gebhart/patrepeval huggingface dataset:
Regulating the Safety of Probiotics - The European Approach (2005)

This article reviews pertinent legislation regulating the safety of probiotics within the European Union (EU). Currently available probiotic organisms and known issues regarding their safety are briefly summarised. While most of the species and genera, particularly lactobacilli and bifidobacteria are apparently safe, certain micro-organisms may be problematic; particularly the enterococci, which are associated with nosocomial infections and harbour transmissible antibiotic resistance determinants. At present, probiotic human foods are not governed under specific EU regulatory frameworks, although the Novel Food Regulation EU 258/97, could be relevant in some specific cases. However, microbial feed additives (regulated by Council Directive 70/254/EEC and in accordance with guidelines of the Scientific Committee on Animal Nutrition (SCAN)) are subjected to detailed safety assessment with the intention of ensuring that they are innocuous to target animals, users and consumers. Particular attention is focused on the presence of transmissible antibiotic resistance markers, and to the potential for production of harmful metabolites. The guidelines do not differentiate between species and strains with long histories of safe use and other micro-organisms. This has caused some concern regarding overregulation, if the same principles are to be applied to probiotics or starter cultures intended for human food use. Accordingly, SCAN has launched an initiative towards a "Qualified Perception of Safety" (QPS) concept, which would allow strains with established safety status to enter the market without extensive testing requirements. It is likely that the European Food Safety Authority (EFSA) will play a central role in the regulation of both human and animal probiotics.
Cannabidivarin (CBDV) suppresses pentylenetetrazole (PTZ)-induced increases in epilepsy-related gene expression (2013)

To date, anticonvulsant effects of the plant cannabinoid, cannabidivarin (CBDV), have been reported in several animal models of seizure. However, these behaviourally observed anticonvulsant effects have not been confirmed at the molecular level. To examine changes to epilepsy-related gene expression following chemical convulsant treatment and their subsequent control by phytocannabinoid administration, we behaviourally evaluated effects of CBDV (400 mg/kg, p.o.) on acute, pentylenetetrazole (PTZ: 95 mg/kg, i.p.)-induced seizures, quantified expression levels of several epilepsy-related genes (Fos, Casp 3, Ccl3, Ccl4, Npy, Arc, Penk, Camk2a, Bdnf and Egr1) by qPCR using hippocampal, neocortical and prefrontal cortical tissue samples before examining correlations between expression changes and seizure severity. PTZ treatment alone produced generalised seizures (median: 5.00) and significantly increased expression of Fos, Egr1, Arc, Ccl4 and Bdnf. Consistent with previous findings, CBDV significantly decreased PTZ-induced seizure severity (median: 3.25) and increased latency to the first sign of seizure. Furthermore, there were correlations between reductions of seizure severity and mRNA expression of Fos, Egr1, Arc, Ccl4 and Bdnf in the majority of brain regions in the CBDV+PTZ treated group. When CBDV treated animals were grouped into CBDV responders (criterion: seizure severity ≤3.25) and non-responders (criterion: seizure severity >3.25), PTZ-induced increases of Fos, Egr1, Arc, Ccl4 and Bdnf expression were suppressed in CBDV responders. These results provide the first molecular confirmation of behaviourally observed effects of the non-psychoactive, anticonvulsant cannabinoid, CBDV, upon chemically-induced seizures and serve to underscore its suitability for clinical development.
Sexual needs of those whose partner has died (1997)

(1997). Sexual needs of those whose partner has died. Bereavement Care: Vol. 16, No. 1, pp. 2-5.
Hepatitis a virus: Growth characteristics of in vivo and in vitro propagated wild and attenuated virus strains (1984)

