gebhart/patrepeval huggingface dataset:
Maturation of Iron-Sulfur Proteins in Eukaryotes: Mechanisms, Connected Processes, and Diseases (2008)

Iron-sulfur (Fe/S) proteins are involved in a wide variety of cellular processes such as enzymatic reactions, respiration, cofactor biosynthesis, ribosome biogenesis, regulation of gene expression, and DNA-RNA metabolism. Assembly of Fe/S clusters, small inorganic cofactors, is assisted by complex proteinaceous machineries, which use cysteine as a source of sulfur, combine it with iron to synthesize an Fe/S cluster on scaffold proteins, and finally incorporate the cluster into recipient apoproteins. In eukaryotes, such as yeast and human cells, more than 20 components are known that facilitate the maturation of Fe/S proteins in mitochondria, cytosol, and nucleus. These biogenesis components also perform crucial roles in other cellular pathways, e.g., in the regulation of iron homeostasis or the modification of tRNA. Numerous diseases including several neurodegenerative and hematological disorders have been associated with defects in Fe/S protein biogenesis, underlining the central importance of this process for life.
PROLIFERATION AND PLANT REGENERATION FROM THE NODAL REGION OF ZEA MAYS L. (MAIZE, GRAMINEAE) EMBRYOS (1983)

Immature embryos of Zea mays L. (maize), cultured on Murashige and Skoog's medium containing 2,4‐dichlorophenoxyacetic acid (2,4‐D, 0.25–1.0 mg/l) and sucrose (3, 6 and 12%), produced a narrow ridge of tissue in the nodal region of the embryo axis, opposite the scutellum. Only those embryos which were placed with the scutellum in contact with medium showed such a response. The ridge of tissue further proliferated and formed a compact and opaque callus that appeared similar to the scutellar callus. Morphogenesis took place on media containing low concentrations of both 2,4‐D and sucrose. Plant regeneration was achieved and is interpreted to take place by the precocious germination of somatic embryos. It is suggested that the ridge of tissue formed at the node may represent an evolutionarily extinct epiblast of the maize embryo and may be cotyledonary in nature.
Aspirin protects against gastric cancer: Results of a case-control study from Moscow, Russia (1999)

A case-control study of stomach cancer which includes 448 cases and 610 hospital controls has been conducted in Moscow, Russia. Information on life-style habits, such as smoking, alcohol consumption, diet, medical history and use of different medications including aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) was collected using a self-administered structured questionnaire. Venous blood was drawn from 361 cases and 441 controls. A serological test for Helicobacter pylori immunoglobulin G was performed to detect infected individuals. Use of aspirin and other NSAIDs was associated with protection against cancer of the stomach (OR = 0.60, 95% CI 0.41-0.90). Analysis by subsite revealed that aspirin did not affect the risk of cancer of the gastric cardia but had a protective effect for non-cardia gastric cancer. The OR associated with use of aspirin adjusted for age and education for both sexes combined was 0.49 (95% CI 0.31-0.77). A decrease in relative risk was statistically significant for men (OR = 0.48, 95% CI 0.25-0.92) and women (OR = 0.52, 95% CI 0.28-0.97). Controlling for major risk factors did not attenuate the reduction in risk. The observed associations were also present in individuals who were H. pylori immunoglobulin G-positive. There was no reduction in risk associated with aspirin and/or non-aspirin NSAIDs among non-infected subjects.
Cloning, expression, purification, and biological activity of recombinant native and variant human alpha 1-antichymotrypsins. (1990)

Human alpha 1-antichymotrypsin has been cloned, sequenced and expressed in Escherichia coli and recombinant protein as well as point-specific mutants have been purified and characterized. The corrected gene-deduced amino acid sequence has 45% overall identity with alpha 1-protease inhibitor, which is higher than the 42% previously reported (Chandra, T., Stackhouse, R., Kidd, V. J., Robson, J. H., and Woo, S. L. C. (1983) Biochemistry 22, 5055-5060). Recombinant antichymotrypsin (rACT) is similar to natural antichymotrypsin with respect to the specificity of its interactions with proteases. Its second-order rate constant for association with bovine chymotrypsin is 6-8 x 10(5) M-1 s-1, which is identical to that of the serum-derived inhibitor. Site-specific mutagenesis has been used to produce two variants of rACT in which the P1 position has been changed from leucine to either methionine (L358M-rACT) or arginine (L358R-rACT). L358M-rACT has a specificity of inhibitory activity toward serine proteases closely similar to that of native rACT. By contrast, the specificity of L358R-rACT is quite different from that of native rACT, most notably in efficiently inhibiting trypsin and human thrombin while showing a decreased ability to inhibit chymotrypsin.
Propulsion of nanowire diodes (2010)

