gebhart/patrepeval huggingface dataset:
Glycosylphosphatidylinositol-specific phospholipase C regulates transferrin endocytosis in the African trypanosome (2008)

GPI-PLC (glycosylphosphatidylinositol-specific phospholipase C) is expressed in bloodstream-form Trypanosoma brucei, a protozoan that causes human African trypanosomiasis. Loss of genes encoding GPI-PLC reduces the virulence of a pleomorphic strain of the parasite, for reasons that are not clear. In the present paper, we report that GPI-PLC stimulates endocytosis of transferrin by 300-500%. Surprisingly, GPI-PLC is not detected at endosomes, suggesting that the enzyme does not interact directly with the endosomal machinery. We therefore hypothesized that a diffusible product of the GPI-PLC enzyme reaction [possibly DAG (diacylglycerol)] mediated the biological effects of the protein. Two sets of data support this assertion. First, a catalytically inactive Q81L mutant of GPI-PLC, expressed in a GPI-PLC-null background, had no effect on endocytosis, indicating that enzyme activity is essential for the protein to stimulate endocytosis. Secondly, the exogenous DAGs OAG (1-oleyl-2-acetyl-sn-glycerol) and DMG (dimyristoylglycerol) independently stimulated endocytosis of transferrin. Furthermore, the DAG mimic PMA, a phorbol ester, also activated endocytosis in T. brucei. DAG-stimulated endocytosis is a novel pathway in the trypanosome. We surmise that (i) GPI-PLC regulates transferrin endocytosis in T. brucei, (ii) GPI-PLC is a signalling enzyme, and (iii) DAG is a second messenger for GPI-PLC. We propose that regulation of endocytosis is a physiological function of GPI-PLC in bloodstream T. brucei.
Cello-Oligosaccharide Oxidation Reveals Differences between Two Lytic Polysaccharide Monooxygenases (Family GH61) from Podospora anserina (2012)

The genome of the coprophilic ascomycete Podospora anserina encodes 33 different genes encoding copper-dependent lytic polysaccharide monooxygenases (LPMOs) from glycoside hydrolase family 61 (GH61). In this study, two of these enzymes (P. anserina GH61A [PaGH61A] and PaGH61B), which both harbored a family 1 carbohydrate binding module, were successfully produced in Pichia pastoris. Synergistic cooperation between PaGH61A or PaGH61B with the cellobiose dehydrogenase (CDH) of Pycnoporus cinnabarinus on cellulose resulted in the formation of oxidized and nonoxidized cello-oligosaccharides. A striking difference between PaGH61A and PaGH61B was observed through the identification of the products, among which were doubly and triply oxidized cellodextrins, which were released only by the combination of PaGH61B with CDH. The mass spectrometry fragmentation patterns of these oxidized products could be consistent with oxidation at the C-6 position with a geminal diol group. The different properties of PaGH61A and PaGH61B and their effect on the interaction with CDH are discussed in regard to the proposed in vivo function of the CDH/GH61 enzyme system in oxidative cellulose hydrolysis.
Naive CD8+ T cells differentiate into protective memory-like cells after IL-2–anti–IL-2 complex treatment in vivo (2007)

An optimal CD8(+) T cell response requires signals from the T cell receptor (TCR), co-stimulatory molecules, and cytokines. In most cases, the relative contribution of these signals to CD8(+) T cell proliferation, accumulation, effector function, and differentiation to memory is unknown. Recent work (Boyman, O., M. Kovar, M.P. Rubinstein, C.D. Surh, and J. Sprent. 2006. Science. 311:1924-1927; Kamimura, D., Y. Sawa, M. Sato, E. Agung, T. Hirano, and M. Murakami. 2006. J. Immunol. 177:306-314) has shown that anti-interleukin (IL) 2 monoclonal antibodies that are neutralizing in vitro enhance the potency of IL-2 in vivo. We investigated the role of IL-2 signals in driving CD8(+) T cell proliferation in the absence of TCR stimulation by foreign antigen. IL-2 signals induced rapid activation of signal transducer and activator of transcription 5 in all CD8(+) T cells, both naive and memory phenotype, and promoted the differentiation of naive CD8(+) T cells into effector cells. IL-2-anti-IL-2 complexes induced proliferation of naive CD8(+) T cells in an environment with limited access to self-major histocompatibility complex (MHC) and when competition for self-MHC ligands was severe. After transfer into wild-type animals, IL-2-activated CD8(+) T cells attained and maintained a central memory phenotype and protected against lethal bacterial infection. IL-2-anti-IL-2 complex-driven memory-like CD8(+) T cells had incomplete cellular fitness compared with antigen-driven memory cells regarding homeostatic turnover and cytokine production. These results suggest that intense IL-2 signals, with limited contribution from the TCR, program the differentiation of protective memory-like CD8(+) cells but are insufficient to guarantee overall cellular fitness.
Safety and Immunogenicity of a Recombinant Sporozoite Malaria Vaccine against Plasmodium Vivax (1991)