Serial passage of the MS-1 strain hepatitis A virus (HAV) in marmosets was shown to increase the yield of virus and to shorten the incubation period from approximately 55 days in the first passage to 3-7 days in the ninth and higher passages. Intravenous inoculation of susceptible chimpanzees with MS-1 HAV was found to result in a typical course of disease in two animals who had received eighth marmoset-passage virus, including the occurrence of elevated ALT activity, presence of HAV antigen in liver and stool, and seroconversion to anti-HAV. Two chimpanzees inoculated with 20th passage MS-1 HAV (M001 liver homogenate) exhibited normal or nearly normal ALT activity and had no demonstrable or significant HAV in weekly liver biopsy specimens or in serial stool suspensions obtained during 64 days of observation. However, both animals seroconverted to anti-HAV within 2 weeks after inoculation, as did the animals who had received eighth passage MS-1 HAV. These findings suggest that subpassage of the MS-1 strain of HAV in marmosets resulted in the generation of an attenuated virus strain that was still capable of inducing a vigorous antibody response in intravenously infected chimpanzees. Serial propagation of wild and attenuated strains of HAV (HAS-15 and MS-1/M001, respectively) in FRhK-4 cells was associated with a significant decrease in the growth period for both viruses. Our studies have also shown that HAS-15 HAV can be recovered in maximum yield in later passages as early as 2 to 3 days after inoculation.
Multiple-symbol differential detection of MPSK (1990)

A differential detection technique for MPSK (multiple-phase shift keying), which uses a multiple-symbol observation interval, is presented, and its performance is analyzed and simulated. The technique makes use of maximum-likelihood sequence estimation of the transmitted phases rather than symbol-by-symbol detection as in the conventional differential detection. Thus, the performance of this multiple-symbol detection scheme fills the gap between conventional (two-symbol observation) differentially coherent detection of MPSK and ideal coherent of MPSK with differential encoding. The amount of improvement gained over conventional differential detection depends on the number of phases M and the number of additional symbol intervals added to the observation. What is particularly interesting is that substantial performance improvement can be obtained for only one or two additional symbol intervals of observation. The analysis and simulation results presented are for uncoded MPSK.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Castleman's Disease: From Basic Mechanisms to Molecular Therapeutics (2011)

Castleman's disease is a rare lymphoproliferative disorder in which there has been recent progress in elucidating underlying mechanisms with potential therapeutic implications. Unicentric Castleman's disease is an indolent condition that is often treated with local approaches. In contrast, patients with multicentric Castleman's disease (MCD) have a less favorable prognosis and require systemic treatment. Cytotoxic chemotherapy, with its attendant risk for toxicity, has been widely used to treat MCD, with variable efficacy. The discovery of putative etiologic factors and targets in MCD, particularly human herpes virus 8, CD20, and interleukin (IL)-6, has been translated into the use of rituximab and anti-IL-6-based therapy, as well as antiviral agents. In this article, we review the current state of the art of our understanding of Castleman's disease and its treatment and we provide insight into future treatment strategies based on disease biology.
Validation of Biomarkers for Early Detection of Pancreatic Cancer (2018)

Pancreatic cancer is the third leading cause of cancer death in the United States, and the 5-year relative survival for patients diagnosed with pancreatic cancer is less than 10%. Early intervention is the key to a better survival outcome. Currently, there are no biomarkers that can reliably detect pancreatic cancer at an early stage or identify precursors that are destined to progress to malignancy. The National Cancer Institute in partnership with the Kenner Family Research Fund and the Pancreatic Cancer Action Network convened a Data Jamboree on Biomarkers workshop on December 5, 2016, to discuss and evaluate existing or newly developed biomarkers and imaging methods for early detection of pancreatic cancer. The primary goal of this workshop was to determine if there are any promising biomarkers for early detection of pancreatic cancer that are ready for clinical validation. The Alliance of Pancreatic Cancer Consortia for Biomarkers for Early Detection, formed under the auspices of this workshop, will provide the common platform and the resources necessary for validation. Although none of the biomarkers evaluated seemed ready for a large-scale biomarker validation trial, a number of them had sufficiently high sensitivity and specificity to warrant additional research, especially if combined with other biomarkers to form a panel.
Brain-Derived Neurotrophic Factor-Dependent Synaptic Plasticity Is Suppressed by Interleukin-1β via p38 Mitogen-Activated Protein Kinase (2012)

