gebhart/patrepeval huggingface dataset:
Antioxidants slow photoreceptor cell death in mouse models of retinitis pigmentosa (2007)

Retinitis pigmentosa (RP) is a heterogeneous group of diseases in which one of a wide variety of mutations selectively causes rod photoreceptor cell death. After rods die, cone photoreceptors gradually die resulting in blindness. Antioxidants reduce cone cell death in rd1/rd1 mice indicating that cones die from oxidative damage in that model of rapidly progressive RP. In this study, we sought to determine if this observation could be generalized to models of other types of RP, rd10/rd10 mice, a model of more slowly progressive recessive RP, and Q344ter mice, a model of rapidly progressive dominant RP. Compared to appropriate vehicle-treated controls, rd10/rd10 and Q344ter mice treated between P18 and P35 with a mixture of antioxidants previously found to be effective in rd1/rd1 mice showed significantly greater cone survival. Antioxidant-treated rd10/rd10 mice showed preservation of cone function as shown by a significant increase in photopic ERG b-wave amplitudes, and surprisingly showed temporary preservation of scotopic a-wave amplitudes, prolonged rod survival, and slowed depletion of rhodopsin mRNA. These data suggest that oxidative damage contributes to cone cell death regardless of the disease causing mutation that leads to the demise of rods, and that in more slowly progressive rod degenerations, oxidative damage may also contribute to rod cell death. Protection from oxidative damage may be a broadly applicable treatment strategy in RP.
DNA fragmentation induced in macrophages by gliotoxin does not require protein synthesis and is preceded by raised inositol triphosphate levels. (1990)

We have shown that the immunomodulating agent gliotoxin induces DNA fragmentation in macrophages characteristic of programmed cell death or apoptosis (Waring, P., Eichner, R. D., Mullbacher, A., and Sjaarda, A. (1988) J. Biol. Chem, 263, 18493-18499). In addition, morphological changes and DNA fragmentation characteristic of apoptosis are induced in 48 h concanavalin A-stimulated T blasts by gliotoxin and these changes are inhibited by Zn2+ (Waring, P., Egan, M., Braithwaite, A., Mullbacher, A., and Sjaarda, A. (1990) Int. J. Immunopharmacol., in press). We have studied the effects of actinomycin D and the protein synthesis inhibitor cycloheximide on apoptosis induced by gliotoxin in these cells, and these studies demonstrate no effect on apoptosis induced by gliotoxin. Cycloheximide and actinomycin D alone induce DNA fragmentation in these cells. Gliotoxin itself proved to be a potent inhibitor of protein synthesis. The fragmentation caused by cycloheximide correlated with the extent of protein synthesis inhibition. The toxin ricin also induced DNA fragmentation in T blasts characteristic of apoptosis. These results indicate that protein synthesis is not required for induction of apoptosis in macrophages or T blasts by gliotoxin. Gliotoxin caused elevated levels of inositol triphosphate in treated macrophages which may be related to mobilization of Ca2+ levels during apoptosis.
Identification of a mammalian glutaminyl cyclase converting glutaminyl into pyroglutamyl peptides. (1987)

Extracts from bovine pituitary were found to contain an activity catalyzing the conversion of glutaminyl peptides such as [Gln1]gonadotropin-releasing hormone, [Gln1, Gly4]thyrotropin-releasing hormone (H-Gln-His-Pro-Gly-OH), and H-Gln-Tyr-Ala-OH to the respective pyroglutamyl peptides. The TRH precursor fragment H-Lys-Arg-Gln-His-Pro-Gly-Lys-Arg-OH and the D-glutaminyl stereoisomer of H-Gln-Tyr-Ala-OH did not react under the same conditions. The conversion products were identified by Edman degradation, amino acid analysis, and reversed-phase HPLC. That this activity was exhibited by an enzyme, glutaminyl cyclase, was concluded from the protein character of the activity (revealed by its abolition with trypsin and heat), the Michaelis-Menten relationship between substrate concentration and conversion rate, and the substrate specificity. It was determined that glutaminyl cyclase had a molecular weight of 43,000-50,000, a pH optimum at pH 8, and Km and Vmax values in the range of 60-130 microM and 390-690 pmol/microgram per hr, respectively. Glutaminyl cyclase was not observed to require ATP and could be inhibited with 1.0 M ammonium chloride, which increased the Km and decreased the Vmax value. The subcellular distribution of glutaminyl cyclase corresponded to the one of peptidylglycine alpha-amidating monooxygenase believed to catalyze C-terminal amidations during posttranslational precursor processing. It was also observed that the formation of pyroglutamyl from glutaminyl peptides occurred nonenzymatically; however, the enzymatic reaction carried out with crude extract was found to be approximately 70 times faster than the nonenzymatic reaction enhanced by phosphate. It is speculated that glutaminyl cyclase may participate in the posttranslational processing of hormonal precursors to pyroglutamyl peptides.
The Evolution of Dip‐Pen Nanolithography (2003)

