gebhart/patrepeval huggingface dataset:
Antigen recognition and allogeneic tumor rejection in CD8+ TCR transgenic/RAG(-/-) mice (1997)

Three sources of help for the development of a CD8+ CTL response have been described: the CD4+ direct and indirect pathways and the CD8+ direct pathway. In an effort to understand the minimal requirements for the development of a CTL response in vivo, we have bred mice transgenic for the 2C TCR onto a RAG(-/-) background. The 2C T cells in this animal are exclusively CD8+ CTLs of a single specificity, and they exhibit altered thymic maturation compared with that of T cells from 2C TCR/RAG(+/+) mice. T cells from 2C TCR/RAG(-/-) mice can be activated to a high level in vivo by administration of a self-MHC-restricted antigenic peptide. The 2C TCR/RAG(-/-) mice are able to reject B7-negative allogeneic tumors bearing the appropriate peptide/MHC ligand p2C/Ld. These mice fail to reject syngeneic tumors, and their RAG(-/-) littermates lacking 2C T cells uniformly succumb to both allogeneic and syngeneic tumors. Moreover, blockade of B7 costimulatory molecules fails to prevent tumor rejection in the 2C TCR/RAG(-/-) mice, suggesting that allorejection is occurring independently of B7-mediated costimulation as well as in the absence of CD4+ T cells. CTLs isolated from the site of the tumor during the period of rejection express the activation marker CD25 and are able to mediate ex vivo cytolysis of tumor cells bearing the appropriate Ag. These results suggest that in this TCR transgenic model with a very high precursor frequency, CTL development can occur in the absence of B7:CD28 costimulation and without CD4+ help.
NF-kappa B subunit-specific regulation of the interleukin-8 promoter. (1993)

Interleukin-8 (IL-8), a chemotactic cytokine for T lymphocytes and neutrophils, is induced in several cell types by a variety of stimuli including the inflammatory cytokines IL-1 and tumor necrosis factor alpha TNF-alpha. Several cis elements, including a binding site for the inducible transcription factor NF-kappa B, have been identified in the regulatory region of the IL-8 gene. We have examined the ability of various NF-kappa B subunits to bind to, and activate transcription from, the IL-8 promoter. A nuclear complex was induced in phorbol myristate acetate-treated Jurkat T cells which bound specifically to the kappa B site of the IL-8 promoter and was inhibited by addition of purified I kappa B alpha to the reaction mixture. Only antibody to RelA (p65), but not to NFKB1 (p50), NFKB2 (p50B), c-Rel, or RelB was able to abolish binding, suggesting that RelA is a major component in these kappa B binding complexes. Gel mobility shift analysis with in vitro-translated and purified proteins indicated that whereas the kappa B element in the human immunodeficiency virus type 1 long terminal repeat bound to all members of the kappa B/Rel family examined, the IL-8 kappa B site bound only to RelA and to c-Rel and NFKB2 homodimers, but not to NFKB1 homodimers or heterodimers of NFKB1-RelA. Transient transfection analysis demonstrated a kappa B-dependent expression of the IL-8 promoter in a human fibrosarcoma cell line (8387) and in Jurkat T lymphocytes. Cotransfection with various NF-kappa B subunits indicated that RelA and c-Rel, but neither NFKB1 nor heterodimeric NFKB1-RelA, was able to activate transcription from the IL-8 promoter. Furthermore, cotransfection of NFKB1 and RelA, although able to support activation from the human immunodeficiency virus type 1 long terminal repeat, failed to activate expression from the IL-8 promoter. Antisense oligonucleotides to RelA, but not NFKB1, inhibited phorbol myristate acetate-induced IL-8 production in Jurkat T lymphocytes. These data demonstrate the differential ability of members of the kappa B/Rel family to bind to, and activate transcription from, the IL-8 promoter. Furthermore, while providing a novel example of a kappa B-regulated promoter in which the classical NF-kappa B complex is unable to activate transcription from the kappa B element, these data provide direct evidence for the role of RelA in regulation of IL-8 gene expression.
A Possible Common Cell Surface Autoantigen in Islet .BETA.-Cells and Thyroid Follicular Cells in Patients with Non-lnsulin Dependent Diabetes Mellitus and Chronic Thyroiditis. (1996)

