gebhart/patrepeval huggingface dataset:
The Structure of the Pantothenate Kinase·ADP·Pantothenate Ternary Complex Reveals the Relationship between the Binding Sites for Substrate, Allosteric Regulator, and Antimetabolites (2004)

Pantothenate kinase catalyzes the first step in the biosynthesis of coenzyme A, the major acyl group carrier in biology. In bacteria, regulation of pantothenate kinase activity is a major factor in controlling intracellular coenzyme A levels, and pantothenate analogs are growth-inhibiting antimetabolites. We have extended the structural information on Escherichia coli pantothenate kinase by determining the structure of the enzyme.ADP. pantothenate ternary complex. Pantothenate binding induces a significant conformational change in amino acids 243-263, which form a "lid" that folds over the open pantothenate binding groove. The positioning of the substrates suggests the reaction proceeds by a concerted mechanism that involves a dissociative transition state, although the negative charge neutralization of the gamma-phosphate by Arg-243, Lys-101, and Mg(2+) coupled with hydrogen bonding of the C1 of pantothenate to Asp-127 suggests different interpretations of the phosphoryl transfer mechanism of pantothenate kinase. N-alkylpantothenamides are substrates for pantothenate kinase. Modeling these antimetabolites into the pantothenate active site predicts that they bind in the same orientation as pantothenate with their alkyl chains interacting with the hydrophobic dome over the pantothenate pocket, which is also accessed by the beta-mercaptoethylamine moiety of the allosteric regulator, coenzyme A. These structural/biochemical studies illustrate the intimate relationship between the substrate, allosteric regulator, and antimetabolite binding sites on pantothenate kinase and provide a framework for studies of its catalysis and feedback regulation.
Optimized Transduction of Human Monocyte-Derived Dendritic Cells by Recombinant Adeno-Associated Virus Serotype 6 (2010)

Dendritic cells are the key antigen-presenting cells involved in the initiation of the adaptive immune response. Recombinant adeno-associated viruses (rAAVs) can transduce dendritic cells and have gained attention as potential vaccines capable of stimulating T cell immunity. Here we show that rAAV2 pseudotyped with type 6 capsid (rAAV2/6) exhibits significantly higher tropism for human monocyte-derived dendritic cells (MoDCs) than other serotypes and variants. Transduction was abolished by a single lysine-to-alanine mutation within the AAV6 capsid previously shown to inhibit binding to heparin. However, unlike rAAV2, soluble heparin did not inhibit rAAV2/6 transduction of MoDCs. Further enhancement of MoDC transduction was observed after mutation of Tyr-731 in the capsid of AAV6 consistent with a report that tyrosine residues are phosphorylated, leading to ubiquitination of capsids during uptake. Pseudotyped rAAV2/6 vectors containing a Y731F mutation minimally altered the immunophenotype of MoDCs, which retained their immunostimulatory ability and were able to stimulate an antigen-specific CD8(+) T cell clone. These findings should assist in the development of rAAV2/6 as a vaccine vector.
Postoperative Obstructive Apnea (1999)

Upper airway obstruction during recovery from general anesthesia induced by i.v. midazolam is associated with low tonic pharyngeal muscular support, which modulates upper airway patency in the postoperative period.
Water-Soluble Lipopolymer for Gene Delivery (2001)

The use of biocompatible polymeric gene carriers may overcome the current problems associated with viral vectors in safety, immunogenicity, and mutagenesis. Nontoxic water-soluble lipopolymer (WSLP), poly(ethylenimine)-co-[N-(2-aminoethyl) ethyleneimin]-co-N-(N-cholesteryloxycarbonyl-(2-aminoethyl)ethylenimine) was synthesized using branched poly(ethylenimine) (PEI, mw 1800) and cholesteryl chloroformate. Following synthesis and purification, the structure and molecular weight of WSLP were confirmed by (1)H NMR and MADI-TOF mass spectrometry, respectively. The percentage of cholesterol conjugated to PEI was about 47%, and the average molecular weight of WSLP was approximately 2000 Da. WSLP/pDNA complexes were prepared at different N/P (nitrogen atoms of WSLP/phosphate of plasmid DNA) ratios and characterized in terms of particle size, zeta potential, osmolarity, surface morphology, and cytotoxicity. WSLP condensed plasmid DNA when N/P ratio reached 2.5/1 and no free DNA was detected at N/P ratio of 5/1 and above, as determined by agarose gel electrophoresis. The mean particle size was in the range of 25.9 to 148.5 nm and was dependent on N/P ratios. Atomic force microscopy (AFM) showed complete condensation of plasmid DNA with spherical particles of approximately 50 nm in diameter. WSLP/pDNA complexes or WSLP itself were nontoxic to CT-26 colon adenocarcinoma and 293 T human embryonic kidney transformed cells when formulated at the N/P ratio of 10/1 and below as determined by MTT assay. In contrast, PEI25000/pDNA complexes were toxic to these cells. Erythrocytes aggregated when incubated with PEI25000/pCMV-Luc complexes at high DNA concentrations, but there was little aggregation with WSLP/pCMV-Luc complexes. WSLP/pCMV-Luc complexes demonstrated higher transfection efficiency in both CT-26 and 293 T cells compared to PEI25000- or PEI1800-based formulations. WSLP/pCMV-Luc complexes are nontoxic and showed enhanced in vitro transfection. Thus, WSLP will be a suitable carrier for in vivo gene delivery.
Pathology of Eosinophilic Esophagitis: What the Clinician Needs to Know (2009)