A recombinant Plasmodium vivax circumsporozoite (CS) antigen representing approximately 70% of the CS protein was expressed in yeast and adsorbed onto aluminum hydroxide for use as a malaria vaccine. In a study of safety and immunogenicity, 30 volunteers were divided into four groups of 5, 5, 10, and 10 individuals, and inoculated intramuscularly with 50, 100, 200, or 400 micrograms of vaccine, respectively. Primary vaccinations were followed by two booster immunizations at six weeks and six months. Overall, the vaccine was well tolerated. Following the third vaccination, one volunteer developed acute hepatitis of uncertain etiology that resolved without sequelae. All volunteers in the 400-micrograms group, and six of 10 in the 200-micrograms group generated IgG against P. vivax CS protein, as determined by Western blot using recombinant CS protein. However, the magnitude of the antibody response measured by indirect immunofluorescence of intact sporozoites or enzyme-linked immunosorbent assay against the recombinant protein was low, and responses could not be boosted. Antigen-driven replication studies using peripheral blood lymphocytes failed to detect proliferative responses specific to peptide sequences represented in the recombinant vaccine, except in one volunteer. Minimal humoral and cell-mediated immune responses developed in most recipients who received this recombinant CS vaccine.
Depletion edge translation waveguide crossing optical switch (1989)

A waveguide crossing optical switch using the depletion edge translation concept is described. By using a single AlGaAs/GaAs material growth and ion implantation technology, an impedance discontinuity is formed at the intersection of two waveguides. Switching operation has been observed, and a high-speed, small-device-size, and high-extinction-ratio optical switch are expected.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Hydrothermal Crystallization of Three Calcium-Based Hybrid Solids with 2,6-Naphthalene- or 4,4′-Biphenyl-Dicarboxylates (2007)

Three new hybrid solids 1, 2, and 3 of calcium dicarboxylates have been obtained using hydrothermal conditions (24 h, 180 °C) with 2,6-naphathalenedicarboxylic acid (H2ndc) and 4,4′-biphenyldicarboxylic acid (H2bpdc) ligands. According to their single-crystal X-ray diffraction analyses, the three compounds exhibit dense networks with distinct dimensionalities for both the inorganic subnetwork and the whole structure. Three-dimensional (3D) 1 (Ca2(OH)2[ndc]) is built from layers of calcium oxo-hydroxide, pillared via the ndc ligands. Calcium is 7-fold coordinated with a monocapped trigonal prismatic surrounding (CaO4(OH)3). In 2 (Ca(H2O)[bpdc]), the structure consists of infinite chains of calcium polyhedra in a pentagonal bipyramidal coordination (CaO6(H2O) unit), the biphenyldicarboxylate species acting as scaffolds for the 3D structure. Complex 3 (Ca(H2O)3[bpdc]) also contains infinite chains of calcium polyhedra (with 8-fold coordination - CaO4(H2O)4 unit) but this time isolated because one of the two carboxylate functions of the ligand is terminal. The structure is therefore one-dimensional. A network of hydrogen bonds ensures the stability of this structure. Crystal data for 1: monoclinic, P21/c, a = 12.627(2), b = 7.8053(13), c = 5.8555(10) Å, β = 95.954(3)°, and V = 573.97(17) Å3; for 2: monoclinic, P21, a = 5.8237(4), b = 6.9339(5), c = 14.7231(11) Å, β = 93.588(3)°, and V = 593.37(7) Å3; for 3: orthorhombic, Ima2, a = 6.5444(3), b = 30.2468(13), c = 7.2194(3) Å, and V = 1429.06(11) Å3.
Does Infant Nutrition Affect Adiposity and Cholesterol Levels in the Adult? (1988)

Journal of Pediatric Gastroenterology and Nutrition: January 1988 - Volume 7 - Issue 1 - p 10-16
BAFF-R promotes cell proliferation and survival through interaction with IKKβ and NF-κB/c-Rel in the nucleus of normal and neoplastic B-lymphoid cells (2009)

