gebhart/patrepeval huggingface dataset:
Immune response to B19 parvovirus and an antibody defect in persistent viral infection. (1989)

B19 parvovirus has been shown to persist in some immunocompromised patients, and treatment with specific antibodies can lead to decreased quantities of circulating virus and hematologic improvement. A defective immune response to B19 parvovirus in these patients was shown by comparison of results using a capture RIA and immunoblotting. In normal individuals, examination of paired sera showed that the dominant humoral immune response during early convalescence was to the virus major capsid protein (58 kD) and during late convalescence to the minor capsid species (83 kD). In patients with persistent parvovirus infection, variable titers against intact particles were detected by RIA, but the sera from these patients had minimal or no IgG to capsid proteins determined by Western analysis. Competition experiments suggested that this discrepancy was not explicable on the basis of immune complex formation alone and that these patients may have a qualitative abnormality in antibody binding to virus. In neutralization experiments, in which erythroid colony formation in vitro was used as an assay of parvovirus activity, sera from patients with poor reactivity on immunoblotting were also inadequate in inhibiting viral infectivity. A cellular response to purified B19 parvovirus could not be demonstrated using proliferation assays and PBMC from individuals with serologic evidence of exposure to virus. These results suggest that production of neutralizing antibody to capsid protein plays a major role in limiting parvovirus infection in man.
Plasmid ColE1 as a Molecular Vehicle for Cloning and Amplification of DNA (1974)

DNA fragments obtained from EcoRI endonuclease digestion of bacteriophage varphi80pt190 (trp(+)) and the plasmid ColE1 were covalently joined with polynucleotide ligase. Transformation of Escherichia coli trp(-) strains to tryptophan independence with the recombined DNA selected for reconstituted ColE1 plasmids containing the tryptophan operon and the varphi80 immunity region. Similarly, an EcoRI endonuclease generated fragment of plasmid pSC105 DNA containing the genetic determinant of kanamycin resistance was inserted into the ColE1 plasmid and recovered in E. coli. The plasmids containing the trp operon (ColE1-trp) and the kanamycin resistance gene were maintained under logarithmic growth conditions at a level of 25-30 copies per cell and accumulate to the extent of several hundred copies per cell in the presence of chloramphenicol. Cells carrying the ColE1-trp plasmid determined the production of highly elevated levels of trp operon-specific mRNA and tryptophan biosynthetic enzymes.
Self‐Replicative RNA Vaccines Elicit Protection against Influenza A Virus, Respiratory Syncytial Virus, and a Tickborne Encephalitis Virus (2001)

In genetic vaccination, recipients are immunized with antigen-encoding nucleic acid, usually DNA. This study addressed the possibility of using the recombinant alpha virus RNA molecule, which replicates in the cytoplasm of transfected cells, as a novel approach for genetic vaccination. Mice were immunized with recombinant Semliki Forest virus RNA-encoding envelope proteins from one of 3 viruses: influenza A virus, a tickborne flavivirus (louping ill virus), or respiratory syncytial virus (RSV). Serologic analyses showed that antigen-specific antibody responses were elicited. IgG isotyping indicated that predominantly Th1 type immune responses were induced after immunization with RSV F protein-encoding RNA, which is relevant for protection against RSV infection. Challenge infection showed that RNA immunization had elicited significant levels of protection against the 3 model virus diseases.
十七、十八世纪小提琴制作师的乐器特征（一） (2006)

随着《乐器》2006年5月刊的出版，细心的读者会发现，《乐器》历经50多年的发展，伴随我们已走过200期的岁月历程。回顾《乐器》的发展，作为乐器科技期刊，杂志不同时期的乐器科技文献，皆为我国乐器制作专业人士提供了有益的借鉴，特别是国外乐器科技文献，而今看来，也是非常具有收藏价值。近期，在我国乐器专家的建议和读者的要求下，同时为了纪念《乐器》杂志200期的出版，《乐器》特别策划了《精典回顾》的乐器科技分栏，用文字来见证《乐器》在不同时期走过的历史足迹。
Intracellular Calcium Waves Accompany Neutrophil Polarization, Formylmethionylleucylphenylalanine Stimulation, and Phagocytosis: A High Speed Microscopy Study (2003)