By an indirect immunofluorescence method with In-111 cells (hamster insulinoma cell line), circulating islet cell surface antibodies (ICSA) were detected in 7 (20%) out of 36 patients with non-insulin dependent diabetes mellitus (NIDDM), 9% of 68 chronic thyroiditis (CT) patients, or 16% of 19 NIDDM patients associated with CT, but not in 18 normal subjects. Sera from five out of nine ICSA-positive patients examined further also showed cell-surface immunofluorescence on TPC-1 cells (human thyroid papillary adenocarcinoma cell line), and prior absorption of the sera with In-111 cells abolished the immunofluorescence. The 64 kDa protein from In-111 cells or human thyroid follicular cells was immunoprecipitated with ICSA-positive sera. In one case of NIDDM associated with CT, 64 kDa protein was detected in both cells. The results indicate that some ICSA in NIDDM patients recognize the same or a very closely-related autoantigen(s) in both islet beta-cells and thyroid follicular cells, suggesting an explanation, at least in part, for the autoimmune mechanism(s) in clinical association of NIDDM and CT.
Linear and Branched PEIs (Polyethylenimines) and Their Property Space (2016)

A chemical property space defines the adaptability of a molecule to changing conditions and its interaction with other molecular systems determining a pharmacological response. Within a congeneric molecular series (compounds with the same derivatization algorithm and thus the same brute formula) the chemical properties vary in a monotonic manner, i.e., congeneric compounds share the same chemical property space. The chemical property space is a key component in molecular design, where some building blocks are functionalized, i.e., derivatized, and eventually self-assembled in more complex systems, such as enzyme-ligand systems, of which (physico-chemical) properties/bioactivity may be predicted by QSPR/QSAR (quantitative structure-property/activity relationship) studies. The system structure is determined by the binding type (temporal/permanent; electrostatic/covalent) and is reflected in its local electronic (and/or magnetic) properties. Such nano-systems play the role of molecular devices, important in nano-medicine. In the present article, the behavior of polyethylenimine (PEI) macromolecules (linear LPEI and branched BPEI, respectively) with respect to the glucose oxidase enzyme GOx is described in terms of their (interacting) energy, geometry and topology, in an attempt to find the best shape and size of PEIs to be useful for a chosen (nanochemistry) purpose.
ChemInform Abstract: REACTION OF NITRILES UNDER ACIDIC CONDITIONS. PART I. A GENERAL METHOD OF SYNTHESIS OF CONDENSED PYRIMIDINES (1981)

Abstract Aus (I) entstehen mit den Nitrilen (II) unter sauren Bedingungen die kondensierten Pyrimidine (III).
Spinning Continuous Fibers for Nanotechnology (2004)

Nanotubes of carbon and other materials are arguably the most fascinating materials playing an important role in nanotechnology today. Their unique mechanical, electronic, and other properties are expected to result in revolutionary new materials and devices. However, these nanomaterials, produced mostly by synthetic bottom-up methods, are discontinuous objects, and this leads to difficulties with their alignment, assembly, and processing into applications. Partly because of this, and despite considerable effort, a viable carbon nanotube–reinforced supernanocomposite is yet to be demonstrated. Advanced continuous fibers produced a revolution in the field of structural materials and composites in the last few decades as a result of their high strength, stiffness, and continuity, which, in turn, meant processing and alignment that were economically feasible. Fiber mechanical properties are known to substantially improve with a decrease in the fiber diameter. Hence, there is a considerable interest in the development of advanced continuous fibers with nanoscale diameters. However, conventional mechanical fiber spinning techniques cannot produce fibers with diameters smaller than about 2 μm robustly. Most commercial fibers are several times that diameter, owing to the trade-offs between the techno¬logical and economic factors.
A real-life clinical evaluation of a next-generation antimicrobial dressing on acute and chronic wounds (2014)