Eosinophilic esophagitis (EOE) is a clinical pathologic syndrome characterized by influx of numerous eosinophils into the esophageal epithelium. It is important for clinicians to be aware of the spectrum, as well as the characteristic location and distribution, of morphologic changes in EOE to maximize the diagnostic yield in mucosal biopsy specimens. The major pathologic features of EOE include eosinophilic microabscesses, surface layering of eosinophils often associated with surface sloughing of necrotic squamous cells, and peak eosinophil counts usually greater than 15 per high power field (hpf) within the squamous epithelium. Minor features, which are frequent but less specific, include marked basal cell hyperplasia, lengthening of lamina propria papillae, intercellular edema, and lamina propria fibrosis with chronic inflammation. The number, distribution, and location of intraepithelial eosinophils in EOE vary greatly between previously published studies. Thus, utilization of a diagnostic cutoff point for intraepithelial eosinophils in EOE, particularly in the absence of other major features of EOE, is currently considered unwise. In fact, some patients may show combined features of both gastroesophageal reflux disease (GERD) and EOE, which complicates the histologic analysis of these patients. In contrast to GERD, EOE typically involves longer lengths of the esophagus, affects the proximal equally, or even more, than the distal esophagus, and the pathologic findings are often patchy in distribution. As a result, it is highly recommended that clinicians obtain biopsies from patients suspected of have EOE only after treatment with high-dose proton pump inhibitor therapy, and that biopsies be obtained from both the proximal and distal esophagus in both normal and abnormal appearing areas.
The Characterization of Neutralizing and Non-neutralizing Monoclonal Antibodies against Equid Herpesvirus Type 1 (1989)

Seven monoclonal antibodies (MAbs) were produced which recognized equid herpesvirus type 1 (EHV-1). Three MAbs neutralized the subtype 1 virus (strain Army 183) in the presence of complement, but did not neutralize the subtype 2 virus (strain MD). All three MAbs immunoprecipitated an Mr 83K glycoprotein from a detergent-solubilized virion envelope preparation of the subtype 1 virus. The target antigens of the four non-neutralizing MAbs (6F11, 2A4, 1F10 and 8D9) were identified by immunoblotting against purified EHV-1 virions and had respective apparent Mr values of greater than 205K, greater than 205K, 97K and 13K.
Striking conformational similarities between the transcription promoters of Thogoto and influenza A viruses: evidence for intrastrand base pairing in the 5' promoter arm (1997)

In the accompanying report, we describe an in vitro polymerase assay based on reconstituted Thogoto virus (THOV) cores which provided evidence of a double-stranded vRNA promoter consisting of both the 3' and 5' sequences of vRNA (M. B. Leahy, J. T. Dessens, and P. A. Nuttall, J. Virol. 71:8347-8351, 1997). This system was used to investigate further the THOV vRNA promoter structure by using short, synthetic vRNA promoters. The results obtained show that interstrand base pairing between residues 10 and 11 of the 3' promoter arm with residues 11 and 12 of the 5' promoter arm, respectively, is important for promoter activity. In addition, intrastrand base pairing between residues 2 and 3 with residues 9 and 8 of the 5' promoter arm, respectively, was shown to be involved in promoter activity, while no evidence of intrastrand base pairing between residues 2 and 9 of the 3' promoter arm was obtained. These observations are consistent with a hook-like structure in the 5' promoter arm of the THOV promoter. The THOV cores were able to transcribe an influenza A virus (FLUA) vRNA-like promoter, as well as hybrid THOV-FLUA promoters. Hence, the THOV and FLUA vRNA promoters appear to be both structurally and functionally similar.
Nitrite is an alternative source of NO in vivo (2004)

