gebhart/patrepeval huggingface dataset:
Phosphorylated and cleaved TDP-43 in ALS, FTLD and other neurodegenerative disorders and in cellular models of TDP-43 proteinopathy (2010)

Transactivation response (TAR) DNA-binding protein of Mr 43 kDa (TDP-43) is a major component of the tau-negative and ubiquitin-positive inclusions that characterize amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration which is now referred to as FTLD-TDP. Concurrent TDP-43 pathology has been reported in a variety of other neurodegenerative disorders such as Alzheimer's disease, forming a group of TDP-43 proteinopathy. Accumulated TDP-43 is characterized by phosphorylation and fragmentation. There is a close relationship between the pathological subtypes of FTLD-TDP and the immunoblot pattern of the C-terminal fragments of phosphorylated TDP-43. These results suggest that proteolytic processing of accumulated TDP-43 may play an important role for the pathological process. In cultured cells, transfected C-terminal fragments of TDP-43 are more prone to form aggregates than full-length TDP-43. Transfecting the C-terminal fragment of TDP-43 harboring pathogenic mutations of TDP-43 gene identified in familial and sporadic ALS cases into cells enhanced the aggregate formation. Furthermore, we found that methylene blue and dimebon inhibit aggregation of TDP-43 in these cellular models. Understanding the mechanism of phosphorylation and truncation of TDP-43 and aggregate formation may be crucial for clarifying the pathogenesis of TDP-43 proteinopathy and for developing useful therapeutics.
Prevention of allergy by a recombinant multi-allergen vaccine with reduced IgE binding and preserved T cell epitopes (2005)

Novel approaches for the prevention of allergy are required, because of the inevitably increasing prevalence of allergic diseases during the last 30 years. Here, a recombinant chimeric protein, which comprises the whole amino acid sequences of three bee venom major allergens has been engineered and used in prevention of bee venom sensitization in mice. Phospholipase A2 (Api m 1), hyaluronidase (Api m 2) and melittin (Api m 3) fragments with overlapping amino acids were assembled in a different order in the Api m (1/2/3) chimeric protein, which preserved entire T cell epitopes, whereas B cell epitopes of all three allergens were abrogated. Accordingly, IgE cross-linking leading to mast cell and basophil mediator release was profoundly reduced in humans. Supporting these findings, the Api m (1/2/3) induced 100 to 1000 times less type-1 skin test reactivity in allergic patients. Treatment of mice with Api m (1/2/3) led to a significant reduction of specific IgE development towards native allergen, representing a protective vaccine effect in vivo. These results demonstrate a novel prototype of a preventive allergy vaccine, which preserves the entire T cell epitope repertoire, but bypasses induction of IgE against native allergen, and side effects related to mast cell/basophil IgE FcepsilonRI cross-linking in sensitized individuals.
Method for Direct Measurement of the Wigner Function in Cavity QED and Ion Traps (1997)

We show that the Wigner function corresponding to an electromagnetic field in a cavity or a vibronic state of a trapped ion can be directly measured by means of a simple experimental procedure. The proposed method is insensitive to the relatively low detection efficiency in cavity QED experiments and yields a direct physical meaning to the Wigner distribution.
Enhancement of glutamate uptake mediates the neuroprotection exerted by activating group II or III metabotropic glutamate receptors on astrocytes (2005)

We investigated whether the activation of astroglial group II and III metabotropic glutamate receptors (mGluRs) could exert neuroprotective effects and whether the neuroprotection was related to glutamate uptake. Our results showed that the activation of astroglial group II or III mGluRs exerted neuroprotection against 1-methyl-4-phenylpyridinium (MPP+) astroglial conditioned medium-induced neurotoxicity in midbrain neuron cultures. Furthermore, MPP+ decreased glutamate uptake of primary astrocytes and C6 glioma cells, which was recovered by activating group II or III mGluRs. Specific group II or III mGluRs antagonists completely abolished the neuroprotective effects and the enhancement of glutamate uptake of their respective agonists. Our results showed that the primary cultured rat astrocytes and C6 glioma cells expressed receptor proteins for group II mGluR2/3, group III mGluR4, mGluR6 and mGluR7. C6 glioma cells expressed mRNA for group II mGluR3, group III mGluR4, mGluR6, mGluR7 and mGluR8. In conclusion, we confirmed that the activation of astroglial mGluRs exerted neuroprotection, and demonstrated that the mechanism underlying this protective role was at least partially related to the enhancement of glutamate uptake.
The Potential Active Site of the Lipoprotein-specific (Type II) Signal Peptidase of Bacillus subtilis (1999)

