gebhart/patrepeval huggingface dataset:
Interferon gama induced Tryptophan Degradation Neuropsychiatric and Immunological Consequences (2000)

Tryptophan is a constituent of proteins and in parallel it represents a source for mainly two pivotal biochemical pathways: the generation of 5-hydroxytryptamine (serotonin), and the formation of kynurenine by the enzymes tryptophan pyrrolase (TP) and indoleamine 2,3-dioxygenase (IDO). IDO is induced by interferon-gamma (IFN-gamma) in a broad variety of cells. Therefore, enhanced tryptophan degradation is observed in diseases and disorders concomitant with cellular immune activation, e.g. infectious diseases, autoimmune diseases, malignant diseases as well as in pregnancy. IFN-gamma-derived tryptophan degradation may represent an effector mechanism within in the comprehensive network of immune stimulation. In addition, the cytostatic and, respectively, antiproliferative properties on e.g., T-lymphocytes may contribute to the immunomodulatory function of IFN-gamma. However, especially in states of persistent immune activation increased tryptophan catabolism leads to the depletion of free serum tryptophan and to the accumulation of neuroactive kynurenine metabolites. As a consequence, serotonergic functions may be affected, and the neurotoxic properties of kynurenine derivatives may lead to neuronal disorders evoking neurological/psychiatric symptoms. This notion provides a basis for the better understanding of mood disorders and related syptoms in chronic diseases. Moreover, IDO could represent a link between the immunological network and neuroendocrine functions with far reaching consequences regarding to the psychological status of patients.
New Design of MHC Class II Tetramers to Accommodate Fundamental Principles of Antigen Presentation (2009)

Direct identification and isolation of Ag-specific T cells became possible with the development of MHC tetramers, based on fluorescent avidins displaying biotinylated peptide-MHC complexes. This approach, extensively used for MHC class I-restricted T cells, has met very limited success with class II peptide-MHC complex tetramers (pMHCT-2) for the detection of CD4(+)-specific T cells. In addition, a very large number of these reagents, although capable of specifically activating T cells after being coated on solid support, is still unable to stain. To try to understand this puzzle and design usable tetramers, we examined each parameter critical for the production of pMHCT-2 using the I-A(d)-OVA system as a model. Through this process, the geometry of peptide-MHC display by avidin tetramers was examined, as well as the stability of rMHC molecules. However, we discovered that the most important factor limiting the reactivity of pMHCT-2 was the display of peptides. Indeed, long peptides, as presented by MHC class II molecules, can be bound to I-A/HLA-DQ molecules in more than one register, as suggested by structural studies. This mode of anchorless peptide binding allows the selection of a broader repertoire on single peptides and should favor anti-infectious immune responses. Thus, beyond the technical improvements that we propose, the redesign of pMHCT-2 will give us the tools to evaluate the real size of the CD4 T cell repertoire and help us in the production and testing of new vaccines.
Networking sensors using belief propagation (2008)

This paper investigates the performance of belief propagation (BP) as a distributed solution to two combinatorial resource allocation problems arising in sensor networks: network formation and fusion center location. We model these problems by max-weight b-matching and uncapacitated facility location, respectively. Each of these is a classical optimization problem. For both problems, we (a) show how BP can be simplified for implementation in distributed environments where transmissions are broadcast and can interfere, (b) derive a principled interpretation of estimates before convergence, and (c) compare the performance of BP to that of linear programming.
Receptor Subtype Mediating the Adrenergic Sensitivity of Pain Behavior and Ectopic Discharges in Neuropathic Lewis Rats (1999)

