gebhart/patrepeval huggingface dataset:
Role of Ced-3/ICE-family proteases in staurosporine-induced programmed cell death. (1996)

In the accompanying paper by Weil et al. (1996) we show that staurosporine (STS), in the presence of cycloheximide (CHX) to inhibit protein synthesis, induces apoptotic cell death in a large variety of nucleated mammalian cell types, suggesting that all nucleated mammalian cells constitutively express all of the proteins required to undergo programmed cell death (PCD). The reliability of that conclusion depends on the evidence that STS-induced, and (STS + CHS)-induced, cell deaths are bona fide examples of PCD. There is rapidly accumulating evidence that some members of the Ced-3/Interleukin-1 beta converting enzyme (ICE) family of cysteine proteases are part of the basic machinery of PCD. Here we show that Z-Val-Ala-Asp-fluoromethylketone (zVAD-fmk), a cell-permeable, irreversible, tripeptide inhibitor of some of these proteases, suppresses STS-induced and (STS + CHX)-induced cell death in a wide variety of mammalian cell types, including anucleate cytoplasts, providing strong evidence that these are all bona fide examples of PCD. We show that the Ced-3/ICE family member CPP32 becomes activated in STS-induced PCD, and that Bcl-2 inhibits this activation. Most important, we show that, in some cells at least, one or more CPP32-family members, but not ICE itself, is required for STS-induced PCD. Finally, we show that zVAD-fmk suppresses PCD in the interdigital webs in developing mouse paws and blocks the removal of web tissue during digit development, suggesting that this inhibition will be a useful tool for investigating the roles of PCD in various developmental processes.
Phenylketonuria: translating research into novel therapies. (2014)

Phenylketonuria (PKU) is an inborn error of metabolism of the amino acid phenylalanine. It is an autosomal recessive disorder with a rate of incidence of 1 in 10,000 in Caucasian populations. Mutations in the phenylalanine hydroxylase (PAH) gene are the major cause of PKU, due to the loss of the catalytic activity of the enzyme product PAH. Newborn screening for PKU allows early intervention, avoiding irreparable neurological damage and intellectual disability that would arise from untreated PKU. The current primary treatment of PKU is the limitation of dietary protein intake, which in the long term may be associated with poor compliance in some cases and other health problems due to malnutrition. The only alternative therapy currently approved is the supplementation of BH4, the requisite co-factor of PAH, in the orally-available form of sapropterin dihydrochloride. This treatment is not universally available, and is only effective for a proportion (estimated 30%) of PKU patients. Research into novel therapies for PKU has taken many different approaches to address the lack of PAH activity at the core of this disorder: enzyme replacement via virus-mediated gene transfer, transplantation of donor liver and recombinant PAH protein, enzyme substitution using phenylalanine ammonia lyase (PAL) to provide an alternative pathway for the metabolism of phenylalanine, and restoration of native PAH activity using chemical chaperones and nonsense read-through agents. It is hoped that continuing efforts into these studies will translate into a significant improvement in the physical outcome, as well as quality of life, for patients with PKU.
Disruption of TBP-2 ameliorates insulin sensitivity and secretion without affecting obesity (2010)

Type 2 diabetes mellitus (T2DM) is characterized by defects in both insulin sensitivity and glucose-stimulated insulin secretion (GSIS) and is often accompanied by obesity. In this study, we show that disruption of thioredoxin binding protein-2 (TBP-2, also called Txnip) in obese mice (ob/ob) dramatically improves hyperglycaemia and glucose intolerance, without affecting obesity or adipocytokine concentrations. TBP-2-deficient ob/ob mice exhibited enhanced insulin sensitivity with activated insulin receptor substrate-1/Akt signalling in skeletal muscle and GSIS in islets compared with ob/ob mice. The elevation of uncoupling protein-2 (UCP-2) expression in ob/ob islets was downregulated by TBP-2 deficiency. TBP-2 overexpression suppressed glucose-induced adenosine triphosphate production, Ca(2+) influx and GSIS. In β-cells, TBP-2 enhanced the expression level and transcriptional activity of UCP-2 by recruitment of peroxisome proliferator-activated receptor-γ co-activator-1α to the UCP-2 promoter. Thus, TBP-2 is a key regulatory molecule of both insulin sensitivity and GSIS in diabetes, raising the possibility that inhibition of TBP-2 may be a novel therapeutic approach for T2DM.
Towards a mature offshore wind energy technology—guidelines from the opti-OWECS project (1999)