Using high sensitivity fluorescence imaging with shutter speeds approximately 600,000 times faster than those of video frames, we have characterized Ca2+ waves within cells in exquisite detail to reveal Ca2+ signaling routes. Polarized neutrophils exhibited a counterclockwise rotating ryanodine-sensitive juxtamembrane Ca2+ wave during temporal calcium spikes. During stimulation with fMLP, a chemotactic factor, two Ca2+ waves traveling in opposite directions around the perimeter of the cell emanated from sites of stimulation (the clockwise wave is verapamil sensitive). Phagocytosed targets exhibit counterclockwise Ca2+ waves traveling about their periphery originating from the plasma membrane. This study: 1) outlines the technology to observe Ca2+ signaling circuitry within small living cells; 2) shows that extracellular spatial information in the form of a chemotactic factor gradient is transduced into intracellular chemical patterns, which provides fresh insights in signaling; 3) suggests that a line of communication exits between the cell surface and phagosomes; and 4) suggests that spatiotemporal Ca2+ patterns contribute to drug actions.
Arterial regeneration following polyglactin 910 suture mesh grafting. (1979)

A suture mesh of polyglactin 910 [Vicryl (polyglactin 910) suture mesh] was placed as a patch graft into the thoracic aorta of 23 growing pigs. In three other pigs the mesh was grafted in the form of a tube to replace a short aortic defect. The biological processes taking place in the grafted area were studied by morphological methods. The following observations were made: (1) Hemostasis readily occurred by fibrin, platelet, and erythrocyte embedding of the mesh. (2) Early outgrowth of smooth muscle cells around the mesh took place from the normal aortic media and from a newly formed subintimal smooth muscle layer. (3) The newly formed arterial tissue was completely endothelialized within 20 days. (4) The polyglactin mesh had disappeared almost completely at 40 days, but the new wall seemed to retain sufficient strength throughout the observation time. (5) Only irregular deposition of elastic fibrils occurred, but in other respects the new tissue structurally resembled normal arterial tissue.
A homogeneous immunoassay for cyclic nucleotides based on chemiluminescence energy transfer (1983)

A chemiluminescent derivative of cyclic AMP, aminobutylethylisoluminol succinyl cyclic AMP (ABEI-scAMP), was synthesized in order to develop a homogeneous immunoassay based on non-radiative energy transfer. ABEI-scAMP was chemiluminescent (5.1 X 10(18) luminescent counts X mol-1 at pH 13), pure (greater than 95%) stable and immunologically active. A conventional immunoassay was established using ABEI-scAMP and a solid-phase anti-(cyclic AMP) immunoglobulin G which could detect cyclic AMP at least down to 25fmol. A homogeneous immunoassay for cyclic AMP was established by measuring the shift in wavelength from 460 to 525nm which occurred when ABEI-scAMP was bound to fluorescein-labelled anti-(cyclic AMP) immunoglobulin G. The assay was at least as sensitive as the conventional radioimmunoassay using cyclic [3H]AMP and could measure cyclic AMP over the range 1-1000nM. The homogeneous chemiluminescent energy transfer assay was also able to quantify the association and dissociation of antibody-antigen complexes. Chemiluminescence energy transfer occurred between fluorescein-labelled antibodies and several other ABEI-labelled antigens (Mr values 314-150000) including progesterone, cyclic GMP, complement component C9 and immunoglobulin G. The results provide a homogeneous immunoassay capable of measuring free cyclic AMP under conditions likely to exist inside cells.
Mutualistic symbiosis betweenBursaphelenchus xylophilusand bacteria of the genusPseudomonas (2005)

Summary Interactions between the pine wood nematode (PWN), Bursaphelenchus xylophilus , and bacteria of the genus Pseudomonas were examined by cultivating axenic PWN and bacterial strains using callus of Pinus thunbergii . Ten ( Pseudomonas fluorescens , Pseudomonas putida , Pseudomonas cepacia and Pseudomonas spp.) of the 29 bacterial strains tested, significantly increased the reproduction of PWN. The rest of the bacteria (19 strains of 10 species) inhibited the reproduction of PWN completely. The growth of 18 of the 29 bacterial strains tested, including the 10 strains promoting PWN reproduction, was significantly increased by the presence of PWN. It indicated a mutualistic symbiotic relationship between PWN and the 10 bacterial strains in the genus Pseudomonas. The bacterial mutualistic symbionts are organisms, which may have co‐evolved with PWN rather than being accidentally associated. The finding provides further evidence for our hypothesis that pine wilt disease is complex, induced by both PWN and associated phytotoxin‐producing bacteria.
Platelet-derived growth factor stimulates formation of active p21ras.GTP complex in Swiss mouse 3T3 cells. (1990)

