gebhart/patrepeval huggingface dataset:
The prognostic significance of specific HOX gene expression patterns in ovarian cancer (2016)

HOX genes are vital for all aspects of mammalian growth and differentiation, and their dysregulated expression is related to ovarian carcinogenesis. The aim of the current study was to establish the prognostic value of HOX dysregulation as well as its role in platinum resistance. The potential to target HOX proteins through the HOX/PBX interaction was also explored in the context of platinum resistance. HOX gene expression was determined in ovarian cancer cell lines and primary EOCs by QPCR, and compared to expression in normal ovarian epithelium and fallopian tube tissue samples. Statistical analysis included one-way ANOVA and t-tests, using statistical software R and GraphPad. The analysis identified 36 of the 39 HOX genes as being overexpressed in high grade serous EOC compared to normal tissue. We detected a molecular HOX gene-signature that predicted poor outcome. Overexpression of HOXB4 and HOXB9 was identified in high grade serous cell lines after platinum resistance developed. Targeting the HOX/PBX dimer with the HXR9 peptide enhanced the cytotoxicity of cisplatin in platinum-resistant ovarian cancer. In conclusion, this study has shown the HOX genes are highly dysregulated in ovarian cancer with high expression of HOXA13, B6, C13, D1 and D13 being predictive of poor clinical outcome. Targeting the HOX/PBX dimer in platinum-resistant cancer represents a potentially new therapeutic option that should be further developed and tested in clinical trials.
Choice of a routine method for detecting methicillin-resistance in staphylococci (1996)

Four methods were compared for their abilities to detect methicillin-resistance of Staphylococcus strains using mecA gene PCR analysis in 6 h as the gold standard. 57 Staphylococcus aureus and 100 coagulase negative staphylococci (CNS) were evaluated by the oxacillin disc diffusion method (Kirby-Bauer), the automated API (ATB-plus) system (bioMérieux, La Balme les Grottes, France) in 24 h, the rapid BBL Crystal MRSA ID system (Becton Dickinson, Cockeysville, Md.), the oxillin MICs using the NCCLS agar dilution method in 24 h, and the mecA gene PCR analysis. For S. aureus, the correlation was excellent between the BBL Crystal MRSA ID system and mecA gene PCR analysis (positive predictive value = 100%; negative predictive value = 97%) and oxacillin MIC (positive predictive value = 96%; negative predictive value = 96%). The correlation between BBL Crystal MRSA ID and mecA gene PCR was not reliable for CNS (negative predictive value = 68%). For CNS, the slower routine susceptibility methods to identify intrinsic methicillin-resistance were better: API ATB Staph has a positive predictive value = 94% and a negative predictive value = 82%, and the disc diffusion test has a positive predictive value = 95% and a negative predictive value = 74%. However, BBL Crystal MRSA ID was as reliable as some of the other methods tested for CNS after 6 h incubation when the inoculum was increased: positive predictive value = 94% and a negative predictive value = 77%. These results emphasize that genotypic detection of methicillin-resistance will undoubtedly become important to detect rapidly methicillin-resistance, especially for CNS.
Chronic Interleukin-6 Alters NMDA Receptor-Mediated Membrane Responses and Enhances Neurotoxicity in Developing CNS Neurons (1998)

Recent studies show that the cytokine interleukin-6 (IL-6) is expressed at elevated levels in the CNS in several disease states and contributes to the neuropathological process. The mechanisms through which IL-6 exerts its CNS effects are primarily unknown. We have investigated the pathophysiological effects of IL-6 on developing CNS neurons using a culture model system and a chronic treatment paradigm. Here, we show, using current- and voltage-clamp recordings, that chronic IL-6 treatment of developing cerebellar granule neurons increases the membrane and current response to NMDA and that these effects are the primary mechanism through which IL-6 produces an enhanced calcium signal to NMDA. We also show that calcium influx through voltage-sensitive calcium channels contributes to the enhanced calcium signal to NMDA in the IL-6-treated neurons in a developmentally regulated manner and that the membrane depolarization to NMDA is more sensitive to the NMDA receptor antagonist ifenprodil in the IL-6-treated neurons compared with control neurons at a late developmental stage, consistent with a larger proportion of NMDA receptors containing the NMDAR2B subunit in the IL-6-treated neurons. Additional studies show that IL-6 treatment reduces the number of granule neurons in culture and enhances neurotoxicity involving NMDA receptors. These results support a pathological role for IL-6 in the CNS and indicate that NMDA receptor-mediated functions are likely to play a critical role in neuropathological changes observed in CNS diseases associated with elevated CNS levels of IL-6.
Selective degradation of cyclin B1 mRNA in rat oocytes by RNA interference (RNAi) (2004)