The article reviews the main results of the recent European research project Opti-OWECS (‘Structural and Economic Optimisation of Bottom-Mounted Offshore Wind Energy Converters'), which has significantly improved the understanding of the requirements for a large-scale utilization of offshore wind energy. An integrated design approach was demonstrated for a 300 MW offshore wind farm at a demanding North Sea site. Several viable solutions were obtained and one was elaborated to include the design of all major components. Simultaneous structural and economic optimization took place during the different design stages. An offshore wind energy converter founded on a soft–soft monopile was tailored with respect to the distinct characteristics of dynamic wind and wave loading. The operation and maintenance behaviour of the wind farm was analysed by Monte Carlo simulations. With an optimized maintenance strategy and suitable hardware a high availability was achieved. Based upon the experience from the structural design, cost models for offshore wind farms were developed and linked to a European database of the offshore wind energy potential. This enabled the first consistent estimate of cost of offshore wind energy for entire European regions. Copyright © 1999 John Wiley & Sons, Ltd.
Avidity of Islet Cell Autoantibodies in Non-Diabetic Children and Children with Insulin-Dependent Diabetes (1999)

Low-avidity immunoglobulin G antibodies, which commonly occur after microbial infections and form unstable complexes with the antigen, are within weeks replaced by high-avidity antibodies, which bind the antigen tightly and characterise mature immune response. We hypothesised that avidity of islet cell autoantibodies (ICA), found in the sera of patients with insulin-dependent diabetes mellitus (IDDM) usually months or years before disease onset, might reflect the stage of progression towards overt IDDM. ICA were quantitated before and after treatment of antigen-antibody complexes with 5 M urea in a new assay, in which the fluorescence intensity of europium chelate-labelled detecting antibody is measured from a digital time-resolved fluorescence image. The proportion of urea-resistant ICA of all ICA was defined as the avidity index. The median avidity indices (range) of 119 children with recent-onset IDDM and 64 non-diabetic ICA-positive children were 74% (23-100%) and 11% (0-100%), respectively (p = 0.0001). The avidity indices of only 3 children with IDDM (2.5%), but of 55 non-diabetic ICA-positive children (86%) were < 40%. In conclusion, our data show that ICA avidity indices of ICA-positive non-diabetic children and children with IDDM differ, suggesting that measurement of ICA avidity may improve prediction of the time of onset of clinical IDDM.
Role of fadR and atoC(Con) mutations in poly(3-hydroxybutyrate-co-3-hydroxyvalerate) synthesis in recombinant pha+ Escherichia coli (1995)

Recombinant Escherichia coli fadR atoC(Con) mutants containing the polyhydroxyalkanoate (PHA) biosynthesis genes from Alcaligenes eutrophus are able to incorporate significant levels of 3-hydroxyvalerate (3HV) into the copolymer poly(3-hydroxybutyrate-co-3-hydroxyvalerate) [P(3HB-co-3HV)]. We have used E. coli fadR (FadR is a negative regulator of fatty acid oxidation) and E. coli atoC(Con) (AtoC is a positive regulator of fatty acid uptake) mutants to demonstrate that either one of these mutations alone can facilitate copolymer synthesis but that 3HV levels in single mutant strains are much lower than in the fadR atoC(Con) strain. E. coli atoC(Con) mutants were used alone and in conjunction with atoA and atoD mutants to determine that the function of the atoC(Con) mutation is to increase the uptake of propionate and that this uptake is mediated, at least in part, by atoD+. Similarly, E. coli fadR mutants were used alone and in conjunction with fadA, fadB, and fadL mutants to show that the effect of the fadR mutation is dependent on fadB+ and fadA+ gene products. Strains that were mutant in the fadB or fadA locus were unable to complement a PHA biosynthesis pathway that was mutant at the phaA locus (thiolase), but a strain containing a fadR mutation and which was fadA+ fadB+ was able to complement the phaA mutation and incorporated 3HV into P(3HB-co-3HV) to a level of 29 mol%.
Petrographic Image Analysis, I. Analysis of Reservoir Pore Complexes (1984)

