biology and *omics data.
Cholestatic liver disease in adults may be due to an inherited defect in bile acid biosynthesis (2007)

This case illustrates that infants with an inherited absence of HSD3B7 may survive the neonatal period of life and childhood without treatment with bile acids. A low level of sulphation of the abnormal trihydroxy bile acid formed as a result of enzyme deficiency may be of importance for survival. The possibility that liver disease presenting in the adult may be due to a mutation in the HSD3B7 gene should be considered, especially in cases with familial occurrence of liver disease and earlier periods of liver dysfunction.
Wavelet and multiscale methods for operator equations (1997)

More than anything else, the increase of computing power seems to stimulate the greed for tackling ever larger problems involving large-scale numerical simulation. As a consequence, the need for understanding something like the intrinsic complexity of a problem occupies a more and more pivotal position. Moreover, computability often only becomes feasible if an algorithm can be found that is asymptotically optimal . This means that storage and the number of floating point operations needed to resolve the problem with desired accuracy remain proportional to the problem size when the resolution of the discretization is refined. A significant reduction of complexity is indeed often possible, when the underlying problem admits a continuous model in terms of differential or integral equations. The physical phenomena behind such a model usually exhibit characteristic features over a wide range of scales. Accordingly, the most successful numerical schemes exploit in one way or another the interaction of different scales of discretization. A very prominent representative is the multigrid methodology; see, for instance, Hackbusch (1985) and Bramble (1993). In a way it has caused a breakthrough in numerical analysis since, in an important range of cases, it does indeed provide asymptotically optimal schemes. For closely related multilevel techniques and a unified treatment of several variants, such as multiplicative or additive subspace correction methods, see Bramble, Pasciak and Xu (1990), Oswald (1994), Xu (1992), and Yserentant (1993). Although there remain many unresolved problems, multigrid or multilevel schemes in the classical framework of finite difference and finite element discretizations exhibit by now a comparatively clear profile. They are particularly powerful for elliptic and parabolic problems.
Application of peptide nucleic acid in cancer therapy (1997)

Peptide nucleic acid (PNA) is a DNA mimic with a pseudopeptide backbone composed of aminoethyl glycine units. Several features of PNA, such as superior hybridization affinities to RNA and DNA, high biological stability, and convenient solid-phase synthesis, make it a promising candidate for use as a gene targeting drug. Here we review the chemical and biological properties of PNA in relation to its potential as an anti-cancer drug.
Modulation of endothelial cell proliferation, adhesion, and motility by recombinant heparin‐binding domain and synthetic peptides from the type I repeats of thrombospondin (1993)

Thrombospondin is an inhibitor of angiogenesis that modulates endothelial cell adhesion, proliferation, and motility. Synthetic peptides from the second type I repeat of human thrombospondin containing the consensus sequence-Trp-Ser-Pro-Trp- and a recombinant heparin binding fragment from the amino-terminus of thrombospondin mimic several of the activities of the intact protein. The peptides and heparin-binding domain promote endothelial cell adhesion, inhibit endothelial cell chemotaxis to basic fibroblast growth factor (bFGF), and inhibit mitogenesis and proliferation of aortic and corneal endothelial cells. The peptides also inhibit heparin-dependent binding of bFGF to corneal endothelial cells. The antiproliferative activities of the peptides correlate with their ability to bind to heparin and to inhibit bFGF binding to heparin. Peptides containing amino acid substitutions that eliminate heparin-binding do not alter chemotaxis or proliferation of endothelial cells. Inhibition of proliferation by the peptide is time-dependent and reversible. Thus, the antiproliferative activities of the thrombospondin peptide and recombinant heparin-binding domain result at least in part from competition with heparin-dependent growth factors for binding to endothelial cell proteoglycans. These results suggest that both the Trp-Ser-Xaa-Trp sequences in the type I repeats and the amino-terminal domain play roles in the antiproliferative activity of thrombospondin.
Epidermal Growth Factor Receptor as a Target for Anti-Cancer Agent Design (2010)

The epidermal growth factor (EGF) receptors, one family of protein tyrosine kinases (PTK), are promising targets for the cancer therapy. Many potential inhibitors including monoclonal antibodies (mAbs), reversible inhibitors and irreversible inhibitors have been developed. Some of them have been approved by the FDA or in the stage of clinical trials. This report reviews the recent progress of the structures, functions and inhibitors of the epidermal growth factor receptor tyrosine kinases.
Isolation of embryonic cell‐lines from porcine blastocysts (1995)

