gebhart/patrepeval huggingface dataset:
Die spezifische Immuntherapie (Hyposensibilisierung) mit Allergenen1 - Positionspapier der Deutschen Gesellschaft für Allergologie und klinische Immunologieinhaltlich abgestimmt mit dem Ärzteverband Deutscher Allergologen - (2001)

Mechanisms of allergen immunotherapy (AIT) are complex inducing numerous immunological effects. Successful AIT is most likely based on a functional switch of and tolerance induction in specific T cells downregulating allergic hypersensitivity and inflammation. Subcutaneous AIT for allergic rhinoconjunctivitis and allergic asthma has been successfully assessed in controlled studies with several clinically important allergens (i. e. birch-, grass- and mugwortpollen, dust mites, animal dander) and has shown convincing clinical efficacy. Considered as the only causal treatment besides allergen avoidance at present, AIT can alter the natural course of allergic diseases. Hymenopteravenom hypersensitivity (to bee- and wasp venom) treated with AIT gives the best results compared to AIT with other allergens. AIT is indicated in patients with IgE-mediated sensitizations and corresponding clinical symptoms to allergens, which do not or hardly permit allergen avoidance and which are available as suitable extracts. Decisions about indication and allergen selection should only be made by a physician with certified training or qualified knowledge and skills in allergology. AIT is administered by physicians experienced in this therapy. After addressing tolerability and present status of health the recommended or individually adjusted does is injected and precisely documented, followed by a mandatory waiting period of 30 minutes. Indication for and application of AIT in children are quite similar compared to the treatment of adults. Children tolerate AIT very well and benefit especially from its immunomodulatory effects. Risk factors for and results of unwanted systemic effects can effectively be minimized by training of the staff members involved, adhering to safety standards and immediate emergency treatment. Modified allergens, recombinant proteins and immunomodulatory adjuvants created by basic research are promises for an improved efficacy of AIT with reduced unwanted effects in the future.
Charge Transfer–Mediated Singlet Fission (2015)

Singlet fission, the splitting of a singlet exciton into two triplet excitons in molecular materials, is interesting not only as a model many-electron problem, but also as a process with potential applications in solar energy conversion. Here we discuss limitations of the conventional four-electron and molecular dimer model in describing singlet fission in crystalline organic semiconductors, such as pentacene and tetracene. We emphasize the need to consider electronic delocalization, which is responsible for the decisive role played by the Mott-Wannier exciton, also called the charge transfer (CT) exciton, in mediating singlet fission. At the strong electronic coupling limit, the initial excitation creates a quantum superposition of singlet, CT, and triplet-pair states, and we present experimental evidence for this interpretation. We also discuss the most recent attempts at translating this mechanistic understanding into design principles for CT state-mediated intramolecular singlet fission in oligomers and polymers.
Processing and characterization of microcellular foamed high‐density polythylene/isotactic polypropylene blends (1998)

Abstract In this paper, a study on the batch processing and characterization of microcellular foamed high‐density polyethylene (HDPE/iPP) blends is reported. A microcellular plastic is a foamed polymer with a cell density greater than 10 9 cells/cm 3 and fully grown cells smaller than 10 µm. Recent studies have shown that the morphology and crystallinity of semicrystalline polymers have a great influence on the solubility and diffusivity of the blowing agent and on the cellular structure of the resulting foam in microcellular batch processing. In this research, blends of HDPE and iPP were used to produce materials with variety of crystalline and phase morphologies to enhance the subsequent microcellular foaming. It was possible to produce much finer and more uniform foams with the blends than with neat HDPE and iPP. Moreover, the mechanical properties and in particular the impact strength of the blends were significantly improved by foaming.
CD39 Expression Identifies Terminally Exhausted CD8+ T Cells (2015)