The propulsion of semiconductor diode nanowires under external AC electric field is described. Such fuel-free electric field-induced nanowire propulsion offers considerable promise for diverse technological applications.
Atlas selection strategy using least angle regression in multi-atlas segmentation propagation (2011)

In multi-atlas based segmentation propagation, segmentations from multiple atlases are propagated to the target image and combined to produce the segmentation result. Local weighted voting (LWV) method is a classifier fusion method which combines the propagated atlases weighted by local image similarity. We demonstrate that the segmentation accuracy using LWV improves as the number of atlases increases. Under this context, we show that introducing diversity in addition to image similarity by using least-angle regression (LAR) criteria is a more efficient way to rank and select atlases. The accuracy of multi-atlas segmentation converges faster when the atlases are selected in the order of LAR. We test the method on a hippocampal atlas set of 138 normal control (NC) subjects and another set of 99 Alzheimer's disease patients provided by ADNI. The result shows that LAR selection is more efficient than similarity based atlas selection. Fewer atlases were required using LAR selected atlases to achieve the same accuracy as fusing atlases from image similarity based selection.
Golden Age of RyR and GABA-R Diamide and Isoxazoline Insecticides: Common Genesis, Serendipity, Surprises, Selectivity, and Safety (2015)

The serendipitous observation of the insecticidal activity of a candidate herbicide was the first in a series of surprises that changed the course of insecticide research and opened the "Golden Age of Diamide and Isoxazoline Insecticides" which have a common genesis. Two novel modes of action were discovered, one involving the γ-aminobutyric acid (GABA) receptor of the chloride channel and the other the ryanodine receptor (RyR) of the calcium-activated calcium channel. These are old insecticide targets, but physiological assays and radioligand binding studies reveal that the new diamides and isoxazolines act at previously unrecognized sites without cross-resistance to other chemotypes and more important differing between insects and mammals resulting in selective toxicity and mechanistically based safety. The phthalic diamide flubendiamide and anthranilic diamides chlorantraniliprole and cyantraniliprole act at an allosteric site of the RyR to activate calcium release in insects but not mammals. They are the most important insecticide introductions of the past decade. Isoxazoline and meta-diamide insecticides and their previously unrecognized GABA-R target are more recent discoveries. Isoxazolines are currently important in flea and tick control in dogs and cats, and meta-diamides show promise for pest management and crop protection. These 21st century RyR and GABA-R diamides and isoxazolines were serendipitous discoveries and developments showing the importance of mechanism studies in maintaining the arsenal of safe and effective insecticides.
Sequences of games: a tool for taming complexity in security proofs. (2004)

This paper is brief tutorial on a technique for structuring security proofs as sequences games.
Effect of Oral Milrinone on Mortality in Severe Chronic Heart Failure (1991)

Our findings indicate that despite its beneficial hemodynamic actions, long-term therapy with oral milrinone increases the morbidity and mortality of patients with severe chronic heart failure. The mechanism by which the drug exerts its deleterious effects is unknown.
Sanguinarine (Pseudochelerythrine) Is a Potent Inhibitor of NF-κB Activation, IκBα Phosphorylation, and Degradation (1997)

