gebhart/patrepeval huggingface dataset:
Translation Initiation Factor 5A and Its Hypusine Modification Are Essential for Cell Viability in the Yeast Saccharomyces cerevisiae (1991)

Translation intitiation factor eIF-5A (previously named eIF-4D) is a highly conserved protein that promotes formation of the first peptide bond. One of its lysine residues is modified by spermidine to form hypusine, a posttranslational modification unique to eIF-5A. To elucidate the function of eIF-5A and determine the role of its hypusine modification, the cDNA encoding human eIF-5A was used as a probe to identify and clone the corresponding genes from the yeast Saccharomyces cerevisiae. Two genes named TIF51A and TIF51B were cloned and sequenced. The two yeast proteins are closely related, sharing 90% sequence identity, and each is ca. 63% identical to the human protein. The purified protein expressed from the TIF51A gene substitutes for HeLa eIF-5A in the mammalian methionyl-puromycin synthesis assay. Strains lacking the A form of eIF-5A, constructed by disruption of TIF51A with LEU2, grow slowly, whereas strains lacking the B form, in which HIS3 was used to disrupt TIF51B, show no growth rate phenotype. However, strains with both TIF51A and TIF51B disrupted are not viable, indicating that eIF-5a is essential for cell growth in yeast cells. Northern (RNA) blot analysis shows two mRNA species, a larger mRNA (0.9 kb) transcribed from TIF51A and a smaller mRNA (0.8 kb) encoded by TIF51B. Under the aerobic growth conditions of this study, the 0.8-kb TIF51B transcript is not detected in the wild-type strain and is expressed only when TIF51A is disrupted. The TIF51A gene was altered by site-directed mutagenesis at the site of hypusination by changing the Lys codon to that for Arg, thereby producing a stable protein that retains the positive charge but is not modified to the hypusine derivative. The plasmid shuffle technique was used to replace the wild-type gene with the mutant form, resulting in failure of the yeast cells to grow. This result indicates that hypusine very likely is required for the vital in vivo function of eIF-5A and suggests a precise, essential role for the polyamine spermidine in cell metabolism.
Focal adhesion kinase in integrin-mediated signaling (1999)

Integrins serve as adhesion receptors for extracellular matrix proteins and also transduce biochemical signals into the cell. These signaling events regulate such cellular processes as proliferation, apoptosis, migration and spreading. Focal adhesion kinase (FAK) is an important protein tyrosine kinase which mediates several integrin signaling pathways. Putative mechanisms of integrin-mediated FAK activation and localization to focal adhesions are discussed here. FAK interacts with a number of signaling and cytoskeletal proteins, including Src, phosphatidylinositol 3-kinase, Grb2, p130Cas and paxillin. Both the mechanisms and outcomes of these interactions are also presented. Finally, FAK's roles in the regulation of several integrin-mediated cellular events are discussed, including the promotion of cell migration, proliferation and spreading, and the prevention of cell apoptosis.
DuraSeal Magnetic Resonance and Computed Tomography Imaging: Evaluation in a Canine Craniotomy Model (2006)

The hydrogel sealant can be observed with cross sectional imaging and can be distinguished from cerebrospinal fluid using a CT scan, complemented by an occasional MRI scan. In addition, complete absorption of the hydrogel, with closure of the remaining void was noted. Histological examination found an unremarkable response with no neurotoxicity or space-filling defect.
Introduction (2011)

This book addresses the recent, and to a large extent still much unexplored, developments concerning care in Europe. It considers care as a crucial part of European restructuring of care labour markets, the contents of care and the different forms of care that range from the EU legislation level to the diversities among the individual care workers’ life situations and experiences of being cared for in present-day Europe. The book argues for a strong statement about the complexity of care research — no longer restricted within the domain of social policy research but pertinently addressed in political science and in governance, legal studies and feminist research, and thus calls for a multidisciplinary approach. The chapters in this book show the variety of care arrangements and the multitude of value judgments behind the family-, market- and state-organized care that prevails in Europe. Therefore, questions about forms of Europeanization, the diverse paths for care arrangements and the gender patterns in relation to citizenship and civil society are important for the Europe of the future.
Gβγ Binding to GIRK4 Subunit Is Critical for G Protein-gated K+ Channel Activation (1998)