Exhausted T cells express multiple co-inhibitory molecules that impair their function and limit immunity to chronic viral infection. Defining novel markers of exhaustion is important both for identifying and potentially reversing T cell exhaustion. Herein, we show that the ectonucleotidse CD39 is a marker of exhausted CD8+ T cells. CD8+ T cells specific for HCV or HIV express high levels of CD39, but those specific for EBV and CMV do not. CD39 expressed by CD8+ T cells in chronic infection is enzymatically active, co-expressed with PD-1, marks cells with a transcriptional signature of T cell exhaustion and correlates with viral load in HIV and HCV. In the mouse model of chronic Lymphocytic Choriomeningitis Virus infection, virus-specific CD8+ T cells contain a population of CD39high CD8+ T cells that is absent in functional memory cells elicited by acute infection. This CD39high CD8+ T cell population is enriched for cells with the phenotypic and functional profile of terminal exhaustion. These findings provide a new marker of T cell exhaustion, and implicate the purinergic pathway in the regulation of T cell exhaustion.
Phase III Randomized Trial of Amifostine as a Radioprotector in Head and Neck Cancer (2000)

Amifostine reduced acute and chronic xerostomia. Antitumor treatment efficacy was preserved.
Agonist‐inverse agonist characterization at CB1 and CB2 cannabinoid receptors of L759633, L759656 and AM630 (1999)

We have tested our prediction that AM630 is a CB2 cannabinoid receptor ligand and also investigated whether L759633 and L759656, are CB2 receptor agonists. Binding assays with membranes from CHO cells stably transfected with human CB1 or CB2 receptors using [3H]-CP55940, confirmed the CB2-selectivity of L759633 and L759656 (CB2/CB1 affinity ratios = 163 and 414 respectively) and showed AM630 to have a Ki at CB2 receptors of 31.2 nM and a CB2/CB1 affinity ratio of 165. In CB2-transfected cells, L759633 and L759656 were potent inhibitors of forskolin-stimulated cyclic AMP production, with EC50 values of 8.1 and 3.1 nM respectively and CB1/CB2 EC50 ratios of > 1000 and > 3000 respectively. AM630 inhibited [35S]-GTPgammaS binding to CB2 receptor membranes (EC50 = 76.6 nM), enhanced forskolin-stimulated cyclic AMP production in CB2-transfected cells (5.2 fold by 1 microM), and antagonized the inhibition of forskolin-stimulated cyclic AMP production in this cell line induced by CP55940. In CB1-transfected cells, forskolin-stimulated cyclic AMP production was significantly inhibited by AM630 (22.6% at 1 microM and 45.9% at 10 microM) and by L759633 at 10 microM (48%) but not 1 microM. L759656 (10 microM) was not inhibitory. AM630 also produced a slight decrease in the mean inhibitory effect of CP55940 on cyclic AMP production which was not statistically significant. We conclude that AM630 is a CB2-selective ligand that behaves as an inverse agonist at CB2 receptors and as a weak partial agonist at CB1 receptors. L759633 and L759656 are both potent CB2-selective agonists.
BET N-terminal bromodomain inhibition selectively blocks Th17 cell differentiation and ameliorates colitis in mice (2017)

T-helper 17 (Th17) cells have important functions in adaptor immunity and have also been implicated in inflammatory disorders. The bromodomain and extraterminal domain (BET) family proteins regulate gene transcription during lineage-specific differentiation of naïve CD4<sup>+</sup> T cells to produce mature T-helper cells. Inhibition of acetyl-lysine binding of the BET proteins by pan-BET bromodomain (BrD) inhibitors, such as JQ1, broadly affects differentiation of Th17, Th1, and Th2 cells that have distinct immune functions, thus limiting their therapeutic potential. Whether these BET proteins represent viable new epigenetic drug targets for inflammatory disorders has remained an unanswered question. In this study, we report that selective inhibition of the first bromodomain of BET proteins with our newly designed small molecule MS402 inhibits primarily Th17 cell differentiation with a little or almost no effect on Th1 or Th2 and Treg cells. MS402 preferentially renders Brd4 binding to Th17 signature gene loci over those of housekeeping genes and reduces Brd4 recruitment of p-TEFb to phosphorylate and activate RNA polymerase II for transcription elongation. We further show that MS402 prevents and ameliorates T-cell transfer-induced colitis in mice by blocking Th17 cell overdevelopment. Thus, selective pharmacological modulation of individual bromodomains likely represents a strategy for treatment of inflammatory bowel diseases.
Internal Breakers for Viscoelastic-Surfactant Fracturing Fluids (2007)