Receptor subtype mediating the adrenergic sensitivity of pain behavior and ectopic discharges in neuropathic Lewis rats. We attempted to identify the subtype of alpha-adrenergic receptor (alpha-AR) that is responsible for the sympathetic (adrenergic) dependency of neuropathic pain in the segmental spinal injury (SSI) model in the Lewis strain of rat. This model was chosen because our previous study showed that pain behaviors in this condition are particularly sensitive to systemic injection of phentolamine (PTL), a general alpha-AR blocker. We examined the effects of specific alpha1- and alpha2-AR blockers on 1) behavioral signs of mechanical allodynia, 2) ectopic discharges recorded in the in vivo condition, and 3) ectopic discharges recorded in an in vitro setup. One week after tight ligation of the L5 and L6 spinal nerves, mechanical thresholds of the paw for foot withdrawals were drastically lowered; we interpreted this change as a sign of mechanical allodynia. Signs of mechanical allodynia were significantly relieved by a systemic injection of PTL (a mixed alpha1- and alpha2-AR antagonist) or terazosin (TRZ, an alpha1-AR antagonist) but not by various alpha2-AR antagonists (idazoxan, rauwolscine, or yohimbine), suggesting that the alpha1-AR is in part the mediator of the signs of mechanical allodynia. Ongoing ectopic discharges were recorded from injured afferents in fascicles of the L5 dorsal root of the neuropathic rat with an in vivo recording setup. Ongoing discharge rate was significantly reduced after intraperitoneal injection of PTL or TRZ but not by idazoxan. In addition, by using an in vitro recording setup, spontaneous activity was recorded from teased dorsal root fibers in a segment in which the spinal nerve was previously ligated. Application of epinephrine to the perfusion bath enhanced ongoing discharges. This evoked activity was blocked by pretreatment with TRZ but not with idazoxan. This study demonstrated that both behavioral signs of mechanical allodynia and ectopic discharges of injured afferents in the Lewis neuropathic rat are in part mediated by mechanisms involving alpha1-ARs. These results suggest that the sympathetic dependency of neuropathic pain in the Lewis strain of the rat is mediated by the alpha1 subtype of AR.
Advances in Peptide Pharmaceuticals (2009)

Drug delivery strategies for peptide pharmaceuticals have incorporated a wide range of structure activity relationships, analog generation to impart protease resistance and increased bioavailability, novel formulations, and delivery systems to target optimal therapeutic dosing requirements. Advances in peptide pharmaceuticals have provided products for the treatment of diabetes, obesity, Crohn's disease, osteoporosis, cancer, cardiovascular disease, immunotherapy, acromegaly, enuresis, pain, and antimicrobials. Here we review these marketed peptides and new peptidomimetic therapies currently in clinical trials.
Synthesis of Human Cartilage Using Organotypic Cell Culture (1993)

The limited supply of fresh autologous cartilage tissue for use in reconstructive surgery necessitates the use of vital banked allografts. A feasible in vitro production of cartilage tissue composed of living cells requires the use of modern tissue culture techniques retaining the phenotypic characteristics of chondrocytes. With this purpose in mind, human chondrocytes were isolated and cultured using different culture procedures: monolayer, suspension and agar gel. The differentiation state of chondrocytes as well as proteoglycan and collagen syntheses were assessed by histochemical and immunohistochemical methods. Whereas chondrocytes in monolayer displayed an unstable phenotype and tended to dedifferentiate, in three-dimensional culture the chondrocytes remained morphologically, phenotypically and functionally differentiated. Furthermore, an accumulation of matrix products pericellularly was observed in the agar gel. The results suggest that three-dimensional cultures in agar gel may allow the in vitro production of bioartificial cartilage for transplantation.
Some properties and applications of monoclonal antibodies (1981)

Research Article| October 15 1981 Some properties and applications of monoclonal antibodies P A W Edwards P A W Edwards Search for other works by this author on: This Site PubMed Google Scholar Biochem J (1981) 200 (1): 1–10. https://doi.org/10.1042/bj2000001 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter LinkedIn Cite Icon Cite Get Permissions Citation P A W Edwards; Some properties and applications of monoclonal antibodies. Biochem J 15 October 1981; 200 (1): 1–10. doi: https://doi.org/10.1042/bj2000001 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Journal Search Advanced Search This content is only available as a PDF. © 1981 London: The Biochemical Society1981 Article PDF first page preview Close Modal You do not currently have access to this content.
Security system for wireless local area networks (2002)

