gebhart/patrepeval huggingface dataset:
Effect of different culture conditions and inducers on production of laccase by a basidiomycete fungal isolate Pleurotus ostreatus HP-1 under solid state fermentation (2009)

The production of laccase by an indigenous strain of Pleurotus ostreatus HP-1 was studied on solid state fermentation. Culture parameters such as type and concentration of substrate, inoculum size, moisture content, pH, surfactant presence, temperature, and nitrogen source were optimized by conventional “one factor at a time” methodology. A maximum laccase yield of 3952 U g-1 of dry substrate optimized was obtained with wheat straw as substrate with five agar plugs as the inoculum, 60% moisture content, pH 5.0, surfactant concentration 0.015 gl-1, and nitrogen source (combination of L-asparagine and NH4NO3 at 10 mM concentration each) at incubation temperature 28oC. Enhancement in laccase activity was achieved with the use of various aromatic inducers and copper sulphate. Highest laccase activity of 14189 U g-1 of dry substrate was achieved using 0.28 mM copper sulphate under optimized conditions. Thus, the indigenous isolate seems to be a potential producer of laccase using SSF and can be exploited for further biotechnological applications. The process also promises economic utilization and value addition of agro-residues.
Prevalence and Clinical Significance of Her-2/neu, p53 and Rb Expression in Primary Superficial Bladder Cancer (1996)

Our study demonstrates the low prevalence of HER2/neu, p53 and altered Rb expression in superficial TCC at initial resection. Only p53 expression was significantly associated with an earlier first tumor recurrence, but this association was not independent of other prognostic factors.
High sensitivity of human melanoma cell lines to the growth inhibitory activity of mycoplasmal arginine deiminase in vitro (1992)

Arginine deiminase (AD) is a potent growth inhibitor for some but not all tumour cell lines in vitro. As AD catalyses the direct conversion of L-arginine to L-citrulline, the AD-sensitivity of various tumour cells might be attributed to the levels of urea cycle enzymes involved in L-arginine biosynthesis. This study demonstrated that human melanoma cells were highly sensitive to the growth inhibitory activity of AD. Five melanoma cell lines tested also exhibited reduced argininosuccinate synthetase (ASS) gene expression--being almost absent in four cell lines and at low level in one cell line. This resulted in an inability of the cells to utilize L-citrulline for growth. Based on the tissue-specific regulation of ASS gene, the feature of melanomas suggests that it might be possible to develop agents with strong AD activity for chemotherapeutic use for human melanomas in vivo.
Periplasmic protein related to the sn-glycerol-3-phosphate transport system of Escherichia coli (1976)

Two-dimensional gel electrophoresis of shock fluids of Escherichia coli K-12 revealed the presence of a periplasmic protein related to sn-glycerol-3-phosphate transport (GLPT) that is under the regulation of glpR, the regulatory gene of the glp regulon. Mutants selected for their resistance to phosphonomycin and found to be defective in sn-glycerol-3-phosphate transport either did not produce GLPT or produced it in reduced amounts. Other mutations exhibited no apparent effect of GLPT. Transductions of glpT+ nalA phage P1 into these mutants and selection for growth on sn-glycerol-3-phosphate revealed a 50% cotransduction frequency to nalA. Reversion of mutants taht did not produce GLPT to growth on sn-glycerol-3-phosphate resulted in strains that produce GLPT. This suggests a close relationship of GLPT to the glpT gene and to sn-glycerol-3-phosphate transport. Attempts to demonstrate binding activity of GLPT in crude shock fluid towards sn-glycerol-3-phosphate have failed so far. However, all shock fluids, independent of their GLPT content, exhibited an enzymatic activity that hydrolyzes under the conditions of the binding assay, 30 to 60% of the sn-glycerol-3-phosphate to glycerol and inorganic orthophosphate.
Mechanisms of Contrast in NMR Imaging (1984)