Abstract Over the past two decades, viscoelastic surfactant (VES) fluids used for gravel packing, frac-packing and conventional hydraulic fracturing have primarily relied on external or reservoir conditions to break the fluid’s viscosity. Unlike polymeric fluids, no internal breakers have been used. Relying on external conditions to break VES fluid has been a point of contention and questionable, especially for dry gas applications. This paper describes how new internal breaker technology has been developed that allows VES fluids to be broken into easily producible fluids, without the need for contacting reservoir hydrocarbons. The reservoir pressure required to produce VES fluid is no longer compromised: very little pressure or time is required when an internal breaker is present. Mechanisms for internally breaking VES viscosity are discussed. New internal breakers have been found to work over a wide fluid temperature and mix water salinity range, and have compatible with newly developed VES stabilizers and fluid loss control agents. Presented are laboratory results that compare VES fluids with and without an internal breaker. Rheological data is presented that show the performance of internal breakers in degrading VES fluid viscosity, in particular at low fluid shear rates. Core clean-up tests were performed at 150°F, using 3% KCl brine and nitrogen gas as the displacement (clean-up) fluid. The results show that use of an internal breaker significantly improves VES fluid clean-up. This paper also presents VES system compatibility and proppant conductivity results.
Glaucoma: Biological Trabecular and Neuroretinal Pathology with Perspectives of Therapy Innovation and Preventive Diagnosis (2017)

Glaucoma is a common degenerative disease affecting <i>retinal ganglion cells</i> (RGC) and optic nerve axons, with progressive and chronic course. It is one of the most important reasons of social blindness in industrialized countries. Glaucoma can lead to the development of irreversible visual field loss, if not treated. Diagnosis may be difficult due to lack of symptoms in early stages of disease. In many cases, when patients arrive at clinical evaluation, a severe neuronal damage may have already occurred. In recent years, newer perspective in glaucoma treatment have emerged. The current research is focusing on finding newer drugs and associations or better delivery systems in order to improve the pharmacological treatment and patient compliance. Moreover, the application of various stem cell types with restorative and neuroprotective intent may be found appealing (intravitreal autologous cellular therapy). Advances are made also in terms of parasurgical treatment, characterized by various laser types and techniques. Moreover, recent research has led to the development of central and peripheral retinal rehabilitation (featuring residing cells reactivation and replacement of defective elements), as well as innovations in diagnosis through more specific and refined methods and inexpensive tests.
Clinical Implications of Circulating Angiogenic Factors in Cancer Patients (2001)

Circulating VEGF seems to be a reliable surrogate marker of angiogenic activity and tumor progression in cancer patients. Evaluation of circulating angiogenic factors is a promising novel approach of prognostication in cancer patients that has the advantages of being convenient and noninvasive, and it may provide new prognostic information that is not afforded by conventional clinicopathologic prognostic indicators.
Layered Microbial Communities and the Search for Life in the Universe (2003)

Searching for life when we do not know what it is like is at best a difficult task, and at worst, an exercise fraught with frustration and potential failure. In developing methods that will have general applicability, one must ascertain first what the general features of life might be that, when present, would provide strong inference of the presence of active life. We propose here that the tendency of life to be associated with energetic gradients, in fact to create its own gradients via the catalytic consumption of nutrients and oxidants, and the production of waste products, is one of the general features of active extant life. As life seeks out and creates such gradients, layered microbial communities, or LMCs, result that are in their own way, prima facie biosignatures. These LMCs are abundant, perhaps ubiquitous in physically stratified environments on our own planet. If energy flows through a given system, and if life has developed efficient catalytic methods to utilize this energy, then LMCs are predicted to be present. Here we discuss the general issues of what can be gleaned from the study of LMCs in terms of energy flow, carbon flow, and carbon storage in earthly ecosystems, as well as the philosophy of using LMCs as biosignatures in the search for life on Earth, and perhaps, in extraterrestrial sites.
Pyrrolidone carboxyl peptidase (Pcp): An enzyme that removes pyroglutamic acid (pGlu) from pGlu‐peptides and pGlu‐proteins (1994)

