gebhart/patrepeval huggingface dataset:
Expression of p21ras in normal and malignant human tissues: lack of association with proliferation and malignancy. (1987)

Proteins encoded by cellular ras oncogenes (p21ras) are expressed in a wide variety of malignant tumors, including carcinomas, lymphomas, and neuroectodermal tumors. The function of p21ras in these tumors and the distribution and role of p21ras in corresponding normal tissues are unclear. This immunohistochemical study examined the relationship between p21ras expression and malignant transformation, cellular differentiation, and proliferative activity in vivo. p21ras was found to be widely expressed in normal tissues, but within those tissues expression was often sharply restricted to cells at specific stages of differentiation; terminally differentiated cells generally showed stronger reactivity with antibodies to p21ras than did rapidly proliferating cells. Fetal and adult tissues had corresponding patterns of p21ras expression, and the distribution of p21ras in neoplasms paralleled the pattern in normal tissue from which they were derived. Thus, p21ras seems to play a role in many fully differentiated cell types, and levels of p21ras expression do not correlate with proliferative activity in normal cell or, in contrast to past reports, with the transformed phenotype.
Silica Films with Bimodal Pore Structure Prepared by Using Membranes as Templates and Amphiphiles as Porogens (2002)

Extended porous silica films with thicknesses in the range of 60 to 130 μm and pores on both the meso- and macroscale have been prepared by simultaneously using porous membrane templates and amphiphilic supramolecular aggregates as porogens. The macropore size is determined by the cellulose acetate or polyamide membrane structure and the mesopores by the chosen ethylene-oxide-based molecular self-assembly (block copolymer or non-ionic surfactants). Both the template and the porogen are removed during an annealing step leaving the amorphous silica material with a porous structure that results from sol–gel chemistry occurring in the aqueous domains of the amphiphilic liquid-crystalline phases and casting of the initial template membrane. The surface area and total pore volume of the inorganic films vary from 473 to 856 m2 g–1, and 0.50 to 0.73 cm3 g–1, respectively, depending on the choice of template and porogen. The combined benefits of both macro- and mesopores can potentially be obtained in one film. Such materials are envisaged to have applications in areas of large molecule (biomolecule) separation and catalysis. Enhanced gas and liquid flow rates through such membranes, due to the presence of the larger pores, also makes them attractive as supports for other catalytic materials.
Cost Drivers in Microlamination Based on a High-Volume Production System Design (2002)

The purpose of this research is to develop a cost estimation model in an attempt to begin exploring the current cost drivers for microlamination. To do this without actual cost information, a production system design is proposed for the high-volume production of MECS devices. Constraints on this facility are that it produces microlaminated structures from stainless steel diffusion bonding. Also, a cost estimation model is developed based on the known cycle time and capital equipment costs from the production system design. Finally, a sensitivity analysis is performed to determine the cost drivers under different market and product scenarios. Results from the sensitivity analysis indicated that device size and production rate do have an effect on the overall manufacturing cost of microlamination devices. Therefore, it is concluded that the emphasis of future research in metallic microlamination should focus on bonding larger laminae and in reducing both cycle time and warpage.
Cost-Effectiveness of Test Phase Implantation Strategies for InterStim® Sacral Neuromodulation (2013)

Bilateral and unilateral stage I lead placement were the only cost-effective strategies. Bilateral stage I was preferred due to greater effectiveness. In probabilistic sensitivity analysis, bilateral stage I was the most likely cost-effective strategy at all willingness-to-pay thresholds greater than $6000 per QALY confirming model robustness.
Hypoxia-inducible factor-1-dependent regulation of the multidrug resistance (MDR1) gene. (2002)