ABSTRACT There exists a need to relate the petrology of reservoirs (pore geometry, surface areas of mineral phases and pores) to geophysical and petrophysical data. The end result is improved assessment of reservoir quality as well as better interpretation of well logs and seismic data. Petrographic Image Analysis (PIA) was developed from the beginning to interface with petrophysical/geophysical data. PIA relies upon computer-based image analysis using pattern recognition/classification programs, and so information can be obtained very rapidly--the rate simply tied to sophistication of the computer in use. PIA consists of a critical mix of hardware and software which perform four separate functions: 1) image acquisition; 2) image digitization; 3) image segmentation; and 4) image analysis. A sp cial effort has been made to characterize the geometry of the pore complex. Separate spectra related to pore size and pore roughness are generated from each image. In addition, surface area per unit volume of pore can be estimated. Pore spectra can be decomposed and classified using pattern recognition/ classification algorithms or used directly to estimate physical parameters.
Development of two new monoclonal antibodies reactive to a surface antigen present on human ovarian epithelial cancer cells. (1991)

Monoclonal antibodies which bind selectively to cancer cells are currently used for tumor localization and for targeting cytotoxic reagents. The success of these approaches depends on the specificity of the antibody and its reactivity to a majority of the tumor samples. Frequently, monoclonal antibodies are generated by immunizing mice with antigenic preparations from a single tumor cell line. Antibodies generated under these conditions often react to a narrow range of tumors. In the present study, mice were immunized with multiple ovarian cancer cell lines in a sequential manner to amplify the immune response against common antigenic determinants expressed in these cell lines. Spleen cells from the immunized mice were then fused with NS-1 myeloma cells to establish hybridomas. Two cell lines were selected on the basis of their selective reactivity to ovarian cancer cells after extensive screening. Monoclonal antibodies OVX1 and OVX2 bound to all 5 ovarian carcinoma cell lines tested and did not bind to normal fibroblast cells. These antibodies recognized a unique antigenic determinant present in ovarian and breast cancer cells. Cross-blocking studies showed that the binding of OVX1 and OVX2 is not displaceable by 10 other previously described anti-ovarian antibodies including OC125. In immunocytochemical studies, OVX1 reacted to a majority of ovarian cancer tissues (17 of 20) and did not bind to normal ovarian tissues. Preliminary results indicate that OVX1 and OVX2 antibodies are directed to a high molecular weight antigen. These antibodies could be used in the preparation of cytotoxic conjugates.
Text-to-speech system for Greek (1991)

A modular software TTS (text-to-speech) system for Greek with good intelligibility and quality of speech and the possibility of being further improved by extending its linguistic knowledge is presented. The system has several peculiarities in comparison to most systems for other languages, combining the advantages of formant synthesis with those of diphone synthesis. In addition to the text normalizer (including numbers) and the sophisticated text preprocessor, the system uses composite speech segments besides phonemes which are concatenated, using a dynamically-adjusted-in-range, sigmoid function. The segments are coded in a novel scheme aiding the rules which manipulate voice onset and duration times. A declined line with its ending part dependent on the punctuation mark or function word, which fluctuates according to the stressed points and unvoiced (voiced) consonant and plosive locations, controls the intonation of the input text. The system is to be improved by incorporating elaborate prosodic rules resulting from syntactic analysis of the text.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
A framework for efficient progressive fine granularity scalable video coding (2001)