BLyS and its major receptor BAFF-R have been shown to be critical for development and homeostasis of normal B lymphocytes, and for cell growth and survival of neoplastic B lymphocytes, but the biologic mechanisms of this ligand/receptor-derived intracellular signaling pathway(s) have not been completely defined. We have discovered that the BAFF-R protein was present in the cell nucleus, in addition to its integral presence in the plasma membrane and cytoplasm, in both normal and neoplastic B cells. BAFF-R interacted with histone H3 and IKKbeta in the cell nucleus, enhancing histone H3 phosphorylation through IKKbeta. Nuclear BAFF-R was also associated with NF-kappaB/c-Rel and bound to NF-kappaB targeted promoters including BLyS, CD154, Bcl-xL, IL-8, and Bfl-1/A1, promoting the transcription of these genes. These observations suggested that in addition to activating NF-kappaB pathways in the plasma membrane, BAFF-R also promotes normal B-cell and B-cell non-Hodgkin lymphoma (NHL-B) survival and proliferation by functioning as a transcriptional regulator through a chromatin remodeling mechanism(s) and NF-kappaB association. Our studies provide an expanded conceptual view of the BAFF-R signaling, which should contribute a better understanding of the physiologic mechanisms involved in normal B-cell survival and growth, as well as in the pathophysiology of aggressive B-cell malignancies and autoimmune diseases.
Efficient Cross-Fade Windows for Transitions between LPC-Based and Non-LPC Based Audio Coding (2009)

The reference model selected by MPEG for the forthcoming unified speech and audio codec (USAC) switches between a non-LPC based coding mode (based on AAC) operating in the transform domain and an LPC-based coding mode (derived from AMR-WB+) operating either in the time domain (ACELP) or in the frequency domain (wLPT). Seamlessly switching between these different coding modes required the design of a new set of cross-fade windows optimized to minimize the amount of overhead information sent during transitions between LPC-based and non-LPC based coding. This paper presents the new set of windows which was designed in order to provide an adequate trade-off between overlap duration and time/frequency resolution, and to maintain the benefits of critical sampling through all coding modes.
Apolipoprotein E Polymorphisms in Age-Related Macular Degeneration in an Italian Population (2001)

The apoE gene polymorphism showed a significant association with the risk of AMD. The lower frequency of the epsilon4 allele in AMD patients suggests that the apoE gene could play a protective role in the pathogenesis of the disease. In contrast, the epsilon2 allele was found associated with a slightly increased risk of AMD, although we did not find a statistically significant effect.
JE-2147: A dipeptide protease inhibitor (PI) that potently inhibits multi-PI-resistant HIV-1 (1999)

We designed, synthesized, and identified JE-2147, an allophenylnorstatine-containing dipeptide HIV protease inhibitor (PI), which is potent against a wide spectrum of HIV-1, HIV-2, simian immunodeficiency virus, and various clinical HIV-1 strains in vitro. Drug-resistant clinical HIV-1 strains, isolated from seven patients who had failed 9-11 different anti-HIV therapeutics after 32-83 months, had a variety of drug-resistance-related amino acid substitutions and were highly and invariably resistant to all of the currently available anti-HIV agents. JE-2147 was, however, extremely potent against all such drug-resistant strains, with IC(50) values ranging from 13-41 nM (<2-fold changes in IC(50) compared with that of wild-type HIV-1). The emergence of JE-2147-resistant HIV-1 variants in vitro was substantially delayed compared with that of HIV-1 resistant to another allophenylnorstatine-containing compound, KNI-272, and other related PIs. Structural analysis revealed that the presence of a flexible P2' moiety is important for the potency of JE-2147 toward wild-type and mutant viruses. These data suggest that the use of flexible components may open a new avenue for designing PIs that resist the emergence of PI-resistant HIV-1. Further development of JE-2147 for treating patients harboring multi-PI-resistant HIV-1 is warranted.
Bone Marrow Monocyte Lineage Cells Adhere on Injured Endothelium in a Monocyte Chemoattractant Protein-1–Dependent Manner and Accelerate Reendothelialization as Endothelial Progenitor Cells (2003)