The cardiac G protein-gated K+ channel, IKACh, is directly activated by G protein beta gamma subunits (Gbeta gamma). IKAChis composed of two inward rectifier K+ channel subunits, GIRK1 and GIRK4. Gbeta gamma binds to both GIRK1 and GIRK4 subunits of the heteromultimeric IKACh. Here we delineate the Gbeta gamma binding regions of IKACh by studying direct Gbeta gamma interaction with native purified IKACh, competition of this interaction with peptides derived from GIRK1 or GIRK4 amino acid sequences, mutational analysis of regions implicated in Gbeta gamma binding, and functional expression of mutated subunits in mammalian cells. Only two GIRK4 peptides, containing amino acids 209-225 or 226-245, effectively competed for Gbeta gamma binding. A single point mutation introduced into GIRK4 at position 216 (C216T) dramatically reduced the potency of the peptide in inhibiting Gbeta gamma binding and Gbeta gamma activation of expressed GIRK1/GIRK4(C216T) channels. Conversion of 5 amino acids in GIRK4 (226-245) to the corresponding amino acids found in the G protein-insensitive IRK1 channel, completely abolished peptide inhibition of Gbeta gamma binding to IKACh and Gbeta gamma activation of GIRK1/mutant GIRK4 channels. We conclude from this data that Gbeta gamma binding to GIRK4 is critical for IKACh activation.
Induction of autophagic cell death in malignant glioma cells by arsenic trioxide. (2003)

Recent clinical data shows that arsenic trioxide (As(2)O(3)) causes remission in patients with acute promyelocytic leukemia and multiple myeloma without severe side effects. Laboratory data suggest that As(2)O(3) induces apoptosis or cell differentiation of hematopoietic or solid tumor cells. To date, there has been no study on the effects of As(2)O(3) on glioma cells. In this study, we investigated the in vitro effect of As(2)O(3) on cell growth inhibition and cell death mechanisms in human glioma cells. As(2)O(3) significantly inhibited the proliferation of all six of the glioma cell lines (U373, U87, U251, GB1, A-172, and T98G) tested in this study in a dose-dependent manner. The IC(50) of As(2)O(3) for all of the tumor cell lines was <2 micro M. Previous studies have shown that this is a clinically safe concentration. Treatment with 2 micro M As(2)O(3) induced G(2)/M arrest in all of the glioma cell lines. Autophagy (programmed cell death type II), but not apoptosis (programmed cell death type I), was detected by electron microscopy in U-373-MG cells treated with 2 micro M As(2)O(3). Caspase inhibitors did not halt As(2)O(3)-induced cell death. Furthermore, combination of As(2)O(3) with bafilomycin A1 autophagy inhibitor enhanced the antitumor effect of As(2)O(3) through induction of apoptosis. These findings suggest that As(2)O(3) at a clinically safe concentration may be an effective chemotherapeutic agent for malignant gliomas.
Estrogens, Progestogens, Normal Breast Cell Proliferation, and Breast Cancer Risk (1993)

Journal Article Estrogens, Progestogens, Normal Breast Cell Proliferation, and Breast Cancer Risk Get access Malcolm C. Pike, Malcolm C. Pike 1Department of Preventive Medicine, School of Medicine, University of Southern CaliforniaLos Angeles, CA Dr. Malcolm C. Pike, Department of Preventive Medicine, School of Medicine, University of Southern California, 1420 San Pablo Street, PMB A 201, Los Angeles, CA 90033-9987 Search for other works by this author on: Oxford Academic PubMed Google Scholar Darcy V. Spicer, Darcy V. Spicer 2Department of Medicine, School of Medicine, University of Southern CaliforniaLos Angeles, CA Search for other works by this author on: Oxford Academic PubMed Google Scholar Laila Dahmoush, Laila Dahmoush 3Department of Pathology, School of Medicine, University of Southern CaliforniaLos Angeles, CA Search for other works by this author on: Oxford Academic PubMed Google Scholar Michael F. Press Michael F. Press 3Department of Pathology, School of Medicine, University of Southern CaliforniaLos Angeles, CA Search for other works by this author on: Oxford Academic PubMed Google Scholar Epidemiologic Reviews, Volume 15, Issue 1, 1993, Pages 17–30, https://doi.org/10.1093/oxfordjournals.epirev.a036102 Published: 01 March 1993 Article history Received: 19 January 1993 Published: 01 March 1993 Revision received: 16 April 1993
[Renal osteodystrophy (2): its treatment in renal insufficiency before dialysis]. (2000)

