gebhart/patrepeval huggingface dataset:
Apolipoprotein C-III deficiency accelerates triglyceride hydrolysis by lipoprotein lipase in wild-type and apoE knockout mice (2001)

Previous studies with hypertriglyceridemic APOC3 transgenic mice have suggested that apolipoprotein C-III (apoC-III) may inhibit either the apoE-mediated hepatic uptake of TG-rich lipoproteins and/or the lipoprotein lipase (LPL)-mediated hydrolysis of TG. Accordingly, apoC3 knockout (apoC3(-/-)) mice are hypotriglyceridemic. In the present study, we attempted to elucidate the mechanism(s) underlying these phenomena by intercrossing apoC3(-/-) mice with apoE(-/-) mice to study the effects of apoC-III deficiency against a hyperlipidemic background. Similar to apoE(+/+) apoC3(-/-) mice, apoE(-/-)apoC3(-/-) mice exhibited a marked reduction in VLDL cholesterol and TG, indicating that the mechanism(s) by which apoC-III deficiency exerts its lipid-lowering effect act independent of apoE. On both backgrounds, apoC3(-/-) mice showed normal intestinal lipid absorption and hepatic VLDL TG secretion. However, turnover studies showed that TG-labeled emulsion particles were cleared much more rapidly in apoC3(-/-) mice, whereas the clearance of VLDL apoB, as a marker for whole particle uptake by the liver, was not affected. Furthermore, it was shown that cholesteryl oleate-labeled particles were also cleared faster in apoC3(-/-) mice. Thus the mechanisms underlying the hypolipidemia in apoC3(-/-) mice involve both a more efficient hydrolysis of VLDL TG as well as an enhanced selective clearance of VLDL cholesteryl esters from plasma. In summary, our studies of apoC3(-/-) mice support the concept that apoC-III is an effective inhibitor of VLDL TG hydrolysis and reveal a potential regulating role for apoC-III with respect to the selective uptake of cholesteryl esters.
Constructing grounded theory : a practical guide through qualitative analysis (2006)

An Invitation to Grounded Theory Gathering Rich Data Coding in Grounded Theory Practice Memo-Writing Theoretical Sampling, Saturation and Sorting Reconstructing Theory in Grounded Theory Studies Writing the Draft Reflecting on the Research Process
Characterization of envelope proteins of infectious bovine rhinotracheitis virus (bovine herpesvirus 1) by biochemical and immunological methods (1986)

Ten glycoproteins of molecular weights of 180,000, 150,000, 130,000, 115,000, 97,000, 77,000, 74,000, 64,000, 55,000, and 45,000 (designated as 180K, 150K, etc.) and a single nonglycosylated 107,000-molecular-weight (107K) protein were quantitatively removed from purified bovine herpesvirus 1 (BHV-1) virions by detergent treatment. Immunoprecipitations with monospecific and monoclonal antibodies showed that three sets of coprecipitating glycoproteins, 180K/97K, 150K/77K, and 130K/74K/55K, were the major components of the BHV-1 envelope. These glycoproteins were present in the envelope of the virion and on the surface of BHV-1-infected cells and reacted with neutralizing monoclonal and monospecific antibodies. Antibodies to 150K/77K protein had the largest proportion of virus-neutralizing antibodies, followed by antibodies to 180K/97K protein. Monoclonal antibodies to 130K/74K/55K protein were neutralizing but only in the presence of complement; however, monospecific antisera produced with 55K protein did not have neutralizing activity. Analysis under nonreducing conditions showed that the 74K and 55K proteins interact through disulfide bonds to form the 130K molecule. Partial proteolysis studies showed that the 180K protein was a dimeric form of the 97K protein and that the 150K protein was a dimer of the 77K protein, but these dimers were not linked by disulfide bonds. The 107K protein was not glycosylated and induced antibodies that did not neutralize BHV-1. The 64K protein was not precipitated by anti-BHV-1 convalescent antisera, and monospecific antisera to this protein precipitated several polypeptides from uninfected cell lysates, suggesting that 64K is a protein of cellular origin associated with the BHV-1 virion envelope.
Turnover of extracellular-superoxide dismutase in tissues. (1994)