The ability to tailor the chemical composition and structure of a surface on the 1-100 nm length scale is important to researchers studying topics ranging from electronic conduction, to catalysis, to biological recognition in nanoscale systems. Dip-pen nanolithography (DPN) is a new scanning-probe based direct-write tool for generating such surface-patterned chemical functionality on the sub-100 nm length-scale, and it is a technique that is accessible to any researcher who can use an atomic force microscope. This article introduces DPN and reviews the rapid growth of the field of DPN-related research over the past few years. Topics covered range from the development of new classes of DPN-compatible chemistry, to experimental and theoretical advances in the understanding of the processes controlling tip-substrate ink transport, to the implementation of micro-electro-mechanical system (MEMS) based strategies for parallel DPN applications.
Molecular analysis of human leukocyte adhesion deficiency. (1988)

The normal response of the immune system to infections of the skin or mucosal tissues requires the ability of peripheral blood leukocytes to mobilize to the site of infection. In a classical inflammatory reaction, neutrophils and monocytes migrate in response to chemotactic factors released at the infection site. However, until recently, the molecular mechanisms which enable leukocytes to migrate across blood vessels have been largely unknown. These mechanisms have been elucidated, in part, by the characterization of a recently defined disease called human leukocyte adhesion deficiency (LAD). Patients with this heritable disease suffer from severe recurrent bacterial and fungal infections of soft tissues, primarily skin and mucous membranes. Infected, necrotic lesions in these patients contain few leukocytes despite the observation that these patients have chronic leukocytosis. In the early 1980's, several laboratories demonstrated that this disease is due to a cell surface deficiency of the LFA-1, Mac-1, and p150, 95 family of leukocyte adhesion proteins. More recently we have shown that LAD is due to heterogenous mutations in the β subunit common to the all three of these leukocyte glycoproteins. Although LAD is a rare disease, the analysis of this disease has greatly increased our understanding of the biology of the leukocyte adhesion proteins and the molecular mechanisms involved in the immune response to infections of the skin.
Quasi Resonant DC Link Inverter with a Simple Auxiliary Circuit (2011)

In this paper, a new soft switching three phase inverter with a quasi-resonant dc-link is presented. The proposed inverter has a dc-link switch and an auxiliary switch. The inverter switches are turned on and off under zero voltage switching condition and all auxiliary circuit switches and diodes are also soft switched. The control utilizes PWM and the auxiliary switch does not require an isolated gate drive circuit. In this paper, the operation analysis and design considerations of the proposed soft switching inverter are discussed. The presented experimental results of a realized prototype confirm the theoretical analysis.
Optimal timing of repeated rh‐erythropoietin administration improves its effectiveness in stimulating erythropoiesis in healthy volunteers (1996)

We studied the effect of recombinant human erythropoietin (rhEPO) on erythropoiesis when given at different time intervals to healthy adults. 15 volunteers were randomly selected to receive rhEPO (2 x 300 U/kg) and parenteral iron (2 x 200mg) either within a 24 h or 72 h interval. Controls received parenteral iron only. Maximum EPO levels were found 24 h after the first intravenous injection (day 1) with a mean value of 364 and 390 U/l for the rhEPO-treated groups. When second rhEPO administration was after 72 h (group III), volunteers showed significantly higher absolute reticulocyte counts and a higher percentage of young RNA-rich reticulocytes (HFR ratio) over several days compared to those who received rhEPO within a 24 h interval (group II). Both rhEPO-treated groups showed an increase in the mean reticulocyte cell volume. Reticulocyte haemoglobin concentration was inversely correlated with the increasing cell size with a nadir on day 8. Reticulocyte haemoglobin content showed a significant decrease in group II after day 5. Serum ferritin levels showed an inverse pattern to the rate of erythropoiesis. After an initial rise, the serum ferritin decrease was most pronounced in group III. Contrary to previous reports with oral iron supplementation, functional iron deficiency was not seen during rhEPO stimulation, due to parenteral iron administration. Our data suggest that the time has interval between repeated administrations of rhEPO has an important influence on its pharmacodynamics. rhEPO given within an interval of 72 h was more effective in stimulating erythropoiesis than administration within 24 h interval for the same total dose.
Antigen-specific immunotherapy of autoimmune and allergic diseases (2010)

