gebhart/patrepeval huggingface dataset:
Homocysteine-lowering treatment: an overview (2001)

Elevated fasting plasma concentrations of homocysteine have a high prevalence in subjects with cardiovascular disease and have also been associated with an increased risk of atherothrombosis in most, but not all, prospective studies. The most frequent causes of hyperhomocysteinaemia are genetic defects, such as cystathionine-beta-synthase (CBS) deficiency, deficiencies of folic acid and/or vitamin B12, renal failure and interference in homocysteine metabolism by drugs or metabolic alterations. In most cases, no underlying cause can be established. Subjects with CBS deficiency are treated with pyridoxine with additional folic acid and betaine if necessary. Folic acid and vitamin B12 deficiencies should be corrected by supplementation. Increases in folate intake by dietary changes or fortification can also lower plasma homocysteine in vitamin-replete subjects with normal plasma homocysteine levels. In renal failure, folic acid treatment (1-5 mg/day) ameliorates the plasma homocysteine level in most cases but hyperhomocysteinaemia persists in the majority of patients. Primary (fasting) hyperhomocysteinaemia can be treated with folic acid (0.5-5 mg/day). An abnormal methionine-loading test identifies additional patients at risk and postmethionine-loading hyperhomocysteinaemia should be treated with a combination of pyridoxine and folic acid. In the absence of dose-effect studies, a combination of pyridoxine (50 mg) and folic acid (5 mg) is advised. Large clinical trials are currently underway to establish the role of homocysteine-lowering therapy in the secondary prevention of atherothrombotic disease. In view of the effective, cheap and safe character of therapy with folic acid and pyridoxine, a policy can be accepted to screen and treat high-risk patients until these trials have been concluded.
Least-squares fitting of carrier phase distribution by using a rational function in fringe projection profilometry (2006)

A least-squares fitting technique for the carrier phase component in fringe projection profilometry is presented. The carrier phase distribution for an arbitrary measurement system can be perfectly described with a rational function, whose coefficients can be estimated by least-squares fitting to the measured reference phases, so that the restrictions and limitations in the existing techniques are eliminated.
Stress and Glucocorticoid (1997)

In his Perspective “Why stress is bad for your brain” ([1][1]), Robert M. Sapolsky concludes that glucocorticoid (GC) excess, sometimes a result of sustained stress, is a “likely culprit in causing [hippocampal] atrophy [in humans].” Although the data demonstrating reduced hippocampal volume
Phosphorothioate oligonucleotides bind in a non sequence‐specific manner to the nucleolar protein C23/nucleolin (1995)

To design optimal strategies for intracellular delivery of antisense phosphorothioate oligonucleotides, it may be useful to understand their interaction with cellular macromolecules. Nuclear extracts from LOX amelanotic myeloma cells were studied for protein binding to phosphorothioate oligonucleotides using a Southwestern protocol. Multiple nuclear proteins bound to the phosphorothioate oligonucleotides but no detectable protein binding was found to phosphodiester oligonucleotides. The protein with the strongest binding signals was shown by immunoprecipitation to be nucleolar C23/nucleolin, a 110 kDa protein. With glutathione S-transferase/nucleolin fusion protein constructs, the region of nucleolin containing the RNA recognition motifs had binding activity to phosphorothioate oligonucleotides.
Increased Levels of Ethane, A Non-invasive Marker of n-3 Fatty Acid Oxidation, in Breath of Children with Attention Deficit Hyperactivity Disorder (2003)

Attention deficit hyperactivity disorder (ADHD) comprises a range of behavioural problems including inattention, hyperactivity and impulsivity. Diagnosis and treatment of the disorder is made difficult due to its unknown biological basis. Several studies have identified abnormalities in membrane fatty acids in some subjects with ADHD, and some success has been reported using lipid therapies. We have measured exhalant ethane levels, a non-invasive measure of oxidative damage to n-3 fatty acids, to probe biochemical alterations in ADHD. Patients with ADHD (N = 10) had higher levels of ethane in exhalant than in healthy volunteers (N = 12) with approximately 50% of ADHD cases being above the control range. In contrast, levels of butane, a marker of protein oxidation, were unaltered. Our data, although preliminary, suggests that some patients with ADHD have higher rates of oxidative breakdown of n-3 polyunsaturated fatty acids (PUFAs). Such a biochemical abnormality may underlie the previously observed fatty acid deficiencies, as well as providing further rationale for the use of anti-oxidant and/or lipid supplementation therapy in the treatment of ADHD. Larger studies of ADHD using this non-invasive assessment of oxidative stress appear warranted.
Nucleotide Sequence and Expression of an AIDS-Associated Retrovirus (ARV-2) (1985)

