gebhart/patrepeval huggingface dataset:
Spinal cord neuroblasts proliferate in response to basic fibroblast growth factor (1994)

Trophic factors may function as one of the epigenic signals responsible for the proliferation, growth, migration, and differentiation of neurons and glia during embryogenesis. The present study reports that basic fibroblast growth factor (bFGF) at high concentrations (10-100 ng/ml) is a mitogen for embryonic spinal cord cells that have already committed to a neuronal pathway and are expressing neuronal phenotypes (neuroblasts). Neuroblasts proliferate with a doubling time of 2.5 d. To characterize the nature of cells proliferating in response to bFGF, we have established long-term cultures of neuroblasts that can be passaged, freeze thawed, and recultured. In cultures the proportion of astrocytes remained the same, indicating limited survival and proliferation of these cells in response to bFGF. These results indicate that bFGF has mitogenic effects preferably on neuroblasts. The morphological and biochemical characterizations of the neuronal populations present in the long-term neuroblast cultures are presented here. The presence of cholinergic and GABAergic neurons in the cultures was established by immunocytochemical analysis. The cultures contain a small number of motoneurons as judged by their immunostaining with ChAT, low-affinity NGF receptor (LNGFR), and large size. Among all other growth factors tested for their mitogenic effects on embryonic spinal cord cells in culture, only epidermal growth factor (EGF) showed such effects, but to a lesser degree. The proliferative nature of neuroblasts has made it possible to transduce the Escherichia coli beta-galactosidase (LacZ) gene stably into these cells in vitro using a retroviral vector. The transfected cells expressing the foreign gene can be passaged, freeze thawed, and recultured without the loss of transgenes. The ability to transduce foreign genes stably into these cells permits implantation of these cells in the spinal cord to study cellular and biochemical behaviors and gene expression in defined neuronal populations in in vivo environments.
Intracellular Aβ1-42 Aggregates Stimulate the Accumulation of Stable, Insoluble Amyloidogenic Fragments of the Amyloid Precursor Protein in Transfected Cells (1995)

We have analyzed the effect of internalized amyloid beta-protein (A beta) 1-42 aggregates on the metabolism of the amyloid precursor protein (APP) in stably transfected 293 cells. The amount of potentially amyloidogenic fragments of APP immunoprecipitated by anti-carboxyl-terminal APP and anti-A beta antibodies is dramatically enhanced by the treatment of the cells with A beta 1-42, which is resistant to degradation, but not A beta 1-28, which does not accumulate in cells. This accumulation of amyloidogenic carboxyl-terminal fragments is specific, since there is relatively little effect of A beta 1-42 on the amount of the nonamyloidogenic alpha-secretase carboxyl-terminal fragment. The amyloidogenic fragments accumulate in the same nonionic detergent-insoluble fraction of the cell that contains the internalized A beta 1-42. Western analysis indicates that a subset of the amyloidogenic fragments react with antibodies that recognize a conformation of A beta that is specifically associated with aggregated forms of A beta, suggesting that the adoption of this aggregation-related conformation may be an early event which precedes the final processing that produces A beta. Pulse-chase analysis of the [35S]Met-labeled 16-kDa amyloidogenic fragment indicates that it is relatively stable in A beta 1-42-treated cells, with a half-life of approximately 50 h. This fragment is degraded with a half-life of 30 min in control cells treated with A beta 1-28. In contrast, the turnover of the nonamyloidogenic alpha-secretase product is not significantly altered by the presence of A beta 1-42. The continuous uptake of A beta 1-42 from the medium is not required for the stimulation of amyloidogenic fragment accumulation, suggesting that the presence of intracellular A beta 1-42 aggregates establishes a new pathway for APP catabolism in cells which leads to the long term stability of the fragments. If these amyloidogenic fragments of APP ultimately give rise to A beta, then the production of A beta may be an autocatalytic, "runaway" process in cells containing A beta 1-42 nuclei. It is conceivable that the accumulation of insoluble APP and amyloidogenic fragments of APP in response to A beta 1-42 aggregates may mimic the pathophysiology of dystrophic neurites, where the accumulation of intracellular APP and APP fragments has been documented by immunohistochemistry.
Transient requirement for ganglion cells during assembly of retinal synaptic layers (2004)

