gebhart/patrepeval huggingface dataset:
Six Generations Of The Insulin Dosage Computer: A New Clinical Device For Diabetes Self-management Through Specialized Centres (2005)

Modern technology and dedicated microprocessors in particular, are revolutionizing the treatment of diabetes. Through specialized centres and a select group of new medical experts, conventional diabetes management is gradually being replaced by a system of technology assisted self-care. The present paper outlines the characteristics of six consecutive generations of a new device called an insulin dosage computer. It facilitates self-care by calculating insulin dosages each day at each meal based on glucose measurements made by the patients themselves. The device was initially developed in 1982 and is now extended to over 1200 patients each of whom has acquired expert skills for self-management and thereby achieved improved metabolic control with freedom both from hypoglycemia and from the psychological dependencies usually accompanying this disorder.
Amyloid Fibrils Activate Tyrosine Kinase-Dependent Signaling and Superoxide Production in Microglia (1997)

Alzheimer's disease (AD) is a devastating neurological disorder characterized by loss of cognitive skills and progressive dementia. The pathological hallmark of AD is the presence of numerous senile plaques throughout the hippocampus and cerebral cortex associated with degenerating axons, neurofibrillary tangles, and gliosis. The core of the senile plaque primarily is composed of the 39-43 amino acid beta-amyloid peptide (Abeta), which forms fibrils of beta-pleated sheets. Although considerable genetic evidence implicates Abeta in the pathogenesis of AD, a direct causal link remains to be established. Senile plaques are foci of local inflammatory processes, as evidenced by the presence of numerous activated microglia and acute phase proteins. Abeta has been shown to elicit inflammatory responses in microglia; however, the intracellular events mediating these effects are largely unknown. We report that exposure of microglia and THP1 monocytes to fibrillar Abeta led to time- and dose-dependent increases in protein tyrosine phosphorylation of a population of proteins similar to that elicited by classical immune stimuli such as immune complexes. The tyrosine kinases Lyn, Syk, and FAK were activated on exposure of microglia and THP1 monocytes to Abeta, resulting in the tyrosine kinase-dependent generation of superoxide radicals. The present data support a role for oxidative damage in the pathogenesis of AD, provide an important mechanistic link between Abeta and the generation of reactive oxygen intermediates, and identify molecular targets for therapeutic intervention in AD.
Human gut bacteria as potent class I histone deacetylase inhibitors in vitro through production of butyric acid and valeric acid (2018)

Overexpression of histone deacetylase (HDAC) isoforms has been implicated in a variety of disease pathologies, from cancer and colitis to cardiovascular disease and neurodegeneration, thus HDAC inhibitors have a long history as therapeutic targets. The gut microbiota can influence HDAC activity via microbial-derived metabolites. While HDAC inhibition (HDI) by gut commensals has long been attributed to the short chain fatty acid (SCFA) butyrate, the potent metabolic reservoir provided by the gut microbiota and its role in host physiology warrants further investigation in a variety of diseases. Cell-free supernatants (CFS) of 79 phylogenetically diverse gut commensals isolated from healthy human donors were screened for their SCFA profile and their total HDAC inhibitory properties. The three most potent HDAC inhibiting strains were further evaluated and subjected to additional analysis of specific class I and class II HDAC inhibition. All three HDAC inhibitors are butyrate producing strains, and one of these also produced substantial levels of valeric acid and hexanoic acid. Valeric acid was identified as a potential contributor to the HDAC inhibitory effects. This bacterial strain, Megasphaera massiliensis MRx0029, was added to a model microbial consortium to assess its metabolic activity in interaction with a complex community. M. massiliensis MRx0029 successfully established in the consortium and enhanced the total and specific HDAC inhibitory function by increasing the capacity of the community to produce butyrate and valeric acid. We here show that single bacterial strains from the human gut microbiota have potential as novel HDI therapeutics for disease areas involving host epigenetic aberrations.
Polymer-stimulated ligation: enhanced blunt- Or cohesive-end ligation of DNA or deoxyribooligonudcleotides by T4 DNA Ugase in polymer solutions (1983)

