gebhart/patrepeval huggingface dataset:
Gene expression profiling identifies significant differences between the molecular phenotypes of bone marrow–derived and circulating human CD34+ hematopoietic stem cells (2002)

CD34+ hematopoietic stem cells are used clinically to support cytotoxic therapy, and recent studies raised hope that they could even serve as a cellular source for nonhematopoietic tissue engineering. Here, we examined in 18 volunteers the gene expressions of 1185 genes in highly enriched bone marrow CD34+ (BM-CD34+) or granulocyte-colony-stimulating factor-mobilized peripheral blood CD34+ (PB-CD34+) cells by means of cDNA array technology to identify molecular causes underlying the functional differences between circulating and sedentary hematopoietic stem and progenitor cells. In total, 65 genes were significantly differentially expressed. Greater cell cycle and DNA synthesis activity of BM-CD34+ than PB-CD34+ cells were reflected by the 2- to 5-fold higher expression of 9 genes involved in cell cycle progression, 11 genes regulating DNA synthesis, and cell cycle-initiating transcription factor E2F-1. Conversely, 9 other transcription factors, including the differentiation blocking GATA2 and N-myc, were expressed 2 to 3 times higher in PB-CD34+ cells than in BM-CD34+ cells. Expression of 5 apoptosis driving genes was also 2 to 3 times greater in PB-CD34+ cells, reflecting a higher apoptotic activity. In summary, our study provides a gene expression profile of primary human CD34+ hematopoietic cells of the blood and marrow. Our data molecularly confirm and explain the finding that CD34+ cells residing in the bone marrow cycle more rapidly, whereas circulating CD34+ cells consist of a higher number of quiescent stem and progenitor cells. Moreover, our data provide novel molecular insight into stem cell physiology.
The C-terminal domain of the largest subunit of RNA polymerase II interacts with a novel set of serine/arginine-rich proteins. (1996)

Although transcription and pre-mRNA processing are colocalized in eukaryotic nuclei, molecules linking these processes have not previously been described. We have identified four novel rat proteins by their ability to interact with the repetitive C-terminal domain (CTD) of RNA polymerase II in a yeast two-hybrid assay. A yeast homolog of one of the rat proteins has also been shown to interact with the CTD. These CTD-binding proteins are all similar to the SR (serine/arginine-rich) family of proteins that have been shown to be involved in constitutive and regulated splicing. In addition to alternating Ser-Arg domains, these proteins each contain discrete N-terminal or C-terminal CTD-binding domains. We have identified SR-related proteins in a complex that can be immunoprecipitated from nuclear extracts with antibodies directed against RNA polymerase II. In addition, in vitro splicing is inhibited either by an antibody directed against the CTD or by wild-type but not mutant CTD peptides. Thus, these results suggest that the CTD and a set of CTD-binding proteins may act to physically and functionally link transcription and pre-mRNA processing.
Batch (One- and Two-Stage) Production of Biodiesel Fuel From Rapeseed Oil (2007)

Biodiesel fuel is an alternative and renewable energy source, which may help to reduce air pollution, as well as our dependence on petroleum for energy. Several processes have already been developed for the production of biodiesel. Alkali-catalyzed transesterification with short-chain alcohols, for example, generates high yields of methyl esters in short reaction times. In this study, we have evaluated the efficacy of batch (one- and two-stage) transesterification of rapeseed oil in the production of rapeseed methyl ester. The conversion of rapeseed oil exhibited similar reaction patterns and yields in 30- and 1-L reaction systems. Approximately 98% of the rapeseed oil was converted at 400 rpm within 20 min, under the following conditions:1% (w/w) KOH, 1:10 methanol molar ratio, and at 60°C. In the 30-L, two-stage transesterification process, approx 98.5% of the rapeseed oil was converted at a 1:4.5 molar ratio and 1% (w/w) KOH at 60°C for 30 min (first reaction condition), and at a 1:1 molar ratio and 0.2% (w/w) KOH at 60°C for 30 min (second reaction condition).
Protein transduction: identification, characterization and optimization (2007)