Type II signal peptidases (SPase II) remove signal peptides from lipid-modified preproteins of eubacteria. As the catalytic mechanism employed by type II SPases was not known, the present studies were aimed at the identification of their potential active site residues. Comparison of the deduced amino acid sequences of 19 known type II SPases revealed the presence of five conserved domains. The importance of the 15 best conserved residues in these domains was investigated using the type II SPase of Bacillus subtilis, which, unlike SPase II of Escherichia coli, is not essential for viability. The results showed that only six residues are important for SPase II activity. These are Asp-14, Asn-99, Asp-102, Asn-126, Ala-128, and Asp-129. Only Asp-14 was required for stability of SPase II, indicating that the other five residues are required for catalysis, the active site geometry, or the specific recognition of lipid-modified preproteins. As Asp-102 and Asp-129 are the only residues invoked in the known catalytic mechanisms of proteases, we hypothesize that these two residues are directly involved in SPase II-mediated catalysis. This implies that type II SPases belong to a novel family of aspartic proteases.
Human Induced Pluripotent Stem Cells Free of Vector and Transgene Sequences (2009)

Reprogramming differentiated human cells to induced pluripotent stem (iPS) cells has applications in basic biology, drug development, and transplantation. Human iPS cell derivation previously required vectors that integrate into the genome, which can create mutations and limit the utility of the cells in both research and clinical applications. We describe the derivation of human iPS cells with the use of nonintegrating episomal vectors. After removal of the episome, iPS cells completely free of vector and transgene sequences are derived that are similar to human embryonic stem (ES) cells in proliferative and developmental potential. These results demonstrate that reprogramming human somatic cells does not require genomic integration or the continued presence of exogenous reprogramming factors and removes one obstacle to the clinical application of human iPS cells.
Polymerase engineering: towards the encoded synthesis of unnatural biopolymers (2009)

DNA is not only a repository of genetic information for life, it is also a unique polymer with remarkable properties: it associates according to well-defined rules, it can be assembled into diverse nanostructures of defined geometry, it can be evolved to bind ligands and catalyse chemical reactions and it can serve as a supramolecular scaffold to arrange chemical groups in space. However, its chemical makeup is rather uniform and the physicochemical properties of the four canonical bases only span a narrow range. Much wider chemical diversity is accessible through solid-phase synthesis but oligomers are limited to <100 nucleotides and variations in chemistry can usually not be replicated and thus are not amenable to evolution. Recent advances in nucleic acid chemistry and polymerase engineering promise to bring the synthesis, replication and ultimately evolution of nucleic acid polymers with greatly expanded chemical diversity within our reach.
Purinergic 2Y 1 Receptor Stimulation Decreases Cerebral Edema and Reactive Gliosis in a Traumatic Brain Injury Model (2012)

Traumatic brain injury (TBI) is the leading cause of death and disability in children and young adults. Neuroprotective agents that may promote repair or counteract damage after injury do not currently exist. We recently reported that stimulation of the purinergic receptor subtype P2Y(1)R using 2-methylthioladenosine 5' diphosphate (2MeSADP) significantly reduced cytotoxic edema induced by photothrombosis. Here, we tested whether P2Y(1)R stimulation was neuroprotective after TBI. A controlled closed head injury model was established for mice using a pneumatic impact device. Brains were harvested at 1, 3, or 7 days post-injury and assayed for morphological changes by immunocytochemistry, Western blot analysis, and wet/dry weight. Cerebral edema and expression of both aquaporin type 4 and glial fibrillary acidic protein were increased at all time points examined. Immunocytochemical measurements in both cortical and hippocampal slices also revealed significant neuronal swelling and reactive gliosis. Treatment of mice with 2MeSADP (100 μM) or MRS2365 (100 μM) 30 min after trauma significantly reduced all post-injury symptoms of TBI including edema, neuronal swelling, reactive gliosis, and AQ4 expression. The neuroprotective effect was lost in IP(3)R2-/- mice treated with 2MeSADP. Immunocytochemical labeling of brain slices confirmed that P2Y(1)R expression was defined to cortical and hippocampal astrocytes, but not neurons. Taken together, the data show that stimulation of astrocytic P2Y(1)Rs significantly reduces brain injury after acute trauma and is mediated by the IP(3)-signaling pathway. We suggest that enhancing astrocyte mitochondrial metabolism offers a promising neuroprotective strategy for a broad range of brain injuries.
Transmission channel model and capacity of overhead multi-conductor medium-voltage power-lines for broadband communications (2005)