The rates of blunt-end and cohesive-end ligation of DNA by T4 DNA ligase are increased by orders of magnitude in the presence of high concentrations of a variety of nonspecific polymers such as polyethylene glycol, Ficoll, bovine plasma albumin, or glycogen. Blunt-end ligation of small self-complementary oligodeoxyribonucleotides is also stimulated. The use of polyethylene glycol 6000 in such systems is characterized in some detail. Conditions are suggested which either greatly increase the rate of formation of and size of linear ligation products or which allow smaller but significant improvements in the amounts of circular ligation products.
Silvicultural management of white pines in western North America (2010)

Summary Since the introduction prior to 1915 of white pine blister rust ( Cronartium ribicola ) into the forests of western North America, many populations of native white pine species have seriously declined. Because western white pine ( Pinus monticola ) and sugar pine ( P. lambertiana ) are highly valued timber species, their silviculture under intensive management is well‐documented. The silviculture of other white pine species has received less attention but is no less important. For all western species, silvicultural management is a key component for sustaining and restoring viable white pine populations. This review examines approaches for assessing and reducing blister rust hazard, regenerating white pine stands, and tending established stands to reduce damage and impact from blister rust. Hazard and risk ratings provide means for assessing the potential severity of blister rust infestation and its probable impacts on management. An epidemiological simulation model is available for describing complex pathosystem interactions, their consequences on white pine growth and survival, and likely outcomes of silvicultural activities. Until the 1960s, Ribes eradication was the principal method for blister rust control; it is now rarely used except for high‐value trees. The choices of harvest and site preparation methods are critical for successful white pine regeneration. As host responses to blister rust infection are inherited, regeneration is an opportunity to increase seedling survival and disease resistance. For artificial regeneration, the western genetics programmes provide improved planting stock. For natural regeneration, the selection and retention of well‐adapted white pines as seed sources can enhance stand genetics. Thinning and pruning are common silvicultural activities for tending stands and are readily modified for blister rust‐infested stands. Although biological and chemical agents have been used, their performance has been less than satisfactory. Likewise, genetics and other silvicultural practices have also demonstrated limited success in blister rust control. An alternative, adaptive approach could use both silvicultural and genetic techniques to mitigate impacts and maintain white pines.
The effects of Mevinolin on The Thiol/Disulfide Exchange between 3-Hydroxy-3-methyglutaryl-coenzyme A Reductase and Glutathione (1989)

The feeding of mevinolin plus cholestyramine to rats results in the production of a form of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR-CM) having thiol/disulfide redox properties different from those of 3-hydroxy-3-methylglutaryl-CoA reductase isolated from animals which had been given only cholestyramine (HMGR-C). The second-order rate constant for the inactivation of HMGR-CM by GSSG is 7-fold slower than for HMGR-C, while the second-order rate constant for the reactivation of oxidized enzyme by GSH is 100-fold slower. However, in the presence of saturating concentrations of both substrates, the rate constants for thiol/disulfide exchange are similar for both forms of the enzyme. HMGR-CM behaves as if a protein-glutathione mixed disulfide having a Kox of 27 +/- 4 is formed at equilibrium. In contrast, HMGR-C has previously been shown to form a protein-protein disulfide (Cappel, R. E., and Gilbert, H. F. (1988) J. Biol. Chem. 263, 12204-12212). Both forms of the enzyme are more difficult to oxidize thermodynamically in the presence of saturating levels of both substrates. For HMGR-CM, NADPH alone has no effect on the equilibrium constant for oxidation, but hydroxymethylglutaryl-CoA alone makes the enzyme approximately twice as difficult to oxidize. Under physiological conditions, HMGR-CM is thermodynamically more difficult to oxidize than HMGR-C. HMGR-C can be converted to HMGR-CM by in vitro treatment with mevinolinate. A direct or indirect interaction of mevinolin with HMGR-C results in some persistent, as yet undefined, structural alteration which inhibits the formation of a protein-SS-protein disulfide upon oxidation by glutathione disulfide.
Carer burden in schizophrenia: considerations for nursing practice (2010)

Neil Small and colleagues describe a study that shows how differently the families of people with mental health problems and healthcare professionals perceive the role of carers
Closed loop solder-lines on heated substrates (2003)