The nucleotide sequence of molecular clones of DNA from a retrovirus, ARV-2, associated with the acquired immune deficiency syndrome (AIDS) was determined. Proviral DNA of ARV-2 (9737 base pairs) has long terminal repeat structures (636 base pairs) and long open reading frames encoding gag (506 codons), pol (1003 codons), and env (863 codons) genes. Two additional open reading frames were identified. Significant amino acid homology with several other retroviruses was noted in the predicted product of gag and pol, but ARV-2 was as closely related to murine and avian retroviruses as it was to human T-cell leukemia viruses (HTLV-I and HTLV-II). By means of an SV-40 vector in transfected simian cells, the cloned gag and env genes of ARV-2 were shown to express viral proteins.
Adventures in the Pathophysiology of Brain Ischemia: Penumbra, Gene Expression, Neuroprotection (2003)

The careful study of rodent ischemia models can yield valuable, clinically relevant insights into the pathophysiology of ischemic stroke.
Clinical and molecular studies in a large Dutch family with Noonan syndrome (1994)

We describe the largest Noonan syndrome (NS) family reported to date. The manifestations of the affected relatives are discussed. In the absence of a biochemical marker NS is still a clinical diagnosis. The diagnostic criteria that were used are presented compared with other published criteria for diagnosing NS. The large size of this family enabled us to test the possible involvement of candidate regions by multipoint linkage analysis. Both the region surrounding the NF1 locus on chromosome 17 and the proximal part of chromosome 22 could be excluded. Since NS may well be heterogeneous, the use of such a large family in linkage studies of NS should prove indispensable.
Involvement of TNF Receptor-Associated Factor 6 in IL-25 Receptor Signaling (2006)

IL-25 (IL-17E) induces IL-4, IL-5, and IL-13 production from an unidentified non-T/non-B cell population and subsequently induces Th2-type immune responses such as IgE production and eosinophilic airway inflammation. IL-25R is a single transmembrane protein with homology to IL-17R, but the IL-25R signaling pathways have not been fully understood. In this study, we investigated the signaling pathway under IL-25R, especially the possible involvement of TNFR-associated factor (TRAF)6 in this pathway. We found that IL-25R cross-linking induced NF-kappaB activation as well as ERK, JNK, and p38 activation. We also found that IL-25R-mediated NF-kappaB activation was inhibited by the expression of dominant negative TRAF6 but not of dominant negative TRAF2. Furthermore, IL-25R-mediated NF-kappaB activation, but not MAPK activation, was diminished in TRAF6-deficient murine embryonic fibroblast. In addition, coimmunoprecipitation assay revealed that TRAF6, but not TRAF2, associated with IL-25R even in the absence of ligand binding. Finally, we found that IL-25R-mediated gene expression of IL-6, TGF-beta, G-CSF, and thymus and activation-regulated chemokine was diminished in TRAF6-deficient murine embryonic fibroblast. Taken together, these results indicate that TRAF6 plays a critical role in IL-25R-mediated NF-kappaB activation and gene expression.
Photorhabdus luminescens W-14 Insecticidal Activity Consists of at Least Two Similar but Distinct Proteins (1999)

