gebhart/patrepeval huggingface dataset:
Mutants of Escherichia coli that do not contain 1,4-diaminobutane (putrescine) or spermidine. (1979)

Strains of Escherichia coli K12 have been constructed which do not contain any of the polyamines normally present in a wild type strain, namely, 1,4-diaminobutane (putrescine) and spermidine. This phenotype arises as a consequence of the assembly into these strains of deletion mutations in speA (arginine decarboxylase), speB (agmatine ureohydrolase), speC (ornithine decarboxylase), and speD (adenosylmethionine decarboxylase). The polyamine-deficient strains grow indefinitely in the absence of polyamines but with a growth rate one-third of that found in the presence of polyamines. These strains can act as hosts for bacteriophages T4, T7, and f2, although the latter phage is poorly adsorbed; they can also maintain F' factors, ColE1 and P1 plasmids, and lysogeny by bacteriophage lambda. In contrast, the production of bacteriophage lambda in the absence of polyamines is strikingly decreased (greater than 99%) either after infection of a nonlysogen or after induction of a lysogen. A polyamine-deficient Hfr strain can transfer its chromosome to a recipient at a normal rate, but the number of recombinants observed in a cross is decreased approximately 300-fold. No such effect is observed when only the F- recipient strain in a cross is polyamine deficient.
Inhibition of GLI-mediated transcription and tumor cell growth by small-molecule antagonists (2007)

The developmentally important Hedgehog (Hh) signaling pathway has recently been implicated in several forms of solid cancer. Current drug development programs focus on targeting the protooncogene Smoothened, a key transmembrane pathway member. These drug candidates, albeit promising, do not address the scenario in which pathway activation occurs downstream of Smoothened, as observed in cases of medulloblastoma, glioma, pericytoma, breast cancer, and prostate cancer. A cellular screen for small-molecule antagonists of GLI-mediated transcription, which constitutes the final step in the Hh pathway, revealed two molecules that are able to selectively inhibit GLI-mediated gene transactivation. We provide genetic evidence of downstream pathway blockade by these compounds and demonstrate the ineffectiveness of upstream antagonists such as cyclopamine in such situations. Mechanistically, both inhibitors act in the nucleus to block GLI function, and one of them interferes with GLI1 DNA binding in living cells. Importantly, the discovered compounds efficiently inhibited in vitro tumor cell proliferation in a GLI-dependent manner and successfully blocked cell growth in an in vivo xenograft model using human prostate cancer cells harboring downstream activation of the Hh pathway.
The multifaceted role of CD146/MCAM in the promotion of melanoma progression (2015)

Human malignant melanoma is a common primary malignant cutaneous tumour derived from transformed epidermal melanocytes. Patients with melanoma have a high rate of mortality due to resistance to chemotherapeutic drugs, a major obstacle to a successful treatment. Several reports have suggested that CD146 plays an important role as a signalling molecule in human melanoma. This role includes CD146 as a participant in inflammation, differentiation, adhesion, tumourigenicity, metastasis, invasion and angiogenesis among other processes, which suggests that this molecule promotes the progression of human melanoma as a multifaceted regulator. In this article, we explore the effects and corresponding mechanisms with respect to the role of CD146/MUC18 in the promotion of human melanoma progression. Collectively, the studies indicated that targeting CD146, because it is a suitable marker of poor patient outcome, might be useful in the design of future strategies for the prevention and treatment of human melanoma.
RPE65 is the isomerohydrolase in the retinoid visual cycle (2005)

RPE65 is an abundant protein in the retinal pigment epithelium. Mutations in RPE65 are associated with inherited retinal dystrophies. Although it is known that RPE65 is critical for regeneration of 11-cis retinol in the visual cycle, the function of RPE65 is elusive. Here we show that recombinant RPE65, when expressed in QBI-293A and COS-1 cells, has robust enzymatic activity of the previous unidentified isomerohydrolase, an enzyme converting all-trans retinyl ester to 11-cis retinol in the visual cycle. The initial rate for the reaction is 2.9 pmol/min per mg of RPE65 expressed in 293A cells. The isomerohydrolase activity of RPE65 requires coexpression of lecithin retinol acyltransferase in the same cell to provide its substrate. This enzymatic activity is linearly dependent on the expression levels of RPE65. This study demonstrates that RPE65 is the long-sought isomerohydrolase and fills a major gap in our understanding of the visual cycle. Identification of the function of RPE65 will contribute to the understanding of the pathogenesis for retinal dystrophies associated with RPE65 mutations.
CREM-Dependent Transcription in Male Germ Cells Controlled by a Kinesin (2002)