Wafer level MEMS vacuum packaging has been newly designed, fabricated, and characterized by utilizing silicon bulk micromachining and closed loop solder-line bonding. For evaluating the proposed MEMS packaging, a packaging specimen is fabricated which comprises of cap and device substrates. AuSn closed loop solder lines are formed on the cap substrate and feedthroughs are fabricated on the device substrate with deflection diaphragms, respectively. The proposed package can be utilized in wafer level packaging, chip scale packaging, and low cost packaging due to the low process temperature, the compatible fabrication sequences with MEMS devices and a specified pressure endurance. It can be also applied in packaging integrated micro-systems comprised of various components, sensors, and actuators with different processing/working temperature by utilizing the closed loop solder-line on the heated substrate.
Impact of LVAD Implantation Site on Ventricular Blood Stagnation (2016)

Treatment of end-stage heart failure includes cardiac transplantation or ventricular assist device (VAD) therapy. Although increasingly prevalent, current VAD therapy has inherent complications, including thrombosis. Studies have demonstrated that VAD implantation alters intracardiac blood flow, creating areas of stagnation that predispose to thrombus formation. Two potential surgical configurations exist for VAD implantation: through the apical or diaphragmatic surfaces of the heart. We hypothesized that diaphragmatic implantation causes more stagnation than apical implantation. We also hypothesized that intermittent aortic valve (AV) opening reduces stagnation of blood inside the left ventricle (LV) when compared with a closed AV. To test these hypotheses, a human LV geometry was recreated in silico and a VAD inflow cannula was virtually implanted in each configuration. A computational indicator-dilution study was conducted where "virtually dyed blood" was washed out of the LV by injecting blood with no dye. Simulations demonstrated a substantial reduction in stagnation with intermittent AV opening. In addition, virtual dye was cleared slightly faster in the apical configuration. Simulations from our study demonstrate the clinical importance of VAD management to allow intermittent opening of the AV to prevent subvalvular stagnation, and also suggests that apical configuration might be more hemodynamically favorable.
Genetic Determinants of Volatile-Thiol Release bySaccharomyces cerevisiaeduring Wine Fermentation (2005)

Volatile thiols, particularly 4-mercapto-4-methylpentan-2-one (4MMP), make an important contribution to the aroma of wine. During wine fermentation, Saccharomyces cerevisiae mediates the cleavage of a nonvolatile cysteinylated precursor in grape juice (Cys-4MMP) to release the volatile thiol 4MMP. Carbon-sulfur lyases are anticipated to be involved in this reaction. To establish the mechanism of 4MMP release and to develop strains that modulate its release, the effect of deleting genes encoding putative yeast carbon-sulfur lyases on the cleavage of Cys-4MMP was tested. The results led to the identification of four genes that influence the release of the volatile thiol 4MMP in a laboratory strain, indicating that the mechanism of release involves multiple genes. Deletion of the same genes from a homozygous derivative of the commercial wine yeast VL3 confirmed the importance of these genes in affecting 4MMP release. A strain deleted in a putative carbon-sulfur lyase gene, YAL012W, produced a second sulfur compound at significantly higher concentrations than those produced by the wild-type strain. Using mass spectrometry, this compound was identified as 2-methyltetrathiophen-3-one (MTHT), which was previously shown to contribute to wine aroma but was of unknown biosynthetic origin. The formation of MTHT in YAL012W deletion strains indicates a yeast biosynthetic origin of MTHT. The results demonstrate that the mechanism of synthesis of yeast-derived wine aroma components, even those present in small concentrations, can be investigated using genetic screens.
GLEPP1, a renal glomerular epithelial cell (podocyte) membrane protein-tyrosine phosphatase. Identification, molecular cloning, and characterization in rabbit. (1994)