Evolving evidence suggests that brain inflammation and the buildup of proinflammatory cytokine increases the risk for cognitive decline and cognitive dysfunction. Interleukin-1β (IL-1β), acting via poorly understood mechanisms, appears to be a key cytokine in causing these deleterious effects along with a presumably related loss of long-term potentiation (LTP)-type synaptic plasticity. We hypothesized that IL-1β disrupts brain-derived neurotrophic factor (BDNF) signaling cascades and thereby impairs the formation of filamentous actin (F-actin) in dendritic spines, an event that is essential for the stabilization of LTP. Actin polymerization in spines requires phosphorylation of the filament severing protein cofilin and is modulated by expression of the immediate early gene product Arc. Using rat organotypic hippocampal cultures, we found that IL-1β suppressed BDNF-dependent regulation of Arc and phosphorylation of cofilin and cAMP response element-binding protein (CREB), a transcription factor regulating Arc expression. IL-1β appears to act on BDNF signal transduction by impairing the phosphorylation of insulin receptor substrate 1, a protein that couples activation of the BDNF receptor TrkB to downstream signaling pathways regulating CREB, Arc, and cofilin. IL-1β upregulated p38 mitogen-activated protein kinase (MAPK), and inhibiting p38 MAPK prevented IL-1β from disrupting BDNF signaling. IL-1β also prevented the formation of F-actin in spines and impaired the consolidation, but not the induction, of BDNF-dependent LTP in acute hippocampal slices. The suppressive effect of IL-1β on F-actin and LTP was prevented by inhibiting p38 MAPK. These findings define a new mechanism for the action of IL-1β on LTP and point to a potential therapeutic target to restore synaptic plasticity.
In vivo Imaging and Quantitation of Adoptively Transferred Human Antigen-Specific T Cells Transduced to Express a Human Norepinephrine Transporter Gene (2007)

Sequential imaging of genetically marked effector cells after adoptive transfer in vivo has greatly enhanced analyses of their biodistribution, growth, and activity both in animal models and in clinical trials of cellular immunotherapy. However, the immunogenicity of cells expressing xenogeneic reporter constructs limits their survival and clinical utility. To address this limitation, we have evaluated a human norepinephrine transporter (hNET) permitting imaging of transduced cells in vivo with a previously approved clinical grade radiolabeled probe, metaiodobenzylguanidine (MIBG). The hNET gene cDNA was cloned from the SK-N-SH cell line and inserted into a bicistronic retroviral vector also encoding green fluorescent protein. Following transfection, human EBV-specific T lymphocytes seemed fully functional in vitro and also selectively accumulated [(123)I]MIBG. In nonobese diabetic/severe combined immunodeficient mice bearing human EBV lymphoma xenografts, as few as 10(4) transduced T cells injected into the tumors could be imaged by single-photon emission computed tomography (SPECT) or positron emission tomography (PET) after i.v. infusion of [(123)I]MIBG or [(124)I]MIBG, respectively. When hNET(+) EBV-specific T cells were infused i.v., their migration and specific accumulation in EBV(+) tumors expressing their restricting HLA allele could be imaged by SPECT or PET over 28 days. Image intensity was closely correlated with the number of T cells accumulated in targeted tumors. The use of two reporter probes (MIBG and 2'-deoxy-2'-fluoro-beta-d-arabinofuranosyl-5-iodouracil) permitted independent contemporaneous tracking of two distinct EBV-specific T-cell subpopulations expressing different reporter genes (hNET-CD4(+) T cells and HSV-TK-CD8(+) T cells) in the same animal using three-dimensional nuclear modalities (SPECT and PET). The hNET-based system described may thus have significant potential as a nonimmunogenic reporter for extended repeated quantitative in vivo imaging of transduced cells in man.
Mapping of Functional Elements in the Stem-Anchor Region of Tick-Borne Encephalitis Virus Envelope Protein E (1999)