A basic framework for efficient scalable video coding, namely progressive fine granularity scalable (PFGS) video coding is proposed. Similar to the fine granularity scalable (PGS) video coding in MPEG-4, the PFGS framework has all the features of FGS, such as fine granularity bit-rate scalability, channel adaptation, and error recovery. On the other hand, different from the PGS coding, the PFGS framework uses multiple layers of references with increasing quality to make motion prediction more accurate for improved video-coding efficiency. However, using multiple layers of references with different quality also introduces several issues. First, extra frame buffers are needed for storing the multiple reconstructed reference layers. This would increase the memory cost and computational complexity of the PFGS scheme. Based on the basic framework, a simplified and efficient PFGS framework is further proposed. The simplified PPGS framework needs only one extra frame buffer with almost the same coding efficiency as in the original framework. Second, there might be undesirable increase and fluctuation of the coefficients to be coded when switching from a low-quality reference to a high-quality one, which could partially offset the advantage of using a high-quality reference. A further improved PFGS scheme can eliminate the fluctuation of enhancement-layer coefficients when switching references by always using only one high-quality prediction reference for all enhancement layers. Experimental results show that the PFGS framework can improve the coding efficiency up to more than 1 dB over the FGS scheme in terms of average PSNR, yet still keeps all the original properties, such as fine granularity, bandwidth adaptation, and error recovery. A simple simulation of transmitting the PFGS video over a wireless channel further confirms the error robustness of the PFGS scheme, although the advantages of PFGS have not been fully exploited.
Loss of Functional Suppression by CD4+CD25+ Regulatory T Cells in Patients with Multiple Sclerosis (2004)

CD4+CD25+ regulatory T cells contribute to the maintenance of peripheral tolerance by active suppression because their deletion causes spontaneous autoimmune diseases in mice. Human CD4+ regulatory T cells expressing high levels of CD25 are suppressive in vitro and mimic the activity of murine CD4+CD25+ regulatory T cells. Multiple sclerosis (MS) is an inflammatory disease thought to be mediated by T cells recognizing myelin protein peptides. We hypothesized that altered functions of CD4+CD25hi regulatory T cells play a role in the breakdown of immunologic self-tolerance in patients with MS. Here, we report a significant decrease in the effector function of CD4+CD25hi regulatory T cells from peripheral blood of patients with MS as compared with healthy donors. Differences were also apparent in single cell cloning experiments in which the cloning frequency of CD4+CD25hi T cells was significantly reduced in patients as compared with normal controls. These data are the first to demonstrate alterations of CD4+CD25hi regulatory T cell function in patients with MS.
Regulation of adenine nucleotide translocase and glycerol 3-phosphate dehydrogenase expression by thyroid hormones in different rat tissues (1996)

Thyroid hormone (T3)-dependent gene expression of the adenine nucleotide translocase (ANT) and the FAD-linked glycerol 3-phosphate dehydrogenase (mGPDH) was investigated in several rat tissues. Both proteins provide an important link between cytosolic and mitochondrial metabolic pathways and seem to be involved in the stimulation of mitochondrial oxygen consumption in response to T3. Here we show that two ANT isoforms are expressed in rat, the muscle-specific ANT1 form and the ubiquitous ANT2 form. The expression of ANT1 mRNA is not sensitive to T3 whereas the amount of ANT2 mRNA is increased 7-9-fold in liver and heart within 12-48 h after T3 application. Little or no effect of T3 on ANT2 mRNA was observed in kidney and brain. The mRNA changes are paralleled by an increase in ANT protein, thus explaining the accelerated ADP/ATP exchange observed in mitochondria isolated from hyperthyroid rats. The key role of ANT2 in the control of hyperthyroid metabolism is evident because the expression of the mersalyl-sensitive phosphate carrier and the mitochondrial creatine kinase mRNA, which are functionally linked to ANT, did not respond to T3. Similarly to the ADP/ATP exchange, the transfer of cytosolic NADH to the respiratory chain via the glycerophosphate shuttle is very sensitive to T3. Recently we demonstrated the 10-15-fold induction of mGPDH mRNA in rat liver after administration of T3 [Müller and Seitz (1994) Proc. Natl. Acad. Sci. U.S.A. 91, 10581-10585]. Here we show that, in contrast with ANT2, the time course of induction is fast (4-6 h). Furthermore, mGPDH mRNA is induced 6-fold by T3 in heart and 4-fold in kidney. From these results we conclude that the T3-mediated transcriptional induction leading to increased activity of ANT2 and mGPDH contributes considerably to the increase in mitochondrial oxygen consumption in rat tissues.
Cellular and Molecular Immunology (1994)