Abstract The establishment of porcine (Sus scrofa) embryonic cell‐lines directly from preimplantation blastocysts is described. The cells may be stably maintained on mouse embryonic fibroblast feeder layers without the use of conditioned medium. When placed in suspension culture the cells spontaneously differentiate into cystic embryoid bodies with ectodermal, endodermal, and mesodermal cell types. Culture of these embryonic cell‐lines to confluence on feeder cell monolayers results in the morphological differentiation into fibroblasts, adipocytes, epithelial, neuronal, and muscle‐like cells. The cell‐lines have a normal diploid complement of 38 chromosomes. Scanning electron microscopy of the embryonic cell‐lines reveals flat, polygonal, epithelial‐like cells with numerous microvilli. The differentiation of these embryonic cell‐lines into several cell types indicates a pluripotential cell. The establishment of embryonic cell‐lines from swine should be useful for studies of cell differentiation, developmental, and gene regulation.
Mesenchymal Stem Cell-Conditioned Medium Induces Neutrophil Apoptosis Associated with Inhibition of the NF-κB Pathway in Endotoxin-Induced Acute Lung Injury (2019)

The immunomodulatory effects of mesenchymal stem cells (MSCs) are established. However, the effects of MSCs on neutrophil survival in acute lung injury (ALI) remain unclear. The goal of this study was to investigate the effect of an MSC-conditioned medium (MSC-CM) on neutrophil apoptosis in endotoxin-induced ALI. In this study, an MSC-CM was delivered via tail vein injection to wild-type male C57BL/6 mice 4 h after an intratracheal injection of lipopolysaccharide (LPS). Twenty-four hours later, bronchoalveolar lavage fluid (BALF) and lung tissue were collected to perform histology, immunohistochemistry, apoptosis assay of neutrophil, enzyme-linked immunosorbent assays, and an electrophoretic mobility shift assay. Human neutrophils were also collected from patients with sepsis-induced acute respiratory distress syndrome (ARDS). Human neutrophils were treated <i>in vitro</i> with LPS, with or without subsequent MSC-CM co-treatment, and were then analyzed. Administration of the MSC-CM resulted in a significant attenuation of histopathological changes, the levels of interleukin-6 and macrophage inflammatory protein 2, and neutrophil accumulation in mouse lung tissues of LPS-induced ALI. Additionally, MSC-CM therapy enhanced the apoptosis of BALF neutrophils and reduced the expression of the anti-apoptotic molecules, Bcl-xL and Mcl-1, both in vivo and <i>in vitro</i> experiments. Furthermore, phosphorylated and total levels of nuclear factor (NF)-κB p65 were reduced in lung tissues from LPS + MSC-CM mice. Human MSC-CM also reduced the activity levels of NF-κB and matrix metalloproteinase-9 in the human neutrophils from ARDS patients. Thus, the results of this study suggest that the MSC-CM attenuated LPS-induced ALI by inducing neutrophil apoptosis, associated with inhibition of the NF-κB pathway.
The Whole Story of the Two-Electron Bond, with the δ Bond as a Paradigm (2000)

It is shown that the delta bond, as found particularly in the Re(2)(6+) and Mo(2)(4+) cores of hundreds of compounds, provides a paradigm for the behavior of two-electron bonds of all types. By control of the angle of twist around the M-M axis, the strength of the bond can be systematically varied. By means of conventional electronic spectroscopy, nuclear magnetic resonance spectroscopy, and two-photon excitation spectroscopy, the entire picture of the manifold of four states for two electrons bonding two atoms, as first described by Coulson and Fischer in 1949, has been confirmed.
Comparison of responses to vasoactive drugs in human and rat cerebral arteries using myography and pressurized cerebral artery method (2012)

All tested substances with the exception of VIP and carbachol have been found to elicit migraine-like attacks in migraineurs. Since these two agents have vasodilatory effects in humans, it suggests that vasodilatation is not the only reason for eliciting a migraine-like attack in migraineurs. In addition, there are significant species differences that show the importance of performing experiments in human vessels.
Inhibition of Pseudomonas aeruginosa Biofilm Formation with Bromoageliferin Analogues (2007)

Two analogues of the marine natural product bromoageliferin have been synthesized and subsequently assayed for the ability to inhibit the formation of Pseudomonas aeruginosa biofilms. Both compounds inhibited the ability of Pseudomonas aeruginosa strains PAO1 and PA14 to form biofilms; however, they displayed differential toxicity to planktonic bacteria. The cis analogue, CAGE, was found to possess greater toxicity than the trans analogue, TAGE. These compounds have no structural homology to any known inhibitors of Pseudomonas aeruginosa biofilms.
Anandamide Hydrolysis by Human Cells in Culture and Brain (1998)

