gebhart/patrepeval huggingface dataset:
Prevention of Cardiac Hypertrophy in Mice by Calcineurin Inhibition (1998)

Hypertrophic cardiomyopathy (HCM) is an inherited form of heart disease that affects 1 in 500 individuals. Here it is shown that calcineurin, a calcium-regulated phosphatase, plays a critical role in the pathogenesis of HCM. Administration of the calcineurin inhibitors cyclosporin and FK506 prevented disease in mice that were genetically predisposed to develop HCM as a result of aberrant expression of tropomodulin, myosin light chain-2, or fetal beta-tropomyosin in the heart. Cyclosporin had a similar effect in a rat model of pressure-overload hypertrophy. These results suggest that calcineurin inhibitors merit investigation as potential therapeutics for certain forms of human heart disease.
Erythropoietin prevents neuronal apoptosis after cerebral ischemia and metabolic stress (2001)

Erythropoietin (EPO) promotes neuronal survival after hypoxia and other metabolic insults by largely unknown mechanisms. Apoptosis and necrosis have been proposed as mechanisms of cellular demise, and either could be the target of actions of EPO. This study evaluates whether antiapoptotic mechanisms can account for the neuroprotective actions of EPO. Systemic administration of EPO (5,000 units/kg of body weight, i.p.) after middle-cerebral artery occlusion in rats dramatically reduces the volume of infarction 24 h later, in concert with an almost complete reduction in the number of terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling of neurons within the ischemic penumbra. In both pure and mixed neuronal cultures, EPO (0.1--10 units/ml) also inhibits apoptosis induced by serum deprivation or kainic acid exposure. Protection requires pretreatment, consistent with the induction of a gene expression program, and is sustained for 3 days without the continued presence of EPO. EPO (0.3 units/ml) also protects hippocampal neurons against hypoxia-induced neuronal death through activation of extracellular signal-regulated kinases and protein kinase Akt-1/protein kinase B. The action of EPO is not limited to directly promoting cell survival, as EPO is trophic but not mitogenic in cultured neuronal cells. These data suggest that inhibition of neuronal apoptosis underlies short latency protective effects of EPO after cerebral ischemia and other brain injuries. The neurotrophic actions suggest there may be longer-latency effects as well. Evaluation of EPO, a compound established as clinically safe, as neuroprotective therapy in acute brain injury is further supported.
Rheumatic Manifestations ofCampylobacter jejuni and C. fetusInfections in Adults (1994)

Reports of the rheumatic manifestations of Campylobacter jejuni and C. fetus infections in adults are reviewed in order to determine the most common presentations and which individuals are at risk for rheumatic disease. Relevant English-language articles were identified through a Medline search and from bibliographies of identified articles. 105 articles were reviewed in detail. 29 cases of reactive arthritis or Reiter's syndrome following Campylobacter jejuni enteritis were identified. The knee is the most commonly involved joint and an average of 3.2 joints were involved in affected persons. HL-A B27 positive patients are more frequently affected and have higher erythrocyte sedimentation rates than HL-A B27 negative patients. Eight cases of septic arthritis and 4 cases of osteomyelitis caused by C. fetus or C. jejuni were identified, and these cases generally occurred in compromised hosts or in diseased joints.
Solution Equilibria in YbDOTMA, a Chiral Analogue of One of the Most Successful Contrast Agents for MRI, GdDOTA (1999)

The structure and the conformational equilibria in aqueous and methanolic solutions of YbDOTMA (DOTMA = (1R,4R,7R,10R)-α,α′,α′′,α′′′′-tetramethyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) are investigated and the dynamics studied by means of NMR methods. The presence of two isomeric forms in slow exchange is confirmed and quantitatively characterized by EXSY. The exchange peaks are assigned to the inversion of the conformation of the macrocycle ring. No evidence is obtained of a reorientation of the methyl acetate substituents. The protons switch between positions with the same geometrical factors, i.e. positions that would have the same pseudocontact shifts were it not for the different magnetic susceptibility anisotropies of the two species; steady-state NOE spectra on the major form allow unequivocal assignment of the conformations of the two isomers.
Thermophoresis-Controlled Size-Dependent DNA Translocation through an Array of Nanopores (2018)