The microenvironment of rapidly growing tumors is associated with increased energy demand and diminished vascular supply, resulting in focal areas of prominent hypoxia. A number of hypoxia-responsive genes have been associated with growing tumors, and here we demonstrate that the multidrug resistance (MDR1) gene product P-glycoprotein, a Mr approximately 170,000 transmembrane protein associated with tumor resistance to chemotherapeutics, is induced by ambient hypoxia. Initial studies using quantitative microarray analysis of RNA revealed an approximately 7-fold increase in MDR in epithelial cells exposed to hypoxia (pO(2) 20 torr, 18 h). These findings were further confirmed at the mRNA and protein level. P-Glycoprotein function was studied by analysis of verapamil-inhibitable efflux of digoxin and rhodamine 123 in intact T84 cells and revealed that hypoxia enhances P-glycoprotein function by as much as 7 +/- 0.4-fold over normoxia. Subsequent studies confirmed hypoxia-elicited MDR1 gene induction and increased P-glycoprotein expression in nontransformed, primary cultures of human microvascular endothelial cells, and analysis of multicellular spheroids subjected to hypoxia revealed increased resistance to doxorubicin. Examination of the MDR1 gene identified a binding site for hypoxia inducible factor-1 (HIF-1), and inhibition of HIF-1 expression by antisense oligonucleotides resulted in significant inhibition of hypoxia-inducible MDR1 expression and a nearly complete loss of basal MDR1 expression. Studies using luciferase promoter constructs revealed a significant increase in activity in cells subjected to hypoxia, and such hypoxia inducibility was lost in truncated constructs lacking the HIF-1 site and in HIF-1 binding site mutants. Extensions of these studies also identified a role for Sp1 in this hypoxia response. Taken together, these data indicate that the MDR1 gene is hypoxia responsive, and such results may identify hypoxia-elicited P-glycoprotein expression as a pathway for resistance of some tumors to chemotherapeutics.
Imaging of Pain (2007)

Vanderbilt University Nashville, Tennessee Reprints: Li Min Chen, MD, PhD, Department of Radiology, Institute of Imaging Science, Vanderbilt University, 1161 21st Ave. S., AA 1105 MCN, Nashville, TN, 37232-2310, E-mail: [email protected]
Novel l-Xylose Derivatives as Selective Sodium-Dependent Glucose Cotransporter 2 (SGLT2) Inhibitors for the Treatment of Type 2 Diabetes (2009)

The prevalence of diabetes throughout the world continues to increase and has become a major health issue. Recently there have been several reports of inhibitors directed toward the sodium-dependent glucose cotransporter 2 (SGLT2) as a method of maintaining glucose homeostasis in diabetic patients. Herein we report the discovery of the novel O-xyloside 7c that inhibits SGLT2 in vitro and urinary glucose reabsorption in vivo.
Non‐thermal food processing/preservation technologies: a review with packaging implications (2007)

Abstract Non‐thermal food processing/preservation methods interest food and food packaging scientists, manufacturers and consumers because they exert a minimal impact on the nutritional and sensory properties of foods, and extend shelf life by inhibiting or killing microorganisms. They are also considered to be more energy efficient and to preserve better quality attributes than conventional thermally based processes. Non‐thermal processes also meet industry needs by offering value‐added products, new market opportunities and added safety margins. This study reviewed non‐thermal processing technologies currently available or developmental for the inactivation of microorganisms and thus microbiological shelf life in foods, and to identify packaging interactions that might result. Processes include ultra‐high pressure, ionizing radiation, pulsed X‐ray, ultrasound, pulsed light and pulsed electric fields, high‐voltage arc discharge, magnetic fields, dense phase carbon dioxide and hurdle technologies. Copyright © 2007 John Wiley &amp; Sons, Ltd.
Prehospital therapeutic hypothermia in cardiac arrest: will there ever be evidence? (2008)

Bruel and colleagues nicely demonstrate that the infusion of 2 l cold saline during resuscitation is a feasible, effective, and safe measure to induce therapeutic hypothermia in out-of-hospital cardiac arrest [1]. Therapeutic hypothermia was induced in 33 eligible advanced life support patients before primary survival was foreseeable, and was continued in 11 patients after intensive care unit admission. The authors conclude that a large randomised trial should be performed.

The design of future trials on therapeutic hypothermia, however, seems challenged by the fact that withholding this treatment in a control arm might be considered unjustifiable from an ethical point of view. In the prehospital setting, such a trial would require a large number of study patients to demonstrate an additional benefit. This is due to the fact that both a spontaneous decline in body core temperature occurs, especially in the no-flow and low-flow phase, and that the overall gain of time (typically around 45 min) may be considered marginal against the background of most published data, indicating that target temperatures cannot be reached until about 6 to 8 hours later [2,3]. Given the optimistic view that prehospital cooling increases the number of favourable neurological outcomes from 55% [4] to 60%, about 750 patients would have to be included in a given randomised trial.