In this study, we investigated whether orally administered nitrite is changed to NO and whether nitrite attenuates hypertension in a dose-dependent manner. We utilized a stable isotope of [15N]nitrite (15NO2-) as a source of nitrite to distinguish between endogenous nitrite and that exogenously administered and measured hemoglobin (Hb)-NO as an index of circulating NO in whole blood using electron paramagnetic resonance (EPR) spectroscopy. When 1 mg/kg Na15NO2 was orally administered to rats, an apparent EPR signal derived from Hb15NO (A(Z) = 23.4 gauss) appeared in the blood. The peak blood HbNO concentration occurred at the first measurement after intake (5 min) for treatment with 1 and 3 mg/kg (HbNO: 4.93 +/- 0.52 and 10.58 +/- 0.40 microM, respectively) and at 15 min with 10 mg/kg (HbNO: 38.27 +/- 9.23 microM). In addition, coadministration of nitrite (100 mg/l drinking water) with N(omega)-nitro-L-arginine methyl ester (L-NAME; 1 g/l) for 3 wk significantly attenuated the L-NAME-induced hypertension (149 +/- 10 mmHg) compared with L-NAME alone (170 +/- 13 mmHg). Furthermore, this phenomenon was associated with an increase in circulating HbNO. Our findings clearly indicate that orally ingested nitrite can be an alternative to L-arginine as a source of NO in vivo and may explain, at least in part, the mechanism of the nitrite/nitrate-rich Dietary Approaches to Stop Hypertension diet-induced hypotensive effects.
Laser treatment for stroke (2007)

Low-level laser therapy is an irradiation technique that has the ability to induce biological processes using photon energy. There are studies showing proliferation and angiogenesis after irradiation in skeletal muscle post-myocardial infarction tissue cells. Most evidence of efficacy is based on the increase in energy state and the activation of mitochondrial pathways. In the brain, there is similar evidence of cellular activity with laser irradiation. In vivo studies reinforced the efficacy of this technique for a better neurological and functional outcome post-stroke. The evidence is based on in vivo animal studies of various models and one human clinical study. Although the data is very promising, some fundamental questions remain to be answered, such as the exact mechanism along the cascade of post-stroke interconnective molecular disturbance, the optimal technique and time of treatment, and the long-term safety aspects. The answers to these questions are expected to evolve within the next few years.
Insulin induction of ornithine decarboxylase. Importance of mRNA secondary structure and phosphorylation of eucaryotic initiation factors eIF-4B and eIF-4E (1991)

We investigated the possibility that insulin could stimulate translation of ornithine decarboxylase (ODC) mRNA in a murine fibroblast cell line that expresses large numbers of human insulin receptors (HIR 3.5 cells). Within 3 h after exposure to 70 nM insulin, ODC enzyme activity increased approximately 50-fold and mRNA accumulation 3-fold in the HIR 3.5 cells but not in normal fibroblasts. Pretreatment of cells with cycloheximide completely inhibited insulin-stimulated ODC expression; actinomycin D partially inhibited this effect. To determine the influence of the 5' untranslated region (5'UTR) of ODC mRNA on insulin-regulated ODC expression, plasmids were constructed which contained sequences from the 5'UTR of a rat ODC mRNA interposed between the ferritin promoter and the coding region of the human growth hormone gene. These constructions were then expressed transiently in HIR 3.5 cells. Insulin stimulated a 2-4-fold change in growth hormone accumulation in the medium of cells transiently expressing plasmids containing the entire 5'UTR of ODC mRNA or just the 5'-most 115 bases, a G/C-rich conserved sequence predicted to form a stem-loop structure and shown previously to be responsible for constitutive inhibition of translation. There was a direct correlation between the extent of insulin stimulation and the predicted secondary structure of the added 5'UTR sequences. To determine whether this effect might be due to insulin activation of initiation factors responsible for melting mRNA secondary structure, we examined the effect of insulin on the phosphorylation states of two such factors, eucaryotic initiation factors eIF-4B and eIF-4E. Insulin stimulated the phosphorylation of both initiation factors; this stimulation was evident at 15 min and maximal by 60 min. These results suggest a potential general mechanism by which insulin could preferentially stimulate translation of mRNAs whose 5'UTRs exhibit significant secondary structure by activating initiation factors involved in melting such secondary structures.
An efficient and secure remote mutual authentication scheme with smart cards (2008)