Podocytes are specialized epithelial cells with delicate interdigitating foot processes which cover the exterior basement membrane surface of the glomerular capillary. They are in part responsible for the extraordinary charge and size filtration characteristics of the glomerulus. To better understand disease processes affecting the glomerular filter, we searched for proteins with relative specificity to the podocyte using a monoclonal antibody strategy. The first such protein characterized (designated glomerular epithelial protein 1 (GLEPP1)) is a membrane protein-tyrosine phosphatase (PTPase) with a large extracellular domain containing eight fibronectin type III-like repeats, a hydrophobic transmembrane segment, and a single PTPase domain. The GLEPP1 PTPase domain shows homology with two other single domain transmembrane PTPases (PTP beta and Drosophila central nervous system PTP10D). This homology includes 2 cysteines in the PTPase domain not present in intracellular or tandem domain membrane PTPases. GLEPP1 PTPase protein is distributed to the podocyte foot processes themselves. RNase protection assay shows that GLEPP1 mRNA is also present in brain. By analogy with the CD45 PTPase of T cells, we expect that this receptor might play a role in maintaining foot process structure and/or function by regulating tyrosine phosphorylation of podocyte proteins.
Conformational Changes of Complement Components C3 and BInduced at Higher Temperature (1985)

When purified C3 or B of human complement was incubated at various temperatures for 30 min, B lost most of its antibody combining capability at 46 degrees C, and C3 lost it at higher than 50 degrees C. When C3, heated B, D and Mg++ ions were incubated, there was a precipitous decrease in C3 conversion in the presence of heated B between 44 and 46 degrees C. No C3 conversion was observed in the presence of B heated at 50 degrees C. When C3 heated higher than 50 degrees C was incubated with B, D and Mg++ ions, C3 conversion decreased dramatically, but B was converted almost normally, suggesting that B could be complexed with heated and conformationally altered C3 and cleaved by D. The fluorescence intensity of heated C3 excited at 288 nm gradually decreased between 44 and 46 degrees C. The fluorescence 288 nm gradually decreased between 44 and 46 degrees C. The fluorescence intensity of C3 was slightly increased by 1-anilino-8-naphthalene sulfonate (ANS) at 50 degrees C and significantly increased at 56 degrees C, while ANS enhancement of fluorescence of B began at 46 degrees C and was significant at 50 degrees C, indicating that the surface of B and C3 became hydrophobic between 44 and 46 degrees C, and 46 and 50 degrees C, respectively. These results suggest that conformations of C3 and B have low melting points at which they change confirmations drastically.
Clinical and genetic studies in hereditary spastic paraplegia with thin corpus callosum (2004)

HSP-TCC is common in Italy. The phenotype is fairly homogeneous and is associated with impaired cognition. There are at least two loci for HSP-TCC, one of which is on chromosome 15q13-15.
Insights into binding cooperativity of MATa1/MATα2 from the crystal structure of a MATa1 homeodomain‐maltose binding protein chimera (2003)

The Yeast MATa1 and MATalpha2 are homeodomain proteins that bind DNA cooperatively to repress transcription of cell type specific genes. The DNA affinity and specificity of MATa1 in the absence of MATalpha2, however, is very low. MATa1 is converted to a higher affinity DNA-binding protein by its interaction with the C-terminal tail of MATalpha2. To understand why MATa1 binds DNA weakly by itself, and how the MATalpha2 tail affects the affinity of MATa1 for DNA, we determined the crystal structure of a maltose-binding protein (MBP)-a1 chimera whose DNA binding behavior is similar to MATa1. The overall MATa1 conformation in the MBP-a1 structure, which was determined in the absence of alpha2 and DNA, is similar to that in the a1/alpha2/DNA structure. The sole difference is in the C-terminal portion of the DNA recognition helix of MATa1, which is flexible in the present structure. However, these residues are not in a location likely to be affected by binding of the MATalpha2 tail. The results argue against conformational changes in a1 induced by the tail of MATalpha2, suggesting instead that the MATalpha2 tail energetically couples the DNA binding of MATalpha2 and MATa1.
<title>Silicon nanofilter with absolute pore size and high mechanical strength</title> (1995)

Microfabricated silicon filters with a nominal pore size of 20 nm have been successfully fabricated and characterized. The filter consists of a filtration membrane on top of a silicon surface and a mechanical support on the silicon substrate. Two polysilicon layers together with a low temperature oxide layer are used to generate the filtration membrane on the front side of silicon wafers. The filtration function is accomplished by the flow channel generated from a sandwiched thin silicon dioxide layer. The thickness of the sandwiched oxide determines the particle size that can pass through the filter. Both distilled water and cell culture medium have been used to test the flow rate for this nanofilter. We have found that the flow rate of the nanofilter is highest at the beginning of the test, and then slowly decreases to its asymptotic values for both water and the cell culture medium. The observed flow rate is linearly proportional to the applied pressure in the ranges tested. The typical flow rate of distilled water for 20 nm filter with 1.19 cm<SUP>2</SUP> effective filtration area is about 0.07 ml/min for applied pressure of 8 PSI. The filter successfully sustained pressure of up to 20 PSI.
The DFR locus: A smart landing pad for targeted transgene insertion in tomato (2018)