The ras gene product (p21) is a GTP-binding protein and is thought to play an important role in signal transduction of growth and differentiation in many types of mammalian cells. The p21.GTP complex is an active conformation, as described previously for polypeptide chain elongation factors (EF-Tu and EF-G) and heterotrimeric GTP-binding proteins (G proteins). In the study reported here, we measured the amounts of p21-bound guanine nucleotides under various conditions in the G54 cell line, a derivative of Swiss 3T3 cells that overexpresses normal c-Ha-ras. More p21.GTP complexes were present in growing cells than in quiescent cells. When quiescent cells were stimulated with fetal bovine serum to promote DNA synthesis, p21.GTP increased approximately 2-fold. Among a number of purified growth factors, platelet-derived growth factor enhanced the formation of p21.GTP, whereas the combination of bombesin and insulin, which also induces DNA synthesis, did not. These results strongly suggest that p21 is a transducer of the growth signal from the platelet-derived growth factor receptor in Swiss 3T3 cells and that the signal is transmitted through a p21.GTP complex.
Human botulism in Canada (1919-1973). (1974)

Since 1919, in Canada, 62 authenticated outbreaks of human botulism have affected 181 persons, with 83 deaths, a fatality rate of 46%. Among these, 41 outbreaks were bacteriologically determined (31 in one laboratory) as six type A, four type B, one both A and B, and 30 type E. About two thirds of the total outbreaks, cases and deaths involved Eskimos and Pacific coast Indians consuming raw marine mammal products and salmon eggs, respectively. Other parts of Canada recorded seven occurrences due to miscellaneous vehicles, three being type B. Since January 1961 there have been 38 outbreaks, involving 94 cases with 33 deaths. These include 18 outbreaks among Eskimos, affecting 51 persons (of whom 24 died) in Labrador, southern Baffin Island, northern Quebec, and the Mackenzie area. Also, putrid salmon eggs caused 15 outbreaks among Pacific coast Indians, totalling 35 cases, of whom only six died, the low fatality rate reflecting the introduction of type E botulinus antitoxin during 1961.
Discovery of Potent Antagonists of the Antiapoptotic Protein XIAP for the Treatment of Cancer (2004)

Inhibitor of apoptosis (IAP) proteins are overexpressed in many cancers and have been implicated in tumor growth, pathogenesis, and resistance to chemo- or radiotherapy. On the basis of the NMR structure of a SMAC peptide complexed with the BIR3 domain of X-linked IAP (XIAP), a novel series of XIAP antagonists was discovered. The most potent compounds in this series bind to the baculovirus IAP repeat 3 (BIR3) domain of XIAP with single-digit nanomolar affinity and promote cell death in several human cancer cell lines. In a MDA-MB-231 breast cancer mouse xenograft model, these XIAP antagonists inhibited the growth of tumors. Close structural analogues that showed only weak binding to the XIAP-BIR3 domain were inactive in the cellular assays and showed only marginal in vivo activity. Our results are consistent with a mechanism in which ligands for the BIR3 domain of XIAP induce apoptosis by freeing up caspases. The present study validates the BIR3 domain of XIAP as a target and supports the use of small molecule XIAP antagonists as a potential therapy for cancers that overexpress XIAP.
Production and characterization of testosterone undecanoate-loaded NLC for oral bioavailability enhancement (2010)

This opens the perspective of administering a single dose of dose of TU in one oral dosage unit and simultaneously having a bioavailability less dependent on the fed state.
DNA Damage–Induced Bcl-xL Deamidation Is Mediated by NHE-1 Antiport Regulated Intracellular pH (2006)

The pro-survival protein Bcl-xL is critical for the resistance of tumour cells to DNA damage. We have previously demonstrated, using a mouse cancer model, that oncogenic tyrosine kinase inhibition of DNA damage-induced Bcl-xL deamidation tightly correlates with T cell transformation in vivo, although the pathway to Bcl-xL deamidation remains unknown and its functional consequences unclear. We show here that rBcl-xL deamidation generates an iso-Asp(52)/iso-Asp(66) species that is unable to sequester pro-apoptotic BH3-only proteins such as Bim and Puma. DNA damage in thymocytes results in increased expression of the NHE-1 Na/H antiport, an event both necessary and sufficient for subsequent intracellular alkalinisation, Bcl-xL deamidation, and apoptosis. In murine thymocytes and tumour cells expressing an oncogenic tyrosine kinase, this DNA damage-induced cascade is blocked. Enforced intracellular alkalinisation mimics the effects of DNA damage in murine tumour cells and human B-lineage chronic lymphocytic leukaemia cells, thereby causing Bcl-xL deamidation and increased apoptosis. Our results define a signalling pathway leading from DNA damage to up-regulation of the NHE-1 antiport, to intracellular alkalanisation to Bcl-xL deamidation, to apoptosis, representing the first example, to our knowledge, of how deamidation of internal asparagine residues can be regulated in a protein in vivo. Our findings also suggest novel approaches to cancer therapy.
Characterization of Clostridium perfringens iota-toxin genes and expression in Escherichia coli (1993)