Protein transduction domains (PTDs), both naturally occurring and synthetic, have been increasingly employed to deliver biologically active agents to a variety of cell types in vitro and in vivo. In addition to the previously characterized arginine-rich PTDs, including Tat (transactivator of transcription), Antp (Antennapedia) and PTD-5, we have demonstrated that lysine and ornithine, as well as arginine, homopolymers are able to mediate transduction of a wide variety of agents. To screen for optimal PTDs, we have used as a therapeutic cargo a peptide derived from IKK {IkappaB [inhibitor of NF-kappaB (nuclear factor kappaB)] kinase} beta, able to bind to the IKK regulatory subunit [NEMO (NF-kappaB essential modulator)], preventing formation of an active kinase complex. This peptide, termed NBD, is able to block activation of NF-kappaB, but not basal activity. We demonstrate that PTD-mediated delivery of NBD using certain PTDs, in particular 8K (octalysine), is therapeutic following systemic delivery in murine models of inflammatory bowel disease, diabetes and muscular dystrophy. In addition, we have developed a peptide phage display library screening method for novel transduction peptides able to facilitate tissue-specific internalization of marker protein complexes. Using this approach, we have identified transduction peptides that are able to facilitate internalization of large protein complexes into tumours, airway epithelia, synovial fibroblasts, cardiac tissue and HEK-293 (human embryonic kidney) cells in culture and/or in vivo.
Human VPAC1 Receptor Selectivity Filter (2002)

The human VPAC1 receptor for vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating peptide (PACAP) belongs to the class II family of G protein coupled receptors with seven transmembrane segments. It recognizes several VIP-related peptides and displays a very low affinity for secretin despite >70% homology between VIP and secretin. Conversely, the human secretin receptor has high affinity for secretin but low affinity for VIP. We took advantage of this reversed selectivity to identify a domain of the VPAC1 receptor responsible for selectivity toward secretin by constructing human VPAC1-secretin receptor chimeras. A first set of chimeras consisted of exchanging the entire N-terminal ectodomain or large parts of this domain. They were constructed by overlap PCR, transfected in COS-7 cells, and their ligand selectivity, expressed as the ratio of EC(50) for secretin/EC(50) for VIP (referred to as S/V), in stimulating cAMP production was measured. Two very informative chimeras respectively referred to as S144V and S123V were obtained by replacing the entire ectodomain or only the first 123 amino acids of the VPAC1 receptor by the corresponding sequences of the secretin receptor. Whereas S144V no longer discriminated between VIP and secretin (S/V = 1.2), S123V discriminated between the two peptides (S/V = 300) in the same manner as the wild-type VPAC1 receptor. The motif responsible for discrimination was determined by introducing small blocks or individual amino acids of secretin receptor in the 123-144 sequence of the S123V chimera. The data obtained from 14 new chimeras sustained that two nonadjacent pairs of amino acids, Gln(135) Thr(136) and Gly(140) Ser(141) in the C-terminal end of the N-terminal VPAC1 receptor ectodomain constitute a selective filter that strongly restricts access of secretin to the VPAC1 receptor.
Development of industrial models of high-power stepped-plate sonic and ultrasonic transducers for use in fluids (2002)

The extension of the high-power applications of sonic and ultrasonic energy in industrial processing requires the development of efficient and powerful transducers. Years ago some of the authors of the present paper proposed a new concept of ultrasonic transducer for use in fluids (more specifically in gases) based on a stepped-plate radiator. This concept was successfully applied to the design and development of a series of circular plate transducers of small and medium power capacities (lower than 1 kW) and radiating surfaces smaller than 0.5 m/sup 2/. Nevertheless, the scale of a great part of industrial applications requires higher powers and larger radiating surfaces. Looking for such applications (i.e. fume precipitation, defoaming, drying and dewatering, etc.) we have designed and developed an industrial model of transducer with a rectangular plate radiator of double-stepped profile. The design of the new model was made with the help of the finite element method (FEM) and the acoustic field was computed by the boundary element method (BEM). In such a way the distribution of displacements and stresses as well as the corresponding radiated field could be known previously to the real construction of the unit. The industrial prototype of macrosonic transducer was designed with a radiating plate of 1.8/spl times/0.9 m/sup 2/ for an estimated power capacity of about 3500 W. Previously a first scale model was developed and tested with a radiating plate of 0.6/spl times/0.3 m/sup 2/ for a frequency of 20 kHz and a power capacity of about 400 W. The industrial prototype was constructed by scaling up the first model in a factor of three. Typical problems faced in the development of the industrial transducers were, the adequate selection and characterisation of the plate material, the excitation of the useful vibration mode without interference of the closer modes of the plate, the decrease of the maximum stress by improving the uniformity of the vibration amplitude, etc. The industrial prototype, constructed initially with an aluminium plate and eventually with a titanium alloy plate, presents an electroacoustic efficiency of 67% and it has been operated in air with an applied power of two kilowatts in continuous wave.
<title>Multiple fault diagnosis in graph-based systems</title> (2002)