The inner plexiform layer (IPL) of the vertebrate retina comprises functionally specialized sublaminae, representing connections between bipolar, amacrine and ganglion cells with distinct visual functions. Developmental mechanisms that target neurites to the correct synaptic sublaminae are largely unknown. Using transgenic zebrafish expressing GFP in subsets of amacrine cells, we imaged IPL formation and sublamination in vivo and asked whether the major postsynaptic cells in this circuit, the ganglion cells, organize the presynaptic inputs. We found that in the lak/ath5 mutant retina, where ganglion cells are never born, formation of the IPL is delayed, with initial neurite outgrowth ectopically located and grossly disorganized. Over time, the majority of early neurite projection errors are corrected, and major ON and OFF sublaminae do form. However, focal regions of disarray persist where sublaminae do not form properly. Bipolar axons, which arrive later, are targeted correctly, except at places where amacrine stratification is disrupted. The lak mutant phenotype reveals that ganglion cells have a transient role organizing the earliest amacrine projections to the IPL. However, it also suggests that amacrine cells interact with each other during IPL formation; these interactions alone appear sufficient to form the IPL. Furthermore, our results suggest that amacrines may guide IPL sublamination by providing stratification cues for other cell types.
Antipeptide antibodies as probes of the recombinant and endogenous murine erythropoietin receptors. (1993)

The binding of erythropoietin (Epo) to its plasma membrane receptor activates signal pathways that result in erythroid cell proliferation and differentiation. To elucidate the structural features of the receptor that are important for hormone binding and signaling, we have developed a series of site-specific antibody probes. These antibodies were raised against synthetic peptides homologous to six exoplasmic domains and one cytoplasmic domain of the murine receptor and were affinity-purified by binding to their respective peptide antigen, immobilized on agarose. Western blot analyses demonstrated that the recombinant receptor expressed transiently in COS-7 cells is synthesized as three protein species of 62, 64, and 66 kd, consistent with previous observations. Importantly, probing the endogenous receptor in both virally transformed erythroleukemia cells and normal erythroid cells demonstrated similar 62- to 66-kd receptor species. The affinity-purified antibodies also recognized several antigenically related proteins. An examination of the capacity of the antireceptor antibodies to block receptor activation by Epo revealed that antibodies to five of the six exoplasmic domains blocked the receptor. This was reversed with excess Epo. Inhibition of receptor activation by antibody probes to five discrete hydrophilic domains suggests that receptor function may be critically dependent on the structural integrity (conformation) of the entire exoplasmic portion.
Aberrant SERCA3 expression during the colorectal adenoma-adenocarcinoma sequence (2013)

Sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) 3 is involved in calcium mobilization from the endoplasmic reticulum into the cytosol and is closely linked to metabolism, neuronal plasticity, gene transcription, cell growth, differentiation, apoptosis, protein folding and carcinogenesis. In order to elucidate the role of SERCA3 in colorectal carcinogenesis and subsequent progression, its expression was examined using immunohistochemistry and in situ hybridization (ISH) on tissue microarrays containing colorectal carcinomas, adjacent non-neoplastic mucosa (NNM) and adenoma, and metastatic carcinoma in lymph node and liver. Colorectal carcinoma tissue and cell lines were assessed for SERCA3 expression by western blotting or RT-PCR, respectively. SERCA3 was distinctively expressed in Colo201, Colo205, DLD-1, HCT-15, HCT-116, HT-29, KM-12, SW480, SW620 and WiDr cells at both the mRNA and protein levels. SERCA3 mRNA expression was low in carcinoma when compared to that in matched NNM by quantitative PCR (P<0.05), while the converse was true by ISH. Lower expression of SERCA3 was immunohistochemically observed in colorectal carcinoma when compared to that in NNM and adenoma (P<0.05). In contrast, primary carcinoma showed high SERCA3 expression when compared to that in metastatic carcinoma in lymph node or liver by IHC (P<0.05). Immunohistochemically, SERCA3 expression was negatively related to lymphatic invasion, but not with age, gender, depth of invasion, venous invasion, lymph node metastasis, distant metastasis, TNM stage, degree of differentiation or survival rate (P>0.05). There was a positive relationship between SERCA3 expression and serum CEA levels in the carcinoma patients (P<0.05). Cox's proportional hazards model indicated that depth of invasion and distant metastasis are independent prognostic factors for overall colorectal carcinomas (P<0.05). These findings suggest that aberrant SERCA3 expression is closely linked to the adenoma-adenocarcinoma sequence and progression of colorectal carcinomas.
Secure Content Sniffing for Web Browsers, or How to Stop Papers from Reviewing Themselves (2009)