Security and privacy issues complicate wireless local area network deployment. For a wired network, certain levels of security are maintained since access to the physical medium is restricted to the devices physically connected to the network. Though wireless local area networks offer some built-in security features, security breaches are possible if appropriate precautions are not taken. This paper describes security issues related to wireless local area networks and presents a software approach for restricting and controlling wireless access. The system authenticates users on the basis of identity, privileges and access hardware by distributed software agents that implement the security policy and restrict unauthorized access.
Glow discharge techniques in analytical chemistry (1990)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTGlow discharge techniques in analytical chemistryW. W. Harrison, C. M. Barshick, J. A. Klingler, P. H. Ratliff, and Y. MeiCite this: Anal. Chem. 1990, 62, 18, 943A–949APublication Date (Print):September 1, 1990Publication History Published online22 September 2008Published inissue 1 September 1990https://pubs.acs.org/doi/10.1021/ac00217a001https://doi.org/10.1021/ac00217a001research-articleACS PublicationsRequest reuse permissionsArticle Views342Altmetric-Citations84LEARN 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
Subcellular effects of nanosecond electrical pulses (2005)

Electrical models for biological cells predict that reducing the duration of applied electrical pulses to values below the charging time of the outer membrane causes a strong increase in the probability for electric field interactions with intracellular structures. For electric field amplitudes exceeding MV/m such pulses are expected to cause electroporation of cell organelles, with the required electric field amplitude scaling linearly with the inverse of pulse duration. Experimental studies where human cells were exposed to pulsed electric field of up to 300 kV/cm amplitude with duration as short as 10 ns, have confirmed this hypothesis. The observed effects include the breaching of intracellular granule membranes without permanent damage to the cell membrane, abrupt rises in intracellular free calcium levels, and enhanced expression of genes. At increased electric fields, the application of nanosecond pulses induces apoptosis in biological cells, an effect that has been shown to reduce the growth of tumors.
Trafficking of B Cell Antigen in Lymph Nodes (2011)

The clonal selection theory first proposed by Macfarlane Burnet is a cornerstone of immunology (1). At the time, it revolutionized the thinking of immunologists because it provided a simple explanation for lymphocyte specificity, immunological memory, and elimination of self-reactive clones (2). The experimental demonstration by Nossal & Lederberg (3) that B lymphocytes bear receptors for a single antigen raised the central question of where B lymphocytes encounter antigen. This question has remained mostly unanswered until recently. Advances in techniques such as multiphoton intravital microscopy (4, 5) have provided new insights into the trafficking of B cells and their antigen. In this review, we summarize these advances in the context of our current view of B cell circulation and activation.
A Method of Photographing Fluorescence in Circulating Blood in the Human Retina (1961)

A simple method, with use of intravenous fluorescein, was used for producing and photographing fluorescence in circulating blood of the human retina. Separate arteriolar and venous filling phases, arteriolovenous shunt, sluggish choroidal circulation, stratified flow of fluorescein, and rapid central retinal circulation times were observed in normal retinas. Similar findings were seen in hypertensive and diabetic patients, and, in addition, neovascularization was clearly defined, and some cotton-wool patches, but not hemorrhages, were found to fluoresce. Limitations and applications of the method are discussed.
The postantibiotic effect of antifungal agents against common pathogenic yeasts (1994)

A total of ten strains of Candida spp. and Cryptococcus neoformans were examined for the presence of the postantibiotic effect (PAE) after 0.5-2 h exposure to amphotericin B, 5-fluorocytosine, miconazole and ketoconazole. Significant PAEs were observed for amphotericin B and 5-fluorocytosine, but none for the imidazoles. The duration of the PAEs of amphotericin B ranged from 0.5-10.4 h for the Candida spp. and 2.8-10.6 h for the cryptococcos, while 5-fluorocytosine induced PAEs from 0.8-7.4 h and 2.4-5.4 h, respectively. Even though no PAEs were demonstrated for the imidazoles, the growth rate was persistently reduced by continuous exposure to concentrations as low as 1/1000 of the MIC of these agents. These findings may have implications for dosing antifungal agents in systemic yeast infections.
High grade prostatic intraepithelial neoplasia. The most likely precursor of prostate cancer (1995)