A channel model suitable for multi-wire overhead medium-voltage lines is proposed. The model, incorporating ground admittance, is more appropriate for broadband communications. This model is then employed in order to evaluate the multipath channel impulse response and the associated transmission capacity limit in actual overhead medium-voltage power distribution networks for broadband power-line communications applications.
Field Evaluation of a Hexaflumuron Bait for Population Suppression of Subterranean Termites (Isoptera: Rhinotermitidae) (1994)

Journal Article Field Evaluation of a Hexaflumuron Bait for Population Suppression of Subterranean Termites (Isoptera: Rhinotermitidae) Get access Nan-Yao Su Nan-Yao Su Ft. Lauderdale Research and Education Center, University of Florida, Institute of Food and Agricultural Sciences, 3205 College Avenue, Ft. Lauderdale, FL 33314 Search for other works by this author on: Oxford Academic PubMed Google Scholar Journal of Economic Entomology, Volume 87, Issue 2, 1 April 1994, Pages 389–397, https://doi.org/10.1093/jee/87.2.389 Published: 01 April 1994 Article history Received: 07 January 1993 Accepted: 25 October 1993 Published: 01 April 1994
Pharmacokinetics and pharmacodynamics of newer macrolides (1997)

Requirements for the antimicrobial activity of an antibiotic are: (1) binding of the drug to a specific site in the bacteria; (2) occupation of a critical number of binding sites; and (3) persistence at these binding sites for a sufficient time. With concentration-dependent antibiotics the ratio of the peak serum drug concentration to the MIC of a pathogen is the primary determinant of bacterial killing; with concentration-independent antibiotics it is the length of time serum concentration remains above the MIC, rather than the peak level. The pharmacokinetics of the new macrolides azithromycin and clarithromycin differ notably from those of conventional antibiotics in a more rapid and extensive distribution to body tissues. Because of these unique tissue pharmacokinetics, the pharmacodynamic models that apply to other classes of antibiotics may not explain the antimicrobial activity and clinical efficacy of azithromycin and clarithromycin.
A Stable Isotope Dilution Assay for the In Vivo Determination of Insulin Levels in Humans by Mass Spectrometry (1997)

Insulin levels in humans were measured by a new assay, the isotope dilution assay (IDA), based on stable isotope dilution mass spectrometry. A known amount of a deuterated analog of insulin was used as an internal standard and added to the serum samples before sample processing. After isolation by immunoaffinity chromatography and solid phase extraction, followed by a purification step on reversed-phase microbore high-performance liquid chromatography (HPLC), the insulin-containing fraction was analyzed by mass spectrometry. The relative intensity of the signals due to insulin and its deuterated analog in the mass spectrum was used to determine the concentration of insulin in the sample. Using serum samples of 0.5-2.0 ml, we were able to measure insulin levels in the range of 3-1700 pmol/l in several clinical samples from type II diabetic patients. The basal level of endogenous insulin was also determined in two normal subjects and found to be approximately 20 pmol/l. Insulin secretion was followed after the ingestion of 75 g glucose in one healthy volunteer. Finally, the determination of the insulin level of one hemolyzed post-mortem blood sample, for which immunoassays gave inconsistent results, was performed to help forensic investigations. Our results showed a good correlation with standard immunoassay data, except in six samples where much lower values were obtained by our stable isotope dilution assay, suggesting an overestimation of insulin levels by immunoassay in some cases. As it is not subject to immunological interferences by insulin-related compounds, this new assay has a major clinical advantage in that it avoids confusions related to hyperinsulinemia.
Effects of Seleniferous Grains and Inorganic Selenium on Tissue and Blood Composition and Growth Performance of Rats and Swine (1984)