Large arrays of nanopores can be used for high-throughput biomolecule translocation with applications toward size discrimination and sorting at the single-molecule level. In this paper, we propose to discriminate DNA length by the capture rate of the molecules to an array of relatively large nanopores (50-130 nm) by introducing a thermal gradient by laser illumination in front of the pores balancing the force from an external electric field. Nanopore arrays defined by photolithography were batch processed using standard silicon technology in combination with electrochemical etching. Parallel translocation of single, fluorophore-labeled dsDNA strands is recorded by imaging the array with a fast CMOS camera. The experimental data show that the capture rates of DNA molecules decrease with increasing DNA length due to the thermophoretic effect of the molecules. It is shown that the translocation can be completely turned off for the longer molecule using an appropriate bias, thus allowing a size discrimination of the DNA translocation through the nanopores. A derived analytical model correctly predicts the observed capture rate. Our results demonstrate that by combining a thermal and a potential gradient at the nanopores, such large nanopore arrays can potentially be used as a low-cost, high-throughput platform for molecule sensing and sorting.
A 23-ns 1-Mb BiCMOS DRAM (1990)

A 1-Mb BiCMOS DRAM having a 23-ns access time is described. The DRAM uses a direct sensing technique and a nonaddress-multiplexing configuration. This technique combines the NMOS differential circuit on each pair of data lines with a common highly sensitive bipolar circuit. The resulting chip has been verified to have high-speed characteristics while maintaining a wide operating margin and a relatively small chip size of 62.2 mm/sup 2/, in spite of a 1.3- mu m lithography level.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Molecular and clinical analysis of ALPL in a cohort of patients with suspicion of Hypophosphatasia (2017)

Hypophosphatasia (HPP) is a rare autosomal dominant or recessive metabolic disorder caused by mutations in the tissue nonspecific alkaline phosphatase gene (ALPL). To date, over 300 different mutations in ALPL have been identified. Disease severity is widely variable with severe forms usually manifesting during perinatal and/or infantile periods while mild forms are sometimes only diagnosed in adulthood or remain undiagnosed. Common clinical features of HPP are defects in bone and tooth mineralization along with the biochemical hallmark of decreased serum alkaline phosphatase activity. The incidence of severe HPP is approximately 1 in 300,000 in Europe and 1 in 100,000 in Canada. We present the clinical and molecular findings of 83 probands and 28 family members, referred for genetic analysis due to a clinical and biochemical suspicion of HPP. Patient referrals included those with isolated low alkaline phosphatase levels and without any additional clinical features, to those with a severe skeletal dysplasia. Thirty-six (43.3%) probands were found to have pathogenic ALPL mutations. Eleven previously unreported mutations were identified, thus adding to the ever increasing list of ALPL mutations. Seven of these eleven were inherited in an autosomal dominant manner while the remaining four were observed in the homozygous state. Thus, this study includes a large number of well-characterized patients with hypophosphatasemia which has permitted us to study the genotype:phenotype correlation. Accurate diagnosis of patients with a clinical suspicion of HPP is crucial as not only is the disease life-threatening but the patients may be offered bone targeted enzymatic replacement therapy. © 2017 Wiley Periodicals, Inc.
Transcriptional Inhibition of the Murine Erythropoietin Receptor Gene by an Upstream Repetitive element (1993)

Transcription of the murine erythropoietin receptor (EpoR) gene is inhibited by a novel repetitive element that is located upstream of the EpoR promoter. Reporter gene studies reveal that the inhibitory effect is both distance and orientation dependent. This element is a member of a family of repetitive elements specific to rodents and is present at approximately 10(5) copies per mouse genome. It encodes approximately 500- to 900-bp-long transcripts in both erythroid and nonerythroid cells. RNase protection analysis with a probe from the 5' flanking murine EpoR gene reveals that the direction of transcription is in the sense orientation, relative to the downstream EpoR gene. We suggest that transcriptional inhibition of the EpoR promoter is mediated by read-through transcripts originating in the upstream repetitive element and that this effect may contribute to the basal level of transcription of the murine EpoR gene in erythroid cells.
Sequences of the recA gene and protein. (1980)

We have determined the nucleotide sequence of the recA gene of Escherichia coli; this permits the formulation of the primary structure for the recA protein. This structure is consistent with the amino acid composition of the tryptic peptides obtained from the recA protein. The coding region of the recA gene has 1059 base pairs, which specify 352 amino acids. The recA protein has alanine and phenylalanine as its NH2- and COOH-terminal amino acids, respectively, and has the following amino acid composition: Cys3 Asp20 Asn15 Met9 Thr17 Ser20 Glu30 Gln13 Pro10 Gly35 Ala38 Val22 Ile27 Leu31 Tyr7 Phe10 His2Lys27 Trp2 Arg14. Of the three cysteine residues, only two can be alkylated under reducing and denaturing conditions. The molecular weight of the recA polypeptide is 37,842.
DH334, a β-carboline anti-cancer drug, Inhibits the CDK activity of budding yeast (2007)