The search for the precursor of prostatic adenocarcinoma has focused in recent years on the spectrum of histopathologic changes referred to as high grade prostatic intraepithelial neoplasia (PIN). This review describes the diagnostic criteria and clinical significance of PIN. PIN coexists with cancer in more than 85% of cases, but retains an intact or fragmented basal cell layer, unlike cancer, which lacks a basal cell layer. High grade PIN in biopsies predicts the presence of cancer in subsequent biopsies, and PIN provides the highest risk ratio of all known predictive factors (14.93). The continuum that culminates in high grade PIN and early invasive cancer is characterized by progressive basal cell layer disruption, loss of markers of secretory differentiation, nuclear and nucleolar abnormalities, increasing proliferative potential, variation in DNA content, and allelic loss. Clinical studies suggest that PIN predates carcinoma by 10 years or more, with low grade PIN first appearing in men in their thirties. The significance of recognizing PIN is based on its strong association with prostatic carcinoma. This finding indicates the need for repeat biopsy and follow-up when PIN is identified on biopsy, especially in patients with elevated serum prostate specific antigen concentration. PIN also offers promise as an intermediate end point in studies of chemoprevention of prostatic carcinoma. Cancer 1995;75:1823–36.
Identifying High-Risk Precursors of Cervical Cancer: How and Why (1989)

Journal Article Identifying High-Risk Precursors of Cervical Cancer: How and Why Get access Christopher P. Crum, M.D. Christopher P. Crum, M.D. Department of Pathology, Microbiology, and Obstetrics and Gynecology University of Virginia Health Sciences Center Charlottesville, Virginia Search for other works by this author on: Oxford Academic Google Scholar American Journal of Clinical Pathology, Volume 92, Issue 3, 1 September 1989, Pages 379–382, https://doi.org/10.1093/ajcp/92.3.379 Published: 01 September 1989
Trifluoromethanesulfanylamides as Easy‐to‐Handle Equivalents of the Trifluoromethanesulfanyl Cation (CF3S+): Reaction with Alkenes and Alkynes (2009)

Elegant eingeführt: Die CF3S-Einheit lässt sich mithilfe des Trifluormethansulfanylamid-Reagens elektrophil an Alkene und Alkine addieren (siehe Schema; Ts=Toluol-4-sulfonyl). Die erhaltenen Produkte könnten beispielsweise in der pharmazeutischen Chemie und den Materialwissenschaften von Interesse sein.
Proteomic profiling of salivary gland after nonviral gene transfer mediated by conventional plasmids and minicircles (2014)

In this study, we compared gene transfer efficiency and host response to ultrasound-assisted, nonviral gene transfer with a conventional plasmid and a minicircle vector in the submandibular salivary glands of mice. Initially, we looked at gene transfer efficiency with equimolar amounts of the plasmid and minicircle vectors, corroborating an earlier report showing that minicircle is more efficient in the context of a physical method of gene transfer. We then sought to characterize the physiological response of the salivary gland to exogenous gene transfer using global proteomic profiling. Somewhat surprisingly, we found that sonoporation alone, without a gene transfer vector present, had virtually no effect on the salivary gland proteome. However, when a plasmid vector was used, we observed profound perturbations of the salivary gland proteome that compared in magnitude to that seen in a previous report after high doses of AAV. Finally, we found that gene transfer with a minicircle induces only minor proteomic alterations that were similar to sonoporation alone. Using mass spectrometry, we assigned protein IDs to 218 gel spots that differed between plasmid and minicircle. Bioinformatic analysis of these proteins demonstrated convergence on 68 known protein interaction pathways, most notably those associated with innate immunity, cellular stress, and morphogenesis.
Attenuated properties of thymidine kinase-negative deletion mutant of pseudorabies virus (1985)