1. In the patient with renal insufficiency before dialysis, the phosphocalcic disorders appear insidiously. They are dominated by hyperparathyroidism which will be diagnosed on the initially yearly determination of plasma intact PTH as soon as creatinine clearance decreases below 60 ml/min, eventhough there is still no modification in plasma concentrations of calcium and phosphate. Its diagnosis should lead to initiate the therapeutic measures in order to prevent the irreversible thining of the corticals by endosteal resorption and later the occurrence of histological and radiological osteitis fibrosa favoring fractures. 2. Hyperparathyroidism prevention relies on two main measures: prevention of phosphate retention and hypocalcemia is implemented by progressive phosphate and protein restriction (from 1 g/kg/day when Ccr < 60 ml/min to 0.6 g/kg/day when Ccr < 20 ml/min) and administration of CaCO3 (1.5 g at lunch and dinner to better complex the phosphate) as soon as PTH is above normal; optimal vitamin D repeletion will be implemented by systematic supplementation of native vitamin D or 25OH vitamin D3 in order to bring P25OHD between 30-60 ng/ml (75-150 nmol/l) or more generally around the upper limit of the epidemiologic range of the laboratory; these measures should aim at maintaining plasma intact PTH in its optimal range variable with the degree of renal insufficiency: 0.5-1; 1-2.5 and 2-3 folds the upper limit of normal for creatinine clearance respectively at 60-30; 30-10 and < 10 ml/min. 3. Because of their hyperphosphatemic and hypercalcemic effect, 1 alpha-hydroxylated vitamin D derivatives will be regularly efficient and safe only when non-calcemic non-aluminic phosphate binder will be available and proven to be without side-effects. 4. Instrumental (surgical or by alcohol injection) parathyroidectomy should be considered when plasma intact PTH is > 5 to 7 times the upper limit of normal in the presence of hypercalcemia (> 2.60 mmol/l) and/or hyperphosphatemia (> 1.70 nmol/l) in spite of the above measures, the decision being reinforced by coexistence of bone radiologic abnormalities and metastatic calcifications. 5. Adynamic bone diseases are rare before hemodialysis in the absence of aluminum exposition by the drinking water or the aluminum-phosphate binders. In absence of aluminum it will be prevented by maintaining PTH in its optimal range. 6. Osteomalacia before hemodialysis is mainly due, in the absence of aluminum exposition, to vitamin D deficiency, hypocalcemia and acidosis. It is readily cured by physiological doses of native vitamin D or 25OH vitamin D3 bringing plasma 25 OHD above 16 ng/ml, in association with alkaline salts of calcium and if necessary of sodium bicarbonate.
Reduction of magnetic interaction in CoB/Pd multilayer perpendicular media using a phase-separated Pd–SiO underlayer (2003)

To realize CoB15/Pd multilayer perpendicular media with weak intergranular exchange coupling, we utilize PdSi18 (at. %) alloy, which contains elements that have large difference of affinity for oxygen, as the underlayer. It is clarified that introducing oxygen into Ar atmosphere during deposition of the underlayer substantially reduces the intergranular exchange coupling of the multilayer. Microstructural analysis reveals that the introduction of oxygen has separated the PdSi18 underlayer into two phases and enhances the formation of grain boundaries of the multilayer. It is suggested that the two-phase-separated Pd–SiO underlayer becomes a template for the growth of the multilayer and promotes the formation of grain boundaries in the multilayer, which reduces the exchange coupling through isolation of grains of the multilayer. In addition, independent of the oxygen pressure, coercivity and anisotropy energy maintain values of around 3.5 kOe and 2.3×106 erg/cm3, respectively. It is concluded that the two-phase-separated Pd–SiO underlayer, fabricated by introducing oxygen during sputtering of PdSi18 underlayer, is effective for reducing the magnetic exchange coupling without degrading the magnetic properties.
Socioeconomic Status and Psychiatric Disorders: The Causation-Selection Issue (1992)

Are inverse relations between psychiatric disorders and socioeconomic status due more to social causation (adversity and stress) or social selection (downward mobility of genetically predisposed)? This classical epidemiological issue is tested by focusing on ethnic status in relation to socioeconomic status. Ethnic status cannot be an effect of disorder because it is present at birth whereas socioeconomic status depends on educational and occupational attainment. A birth cohort sample of 4914 young, Israel-born adults of European and North African background was selected from the country's population register, screened, and diagnosed by psychiatrists. Results indicate that social selection may be more important for schizophrenia and that social causation may be more important for depression in women and for antisocial personality and substance use disorders in men.
Immunotherapy for West Nile virus infection (2005)

The treatment for infection by West Nile virus (WNV) is currently supportive. New research, however, suggests that a monoclonal antibody may prove an effective treatment in the future.[1][1] ![Figure][2]</img> Figure. Photo by: JupiterImages WNV is a single-stranded RNA flavivirus related to
Boron neutron capture therapy for cancer. Realities and prospects (1992)