The beta-carboline alkaloids present in medicinal plants, such as Peganum harmala and Eurycoma longifolia, have recently drawn attention due to their antitumor activities. Further mechanistic studies indicate that beta-carboline derivatives inhibit DNA topoisomerases and interfere with DNA synthesis. Moreover, some beta-carboline compounds are specific inhibitors of cyclin dependent kinases (CDKs). In this study we used budding yeast as a model system to investigate the antitumor mechanism of beta-carboline drugs. We found that DH334, a beta-carboline derivative, inhibits the growth of budding yeast. Strikingly, deletion of SIC1, which encodes the budding yeast CDK inhibitor, results in resistance to DH334. In contrast, yeast cells defective for Sic1 degradation exhibit morepronounced sensitivity to DH334. The presence of DH334 causes accumulation of yeast cells in G(1) phase, indicating that DH334 blocks cell cycle initiation. We further demonstrated that DH334 inhibits CDK activity as indicated by the decreased phosphorylation of a CDK substrate. All these data suggest that the inhibition of CDK contributes to the toxicity of beta-carboline derivatives to budding yeast. DH334 also inhibits the kinase activity of Cdk2/CyclinA in vitro. Therefore, we speculate that the antitumor activity of beta-carboline drugs could be attributable to their inhibition of CDK.
Sex Differences in Brain Gray and White Matter in Healthy Young Adults: Correlations with Cognitive Performance (1999)

Sex-related differences in behavior are extensive, but their neuroanatomic substrate is unclear. Indirect perfusion data have suggested a higher percentage of gray matter (GM) in left hemisphere cortex and in women, but differences in volumes of the major cranial compartments have not been examined for the entire brain in association with cognitive performance. We used volumetric segmentation of dual echo (proton density and T2-weighted) magnetic resonance imaging (MRI) scans in healthy volunteers (40 men, 40 women) age 18-45. Supertentorial volume was segmented into GM, white matter (WM), and CSF. We confirmed that women have a higher percentage of GM, whereas men have a higher percentage of WM and of CSF. These differences sustained a correction for total intracranial volume. In men the slope of the relation between cranial volume and GM paralleled that for WM, whereas in women the increase in WM as a function of cranial volume was at a lower rate. In men the percentage of GM was higher in the left hemisphere, the percentage of WM was symmetric, and the percentage of CSF was higher in the right. Women showed no asymmetries. Both GM and WM volumes correlated moderately with global, verbal, and spatial performance across groups. However, the regression of cognitive performance and WM volume was significantly steeper in women. Because GM consists of the somatodendritic tissue of neurons whereas WM comprises myelinated connecting axons, the higher percentage of GM makes more tissue available for computation relative to transfer across distant regions. This could compensate for smaller intracranial space in women. Sex difference in the percentage and asymmetry of the principal cranial tissue volumes may contribute to differences in cognitive functioning.
Chaostheoretische Betrachtungen zu Psychiatrie, Psychologie und Psychotherapie (Part 1 of 2) (1997)