Nevertheless, although we totally agree with Bruel and colleagues that the intervention is safe and feasible, and that a clear biological rationale for the earliest possible induction of therapeutic hypothermia exists [2-5], we doubt that a prospective randomised trial on additional prehospital cooling is feasible and justifiable. We may have reached another boundary of evidence-based medicine.
Fractional Photothermolysis: A New Concept for Cutaneous Remodeling Using Microscopic Patterns of Thermal Injury (2004)

FP is a new concept for skin restoration treatment. Safety and efficacy were demonstrated with a prototype device. Further clinical studies are necessary to refine the optimum parameters and to explore further dermatological applications.
Precise excision of TTAA‐specific lepidopteran transposons piggyBac (IFP2) and tagalong (TFP3) from the baculovirus genome in cell lines from two species of Lepidoptera (1996)

Transposon mutagenesis of baculoviruses provides an ideal experimental system for analysis of the movement of a unique family of mobile element identified from lepidopteran genomes. Members of this family of short-inverted-repeat elements are characterized by their extreme specificity for TTAA target sites. This report describes the analysis of excision events for two representatives of this family, tagalong (formerly TFP3) and piggyBac (formerly IFP2). These elements were tagged with a polyhedrin/lacZ reporter gene and inserted back into the virus genome either by homologous recombination or by transposition. Revertants were selected based on a white plaque phenotype. Both elements excise in a precise fashion from their positions in the baculovirus genome in either TN-368 cells or IPLB-SF21 AE cells. The precise excision of these elements in infected IPLB-SF21 AE cells occurs in the absence of either tagalong or piggyBac element encoded functions. The common characteristics of both insertion and excision for these elements provides further validation for their inclusion in a single family of unique transposons.
Autoantibodies directed against the protease inhibitor calpastatin in psoriasis (2004)

Psoriasis is believed to be a T cell-mediated autoimmune disease, but also exhibits autoantibody production. Calpastatin is an endogenous inhibitor of calpain, a ubiquitous protease that regulates inflammatory processes. Anti-calpastatin autoantibody was first identified as an autoantibody specific to rheumatoid arthritis, but has been also detected in other autoimmune diseases. In this study, we examined the presence and levels of anti-calpastatin antibody in 77 psoriasis patients by enzyme-linked immunosorbent assay. Compared with normal controls, psoriasis patients exhibited significantly elevated IgG anti-calpastatin antibody levels that were similar to those found in rheumatoid arthritis patients. Remarkably, IgG anti-calpastatin autoantibody in sera from psoriasis patients inhibited calpastatin activity. Calpain II expression was up-regulated in psoriasis skin lesions compared with normal skin while calpastatin expression was normal. The results of this study reveal the presence of anti-calpastatin autoantibody in psoriasis.
Intranasal Sufentanil for Postoperative Pain Control in Lower Abdominal Pediatric Surgery (2006)

The most important role in postoperative pain management is still played by opioid administration through various modes. For the last few years, there has been an intensive search for alternative mode of opioid administration in pain management. The intranasal modes of opioid administration seems to be an attractive alternative. Sixty boys (aged 0.5-6 yr); ASA (American Society of Anesthesiologists) physical status I, who were candidates for lower abdominal surgery, were included in this prospective randomized, controlled study. Five minutes before extubation, patients were randomized to two groups and allocated to receive intranasal sufentanil (0.7 μg/kg) or normal saline, using a double-blinded study design. Satisfactory analgesia was achieved with intranasal sufentanil. It was effective after 10 minutes with the least pain scores (pain score 2.3±0.4 vs. 4.1±0.5) (p = 0.001). Pain scores in 15, 20 and 25 minutes were similar in sufentanil group. None of patients had bradycardia, hypotension or SpO2 (arterial O2 saturation) &lt;95%. High bioavailability of sufentanil after intranasal administration due to direct entrance of the drug into the systemic circulation and avoidance of the hepatic first- pass effect makes sufentanil an opioid with rapid onset and limited duration. As it has minimal side effects, sufentanil is one of the best choices for postoperative pain control in children. We used 0.7 μg/kg of intranasal sufentanil and found satisfactory analgesia accompanied with least side effects.
Long-term survival of skin allografts induced by donor splenocytes and anti-CD154 antibody in thymectomized mice requires CD4(+) T cells, interferon-gamma, and CTLA4. (1998)