Cross-site scripting defenses often focus on HTML documents, neglecting attacks involving the browser's content-sniffing algorithm, which can treat non-HTML content as HTML. Web applications, such as the one that manages this conference, must defend themselves against these attacks or risk authors uploading malicious papers that automatically submit stellar self-reviews. In this paper, we formulate content-sniffing XSS attacks and defenses. We study content-sniffing XSS attacks systematically by constructing high-fidelity models of the content-sniffing algorithms used by four major browsers. We compare these models with Web site content filtering policies to construct attacks. To defend against these attacks, we propose and implement a principled content-sniffing algorithm that provides security while maintaining compatibility. Our principles have been adopted, in part, by Internet Explorer 8 and, in full, by Google Chrome and the HTML 5 working group.
Notes- Preparation of m- and p-Diethynylbenzenes (1960)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNotes- Preparation of m- and p-DiethynylbenzenesAllan HayCite this: J. Org. Chem. 1960, 25, 4, 637–638Publication Date (Print):April 1, 1960Publication History Published online13 March 2003Published inissue 1 April 1960https://pubs.acs.org/doi/10.1021/jo01074a603https://doi.org/10.1021/jo01074a603research-articleACS PublicationsRequest reuse permissionsArticle Views331Altmetric-Citations106LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Biopharmaceuticals: Biochemistry and Biotechnology (1998)

Preface. Chapter 1. Pharmaceuticals, biologies and biopharmaceuticals. Chapter 2. The drug development process. Chapter 3. The drug manufacturing process. Chapter 4. The cytokines--the interferon family. Chapter 5. Cytokines: interleukins and tumour necrosis factor. Chapter 6. Haemopoietic growth factors. Chapter 7. Growth factors. Chapter 8. Hormones of therapeutic interest. Chapter 9. Blood products and therapeutic enzymes. Chapter 10. Antibodies, vaccines and adjuvants. Chapter 11. Nucleic acid therapeutics. Appendix 1. Biopharmaceuticals thus far approved in the USA or European Union. Appendix 2. Some Internet addresses relevant to the biopharmaceutical sector. Appendix 3. Two selected monographs reproduced from the European Pharmacopoeia with permission from the European Commission: I. Products of recombinant DNA Technology II. Interferon a --2 concentrated solution. Appendix 4. Manufacture of biological medicinal products for human use. (Annex 2 from The Rules Governing Medicinal Products in the European Community, Vol. 4, Good Manufacturing Practices for Medicinal Products). Index.
Effect of Trichostatin A on Chromatin Remodeling, Histone Modifications, DNA Replication, and Transcriptional Activity in Cloned Mouse Embryos1 (2010)

Our group and others have found that the treatment of embryos with trichostatin A (TSA) after cloning by somatic cell nuclear transfer (SCNT) results in a significant improvement in efficiency. We believe that TSA treatment improves nuclear remodeling via histone modifications, which are important in the epigenetic regulation of gene silencing and expression. Some studies found that treatment of SCNT-generated embryos with TSA improved lysine acetylation of core histones in a manner similar to that seen in normally fertilized embryos. However, how histone methylation is modified in TSA-treated cloned embryos is not completely understood. In the present study, we found that TSA treatment caused an increase in chromosome decondensation and nuclear volume in SCNT-generated embryos similar to that in embryos produced by intracytoplasmic sperm injection. Histone acetylation increased in parallel with chromosome decondensation. This was associated with a more effective formation of DNA replication complexes in treated embryos. We also found a differential effect of TSA on the methylation of histone H3 at positions K4 and K9 in SCNT-generated embryos that could contribute to genomic reprogramming of the somatic cell nuclei. In addition, using 5-bromouridine 5'-triphosphate-labeled RNA, we showed that TSA enhanced the levels of newly synthesized RNA in 2-cell embryos. Interestingly, the amount of SCNT-generated embryos showing asymmetric expression of nascent RNA was reduced significantly in the TSA-treated group compared with the nontreated group at the 2-cell stage. We conclude that the incomplete and inaccurate genomic reprogramming of SCNT-generated embryos was improved by TSA treatment. This could enhance the reprogramming of somatic nuclei in terms of chromatin remodeling, histone modifications, DNA replication, and transcriptional activity.
2004년도 상반기 학술대회 발표논문 : 지역사회 경찰 활동에 근거한 지역 경찰제의 실행 과제 (2004)

