gebhart/patrepeval huggingface dataset:
Systematic Evaluation of Chimeric Marker Genes on Dicistronic Transcription Units for Regulated Expression of Transgenes In Vitro and In Vivo (1996)

Plasmid expression vectors combining human cytokine cDNAs and selectable marker genes on dicistronic transcription units were functionally characterized in vitro and in vivo. The internal ribosome entry sequence (IRES) of encephalomyocarditis virus mediated cap-independent translation of the downstream cistron. After cationic lipofection of cells with a dicistronic construct containing the Neor gene downstream of a human interleukin-2 (IL-2) cDNA, all G418-resistant clones secreted high amounts of IL-2. Reversal of the order of the cDNAs was associated with less efficient transgene expression and represented no advantage in comparison to separate expression cassettes. To combine direct in vitro selection of expression with in vivo elimination of cytokine-secreting cells, an improved chimeric cDNA of the Neor and herpes simplex virus (HSV) thymidine kinase (TK) genes was constructed and shown to confer sensitivity to ganciclovir concentrations that can be achieved in human patients. This chimeric marker was coupled on dicistronic constructs with a granulocyte colony-stimulating factor (G-CSF) cDNA as a molecule with easily detectable bioactivity in vivo. Subcutaneous implantation of pCMV.GCSF.ires TK/NEO-transfected CMS-5 cells into syngeneic BALB/c mice resulted in excessive leukocytosis and progressively growing tumors. Treatment with ganciclovir led to normalization of leukocyte counts in all animals, whereas complete regression of tumors was observed in only 3/5 mice. Hypermethylation of the transfected promoter was demonstrated in both ganciclovir-resistant tumors. Thus, transcription units combining selectable markers and genes of interest allow selection of high producer cells in vitro and efficient elimination of transgene-expressing cells in vivo. However, cells that hypermethylate transfected genes to terminate gene expression in vivo may escape conditional ablation.
Performance and fluid simulations of a novel shared buffer management system (2002)

We consider a switching system which has multiple ports that share a common buffer, in which there is a FIFO logical queue for each port. Each port may support a large number of flows or connections, which are approximately homogeneous in their statistical characteristics, with common QoS requirements in cell loss and maximum delay. Heterogeneity may exist across ports. Our first contribution is a buffer management scheme based on buffer admission control, which is integrated with connection admission control at the switch, and is at the same time fair, efficient and robust in sharing the buffer resources across ports. Our scheme is based on the resource-sharing technique of virtual partitioning. Our second major contribution is to advance the practice of discrete-event fluid simulations. Such simulations are approximations to cell-level simulations and offer orders of magnitude speed-up. A third contribution of the paper is the formulation and solution of a problem of optimal allocation of bandwidth and buffers to each port having specific delay bounds, in a lossless multiplexing framework. Finally, we report on extensive simulation results. The scheme is found to be effective, efficient and robust.
Omentin Plasma Levels and Gene Expression Are Decreased in Obesity (2007)

Central obesity and the accumulation of visceral fat are risk factors for the development of type 2 diabetes and cardiovascular disease. Omentin is a protein expressed and secreted from visceral but not subcutaneous adipose tissue that increases insulin sensitivity in human adipocytes. To determine the impact of obesity-dependent insulin resistance on the regulation of two omentin isoforms, gene expression and plasma levels were measured in lean, overweight, and obese subjects. Omentin 1 was shown to be the major circulating isoform in human plasma. Lean subjects had significantly higher plasma omentin 1 levels than obese and overweight subjects. In addition, higher plasma omentin 1 levels were detected in women compared with men. Plasma omentin 1 levels were inversely correlated with BMI, waist circumference, leptin levels, and insulin resistance as measured by homeostasis model assessment and positively correlated with adiponectin and HDL levels. Both omentin 1 and omentin 2 gene expression were decreased with obesity and were highly correlated with each other in visceral adipose tissue. In summary, decreased omentin levels are associated with increasing obesity and insulin resistance. Therefore, omentin levels may be predictive of the metabolic consequences or co-morbidities associated with obesity.
Loss of homotypic cell adhesion by epithelial-mesenchymal transition or mutation limits sensitivity to epidermal growth factor receptor inhibition (2007)