Cyclic adenosine monophosphate (cAMP) keeps oocytes in meiotic arrest, thereby preventing activation of the key regulators of meiosis, p34cdc2/cyclin B1, (known as maturation-promoting factor (MPF)) and Erk 1 and 2, members of the mitogen-activated protein kinase (MAPK) family. The activity of MAPK in oocytes is upregulated by Mos. We previously demonstrated that Mos translation in rat oocytes is negatively regulated by a PKA-mediated cAMP action, which inhibits c-mos mRNA polyadenylation and is associated with the suppression of p34 cdc2 kinase. The goal of the present study was to provide definitive evidence that Mos translation is subjected to MPF regulation. In order to inhibit MPF activity, we employed the double-stranded (ds) RNA interference (RNAi) of gene expression. We demonstrated that the introduction of cyclin B1 dsRNA into rat oocytes selectively depleted the corresponding mRNA, further ablating its protein product. These oocytes, which exhibit low MPF activity, failed to elongate the c-mos mRNA poly(A) tail, did not accumulate Mos and were unable to activate MAPK. We conclude that an active MPF in rat oocytes is necessary for c-mos mRNA polyadenylation and Mos translation.
An FPGA design of AES encryption circuit with 128-bit keys (2005)

This paper addresses a pipelined partial rolling (PPR) architecture for the AES encryption. The key technique is the PPR architecture, which is suitable for FPGA implementation. Using the proposed architecture on the Altera Stratix EP1S20F780C5 FPGA, the AES-4SM achieves a throughput of 5.61 Gbps by using 20 M4Ks, and the AES-8SM achieves a throughput of 10.49 Gbps by using 40 M4Ks. Compared with the unrolling implementation that achieves a throughput of 20.48 Gbps by using 80 M4Ks on the same FPGA, implementations with the PPR architecture reduce the amount of memory up to 75% while increasing the memory efficiency (i.e., throughput divided by the size of memory for core) up to 9.6%.The PPR architecture.lls the gap between unrolling and rolling architectures,and.ts on less expensive FPGAs.
Silicon on Insulator Diode Temperature Sensor– A Detailed Analysis for Ultra-High Temperature Operation (2010)

Silicon diodes can be used for accurate temperature monitoring up to higher temperatures in a variety of sensors such as micro-machined resistive and calorimetric gas sensors, thermal flow sensors, exhausts, etc. This paper investigates the performance of a diode temperature sensor when operated at ultra high temperatures (up to 780°C ). A low leakage silicon on insulator (SOI) diode was designed and fabricated in a 1.0 ¿m CMOS (complementary metal oxide semiconductor) process. The diodes were suspended within a dielectric membrane [formed by post CMOS deep reactive ion etching (DRIE)] for efficient thermal insulation. A CMOS compatible micro-heater was integrated with the diode on the dielectric membrane for local heating. It was found that the diode forward voltage exhibited a linear dependence on temperature as long as the reverse saturation current remained below the forward driving current. We show experimentally that the maximum temperature up to which the linearity of diode's forward voltage output is maintained can be as high as 550°C . Long term continuous operation at high temperatures (400°C and 500°C ) showed good stability of the diode voltage drop. Finally, we present a detailed theoretical analysis that helps to determine the maximum operating temperature for the diode and also explains the presence of nonlinearity factors in diode voltage output at ultra high temperatures.
Type I-E CRISPR-Cas system as an immune system in a eukaryote (2018)

Abstract Defense against viruses and other mobile genetic elements (MGEs) is important in many organisms. The CRISPR-Cas systems found in bacteria and archaea constitute adaptive immune systems that acquire the ability to recognize MGEs by introducing nucleic acid samples, spacers, in the CRISPR locus. The CRISPR is transcribed and processed, and the produced CRISPR RNAs guide Cas proteins to degrade matching nucleic acid sequences. No CRISPR-Cas system is found to occur naturally in eukaryotic cells but here we demonstrate interference by type I-E CRISPR-Cas system from Escherichia coli introduced in Saccharomyces cerevisiae . The designed CRISPR arrays are properly expressed and processed in S. cerevisiae . Targeted plasmids display reduced transformation efficiency, indicative of DNA cleavage. Unlike e.g. Cas9-based systems, which can be used to inactivate MGEs in eukaryotes by introducing specific mutations, type I-E systems processively degrade the target. The type I-E system thus allows for defense without knowledge of MGE gene function. The reconstituted CRISPR-Cas system in S. cerevisiae can also function as a basic research platform for testing the role of various factors in the interference process.
A Flow Cytometric Assay for Screening Improved Heterologous Protein Secretion in Yeast (2006)

Selection of highly productive hosts for protein expression is a significant component of bioprocess design. As an alternative to traditional plate, halo, and suppression-based screens, we describe a high-throughput, flow cytometric assay, the Cell Surface Secretion Assay (CeSSA), that can be used to select for improved heterologous protein secretion from a population of S. cerevisiae mutants. A ligand is covalently attached to the cell surface via a PEG linker, and as cells secrete a protein that binds the tethered ligand, the protein is captured on the surface where it can be labeled and the cells sorted using flow cytometry. This report describes three different protein/ligand interactions that have been demonstrated with this system. Single-pass sorting enrichments from 23- to 54-fold have been validated in the separation of a 3-fold higher secretor from a background population of wild-type secretors making this system applicable to large library screening (10(8) clones). A mathematical model was developed to improve the parameters of the assay further. The model was validated with time course data and predicts an optimal screening window. The model also predicts a 60-fold enrichment rate for the validation experiment described above. With the development of this selection system, limitations presented by traditional, particularly plate-based, secretion assays can be overcome so that a larger search space can be examined under conditions closer to the growth physiology experienced by cells in fermentors.
Cereal seed storage proteins: structures, properties and role in grain utilization (2002)