The findings established that EC-SOD C in the tissue interstitium exists almost completely anchored to heparan sulfate proteoglycan via the carboxyterminal heparin-binding domains, and that this binding is the determinant of the long tissue retention of the enzyme. The findings further suggest that reductions in heparin-affinity, e.g., by proteolytic truncation of the highly susceptible heparin-binding domain, may be an important mechanism of elimination of EC-SOD from tissues, both physiologically and as enhanced under pathologic conditions.
HLA associations with leukemia (1987)

Frequencies of 35 HLA A, B, C, and DR antigens were determined in 1,834 leukemic Caucasoids to evaluate possible associations between HLA and leukemia. In comparison with the frequencies of HLA antigens in published controls, the frequency of Cw3 was significantly higher in patients with acute lymphoblastic leukemia (relative risk = 2.64, P less than 0.0002), acute myelogenous leukemia (relative risk = 1.92, P less than 0.0007), and chronic myelogenous leukemia (relative risk = 2.07, P less than 0.002; P values adjusted for multiple comparisons). The frequency of Cw4 was elevated in patients with acute lymphoblastic leukemia (relative risk = 2.01, P less than 0.0003), acute myelogenous leukemia (relative risk = 2.06, P less than 0.0002), and chronic myelogenous leukemia (relative risk = 2.14, P less than 0.0008). The frequency of Aw19 was significantly decreased in patients with acute myelogenous leukemia (relative risk = 0.68, P less than 0.01) and chronic myelogenous leukemia (relative risk = 0.59, P less than 0.005). None of the other 32 HLA antigens investigated had a statistically significant association with leukemia. The data suggest that Cw3 and Cw4 may be markers for leukemia susceptibility genes, while Aw19 may be a marker for decreased susceptibility to leukemia.
Protein modification by the lipid peroxidation product 4‐hydroxynonenal in the spinal cords of amyotrophic lateral sclerosis patients (1998)

We report increased modification of proteins by 4-hydroxynonenal (HNE), a product of membrane lipid peroxidation, in the lumbar spinal cord of sporadic amyotrophic lateral sclerosis (ALS) patients versus that of neurologically normal controls. By immunohistochemistry, HNE-protein modification was detected in ventral horn motor neurons, and immunoprecipitation analysis revealed that one of the proteins modified by HNE was the astrocytic glutamate transporter EAAT2. Given that the function of proteins modified by HNE can be severely compromised as previously demonstrated for glutamate transporters in cortical synaptosome preparations, our findings suggest a scenario in which oxidative stress leads to the production of HNE, impairment of glutamate transport, and excitotoxic motor neuron degeneration in ALS.
Molecular characterization of mlo-based powdery mildew resistance and the role of heterotrimeric G-protein signaling in Arabidopsis defense (2011)

Powdery mildew is a common fungal disease of monocotyledonous and dicotyledonous plant species. Successful pathogenesis by the biotrophic fungus depends on the presence of plant-specific MLO (MILDEW RESISTANCE LOCUS O) proteins, as mutations in particular MLO genes confer durable powdery mildew resistance in barley, tomato and Arabidopsis. In the absence of MLO, fungal spores fail to invade the host epidermal cell, resulting in an early termination of fungal pathogenesis.&#13;\nMLO proteins define a family of heptahelical plasma membrane-localized proteins, reminiscent of G-protein coupled receptors (GPCRs) in metazoans that activate heterotrimeric G-protein signaling. A genetic approach was chosen in this study to assess the role of MLO proteins as putative plant GPCRs and results from these experiments demonstrate that powdery mildew susceptibility conferred by MLO is independent of the heterotrimeric G-protein complex. However, data from this analysis suggest a function of the heterotrimeric G-protein in basal defense mechanisms against powdery mildew fungi as well as in the integration of MAMP (microbe-associated molecular patterns) perception into downstream immune responses.&#13;\nMetabolomic analysis performed in this study indicate that the adapted powdery mildew fungus, Golovinomyces orontii, is able to suppress the accumulation of the defense-relevant indolic glucosinolate, 4MI3G (4-methoxyindol-3-ylmethylglucosinolate) in Arabidopsis, thereby inhibiting the PEN2-dependent glucosinolate defense pathway. This inhibition requires functional MLO, suggesting that successful defense suppression either operates through the MLO protein or that it requires the formation of post-invasive fungal infection structures. Other data obtained here demonstrate that MLO proteins negatively regulate transcriptional activation of defense-related genes in response to powdery mildew challenge as well as upon MAMP treatment, implicating MLO functions in MAMP-triggered defense signaling.
The normal IGHV1-69–derived B-cell repertoire contains stereotypic patterns characteristic of unmutated CLL (2009)