Die Gesamtarbeit (Teil 1 und 2) befasst sich mit der Semantik der Chaostheorie. Mit Hilfe der sechs allgemeinen und sechs speziellen empirischen Grundeigenschaften, die unmittelbar aus Beobachtungen chaotischer Systeme erhoben werden können, haben wir im ersten Teil dieser Arbeit, «Die sechs Grundeigenschaften des Chaos und eine Prozess-Orientierte Psychiatrie (POPSY)», eine mathematisch-physikalisch stichhaltige Betrachtung psychiatrischer Phänomene erlangt, die bisher nur intuitiv erfasst werden konnten. Wir haben sodann gesehen, inwiefern Begriffe der Chaostheorie mit entsprechenden Begriffen der Psychiatrie in Einklang gebracht werden können. Verschiedene psychiatrische Phänomene, vor allem die Schizophrenie, wurden als chaotische Prozesse analysiert. Insbesondere wurde eine kritische Gegenüberstellung klassifizierender und prozessorientierter Psychiatrie vorgestellt. Das Thema «Psychiatrische Störung als dynamische Krankheit bzw. als Informationsverarbeitungspathologie» wurde auch in Teil 1 eingehend diskutiert. In diesem zweiten Teil der Gesamtarbeit, «Neue Hypothese zur Natur der Psychose», erweitern wir die oben erwähnten Überlegungen zum Gebiet Psychiatrie auf die Gebiete Psychologie und Psychotherapie. Somit erlangen wir eine Auffassung der «normalen» oder «ungestörten» Psyche als chaotisches System mit entsprechenden fraktalen Prozessbildern im geeigneten Zustandsraum. Insbesondere werden wir anhand derselben obenerwähnten sechs allgemeinen und sechs speziellen empirischen Grundeigenschaften den Zusammenhang zwischen chaostheoretischen Begriffen und entsprechenden Begriffen aus den Bereichen Psychologie und Psychotherapie verstehen. Dies ermöglicht eine mathematisch-physikalische Betrachtung psychologischer und psychotherapeutischer Phänomene, die bislang nur metaphorisch aufgefasst werden konnten. Verschiedene psychologische und psychotherapeutische Phänomene, vor allem der Verlauf der Psychose bzw. der Prozess der Aktiven Imagination, werden als chaotische Prozesse analysiert. Obwohl einerseits argumentiert wird, dass der Verlauf einer Psychose, d.h. die zeitliche Reihenfolge spontaner psychotischer Ausbrüche eines Individuums, chaotisch ist, werden wir eine neue Hypothese zur Natur des psychotischen«mind/brain»-Zustandes als eine «lineare» (im Gegensatz zu einer «chaotischen») Informationsverarbeitungspathologie aufstellen.
Direct Asymmetric anti-Mannich-Type Reactions Catalyzed by a Designed Amino Acid (2006)

The development of catalysts for Mannich-type reactions that afford anti-products with excellent diastereo- and enantioselectivities under mild conditions and low catalyst loadings (1-5 mol %) is reported. Based on principles gained from the study of (S)-proline-catalyzed Mannich-type reactions that afford enantiomerically enriched syn-products, (3R,5R)-5-methyl-3-pyrrolidinecarboxylic acid (RR35) has been designed to catalyze the direct enantioselective anti-selective Mannich-type reactions. Computational studies of the above reaction using HF/6-31G* level of theory suggested that this design would be highly effective. The catalyst was subsequently synthesized and studied in organocatalytic Mannich-type reactions between unmodified aldehydes and N-PMP-protected alpha-imino esters. In accord with the design principles and in quantitative agreement with the theoretical predictions, reactions catalyzed by this catalyst afforded anti-products in good yields with excellent diastereo- and enantioselectivities (anti:syn 94:6 to 98:2, >97 to >99% ee).
Retroviral transfer of a murine cDNA for multidrug resistance confers pleiotropic drug resistance to cells without prior drug selection. (1988)

We have constructed a retrovirus expression vector that carries the murine mdr cDNA transcribed under the control of the human H4 histone promoter to examine the feasibility of efficiently transferring a multidrug resistance phenotype to cells without requiring drug selection. This approach will facilitate the transfer of mdr cDNA to hematopoietic progenitor cells for the study of multidrug resistance in vivo. The retrovirus vector pHmdr has been used for transmission and expression of the mdr cDNA in initially drug-sensitive NIH 3T3 fibroblasts. Selection of pHmdr infectants in the cytotoxic agents colchicine or doxorubicin gave rise to highly multidrug-resistant colonies containing a single gene copy of the vector. Moreover, in the analysis of 12 cloned unselected NIH 3T3 cell infectants, a multidrug resistance phenotype was conferred by as few as two copies of the pHmdr vector. Overexpression of the mdr cDNA in drug-selected and unselected pHmdr infectants was directly related to cell survival in three cytotoxic agents tested. These results hold significant implications for the study of multidrug resistance in vivo.
Estimation of trans-Resveratrol in Herbal Extracts and Dosage Forms by High-Performance Thin-Layer Chromatography (2005)