Abstract Overexpression and enhanced activation of the epidermal growth factor receptor (EGFR) is frequently observed in human carcinomas. Inhibitors of EGFR signaling have shown clinical utility; however, understanding response at the molecular level is important to define patient subsets most likely to benefit, as well as to support the rational design of drug combinations. Pancreatic and colorectal tumor cell lines insensitive to EGFR inhibition were those that had lost or mutated the epithelial junction constituents E-cadherin and γ-catenin, had lost homotypic adhesion, and often gained proteins associated with an epithelial to mesenchymal–like transition, such as vimentin, zeb1, or snail. In matched pairs of colorectal tumor cells, the epithelial lines showed an average 7-fold greater sensitivity than mesenchymal-like lines. In human pancreatic and colorectal tumor tissues, gain of mesenchymal characteristics and loss of epithelial characteristics correlated with advancing tumor stage. These data indicate an especially sensitive patient subset as well as a rationale for the combination of EGFR antagonists with agents that affect the epithelial to mesenchymal–like transition process as a mechanism to enhance sensitivity for more advanced mesenchymal-like tumors. [Mol Cancer Ther 2007;6(2):532–41]
Tobacco-specific nitrosamines (1996)

Division of Toxicology and Cancer Risk Factors, German Cancer Research Centre, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany. (+49) 6221 423 359
Bone mineralization‐dependent craniosynostosis and craniofacial shape abnormalities in the mouse model of infantile hypophosphatasia (2015)

These results indicate that variability of the HPP phenotype is not entirely dependent upon the type of genetic mutation and level of residual alkaline phosphatase activity. Additionally, despite a severity continuum of the bone hypomineralization phenotype, craniofacial skeletal shape abnormalities and craniosynostosis occur only in the context of severely diminished bone mineralization in the Alpl(-/-) mouse model of HPP.
Dexmedetomidine Infusion as Adjunctive Therapy to Benzodiazepines for Acute Alcohol Withdrawal (2008)

In patients with delirium tremens, dexmedetomidine should be considered as an option for primary treatment. This case illustrates the need for further studies to investigate other potential uses for dexmedetomidine.
Increased expression of procoagulant activity on the surface of human platelets exposed to heavy-metal compounds (1995)

One of the essential roles for platelets in haemostasis is in the potentiation of blood clotting due to the contribution of anionic phospholipid from the surface of the cells, as an essential cofactor to the proteolytic reactions of coagulation (platelet procoagulant activity). Only a limited number of agonists are known to initiate platelet procoagulant activity. In this study the rate of thrombin formation on the platelet surface was observed to increase in a dose-dependent manner upon treatment of washed platelets with heavy-metal compounds. Unlike the immediate increase observed upon treatment of platelets with calcium ionophore, A23187, the change due to these agents was progressive, approaching a maximum after 10 min. The maximum-fold acceleration of the rate of thrombin formation compared with control platelets was calculated for HgCl2 (56-fold), AgNO3 (42-fold) phenylmercuriacetate (24-fold) and thimerosal (14-fold), compared with 70-fold observed for calcium ionophore. The increase in procoagulant activity due to HgCl2 coincided with a large increase in intracellular calcium and phosphorylation of 22 and 45 kDa proteins. It is considered that the mechanism responsible for the increase in procoagulant activity is exposure of anionic phospholipids. This was detected by a 2-fold increase in the binding of 125I-annexin V upon addition of HgCl2, compared with resting platelets (3-fold on treatment of platelets with calcium ionophore). In contrast to the generation of activity by A23187 and other known agonists of this reaction, heavy-metal compounds appeared to cause little or no release of microparticles from the platelet surface. Since HgCl2 did not cause aggregation of platelets or significant release of serotinin, these findings may give further support to the need for exposure and ligation of glycoprotein IIb:IIIa for vesiculization to occur. Treatment of platelets with heavy metals may constitute a new approach to investigating the early changes in the cell membrane which lead to increased expression of anionic phospholipid.
Repurposing Salicylanilide Anthelmintic Drugs to Combat Drug Resistant Staphylococcus aureus (2015)