The iota toxin which is produced by Clostridium perfringens type E, is a binary toxin consisting of two independent polypeptides: Ia, which is an ADP-ribosyltransferase, and Ib, which is involved in the binding and internalization of the toxin into the cell. Two degenerate oligonucleotide probes deduced from partial amino acid sequence of each component of C. spiroforme toxin, which is closely related to the iota toxin, were used to clone three overlapping DNA fragments containing the iota-toxin genes from C. perfringens type E plasmid DNA. Two genes, in the same orientation, coding for Ia (387 amino acids) and Ib (875 amino acids) and separated by 243 noncoding nucleotides were identified. A predicted signal peptide was found for each component, and the secreted Ib displays two domains, the propeptide (172 amino acids) and the mature protein (664 amino acids). The Ia gene has been expressed in Escherichia coli and C. perfringens, under the control of its own promoter. The recombinant polypeptide obtained was recognized by Ia antibodies and ADP-ribosylated actin. The expression of the Ib gene was obtained in E. coli harboring a recombinant plasmid encompassing the putative promoter upstream of the Ia gene and the Ia and Ib genes. Two residues which have been found to be involved in the NAD+ binding site of diphtheria and pseudomonas toxins are conserved in the predicted Ia sequence (Glu-14 and Trp-19). The predicted amino acid Ib sequence shows 33.9% identity with and 54.4% similarity to the protective antigen of the anthrax toxin complex. In particular, the central region of Ib, which contains a predicted transmembrane segment (Leu-292 to Ser-308), presents 45% identity with the corresponding protective antigen sequence which is involved in the translocation of the toxin across the cell membrane.
Topographical Analysis of Adolescent Affective Disorders (1996)

This study evaluated the EEG spectral content and the components of the cognitive ERPs evoked by a visual sustained-selective attention task from adolescents diagnosed as having an affective disorder and those who did not (nonreferred controls, CON) to determine if there were different electrophysiological profiles associated with major subtypes of affective disorders; i.e., Dysthymic Disorder (DysD) and Cyclothymic Disorder (CycD). Distinctive ERP and EEG profiles were found to be associated with the DysD and CycD groups. While both groups of depressives presented diminished P3b amplitudes, the DysD group showed a relatively greater suppression over the right temporal regions, whereas the CycD group exhibited relatively greater suppression over the left temporal region. In addition, there were differences with respect to the earlier components associated with information processing. For instance, the P1 was found deficient in the DysD group as compared to the other groups, whereas the N2 component was deficient in the CycD groups as compared to CON and DysD groups. In contrast to these amplitude differences, no significant latency differences were seen with respect to any component elicited by this paradigm. With respect to the EEG spectra, the CON group showed greater relative power in the Beta range than either the CycD or the DysD group, with the depressives featuring more midline frontal Theta activity. Characteristically, both depressant groups showed a greater anterior distribution of Alpha activity. In addition, the foci of the various spectral bands for the DysD subjects were shifted away from the right hemisphere as was the case for the P3b. Overall, the profiles suggested that those who fit the diagnostic classification of DysD have deficit function in right post-Rolandic zones, along with anomalous frontal function. It was also suggested that there may be a core disturbance of physiological arousal in unipolar depression. The CycD subjects, on the other hand, featured no hemispheric bias with respect to the P3b components or spectral foci, but did not show similar features of being cortically "hypoaroused" so that actively depressed adolescent CycD subjects did share certain physiological features with unipolar subjects.
Weight change and obesity after liver transplantation: Incidence and risk factors (1998)