Treatment of C57BL/6 mice with one transfusion of BALB/c spleen cells and anti-CD154 (anti-CD40-ligand) antibody permits BALB/c islet grafts to survive indefinitely and BALB/c skin grafts to survive for approximately 50 d without further intervention. The protocol induces long-term allograft survival, but the mechanism is unknown. We now report: (a) addition of thymectomy to the protocol permitted skin allografts to survive for > 100 d, suggesting that graft rejection in euthymic mice results from thymic export of alloreactive T cells. (b) Clonal deletion is not the mechanism of underlying long-term graft survival, as recipient thymectomized mice were immunocompetent and harbor alloreactive T cells. (c) Induction of skin allograft acceptance initially depended on the presence of IFN-gamma, CTLA4, and CD4(+) T cells. Addition of anti-CTLA4 or anti-IFN-gamma mAb to the protocol was associated with prompt graft rejection, whereas anti-IL-4 mAb had no effect. The role of IFN-gamma was confirmed using knockout mice. (d) Graft survival was associated with the absence of IFN-gamma in the graft. (e) Long-term graft maintenance required the continued presence of CD4(+) T cells. The results suggest that, with modification, our short-term protocol may yield a procedure for the induction of long-term graft survival without prolonged immunosuppression.
Granzyme A binding to target cell proteins. Granzyme A binds to and cleaves nucleolin in vitro (1991)

The physiologic substrates of cytotoxic T lymphocyte granule-associated serine esterases (referred to hereafter as proteases or "granzymes"), and the role of these enzymes in cell-mediated activity remain unclear. We have developed an assay for possible ligands of the trypsin-like dimeric serine protease granzyme A based on Western immunoblotting techniques. This protein-binding assay demonstrates the selective binding of granzyme A to several proteins present in the target cell P815. The binding specificity is preserved when enzyme binding is performed in the presence of excess competing proteins, including such cationic species as lysozyme and RNase. Enzyme binding is inhibited, however, by heat or detergent inactivation of granzyme A. Subcellular fractionation of target cells shows that the nuclear fraction contains most granzyme A binding reactivity, which is recovered in the nuclear salt wash fraction. A protein with Mr = 100,000 and two closely migrating proteins with Mr = 35,000 and 38,000 are the predominant reactive moieties, and the N-terminal sequence of the 100-kDa protein confirmed that this protein was murine nucleolin. Incubation of granzyme A with nucleolin generates a discrete proteolytic cleavage product of Mr = 88,000. Since nucleolin is known to shuttle between nucleus and cytoplasm, the interaction of granzyme A and nucleolin may be important in the process of apoptosis which accompanies cytotoxic T lymphocyte-mediated lysis of target cells.
All for one and one for all: condensations and the initiation of skeletal development (2000)

Condensation is the pivotal stage in the development of skeletal and other mesenchymal tissues. It occurs when a previously dispersed population of cells gathers together to differentiate into a single cell/tissue type such as cartilage, bone, muscle, tendon, kidney, and lung and is the earliest stage during organ formation when tissue-specific genes are upregulated. We present a synopsis of our current understanding of how condensations are initiated and grown, how their boundaries and sizes are set, how condensation ceases, and how overt differentiation begins. Extracellular matrix molecules, cell surface receptors and cell adhesion molecules, such as fibronectin, tenascin, syndecan, and N-CAM, initiate condensation formation and set condensation boundaries. Hox genes (Hoxd-11-13) and other transcription factors (CFKH-1, MFH-1, osf-2), modulate the proliferation of cells within condensations. Cell adhesion is ensured indirectly through Hox genes (Hoxa-2, Hoxd-13), and directly via cell adhesion molecules (N-CAM and N-cadherin). Subsequent growth of condensations is regulated by BMPs, which activate Pax-2, Hoxa-2 and Hoxd-11 among other genes. Growth of a condensation ceases when Noggin inhibits BMP signalling, setting the stage for transition to the next stage of skeletal development, namely overt cell differentiation. BioEssays 22:138-147, 2000.
Unusual DNA sequences located within the promoter region and the first intron of the chicken pro-alpha 1(I) collagen gene. (1987)