Nuclear magnetic resonance pixel intensity and contrast-to-noise has been computed and presented in graphical form for various tissues in the normal central nervous system, on the assumption that the signal intensity is proportional to the macroscopic transverse spin magnetization at the time of detection. T1, T2, and spin density values were experimentally determined using chi-square minimization techniques. Additionally, spin density was derived from partial saturation scans obtained with a long repetition time compared with the spin-lattice relaxation time. Pulse sequences discussed comprise partial saturation, saturation recovery, spin echo, and Carr- Purcell - Meiboom -Gill ( CPMG ). The complicated dependence of signal and contrast-to-noise on the pulse timing parameters and the specific pulse sequence makes it appear desirable to display image intensity so that the dependence on the extrinsic (operator-selectable parameter) is eliminated. Whereas T2 images can be derived from CPMG scans without excessive time penalty, this is not the case for T1 and spin density.
Sub‐lingual Immunotherapy: World Allergy Organization Position Paper 2009 (2009)

Udgivelsesdato: 2009-Dec
Molecular modeling studies of HIV‐1 reverse transcriptase nonnucleoside inhibitors: Total energy of complexation as a predictor of drug placement and activity (1995)

Computer modeling studies have been carried out on three nonnucleoside inhibitors complexed with human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT), using crystal coordinate data from a subset of the protein surrounding the binding pocket region. Results from the minimizations of solvated complexes of 2-cyclopropyl-4-methyl-5,11-dihydro-5H-dipyrido[3,2-b :2',3'-e][1,4] diazepin-6-one (nevirapine), alpha-anilino-2, 6-dibromophenylacetamide (alpha-APA), and 8-chloro-tetrahydro-imidazo(4,5,1-jk)(1,4)-benzodiazepin-2(1H)-thi one (TIBO) show that all three inhibitors maintain a very similar conformational shape, roughly overlay each other in the binding pocket, and appear to function as pi-electron donors to aromatic side-chain residues surrounding the pocket. However, side-chain residues adapt to each bound inhibitor in a highly specific manner, closing down around the surface of the drug to make tight van der Waals contacts. Consequently, the results from the calculated minimizations reveal that only when the inhibitors are modeled in a site constructed from coordinate data obtained from their particular RT complex can the calculated binding energies be relied upon to predict the correct orientation of the drug in the pocket. In the correct site, these binding energies correlate with EC50 values determined for all three inhibitors in our laboratory. Analysis of the components of the binding energy reveals that, for all three inhibitors, solvation of the drug is endothermic, but solvation of the protein is exothermic, and the sum favors complex formation. In general, the protein is energetically more stable and the drug less stable in their complexes as compared to the reactant conformations. For all three inhibitors, interaction with the protein in the complex is highly favorable. Interactions of the inhibitors with individual residues correlate with crystallographic and site-specific mutational data. pi-Stacking interactions are important in binding and correlate with drug HOMO RHF/6-31G* energies. Modeling results are discussed with respect to the mechanism of complex formation and the design of nonnucleoside inhibitors that will be more effective against mutants of HIV-1 RT that are resistant to the currently available drugs.
Ubiquitous B-Tree (1979)

B-trees have become, de facto, a standard for file organization. File indexes of users, dedicated database systems, and general-purpose access methods have all been proposed and nnplemented using B-trees This paper reviews B-trees and shows why they have been so successful It discusses the major variations of the B-tree, especially the B+-tree, contrasting the relatwe merits and costs of each implementatmn. It illustrates a general purpose access method whmh uses a B-tree.
Chimeric infectious bursal disease virus-like particles expressed in insect cells and purified by immobilized metal affinity chromatography (1999)

Chimeric virus-like particles (VLPs) of infectious bursal disease virus (IBDV) were produced by coinfecting Spodoptera frugiperda (Sf-9) insect cells with two recombinant baculoviruses, vIBD-7 and vEDLH-22. vIBD-7 encodes VP2, VP3, and VP4 of the IBDV structural proteins. vEDLH-22 encodes VP2 with five histidine residues at the carboxy-terminus (VP2H). Coinfection produced hybrid VLPs composed of VP2, VP2H, and VP3. The additional histidine residues on VP2H enabled the efficient purification of VLPs based on immobilized metal affinity chromatography (IMAC). These results demonstrated that the VLPs formed are comprised of chimeric subunits with attached affinity ligands, and further, that sufficient His5 ligand was available for binding to the IMAC metal-chelating resin. Additionally, these novel particles were fully characterized for antigenicity by a series of monoclonal antibodies, and appeared identical to the two wild-type IBDV strains contributing subunits to the chimeric VLP. IMAC purification provides a promising low-cost and simple scheme to purify VLPs as vaccines.
Effect of Urodilatin Infusion on Renal Haemodynamics, Tubular Function and Vasoactive Hormones (1997)