Staphylococcus aureus is a Gram-positive bacterium that has become the leading cause of hospital acquired infections in the US. Repurposing Food and Drug Administration (FDA) approved drugs for antimicrobial therapy involves lower risks and costs compared to de novo development of novel antimicrobial agents. In this study, we examined the antimicrobial properties of two commercially available anthelmintic drugs. The FDA approved drug niclosamide and the veterinary drug oxyclozanide displayed strong in vivo and in vitro activity against methicillin resistant S. aureus (minimum inhibitory concentration (MIC): 0.125 and 0.5 μg/ml respectively; minimum effective concentration: ≤ 0.78 μg/ml for both drugs). The two drugs were also effective against another Gram-positive bacteria Enterococcus faecium (MIC 0.25 and 2 μg/ml respectively), but not against the Gram-negative species Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter aerogenes. The in vitro antimicrobial activity of niclosamide and oxyclozanide were determined against methicillin, vancomycin, linezolid or daptomycin resistant S. aureus clinical isolates, with MICs at 0.0625-0.5 and 0.125-2 μg/ml for niclosamide and oxyclozanide respectively. A time-kill study demonstrated that niclosamide is bacteriostatic, whereas oxyclozanide is bactericidal. Interestingly, oxyclozanide permeabilized the bacterial membrane but neither of the anthelmintic drugs exhibited demonstrable toxicity to sheep erythrocytes. Oxyclozanide was non-toxic to HepG2 human liver carcinoma cells within the range of its in vitro MICs but niclosamide displayed toxicity even at low concentrations. These data show that the salicylanilide anthelmintic drugs niclosamide and oxyclozanide are suitable candidates for mechanism of action studies and further clinical evaluation for treatment of staphylococcal infections.
Fecal Bacteriotherapy for Relapsing Clostridium difficile Infection in a Child: A Proposed Treatment Protocol (2010)

Clostridium difficile infection (CDI) is a potentially serious emerging infectious disease. The incidences of CDI in childhood and CDI cases complicated by relapses have increased by 50% or more in North America during the past 2 decades. We report here the case of a 2-year-old child with relapsing CDI caused by the epidemic strain BI/NAP1/O27 that was refractory to Saccharomyces boulardii and Lactobacillus rhamnosus GG probiotics and to intensive therapy with traditional (metronidazole, vancomycin) and experimental (rifaximin, nitazoxanide) antibiotics despite its apparent antimicrobial-susceptible phenotype. After excluding other infectious causes of diarrhea and inflammatory bowel disease, we designed a protocol to safely administer fecal bacteriotherapy via a temporary nasogastric tube. We demonstrated for the first time that fecal transplantation is practical and effective for treating relapsing CDI in a young child. We recommend that this strategy be reserved for complicated cases of CDI that fail conventional therapy until randomized studies can confirm the safety and effectiveness of fecal bacteriotherapy in children.
Local intratumor immunotherapy of prostate cancer with interleukin-2 reduces tumor growth. (1999)

IL-2 depot preparations reduce tumor growth in Dunning adenocarcinoma of the prostate significantly without toxicity.
Subtilases: The superfamily of subtilisin-like serine proteases (1997)

Subtilases are members of the clan (or superfamily) of subtilisin-like serine proteases. Over 200 subtilases are presently known, more than 170 of which with their complete amino acid sequence. In this update of our previous overview (Siezen RJ, de Vos WM, Leunissen JAM, Dijkstra BW, 1991, Protein Eng 4:719-731), details of more than 100 new subtilases discovered in the past five years are summarized, and amino acid sequences of their catalytic domains are compared in a multiple sequence alignment. Based on sequence homology, a subdivision into six families is proposed. Highly conserved residues of the catalytic domain are identified, as are large or unusual deletions and insertions. Predictions have been updated for Ca(2+)-binding sites, disulfide bonds, and substrate specificity, based on both sequence alignment and three-dimensional homology modeling.
Multicolored Light-Emitting Diodes Based on All-Quantum-Dot Multilayer Films Using Layer-by-Layer Assembly Method (2010)

A systematic analysis of the exciton-recombination zone within all-quantum dot (QD) multilayer films prepared by a layer-by-layer assembly method was made, using sensing QD layers in QD-based light-emitting diodes (QLEDs). Large area practical multicolored colloidal QLEDs were also demonstrated by patterning and placing variously colored QDs (red, orange, yellow-green, and green) in the exciton-recombination zone.
Tumor necrosis factor (1993)

Wenzel, Richard P. MD, MSc; Bone, Roger C. MD, FCCM; Glauser, Michel P. MD Author Information
Expression of the Kp43 (CD 94) receptor by natural killer (NK) cells in ulcerative colitis. (2002)