Graph-based systems are models wherein the nodes represent the components and the edges represent the fault propagation between the components. For critical systems, some components are equipped with smart sensors for on-board system health management. When an abnormal situation occurs, alarms will be triggered from these sensors. This paper considers the problem of identifying the set of potential failure sources from the set of ringing alarms in graph-based systems. However, the computational complexity of solving the optimal multiple fault diagnosis problem is super-exponential. Based on Lagrangian relaxation and subgradient optimization, we present a heuristic algorithm to find the most likely candidate fault set. A computationally cheaper heuristic algorithm - primal heuristic - has also been applied to the problem so that real-time multiple fault diagnosis in systems with several thousand failure sources becomes feasible in a fraction of a second.
A versatile approach to analogues of the cannabinoid‐like anti‐emetic nonabine (BRL 4664) (1984)

Abstract Analogues of the cannabinoid‐like anti‐emetic nonabine (BRL 4664), in which the 4‐pyridinyl and 1,2‐dimethylheptyl groups have been replaced by other aryl and alky groups respectively, have been synthesised from the appropriate resorcinol by a novel procedure. The route has been shown to be of general applicability, although in the case of nonabine itself the procedure does not represent a viable alternative to that previously published.
TECHNIQUES FOR SELECTION OF INDUSTRIALLY IMPORTANT MICROORGANISMS (1991)

The screening of microorganisms for the production of useful products continues to be an important aspect of biotechnology. Although advances in instrumentation, genetics, and microbial physiology are having an impact, screening programs are still primarily based on so-called classical techniques of enrichment and mutagenesis. One area that needs strengthening is the advancement of knowledge in microbial physiology. Recent surveys indicate that industry leaders see trained microbial physiologists as being the limiting factor in development of biotechnology in the coming decade. The largest impediment to development of new screening techniques is the ironic lack of programs specifically directed at developing new techniques. Too much emphasis is placed on using available techniques and relying on sheer labor and screening of vast numbers of organisms to produce novel products. In this respect, the Japanese are the exception and have proven that the establishment of new programs is worth the cost and effort. They are undoubtedly the world leaders in development of screening techniques and consequently the discovery of novel products. The isolation of microbes from novel and extreme environments holds tremendous promise in two areas. First, as Omura (46) and others (9, 48, 65) state, novel organisms will yield novel products. Second, such organisms serve as models for the understanding of structure and function that will facilitate the genetic manipulation of organisms and advance our ability to engineer novel enzymes. Hopefully such advances will enable genetic and protein engineering to have a greater impact on screening programs and techniques in the future. The earth holds a vast amount of varied and unique environments, from natural extremes such as high-altitude deserts and thermal springs, to manmade environments such as industrial-waste-treatment facilities, from which, with the appropriate methods and techniques, we may isolate and evaluate new potential products.
Hemodynamic effects of potentially useful antineoplastic agents. (1983)

Adenosine (Ado) and Ado analogues produce multiple hemodynamic effects including coronary vasodilation, bradycardia, alterations in left ventricular contractility, and peripheral vasodilation or vasoconstriction depending on the vascular bed. The intact anesthetized Sprague-Dawley rat was examined in relation to electrocardiogram and blood pressure alterations induced by a series of potentially useful antineoplastic agents that are purine or pyrimidine analogues as part of a preclinical evaluation of these agents. The drugs tested were arabinosyladenine and its 5'-monophosphate derivative arabinosyladenine-5'-monophosphate (ara-AMP), the 2-fluoro derivative of ara-AMP, the pyrazolo[4,3-d]pyrimidines (formycin and formycin B), 8-azaadenosine, 6-methylmercaptopurine riboside, tricyclic nucleoside-5'-monophosphate, 5-fluorouracil, arabinosylcytosine, and 3-deazauridine. Those Ado analogues subject to deamination by adenosine deaminase (ADA) were also studied in the intact Sprague-Dawley rat after pretreatment with the ADA inhibitor 2'-deoxycoformycin. The results indicate that these agents have significant hemodynamic effects and should alert clinicians to potential adverse reactions when infusing these drugs.
Psr1, a nuclear localized protein that regulates phosphorus metabolism in Chlamydomonas (1999)