The cell of origin of chronic lymphocytic leukemia (CLL) has long been sought, and immunoglobulin gene analysis provides new clues. In the unmutated subset (U-CLL), there is increased usage of the 51p1-related alleles of the immunoglobulin heavy chain variable 1-69 gene, often combined with selected genes and with immunoglobulin heavy chain diversity IGHJ6. Stereotypic characteristics of the HCDR3 result and suggest antigen selection of the leukemic clones. We have now analyzed 51p1/IGHJ6 combinations in normal blood B cells from 3 healthy persons for parallel sequence patterns. A high proportion (33.3% of sequences) revealed stereotypic patterns, with several (15.0%) being similar to those described in U-CLL. Previously unreported CLL-associated stereotypes were detected in 4.8%. Stereotypes (13.6%) not detected in CLL also were found. The HCDR2-IGHJ6 sequences were essentially unmutated. Junctional amino acids in normal B cells were heterogeneous, as in cases of stereotyped CLL. Phenotypically, normal B cells expressing 51p1-derived immunoglobulin M were naive. This snapshot of the naive B-cell repertoire reveals subsets of B cells closely related to those characteristic of CLL. Conserved patterns in the 51p1-encoded immunoglobulin M of normal B cells suggest a restricted sequence repertoire shaped by evolution to recognize common pathogens. Proliferative pressure on these cells is the likely route to U-CLL.
Antisense oligonucleotides: modifications and clinical trials (2014)

There has been an upsurge in the number of clinical trials involving chemically modified oligonucleotide-based drug candidates after the FDA approval of Vitravene, Macugen, and recently, Kynamro. Over the years, different types of backbone, nucleobase and/or sugar-modified oligonucleotides have been synthesized because natural DNA/RNA based oligonucleotides pose some limitations, such as poor binding affinity, low degree of nuclease resistance, affecting their direct use in antisense therapeutics. In this review article, we discuss in detail different modifications of nucleosides/oligonucleotides along with the related clinical trials, which demonstrated their potential as drug candidates for antisense and related nucleic acid based therapeutics.
Interacalation of ethidium ion into DNA and RNA oligonucleotides (1984)

Abstract The thermodynamics of ethidium ion binding to the double strands formed by the ribooligonucleotides rCA 5 G + rCU 5 G and the analogous deoxyribo‐oligonucleotides dCA 5 G + dCT 5 G were determined by monitoring the absorbance versus temperature at 260 and 283 nm at several concentrations of oligonucleotides and ethidium bromide. A maximum of three ethidium ions bind to the oligonucleotides, which is consistent with intercalation and nearest‐neighbor exclusion. For the ribo‐oligonucleotide the binding mechanism is complex. Either two sites (assumed to be the intercalation sites at the two ends of the oligonucleotide) bind more strongly by a factor of 140 than the third site, or all sites are identical, but there is strong anticooperativity on binding (cooperativity parameter, 0.1). In sharp contrast, the binding to the same sequence (with thymine substituted for uracil) in the deoxyribo‐oligonucleotide showed all sites equivalent and no cooperativity. For the ribo‐oligonucleotides the enthalpy for ethidium binding is −14 kcal/mol. The equilibrium constants at 25°C depend on the model; either K = 6 × 10 5 M −1 for the two strong sites (4 × 10 3 M −1 for the weak site) or K = 2.5 × 10 5 M −1 for the intrinsic constant of the anticooperative model. For the equivalent deoxyribo‐oligonucleotide the enthalpy of binding is ‐9 kcal/mol and the equilibrium constant at 25°C is a factor of 10 smaller ( K = 2.5 × 10 4 M −1 ).
Cardiocyte Adaptation to Chronically Altered Load (1987)