Anandamide (arachidonylethanolamide; AnNH) has important neuromodulatory and immunomodulatory activities. This lipid is rapidly taken up and hydrolyzed to arachidonate and ethanolamine in many organisms. As yet, AnNH inactivation has not been studied in humans. Here, a human brain fatty-acid amide hydrolase (FAAH) has been characterized as a single protein of 67 kDa with a pI of 7.6, showing apparent Km and Vmax values for AnNH of 2.0 +/- 0.2 microM and 800 +/- 75 pmol.min-1.mg of protein-1, respectively. The optimum pH and temperature for AnNH hydrolysis were 9.0 and 37 degreesC, respectively, and the activation energy of the reaction was 43.5 +/- 4.5 kJ.mol-1. Hydro(pero)xides derived from AnNH or its linoleoyl analogues by lipoxygenase action were competitive inhibitors of human brain FAAH, with apparent Ki values in the low micromolar range. One of these compounds, linoleoylethanolamide is the first natural inhibitor (Ki = 9.0 +/- 0.9 microM) of FAAH as yet discovered. An FAAH activity sharing several biochemical properties with the human brain enzyme was demonstrated in human neuroblastoma CHP100 and lymphoma U937 cells. Both cell lines have a high affinity transporter for AnNH, which had apparent Km and Vmax values for AnNH of 0.20 +/- 0.02 microM and 30 +/- 3 pmol.min-1.mg of protein-1 (CHP100 cells) and 0.13 +/- 0.01 microM and 140 +/- 15 pmol.min-1.mg of protein-1 (U937 cells), respectively. The AnNH carrier of both cell lines was activated up to 170% of the control by nitric oxide.
Ligand discovery and virtual screening using the program LIDAEUS (2007)

This paper discusses advances in docking and scoring approaches with examples from the high-throughput virtual screening program LIDAEUS. We describe the discovery of small molecule inhibitors for the immunophilin CypA, the cyclin-dependent kinase CDK2 and the cyclapolin series of potent Polo-like kinase inhibitors. These results are discussed in the context of advances in massively parallel computing and in the development of annotated databases.
Natural treatment of chronic rhinosinusitis. (2006)

Chronic rhinosinusitis (CRS) is one of the most common long-term illnesses in the United States, affecting approximately 14 percent of the population. CRS is a challenging condition to treat, partly due to its multifaceted, poorly understood pathophysiology. Treatment goals include maintaining open drainage and decreasing inflammation while improving tissue integrity and limiting causative factors. This review covers the etiology, pathology, and diagnosis of CRS, as well as mainstream and alternative treatments. Discussion of alternative therapeutics includes nutrients and botanicals (ascorbic acid, bromelain, N-acetylcysteine, quercetin, undecylenic acid, and Urtica dioica and other herbal medicines) and procedures (nasal irrigation and naso-sympatico treatments). The influences of diet and air quality on CRS are also discussed.
DEFINING THE FULL THERAPEUTIC POTENTIAL OF RECOMBINANT GROWTH FACTORS IN THE POST RADIATION-ACCIDENT ENVIRONMENT: THE EFFECT OF SUPPORTIVE CARE PLUS ADMINISTRATION OF G-CSF (2005)

Radiation accidents are uncontrolled and ill-defined, the exposure is nonuniform and may be partial body, forecasting a variable dose distribution and sparing of hematopoietic stem cells. We propose that the "best" treatment protocol available now for severely irradiated personnel with acute hematopoietic syndrome is the combination of supportive care and administration of recombinant cytokines as soon as possible after irradiation. Herein, we demonstrate the significant effect of G-CSF administration on lethally irradiated canines. G-CSF administered early and continuously after irradiation increased neutrophil recovery and survival over a lethal and supralethal dose range. The respective LD50/30 for the control, supportive care-alone cohorts of 338 cGy, was increased to 488 cGy with administration of G-CSF. Clearly, the use of supportive care and G-CSF enhanced recovery of myelopoiesis and survival after lethal doses of irradiation.
Virtualized in-cloud security services for mobile devices (2008)

Modern mobile devices continue to approach the capabilities and extensibility of standard desktop PCs. Unfortunately, these devices are also beginning to face many of the same security threats as desktops. Currently, mobile security solutions mirror the traditional desktop model in which they run detection services on the device. This approach is complex and resource intensive in both computation and power. This paper proposes a new model whereby mobile antivirus functionality is moved to an off-device network service employing multiple virtualized malware detection engines. Our argument is that it is possible to spend bandwidth resources to significantly reduce on-device CPU, memory, and power resources. We demonstrate how our in-cloud model enhances mobile security and reduces on-device software complexity, while allowing for new services such as platform-specific behavioral analysis engines. Our benchmarks on Nokia's N800 and N95 mobile devices show that our mobile agent consumes an order of magnitude less CPU and memory while also consuming less power in common scenarios compared to existing on-device antivirus software.
A Valved Hepatic Portoduodenal Intestinal Conduit for Biliary Atresia (1991)