1. The renal efficacy of urodilatin in humans has only been partly investigated. It is unknown whether intravenously infused urodilatin has an effect on sodium reabsorption in both the proximal and distal part of the nephron. 2. Twelve healthy subjects participated in this double-blind, placebo-controlled study in a cross-over design. They received, in a randomized order, a short term (60 min) infusion of urodilatin in three different doses (10, 20 and 40 ng min-1 kg-1 of body weight) and placebo. Renal haemodynamics were estimated by clearance technique with radioactive tracers, and proximal tubular handling of sodium was evaluated by lithium clearance. 3. The 20 ng min-1 kg-1 dose increased the urinary sodium excretion and urinary flow rate compared with the effects of placebo. It increased the glomerular filtration rate and decreased the effective renal plasma flow. In addition, the dose increased the lithium clearance compared with placebo, but did not significantly change the fractional excretion of lithium. On the other hand, it markedly decreased the distal fractional reabsorption of sodium. It also had a suppressive effect on renin secretion. The systemic arterial blood pressure was unchanged, but the dose increased the pulse rate and the haematocrit. The highest dose (40 ng min-1 kg-1) induced a wide variation in the natriuretic and diuretic responses, probably due to a blood-pressure-lowering effect. 4. We conclude, that the urodilatin dose of 20 ng min-1 kg-1 of body weight was most efficacious in this short-term infusion study, and that it had potent natriuretic and diuretic qualities, probably due to stimulation of the glomerular filtration rate and inhibition of sodium reabsorption in the distal part of the nephron.
Severe immune-related adverse effects (irAE) requiring hospital admission in patients treated with immune checkpoint inhibitors for advanced malignancy: Temporal trends and clinical significance. (2018)

3096 Background: Disruption of the immune system using immune checkpoint inhibitors can result in a multitude of immune-related adverse effects (irAE). While irAEs have been well-reported in clinical trials, the impact and magnitude in the real world is unclear. Methods: Data was collected on patients with advanced malignancy who experienced a suspected irAE requiring admission to an academic hospital (02/11-06/17). Each case was comprehensively reviewed by a minimum of two reviewers, including one sub-specialist. In addition, oncologists were surveyed regarding their confidence about managing irAEs. Results: From 2011-2017, there were 343 hospitalizations for suspected irAEs, and the majority (65%; N = 223) were confirmed irAEs from immunotherapy: PD1 (31.8%), CTLA4 (29.2%), CTLA4 + PD1 (15.7%), PD1 à CTLA4 (14.8%), CTLA4àPD1 (8.5%), and PDL1 (3.1%). The most common irAEs were gastrointestinal (43.9%), pulmonary (16%), hepatic (15%), neurologic (8.9%), endocrine (7.1%), rheumatologic (4%), dermatologic (3%), cardiac (3%), renal (1.8%), and allergy (1.3%). Mean length of stay was 6.4 days, readmission rate for irAE 25%, and inpatient mortality 4%. Majority of patients (92%) required continuation of immunosuppressive medication on discharge. Disposition was to home (87%), skilled facility (8.8%), or hospice (4.2%). Inpatient admissions due to irAEs has increased significantly over time (2016 vs 2011, odds ratio = 3.07; p < 0.01). However, a survey (N = 26) revealed that oncologists do not feel very comfortable managing irAEs, and 48% felt irAEs should be managed by different service. Conclusions: irAEs from immune checkpoint inhibitors can result in prolonged hospitalizations, need for immunosuppression, inpatient mortality, and high readmission rate. The number of admissions due to irAEs has increased by more than three-fold in the recent years, but comfort level in managing these complications is low. Consequently, there is a critical need for coordinated multidisciplinary approach, comprehensive provider education, and translational research programs for early detection and intervention.
Neutrophils roll on adherent neutrophils bound to cytokine-induced endothelial cells via L-selectin on the rolling cells. (1994)