Nearly a century has passed since the first report describing antigen-specific immunotherapy (antigen-SIT) was published. Research into the use of antigen-SIT in the treatment of both allergic and autoimmune disease has increased dramatically since, although its mechanism of action is only slowly being unravelled. It is clear though, from recent studies, that success of antigen-SIT depends on the induction of regulatory T (T reg) cell subsets that recognise potentially disease-inducing epitopes. The major challenge remaining for the widespread use of antigen-SIT is to safely administer high doses of immunodominant and potentially pathogenic epitopes in a manner that induces T cell tolerance rather than activation. This review illustrates that intelligent design of treatment agents and strategies can lead to the development of safe and effective antigen-SIT.
Interruption of cytokine networks by poxviruses: lessons from myxoma virus (1995)

Myxoma virus is an infectious poxvirus pathogen that induces a virulent systemic disease called myxomatosis in European rabbits. The disease is rapidly and uniformly fatal to susceptible rabbits and is characterized by generalized dysfunction of cellular immunity and multiple interruptions of the host cytokine network. A number of virus genes are classified as virulence factors because virus constructs bearing targeted gene disruptions induce attenuated disease symptoms. Many of these genes encode proteins that interact directly with effector elements of the host immune system. Included among these immunosubversive viral proteins are secreted mimics of host ligands or regulators (virokines) and homologues of cellular cytokine receptors (viroceptors). Five examples of these immune modulator proteins encoded by myxoma virus are reviewed: (1) myxoma growth factor, a member of the epidermal growth factor ligand superfamily; (2) SERP-1, a secreted serine proteinase inhibitor; (3) M11L, a receptor-like surface protein; (4) T2, a tumor necrosis factor receptor homologue; and (5) T7, an interferon-gamma receptor homologue. The origin of viral strategies designed to subvert immune regulation by host cytokines is considered in the context of the biology of myxoma virus within immunocompetent hosts.
A Bacillus subtilis chromosome segment at the 100° to 102° position encoding 11 membrane proteins (1997)

The 25.9 kbp region upstream of nprB at 100 degrees-102 degrees on the Bacillus subtilis chromosome was sequenced. This revealed a known gene, degA, which was previously mislocated on the genetic map. A total of 29 putative ORFs were identified including a cluster of three ORFs whose products show clear homology with sulphate adenylyl pathway enzymes and, in addition, 11 ORFs whose products have one or more membrane domains, as indicated by their hydropathy profiles.
Preparation and Sterilization of Blood Plasma (1954)

Journal Article Preparation and Sterilization of Blood Plasma Get access Frank W. Hartman, M.D., Frank W. Hartman, M.D. Department of Laboratories, Henry Ford Hospital, Detroit, Michigan Search for other works by this author on: Oxford Academic Google Scholar Gerald LoGrippo, M.D., Gerald LoGrippo, M.D. Department of Laboratories, Henry Ford Hospital, Detroit, Michigan Search for other works by this author on: Oxford Academic Google Scholar A. R. Kelly, Ph.D A. R. Kelly, Ph.D Department of Laboratories, Henry Ford Hospital, Detroit, Michigan Search for other works by this author on: Oxford Academic Google Scholar American Journal of Clinical Pathology, Volume 24, Issue 3, 1 March 1954, Pages 339–348, https://doi.org/10.1093/ajcp/24.3.339 Published: 01 March 1954 Article history Received: 13 October 1953 Published: 01 March 1954
Piezoelectricity in Single Crystal of Pentaerythritol Tetranitrate (1991)