A simple, sensitive and precise high-performance thin-layer chromatographic (HPTLC) method of analysis of trans-resveratrol in Polygonum cuspidatum root extracts and in dosage forms was developed and validated. The separation was carried out on a TLC aluminium plates precoated with silica gel 60F-254 as the stationary phase, eluted with chloroform-ethylacetate-formic acid (2.5 : 1 : 0.1) as mobile phase. Densitometric analysis of trans-resveratrol was carried out in the absorbance mode at 313 nm. This system was found to give compact spot for trans-resveratrol (Rf value of 0.40+/-0.03). A good linear regression relationship between peak areas and the concentrations was obtained over the range of 0.5-3.0 microg/spot with correlation coefficient 0.9989. The limit of detection and quantification was found to be 9 and 27 ng/spot. The method was validated for precision and recovery. The spike recoveries were within 99.85 to 100.70%. The RSD values of the precision in the range 0.37-1.84%. The proposed developed HPTLC method can be applied for identification and quantitative determination of trans-resveratrol in herbal extracts and dosage forms.
Treatment of Infected Total Knee Arthroplasty Using an Articulating Spacer (1995)

Twenty-six patients with late infected total knee arthroplasties were treated by debridement and removal of components and all cement, preserving collateral ligaments. At time of debridement, an articulating spacer was fashioned to allow partial weightbearing and knee range of motion (ROM) during rehabilitation. This spacer was implanted using antibiotic-impregnated bone cement. For this purpose, 4.8 g of powdered tobramycin was mixed with each 40-g batch of Simplex cement. Cement was applied early to the components, but applied late to the femur, tibia, and patella to allow molding to the defects and bone without adherence to bone. Patients received tailored intravenous antibiotic therapy for 6 weeks in addition to this antibiotic-impregnated cement for treatment of a variety of gram positive and gram negative organisms. All patients had cemented revision total knee arthroplasty using antibiotic-impregnated cement with standard cementing techniques used. All patients but 1 had reimplantation; this patient died of unrelated causes before revision. Range of motion before revision was 10 degrees to 95 degrees. Followup averaged 30 months (range, 13-70 months). The average Modified Hospital for Special Surgery Knee Score after revision was 87 points (range, 53-100 points), with 92% good to excellent results. Range of motion after reimplantation was 5 degrees to 106 degrees. There have been no recurrences of infection. Use of an articulating spacer to treat infected total knee arthroplasty improves ultimate ROM and soft tissue health and significantly decreases the risk of reinfection.
A pharmacokinetic evaluation of 14C-labeled afovirsen sodium in patients with genital warts (1994)

Afovirsen sodium is a 20-mer phosphorothioate oligonucleotide designed to be complementary to the messenger ribonucleic acid sequence for the translation initiation codon of the E2 protein vital to replication of human papillomaviruses types 6 and 11. 14C-Labeled afovirsen was given as a single-dose intradermal injection in each of four warts of five patients to determine the time-dependent changes in concentration of intact afovirsen in genital warts and to determine the systemic absorption and elimination of radiolabeled compound. Intact afovirsen in genital warts was determined by high pressure liquid chromatography analysis of protease K digested extracts. Intact afovirsen was present in wart tissue for at least 72 hours at concentrations several times in excess of the estimated minimal inhibitory concentration of 1 mumol/L. Absorption of radiolabeled afovirsen from the injection site was rapid, with a peak plasma concentration achieved within 1 hour. Clearance of afovirsen was primarily attributable to slow metabolism, with about 30% of the radiolabel eliminated as 14C-CO2 in expired air over a 6-day period after dosing. Radioactivity eliminated in urine represented metabolites of afovirsen. From the clinical pharmacokinetic data presented here and from previously published pharmacokinetic data in rats, the disposition of afovirsen in humans appears to be relatively similar to that in rats. These data suggest that once or twice weekly dosing regimen in the clinic may be appropriate.
Increased Intraventricular Pressure without Ventriculomegaly in Children with Shunts (1979)

Five patients with shunt-dependent hydrocephalus were observed to have apparently normal ventricular size despite marked increases in ventricular pressure after shunt malfunction. Elastance (dP/dV) was determined in four of these patients by removing increments of cerebrospinal fluid and measuring the resulting pressure. These patients without ventricular enlargement and with markedly increased ventricular pressure had high elastance. This group of patients with "normal volume" hydrocephalus had distal shunt occlusions, in contrast to previously reported patients with cephalic shunt obstructions after ventricular decompression. Initial shunting in early infancy, prolonged shunt dependency, and lack of recent shunt revision were common factors in these patients. Markedly elevated pressure with normal volume is a threatening clinical entity, requiring prompt surgical intervention