Obesity is a concern in the long-term management of patients following liver transplantation, yet the risk of obesity and the factors that influence its development have not been well defined. We evaluated posttransplantation weight change among a cohort of 774 adults who had their height and weight recorded before liver transplantation at three major centers. Obesity was defined as a body mass index (BMI) of at least 30 kg/m2. Weight at transplantation was adjusted by the amount of ascites removed. Mean BMI increased from 24.8 kg/m2 pretransplantation to 27.0 kg/m2 in the first posttransplantation year, to 28.1 kg/m2 in the second year, and very little with subsequent observation. Among 320 patients who were not obese before transplantation, 21.6% became obese within 2 years after transplantation. On evaluation of numerous potential donor and pretransplantation risk factors, greater recipient BMI, greater donor BMI, and being married were found to be predictors of subsequent obesity (P < .05). Posttransplantation predictors of obesity included absence of acute cellular rejection, higher cumulative prednisone dose in the second year, and cyclosporine-based immunosuppression, although only rejection and prednisone dose remained predictors on multivariate analysis. Despite the marked weight gain after transplantation, prevalence of obesity at 2 years was only slightly greater than in the general US population. Obesity occurred commonly after liver transplantation, sometimes with a striking gain in weight. In addition to BMI at transplantation, donor BMI, marital status, occurrence of acute rejection, and prednisone dose affected the incidence of obesity.
Advanced glycation end products and vascular inflammation: implications for accelerated atherosclerosis in diabetes (2004)

The formation of advanced glycation end products (AGEs) is an important biochemical abnormality that accompanies diabetes mellitus and, likely, inflammation in general. Here we summarize and discuss recent studies indicating that the effects of AGEs on vessel wall homeostasis may account for the rapidly progressive atherosclerosis associated with diabetes mellitus. Driven by hyperglycemia and oxidant stress, AGEs form to a greatly accelerated degree in diabetes. Within the vessel wall, collagen-linked AGEs may "trap" plasma proteins, quench nitric oxide (NO) activity and interact with specific receptors to modulate a large number of cellular properties. On plasma low density lipoproteins (LDL), AGEs initiate oxidative reactions that promote the formation of oxidized LDL. Interaction of AGEs with endothelial cells as well as with other cells accumulating within the atherosclerotic plaque, such as mononuclear phagocytes and smooth muscle cells (SMCs), provides a mechanism to augment vascular dysfunction. Specifically, the interaction of AGEs with vessel wall components increases vascular permeability, the expression of procoagulant activity and the generation of reactive oxygen species (ROS), resulting in increased endothelial expression of endothelial leukocyte adhesion molecules. AGEs potently modulate initiating steps in atherogenesis involving blood-vessel wall interactions, triggering an inflammatory-proliferative process and, furthermore, critically contribute to propagation of inflammation and vascular perturbation in established disease. Thus, a better understanding of the biochemical mechanisms by which AGEs contribute to such processes in the vessel wall could be relevant to devise preventive and therapeutic strategies for diabetic atherosclerosis.
LSD1-mediated epigenetic modification contributes to proliferation and metastasis of colon cancer (2013)

Lysine-specific demethylase 1 downregulates the expression of CDH-1 by epigenetic modification, and consequently promotes metastasis of colon cancer cells. The LSD1 antagonists might be a useful strategy to suppress metastasis of colon cancer.
Incomplete reactivation ofOct4-related genes in mouse embryos cloned from somatic nuclei (2003)

The majority of cloned animals derived by nuclear transfer from somatic cell nuclei develop to the blastocyst stage but die after implantation. Mouse embryos that lack an Oct4 gene, which plays an essential role in control of developmental pluripotency, develop to the blastocyst stage and also die after implantation, because they lack pluripotent embryonic cells. Based on this similarity, we posited that cloned embryos derived from differentiated cell nuclei fail to establish a population of truly pluripotent embryonic cells because of faulty reactivation of key embryonic genes such as Oct4. To explore this hypothesis, we used an in silico approach to identify a set of Oct4-related genes whose developmental expression pattern is similar to that of Oct4. When expression of Oct4 and 10 Oct4-related genes was analyzed in individual cumulus cell-derived cloned blastocysts, only 62% correctly expressed all tested genes. In contrast to this incomplete reactivation of Oct4-related genes in somatic clones, ES cell-derived cloned blastocysts and normal control embryos expressed these genes normally. Notably, the contrast between expression patterns of the Oct4-related genes correlated with efficiency of embryonic development of somatic and ES cell-derived cloned blastocysts to term. These observations suggest that failure to reactivate the full spectrum of these Oct4-related genes may contribute to embryonic lethality in somatic-cell clones.