Specific arrest of neutrophils in venules is central to their rapid accumulation during local inflammatory responses. Initial neutrophil rolling on endothelium is mediated by leukocyte L-selectin and the inducible vascular adhesion proteins P- and E-selectin. This rolling is a prerequisite for endothelial-dependent neutrophil arrest. Here we describe rolling of neutrophils on the surface of previously arrested neutrophils and demonstrate that this interaction involves L-selectin exclusively on rolling cells. The adherent neutrophil support of L-selectin-dependent neutrophil rolling in vivo can promote continuous and augmented leukocyte recruitment at sites of previous neutrophil accumulation.
Production of prostaglandin E and an interleukin-1 like factor by cultured astrocytes and C6 glioma cells. (1982)

When treated with lipopolysaccharide (LPS), cultured murine astrocytes released significant amounts of prostaglandin E, which caused an inhibition of the in vitro proliferative response of C3H/HeJ thymocytes to mitogen. In addition, an interleukin 1 (IL 1)-like factor secreted by LPS-treated glia cell cultures and by C6 glioma cells was detected. The characterization of the factor as an IL 1-like mediator is based on the findings that the factor 1) enhances the mitogen-induced thymocyte proliferation, 2) exhibits no interleukin 2 (IL 2) activity, but 3) augments IL 2 production by mitogen-stimulated thymocytes, and 4) has a m.w. between 13,500 and 18,000 when generated in serum-free conditions. These observations suggest that astrocytes may interact with the immune system by elaborating nonspecific factors that modulate lymphocyte proliferation. This property of astrocytes may be important in the generation of specific immune responses in the brain, which is considered to be an immunologically privileged organ as it is anatomically sequestered from the immune system.
Single Day 2 embryo versus blastocyst-stage transfer: a prospective study integrating fresh and frozen embryo transfers (2009)

The observed cumulative delivery rates in this study do not allow us to take a position in favor of SBT or eSET. An improvement in blastocyst cryopreservation may change this attitude.
Emergence and Reflexive Downward (2002)

This paper responds to Jaegwon Kim's powerful objection to the very possibility of geninely novel emergent properties. Kim argues that the incoherence of reflexive downward causation means that the causal power of an emergent phenomenon is ultimately reducible to the causal powers of the causal powers of its constituents. I offer a simple argument showing how to claracterize emergent properties in terms of the effects of structural relations on the causal powers of their constituents.
Fabrication of affordable metallic microstructures by electroplating and photoresist molds (2002)

Electroforming processes such as electroplating was used in conjunction with photoresist mold to fabricate surface and substrate micromachined structure. Gold, gold alloys and nickel and nickel-iron alloys were used as structural material in this technique. In case of surface micromachining free standing, cantilevers, bridges and linear and torsional comb drives on silicon substrate were fabricated, whereas in case of substrate micromachined magnetic actuators were fabricated using the above mentioned technology. The thickness of metallic microstructures varied from 8 /spl mu/m to 20 /spl mu/m. This presentation discusses the technology we have developed in our laboratory to fabricate affordable metallic microstructures, as well as presenting functional devices we have built to demonstrate the potential of this technology.
Impairment of chaperone‐mediated autophagy leads to selective lysosomal degradation defects in the lysosomal storage disease cystinosis (2015)

Metabolite accumulation in lysosomal storage disorders (LSDs) results in impaired cell function and multi-systemic disease. Although substrate reduction and lysosomal overload-decreasing therapies can ameliorate disease progression, the significance of lysosomal overload-independent mechanisms in the development of cellular dysfunction is unknown for most LSDs. Here, we identify a mechanism of impaired chaperone-mediated autophagy (CMA) in cystinosis, a LSD caused by defects in the cystine transporter cystinosin (CTNS) and characterized by cystine lysosomal accumulation. We show that, different from other LSDs, autophagosome number is increased, but macroautophagic flux is not impaired in cystinosis while mTOR activity is not affected. Conversely, the expression and localization of the CMA receptor LAMP2A are abnormal in CTNS-deficient cells and degradation of the CMA substrate GAPDH is defective in Ctns(-/-) mice. Importantly, cysteamine treatment, despite decreasing lysosomal overload, did not correct defective CMA in Ctns(-/-) mice or LAMP2A mislocalization in cystinotic cells, which was rescued by CTNS expression instead, suggesting that cystinosin is important for CMA activity. In conclusion, CMA impairment contributes to cell malfunction in cystinosis, highlighting the need for treatments complementary to current therapies that are based on decreasing lysosomal overload.
Active specific immunotherapy: PEM as a potential target molecule. (1993)