Genomic clones corresponding to the amino-terminal propeptide and 5'-flanking sequences of the chicken pro-alpha 1(I) collagen gene were isolated as a first step in the identification of DNA sequences important for transcriptional regulation of the pro-alpha 1(I) collagen gene. Due to the failure to identify positive clones in either primary or amplified genomic libraries, a 5.1-kilobase pair StuI genomic fragment identified by Southern blotting was enriched by sucrose gradient fractionation of genomic DNA and cloned into lambda gt11. Comparison of the DNA sequence of the 5.1-kilobase pair StuI fragment to the DNA sequence of a cDNA clone encoding the amino-terminal propeptide, signal peptide, and the 5'-untranslated region identified the first four exons and most of the fifth. Exon size and intron position have been largely conserved between human and chicken alpha 1(I) genes. DNA sequence analysis of the region 5' to the transcription initiation site identified the canonical TATA and CAAT boxes. However, the 40-nucleotide pyrimidine stretch centered between -150 and -180 nucleotides, found in all previously isolated type I procollagen genes from chicken, mouse, and human, was absent in the chicken pro-alpha 1(I) collagen gene. This sequence corresponds to the in vivo DNase I hypersensitive site in the chicken pro-alpha 2(I) and mouse pro-alpha 1(I) collagen genes, as well as the in vitro S1 nuclease hypersensitive site in both chicken and mouse pro-alpha 2(I) collagen genes. Two unusual DNA sequences were identified within the chicken pro-alpha 1(I) collagen gene. Fifteen tandem repeats of the sequence GGGGAGA were identified within the first intron, 300 nucleotides 3' to the first exon. This sequence was identified due to its hypersensitivity to S1 nuclease in vitro in supercoiled plasmids. The second sequence located 5' to -180 contained at least 25 copies of a polymorphic, 23-base pair tandemly repeated sequence not identified in other type I procollagen genes. Both of these tandem repeat sequences were identified at other locations in the chicken genome by Southern blot hybridization.
Interaction of hnRNPA1/A2 and DAZAP1 with an Alu-Derived Intronic Splicing Enhancer Regulates ATM Aberrant Splicing (2011)

We have previously identified an Alu-derived Intronic Splicing enhancer (ISE) in the Ataxia Teleangectasia Mutated gene (ATM) that facilitates intron pre-mRNA processing and leads to the inclusion of a cryptic exon in the final mRNA transcript. By using an RNA pull-down assay, we show here that hnRNPA1/A2, HuR and DAZAP1 splicing factors and DHX36 RNA helicase bind to the ISE. By functional studies (overexpression and siRNA experiments), we demonstrate that hnRNPA1 and DAZAP1 are indeed involved in ISE-dependent ATM cryptic exon activation, with hnRNPA1 acting negatively and DAZAP1 positively on splicing selection. On the contrary, HuR and DHX36 have no effect on ATM splicing pattern. These data suggest that splicing factors with both negative and positive effect can assemble on the intronic Alu repeats and regulate pre-mRNA splicing.
Cdc7p-Dbf4p becomes famous in the cell cycle (2000)

Great insight into the molecular details of cell cycle regulation has been obtained in the past decade. However, most of the progress has been in defining the regulation of the family of cyclin-dependent kinases (CDKs). Recent studies of a myriad of eukaryotic organisms have defined both the regulation and substrates of Cdc7p kinase, which forms a CDK-cyclin-like complex with Dbf4p, is necessary for the initiation of DNA replication and has been conserved in evolution. This kinase is also required for the induction of mutations after DNA damage and for commitment to recombination in the meiotic cell cycle. However, less is known about the role of the kinase in these processes. In a manner similar to CDKs, Cdc7p is activated by a regulatory subunit, Dbf4, the levels of which fluctuate during the cell cycle. One or more subunits of the conserved MCM helicase complex at chromosomal origins of DNA replication are substrates for the kinase during S phase. Phosphorylation of the MCM complex by Cdc7p-Dbf4p might activate DNA replication by unwinding DNA. Therefore, activation of Cdc7p is required for DNA replication. Given that Cdc7p-Dbf4 kinase is overexpressed in many neoplastic cells and tumors, it might be an important early biomarker during cancer progression.