These findings suggest that natural killer cells are increased in active ulcerative colitis subjects and that the affected mucosa of ulcerative colitis patients with inactive disease is in state of "latent" inflammation. On the other hand, the normal looking mucosa from active ulcerative colitis patients does not differ from the mucosa of control subjects. Therefore, it seems that in ulcerative colitis the immunological alterations are limited to the affected mucosa.
Production of Complex Human Glycoproteins in Yeast (2003)

We report the humanization of the glycosylation pathway in the yeast Pichia pastoris to secrete a human glycoprotein with uniform complex N-glycosylation. The process involved eliminating endogenous yeast glycosylation pathways, while properly localizing five active eukaryotic proteins, including mannosidases I and II, N-acetylglucosaminyl transferases I and II, and uridine 5'-diphosphate (UDP)-N-acetylglucosamine transporter. Targeted localization of the enzymes enabled the generation of a synthetic in vivo glycosylation pathway, which produced the complex human N-glycan N-acetylglucosamine2-mannose3-N-acetylglucosamine2 (GlcNAc2Man3GlcNAc2). The ability to generate human glycoproteins with homogeneous N-glycan structures in a fungal host is a step toward producing therapeutic glycoproteins and could become a tool for elucidating the structure-function relation of glycoproteins.
Generation of packaging cell lines for pseudotyped retroviral vectors of the G protein of vesicular stomatitis virus by using a modified tetracycline inducible system. (1996)

We have previously shown that the G protein of vesicular stomatitis virus (VSV-G) can be incorporated into the virions of retroviruses. Since expression of VSV-G is toxic to most mammalian cells, development of stable VSV-G packaging cell lines requires inducible VSV-G expression. We have modified the tetracycline-inducible system by fusing the ligand binding domain of the estrogen receptor to the carboxy terminus of a tetracycline-regulated transactivator. Using this system, we show that VSV-G expression is tetracycline-dependent and can be modulated by beta-estradiol. Stable packaging cell lines can readily be established and high-titer pseudotyped retroviral vectors can be generated upon induction of VSV-G expression.
Framework for a Comparative Environmental Assessment of Drilling Fluids Used Offshore (1999)

Abstract In response to effluent limitation guidelines promulgated by the United States Environmental Protection Agency, industry has developed alternatives to the water and oil-based drilling fluids used offshore. These synthetic-based muds (SBMs), enhanced mineral oils (EMOs) and purified paraffin oils have lower toxicity and smaller environmental impacts than diesel or conventional mineral oil-based muds (OBMs). EPA is developing new guidelines for the discharge of these fluids and the associated cuttings. The decision about allowing or disallowing the discharge of cuttings with small amounts of associated SBMs, EMOs and purified paraffin oils should not be based solely on potential environmental impacts, especially those such as bioaccumulation or biodegradation that may not be directly connected to effects on populations or ecosystems. Regulatory decisions about drilling fluid discharges should also consider potential impacts associated with the alterna-tives; including occupational accidents and chemical expo-sures, impacts associated with disposal, air emissions, and transportation risks. Because these new fluids are expensive, industry will not continue to use them if the cuttings cannot be discharged offshore. The alternative to allowing the discharge of these new drilling fluids is the continuing use of OBMs in difficult drilling situations. This paper develops a framework for a comparative environmental assessment for the discharge of drilling fluids, to help support a risk-based, integrated approach to regulatory decision making.
A cartilage‐derived growth factor enhances hyaluronate synthesis and diminishes sulfated glycosaminoglycan synthesis in chondrocytes (1986)

Cartilage-derived growth factor purified to homogeneity by affinity chromatography on columns of heparin-Sepharose was mitogenic for early passage bovine fetal chondrocytes. Hyaluronate and sulfated glycosaminoglycan synthesis in these cells was analyzed by differential enzymatic digestion of the glycosaminoglycans labeled with [14C] glucosamine or [35S]. It was found that chondrocyte proliferation was accompanied by about a four-fold increase in hyaluronate synthesis over a two-day period, while the synthesis of sulfated glycosaminoglycans decreased by about 2-fold. Chromatographic analysis of the sulfated glycosaminoglycans showed decreases in chondroitin 4 and 6 sulfates. It was concluded from these results that cartilage-derived growth factor was a proliferative factor for chondrocytes and differed from the somatomedins.
Using latent semantic indexing for information filtering (1990)