The nuclear factor NF-kappaB is a pleiotropic transcription factor whose activation results in inflammation, viral replication, and growth modulation. Due to its role in pathogenesis, NF-kappaB is considered a key target for drug development. In the present report we show that sanguinarine (a benzophenanthridine alkaloid), a known anti-inflammatory agent, is a potent inhibitor of NF-kappaB activation. Treatment of human myeloid ML-1a cells with tumor necrosis factor rapidly activated NF-kappaB, this activation was completely suppressed by sanguinarine in a dose- and time-dependent manner. Sanguinarine did not inhibit the binding of NF-kappaB protein to the DNA but rather inhibited the pathway leading to NF-kappaB activation. The reversal of inhibitory effects of sanguinarine by reducing agents suggests a critical sulfhydryl group is involved in NF-kappaB activation. Sanguinarine blocked the tumor necrosis factor-induced phosphorylation and degradation of IkappaBalpha, an inhibitory subunit of NF-kappaB, and inhibited translocation of p65 subunit to the nucleus. As sanguinarine also inhibited NF-kappaB activation induced by interleukin-1, phorbol ester, and okadaic acid but not that activated by hydrogen peroxide or ceramide, the pathway leading to NF-kappaB activation is likely different for different inducers. Overall, our results demonstrate that sanguinarine is a potent suppressor of NF-kappaB activation and it acts at a step prior to IkappaBalpha phosphorylation.
Bone Implants (1957)

Of the various materials used, it would appear that the best substitute for fresh autogenous-bone grafts (if mechanical factors are not a consideration) is the organic matrix of bone devoid of its inorganic salt. This conclusion, incidentally, is not new. Nicholas Senn came to the same conclusion in 1889 on the basis of a series of experiments in which filled bone defects with heterogenous bone previously treated with dilute hydrochloric acid. To quote Senn : "Antiseptic decalcified bone is the best substitute for living bone grafts and the restoration of loss of substance in bone . . . [such a] packing furnished the best medium for the growth and development of the tissue resulting from the regenerative process initiated by the trauma." Miller, in a clinical report in 1890, stated that pieces of ox ribs, decalcified with dilute hydrochloric acid and sterilized by soaking in dilute carbolic acid, appeared to be superior to fresh bone in obtaining repair of a tibial defect. Apparently successful replacement of an implant depends on the readiness with which it can be invaded by vascular elements. The presence of inorganic salts in the implant would appear to impede rather than accelerate the process of replacement. In this connection Cohen, Maletskos, Marshall, and Williams reported that a study of the fate of bone grafts by means of radioactive tracers revealed that all of the calcium incorporated into the callus came by way of the circulating blood from skeletal sources situated throughout the body rather than through diffusion from the graft. Whether any antigenic factors are present in decalcified matrix implants or whether the organic matrix can be further fractionated has not yet been determined.
THERMOGRAPHY AND RHEUMATOLOGY (1970)

Journal Article THERMOGRAPHY AND RHEUMATOLOGY Get access J.A. COSH, J.A. COSH Clinical Research Department, Royal National Hospital for Rheumatic DiseasesBath Search for other works by this author on: Oxford Academic PubMed Google Scholar E.F.J. RING E.F.J. RING Clinical Research Department, Royal National Hospital for Rheumatic DiseasesBath Search for other works by this author on: Oxford Academic PubMed Google Scholar Rheumatology, Volume 10, Issue 7, August 1970, Pages 342–348, https://doi.org/10.1093/rheumatology/10.7.342 Published: 01 August 1970
Probing Multidrug‐Resistance and Protein–Ligand Interactions with Oxatricyclic Designed Ligands in HIV‐1 Protease Inhibitors (2010)

A healthier HAART: We report the design, synthesis, biological evaluation, and X-ray crystallographic analysis of a new class of HIV-1 protease inhibitors. Compound 4 proved to be an extremely potent inhibitor toward various multidrug-resistant HIV-1 variants, representing a near 10-fold improvement over darunavir (DRV). Compound 4 also blocked protease dimerization with at least 10-fold greater potency than DRV. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Chromosome I rearrangements involving the genes TPR and NTRK1 produce structurally different thyroid-specific TRK oncogenes (1997)