ACT is a LIM-only protein expressed exclusively in round spermatids, where it cooperates with transcriptional activator CREM in regulating various postmeiotic genes. Targeted inactivation of CREM leads to a complete block of mouse spermiogenesis. We sought to identify the regulatory steps controlling the functional interplay between CREM and ACT. We found that ACT selectively associates with KIF17b, a kinesin highly expressed in male germ cells. The ACT-KIF17b interaction is restricted to specific stages of spermatogenesis and directly determines the intracellular localization of ACT. Sensitivity to leptomycin B indicates that KIF17b can be actively exported from the nucleus through the Crm1 receptor. Thus, a kinesin directly controls the activity of a transcriptional coactivator by a tight regulation of its intracellular localization.
Cytosolic deglycosylation process of newly synthesized glycoproteins generates oligomannosides possessing one GlcNAc residue at the reducing end (1998)

Recent studies on the mechanism of degradation of newly synthesized glycoproteins suggest the involvement of a retrotranslocation of the glycoprotein from the lumen of the rough endoplasmic reticulum into the cytosol, where a deglycosylation process takes place. In the studies reported here, we used a glycosylation mutant of Chinese hamster ovary cells that does not synthesize mannosylphosphoryldolichol and has an increased level of soluble oligomannosides originating from glycoprotein degradation. In the presence of anisomycin, an inhibitor of protein synthesis, we observed an accumulation of glucosylated oligosaccharide-lipid donors (Glc3Man5GlcNAc2-PP-Dol), which are the precursors of the soluble neutral oligosaccharide material. Inhibition of rough endoplasmic reticulum glucosidase(s) by castanospermine led to the formation of Glc3Man5GlcNAc2(OSGn2) (in which OSGn2 is an oligomannoside possessing two GlcNAc residues at its reducing end), which was then retained in the lumen of intracellular vesicles. Thus they were protected during an 8 h chase period from the action of cytosolic chitobiase, which is responsible for the conversion of OSGn2 to oligomannosides possessing one GlcNAc residue at the reducing end (OSGn1). In contrast, when protein synthesis was maintained in the presence of castanospermine, glucosylated oligomannosides (Glc1-3Man5GlcNAc1) were recovered in cytosol. Except for monoglucosylated Man5 species, which are potential substrates for luminal calnexin and calreticulin, the pattern of oligomannosides was similar to that observed on glycoproteins. The occurrence in the cytosol of glucosylated species with one GlcNAc residue at the reducing end implies that the deglycosylation process that generates glucosylated OSGn1 from glycoproteins occurs in the cytosol.
Ultrathin nitrided-nanolaminate (Al2O3/ZrO2/Al2O3) for metal–oxide–semiconductor gate dielectric applications (2002)

An ultrathin nanolaminate (Al2O3/ZrO2/Al2O3) film prepared by atomic layer chemical vapor deposition was investigated for use in metal–oxide–semiconductor field effect transistor (MOSFET) gate dielectric applications. Based on transmission electron microscopy and medium-energy ion scattering spectroscopy (MEIS) analysis, an abrupt interface between stoichiometric top-layer Al2O3 and ZrO2 was found. Interfacial layers such as Zr–Al–O and Al–Si–O were also observed. An electrical equivalent oxide thickness as thin as 10.2 Å with a quantum mechanical correction was obtained. Additional plasma nitridation of nanolaminte in N2 led to a significant reduction in the interfacial oxidation of nanolaminate which was confirmed by x-ray photoelectron spectroscopy, MEIS, and capacitance–voltage (C–V) analysis. The nanolaminate film represents a promising alternative for gate dielectric applications of future sub-100 nm MOSFET.
Unsteady numerical investigation of back‐step three‐dimensional slots on film cooling effectiveness (2008)