Peripheral blood (PB)-derived CD14+ monocytes were shown to transdifferentiate into endothelial cell (EC) lineage cells and contribute to neovascularization. We investigated whether bone marrow (BM)- or PB-derived CD34-/CD14+ cells are involved in reendothelialization after carotid balloon injury. Although neither hematopoietic nor mesenchymal stem cells were included in human BM-derived CD34-/CD14+ monocyte lineage cells (BM-MLCs), they expressed EC-specific markers (Tie2, CD31, VE-cadherin, and endoglin) to an extent identical to mature ECs. When BM-MLCs were cultured with vascular endothelial growth factors, hematopoietic markers were drastically decreased and new EC-specific markers (Flk and CD34) were induced. BM-MLCs were intra-arterially transplanted into balloon-injured arteries of athymic nude rats. When BM-MLCs were activated by monocyte chemoattractant protein-1 (MCP-1) in vivo or in vitro, they adhered onto injured endothelium, differentiated into EC-like cells by losing hematopoietic markers, and inhibited neointimal hyperplasia. Ability to prevent neointimal hyperplasia was more efficient than that of BM-derived CD34+ cells. MCP-dependent adhesion was not observed in PB-derived CD34-/CD14+ monocytes. Regenerated endothelium exhibited a cobblestone appearance, blocked extravasation of dye, and induced NO-dependent vasorelaxation. Basal adhesive activities on HUVECs under laminar flow and beta1-integrin expression (basal and active forms) were significantly increased in BM-MLCs compared with PB-derived monocytes. MCP-1 markedly enhanced adhesive activity of BM-MLCs (2.8-fold) on HUVECs by activating beta1-integrin conformation. Thus, BM-MLCs can function as EC progenitors that are more potent than CD34+ cells and acquire the ability to adhere on injured endothelium in a MCP-1-dependent manner, leading to reendothelialization associated with inhibition of intimal hyperplasia. This will open a novel window to MCP-1-mediated biological actions and vascular regeneration strategies by cell therapy.
Noncontiguous I/O accesses through MPI-IO (2003)

I/O performance remains a weakness of parallel computing systems today. While this weakness is partly attributed to rapid advances in other system components, I/O interfaces available to programmers and the I/O methods supported by file systems have traditionally not matched efficiently with the types of I/O operations that scientific applications perform, particularly noncontiguous accesses. The MPI-IO interface allows for rich descriptions of the I/O patterns desired for scientific applications and implementations such as ROMIO have taken advantage of this ability while remaining limited by underlying file system methods. A method of noncontiguous data access, list I/O, was recently implemented in the Parallel Virtual File System (PVFS). We implement support for this interface in the ROMIO MPI-IO implementation. Through a suite of noncontiguous I/O tests we compared ROMIO list I/O to current methods of ROMIO noncontiguous access and found that the list I/O interface provides performance benefits in many noncontiguous cases.
影响与创新：遍布国内外－密歇根州立大学建校150周年庆典演讲 (2010)

今天，很荣幸在这里见证各位同僚所做出杰出的贡献并出席密歇根州立大学的庆典。每年，我们都借此机会集中对那些在我校学术领域做出非凡成就的人给予致谢，同时反思在过去一年中面临的挑战和取得的成就，并憧憬下一年度的目标。
Understanding the determinants for substrate recognition, regulation of enzymatic activity and the development of broad-spectrum inhibitors of coronavirus 3-chymotrypsin-like proteases (2015)

Coronaviruses include lethal human pathogens like severe acute respiratory syndrome coronavirus (SARS-CoV) and the recently emerged Middle-east respiratory coronavirus (MERS-CoV). Coronavirus also impact global economy by infecting farm animals like pigs (porcine epidemic diarrhea virus, PEDV), cows (bovine coronavirus, BCoV) and poultry (avian infectious bronchitis virus, IBV). Moreover, the global distribution of bats that naturally harbor one or more coronavirus strains heightens the likelihood of emergence of a novel highly pathogenic coronavirus in the near future. To combat infections of existing and emerging coronaviruses, it is important to identify coronavirus drug targets that can be utilized for the development of broad-spectrum anti-coronaviral therapeutics. Viral encoded 3-Chymotrypsin-like protease (3CLpro) is essential for viral polyprotein processing to release non-structural proteins that form the replicase complex machinery for viral genome replication. Due to its indispensable role in coronaviral replication, 3CLpro is an attractive drug target. Moreover, high sequence conservation in the vicinity of active site among 3CLpro proteases from different coronavirus subclasses make them an excellent target for the development of broad-spectrum therapeutics for coronavirus infections. The overarching goal of this project is to investigate enzymatic and structural properties of multiple 3CLpro enzymes encompassing different coronavirus subclasses. Understanding the determinants of structural and functional disparity between different 3CLpro enzymes and the factors regulating these properties will aid in the design of broad-spectrum inhibitors of 3CLpro enzymes. (Abstract shortened by ProQuest.)
Effects of ionophore feeding and anthelmintic administration on age and weight at puberty in spring-born beef heifers. (1996)