Understanding the ways in which phosphorus metabolism is regulated in photosynthetic eukaryotes is critical for optimizing crop productivity and managing aquatic ecosystems in which phosphorus can be a major source of pollution. Here we describe a gene encoding a regulator of phosphorus metabolism, designated Psr1 (phosphorus starvation response), from a photosynthetic eukaryote. The Psr1 protein is critical for acclimation of the unicellular green alga Chlamydomonas reinhardtii to phosphorus starvation. The N-terminal half of Psr1 contains a region similar to myb DNA-binding domains and the C-terminal half possesses glutamine-rich sequences characteristic of transcriptional activators. The level of Psr1 increases at least 10-fold upon phosphate starvation, and immunocytochemical studies demonstrate that this protein is nuclear-localized under both nutrient-replete and phosphorus-starvation conditions. Finally, Psr1 and angiosperm proteins have domains that are similar, suggesting a possible role for Psr1 homologs in the control of phosphorus metabolism in vascular plants. With the identification of regulators such as Psr1 it may become possible to engineer photosynthetic organisms for more efficient utilization of phosphorus and to establish better practices for the management of agricultural lands and natural ecosystems.
Immunoscintigraphy of tumours using 99Tcm-labelled monoclonal antibodies (1993)

99Tcm is the optimum radionuclide for imaging in nuclear medicine due to its superior physical properties (E gamma of 140 keV and t1/2 of 6 h). Several techniques have recently been developed for labelling monoclonal antibodies with 99Tcm for immunoscintigraphy of human malignancies. These techniques primarily consist of either direct labelling of endogenous sulphydryl groups on the immunoglobulin with 99Tcm or indirect labelling through conjugation of a preformed 99Tcm-chelate. Direct methods offer the best promise for a one-step labelling kit but the 99Tcm-antibody may be unstable in vivo. This instability has been advantageous, however, in reducing blood background radioactivity and achieving sufficiently high tumour/blood ratios for clinical imaging. Over 1200 patients have been studied with 99Tcm-labelled monoclonal antibodies in the past decade. The majority of studies have been carried out in melanoma or colon cancer but other malignancies have also been investigated. The sensitivity has been variable and depended both on the size of the lesion and its location. Single photon emission computed tomographic imaging was helpful in some instances. Further study of labelling techniques and their effect on the pharmacokinetics of 99Tcm-labelled monoclonal antibodies as well as additional clinical evaluation of these agents is indicated.
Photoluminescence wandering in single CdSe nanocrystals (1996)

Low temperature two-photon fluorescence excitation microscopy was used to obtain fluorescence spectra of single CdSe colloidal nanocrystals or quantum dots. The fluorescence spectra reveal large, 0.02 eV shifts of the peak emission wavelength on times of the order of 100 s were also observed in some instances. We attribute this behavior to excited state coupling to photoinduced changes at the nanocrystal surface.
MicroRNA-146a and MicroRNA-146b Regulate Human Dendritic Cell Apoptosis and Cytokine Production by Targeting TRAF6 and IRAK1 Proteins (2014)