급증하는 치안수요에 효과적으로 대응하기 위해 경찰은 2003년 8월부터 경찰서단위의 파출소 3-5개를 통합한 광역권 순찰지구대를 중심으로 `지역 경찰제`를 실시하고 있다. 지역경찰제의 핵심은 지역적 특수성을 고려하여 치안수요가 많은 지역에 인력과 장비를 증가시켜 현장대응력을 증대시키는 한편 순찰과 대민봉사에 주력하여 범죄예방력을 향상시키고자 하는데 있다. 특히 지역적 특수성을 반영한 범죄예방과 지역주민들과의 협력관계의 강화라는 점에 있어서 지역경찰제는 지역사회 경찰활동의 이념에 근거한다고 하겠다. 그러나 현형 순찰지구대의 현황을 살펴보면, 지역사회 경찰활동의 핵심적인 내용이라고 할 수 있는 범죄예방과 주민 참여에 있어서 오히려 기존의 파출소제도보다 못하다는 평가를 받고 있어 지역경찰제 실시의 정당성을 점차 상실해가고 있는 상황이다. 따라서 이 연구의 목적은 우리나라 지역경찰제가 지역사회 경찰활동이라는 이론적 근거에 맞게 현행 제도를 실행할 수 있는 방향을 제시하는데 있다.
Global Analysis of Circadian Expression in the Cyanobacterium Synechocystis sp. Strain PCC 6803 (2005)

Cyanobacteria are the only bacterial species found to have a circadian clock. We used DNA microarrays to examine circadian expression patterns in the cyanobacterium Synechocystis sp. strain PCC 6803. Our analysis identified 54 (2%) and 237 (9%) genes that exhibited circadian rhythms under stringent and relaxed filtering conditions, respectively. The expression of most cycling genes peaked around the time of transition from subjective day to night, suggesting that the main role of the circadian clock in Synechocystis is to adjust the physiological state of the cell to the upcoming night environment. There were several chromosomal regions where neighboring genes were expressed with similar circadian patterns. The physiological functions of the cycling genes were diverse and included a wide variety of metabolic pathways, membrane transport, and signal transduction. Genes involved in respiration and poly(3-hydroxyalkanoate) synthesis showed coordinated circadian expression, suggesting that the regulation is important for the supply of energy and carbon source in the night. Genes involved in transcription and translation also followed circadian cycling patterns. These genes may be important for output of the rhythmic information generated by the circadian clock. Our findings provided critical insights into the importance of the circadian clock on cellular physiology and the mechanism of clock-controlled gene regulation.
Diabetic neuropathy: mechanisms and future treatment options (1999)

There is no single diabetic neuropathy. A wide variety of syndromes involving the peripheral nerves may be encountered in patients with diabetes mellitus, implying a correspondingly diverse range of underlying causative mechanisms. The classification of the diabetic neuropathies is not yet finalised and has required successive modifications in the light of accumulating knowledge. The scheme favoured by myself is given in the table. This broadly categorises the manifestations into (1) rapidly reversible phenomena, (2) generalised polyneuropathies, (3) focal and multifocal neuropathies, and (4) superimposed chronic inflammatory demyelinating polyneuropathy.
Differential regulation of diverse physiological responses to VEGF in pulmonary endothelial cells (2001)