Abstract A numerical investigation was carried out to study the aerodynamics and cooling effects of a trailing edge. For a greater understanding and to learn more details, an unsteady numerical model has been proposed based on a steady model. The unsteady numerical simulation was conducted under different blowing ratios (0.5, 2.0) to show their effects on film cooling effectiveness. The computational results show that the turbulence intensity downstream of a trailing edge outlet tends to be enhanced by the unsteady flow effect. Film cooling effectiveness of an unsteady model is weaker than that obtained by a steady model. When the blowing ratio is 0.5, the mixing and intersecting of the main flow and secondary flow is rapid and fierce; with the increase of blowing ratio up to 2.0, the secondary flow plays a dominant role on the flow characteristics near the outlet of the trailing edge. The mixing and intersecting of the main flow and secondary flow become smooth. The unsteady computational results agree better with the experiment results than those of steady computation. © 2008 Wiley Periodicals, Inc. Heat Trans Asian Res; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/htj.20236
Effects of computer-based clinical decision support systems on physician performance and patient outcomes: a systematic review. (1998)

Published studies of CDSSs are increasing rapidly, and their quality is improving. The CDSSs can enhance clinical performance for drug dosing, preventive care, and other aspects of medical care, but not convincingly for diagnosis. The effects of CDSSs on patient outcomes have been insufficiently studied.
Reactivity of murine cytokine fusion toxin, diphtheria toxin390-murine interleukin-3 (DT390-mIL-3), with bone marrow progenitor cells (1996)

Myeloid leukemias can express interleukin-3 receptors (IL-3R). Therefore, as an antileukemia drug, a fusion immunotoxin was synthesized consisting of the murine IL-3 (mIL-3) gene spliced to a truncated form of the diphtheria toxin (DT390) gene coding for a molecule that retained full enzymatic activity, but excluded the native binding domain. The DT390-mIL-3 hybrid gene was cloned into a vector under the control of an inducible promote. The fusion protein was expressed in Escherichia coli and then purified from inclusion bodies. The fusion toxin was potent because it inhibited FDC-P1, an IL-3R-expressing murine myelomonocytic tumor line (IC50 = 0.025 nmol/L or 1.5 ng/mL). Kinetics were rapid and cell-free studies showed that DT390-mIL-3 was as toxic as native DT. DT390-mIL-3 was selective because anti-mIL-3 monoclonal antibody, but not irrelevant antibody, inhibited its ability to kill. Cell lines not expressing IL-3R were not inhibited by the fusion protein. Because the use of DT390-mIL-3 as an antileukemia agent could be restricted by its reactivity with committed and/or primitive progenitor cells, bone marrow (BM) progenitor assays were performed. DT390-mIL-3 selectively inhibited committed BM progenitor cells as measured by in vitro colony-forming unit-granulocyte-macrophage and in vivo colony-forming unit-spleen colony assays. To determine if this fusion protein was reactive against BM progenitor cells required to rescue lethally irradiated recipients, adoptive transfer experiments were performed. Eight million DT390-mIL-3-treated C57BL/6 Ly5.2 BM cells, but not 4 million, were able to rescue lethally irradiated congenic C57BL/6 Ly5.1 recipients, suggesting that progenitor cells might be heterogenous in their expression of IL-3R. This idea was supported in competitive repopulation experiments in which DT390-mIL-3 treated C57BL/6 Ly5.2 BM cells were mixed with nontreated C57BL/6 Ly5.1 BM cells and used to reconstitute C57BL/6 Ly5.1 mice. A significant reduction, but not elimination, of Ly5.2-expressing cells 95 days post-BM transplantation and secondary transfer experiments indicated that IL-3R is not uniformly expressed on all primitive progenitor cells. The fact that some early progenitor cells survived DT390-mIL-3 treatment indicates that this fusion toxin may be useful in the treatment of myeloid leukemias that express the IL-3R.
Genetic and Phenotypic Analysis ofEscherichia coliwith Enteropathogenic Characteristics Isolated from Seattle Children (1997)

