gebhart/patrepeval huggingface dataset:
Pathogenic Role of the CRL4 Ubiquitin Ligase in Human Disease (2012)

The cullin 4-RING ubiquitin ligase (CRL4) family employs multiple DDB1-CUL4 associated factors substrate receptors to direct the degradation of proteins involved in a wide spectrum of cellular functions. Aberrant expression of the cullin 4A (CUL4A) gene is found in many tumor types, while mutations of the cullin 4B (CUL4B) gene are causally associated with human X-linked mental retardation. This focused review will summarize our current knowledge of the two CUL4 family members in the pathogenesis of human malignancy and neuronal disease, and discuss their potential as new targets for cancer prevention and therapeutic intervention.
Ferulic Acid: An Antioxidant Found Naturally in Plant Cell Walls and Feruloyl Esterases Involved in its Release and Their Applications (2004)

Ferulic acid is the most abundant hydroxycinnamic acid in the plant world and maize bran with 3.1% (w/w) ferulic acid is one of the most promising sources of this antioxidant. The dehydrodimers of ferulic acid are important structural components in the plant cell wall and serve to enhance its rigidity and strength. Feruloyl esterases are a subclass of the carboxylic acid esterases that hydrolyze the ester bond between hydroxycinnamic acids and sugars present in plant cell walls and they have been isolated from a wide range of microorganisms, when grown on complex substrates such as cereal brans, sugar beet pulp, pectin and xylan. These enzymes perform a function similar to alkali in the deesterification of plant cell wall and differ in their specificities towards the methyl esters of cinnamic acids and ferulolylated oligosaccharides. They act synergistically with xylanases and pectinases and facilitate the access of hydrolases to the backbone of cell wall polymers. The applications of ferulic acid and feruloyl esterase enzymes are many and varied. Ferulic acid obtained from agricultural byproducts is a potential precursor for the production of natural vanillin, due to the lower production cost.
All mixed up: defining roles for β-cell subtypes in mature islets (2017)

Following differentiation during fetal development, β cells further adapt to their postnatal role through functional maturation. While adult islets are thought to contain functionally mature β cells, recent analyses of transgenic rodent and human pancreata reveal a number of novel heterogeneity markers in mammalian β cells. The marked heterogeneity long after maturation raises the prospect that diverse populations harbor distinct roles aside from glucose-stimulated insulin secretion. In this review, we outline our current understanding of the β-cell maturation process, emphasize recent literature on novel heterogeneity markers, and offer perspectives on reconciling the findings from these two areas.
Endoproteinase‐protein inhibitor interactions (1999)

Nature uses protein inhibitors as important tools to regulate the proteolytic activity of their target proteinases. Most of these inhibitors for which 3D structures are available are directed towards serine proteinases, interacting with their active-sites in a substrate-like "canonical" manner via an exposed reactive-site loop of conserved conformation. More recently, some non-canonically binding serine proteinase inhibitors, two cysteine proteinase inhibitors, and three zinc endopeptidase inhibitors have been characterized in the free and complexed state, displaying novel mechanisms of inhibition with their target proteinases. These different interaction modes are briefly discussed, with particular emphasis on the interaction between matrix metalloproteinases (MMPs) and their endogenous tissue inhibitors of metalloproteinases (TIMPs).
MaskerAid : a performance enhancement to RepeatMasker (2000)

maskeraid@watson.wustl.edu
Tumor-specific apoptosis induced by the human monoclonal antibody SC-1: a new therapeutical approach for stomach cancer. (1998)

Stomach cancer is one of the most frequently occurring cancers worldwide, with a very poor prognosis, even after complete gastrectomy. We describe here an alternative therapeutical approach using a human monoclonal antibody (SC-1), which was isolated from a patient with diffuse-type gastric adenocarcinoma. We demonstrate that the antibody significantly reduces stomach cancer growth in vivo, by inducing tumor-specific apoptosis and that the antibody, even delivered in high doses, shows no toxic crossreactivity to other organs or tissues. The data presented here show that tumor-specific apoptosis can be induced and they give rise to the hope that human monoclonal antibodies with biological activity might present a completely new type of adjuvant cancer therapy.
Experimental Investigations on the Penetration of198Au from Nasal Mucous Membrane into Cerebrospinal Fluid (1970)