The piezoelectric constants perpendicular to (110) and (001) of single crystal f pentaerythritol tetranitrate (PETN) are determined to be (3.2+-0.30)x10/sup-13/and (1.5+-0.30)x10/sub-13/CN/sub-1/. The charge development on these faces under static loading has been confirmed to be true piezoelectric in origin. The crystal seems to experience a quasi permanent deformation under repeated and successive compression with a very long relaxation time. This gives rise to a unique behaviour of individual crystal of PETN under identical stress condition. Mechanical stress relaxation measurements have also been carried out to provide additional evidence on the uniqueness of the crystal. Dielectric constant of the crystal along the directions perpendicular to (110) and (001) are 3.50+-0.12 and 4.57+-0.17; Young's modulus along the directions are (1.24+- 0.30)x10/sub6/g cm/sup-2/ respectively. Single crystals of one cm/sub3/ of PETN develops about 10 V cm/sup-1/ field under a force of 1 kg across (110)face.
Low cost DC to AC converter for photovoltaic power conversion in residential applications (2002)

The development and experimental results of a low-cost 500-W DC-AC power converter for photovoltaic power conversion in residential applications are described. The converter uses low-cost technology usually applied in consumer products. The DC-AC converter is specially designed for operation at a wide DC input voltage range (30-170 V) in order to allow optimal power conversion with an arbitrary number of series connected solar arrays. A step-up chopper is used for MPP tracking and provides a constant 200-V DC link for the following push-pull power converter. This galvanic isolating power converter operates at 100 kHz and controls the current in the mains sinusoidally. A thyristor bridge alternates the current after each half line period. The required auxiliary power is kept below 7 W and is taken from the choke of the step-up chopper.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Attempting to understand (and control) the relationship between structure and magnetism in an extended family of Mn6 single-molecule magnets (2009)

The synthesis and characterisation of a large family of hexametallic [Mn(III)(6)] Single-Molecule Magnets of general formula [Mn(III)(6)O(2)(R-sao)(6)(X)(2)(sol)(4-6)] (where R = H, Me, Et; X = (-)O(2)CR' (R' = H, Me, Ph etc) or Hal(-); sol = EtOH, MeOH and/or H(2)O) are presented. We show how deliberate structural distortions of the [Mn(3)O] trinuclear moieties within the [Mn(6)] complexes are used to tune their magnetic properties. These findings highlight a qualitative magneto-structural correlation whereby the type (anti- or ferromagnetic) of each Mn(2) pairwise magnetic exchange is dominated by the magnitude of each individual Mn-N-O-Mn torsion angle. The observation of magneto-structural correlations on such large polymetallic complexes is rare and represents one of the largest studies of this kind.
Two new monoclonal antibodies, EPB-1 and EPB-2, reactive with human lymphoma. (1989)

Using the Raji cell line as the immunogen source, we established stable murine hybridomas that secrete B-lymphocyte-specific monoclonal antibodies (MAbs). Two clones, designated EPB-1 and EPB-2, were selected for further study. Both EPB-1 and EPB-2 were typed by reaction with subclass-specific rabbit anti-mouse antibodies and were found to be IgG1 and IgG2a, with kappa-light chains, respectively. In radioimmunobinding and flow cytometric assays, EPB-1 and EPB-2 did not react with T-cell lines, nor with normal diploid cells. EPB-2, in contrast to EPB-1, did not react by flow cytometry with normal peripheral or bone marrow leukocytes. In normal lymphoid tissues, both antibodies were positive with germinal center and mantle zone B-lymphocytes. Additionally, EPB-1 also labeled interdigitating histiocytes in the T-cell zones. Both MAbs discriminated very well between lymphoid and nonlymphoid tissues; neither MAb cross-reacted with tested normal and solid tumor tissue specimens, or with cell lines of non-B-cell origin. Immunohistology also revealed that both MAbs stained malignant lymphoma tissue sections and cloned B-cell lymphomas, both in tissue culture and as human xenografts in nude mice. Due to the radiosensitivity of human lymphomas and the relative specificity of these two new MAbs, they appear to be potential radioimmunotherapeutic agents for human lymphoma.
Type 2N von Willebrand disease: rapid genetic diagnosis of G2811A (R854Q), C2696T (R816W), T2701A (H817Q) and G2823T (C858F)--detection of a novel candidate type 2N mutation: C2810T (R854W). (1998)