Two experiments were conducted to determine the effect of varying dietary selenium (Se) levels and Se source on growing swine. In Exp. 1, seleniferous wheat and oats were used to formulate diets containing .47, 2.58, 5.60 or 8.40 micrograms/g organic Se. Dietary Se level had no effect on pig performance during the 6-wk experiment as measured by daily gain, daily feed intake or feed/gain. Blood composition and enzyme activity were not affected by dietary treatment. Selenium concentrations of blood, hair, liver, kidney, heart, spleen and diaphragm muscle were increased linearly (P less than .01) as dietary Se increased. In addition, liver weight as a percentage of body weight was increased linearly (P less than .01) as dietary Se level increased. No signs of chronic Se poisoning were observed. Dietary treatments in Exp. 2 were similar to Exp. 1 with the exception that sodium selenite was utilized as the Se source and the diets were fed for 17 wk. Inorganic Se levels of .54, 2.63, 5.69 or 8.33 micrograms/g had no effect on pig performance as measured by daily gain, daily feed intake or feed/gain. Selenium concentrations of blood, hair, liver, kidney, spleen and diaphragm muscle were significantly increased as dietary Se level increased. Liver weight as a percentage of body weight was increased at the two highest dietary Se levels. Blood glutathione peroxidase activity was significantly increased by dietary treatment, while other blood variables were not affected. No signs of chronic Se poisoning were observed.(ABSTRACT TRUNCATED AT 250 WORDS)
Sequence Divergence of 5′ Extremities in Rat Liver Alkaline Phosphatase mRNAs1 (1989)

Structural analysis of 55 nearly full-length cDNA clones of rat liver alkaline phosphatase mRNAs revealed the presence of two totally different sequence stretches at the 5'-distal region starting from the position 88 nucleotides upstream of the initiation codon ATG. Since each of these two sequences, E1 and E2, was assigned on the rat genome about 36 kilobase pairs (kbp) and 10 kbp upstream of the common exon E3, respectively, they are presumably used as alternatively spliced exons. The distances between these sequences and E3 were unusually long, as compared with other intronic distances (0.4-4 kbp) observed between successive pairs of the eleven exons which are common to both types of mRNAs. The relative ratio of E1-containing mRNA to E2-mRNA was about three in the liver after bile-duct ligation and colchicine treatment.
Stereocontrolled Synthesis of Oligoribonucleoside Phosphorothioates by an Oxazaphospholidine Approach (2009)

Oligoribonucleoside phosphorothioates (PS-ORNs) stereodefined at the phosphorus atoms were synthesized on solid support. Thermal denaturating experiments of the resultant PS-ORNs showed that a backbone consisting of (Sp)-PS-linkages as well as stereorandom PS-linkages had an unexpectedly large destabilizing effect on a PS-ORN−ORN duplex, whereas a backbone consisting of (Rp)-PS-linkages slightly stabilized a duplex.
Linac Options for the Ion Injector of MEIC (2016)

In the current baseline design of the Medium-energy Electron-Ion Collider (MEIC) proposed by Jefferson Lab, a green field ion injector complex is composed of several ion sources, one linac with charge stripper, and one booster ring. The original linac design contains a short warm front end and a long SRF section with QWR/HWR cavities, capable of accelerating H^{−} to 285 MeV or Pb⁶⁷⁺ to 100 MeV/u. Such a linac is a major cost driver of the project, despite that the required duty factor of this linac is very low. In this paper, we will compare alternative options for this ion linac, including the possibilities to lower the linac energy and choose a warm linac.
Anti–high mobility group box‐1 antibody therapy for traumatic brain injury (2012)

Anti-HMGB1 mAb may provide a novel and effective therapy for TBI by protecting against BBB disruption and reducing the inflammatory responses induced by HMGB1.
Relaxed Si1−xGex/Si1−x−yGexCy buffer structures with low threading dislocation density (1997)

We demonstrate the growth of a relaxed, only 1 μm thick, stepwise graded buffer based on a combination of Si1−xGex and Si1−x−yGexCy. This buffer concept relies on the retardation of dislocation glide in Si1−x−yGexCy relative to strain equivalent Si1−xGex on silicon. The homogeneous Si1−xGex layer with x=30% on top of the buffer structure is (73±5)% relaxed. For the nonoptimized buffer growth, we already find a threading dislocation density below 105 cm−2. A stepped Si1−xGex buffer with the identical thickness and strain profile grown with the same temperature ramp yields a threading dislocation density above 107 cm−2. This indicates that the addition of carbon is a promising way for new relaxed buffer concepts with low threading dislocation densities.
Ketamine alleviates LPS induced lung injury by inhibiting HMGB1-RAGE level. (2018)