Determinations of the activity of the cerebrospinal fluid in 32 rabbits were made after administering the isotope 198Au under the mucous membrane of the olfactory region of the nose. Such activity indicates the direct penetration of 198Au from this membrane into the cerebrospinal fluid of the anterior cranial fossa.
Soiving problems associated with large-volume parenterals, ii: a hospital surveillance and reporting system (1975)

Journal Article Soiving problems associated with large-volume parenterals, ii: a hospital surveillance and reporting system Get access William A. Zellmer William A. Zellmer Search for other works by this author on: Oxford Academic Google Scholar American Journal of Hospital Pharmacy, Volume 32, Issue 12, 1 December 1975, Page 1231, https://doi.org/10.1093/ajhp/32.12.1231a Published: 01 December 1975
Nucleotide sequence, expression and transcriptional analysis of the Corynebacterium glutamicum gltA gene encoding citrate synthase (1994)

Citrate synthase catalyses the initial reaction of the citric acid cycle and can therefore be considered as the rate-controlling enzyme for the entry of substrates into the cycle. In Corynebacterium glutamicum, the specific activity of citrate synthase was found to be independent of the growth substrate and of the growth phase. The enzyme was not affected by NADH or 2-oxoglutarate and was only weakly inhibited by ATP (apparent Ki = 10 mM). These results suggest that in C. glutamicum neither the formation nor the activity of citrate synthase is subject to significant regulation. The citrate synthase gene, gltA, was isolated, subcloned on plasmid pJC1 and introduced into C. glutamicum. Relative to the wild-type the recombinant strains showed six- to eightfold higher specific citrate synthase activity. The nucleotide sequence of a 3007 bp DNA fragment containing the gltA gene and its flanking regions was determined. The predicted gltA gene product consists of 437 amino acids (M(r) 48,936) and shows up to 49.7% identity with citrate synthase polypeptides from other organisms. Inactivation of the chromosomal gltA gene by gene-directed mutagenesis led to absence of detectable citrate synthase activity and to citrate (or glutamate) auxotrophy, indicating that only one citrate synthase is present in C. glutamicum. Transcriptional analysis by Northern (RNA) hybridization and primer extension experiments revealed that the gltA gene is monocistronic (1.45 kb mRNA) and that its transcription initiates at two consecutive G residues located 121 and 120 bp upstream of the translational start.
Antiangiogenic scheduling of chemotherapy improves efficacy against experimental drug-resistant cancer. (2000)

To reveal the antiangiogenic capability of cancer chemotherapy, we developed an alternative antiangiogenic schedule for administration of cyclophosphamide. We show here that this antiangiogenic schedule avoided drug resistance and eradicated Lewis lung carcinoma and L1210 leukemia, an outcome not possible with the conventional schedule. When Lewis lung carcinoma and EMT-6 breast cancer were made drug resistant before therapy, the antiangiogenic schedule suppressed tumor growth 3-fold more effectively than the conventional schedule. When another angiogenesis inhibitor, TNP-470, was added to the antiangiogenic schedule of cyclophosphamide, drug-resistant Lewis lung carcinomas were eradicated. Each dose of the antiangiogenic schedule of cyclophosphamide induced the apoptosis of endothelial cells within tumors, and endothelial cell apoptosis preceded the apoptosis of drug-resistant tumor cells. This antiangiogenic effect was more pronounced in p53-null mice in which the apoptosis of p53-null endothelial cells induced by cyclophosphamide was so vigorous that drug-resistant tumors comprising 4.5% of body weight were eradicated. Thus, by using a dosing schedule of cyclophosphamide that provided more sustained apoptosis of endothelial cells within the vascular bed of a tumor, we show that a chemotherapeutic agent can more effectively control tumor growth in mice, regardless of whether the tumor cells are drug resistant.
Leptospirosis in Equine Fetuses, Stillborn Foals, and Placentas (1993)