The majority of patients with type 2N von Willebrand disease (VWD type 2N) have mutations in the region of the von Willebrand factor (VWF) gene encoding the factor VIII binding domain of VWF. Two mutations predominate among VWD type 2N patients: G2811A and C2696T, which respectively bring about the amino acid substitutions R854Q and R816W in VWF. Several other mutations have been found in VWD type 2N, including T2701A (H817Q) and G2823T (C858F). We have developed a genetic test which permits rapid screening for these four mutations in a single polymerase chain reaction (PCR). The test employs induced heteroduplex formation using two universal heteroduplex generators, one of which detects G2811A (R854Q) and G2823T (C858F), the other detects C2696T (R816W) and T2701A (H817Q). The allele frequency of the common G2811A (R854Q) mutation was investigated in the local (S. Wales) population by examination of 216 VWF genes (108 individuals) and was found to be 0.01. The heteroduplex-based test additionally detected a novel candidate type 2N mutation, C2810T (R854W) and a previously described polymorphism, G2805A (R852Q). The polymorphism showed allele frequencies of 0.92 (G nucleotide) and 0.08 (A nucleotide) in the population study.
Automated visual analysis in large scale sensor networks (2008)

Modern automated video analysis systems consist of large networks of heterogeneous sensors. These systems must extract, integrate and present relevant information from the sensors in real-time. This paper addresses some of the major challenges such systems face: efficient video processing for high-resolution sensors; data fusion across multiple modalities; robustness to changing environmental conditions and video processing errors; and intuitive user interfaces for visualization and analysis. The paper discusses enabling technologies to overcome these challenges and presents a case study of a wide area video analysis system deployed at a port in the state of Florida, USA. The components of the system are also detailed and justified using quantitative and qualitative results.
Biophysical Characterization of the α-Globin Binding Protein α-Hemoglobin Stabilizing Protein (2002)

Alpha-hemoglobin stabilizing protein (AHSP) is a small (12 kDa) and abundant erythroid-specific protein that binds specifically to free alpha-(hemo)globin and prevents its precipitation. When present in excess over beta-globin, its normal binding partner, alpha-globin can have severe cytotoxic effects that contribute to important human diseases such as beta-thalassemia. Because AHSP might act as a chaperone to prevent the harmful aggregation of alpha-globin during normal erythroid cell development and in diseases of globin chain imbalance, it is important to characterize the biochemical properties of the AHSP.alpha-globin complex. Here we provide the first structural information about AHSP and its interaction with alpha-globin. We find that AHSP is a predominantly alpha-helical globular protein with a somewhat asymmetric shape. AHSP and alpha-globin are both monomeric in solution as determined by analytical ultracentrifugation and bind each other to form a complex with 1:1 subunit stoichiometry, as judged by gel filtration and amino acid analysis. We have used isothermal titration calorimetry to show that the interaction is of moderate affinity with an association constant of 1 x 10(7) m(-1) and is thus likely to be biologically significant given the concentration of AHSP (approximately 0.1 mm) and hemoglobin (approximately 4 mm) in the late pro-erythroblast.
Widespread Hypomethylation Occurs Early and Synergizes with Gene Amplification during Esophageal Carcinogenesis (2011)

Although a combination of genomic and epigenetic alterations are implicated in the multistep transformation of normal squamous esophageal epithelium to Barrett esophagus, dysplasia, and adenocarcinoma, the combinatorial effect of these changes is unknown. By integrating genome-wide DNA methylation, copy number, and transcriptomic datasets obtained from endoscopic biopsies of neoplastic progression within the same individual, we are uniquely able to define the molecular events associated progression of Barrett esophagus. We find that the previously reported global hypomethylation phenomenon in cancer has its origins at the earliest stages of epithelial carcinogenesis. Promoter hypomethylation synergizes with gene amplification and leads to significant upregulation of a chr4q21 chemokine cluster and other transcripts during Barrett neoplasia. In contrast, gene-specific hypermethylation is observed at a restricted number of loci and, in combination with hemi-allelic deletions, leads to downregulatation of selected transcripts during multistep progression. We also observe that epigenetic regulation during epithelial carcinogenesis is not restricted to traditionally defined "CpG islands," but may also occur through a mechanism of differential methylation outside of these regions. Finally, validation of novel upregulated targets (CXCL1 and 3, GATA6, and DMBT1) in a larger independent panel of samples confirms the utility of integrative analysis in cancer biomarker discovery.