Ketamine can alleviate LPS induced lung injury through inhibiting HMGB1-RAGE level. It could be treated as a new choice for ALI treatment.
Renal hyporesponsiveness to atrial natriuretic peptide in congestive heart failure results from reduced atrial natriuretic peptide receptor concentrations (2007)

Atrial natriuretic peptide (ANP) and B-type natriuretic peptide decrease blood pressure and cardiac hypertrophy by activating natriuretic peptide receptor A (NPR-A), a transmembrane guanylyl cyclase also known as guanylyl cyclase A. Inactivation of NPR-A is a potential mechanism for the renal hyporesponsiveness observed in congestive heart failure (CHF) but direct data supporting this hypothesis are lacking. We examined whether NPR-A activity was reduced in CHF, and if so, by what mechanism. In two separate trials, CHF was induced in mice by 8-wk transverse aortic constriction. Sham controls underwent surgery without constriction. The constricted animals developed severe heart failure as indicated by increased heart weight, increased left ventricular end diastolic and systolic diameters, and decreased left ventricular ejection fractions. Kidney membranes were assayed for guanylyl cyclase activity or used to purify NPR-A by sequential immunoprecipitation/SDS-PAGE. Maximal ANP-dependent guanylyl cyclase activities were reduced by 44 or 43% in kidney membranes from CHF animals in two independent trials. Basal cyclase activities were also reduced by 31% in the second trial. The amount of phosphorylated NPR-A was reduced by 25 or 24% in kidney membranes from CHF animals as well. SYPRO Ruby staining suggested that NPR-A protein levels were similar between treatments in the first trial. However, more accurate estimates of NPR-A protein levels by immunoprecipitation/Western analysis in the second trial indicated that NPR-A protein was reduced by 30%. We conclude that reduced NPR-A protein levels, not receptor dephosphorylation, explain the renal hyporesponsiveness to natriuretic peptides in CHF.
Induction of Arabidopsis Defense Genes by Virulent and Avirulent Pseudomonas syringae Strains and by a Cloned Avirulence Gene (1991)

Xinnian Dong, Michael Mindrinos, Keith R. Davis, Frederick M. Ausubel, Induction of Arabidopsis Defense Genes by Virulent and Avirulent Pseudomonas syringae Strains and by a Cloned Avirulence Gene, The Plant Cell, Vol. 3, No. 1 (Jan., 1991), pp. 61-72
Effect of the expression of cyanamide hydratase on metabolites in cyanamide-treated soybean plants kept in the light or dark (2007)

Metabolite profiling of untransformed and cyanamide hydratase- (Cah) transformed (denoted 1C) soybean (Glycine max [L.] Merrill) leaves revealed only small differences in plants grown in the greenhouse or in the dark for 24 h, indicating that the Cah enzyme that converts cyanamide to urea has no substrates in soybean leaves and does not affect metabolism. Untransformed leaves sprayed with 0.5% cyanamide developed necrotic lesions within 2 h in the light but not in the dark. The sprayed 1C leaves showed little visible damage and accumulated high concentrations of urea, amino acids, and some sugars, but sucrose decreased over a 24 h period. The untransformed necrotic leaves also accumulated some urea and amino acids apparently due to cyanamide degradation, while sucrose and some organic acids decreased. Sprayed 1C leaves in the dark for 24 h contained very little urea and lower sugar levels. The untransformed sprayed leaves accumulated some organic acids, some sugars including sucrose, and urea and total amino acids. Unsprayed plants of both lines placed in the dark for 24 h showed increases in some amino acids and phosphate, and decreases in other amino acids, sugars, and organic acids. Thus the Cah enzyme can detoxify cyanamide by conversion to urea that is converted to amino acids. Other metabolic changes associated with leaf necrosis and darkness are also described. Principal component analysis confirmed the similarities and differences observed. Comparison of the GC-MS metabolic profiling analysis of amino acids with a dedicated system shows large differences, indicating a limitation of the former system.