Boron neutron capture therapy (BNCT) is based on the nuclear reaction that occurs when a stable isotope, boron-10 (10B), is irradiated with low-energy thermal neutrons (nth) to yield (4He) alpha-particles and 7Li nuclei (10B+nth-->[11B]-->4He+7Li+2.31 MeV). The success of BNCT as a tumoricidal modality is dependent on the delivery of a sufficient quantity of 10B and nth to individual cancer cells to sustain a lethal 10B(n, alpha) 7Li reaction. The current review covered the radiobiologic considerations on which BNCT is based, including a brief discussion of microdosimetry and normal tissue tolerance. The development of tumor-localizing boron compounds was discussed, including the sulfhydryl-containing polyhedral borane, sodium borocaptate (Na2B12H11SH), and boronophenylalanine (BPA), both of which are currently being used clinically in Japan as capture agents for malignant brain tumors and melanomas, respectively. Compounds currently under evaluation, such as boronated porphyrins, nucleosides, liposomes, and monoclonal antibodies (MoAbs), were also considered. Nuclear reactors have been used as the exclusive source of neutrons for BNCT. The use of low-energy (0.025 eV) thermal neutrons and higher-energy (1-10,000 eV) epithermal beams, beam optimization, and possible alternative neutron sources (accelerators) were also discussed. Clinical studies performed in the United States during the 1950s and 1960s for the treatment of malignant brain tumors were reviewed. Current studies in Japan and future studies in Europe and the United States concerning the treatment of glioblastomas and melanomas by BNCT were discussed, as were critical issues that must be addressed if BNCT is ever to be a useful therapeutic modality.
Assessment of whole-body composition with dual-energy x-ray absorptiometry. (1992)

Dual-energy x-ray absorptiometry (DXA) allows noninvasive direct measurement of the three major components of body composition: lean body mass (LBM), fat body mass (FBM), and bone mineral body mass (BBM). To study the accuracy and short-term and long-term precision of body composition measurements, the authors measured body composition with DXA in 60 healthy young adults. Independent measurement of LBM (LBMK-40), obtained from the determination of the whole-body content of potassium-40 with a whole-body scintillation detector, was highly correlated with LBM determined with DXA (LBMDXA) (LBMK-40 = 1.069.LBMDXA,R2 = .996). Assessment of body composition in 10 patients with acquired immunodeficiency syndrome (AIDS) and 10 patients with cystic fibrosis was performed with DXA. The AIDS patients showed a marked decrease in LBM, while in patients with cystic fibrosis, LBM and BBM were decreased. DXA measurements of body composition appeared accurate and precise enough to be of clinical relevance in detecting specific alterations of body composition.
Systemic expression of a bacterial gene by a tobacco mosaic virus-based vector. (1991)

Tobacco mosaic virus (TMV) produces large quantities of RNA and protein on infection of plant cells. This and other features, attributable to its autonomous replication, make TMV an attractive candidate for expression of foreign sequences in plants. However, previous attempts to construct expression vectors based on plant RNA viruses, such as TMV, have been unsuccessful in obtaining systemic and stable movement of foreign genes to uninoculated leaves in whole plants. A hybrid viral RNA (TB2) was constructed, containing sequences from two tobamoviruses (TMV-U1 and odontoglossum ringspot virus). Two bacterial sequences inserted independently into TB2 moved systemically in Nicotiana benthamiana, although they differed in their stability on serial passage. Systemic expression of the bacterial protein neomycin phosphotransferase was demonstrated. Hybrid RNAs containing both TMV-U1 and the inserted bacterial gene sequences were encapsidated by the odontoglossum ringspot virus coat protein, facilitating their transmission and amplification on passaging to subsequent plants. The vector TB2 provides a rapid means of expressing genes and gene variants in plants.
Cytotoxicity of mitomycin C and adriamycin in freshly isolated rat hepatocytes: the role of cytochrome P450. (1994)