Both the bacterium Photorhabdus luminescens alone and its symbiotic Photorhabdus-nematode complex are known to be highly pathogenic to insects. The nature of the insecticidal activity of Photorhabdus bacteria was investigated for its potential application as an insect control agent. It was found that in the fermentation broth of P. luminescens strain W-14, at least two proteins, toxin A and toxin B, independently contributed to the oral insecticidal activity against Southern corn rootworm. Purified toxin A and toxin B exhibited single bands on native polyacrylamide gel electrophoresis and two peptides of 208 and 63 kDa on SDS-polyacrylamide gel electrophoresis. The native molecular weight of both the toxin A and toxin B was determined to be approximately 860 kDa, suggesting that they are tetrameric. NH2-terminal amino acid sequencing and Western analysis using monospecific antibodies to each toxin demonstrated that the two toxins were distinct but homologous. The oral potency (LD50) of toxin A and toxin B against Southern corn rootworm larvae was determined to be similar to that observed with highly potent Bt toxins against lepidopteran pests. In addition, it was found that the two peptides present in toxin B could be processed in vitro from a 281-kDa protoxin by endogenous P. luminescens proteases. Proteolytic processing was shown to enhance insecticidal activity.
Phase-separated Fe and Co particles in a BN matrix (1987)

Using co-sputtering, 10–300 Å particles of Fe and Co have been prepared in an insulating BN matrix. The Fe particles have the α-Fe structure. The saturation magnetic moment of the iron particles per at. % Fe was found to be approximately independent of the Fe concentration and equal to the value of α-Fe. The system undergoes a metal–nonmetal transition at approximately 40 vol % Fe. For concentrations of Fe particles above this threshold the temperature dependence of the resistivity is metallic and the room-temperature coercivity is large (50–100 Oe). For the Co particles, the room-temperature coercivity is about twice as large as Fe above the metal–nonmetal threshold. Below the metal–nonmetal threshold the particles behave as superparamagnets and the coercivity is approximately zero.
Antibody-Maytansinoid Conjugates Are Activated in Targeted Cancer Cells by Lysosomal Degradation and Linker-Dependent Intracellular Processing (2006)

Antibody-drug conjugates are targeted anticancer agents consisting of a cytotoxic drug covalently linked to a monoclonal antibody for tumor antigen-specific activity. Once bound to the target cell-surface antigen, the conjugate must be processed to release an active form of the drug, which can reach its intracellular target. Here, we used both biological and biochemical methods to better define this process for antibody-maytansinoid conjugates. In particular, we examined the metabolic fate in cells of huC242-maytansinoid conjugates containing either a disulfide linker (huC242-SPDB-DM4) or a thioether linker (huC242-SMCC-DM1). Using cell cycle analysis combined with lysosomal inhibitors, we showed that lysosomal processing is required for the activity of antibody-maytansinoid conjugates, irrespective of the linker. We also identified and characterized the released maytansinoid molecules from these conjugates, and measured their rate of release compared with the kinetics of cell cycle arrest. Both conjugates are efficiently degraded in lysosomes to yield metabolites consisting of the intact maytansinoid drug and linker attached to lysine. The lysine adduct is the sole metabolite from the thioether-linked conjugate. However, the lysine metabolite generated from the disulfide-linked conjugate is reduced and S-methylated to yield the lipophilic and potently cytotoxic metabolite, S-methyl-DM4. These findings provide insight into the mechanism of action of antibody-maytansinoid conjugates in general, and more specifically, identify a biochemical mechanism that may account for the significantly enhanced antitumor efficacy observed with disulfide-linked conjugates.
Molecular genetics of long-QT syndrome (1998)

Recent discoveries of genes involved in long-QT syndrome (LQTS) have led to extensive progress in understanding the molecular basis for this disorder of syncope and sudden cardiac death secondary to ventricular arrhythmias. The emerging unifying theme is that all genes identified to date encode either structural or regulatory subunits for ion channels involved in cardiac repolarization. Defects have been identified in the KCNQ1, HERG, and KCNE1 genes, whose proteins form the K+ channels for the slowly and rapidly inwardly rectifying K+ currents IKs and IKr. Depending on their location and copy number, mutations of KCNQ1 and KCNE1 can cause either autosomal dominant Romano-Ward syndrome or autosomal recessive Jervell and Lange-Nielsen syndrome. The cardiac sodium channel gene, SCN5A, is also mutated in some Romano-Ward cases to produce defects in INa, the cardiac inward Na+ current. The fact that multiple genes are involved and that most LQTS mutations are "private" or "family-specific" complicates molecular diagnosis of LQTS which, currently, is limited to a small number of research laboratories. In future, genotypic determination of LQTS patients and their family members will hopefully lead to improved gene-specific prognostic determinations and therapeutic interventions.
Polymorphism in apolipoprotein E among migraineurs and tension-type headache subjects (2009)