Leptospirosis was diagnosed in 51 equine fetuses and 16 stillborn foals with gestational ages from 3 1/2 to 11 months. Diagnosis was based on one or more of the following: positive fetal antibody titer, positive fluorescent antibody test, demonstration of spirochetes in kidney and/or placental sections stained by the Warthin-Starry technique, high leptospiral titers in aborting mares, or isolation of Leptospira spp. from fetal organs. Gross lesions were observed in 80.3% of the fetuses, stillborn foals, and placentas. Gross placental lesions included nodular cystic allantoic masses, edema, areas of necrosis of the chorion, and necrotic mucoid exudate coating the chorion. The liver (23 cases) was enlarged, mottled, and pale to yellow. The kidneys (seven cases) were swollen and edematous with pale white radiating streaks in cortex and medulla. Microscopic lesions were observed in 96% of fetuses, stillborn foals, and placentas. Placental lesions consisted of thrombosis, vasculitis, mixed inflammatory cell infiltration of the stroma and villi, cystic adenomatous hyperplasia of allantoic epithelium, and villous necrosis and calcification. Fetal lesions included hepatocellular dissociation, mixed leukocytic infiltration of the portal triads, giant cell hepatopathy, suppurative and nonsuppurative nephritis, pulmonary hemorrhages, pneumonia, and myocarditis. Spirochetes were demonstrated with the Warthin-Starry stain in the allantochorion and/or kidney of 69 of the 71 cases. Using the direct fluorescent antibody technique, 56/60 cases tested positively for leptospires. Leptospires were isolated from fetal tissues in 20/42 cases. Sixteen of the isolates were identified by restriction enzyme analysis as Leptospira interrogans serogroup Pomona serovar kennewicki; case Nos. 36 and 41 were serovar grippotyphosa.(ABSTRACT TRUNCATED AT 250 WORDS)
Parallelization of Snort on a multi-core platform (2009)

We design and test a multithreaded Snort which uses flow pinning as a major optimization. The insights derived in improving Snort's performance will apply generally to any parallel networking application that uses flow pinning as an optimization.
Different half-lives of the carbohydrate and protein moieties of a 110,000-dalton glycoprotein isolated from plasma membranes of rat liver. (1980)

By using a four-step procedure (i, solubilization with Triton X-100; ii, affinity chromatography on concanavalin A-Sepharose; iii, affinity chromatography on wheat germ lectin-Sepharose; iv, preparative sodium dodecyl sulfate gel electrophoresis) a glycoprotein was isolated from rat liver plasma membrane. The molecular weight is 110,000 and the isoelectric point is 5.8. It contains L-fucose, N-acetylneuraminic acid, D-galactose, D-mannose, N-acetyl-D-glucosamine, N-acetyl-D-galactosamine, and considerable quantities of aspartate, threonine, serine, and leucine. In pulse-chase experiments the half-lives of methionine and arginine, representing the half-life of the protein, were determined as 70 hr and 78 hr, respectively. The half-lives of the terminal carbohydrates L-fucose and N-acetylneuraminic acid were 12.5 and 33 hr, respectively. The galactose half-life was 20 hr. From this it is concluded that terminal sugars turn over several times in the life-span of this protein molecule. This process may be operative during membrane recycling mechanisms.
Two cases of delayed-onset suicidal ideation, dysphoria and anxiety after ketamine infusion in patients with obsessive–compulsive disorder and a history of major depressive disorder (2013)

Ketamine is a non-competitive N-methyl-D-aspartate receptor antagonist that is Food and Drug Administration-approved in the United States for anesthesia due to its sedative effects with low risk of severe respiratory depression. Subanesthetic dose intravenous ketamine has rapidly acting antidepressant effects in treatment-resistant unipolar and bipolar depression. We recently reported an open-label trial of ketamine in 10 subjects with treatment-refractory obsessive-compulsive disorder, seven of whom had active comorbid depression. Although ketamine had no sustained anti-obsessive effect, four of the seven subjects with comorbid depression experienced an acute antidepressant effect. However, we unexpectedly observed delayed-onset dysphoria, worsening anxiety and suicidal thinking in two of the three subjects with obsessive-compulsive disorder and extensive psychiatric comorbidity but minimal depressive symptoms at the start of infusion. The implications of these adverse neuropsychiatric effects in two patients with similar psychiatric comorbidity are discussed. We conclude that there remains insufficient data on therapeutic ketamine in the presence of comorbid psychiatric disorders to promote its off-label use in a non-research milieu.
Damping Properties of Sandwich Metal-Polymer-Ceramic Coating (2007)