The role of cytochrome P450 (P450) in the cytotoxicity of mitomycin C (MMC) and Adriamycin (ADR) was investigated in freshly isolated hepatocytes from phenobarbital-induced rats. The loss of cell viability [measured as lactate dehydrogenase (LDH) leakage] upon MMC exposure was accompanied by a rapid and extensive intracellular glutathione (GSH) depletion and followed by minor lipid peroxidation (LPO). Coincubation of the hepatocytes with the P450 inhibitors, metyrapone and SK&F 525-A, strongly protected against MMC-induced LDH leakage, GSH depletion, and LPO. Inasmuch as the depletion of intracellular GSH by MMC, which is considered as a critical event in the development of MMC cytotoxicity, was not accompanied by a stoichiometric oxidation to oxidized GSH (GSSG), the formation of a MMC-GSH conjugate after one-electron reductive bioactivation of MMC by P450 was anticipated. In contrast to MMC, ADR was only cytotoxic to the hepatocytes upon prior depletion of intracellular GSH with diethylmaleate. Addition of metyrapone and SK&F 525-A completely protected the hepatocytes against ADR-induced LDH leakage and LPO. Moreover, the ADR-induced LDH leakage and LPO were strongly inhibited by dimethyl sulfoxide and ethanol, indicating that hydroxyl radicals were involved in the cytotoxicity of ADR. In conclusion, the present investigations indicate that P450 plays a major role in the cytotoxicity of both MMC and ADR in freshly isolated hepatocytes from phenobarbital-induced rats. The present findings lead to a better understanding of the mechanism of the cytotoxic actions of both MMC and ADR.
Endotoxin and cisplatin synergistically induce renal dysfunction and cytokine production in mice (2007)

A major toxicity of the cancer chemotherapeutic agent cisplatin is acute renal failure. Sepsis is a common cause of acute renal failure in humans and patients who receive cisplatin are at increased risk for sepsis. Accordingly, this study examined the interactions between cisplatin and endotoxin in vivo with respect to renal function and cytokine production. Mice were treated with either a single dose of cisplatin or two doses of LPS administered 24 h apart, or both agents in combination. Administration of 10 mg/kg cisplatin had no effect on blood urea nitrogen or creatinine levels throughout the course of the study. LPS resulted in a modest rise in blood urea nitrogen at 24 and 48 h, which returned to normal by 72 h. In contrast, mice treated with both cisplatin and LPS developed severe renal failure and an increase in mortality. Urine, but not serum, TNF-alpha levels showed a synergistic increase by cisplatin and LPS. Urinary IL-6, MCP-1, KC, and GM-CSF also showed a synergistic increase with cisplatin+LPS treatment. The renal dysfunction induced by cisplatin+LPS was completely dependent on TLR4 signaling and partially dependent on TNF-alpha production. Increased cytokine production was associated with a moderate increase in infiltrating leukocytes which was not different between cisplatin+LPS and LPS alone. These results indicate that cisplatin and LPS act synergistically to produce nephrotoxicity which may involve proinflammatory cytokine production.
Synthesis and Evaluation of 2‘-Substituted 4-(4‘-Carboxy- or 4‘-carboxymethylbenzylidene)-N-acylpiperidines: Highly Potent and in Vivo Active Steroid 5α-Reductase Type 2 Inhibitors (2002)

Sixteen compounds derived from N-acyl-4-benzylidenepiperidine-4'-carboxylic acids were synthesized and evaluated for inhibition of rat and human steroid 5alpha-reductase isozymes types 1 and 2. In the dicyclohexylacetyl series, fluorination in the 2-position of the benzene nucleus (15), exchange of the carboxy group by a carboxymethyl moiety (20), and combination of both structural modifications (25) led to highly active inhibitors of the human type 2 isozyme (IC(50) values: 15, 11 nM; 20, 6 nM; 25, 7 nM; finasteride, 5 nM). In vivo all compounds tested markedly reduced the prostate weights in castrated testosterone-treated rats. Oral activity was shown for compound 7. From the finding that compound 15 is active in the rat, although it is a rather poor inhibitor of the rat enzyme and is a strong inhibitor of the human enzyme, it is concluded that it should be highly potent in men.
Selecting Machine Learning Algorithms Using Regression Models (2015)

In performing data mining, a common task is to search for the most appropriate algorithm(s) to retrieve important information from data. With an increasing number of available data mining techniques, it may be impractical to experiment with many techniques on a specific dataset of interest to find the best algorithm(s). In this paper, we demonstrate the suitability of tree-based multi-variable linear regression in predicting algorithm performance. We take into account prior machine learning experience to construct meta-knowledge for supervised learning. The idea is to use summary knowledge about datasets along with past performance of algorithms on these datasets to build this meta-knowledge. We augment pure statistical summaries with descriptive features and a misclassification cost, and discover that transformed datasets obtained by reducing a high dimensional feature space to a smaller dimension still retain significant characteristic knowledge necessary to predict algorithm performance. Our approach works well for both numerical and nominal data obtained from real world environments.