Envelope protein E of the flavivirus tick-borne encephalitis virus mediates membrane fusion, and the structure of the N-terminal 80% of this 496-amino-acid-long protein has been shown to differ significantly from that of other viral fusion proteins. The structure of the carboxy-terminal 20%, the stem-anchor region, is not known. It contains sequences that are important for membrane anchoring, interactions with prM (the precursor of membrane protein M) during virion assembly, and low-pH-induced structural changes associated with the fusion process. To identify specific functional elements in this region, a series of C-terminal deletion mutants were constructed and the properties of the resulting truncated recombinant E proteins were examined. Full-length E proteins and proteins lacking the second of two predicted transmembrane segments were secreted in a particulate form when coexpressed with prM, whereas deletion of both segments resulted in the secretion of soluble homodimeric E proteins. Sites located within a predicted alpha-helical region of the stem (amino acids 431 to 449) and the first membrane-spanning region (amino acids 450 to 472) were found to be important for the stability of the prM-E heterodimer but not essential for prM-mediated intracellular transport and secretion of soluble E proteins. A separate site in the stem, also corresponding to a predicted alpha-helix (amino acids 401 to 413), was essential for the conversion of soluble protein E dimers to a homotrimeric form upon low-pH treatment, a process resembling the transition to the fusogenic state in whole virions. This functional mapping will aid in the understanding of the molecular mechanisms of membrane fusion and virus assembly.
Role of the conserved C-terminal region of thyroid hormone receptor-α in ligand-dependent transcriptional activation (1998)

The ligand binding domain (LBD) of thyroid hormone (T3) receptors contains subdomains that participate in transcriptional activation, hormone-relieved repression and dimerization. A sequence conserved within the nuclear receptor superfamily is found at positions 397-405 of the 408-amino acid chicken T3 receptor-alpha (cTR alpha) and is deleted in the related avian v-erbA. Since v-erbA exhibits compromised ligand binding and transcriptional activation, this conserved region may play a role in ligand-dependent transcriptional activation. Transfections reveal that cTR alpha(1-392) and site-directed mutants cTR alpha(L398R) and cTR alpha(F399E) are inactive, while cTR alpha(1-403) displays reduced ligand-dependent transcriptional activity. The loss of transcriptional activity in cTR alpha(1-392) is not caused by impaired DNA binding or receptor dimer formation. Proteolytic protection assays reveal that both transcriptionally active and inactive cTR alpha derivatives undergo T3-mediated conformational changes. Gal4 chimeras containing the final 16, 35 or 44 amino acids of cTR alpha indicate that the conserved C-terminal region does not function as an independent transactivation domain. Our results are consistent with a model in which ligand plays a structural role to position the conserved C-terminal regions of cTR alpha and related receptors in a transcriptionally active conformation.
Initial Clinical Experience With Intraaortic Balloon Pumping in Cardiogenic Shock (1968)