The focus in this paper is directed toward to the investigation into hybrid metal-polymer-ceramic damping coatings for pipelines and fuel tanks. Recently sandwiched coatings have been manufactured by advanced technology based on thermal flame spraying of foamy aluminum or its alloy and viscoelastic polymeric layers (ultra high molecular weight polyethylene). Technological aspects of manufacturing are discussed for tailoring safety and reliability of pipeline structure affected by external shock impact and vibrations. The particle-reinforced coatings is further formed as a constrained-layer damping coating system (CLD) showing the greatest range over which damping coatings have excellent energy absorbing/damping properties over bulk materials. Modal loss factors of clamped specimen obtained at 60–80% coverage were higher than maximum damping values obtained in the case of 100% specimen coverage. FEM-based computer modeling was used to predict the damping of multilayer materials by a strain energy method.
Generation of Globular Fragment of Adiponectin by Leukocyte Elastase Secreted by Monocytic Cell Line THP-1 (2004)

Previous studies revealed that carboxyl-terminal fragment containing the globular domain of adiponectin exists in human plasma. Although it is proposed that the globular fragment is generated by proteolytic cleavage, the place and responsible enzyme of the cleavage are still unclear. In this study, we evaluated the activity to cleave adiponectin in culture medium of several cell lines in vitro. Adiponectin cleavage into several carboxyl-terminal fragments containing the globular domain was observed in the medium of phorbol 12-myristate 13-acetate-stimulated monocytic cell lines THP-1 and U937. The molecular masses of the major products were 25, 20, and 18 kDa. The cleavage was thought to be mediated by leukocyte elastase (also known as neutrophil elastase) based on the following observations. First, the cleavage was inhibited by serine-protease inhibitors [phenylmethylsulfonylfluoride, Pefabloc SC (Roche Diagnostics, Basel, Switzerland) and aprotinin] and by the leukocyte elastase-specific peptide inhibitor MeOSuc-AAPV-CMK. Second, no activity was detected after THP-1 cells had fully differentiated into macrophages. Third, purified leukocyte elastase cleaved adiponectin with the same cleavage pattern as THP-1 cells. Finally, leukocyte elastase secreted by activated neutrophils cleaved adiponectin into the globular fragments. Amino-terminal sequence analysis revealed that cleavage sites of adiponectin by purified leukocyte elastase were between 38Thr and 39Cys, 40Ala and 41Gly, 44Ala and 45Gly, 91Ala and 92Glu, and 110Ala and 111Ala (the numbering of the positions of the amino acids starts at the signal sequence), suggesting that the cleavage occurs in the collagenous domain. These data indicate that the cleavage of adiponectin by leukocyte elastase secreted from activated monocytes and/or neutrophils could be a candidate for the mechanism of the generation of the globular fragment of adiponectin.
Functional Relationship between Calreticulin, Calnexin, and the Endoplasmic Reticulum Luminal Domain of Calnexin (2000)

Calnexin is a membrane protein of the endoplasmic reticulum (ER) that functions as a molecular chaperone and as a component of the ER quality control machinery. Calreticulin, a soluble analog of calnexin, is thought to possess similar functions, but these have not been directly demonstrated in vivo. Both proteins contain a lectin site that directs their association with newly synthesized glycoproteins. Although many glycoproteins bind to both calnexin and calreticulin, there are differences in the spectrum of glycoproteins that each binds. Using a Drosophila expression system and the mouse class I histocompatibility molecule as a model glycoprotein, we found that calreticulin does possess apparent chaperone and quality control functions, enhancing class I folding and subunit assembly, stabilizing subunits, and impeding export of assembly intermediates from the ER. Indeed, the functions of calnexin and calreticulin were largely interchangeable. We also determined that a soluble form of calnexin (residues 1-387) can functionally replace its membrane-bound counterpart. However, when calnexin was expressed as a soluble protein in L cells, the pattern of associated glycoproteins changed to resemble that of calreticulin. Conversely, membrane-anchored calreticulin bound to a similar set of glycoproteins as calnexin. Therefore, the different topological environments of calnexin and calreticulin are important in determining their distinct substrate specificities.
Diagnosis of HNF-1 mutations on a PNA zip-code microarray by single base extension (2005)