Two hundred eighty-eight heifer calves in two 1-yr replications were used to test the hypothesis that ionophore (ION) feeding, anthelmintic (ANT) administration, or the combination (COMB) would cause heifers to express pubertal estrus at a younger age than control (CONT) heifers. Heifers were assigned randomly within three weight blocks in a randomized complete block design with a 2 x 2 factorial arrangement of treatments. A high-fiber diet was fed for 172 d during yr 1 (Y1) and 199 d during yr 2 (Y2). Monensin sodium (200mg.animal-1.d-1) was fed to ION and COMB treatments and ivermectin (200 micrograms/kg of BW) was given to ANT and COMB groups at weaning and 84 d later. Rate of gain was monitored every 21 d and diet intake was adjusted to obtain equal rates of gain across treatments. Fecal samples were collected from one-third of the heifers in each group and analyzed for internal parasite egg counts every 21 d. Serum progesterone samples taken twice weekly were used to estimate onset of puberty. There was no treatment x year interaction in any parameter measured and the data were pooled across both years. Total weight gain was similar (P > .10) for all treatments. Fecal egg output decreased (P < .01) after initial application of anthelmintic. The ANT, ION, and COMB heifers had greater (P < .05) gain:feed ratios than did CONT (.132, .142, and .148 vs .125 kg for ANT, ION, COMB, and CONT, respectively). Age and weight at puberty were different (P < .05) for ION (425 d, 351.8 kg), COMB (425 d, 349.5 kg), and ANT (424 d, 348.8 kg) compared with CONT (433 d, 362.5 kg). There was no difference (P > .10) in age and weight at puberty between COMB, ION, or ANT heifers. During Y1, but not Y2, there were a greater (P < .05) number of COMB, ION, and ANT heifers pubertal before the breeding season. Additionally, there was a tendency (P = .12) for higher first-service conception in the COMB, ION, and ANT heifers than in the CONT heifers. Final pregnancy rates among treatments were similar (P > .10).
Effects of gamma irradiation on the initial mechanical and material properties of goat bone‐patellar tendon‐bone allografts (1991)

The effects of 60Co gamma irradiation on the initial mechanical properties of the composite bone-patellar tendon-bone unit (CU) and the tendon midsubstance (TM) were studied. Frozen specimens were exposed to either 2 or 3 Mrad of gamma irradiation. Paired frozen specimens served as intraanimal controls. Treatment effects on the CU were assessed using four mechanical parameters. Effects on the TM were assessed using four material parameters measured using an optical surface-strain analysis system. The maximum force and strain energy to maximum force of the composite unit were significantly reduced 27% and 40%, respectively, after 3 Mrad of irradiation (p less than .05). Mechanical properties of the CU were not significantly altered, however, following 2 Mrad of irradiation. Based on individual paired contrasts between treatment and control, significant differences were also found in the material properties of the tendon midsubstance. The maximum stress, maximum strain, and strain energy density to maximum stress were significantly reduced following 3 Mrad, but not 2 Mrad, of irradiation. The results provide important "time zero" material property data, which will be useful for later anterior cruciate ligament reconstruction studies using irradiated allograft patellar tendons in the goat model and other animal models as well.
Nonspecific Reactions to Mycoplasma Antigens Caused in Turkey Sera by Erysipelothrix insidiosa Bacterin (1975)

Nonspecific reactions to Mycoplasma meleagridis (MM) and M. gallisepticum antigens were found in the sera of turkeys vaccinated with Erysipelothrix insidiosa (EI) bacterin, but they could be removed by adsorption with EI bacterin. True reactions to MM could not be so removed.
Ovarian brain-derived neurotrophic factor (BDNF) promotes the development of oocytes into preimplantation embryos (2005)

Optimal development of fertilized eggs into preimplantation embryos is essential for reproduction. Although mammalian oocytes ovulated after luteinizing hormone (LH) stimulation can be fertilized and promoted into early embryos in vitro, little is known about ovarian factors important for the conditioning of eggs for early embryo development. Because LH interacts only with ovarian somatic cells, its potential regulation of oocyte functions is presumably mediated by local paracrine factors. We performed DNA microarray analyses of ovarian transcripts and identified brain-derived neurotrophic factor (BDNF) secreted by granulosa and cumulus cells as an ovarian factor stimulated by the preovulatory LH surge. Ovarian BDNF acts on TrkB receptors expressed exclusively in oocytes to enhance first polar body extrusion of oocytes and to promote the in vitro development of zygotes into preimplantation embryos. Furthermore, in vivo treatment with a Trk receptor inhibitor suppressed first polar body extrusion and the progression of zygotes into blastocysts. Thus, ovarian BDNF is important to nuclear and cytoplasmic maturation of the oocyte, which is essential for successful oocyte development into preimplantation embryos. Treatment with BDNF could condition the cultured oocytes for optimal progression into the totipotent blastocysts.