The long-standing multidisciplinary interest in myocardial hypertrophy re­ cently has evolved from a description of specific forms of this entity to a more general consideration of the basic mechanisms by which the entire potential spectrum of cardiac loading conditions regulates the biology both of the myocardium and of the constituent striated muscle cell of this tissue, the cardiocyte. This is not to suggest that the understanding of hypertrophied myocardium is now complete. Although there have been significant recent refinements in the pathophysiologically relevant models of cardiac hypertro­ phy, the most important work in this area, which may lead to a clearer understanding of the bases for the transition from compensated cardiac hypertrophy to decompensated cardiac failure, remains to be done. Nonethe­ less, other recent work having a broader scope is clarifying the relative importance of loading conditions and other potential regulatory factors to the control of myocardial biology. A natural outgrowth of this investigative interest would be the elucidation of the mechanisms controlling growth and differentiation in both neonatal and adult mammalian myocardium. The expectation that such an approach may allow the basis for cardiocyte adapta­ tion to chronically altered loads to be understood at the molecular level is one of the most exciting prospects in cardiovascular physiology.
Aminomethylene Peptide Nucleic Acid (am-PNA): Synthesis, Regio-/Stereospecific DNA Binding, And Differential Cell Uptake of (α/γ,R/S)am-PNA Analogues (2012)

Inherently chiral, cationic am-PNAs having pendant aminomethylene groups at α(R/S) or γ(S) sites on PNA backbone have been synthesized. The modified PNAs are shown to stabilize duplexes with complementary cDNA in a regio- and stereo-preferred manner with γ(S)-am PNA superior to α(R/S)-am PNAs and α(R)-am PNA better than the α(S) isomer. The enhanced stabilization of am-PNA:DNA duplexes is accompanied by a greater discrimination of mismatched bases. This seems to be a combined result of both electrostatic interactions and conformational preorganization of backbone favoring the cDNA binding. The am-PNAs are demonstrated to effectively traverse the cell membrane, localize in the nucleus of HeLa cells, and exhibit low toxicity to cells.
A Fully Automatic Multimodality Image Registration Algorithm (1995)

The algorithm presented in this article requires no user interaction and can be applied to a wide range of registration problems. Quantitative and qualitative evaluations of the algorithm indicate a high degree of accuracy.
Modulation of Mucosal Immune Response, Tolerance, and Proliferation in Mice Colonized by the Mucin-Degrader Akkermansia muciniphila (2011)

Epithelial cells of the mammalian intestine are covered with a mucus layer that prevents direct contact with intestinal microbes but also constitutes a substrate for mucus-degrading bacteria. To study the effect of mucus degradation on the host response, germ-free mice were colonized with Akkermansia muciniphila. This anaerobic bacterium belonging to the Verrucomicrobia is specialized in the degradation of mucin, the glycoprotein present in mucus, and found in high numbers in the intestinal tract of human and other mammalian species. Efficient colonization of A. muciniphila was observed with highest numbers in the cecum, where most mucin is produced. In contrast, following colonization by Lactobacillus plantarum, a facultative anaerobe belonging to the Firmicutes that ferments carbohydrates, similar cell-numbers were found at all intestinal sites. Whereas A. muciniphila was located closely associated with the intestinal cells, L. plantarum was exclusively found in the lumen. The global transcriptional host response was determined in intestinal biopsies and revealed a consistent, site-specific, and unique modulation of about 750 genes in mice colonized by A. muciniphila and over 1500 genes after colonization by L. plantarum. Pathway reconstructions showed that colonization by A. muciniphila altered mucosal gene expression profiles toward increased expression of genes involved in immune responses and cell fate determination, while colonization by L. plantarum led to up-regulation of lipid metabolism. These indicate that the colonizers induce host responses that are specific per intestinal location. In conclusion, we propose that A. muciniphila modulates pathways involved in establishing homeostasis for basal metabolism and immune tolerance toward commensal microbiota.
Lessons Learned from Experiments Conducted on Radar Data Management System (1994)

The thesis provides lessons learned from experiments conducted by the 11th Air Force to verify the capabilities of two vendor-produced Radar Data Management Systems (RDMS). The first part of the thesis provides background information explaining the impetus for such experiments and why a lessons learned approach was taken. The experimental plan and the final report from the PACAF experiments are analyzed using evaluation tools taught in the C3 curriculum at the Naval Postgraduate School. The lessons learned from the mistakes made during these experiments are applied to produce a revised Experimental Plan. A lessons learned section follows the analysis. This section discusses specific lessons learned from the llth Air Force experiments as well as more general lessons learned by the author. The thesis concludes with two chapters that provide overall conclusions and a summary, and recommendations for future work that can be accomplished in the area of radar data management. Minimally Attended Radars, Radar Data Management Systems (RDMS), Region Operations Control Center (ROCC)
The Regulatory Particle of the Saccharomyces cerevisiae Proteasome (1998)