Coliform colonies from children whose stools were submitted for microbiologic analysis were studied prospectively to determine the frequency of shedding of enteropathogenic Escherichia coli (EPEC). In total, 2225 isolates from 445 patients were probed with eaeA (encoding intimin) and the EAF (EPEC adherence factor) probe, and adherence and actin-aggregating phenotypes were determined. Twenty-five patients (5.6%) shed non-O157:H7 eaeA+ EAF- E. coli. Of these 25 patients, isolates from 5 produced Shiga toxins and from 3 possessed bfpA (encoding the bundle-forming pilus) sequences. Non-O157:H7 eaeA+ E. coli from 21 (84%) of 25 patients adhered locally to and aggregated actin in HeLa cells. Four patients shed nonadherent EAF+ eaeA- E. coli. Non-O157:H7 eaeA+ and EAF- isolates belonged to diverse electrophoretic types and classical and nonclassical enteropathogenic serotypes. EPEC are relatively common in stools submitted for analysis in this North American pediatric hospital. Their etiologic role in childhood diarrhea warrants elucidation.
Characterization of hemopoietic stem cells (CFUc) in cord blood. (1981)

Some properties of hemopoietic stem cells (CFUc) in human cord blood and peripheral blood of neonates were compared with those in bone marrow, by the method for in vitro growth of colony-forming cells in semisolid agar. The number of CFUc circulating in cord blood was 93.5 +/- 57.8 (mean +/- 1 SD)/10(5) cells, which was slightly less than that of bone marrow. The number of CFUc in peripheral blood decreased promptly following birth. From cord and neonatal blood, most colonies were monocyte/macrophage colonies (60.0 +/- 4.6%), whereas those from bone marrow were largely granulocyte colonies (88.3 +/- 6.2%). The differences of growth curve, colony size, and turnover state of CFUc between cord blood and bone marrow seemed, in part, to result from the dominancy of monocyte/macrophage colony-forming cells in cord blood. The cell cycling rate of CFUc in cord blood was remarkably lower than that in bone marrow. From these results, it seems clear that CFUc in cord blood differ in some aspects from those in bone marrow. However, the precise physiologic and functional significance of CFUc circulating in cord and neonatal blood remains unknown.
Microchip Injection and Separation Anomalies Due to Pressure Effects (2001)

While performing routine electroosmotically driven CE separations on microfluidic chips, we have observed peak shape, migration time, and baseline drift anomalies. Pressure-driven backflow (opposing electroosmotic flow (EOF)) has been observed and characterized, and meniscus surface tension (Laplace pressure) is cited as the likely cause. However, there are a number of interdependent factors that affect bulk flow in a microchip environment, including evaporation, buffer depletion due to hydrolysis, EOF pumping, siphoning, viscosity changes due to Joule heating, and Laplace pressure. Given the complexity of such a system, pressure effects were isolated from EOF, and to some extent, siphoning effects were isolated from suspected meniscus effects. Pressure flow observed in the absence of an applied field ranged from 0.4 to 0.8 mm/s, which was on the order of the EOF generated experimentally, 0.6 mm/s at a field of 150 V/cm, and was some 10-20 times larger than what would be predicted merely from a difference in liquid levels (siphoning). Furthermore, experiments were performed without an electric field and with the chip tilted so that meniscus flow ran "uphill" against a siphoning backflow and showed siphoning flow to have a negligible effect upon meniscus flow under the microchip conditions studied. These findings are relevant to the profusion of microfluidic and array-based technology that also use microliter liquid volumes in like-sized reservoirs with similar menisci.
THE GREAT ESCAPE: When Cancer Cells Hijack the Genes for Chemotaxis and Motility (2005)

The combined use of the new technologies of multiphoton-based intravital imaging, the chemotaxis-mediated collection of invasive cells, and high sensitivity expression profiling has allowed the correlation of the behavior of invasive tumor cells in vivo with their gene expression patterns. New insights have resulted including a gene expression signature for invasive cells and the tumor microenvironment invasion model. This model proposes that tumor invasion and metastasis can be studied as a problem resembling normal morphogenesis. We discuss how these new insights may lead to a better understanding of the molecular basis of the invasive behavior of tumor cells in vivo, which may result in new strategies for the diagnosis and treatment of metastasis.
Traffic characteristics of the T1 NSFNET backbone (2002)