Pyrrolidone carboxyl peptidase (EC 3.4.11.8) is an exopeptidase commonly called PYRase, which hydrolytically removes the pGlu-proteins. pGlu also known as pyrrolidone carboxylic acid may occur naturally by an enzymatic procedure or may occur as an artifact in proteins or peptides. The enzymatic synthesis of pGlu suggests that this residue may have important biological and physiological functions. Several studies are consistent with this supposition. PYRase has been found in a variety of bacteria, and in plant, animal, and human tissues. For over two decades, biochemical and enzymatic properties of PYRase have been investigated. At least two classes of PYRase have been characterized. The first one includes the bacterial and animal type I PYRases and the second one the animal type II and serum PYRases. Enzymes from these two classes present differences in their molecular weight and in their enzymatic properties. Recently, the genes of PYRases from four bacteria have been cloned and characterized, allowing the study of the primary structure of these enzymes, and their over-expression in heterelogous organisms. Comparison of the primary structure of these enzymes revealed striking homologies. Type I PYRases and bacterial PYRases are generally soluble enzymes, whereas type II PYRases are membrane-bound enzymes. PYRase II appears to play as important a physiological role as other neuropeptide degrading enzymes. However, the role of type I and bacterial PYRases remains unclear. The primary application of PYRase has been its utilization for some protein or peptide sequencing. Development of chromogenic substrates for this enzyme has allowed its use in bacterial diagnosis.
TAAABLE: Text Mining, Ontology Engineering, and Hierarchical Classification for Textual Case-Based Cooking (2008)

International audience
Involvement of p21cip-1 and p27kip-1 in the molecular mechanisms of steel factor-induced proliferative synergy in vitro and of p21cip-1 in the maintenance of stem/progenitor cells in vivo (1996)

Steel factor (SLF) is a hematopoietic cytokine that synergizes with other growth factors to induce a greatly enhanced proliferative state of hematopoietic progenitor cells and factor-dependent cell lines. Even though the in vivo importance of SLF in the maintenance and responsiveness of stem and progenitor cells is well documented, the molecular mechanism involved in its synergistic effects are mainly unknown. Some factor-dependent myeloid cell lines respond to the synergistic proliferative effects of SLF plus other cytokines in a manner similar to that of normal myeloid progenitor cells from bone marrow and cord blood. We show here that SLF can synergize with granulocyte-macrophage colony-stimulating factor (GM-CSF) to induce an enhanced phosphorylation of the retinoblastoma gene product and a synergistic increase in the total intracellular protein level of the cyclin-dependent kinase inhibitor, p21cip-1, which is correlated with a simultaneous decrease in p27kip-1 in the human factor-dependent myeloid cell line, M07e. Moreover, these cytokines synergize to increase p21cip- 1 binding and decrease p27kip-1 binding to cyclin-dependent kinase-2 (cdk2), an enzyme required for normal cell cycle progression; these inverse events correlated with increased cdk2 kinase activity. It is also shown that exogenous purified p21cip-1 can displace p27kip-1 already bound to cdk2 in vitro. These data implicate increased p21cip-1 and decreased p27kip-1 intracellular concentrations and their stoichiometric interplay in the enhanced proliferative status of cells stimulated by the combination of SLF and GM-CSF. In support of these findings, it is shown that hematopoietic progenitor cells from mice lacking p21cip-1 are defective in SLF synergistic proliferative response in vitro. Moreover, the cycling status of marrow and spleen progenitors and absolute numbers of marrow progenitors were significantly decreased in the p21cip-1 -/-, compared with the +/+ mice. We conclude that the cdk threshold regulators p21cip-1 and p27kip- 1 play a critical role in the normal mitogenic response of M07e cells and murine myeloid progenitor cells to these cytokines and particularly in the SLF synergistic proliferative response that is important to the normal maintenance of the stem/progenitor cell compartment.
The 3′‐UTR of the mRNA coding for the major protein kinase C substrate MARCKS contains a novel CU‐rich element interacting with the mRNA stabilizing factors HuD and HuR (2002)