Forty-six consecutive patients with biliary atresia were operated on at our institution during the 11-year period between 1978 and 1989. Their ages at operation ranged from 18 to 153 days (mean, 59 days). After dissecting the porta hepatis structures by Kasai operation, a biliointestinal anastomosis was constructed with a valved hepatic portoduodenal intestinal conduit in all cases. The intestinal valve is an intussuscepted muscular valve. Valvular function was examined radiologically. The upper gastrointestinal series demonstrated no reflux of contrast material into the conduit proximal to the valve and liver scintigraphy demonstrated that radioactive isotope drained readily into the duodenum through the valve. Thirty-nine of the forty-six patients (85%) had bile drainage after initial operation. At present 30 patients (65%) are alive without jaundice, 6 (13%) are alive with jaundice, and 10 (22%) are dead. The 5-year jaundice-free survival rate was 64%. Cholangitis occurred in 9 of 39 patients (23%) who had obtained apparent bile drainage: 5 had tractable cholangitis and 4 had refractory cholangitis. Reoperation restored bile flow in 2 of 8 patients who abruptly ceased to have bile drainage without cholangitis. In conclusion, with a valved hepatic portoduodenal intestinal conduit, the incidence of cholangitis was decreased, its medical control became easier, and the survival rate was improved.
Detection of somatic mutations in the mitochondrial DNA control region of colorectal and gastric tumors by heteroduplex and single‐strand conformation analysis (1997)

Each entire hypervariable region of the mitochondrial DNA control region was screened for mutations from paired normal and tumor DNA corresponding to a group of 21 patients (13 colorectal and 8 gastric adenocarcinomas) using both heteroduplex analysis and single-strand conformation analysis. These two mutation scanning strategies allowed the identification of sequence alterations in 3/13 (23%) colorectal tumors and in 3/8 (37%) gastric tumors. Heteroduplex analysis showed the heteroplasmic state of the majority of these tumor mutations. Sequence analysis revealed two A:T/G:C transitions (nucleotide positions: 16241 and 16166) in hypervariable region 1 (HV1) and two C:G/T:A transitions (nucleotide positions: 76 and 312), one A:T/G:C transition (nucleotide position: 93), a 1-basepair C:G deletion (nucleotide position: 309), and a 2-base-pair CC:GG insertion (nucleotide position: 309) in the HV 2 region. A considerable proportion of these mutations was found in homopolymeric regions which are highly polymorphic among humans. Different mechanisms (clonal expansion, increased oxidative damage, and nuclear mutator mutations) were suggested to explain the increased mitochondrial DNA mutation rate observed in cancer.
Ligand-Induced Conformational Changes of Thymidylate Synthase Detected by Limited Proteolysis (1995)

Limited tryptic proteolysis was used to investigate conformational changes of thymidylate synthase from Lactobacillus casei induced by ligand binding. Most of the identified sites of proteolysis were between R72 and R178, a region that includes a large loop containing residues 90-139 that is absent in thymidylate synthase from most other sources. Hydrolysis at both ends of this region was affected by the presence of dUMP. With dUMP, the preference of initial hydrolysis at the N-terminus of this region was switched from R78 to R72, and hydrolysis at R178 was retarded; the latter effect may be primarily a consequence of steric hinderance since R178 is involved in binding the phosphate moiety of dUMP. Orthophosphate had an effect similar to that of dUMP, not only in retarding hydrolysis at the phosphate binding site (R178) but also in retarding hydrolysis at R78 in favor of R72. Alkylation of the catalytically essential sulfhydryl group of thymidylate synthase by iodoacetamide also resulted in R72 being favored over R78 as a site of initial proteolysis. Its effect on hydrolysis at R178 was, as expected, less than that of dUMP or phosphate. These results indicate that dUMP binding induces conformational changes in thymidylate synthase. Phosphate binding and sulfhydryl alkylation also induce conformational changes similar to those resulting from dUMP binding. While the similarity of the proteolytic behavior of thymidylate synthase in the presence of dUMP or phosphate agrees with the report by Finer-Moore et al.(ABSTRACT TRUNCATED AT 250 WORDS)