The proteasome is a multisubunit protease responsible for degrading proteins conjugated to ubiquitin. The 670-kDa core particle of the proteasome contains the proteolytic active sites, which face an interior chamber within the particle and are thus protected from the cytoplasm. The entry of substrates into this chamber is thought to be governed by the regulatory particle of the proteasome, which covers the presumed channels leading into the interior of the core particle. We have resolved native yeast proteasomes into two electrophoretic variants and have shown that these represent core particles capped with one or two regulatory particles. To determine the subunit composition of the regulatory particle, yeast proteasomes were purified and analyzed by gradient sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Resolution of the individual polypeptides revealed 17 distinct proteins, whose identities were determined by amino acid sequence analysis. Six of the subunits have sequence features of ATPases (Rpt1 to Rpt6). Affinity chromatography was used to purify regulatory particles from various strains, each of which expressed one of the ATPases tagged with hexahistidine. In all cases, multiple untagged ATPases copurified, indicating that the ATPases assembled together into a heteromeric complex. Of the remaining 11 subunits that we have identified (Rpn1 to Rpn3 and Rpn5 to Rpn12), 8 are encoded by previously described genes and 3 are encoded by genes not previously characterized for yeasts. One of the previously unidentified subunits exhibits limited sequence similarity with deubiquitinating enzymes. Overall, regulatory particles from yeasts and mammals are remarkably similar, suggesting that the specific mechanistic features of the proteasome have been closely conserved over the course of evolution.
An S receptor kinase gene in self-compatible Brassica napus has a 1-bp deletion. (1993)

S locus glycoprotein (SLG) and S locus receptor kinase (SRK) cDNAs were isolated from an S allele present in a number of self-compatible Brassica napus lines. This A10 allele did not segregate with self-incompatibility in crosses involving other self-incompatible B. napus lines. The SLG-A10 cDNA was found to contain an intact open reading frame and was predicted to encode an SLG protein with sequence similarities to those previously associated with phenotypically strong self-incompatibility reactions. SLG-A10 transcripts were detected in the developing stigma at steady state levels even higher than those detected for SLG alleles linked with self-incompatibility. Analysis of the corresponding SRK-A10 cDNA showed that it was very similar to other S locus receptor kinase genes and was expressed predominantly in the stigma. However, a 1-bp deletion was detected in the SRK gene toward the 3' end of the SLG homology domain. This deletion would lead to premature termination of translation and the production of a truncated SRK protein. The A10 allele was determined to represent a B. oleracea S allele based on its segregation pattern with the B. oleracea S24 allele when both these alleles were present in the same B. napus background. These results suggest that a functional SRK gene is required for Brassica self-incompatibility.
Ischemic Bowel Necrosis Induced by Endothelin-1: An Experimental Model in Rats (1991)

Local intra-arterial administration of endothelin-1 induced small intestinal mucosal damage in rats in a dose-dependent manner. A remarkable decrease in mucosal blood flow (15% of control values) was observed by a laser Doppler flowmetry 10 min after injection of endothelin-1 (1 nmol/kg). Endothelin-1 at this dose induced significant hemorrhagic and necrotic lesions in the small intestinal mucosa 30 min after the injection. Decreased mucosal blood flow was attenuated to some extent by the pretreatment with platelet-activating factor (PAF) inhibitor, CV-6209, superoxide dismutase plus catalase or the calcium antagonist, nicorandil. All these inhibitors significantly prevented the endothelin-1-induced ischemic necrotic damage in the small intestine. These results suggest a potential role of endothelin-1 in the pathogenesis of ischemic bowel diseases in clinical situations and also the possibility that PAF and oxygen-derived free radicals may be involved as secondary mediators in endothelin-induced intestinal tissue damage.
Improved neuronal transgene expression from an AAV‐2 vector with a hybrid CMV enhancer/PDGF‐β promoter (2005)

Enhanced transgene capacity plus neuron-specificity of the AAV-2 vectors developed in this study might prove valuable for gene therapy of Parkinson's disease.