Targeted insertion of transgenes in plants is still challenging and requires further technical innovation. In the present study, we chose the tomato DFR gene involved in anthocyanin biosynthesis as a landing pad for targeted transgene insertion using CRISPR-Cas9 in a two-step strategy. First, a 1013 bp was deleted in the endogenous DFR gene. Hypocotyls and callus of in vitro regenerated plantlets homozygous for the deletion were green instead of the usual anthocyanin produced purple colour. Next, standard Agrobacterium-mediated transformation was used to target transgene insertion at the DFR landing pad in the dfr deletion line. The single binary vector carried two sgRNAs, a donor template containing two homology arms of 400 bp, the previously deleted DFR sequence, and a NptII expression cassette. Regenerating plantlets were screened for a purple-colour phenotype indicating that DFR function had been restored. Targeted insertions were identified in 1.29% of the transformed explants. Thus, we established an efficient method for selecting HDR-mediated transgene insertion using the CRISPR-Cas9 system in tomato. The visual screen used here facilitates selection of these rare gene targeting events, does not necessitate the systematic PCR screening of all the regenerating material and can be potentially applied to other crops.
Use of a Nonmedicated Dietary Supplement Correlates with Increased Prevalence of Streptomycin-Sulfa-Tetracycline-Resistant Escherichia coli on a Dairy Farm (2006)

We examined how a dietary supplement affects the prevalence of antibiotic-resistant Escherichia coli on a dairy farm in Washington State. Between 2001 and 2004 the prevalence of fecal E. coli strains resistant to streptomycin, sulfadiazine, and tetracycline (SSuT strains) declined from 59.2% to 26.1% in the calf population. In 2003 the dairy discontinued use of a dietary supplement, and we hypothesized that the decline in prevalence of SSuT strains was related to this change in management. To test this we established three treatments in which calves received no supplement, the dietary supplement with oxytetracycline, or the dietary supplement without oxytetracycline. Calves receiving either dietary supplement had a significantly higher prevalence of SSuT E. coli than the no-supplement control group (approximately 37% versus 20%, respectively; P = 0.03). Importantly, there was no evidence that oxytetracycline contributed to an increased prevalence of fecal SSuT E. coli. We compared the growth characteristics of SSuT and non-SSuT E. coli in LB broth enriched with either the complete dietary supplement or its individual constituents. Both the complete dietary supplement and its vitamin D component supported a significantly higher cell density of SSuT strains (P = 0.003 and P = 0.001, respectively). The dry milk and vitamin A components of the dietary supplement did not support different cell densities. These results were consistent with selection and maintenance of SSuT E. coli due to environmental components independent of antibiotic selection.
Small Molecule Inhibitors of Stat3 Signaling Pathway (2007)

Constitutive activation of the Signal Transducers and Activators of Transcription 3 (Stat3) meditated signaling pathway is very important for cell growth and survival. Compelling evidence from mechanistic studies with antisense, RNA interference (RNAi), peptides, and small molecular inhibitors indicate that blocking Stat3 signaling can lead to successful suppression of tumor cell growth and apoptosis. Thus, Stat3 is an attractive molecular target for the development of novel cancer therapeutics. In this article, we present the first comprehensive review focusing on small molecule inhibitors that effectively block the Stat3 signaling pathway. These inhibitors, from a structural point of view, are divided into five classes of compounds. They include (1) natural products and derivatives, such as curcumin, resveratrol and others, (2) tyrphostins, (3) platinum-containing complexes, (4) peptidomimetics, and (5) azaspiranes. Some compounds may have multiple targets including Stat3 protein, therefore these compounds need further optimization and validation. The purpose of this review is to provide a resource for researchers interested in Stat3 targeted small molecules which will be beneficial for database development and template design for future drug development.