Nitric oxide plays an important role in the pathogenesis of migraine as well as tension-type headache. Studies suggest that the expression of molecules involved in the pathogenesis of headache, i.e., nitric oxide and interleukin, is influenced by apolipoprotein E (APOE) and is gene specific. Hence, we hypothesized that APOE polymorphism may be associated with migraine as well as tension-type headache.The study sample comprised of three groups: migraineurs, tension-type headache subjects as well as a healthy control group. A total of 50 subjects in each group were included after screening for the inclusion and exclusion criteria. None of the subjects was a blood relative of any other subject included in the present study. Their venous blood was drawn and stored at -20 degrees C. Genomic DNA extraction was performed with a commercial kit and simple sequence-specific primer PCR was performed to assess the APOE polymorphism. Data were analyzed with the help of SPSS V11.0 for Windows. chi(2) test and logistic regression analysis were run. The results of the study showed that APOE epsilon2 gene increases the risk of migraine as compared to the control group and the tension-type headache group (OR=4.85; 95% CI=1.92-12.72; P<0.001 and OR=2.31; 95% CI=1.08-4.94; P=0.01, respectively). Interestingly, APOE epsilon4 gene was protective against migraine as well as tension-type headache. This study shows that APOE epsilon2 gene increases the risk of migraine, while APOE epsilon4 gene is protective against migraine and tension-type headache. Further research is required to confirm the findings of the present study in a larger sample and to elucidate the role of APOE polymorphism in headache.
Factor Analysis Applied to a Silane Coupling Agent on E-Glass Fiber System (1984)

The system γ-aminopropyltriethoxysilane coupling agent on E-glass mats has been analyzed by the use of factor analysis to determine the number of pure components and extract the pure component spectra, to improve the signal-to-noise (S/N) ratio of the collected spectra, and to determine the concentration of unknown mixtures. Normalization of the scaling coefficients allows the construction of a calibration curve for the determination of the treating solution concentration by examination of the silane coupling agent on the glass mats.
Effects of Multispecies Probiotic Combination on Helicobacter pylori Infection In Vitro (2008)

Probiotic bacteria alleviate many gastrointestinal symptoms, but the current trend of combining bacteria for additional benefit may make their effects more complex. We characterize four probiotics and their combination in terms of pathogen adhesion, barrier function, cell death, and inflammatory response in Helicobacter pylori-infected epithelial cells. H. pylori-infected Caco-2 cells were pretreated with Lactobacillus rhamnosus GG, Lactobacillus rhamnosus Lc705, Propionibacterium freudenreichii subsp. shermanii Js, Bifidobacterium breve Bb99, or all four organisms in combination. We evaluated the adhesion of H. pylori by in situ immunofluorescence; epithelial barrier function by measurement of transepithelial resistance; apoptosis by measurement of caspase 3 activation; cell membrane leakage by measurement of lactate dehydrogenase release; and inflammation by measurement of interleukin-8 (IL-8), IL-10, prostaglandin E(2) (PGE(2)), and leukotriene B(4) (LTB(4)) release. All probiotics inhibited H. pylori adhesion. L. rhamnosus GG, L. rhamnosus Lc705, P. freudenreichii subsp. shermanii Js, and the combination inhibited H. pylori-induced cell membrane leakage. L. rhamnosus GG, L. rhamnosus Lc705, and the combination initially improved epithelial barrier function but increased the H. pylori-induced barrier deterioration after incubation for 24 to 42 h. L. rhamnosus GG, L. rhamnosus Lc705, and P. freudenreichii subsp. shermanii Js inhibited H. pylori-induced IL-8 release, whereas L. rhamnosus GG, L. rhamnosus Lc705, and B. breve Bb99 suppressed PGE(2) release. None of these anti-inflammatory effects persisted when the probiotics were used in combination. The combination thus increased the levels of IL-8, PGE(2), and LTB(4) released from H. pylori-infected epithelial cells. The proinflammatory actions of the individual components dominated the anti-inflammatory effects when the probiotic bacteria were used in combination. Our results stress that the therapeutic response can be optimized if probiotic strains are characterized before they are used in combination.
Episelection: Novel Ki .apprx. Nanomolar Inhibitors of Serine Proteases Selected by Binding or Chemistry on an Enzyme Surface (1995)