In the present study, we exploited the superior features of peptide nucleic acids (PNAs) to develop an efficient PNA zip-code microarray for the detection of hepatocyte nuclear factor-1alpha (HNF-1alpha) mutations that cause type 3 maturity onset diabetes of the young (MODY). A multi-epoxy linker compound was synthesized and used to achieve an efficient covalent linking of amine-modified PNA to an aminated glass surface. PCR was performed to amplify the genomic regions containing the mutation sites. The PCR products were then employed as templates in a subsequent multiplex single base extension reaction using chimeric primers with 3' complementarity to the specific mutation site and 5' complementarity to the respective PNA zip-code sequence on the microarray. The primers were extended by a single base at each corresponding mutation site in the presence of biotin-labeled ddNTPs, and the products were hybridized to the PNA microarray. Compared to the corresponding DNA, the PNA zip-code sequence showed a much higher duplex specificity for the complementary DNA sequence. The PNA zip-code microarray was finally stained with streptavidin-R-phycoerythrin to generate a fluorescent signal. Using this strategy, we were able to correctly diagnose several mutation sites in exon 2 of HNF-1alpha with a wild-type and mutant samples including a MODY3 patient. This work represents one of the few successful applications of PNA in DNA chip technology.
Advanced Turbine Systems Program industrial system concept development (1995)

Solar approached Phase II of ATS program with the goal of 50% thermal efficiency. An intercolled and recuperated gas turbine was identified as the ultimate system to meet this goal in a commercial gas turbine environment. With commercial input from detailed market studies and DOE`s ATS program, Solar redefined the company`s proposed ATS to fit both market and sponsor (DOE) requirements. Resulting optimized recuperated gas turbine will be developed in two sizes, 5 and 15 MWe. It will show a thermal efficiency of about 43%, a 23% improvement over current industrial gas turbines. Other ATS goals--emissions, RAMD (reliability, availability, maintainability, durability), cost of power--will be met or exceeded. During FY95, advanced development of key materials, combustion and component technologies proceeded to the point of acceptance for inclusion in ATS Phase III.
Synthesis and Glycosidase Inhibitory Activities of 5‐(1′,4′‐Dideoxy‐1′,4′‐imino‐D‐erythrosyl)‐2‐methyl‐3‐furoic Acid (=5‐[(3S,4R)‐3,4‐Dihydroxypyrrolidin‐2‐yl]‐2‐methylfuran‐3‐carboxylic Acid) Derivatives: New Leads as Selective α‐L‐Fucosidase and β‐Galactosidase Inhibitors (2003)

Abstract The García‐González reaction of D ‐glucose and ethyl acetoacetate generated ethyl 5‐[(1′ S )‐ D ‐erythrosyl]‐2‐methyl‐3‐furoate ( 5 ), which was converted to ethyl 5‐[(1′ R )‐1′,4′‐dideoxy‐1′,4′‐imino‐ D ‐erythrosyl]‐2‐methyl‐3‐furoate ( 3c ) and to ethyl 5‐[(1′ S )‐1′,4′‐dideoxy‐1′,4′‐imino‐ D ‐erythrosyl]‐2‐methyl‐3‐furoate ( 4c ). Similar methods were developed to generate other carboxylic acid derivatives such as methyl (see 3e and 4e ), isopropyl (see 3f ), and butyl esters (see 3g ), S ‐phenyl (see 3a ) and S ‐ethyl thioesters (see 3m ), N ‐benzylcarboxamides 3b and 4b , glycine‐derived amide 3h , and N ‐phenyl (see 3i ), N ‐isopropyl (see 3j and 4j ), N , N ‐diethyl‐ (see 3k and 4k ), and N ‐ethyl‐carboxamides (see 3l ). All the new 5‐(1′,4′‐dideoxy‐1′,4′‐imino‐ D ‐erythrosyl)‐3‐furoic acid (=5‐[(3 S ,4 R )‐3,4‐dihydroxypyrrolidin‐2‐yl)furan‐3‐carboxylic acid) derivatives 3 and 4 were assayed for inhibitory activity towards 25 commercially available glycosidases. Derivative 3a with a S ‐phenyl thioester group is a good and selective α ‐ L ‐fucosidase inhibitor ( K i =2–4 μ M ), whereas 4b (with a N ‐benzylcarboxamide group) is a good β ‐galactosidase inhibitor.