Objective: To assess the effectiveness of a new, next-generation antimicrobial dressing (AQUACEL Ag+ dressing) in facilitating healing in a variety of hard-to-heal wounds that may have been compromised by infection and/or biofilm. Method: This was an international, multi-centred, real-life, non-randomised evaluation involving patients with a wide variety of slow-, non-healing or deteriorating chronic and acute wounds. There were no strict inclusion or exclusion criteria and the clinicians were asked to use their discretion in the selection of patients. The clinicians continued to use their standard protocol of care but replaced their existing primary wound-contact dressing with the next-generation antimicrobial dressing (NGAD) for up to 4 weeks. Clinicians could extend the treatment period if this was deemed clinically appropriate. Baseline assessments included wound bed characteristics, exudate level, indicators of wound biofilm, and signs and symptoms of infection. At the final assessment, the investigators reported the wound size, wound bed characteristics, and exudate level. Results: A total of 121 patients were recruited into the original evaluation, of which eight were excluded for incomplete data sets. Most wounds (73; 64%) were either venous leg ulcers (59; 52%) or diabetic foot ulcers (14; 12%). At baseline, the wounds of (26; 23%) patients were slowly improving, 65 were stagnant (58%) and 22 (19%) were deteriorating. Just under three-quarters (74%) of the wounds had suspected biofilm (criteria including failure of a wound to heal, lack of response to topical and systemic antimicrobial agents, or the presence of slimy substances on the wound surface). Following the evaluations, the average wound closure achieved for all wounds was 72.6%, 19 (17%) wounds healed, 47 (42%) achieved at least 90% wound closure, and 71 (63%) achieved at least 75% closure. The average treatment period was 4.1 weeks; 35 wounds were treated with the dressing for more than 4 weeks. Cost analysis indicated that potential antimicrobial dressing cost reductions of approximately 30% were realised using the NGAD. Conclusion: This real-life, non-randomised evaluation provides encouraging evidence that the NGAD may have a role to play in facilitating wound progression towards healing by helping to eliminate the biofilm barrier. Declaration of interest: M. Walker, D. Metcalf, D. Parsons and P. Bowler are all employees of ConvaTec Ltd. Aysha Mendes da Mata is an independent writer and Annemarie Brown is an independent clinician, both received a fee and support from MA Healthcare to write up the evaluation using data supplied by ConvaTec.
Feedback for enhanced student performance: lessons from simple control theory (2012)

Students repeatedly express dissatisfaction with the feedback they receive, and academic staff express similar levels of frustration, with students not reading, let alone applying, the feedback they have spent so much time generating. The problems surrounding academic feedback are perhaps surprising, considering the ubiquitous and necessary nature of feedback in our everyday lives and our successful use of it without giving it much conscious thought. This paper investigates the comparison between the nature, value and use of feedback in simple control systems and the feedback offered to students in the academic world. It firstly considers how feedback is utilised to produce closed-loop control systems (compared to open-loop systems) and the advantages of this. It then discusses three aspects of the successful implementation of control system feedback (timeliness, appropriateness and application) and applies them to academic feedback, with a view to improving understanding and effectiveness in enhancing student performance. A case is made for student generated feedback and a trial is described which endeavoured to encourage this. Whilst recognising the complex nature of the role of feedback within the total student experience, an attempt is made to look afresh at the requirements of successful academic feedback from a novel perspective.
Autocatalytic Alkyne Cycloadditions:  Evidence for Colloidal Pt Catalysis (2005)

Treatment of the four-membered platinacycle L2Pt(1,8-naphthalendiyl) (1) or the five-membered platinacycle L2Pt(1,12-triphenylendiyl) with excess PhCCPh at 120-150 degrees C gives the coupling products 1,2-diphenylacenaphthalene or 4,5-diphenylbenzo[e]pyrene and the alkyne complex L2Pt(eta2-PhCCPh). Both reactions show an accelerating rate, which has been traced to catalysis of the reaction by colloidal platinum formed by the reaction of O2 with L2Pt(eta2-PhCCPh).
Adjunctive Dopamine Agonists in Treatment-Resistant Bipolar II Depression: an Open Case Series (2001)

From the results, PPX and RPN appear to be well tolerated and potentially useful in the adjunctive treatment of drug-resistant bipolar II depression.
The role of progenitor cells in repair of liver injury and in liver transplantation (2001)

There are three levels of cells in the hepatic lineage that respond to injury or carcinogenesis: the mature hepatocyte, the ductular "bipolar" progenitor cell, and a putative periductular stem cell. Hepatocytes are numerous, and respond rapidly to liver cell loss by one or two cell cycles but can only produce other hepatocytes. The ductular progenitor cells are less numerous, may proliferate for more cycles than hepatocytes, and are generally considered "bipolar," i.e., they can give rise to biliary cells or hepatocytes. Periductular stem cells are rare in the liver, have a very long proliferation potential, and may be multipotent. Extrahepatic (bone marrow) origin of the periductular stem cells is supported by recent data showing that hepatocytes may express genetic markers of donor hematopoietic cells after bone marrow transplantation. These different regenerative cells with variations in potential for proliferation and differentiation may provide different sources of cells for liver transplantation: hepatocytes for treatment of acute liver damage, liver progenitor cell lines for liver-directed gene therapy, and bone marrow-derived cells for chronic long-term liver replacement. A limiting factor in the success of liver cell transplantation is the condition of the hepatic microenvironment in which the cells must proliferate and set up housekeeping.
Identification of Clostridium difficile toxin B cardiotoxicity using a zebrafish embryo model of intoxication (2006)