A thymidine kinase (TK)-negative (TK-) deletion mutant of the Bucharest (BUK) strain of pseudorabies virus (PRV) was isolated. The mutant, designated as PRV (BUK d13), did not revert to TK-positive (TK+), even when propagated in medium that selected for TK+ viruses. The mutant also replicated equally well at 39.1 C and 34.5 C, and was easily distinguished from other PRV strains by molecular hybridization experiments, restriction nuclease fingerprints, and plaque autoradiography or other assays for the TK phenotype. The PRV (BUK d13) had greatly reduced virulence for mice and rabbits, compared with parental TK+ strains, PRV (BUK-5) and PRV (BUK-5A-R1), and provided mice with solid protection against the TK+ BUK and Aujeszky strains of PRV. Experiments were done in 5- to 6-week-old pigs to assess the safety and efficacy of PRV (BUK d13) in the natural host. In one experiment, pigs were vaccinated IM with 7.5 X 10(8) plaque-forming units of TK- PRV (BUK d13), and were then challenge exposed intranasally (IN) with 4.3 X 10(8) TCID50 of virulent PRV [Indiana-Funkhauser (IND-F)]. Vaccinated pigs did not have clinical signs of illness after vaccination or after challenge exposure. One nonvaccinated control pig died on postchallenge day 4; a 2nd nonvaccinated control pig became moribund, but eventually recovered. Pigs developed virus-neutralizing antibodies after vaccination, and had a secondary immunologic response after challenge exposure; however, PRV was not isolated from the tonsils or trigeminal ganglia of vaccinated pigs at postchallenge exposure day 11.(ABSTRACT TRUNCATED AT 250 WORDS)
Immature human monocyte-derived dendritic cells migrate rapidly to draining lymph nodes after intradermal injection for melanoma immunotherapy (1999)

Injected antigen-loaded immature monocyte-derived dendritic cells (DCs) may be incapable of migrating from skin to draining lymph nodes for antigen presentation. The in vivo migratory capacity of intradermally administered immature monocyte-derived DCs was therefore investigated during a phase I/II clinical trial for metastatic melanoma. DCs cultured from adherent monocytes in the presence of autologous serum, granulocyte-macrophage colony stimulating factor and interleukin-4 were pulsed with antigen and labelled with technetium-99m hexamethylpropylene-amineoxime (99mTc-HMPAO) ex vivo, then injected intradermally. A 99mTc-HMPAO control containing an equivalent amount of radioactivity was injected into the opposite thigh. The pelvis was then imaged with a gamma camera. The DCs were characterized as immature by functional and phenotypic analysis. Labelled DCs travelled to the draining inguinal lymph nodes within 10 min, and the draining lymph nodes were clearly outlined up to 4 h after injection. Free NmTc outlined draining lymph nodes after 10 min but was cleared from the nodes within 1 h. Thus, immature human monocyte-derived DCs migrate rapidly to and remain in draining lymph nodes after intradermal injection for immunotherapy.
2-[(3aR,4R,5S,7aS)-5-{(1S)-1-[3,5-Bis(trifluoromethyl)phenyl]-2-hydroxyethoxy}-4-(2-methylphenyl)octahydro-2H-isoindol-2-yl]-1,3-oxazol-4(5H)-one: A Potent Human NK1 Receptor Antagonist with Multiple Clearance Pathways (2013)

Hydroisoindoline 2 has been previously identified as a potent, brain-penetrant NK1 receptor antagonist with a long duration of action and improved profile of CYP3A4 inhibition and induction compared to aprepitant. However, compound 2 is predicted, based on data in preclinical species, to have a human half-life longer than 40 h and likely to have drug-drug-interactions (DDI), as 2 is a victim of CYP3A4 inhibition caused by its exclusive clearance pathway via CYP3A4 oxidation in humans. We now report 2-[(3aR,4R,5S,7aS)-5-{(1S)-1-[3,5-bis(trifluoromethyl)phenyl]-2-hydroxyethoxy}-4-(2-methylphenyl)octahydro-2H-isoindol-2-yl]-1,3-oxazol-4(5H)-one (3) as a next generation NK1 antagonist that possesses an additional clearance pathway through glucuronidation in addition to that via CYP3A4 oxidation. Compound 3 has a much lower propensity for drug-drug interactions and a reduced estimated human half-life consistent with once daily dosing. In preclinical species, compound 3 has demonstrated potency, brain penetration, and a safety profile similar to 2, as well as excellent pharmacokinetics.