We have previously reported 27 differentially expressed microRNAs (miRNAs) during human monocyte differentiation into immature dendritic cells (imDCs) and mature DCs (mDCs). However, their roles in DC differentiation and function remain largely elusive. Here, we report that microRNA (miR)-146a and miR-146b modulate DC apoptosis and cytokine production. Expression of miR-146a and miR-146b was significantly increased upon monocyte differentiation into imDCs and mDCs. Silencing of miR-146a and/or miR-146b in imDCs and mDCs significantly prevented DC apoptosis, whereas overexpressing miR-146a and/or miR-146b increased DC apoptosis. miR-146a and miR-146b expression in imDCs and mDCs was inversely correlated with TRAF6 and IRAK1 expression. Furthermore, siRNA silencing of TRAF6 and/or IRAK1 in imDCs and mDCs enhanced DC apoptosis. By contrast, lentivirus overexpression of TRAF6 and/or IRAK1 promoted DC survival. Moreover, silencing of miR-146a and miR-146b expression had little effect on DC maturation but enhanced IL-12p70, IL-6, and TNF-α production as well as IFN-γ production by IL-12p70-mediated activation of natural killer cells, whereas miR-146a and miR-146b overexpression in mDCs reduced cytokine production. Silencing of miR-146a and miR-146b in DCs also down-regulated NF-κB inhibitor IκBα and increased Bcl-2 expression. Our results identify a new negative feedback mechanism involving the miR-146a/b-TRAF6/IRAK1-NF-κB axis in promoting DC apoptosis.
p-capped GaN-AlGaN-GaN high-electron mobility transistors (HEMTs) (2002)

A novel p-capped GaN-AlGaN-GaN high-electron mobility transistor has been developed to minimize radio-frequency-to-dc (RF-DC) dispersion before passivation. The novel device uses a p-GaN cap layer to screen the channel from surface potential fluctuations. A low-power reactive ion etching gate recess combined with angle evaporation of the gate metal has been used to prevent gate extension and maintain breakdown voltage. Devices with gate lengths of 0.7 μm have been produced on sapphire. Current-gain cutoff frequencies (f/sub /spl tau//) of 20 GHz and maximum frequencies of oscillation (f <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">max</sub> ) of 38 GHz have been achieved. Unpassivated devices demonstrated a saturated output power of 3.0 W/mm and peak power-added efficiency of 40% at 4.2 GHz (V/sub DS/ = +20 V).
Expression of IGF-II mRNA-binding proteins (IMPs) in gonads and testicular cancer (2005)

Insulin-like growth factor-II mRNA-binding proteins 1, 2 and 3 (IMP1, IMP2 and IMP3) belong to a family of RNA-binding proteins implicated in mRNA localization, turnover and translational control. We examined their expression pattern during development of murine and human testis and ovaries. In the mouse, IMPs were expressed in male and female gonadal cells at embryonic day 12.5 (E12.5). From E16.5, IMP1 and IMP3 became restricted to the developing germ cells, whereas IMP2 expression persisted in the interstitial cells. In mature mouse and human ovaries, IMP1, IMP2 and IMP3 were detected in resting and growing oocytes and in the granulosa cells. In testis, IMP1 and IMP3 were found mainly in the spermatogonia, whereas IMP2 was expressed in the immature Leydig cells. Moreover, all three IMPs were detected in human semen. The developmental expression pattern of IMP1 and IMP3 in the human testis prompted us to examine their possible involvement in testicular neoplasia. IMPs were detected primarily in germ-cell neoplasms, including preinvasive testicular carcinoma in situ, classical and spermatocytic seminoma, and nonseminomas, with particularly high expression in undifferentiated embryonal carcinoma. The relative expression of IMP1, IMP2 and IMP3 varied among tumor types and only IMP1 was detected in all carcinoma in situ cells. Thus IMPs, and in particular IMP1, may be useful auxiliary markers of testicular neoplasia.
Binding of a potent small-molecule inhibitor of six-helix bundle formation requires interactions with both heptad-repeats of the RSV fusion protein (2009)

Six-helix bundle (6HB) formation is an essential step for many viruses that rely on a class I fusion protein to enter a target cell and initiate replication. Because the binding modes of small molecule inhibitors of 6HB formation are largely unknown, precisely how they disrupt 6HB formation remains unclear, and structure-based design of improved inhibitors is thus seriously hampered. Here we present the high resolution crystal structure of TMC353121, a potent inhibitor of respiratory syncytial virus (RSV), bound at a hydrophobic pocket of the 6HB formed by amino acid residues from both HR1 and HR2 heptad-repeats. Binding of TMC353121 stabilizes the interaction of HR1 and HR2 in an alternate conformation of the 6HB, in which direct binding interactions are formed between TMC353121 and both HR1 and HR2. Rather than completely preventing 6HB formation, our data indicate that TMC353121 inhibits fusion by causing a local disturbance of the natural 6HB conformation.