The NTRK1 gene in the q arm of chromosome 1 encodes one of the receptors for the nerve growth factor and is frequently activated as an oncogene in papillary thyroid carcinomas. The activation is due to chromosomal rearrangements juxtaposing the NTRK1 tyrosine kinase domain to 5'-end sequences from different genes. The thyroid TRK oncogenes are activated by recombination with at least three different genes: the gene coding for tropomyosin and TPR, both on chromosome 1,and TFG on chromosome 3. In a previous study, we showed that two tumors carrying the TPR/NTRK1 rearrangement contained structurally different oncogenes named TRK-T1 and TRK-T2. In this paper, we report (1) the cDNA structure of TRK-T2, (2) evidence that TRK-T2 is generated by different rearrangements in two thyroid tumors, and (3) a detailed analysis of the three different TPR/NTRK1 rearrangements. With molecular studies based on Southern blot hybridization, cloning, and sequencing, we show that all the rearrangements are nearly balanced, involving deletion, insertion, or duplication of only few nucleotides. In one case, an additional rearrangement involving sequences derived from chromosome 17 was detected.
Designing conditions for in vitro formation of amyloid protofilaments and fibrils (1999)

We have been able to convert a small alpha/beta protein, acylphosphatase, from its soluble and native form into insoluble amyloid fibrils of the type observed in a range of pathological conditions. This was achieved by allowing slow growth in a solution containing moderate concentrations of trifluoroethanol. When analyzed with electron microscopy, the protein aggregate present in the sample after long incubation times consisted of extended, unbranched filaments of 30-50 A in width that assemble subsequently into higher order structures. This fibrillar material possesses extensive beta-sheet structure as revealed by far-UV CD and IR spectroscopy. Furthermore, the fibrils exhibit Congo red birefringence, increased fluorescence with thioflavine T and cause a red-shift of the Congo red absorption spectrum. All of these characteristics are typical of amyloid fibrils. The results indicate that formation of amyloid occurs when the native fold of a protein is destabilized under conditions in which noncovalent interactions, and in particular hydrogen bonding, within the polypeptide chain remain favorable. We suggest that amyloid formation is not restricted to a small number of protein sequences but is a property common to many, if not all, natural polypeptide chains under appropriate conditions.
Assays for Qualification and Quality Stratification of Clinical Biospecimens Used in Research: A Technical Report from the ISBER Biospecimen Science Working Group (2016)

This technical report presents quality control (QC) assays that can be performed in order to qualify clinical biospecimens that have been biobanked for use in research. Some QC assays are specific to a disease area. Some QC assays are specific to a particular downstream analytical platform. When such a qualification is not possible, QC assays are presented that can be performed to stratify clinical biospecimens according to their biomolecular quality.
Controversies in the Mechanism of Total Parenteral Nutrition Induced Pathology (2015)

Over 30,000 patients are permanently dependent on Total Parenteral Nutrition (TPN) for survival with several folds higher requiring TPN for a prolonged duration. Unfortunately, it can cause potentially fatal complications. TPN infusion results in impairment of gut mucosal integrity, enhanced inflammation, increased cytokine expression and trans-mucosal bacterial permeation. It also causes endotoxin associated down regulation of bile acid transporters and Parenteral Nutrition Associated Liver Disease (PNALD), which includes steatosis, disrupted glucose metabolism, disrupted lipid metabolism, cholestasis and liver failure. Despite multiple theories, its etiology and pathophysiology remains elusive and is likely multifactorial. An important cause for TPN related pathologies appears to be a disruption in the normal enterohepatic circulation due to a lack of feeding during such therapy. This is further validated by the fact that in clinical settings, once cholestasis sets in, its reversal occurs when a patient is receiving a major portion of calories enterally. There are several other postulated mechanisms including gut bacterial permeation predisposing to endotoxin associated down regulation of bile acid transporters. An additional potential mechanism includes toxicity of the TPN solution itself, such as lipid mediated hepatic toxicity. Prematurity, leading to a poor development of bile acid regulating nuclear receptors and transporters has also been implicated as a causative factor. This review presents the current controversies and research into mechanisms of TPN associated injury.
3α-Hydroxy-3β-(phenylethynyl)-5β-pregnan-20-ones:  Synthesis and Pharmacological Activity of Neuroactive Steroids with High Affinity for GABAA Receptors (1997)