The mechanisms responsible for the divergent physiological responses of endothelial cells to vascular endothelial growth factor (VEGF) are incompletely understood. We hypothesized that VEGF elicits increased endothelial permeability and cell migration via differential activation of intracellular signal transduction pathways. To test this hypothesis, we established a model of VEGF-induced endothelial barrier dysfunction and chemotaxis with bovine pulmonary endothelial cells. We compared the effects of VEGF on transendothelial electrical resistance (TER), actin cytoskeletal remodeling, and chemotaxis of lung endothelial cells and then evaluated the role of the mitogen-activated protein kinases (MAPKs) p38 and extracellular signal-regulated kinase (ERK)1/2 in VEGF-mediated endothelial responses. The dose response of pulmonary arterial and lung microvascular endothelial cells to VEGF differed when barrier regulation and chemotaxis were evaluated. Inhibition of tyrosine kinase, phosphoinositol 3-kinase, or p38 MAPK significantly attenuated VEGF-mediated TER, F-actin remodeling, and chemotaxis. VEGF-mediated decreased TER was also significantly attenuated by inhibition of ERK1/2 MAPK but not by inhibition of fetal liver kinase-1 (flk-1) or Src kinase. In contrast, VEGF-mediated endothelial migration was not attenuated by ERK1/2 inhibition but was abolished by inhibition of either flk-1 or Src kinase. These data suggest potential mechanisms by which VEGF may differentially mediate physiological responses in vivo.
Scandium(III) Catalysis of Transimination Reactions. Independent and Constitutionally Coupled Reversible Processes (2005)

Sc(OTf)(3) efficiently catalyzes the self-sufficient transimination reaction between various types of C=N bonds in organic solvents, with turnover frequencies up to 3600 h(-)(1) and rate accelerations up to 6 x 10(5). The mechanism of the crossover reaction in mixtures of amines and imines is studied, comparing parallel individual reactions with coupled equilibria. The intrinsic kinetic parameters for isolated reactions cannot simply be added up when several components are mixed, and the behavior of the system agrees with the presence of a unique mediator that constitutes the core of a network of competing reactions. In mixed systems, every single amine or imine competes for the same central hub, in accordance with their binding affinity for the catalyst metal ion center. More generally, the study extends the basic principles of constitutional dynamic chemistry to interconnected chemical transformations and provides a step toward dynamic systems of increasing complexity.
Involvement of Sialic Acid on Endothelial Cells in Organ-Specific Lymphocyte Recirculation (1985)

Mouse lymphocytes incubated on cryostat-cut sections of lymphoid organs (lymph nodes and Peyer's patches) specifically adhere to the endothelium of high endothelial venules (HEV), the specialized blood vessels to which recirculating lymphocytes attach as they migrate from the blood into the parenchyma of the lymphoid organs. Treatment of sections with sialidase eliminated the binding of lymphocytes to peripheral lymph node HEV, had no effect on binding to Peyer's patch HEV, and had an intermediate effect on mesenteric lymph node HEV. These results suggest that sialic acid on endothelial cells may be an organ-specific recognition determinant for lymphocyte attachment.
Temperature effects on permeation of modified atmosphere gas mixtures through a low density polyethylene package film (1993)

Abstract Permeation of CO 2 and O 2 through a low density polyethylene film was studied with CO 2 ‐N 2 mixtures in the temperature range 263‐283 K, and with CO 2 ‐O 2 ‐N 2 mixtures in the range 257‐313 K. The temperature dependence of the permeabilities of these gases agreed with the Arrhenius expression. The activation energy for carbon dioxide diffusion was between 3.53 × 10 4 and 3.74 × 10 4 J/mol; the activation energy for oxygen diffusion was 3.13 × 10 4 J/mol. The pre‐exponential constant for oxygen was higher than that of carbon dioxide in various mixtures. It was also found that the pre‐exponential constant of carbon dioxide decreased with increasing CO 2 concentration in the mixtures.
Discovery and validation of breast cancer subtypes (2006)

As a consequence of the statistical validation procedure we have a set of centroids which can be applied to any microarray (indexed by UniGene Cluster ID) to classify it to one of the ESR1/ERBB2 subtypes. Moreover, the method used to define the ESR1/ERBB2 subtypes is not specific to the disease. The method can be used to identify subtypes in any disease for which there are at least two independent microarray datasets of disease samples.