Clostridium difficile toxin B (TcdB) has been studied extensively by using cell-free systems and tissue culture, but, like many bacterial toxins, the in vivo targets of TcdB are unknown and have been difficult to elucidate with traditional animal models. In the current study, the transparent Danio rerio (zebrafish) embryo was used as a model for imaging of in vivo TcdB localization and organ-specific damage in real time. At 24 h after treatment, TcdB was found to localize at the pericardial region, and zebrafish exhibited the first signs of cardiovascular damage, including a 90% reduction in systemic blood flow and a 20% reduction in heart rate. Within 72 h of exposure to TcdB, the ventricle chamber of the heart became deformed and was unable to contract or pump blood, and the fish exhibited extensive pericardial edema. In line with the observed defects in ventricle contraction, TcdB was found to directly disrupt coordinated contractility and rhythmicity in primary cardiomyocytes. Furthermore, using a caspase-3 inhibitor, we were able to block TcdB-related cardiovascular damage and prevent zebrafish death. These findings present an insight into the in vivo targets of TcdB, as well as demonstrate the strength of the zebrafish embryo as a tractable model for identification of in vivo targets of bacterial toxins and evaluation of novel candidate therapeutics.
Freeze-Dried Grape Powder Attenuates Mitochondria- and Oxidative Stress-Mediated Apoptosis in Liver Cells (2009)

The beneficial effects of grape consumption have been attributed to the antioxidant activity of its polyphenols. This study was conducted to investigate the cytoprotective effects of a freeze-dried grape powder (FDGP) on liver cells. FDGP treatment of primary hepatocytes and hepatoma cells revealed increased metabolic activity of cells and phosphorylation of Akt and IkappaBalpha, as well as up-regulation of proliferating cell nuclear antigen (PCNA) level. To study the molecular mechanisms of FDGP effects, cells were treated with TNF-related apoptosis-inducing ligand (TRAIL); taurodeoxycholic acid (TDCA); thapsigargin (TG), to induce cell apoptosis through death receptor-, mitochondria-, or ER-mediated pathway; and H(2)O(2), to induce oxidative stress, respectively. TDCA-induced activation of caspase-3, caspase-7, caspase-9, and Bax was dramatically decreased with cotreatment of FDGP. Furthermore, FDGP reduced levels of annexin V positive cells by 4-fold. Also, FDGP pretreatment restored cellular glutathione content by 71% in cells treated with H(2)O(2). However, FDGP did not inhibit ER-mediated apoptosis. In conclusion, FDGP increased the viability and metabolic activity of liver cells and attenuated oxidative stress- and mitochondria-mediated apoptosis. These data may contribute to the understanding of the mechanisms involved in protective effects of grape in a variety of liver conditions associated with cellular stress.
ChemInform Abstract: THE GROWTH‐INHIBITORY ACTION OF SOME 1‐AMINOISOQUINOLINES AND RELATED COMPOUNDS ON MYCOPLASMA GALLISEPTICUM (1976)

Abstract Die inhibierenden Aktivitäten der Isochinolinderivate (III)‐(V), die zumeist nach bekannten Verfahren dargestellt werden [z. B. aus entsprechenden Nitrilen (I) und (II)], auf das Wachstum von M. gallisepti‐ 311g werden untersucht.
Exposure to Ultraviolet B Radiation Increases the Tolerance of Mouse Skin to Daily X Irradiation (1996)

Based on the hypothesis that acceleration of repopulation in skin during fractionated irradiation is triggered by an inflammatory response of the dermis to radiation-induced epidermal hypoplasia, we produced a mild erythema by exposure to UVB radiation before applying different X-irradiation schedules. At different times ranging from 6 h to 14 days after a single exposure to UVB radiation which caused a distinct erythema, a 2-cm skin field on the legs of mice was irradiated with either different single doses or five daily fractions of 3 Gy followed by different single top-up doses of 300 kV X rays. Skin reactions were scored daily for 4 weeks and the occurrence of moist desquamation was taken to construct dose-response curves and to calculate ED50 values. Five days after exposure to UVB radiation and later, radioresistance of epidermis to single and fractionated X irradiation was significantly increased. Results were analyzed using the linear-quadratic formalism to identify possible mechanisms for this UV-radiation-induced radioresistance. The data suggest that exposure to UVB radiation led to a gradual increase in the number of epidermal stem cells and their repopulation rate.
Characterization of Arabidopsis ZIM, a member of a novel plant-specific GATA factor gene family (2004)