A novel class of mechanism-based inhibitors of the serine proteases is developed using epitaxial selection. Tripeptide boronates esterified by an alcohol or alcohols at the boron retain the tight binding to trypsin-like enzymes associated with transition-state analogs and incorporate additional groups that can be utilized for selectivity between proteases. Formed by reaction of a series of alcohols with the inhibitor boronate oxygen(s), the most structurally compatible alcohol-derivatized inhibitors are either selected by binding to the enzyme (epitaxial selection) or assembled by epitaxial reaction on the enzyme surface. Mass spectrometry of the derivatized boronates and X-ray crystallography of the complexes identify the chemical structures and the three-dimensional interactions of inhibitors generated. This scheme also engineers novel, potent (Ki approximately 7 nM), and more specific inhibitors of individual serine proteases, by derivitizations of compounds obtained by epitaxial selection.
Wireless miniature implantable devices and ASICs for monitoring, treatment, and study of glaucoma and cardiac disease (2009)

Glaucoma affects about 65 million people and is the second leading cause of blindness in the world. Although the condition is irreversible and incurable, early detection is vital to slowing and even stopping the progression of the disease. Our work focuses on the design, fabrication, and assembly of a continuous active glaucoma intraocular pressure (IOP) monitor that provides clinicians with the necessary data to more accurately diagnose and treat patients. Major benefits of an active monitoring device include the potential to develop a closed-loop treatment system and to operate independently for extended periods of time. The fully wireless operation uses gigahertzfrequency electromagnetic wave propagation, which allows for an orientation independent transfer of power and data over reasonable distances. Our system is comprised of a MEMS capacitive sensor, capacitive power storage array, ASIC, and monopole antenna assembled into a biocompatible liquid crystal polymer (LCP) package. We have performed in vivo trials on rabbits, both chronic and acute, to validate system functionality, fully wireless feasibility, and biocompatibility. Heart failure (HF) affects approximately 2% of the adult population in developed countries and 6-10% of people over the age of 65. Continuous monitoring of blood pressure, flow, and chemistry from a minimally invasive device can serve as a diagnostic and early-warning system for cardiac health. We developed a miniaturized system attached to the outer surface of an FDA approved stent, used as both the antenna for wireless telemetry/powering and structural support. The system comprises of a MEMS pressure sensor, ASIC for the sensor interface and wireless capabilities, LCP substrate, and FDA approved stent. In vivo studies on pigs validated functionality and fully wireless operation and demonstrate the feasibility of a stent-based wireless implant for continuous monitoring of blood pressure as well as other parameters including oxygen, flow and turbulence, chemistry, and glucose.
From MOFs to zeolites: zirconium sites for epoxide rearrangement (2013)

Zirconium Lewis acid sites grafted onto a mesoporous silicate (MCM-41) and zirconium sites incorporated into inorganic–organic MOF materials are employed successfully in the rearrangement of β-pinene epoxide into myrtanal, which is a relevant compound for the fragrance industry. The materials are characterized and the strength of the active sites is evaluated by in situ IR spectroscopy with cyclohexanone as a probe molecule. It is shown that besides isolated zirconium sites, zirconium–oxygen–zirconium species might also be active species for the rearrangement.
352. The synthesis of some 6-thioxanthines (1962)

K. R. H. Wooldridge and R. Slack, J. Chem. Soc., 1962, 1863 DOI: 10.1039/JR9620001863