An understanding of the mechanisms involved in a biological phenomenon increases its potential for clinical exploitation. Thus, the simultaneous identification of TAA and the molecular mechanisms involved in antigen presentation and recognition by the immune system make the use of ASI a real possibility. The polymorphic epithelial mucin is expressed on most carcinomas and is highly immunogenic. Furthermore, it has many characteristics that make it potentially an ideal target molecule for ASI: (a) not only is it expressed, but it is upregulated by most carcinomas; (b) it is aberrantly glycosylated by carcinomas, resulting in the exposure of cryptic epitopes; (c) its tandem repeat structure results in there being many epitopes per molecule; (d) its extended structure at the surface means it is one of the first molecules the cells of the immune system encounter; and (e) its apparent ability to elicit HLA unrestricted killing already demonstrated in cancer patients makes it applicable to all individuals.
Discovery, development, and some uses of vasopressin and oxytocin antagonists. (1989)

The past decade has witnessed an astonishing resurgence of interest in the neurohypophysial peptides oxytacin and vasopressin. The availability of antagonists for vasopressin and oxytocin has been a major factor responsible for the increased number of studies on these peptides. Oxytocin antagonists and, more particularly, vasopressin antagonists have been and are being used worldwide as pharmacologic tools in a broad range of studies on the putative physiological and pathophysiological roles of vasopressin and of oxytocin. Also, antagonists of the antidiuretic effects of vasopressin are currently being developed as therapeutic candidates for the treatment of excessive water retention caused by SIADH. Antagonists of oxytocin are also potential therapeutic agents for the prevention of premature labor
A Sudden Decline in Active Membrane-Bound TGF-β Impairs Both T Regulatory Cell Function and Protection against Autoimmune Diabetes (2004)

Autoimmunity presumably manifests as a consequence of a shortfall in the maintenance of peripheral tolerance by CD4(+)CD25(+) T regulatory cells (Tregs). However, the mechanism underlying the functional impairment of Tregs remains largely undefined. In this study a glutamic acid decarboxylase (GAD) diabetogenic epitope was expressed on an Ig to enhance tolerogenic function, and the resulting Ig-GAD expanded Tregs in both young and older insulitis-positive, nonobese diabetic (NOD) mice, but delayed autoimmune diabetes only in the former. Interestingly, Tregs induced at 4 wk of age had significant active membrane-bound TGF-beta (mTGF-beta) and sustained protection against diabetes, whereas Tregs expanded during insulitis had minimal mTGF-beta and could not protect against diabetes. The Tregs probably operate suppressive function through mTGF-beta, because Ab blockade of mTGF-beta nullifies protection against diabetes. Surprisingly, young Tregs that modulated pathogenic T cells maintained stable frequency over time in the protected animals, but decreased their mTGF-beta at the age of 8 wk. More strikingly, these 8-wk-old mTGF-beta-negative Tregs, which were previously protective, became unable to confer resistance against diabetes. Thus, a developmental decline in active mTGF-beta nullifies Treg function, leading to a break in tolerance and the onset of diabetes.
Capturing novel mouse genes encoding chromosomal and other nuclear proteins (1998)

The burgeoning wealth of gene sequences contrasts with our ignorance of gene function. One route to assigning function is by determining the sub-cellular location of proteins. We describe the identification of mouse genes encoding proteins that are confined to nuclear compartments by splicing endogeneous gene sequences to a promoterless betageo reporter, using a gene trap approach. Mouse ES (embryonic stem) cell lines were identified that express betageo fusions located within sub-nuclear compartments, including chromosomes, the nucleolus and foci containing splicing factors. The sequences of 11 trapped genes were ascertained, and characterisation of endogenous protein distribution in two cases confirmed the validity of the approach. Three novel proteins concentrated within distinct chromosomal domains were identified, one of which appears to be a serine/threonine kinase. The sequence of a gene whose product co-localises with splicesome components suggests that this protein may be an E3 ubiquitin-protein ligase. The majority of the other genes isolated represent novel genes. This approach is shown to be a powerful tool for identifying genes encoding novel proteins with specific sub-nuclear localisations and exposes our ignorance of the protein composition of the nucleus. Motifs in two of the isolated genes suggest new links between cellular regulatory mechanisms (ubiquitination and phosphorylation) and mRNA splicing and chromosome structure/function.