Our intraaortic cardiac assistance system for patients in cardiogenic shock following myocardial infarction consists of a catheter and balloon inserted through a femoral arteriotomy into the thoracic aorta. The pumping chamber, activated by helium, is synchronized with the heart by signals from the electrocardiogram or the central aortic pressure transducer. Pumping improved two patients' circulatory status; one survived. Two patients died before pumping could begin; in another, an abdominal aortic aneurysm prevented insertion of the pump. Thrombosis did not occur during pumping; hemolysis appeared minimal. Although final evaluation must await more data, balloon pumping appears to be effective in cardiogenic shock. Further study may establish a place for the procedure in myocardial infarction without cardiogenic shock and in low cardiac output syndromes associated with open-heart surgery.
Alkylation of Si Surfaces Using a Two-Step Halogenation/Grignard Route (1996)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTAlkylation of Si Surfaces Using a Two-Step Halogenation/Grignard RouteAshish Bansal, Xiuling Li, Iver Lauermann, Nathan S. Lewis, Sang I. Yi, and W. H. WeinbergView Author Information Division of Chemistry and Chemical Engineering California Institute of Technology Pasadena, California 91125 Department of Chemical Engineering, University of California, Santa Barbara, California 93106 Cite this: J. Am. Chem. Soc. 1996, 118, 30, 7225–7226Publication Date (Web):July 31, 1996Publication History Received1 February 1996Published online31 July 1996Published inissue 1 January 1996https://pubs.acs.org/doi/10.1021/ja960348nhttps://doi.org/10.1021/ja960348nrapid-communicationACS PublicationsCopyright © 1996 American Chemical SocietyRequest reuse permissionsArticle Views3571Altmetric-Citations404LEARN 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 SUBJECTS:Alkyls,Desorption,Functionalization,Oxidation,Silicon Get e-Alerts
Autologous transplantation of bone marrow purged in vitro with anti-CD7- (WT1-) ricin A immunotoxin in T-cell lymphoblastic leukemia and lymphoma (1989)

Seven patients with high-risk acute T-cell lymphoblastic leukemia (T- ALL) and six with T cell lymphoma (T-LL) were treated with autologous bone marrow transplantation (ABMT) after in vitro purging of their bone marrow with WT1 (CD7)-ricin A-chain immunotoxin. CD7 expression on the tumor cells showed large variations between the individual patients and was highly related to the specific cytotoxicity of WT1-ricin A. Incubation of bone marrow with up to 10(-8)mol/L WT1-ricin A in the presence of 6 mmol/L NH4Cl did not compromise the growth potential of the hematopoietic progenitors CFU-GM, CFU-GEMM, and BFU-E. Hematologic engraftment (greater than 10(9) leukocytes/L) occurred within a normal time period (median, 17 days). Seven patients are alive and in complete remission (CR) at 48+, 44+, 40+, 26+, 11+, 7+, and 6+ months after ABMT. Four patients relapsed within 6 months after ABMT. Two of them had the lowest CD7 expression on their tumor cells, the other two were transplanted in CR2 and CR3. Two patients died from transplantation related infections. The immunologic reconstitution was delayed, although the numbers of T cells reached normal levels within 1 month. The number of CD7+ cells remained low up to 1 year after transplantation. The T4/T8-ratio was decreased for at least 6 months. The T-cell response to mitogens recovered to normal levels after 1 year. This study shows that ABMT with WT1-ricin A purged bone marrow in high-risk T-cell malignancies results in a complete hematopoietic and a delayed immunologic reconstitution. The actuarial relapse free survival is 61% at 3 years.
The spectral characteristics of luminous marine organisms (1983)

Abstract Measurements of the bioluminescent emission spectra of a wide range of marine animals demonstrate considerable differences between taxa in both the position of the peak emission and the half bandwidth. Although most of the measured spectra are unimodal, some species have either two peaks or one main peak with subsidiary shoulders. Such structured emission spectra are present in several systematic groups and in some cases the emission characteristics have been observed to vary with time. The emission maxima of most species fall within the range 450—490 nm, though maxima from 395-545 nm have been recorded. Species found in the pelagic environment are mostly blue-emitting but there is some indication of relative increase in green-emitting species in the benthic environment. Terrestrial organisms are predominantly yellow-green luminescent. The ecological value of the observed spectral differences is discussed. While the characteristics of the emission spectra have considerable adaptive value for certain functions, some minor spectral variations may not be of ecological significance. Selection for increased quantum efficiency of the luminescence may sometimes predominate over spectral considerations.
Simulation Tests of a Novel Criterion for Neutral Current Differential Protection (2006)

A novel criterion for neutral current differential protection is presented in this paper, which is based on a full research into traditional neutral current differential protection schemes used in transmission lines. Compared to traditional criteria, the novel one is able to increase sensitivity for an internal fault and remain stable for an external fault. Simulation studies show that the sensitivity of neutral differential protection is improved greatly especially under single-pole open condition.