Recently, Wu-Chieu proposed a user friendly remote user authentication scheme with smart cards. In this paper, we demonstrate that their scheme is vulnerable and susceptible to the attack and has some practical pitfalls. Their scheme performs unilateral authentication (only client authentication) and there is no mutual authentication between user and remote system, so their scheme suspects from the server spoofing attack. Furthermore, their scheme is slow in detecting the wrong input-password, and users cannot change their passwords. To solve the problems found in Wu-Chieu's scheme, we propose an efficient and secure remote mutual authentication scheme by using one-way hash functions. The computational cost and efficiency of the proposed scheme are better than other related published schemes.
Tumor necrosis factor receptor-associated factor 1 gene overexpression in B-cell chronic lymphocytic leukemia: analysis of NF-κB/Rel–regulated inhibitors of apoptosis (2002)

B-cell chronic lymphocytic leukemia (B-CLL) is characterized by a resistance toward apoptosis-inducing agents. Nuclear factor-kappaB (NF-kappaB)/Rel has been shown to regulate the expression of antiapoptotic genes, such as members of the inhibitor of apoptosis protein (IAP) and tumor necrosis factor receptor-associated factor (TRAF) gene families. Expression and regulation of NF-kappaB/Rel-dependent inhibitors of apoptosis have not been collectively studied in B-CLL. We examined expression of known NF-kappaB/Rel-regulated antiapoptotic genes by RNAse protection assay, real-time polymerase chain reaction, and immunoblotting in patients with B-CLL. TRAF1 and to a lesser extent TRAF2 were overexpressed in B-CLL lymphocytes as compared with normal CD19(+) B cells. TRAF1 overexpression did not correlate with markers of disease progression or overall survival. Furthermore, we found high constitutive expression of the IAP genes c-IAP-1, c-IAP-2, and XIAP both in normal and B-CLL lymphocytes. Focusing on the regulation of TRAF1, NF-kappaB/Rel activity in B-CLL nuclear extracts was shown to bind to TRAF1 promoter elements. However, IkappaB kinase (IKK) activity was not increased in CLL lymphocytes as compared with normal CD19(+) B cells. The known IKK inhibitor sulfasalazine did not compromise TRAF1 expression. Thus, although our study revealed a common expression pattern of NF-kappaB/Rel-regulated inhibitors of apoptosis, our findings indicate an IKK-independent regulation of TRAF1 in B-CLL.
Studies by competitive PCR of glomerulosclerosis in growth hormone transgenic mice. (1993)

We have shown that the glomerulosclerotic lesions of mice transgenic for bovine growth hormone (bGH mice) consisted of a change in the phenotype of glomerular collagens and an elevation of the mRNAs for these collagens in whole kidney. The purpose of this study was to determine whether these phenotypic and quantitative changes were present in the glomeruli. We used the increased sensitivity afforded by reverse transcription followed by the polymerase chain reaction (RT-PCR) to detect type I collagen mRNA and a quantitative PCR assay to quantitate type IV collagen mRNA in microdissected glomeruli. There was a six- to eightfold increase in alpha 1IV collagen mRNA in the glomeruli of bGh mice. alpha 1(I) collagen mRNA was present in glomeruli of bGH mice, which is consistent with our previous findings that the sclerotic mesangium contained type I collagen peptides by immunofluorescence microscopy. Normal glomeruli did not contain detectable amounts of alpha 1I collagen mRNA. In summary, we found a phenotypic change in glomeruli of mice transgenic for bGH consisting of increased type IV collagen mRNA levels and the appearance of type I collagen mRNA. Thus, the development of glomerulosclerosis appeared to be at least partially regulated at a pretranslational level.
Greater than 20%-efficient frequency doubling of 1532-nm nanosecond pulses in quasi-phase-matched germanosilicate optical fibers (1999)

We fabricated second-order nonlinear gratings in D-shaped germanosilicate fibers, using thermal poling and periodic electrodes defined by standard photolithography. These gratings, which are up to 75 mm long, were used for efficient quasi-phase-matched frequency doubling of 1.532-mum nanosecond pulses from a high-power erbium-doped fiber amplifier. Average second-harmonic powers as high as 6.8 mW and peak powers greater than 1.2 kW at 766 nm were generated, with average and peak conversion efficiencies as high as 21% and 30%, respectively.
Design and implementation of power-aware virtual memory (2003)