The results of a measurement study of the T1 NSFNET backbone are presented. The measurement environment and the approach to data collection are discussed. Measurements results are then presented for: long-term growth in traffic volume, including attribution to domains and protocols; trends in average packet size on the network, over both long- and medium-term intervals; most popular sources, destinations, and site pairs; traffic locality; international distribution of traffic; mean utilization statistics of the overall backbone as well as of specific links of interest: and delay statistics.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Platelet-activating factor: a phospholipid autacoid with diverse actions (1993)

Platelet-activating factor (PAF, 1-0-alkyl-2-acetyl-snglycero-3-phosphocholine) is a potent biological mediator that exerts its effects in a variety of cells and tissues (1-3). This phospholipid mediator was discovered during concurrent investigations of a factor derived from the blood of rabbits undergoing anaphylaxis that activated platelets, and an endogenous polar lipid from kidney that lowered blood pressure. When the common structures were elucidate,d, a new field of research had emerged (reviewed in 1, 2 by the leaders of the two groups that determined the structure). The trivial name, .PAF, is a misnomer as it describes only one of the compound’s many effects. This name, however, has been retained due to the lack of a suitable alternative. Other acronyms that include structural information, e.g., AGEPC (alkyl glycerol ether phosphoryl choline) and PAFacether, have been proposed as substitutes but have not found wide acceptance. PAF is unique in its role as a phospholipid that functions as an intercellular mediator, and it may also function as an intracellular messenger. It acts through a specific receptor, for which a cDNA has been cloned and expressed in mammalian cells. PAF is synthesized by one of two pathways, the first involving the remodeling of cell membrane phospholipids by the hydrolysis of an arachidonate from the sn-2 position and its replacement with an acetate. The second route entails its de novo synthesis from 1-0-alkyl-sn-glycero-3-phosphate hrough the incorporation of an acetate, removal of the phosphate, and its replacement with phosphocholine. PAF is degraded by the removal of the acetate and re-acylation with a fatty acid. The structural elements of PAF are each important for optimal biological activity. Modification of the etherlinkage of the fatty alkyl group at the sn-1 position of the glycerol backbone, the short chain acyl residue (acetate) sn-glycero-3-phosphocholine as PAF, without regard for the length or the degree of unsaturation of the alkyl chain at the sn-1 position, and to refer to structurally related compounds as PAF analogs. These PAF analogs may have substantial bioactivity and participate in signaling in vivo. Some of the most recent findings were presented at the Fourth International Congress on PAF and Related Lipid Mediators in September, 1992 and will be published as brief reports in a special issue of the Jouml OfLipid Mediaton.
Host immune response to cytomegalovirus: products of transfected viral immediate-early genes are recognized by cloned cytolytic T lymphocytes (1987)

To confirm that immediate-early (IE) genes of murine cytomegalovirus (MCMV) give rise to antigens recognized by specific cytolytic T lymphocytes (CTL), a 10.8-kilobase fragment of MCMV DNA which is abundantly transcribed at IE times was transfected into L cells expressing the Ld class I major histocompatibility glycoprotein. The viral genome fragment contains sequences of the three IE transcription units of MCMV: ie1, ie2, and ie3. In the transfected cell lines, only the predominant 2.75-kilobase transcript of ie1 and its translation product pp89 could be detected. The transfectants were analyzed for membrane expression of an IE antigen by employing clone IE1, an IE-specific CTL clone, as the probe. Only cells that expressed both the MCMV IE gene(s) and the Ld gene were recognized by the CTL clone.
New standard helps multimedia get off the ground (1996)

The Institute of Electrical and Electronics Engineers began working on a transmission standard for multimedia networking almost a decade ago. Since the standard's recommendation in December 1994, it has taken little more than a year to capture the attention of manufacturers, vendors, resellers, systems integrators, and network users. The IEEE standard for multimedia in a local area network (LAN) is based on ISLAN-1GT, or isochronous Ethernet. Better known as isoEthernet, the standard incorporates an integrated services digital network phone system with LAN-based Ethernet for mixed data transmission. The IEEE standard, designated 802.9a for LANs and metropolitan area networks, is simply a physical layer standard-just like Ethernet 802.3/ISO 8802-3 and Token Ring 802.5-in that it defines the standard's media access control and physical layer.