Cellular and molecular immunology , Cellular and molecular immunology , کتابخانه الکترونیک و دیجیتال - آذرسا
Roles of the mammalian target of rapamycin, mTOR, in controlling ribosome biogenesis and protein synthesis (2012)

mTORC1 (mammalian target of rapamycin complex 1) is controlled by diverse signals (e.g. hormones, growth factors, nutrients and cellular energy status) and regulates a range of processes including anabolic metabolism, cell growth and cell division. We have studied the impact of inhibiting mTOR on protein synthesis in human cells. Partial inhibition of mTORC1 by rapamycin has only a limited impact on protein synthesis, but inhibiting mTOR kinase activity causes much greater inhibition of protein synthesis. Using a pulsed stable-isotope-labelling technique, we show that the rapamycin and mTOR (mammalian target of rapamycin) kinase inhibitors have differential effects on the synthesis of specific proteins. In particular, the synthesis of proteins encoded by mRNAs that have a 5'-terminal pyrimidine tract is strongly inhibited by mTOR kinase inhibitors. Many of these mRNAs encode ribosomal proteins. mTORC1 also promotes the synthesis of rRNA, although the mechanisms involved remain to be clarified. We found that mTORC1 also regulates the processing of the precursors of rRNA. mTORC1 thus co-ordinates several steps in ribosome biogenesis.
Exclusion of the retinoblastoma gene and chromosome 13q as the site of a primary lesion for human breast cancer. (1990)

Chromosome 13q has been suggested as the site of a gene predisposing to human breast cancer, because loss of heterozygosity of alleles on this chromosome has been observed in some ductal breast tumors and because two breast cancer lines are altered at the retinoblastoma gene (RB1) at 13q14. To test this possibility, linkage of breast cancer susceptibility to 14 loci on chromosome 13q loci was assessed in extended families in which breast cancer is apparently inherited as an autosomal dominant trait. RB1 was excluded as the site of a breast cancer gene by a lod score of Z = -7.60 at close linkage for 13 families. Multipoint analysis yielded negative lod scores throughout the region between 13q12 and 13q34; over most of this distance, Z less than -2.0. Therefore, chromosome 13q appears to be excluded as the site of primary lesion for breast cancer in these families. In addition, comparison of tumor versus normal tissues of nonfamilial breast cancer patients revealed an alteration at the 5' end of RB1 in a mucoid carcinoma but no alterations of RB1 in five informative ductal adenocarcinomas. Linkage data and comparisons of tumor and normal tissues suggest that changes in the RBI locus either are secondary alterations associated with progression of some tumors or occur by chance.
Pain assessment: global use of the Brief Pain Inventory. (1994)

Poorly controlled cancer pain is a significant public health problem throughout the world. There are many barriers that lead to undertreatment of cancer pain. One important barrier is inadequate measurement and assessment of pain. To address this problem, the Pain Research Group of the WHO Collaborating Centre for Symptom Evaluation in Cancer Care has developed the Brief Pain Inventory (BPI), a pain assessment tool for use with cancer patients. The BPI measures both the intensity of pain (sensory dimension) and interference of pain in the patient's life (reactive dimension). It also queries the patient about pain relief, pain quality, and patient perception of the cause of pain. This paper describes the development of the Brief Pain Inventory and the various applications to which the BPI is suited. The BPI is a powerful tool and, having demonstrated both reliability and validity across cultures and languages, is being adopted in many countries for clinical pain assessment, epidemiological studies, and in studies of the effectiveness of pain treatment.
Synthesis of Amino Acid Ester Isocyanates: Methyl (S)‐2‐Isocyanato‐3‐Phenylpropanoate (2003)

Abstract Methyl (S)‐2‐isocyanato‐3‐phenylpropanoate R L‐Phenylalanine methyl ester hydrochloride P Methyl (S)‐2‐isocyanato‐3‐phenylpropanoate
Make Your Mark in Spreadsheets (2001)

The concentration of the activator ion (Eu(2+)) significantly affects radiation detection properties of the storage phosphor KCl:Eu(2+). An activator concentration between 0.01 and 0.05 mol.% Eu in KCl:Eu(2+) storage phosphor detectors is recommended for linear dose response, good PSL sensitivity, predictable temporal stability, and high reusability for megavoltage radiation detection.
Fresh whole blood use by forward surgical teams in Afghanistan is associated with improved survival compared to component therapy without platelets (2013)

The use of FWB in austere combat environments appears to be safe and is independently associated with improved survival to discharge when compared with resuscitation with RBCs and FFP alone. Mortality was similar for patients transfused uncrossmatched Type O compared with ABO type-specific FWB in an austere setting.