Despite constant improvements in fabrication technology, hardware components are consuming more power than ever. With the everincreasing demand for higher performance in highly-integrated systems, and as battery technology falls further behind, managing energy is becoming critically important to various embedded and mobile systems. In this paper, we propose and implement power-aware virtual memory to reduce the energy consumed by the memory in response to workloads becoming increasingly data-centric. We can use the power management features in current memory technology to put individual memory devices into low power modes dynamically under software control to reduce the power dissipation. However, it is imperative that any techniques employed weigh memory energy savings against any potential energy increases in other system components due to performance degradation of the memory. Using a novel power-aware virtual memory implementation, we show a significant reduction in memory power dissipation, from 4.1 W to 0.5--2.7 W, when using Rambus memory and running various real-world applications in a working Linux system. Applying more advanced techniques, we can reduce this further to 0.2--1.7 W, depending on the actual workload, with negligible effects on performance. We also show this work is applicable to other memory architectures, and is orthogonal to previouslyproposed hardware-controlled power-management techniques, so it can be applied simultaneously to further enhance energy conservation in a variety of platforms.
Accurate power supply and ground plane pair models (2002)

This paper derives the theory and method for the two dimensional discrete transmission line (TL) and coupled transmission line (CTL) models, including the high frequency skin effect for an arbitrarily shaped plane pair in a multiple dielectric layer structure. The null or peak of the S parameter frequency response represents the test port interaction with the resonant standing wave of these planes at that frequency. The resultant S parameter data of these models can be condensed into a simpler N port equivalent circuit to represent a larger hierarchical power and ground plane network for fast simulation.
Differentiation of mesenchymal stem cells into osteoblasts on honeycomb collagen scaffolds (2006)

Tissue engineering using living cells is emerging as an alternative to tissue or organ transplantation. The adult mesenchymal stem cells can be differentiated into multilineage cells, such as adipocytes, chondrocytes, or osteoblasts when cultured with specific growth factors. In the present investigation, we have studied the effect of honeycomb collagen scaffolds for the adhesion, differentiation and proliferation of bone marrow-derived mesenchymal stem cells into osteoblasts. Mesenchymal stem cells were isolated from 6-week old albino rat femur bone marrow, and cultured in alpha-MEM medium without beta-glycerophosphate and dexamethasone. Honeycomb collagen discs were prepared from bovine dermal atelocollagen, cross-linked by UV-irradiation and sterilized by heat. The honeycomb discs were placed on the culture dishes before seeding the stem cells. The cells attached quickly to the honeycomb collagen scaffold, differentiated and proliferated into osteoblasts. The differentiated osteoblasts were characterized by morphological examination and alkaline phosphatase activity. The osteoblasts also synthesized calcium-deficient hydroxyapatite (pseudo-hydroxyapatite) crystals in the culture. The mineralization was confirmed by Von Kossa staining and the crystals were analyzed by X-ray diffraction. Light microscopy and DNA measurements showed that the differentiated osteoblasts multiplied into several layers on the honeycomb collagen scaffold. The results demonstrated that the honeycomb collagen sponge is an excellent scaffold for the differentiation and proliferation of mesenchymal stem cells into osteoblasts. The data further proved that honeycomb collagen is an effective substrate for tissue engineering applications, and is very useful in the advancing field of stem cell technology and cell-based therapy.
Pathogenicity studies with a strain of fowl adenovirus serotype 8 (VRI‐33) in chickens (1987)

Experiments were undertaken to study the pathogenesis of VRI-33, a strain of fowl adenovirus serotype 8 isolated from the liver of a broiler chicken with inclusion body hepatitis. A 30% death rate resulted from oral infection of one-day-old specific pathogen free chickens with 10(6) plaque forming units of VRI-33. Chickens 10, 14, 21 and 28 days of age did not die following infection via natural routes but there were some motalities following infection via parenteral routes. Immunodepression by neonatal cyclophosphamide treatment, followed by infection with VRI-33 via non-parenteral routes, caused varying degrees of hepatitis with basophilic intranuclear inclusion bodies in hepatocytes. The mortality rate of cyclophosphamide-treated, VRI-33 infected chickens, was not significantly altered by post-infection temperature stress. Infection with infectious bursal disease virus, followed by infection with VRI-33 via natural routes at 14 days of age, was not associated with mortalities.