The Arabidopsis gene ZIM encodes a putative transcription factor containing a novel GATA-type zinc-finger domain with a longer spacer between its two sets of conserved cysteine residues (C-X2-C-X20-C-X2-C). In Arabidopsis, ZIM and homologous proteins, ZML1 and ZML2, were identified as GATA factors containing the C-X2-C-X20-C-X2-C motif, a CCT domain, and an uncharacterized conserved domain. Proteins that possess this domain structure were found exclusively in plants, indicating that they belong to a novel family of plant-specific GATA-type transcription factors. When ZIM was overexpressed using a CaMV 35S promoter in Arabidopsis, hypocotyls and petioles were elongated. The elongation phenotype was observed under all wavelengths of light tested and even in the presence of biosynthetic inhibitors of either brassinosteroid or gibberellin. In ZIM-overexpressing plants, XTH33 which is predicted to function in cell wall modification was detected as an up-regulated gene by microarray analysis, and this could account for the elongation phenotype. Genes in ZIM-overexpressing plants were identified that were up-regulated in a tissue-specific manner, which suggests that transcriptional regulation by ZIM and its consequent effects are spatially controlled.
Identification and Expression of a Rat Fatty Acid Elongase Involved in the Biosynthesis of C18 Fatty Acids (2002)

A major part of the palmitic acid (C16:0) generated by fatty acid synthase is converted into stearic acid (C18:0) via carbon chain elongation. Here, we describe the cloning and expression of a rat hepatic enzyme, rELO2, responsible for the elongation of C16:0, presumably at the condensing reaction. Heterologous expression experiments in a yeast, Saccharomyces cerevisiae, demonstrated the elongation activity of rELO2 on C16:0 and to a lesser extent, C18:0 and fatty acids with low desaturation degree. This was distinct from that rELO1, a rat homolog of HELO1, which preferably catalyzed the elongation of mono- and polyunsaturated fatty acids of C16–C20. The Northern analysis showed that the expression of rELO2, but not rELO1, in hepatocytes was activated by the cycles of fasting and refeeding rats on a fat-free diet. Under these conditions, the rELO1 was expressed constitutively in various tissues but the rELO2 transcripts were detected predominantly in liver.
Assessment of the pulmonary origin of bronchoconstrictor vagal tone (1979)

1. In anaesthetized spontaneously breathing cats, the sensory component of the vagal nerves was sectioned at the level of nodose ganglion, using a method described previously (Mei, 1966; Mei & Dussardier, 1966).2. The strength of the Hering-Breuer reflex (inhibitory ratio, i.e. T(1)/T(0)) provided a test for effectiveness of section of vagal afferents, particularly respiratory afferents. On the other hand, by studying the cardiac and bronchomotor effects induced by electrical stimulation of the supranodose portion of the vagal nerve, it was possible to test the integrity of the efferent vagal component.3. Unilateral right sensory vagotomy was followed by a 29% reduction in total pulmonary resistance.4. Section of the contralateral sensory vagal component (sensory bivagotomy), produced a weak supplementary effect (total decrease of total pulmonary resistance: 31%).5. No additive bronchomotor effect could be observed after the bilateral section of efferent vagal fibres (total bivagotomy).6. In intact cats, blockade of the two vagal nerves by procaine induced a decrease in pulmonary resistance similar to those produced by the sensory bivagotomy (23%). This bronchodilatator effect was concomitant with a complete disappearance of the C wave of the compound vagal potential.7. Intravenous injection of phenyl diguanide, immediately after the blockade of the C vagal fibres by procaine did not modify bronchomotor tone. This result confirms that the C pulmonary afferents, which are activated by phenyl diguanide, are mainly involved in this mechanism.8. The pulmonary irritant receptors seem to play a minor role. In fact, the I.V. administration of histamine under the same conditions, provides evidence that the corresponding neurones (small sized myelinated fibres) are potent during the procaine application.9. From these results, it appears that bronchoconstrictor vagal tone has an exclusive peripheral origin and that pulmonary endings, in particular those connected with non-medullated fibres, are probably involved in this mechanism.