Neuroactive steroids that allosterically modulate GABAA receptors have potential uses as anticonvulsants, anxiolytics, and sedative-hypnotic agents. Recently, a series of pregnanes substituted with simple alkyl groups at the 3 beta-position were synthesized and found to be active in vitro. The present report describes the synthesis of a series of substituted 3 alpha-hydroxy-3 beta-(phenylethynyl)pregnan-20-ones and their in vitro structure-activity relationship determined by their potency for inhibition of [35S]TBPS binding in rat brain membranes. Appropriate substitution of the phenyl group results in ligands with particularly high affinity for the neuroactive steroid site on GABAA receptors (e.g., 4-acetyl 28, IC50 10 nM). The potency of selected steroids was confirmed electrophysiologically in oocytes expressing cloned human GABAA alpha 1 beta 2 gamma 2L receptors (e.g., compound 28, EC50 6.6 nM). Consistent with their in vitro activity, some of the 3 beta-(phenylethynyl)-substituted steroids displayed anticonvulsant activity in the pentylenetetrazol (PTZ) and maximal electroshock (MES) tests following ip administration in mice. Notably, the 3 beta-[(4-acetylphenyl)ethynyl]-19-nor derivative 36 demonstrated an attractive anticonvulsant profile (PTZ and MES ED50 values of 2.8 and 9.2 mg/kg, respectively). A new pharmacophore for the neuroactive steroid site of GABAA receptors is proposed based upon the high affinity of certain substituted 3 beta-(phenylethynyl) steroids.
Models of infantile malnutrition in rats: Effects on maternal behavior (1980)

The effects of 6 commonly used methods for producing malnutrition in suckling rats upon the behavior of their dams were examined. In these methods, (1) large litters were fostered on the dams; (2) dams were fed low-protein diets; (3) dams were fed an inadequate amount of a good quality diet; (4) pups were removed from the dams and kept with a nonlactating female for half of the day; (5) pups were removed from the dams and kept in an incubator for half of the day; or (6) some of th dams' teats were destroyed. Dams that were themselves food deprived showed a shift from resting to exploratory behaviors with some indication of increased attention to the pups compared to controls. Dams whose pups were starved but that were well fed themselves showed lower levels of resting and higher levels of attention to pups but no elevation in exploratory activity. Although the long-term significance of the behavioral changes of the dams is not known, the immediate effect was to minimize the impact of the experimenter's manipulations on the metabolic energy available to the pups for growth and development.
Genomic organization and mutation analysis of Hel-N1 in lung cancers with chromosome 9p21 deletions. (1997)

Allelic loss of chromosome 9p21 is common in small cell lung cancer (SCLC), but inactivation of the tumor suppressor gene CDKN2a is rare, implying the existence of another target gene at 9p21. A recent deletion mapping study of chromosome 9p has also identified a site of deletion in non-small cell lung cancer (NSCLC) centered around D9S126. The Hel-N1 (human elav-like neuronal protein 1) gene encodes a neural-specific RNA binding protein that is expressed in SCLC. We have mapped this potentially important gene in lung tumorigenesis to within 100 kb of the D9S126 marker at chromosome band 9p21 by using homozygously deleted tumor cell lines and fluorescence in situ hybridization to normal metaphase spreads. Hel-N1 is, therefore, a candidate target suppressor gene in both SCLC and NSCLC. We have determined the genomic organization and intron/exon boundaries of Hel-N1 and have screened the entire coding region for mutations by sequencing 14 primary SCLCs and cell lines and 21 primary NSCLCs preselected for localized 9p21 deletion or monosomy of chromosome 9. A homozygous deletion including Hel-N1 and CDKN2a was found in a SCLC cell line, and a single-base polymorphism in exon 2 of Hel-N1 was observed in eight tumors. No somatic mutations of Hel-N1 were found in this panel of lung tumors. Hel-N1 does not appear to be a primary inactivation target of 9p21 deletion in lung cancer.
Hypersensitivity Syndrome and Pure Red Cell Aplasia Following Allopurinol Therapy in a Patient with Chronic Kidney Disease (2005)

To minimize serious DHS, proper indications for treatment and dosage adjustment should be closely observed when starting allopurinol therapy in patients with chronic kidney disease.
Characterization of a semi‐replicative gene delivery system allowing propagation of complementary defective retroviral vectors (2004)

This study is an initial proof of principle for the use of complementary retroviral vectors to deliver and propagate transgenes in vitro and in solid tumors in vivo, but with reduced pathogenicity compared to its parental virus. In-between replication-defective and replication-competent retroviral vectors, this semi-replicative system offers good grounds for its application in in vitro studies and allows envisioning its further development for cancer gene therapy.