The expression of the major protein kinase C substrate MARCKS (myristoylated alanine-rich C kinase substrate) is controlled by the stability of its mRNA. While the MARCKS mRNA is long living in quiescent fibroblasts (t1/2 = 14 h), its half-life time is drastically reduced (t1/2 = 2 h) in cells treated with phorbol esters to activate protein kinase C (PKC) or treated with growth factors. In a first step to study the underlying mechanism we identified both a cis-element on the MARCKS mRNA and the corresponding trans-acting factors. Fusing the complete 3'-UTR or specific regions of the 3'-UTR of the MARCKS gene to a luciferase reporter gene caused a drastic decrease in luciferase expression to as low as 5-10% of controls. This down-regulation was a result of destabilization of the chimeric transcript as shown by RNA run-off and Northern blot-assays. By RNase/EMSA and UV-cross-linking experiments, we identified a stretch of 52 nucleotides [(CUUU)11(U)8] in the 3'-UTR of the MARCKS mRNA specifically recognized by two RNA-binding proteins, HuD and HuR. These trans-acting factors are members of the ELAV gene family and bind the MARCKS CU-rich sequence with high affinity. Overexpression of HuD and HuR in murine fibroblasts caused a striking stabilization of the endogenous MARCKS mRNA even under conditions when the MARCKS mRNA is normally actively degraded, i.e. after treating cells with phorbol ester. These data imply, that the identified CU-rich cis-element of the MARCKS 3'-UTR is involved in conferring instability to mRNAs and that members of the ELAV gene family oppose this effect. Based on its structural and functional properties, the (CUUU)11(U)8 sequence described here can be grouped into class III of AU-rich elements.
Combination of MUC5ac and WT‐1 immunohistochemistry is useful in distinguishing pancreatic ductal carcinoma from ovarian serous carcinoma in effusion cytology (2009)

Malignant ascites may be the first presentation of an unsuspected cancer. Pancreas and ovary are among the organs that are usually evaluated as a source of primary. The purpose of this study is to investigate a panel of immunohistochemical stains to help differentiate pancreatic from ovarian carcinoma. We evaluated the immunohistochemical staining of eight commercially available antibodies MUC1, MUC2, MUC5ac, Wilm's tumor susceptibility gene 1 (WT1), cytokeratin 7 (CK7), CK20, CA125, and CA19.9 in 25 effusion specimens with evidence of metastatic carcinoma including 14 ovarian serous carcinomas, 9 pancreatic adenocarcinomas, and 2 unknown primaries. Primary ovarian serous carcinomas were positive for WT-1 (100%), CK7 (93%), CK20 (43%), CA125 (100%), CA19.9 (50%), MUC1 (100%), MUC2 (0%), and MUC5ac (0%). Primary pancreatic carcinomas were positive for MUC5ac (100%), MUC1 (100%), CA19.9 (100%), CK7 (78%), CK20 (22%), CA125 (89%), WT-1 (0%), and MUC 2 (0%). The combination of MUC5ac positivity/WT-1 negativity was seen in 100% of pancreatic carcinoma, whereas MUC5ac negativity/WT-1 positivity in 100% of ovarian serous carcinoma. It appears that the combination of MUC5ac and WT-1 stains is useful in distinguishing pancreatic ductal from ovarian serous carcinoma in body fluid cytology.
Requirement for Transcription Factor IRF-1 in NO Synthase Induction in Macrophages (1994)

Production of nitric oxide (NO) by macrophages is important for the killing of intracellular infectious agents. Interferon (IFN)-gamma and lipopolysaccharide stimulate NO production by transcriptionally up-regulating the inducible NO synthase (iNOS). Macrophages from mice with a targeted disruption of the IFN regulatory factor-1 (IRF-1) gene (IRF-1-/- mice) produced little or no NO and synthesized barely detectable iNOS messenger RNA in response to stimulation. Two adjacent IRF-1 response elements were identified in the iNOS promoter. Infection with Mycobacterium bovis (BCG) was more severe in IRF-1-/- mice than in wild-type mice. Thus, IRF-1 is essential for iNOS activation in murine macrophages.
Controlled Surface-Initiated Polymerizations in Aqueous Media (2001)

The rapid, controlled formation of thick brushes (up to 125 nm thick) from self- assembled monolayer-bound initiators under mild conditions using aqueous solutions is demonstrated. Atom transfer radical polymerization (ATRP) has been employed to create polymers and copolymers from surfaces (see Figure). This technology may lead to molecular “ultra-glues” for adhesion to suitable substrates.
Danazol Therapy in Immune Thrombocytopenic Purpura (1990)

Nine children with chronic refractory immune thrombocytopenic purpura and moderate to severe episodes of bleeding were treated with Danazol in an attempt to increase their platelet counts and improve clinical hemostasis. Only one patient experienced an excellent response while a good response was obtained in another. Cessation of bleeding episodes was observed in two other children with only marginal increases in platelet counts. Four of the nine patients failed to show any clinical or hematological improvement. The drug was well tolerated but its efficacy in childhood ITP needs further evaluation.