Latent Semantic Indexing (LSI) is an information retrieval method that organizes information into a semantic structure that takes advantage of some of the implicit higher-order associations of words with text objects. The resulting structure reflects the major associative patterns in the data while ignoring some of the smaller variations that may be due to idiosyncrasies in the word usage of individual documents. This permits retrieval based on the “latent” semantic content of the documents rather than just on keyword matches. This paper evaluates using LSI for filtering information such as Netnews articles based on a model of user preferences for articles. Users judged articles on how interesting they were and based on these judgements, LSI predicted whether new articles would be judged interesting. LSI improved prediction performance over keyword matching an average of 13% and showed a 26% improvement in precision over presenting articles in the order received. The results indicate that user preferences for articles tend to cluster based on the semantic similarities between articles.
Expression and characterization of genetically engineered human immunodeficiency virus-like particles containing modified envelope glycoproteins: implications for development of a cross-protective AIDS vaccine (1992)

Noninfectious human immunodeficiency virus type 1 (HIV-1) viruslike particles containing chimeric envelope glycoproteins were expressed in mammalian cells by using inducible promoters. We engineered four expression vectors in which a synthetic oligomer encoding gp120 residues 306 to 328 (amino acids YNKRKRIHIGP GRAFYTTKNIIG) from the V3 loop of the MN viral isolate was inserted at various positions within the endogenous HIV-1LAI env gene. Expression studies revealed that insertion of the heterologous V3(MN) loop segment at two different locations within the conserved region 2 (C2) of gp120, either 173 or 242 residues away from the N terminus of the mature subunit, resulted in the secretion of fully assembled HIV-like particles containing chimeric LAI/MN envelope glycoproteins. Both V3 loop epitopes were recognized by loop-specific neutralizing antibodies. However, insertion of the V3(MN) loop segment into other regions of gp120 led to the production of envelope-deficient viruslike particles. Immunization with HIV-like particles containing chimeric envelope proteins induced specific antibody responses against both the autologous and heterologous V3 loop epitopes, including cross-neutralizing antibodies against the HIV-1LAI and HIV-1MN isolates. This study, therefore, demonstrates the feasibility of genetically engineering optimized HIV-like particles capable of eliciting cross-neutralizing antibodies.
Selective Induction of Th2-Attracting Chemokines CCL17 and CCL22 in Human B Cells by Latent Membrane Protein 1 of Epstein-Barr Virus (2004)

Chemokines are likely to play important roles in the pathophysiology of diseases associated with Epstein-Barr virus (EBV). Here, we have analyzed the repertoire of chemokines expressed by EBV-infected B cells. EBV infection of B cells induced expression of TARC/CCL17 and MDC/CCL22, which are known to attract Th2 cells and regulatory T cells via CCR4, and also upregulated constitutive expression of MIP-1 alpha/CCL3, MIP-1 beta/CCL4, and RANTES/CCL5, which are known to attract Th1 cells and cytotoxic T cells via CCR5. Accordingly, EBV-immortalized B cells secreted these chemokines, especially CCL3, CCL4, and CCL22, in large quantities. EBV infection or stable expression of LMP1 also induced CCL17 and CCL22 in a B-cell line, BJAB. The inhibitors of the TRAF/NF-kappa B pathway (BAY11-7082) and the p38/ATF2 pathway (SB202190) selectively suppressed the expression of CCL17 and CCL22 in EBV-immortalized B cells and BJAB-LMP1. Consistently, transient-transfection assays using CCL22 promoter-reporter constructs demonstrated that two NF-kappa B sites and a single AP-1 site were involved in the activation of the CCL22 promoter by LMP1. Finally, serum CCL22 levels were significantly elevated in infectious mononucleosis. Collectively, LMP1 induces CCL17 and CCL22 in EBV-infected B cells via activation of NF-kappa B and probably ATF2. Production of CCL17 and CCL22, which attract Th2 and regulatory T cells, may help EBV-infected B cells evade immune surveillance by Th1 cells. However, the concomitant production of CCL3, CCL4, and CCL5 by EBV-infected B cells may eventually attract Th1 cells and cytotoxic T cells, leading to elimination of EBV-infected B cells at latency III and to selection of those with limited expression of latent genes.