Storage proteins account for about 50% of the total protein in mature cereal grains and have important impacts on their nutritional quality for humans and livestock and on their functional properties in food processing. Current knowledge of the structures and properties of the prolamin and globulin storage proteins of cereals and their mechanisms of synthesis, trafficking and deposition in the developing grain is briefly reviewed here. The role of the gluten proteins of wheat in determining the quality of the grain for breadmaking and how their amount and composition can be manipulated leading to changes in dough mixing properties is also discussed.
Oxymorphone Hydrochloride, a Potent Opioid Analgesic, Is Not Carcinogenic in Rats or Mice (2006)

Despite their long history of chronic use, little information is available regarding the carcinogenicity of opioid analgesics. Oxymorphone is a potent morphinan-type mu-opioid analgesic used for treatment of moderate-to-severe pain. Oxymorphone was tested for carcinogenicity in Crl:CD IGS BR rats and CD-1 mice. Oxymorphone hydrochloride was administered orally once daily for 2 years to rats at doses of 2.5, 5 and 10 mg/kg/day (males) and 5, 10 and 25 mg/kg/day (females), and mice at 10, 25, 75 and 150 mg/kg/day (65 animals per sex per group; 100 animals per sex in controls). In rats, survival was generally higher than controls in oxymorphone-treated groups, attributable to lower body weight gain. In mice, survival was generally higher than controls in females at all doses and males given < or = 25 mg/kg/day but lower in males given > or = 75 mg/kg/day due to a high incidence of obstructive uropathy. Opioid-related clinical signs and reduced body weight gain occurred in both species throughout the study. Nonneoplastic findings associated with oxymorphone pharmacology included ocular and pulmonary changes in rats considered secondary to inhibition of blinking and mydriasis, and antitussive activity, respectively, and urinary tract and renal findings in mice considered secondary to urinary retention. There was no target organ toxicity, and no increase in any neoplastic lesions attributed to oxymorphone. Plasma oxymorphone levels achieved in these studies exceeded those in patients taking high therapeutic doses of oxymorphone (Area under the curve [AUC(0-24 h)] values up to 5.6-fold and 64-fold in rats and mice, respectively). Oxymorphone is not considered to be carcinogenic in rats or mice under the conditions of these studies.
Studies in the development of Japanese encephalitis vaccine: expression of virus envelope glycoprotein V3 (E) gene in yeast. (1987)

A safe, effective and economical vaccine is required for the prevention of Japanese encephalitis (JE), a disease with high mortality and grave sequelae, which is prevalent in Japan and other countries in east, south-east and southern Asia. As the initial step to produce a second-generation vaccine, recombinant DNA technology was utilized to express the JE virus envelope glycoprotein V3 (E) gene in yeast cells.This report describes the construction of a yeast expression vector in which a cDNA clone covering the V3 gene was connected to the acid-phosphatase promoter of a yeast vector plasmid. Successful expression of the V3 gene was detected by ELISA and Western blotting using monoclonal antibodies against JE V3. Immunization of mice with the V3 antigen expressed in yeast produced limited but definite levels of anti-JE antibodies which could neutralize JE virus. The results are an encouraging step in the development of a practical second-generation JE vaccine.
Antisense therapy specific to mutated K-ras gene in hamster pancreatic cancer model. Can it inhibit the growth of 5-FU and MMC-resistant metastatic and remetastatic cell lines? (2004)

Antisense oligonucleotide-targeted K-ras gene may be a good choice for therapy because it could inhibit the growth in metastatic and remetastatic cells as well as in primary tumor cells.
Suppressive properties of human CD4+CD25+ regulatory T cells are dependent on CTLA‐4 expression (2004)

It has been demonstrated that T cells with regulatory properties are present within the peripheral blood CD4(+)CD25(+) T cell compartment. Here, we describe an original method to purify human CD4(+)CD25(+)CD152(+) T lymphocytes as living cells by forcing the exportation of CTLA-4 molecules stored in intracellular vesicules at the cell surface. By doing so, we demonstrate that CD4(+)CD25(+) T cells contain a smaller and more homogeneous population enriched in cells with in vitro regulatory activity. Moreover, we show that this enrichment in regulatory T cells is associated with an increased expression of Foxp3 and that CD4(+)CD25(+)CD152(+) T lymphocytes display a much stronger suppressive activity in controlling in vitro proliferation of alloantigen-specific T cells than CD4(+)CD25(+)CD152(-) T lymphocytes purified in parallel. Lastly, by purifying such cells expressing CTLA-4, we demonstrate that indeed CTLA-4 is involved in CD4(+)CD25(+)CD152(+) T cell regulatory activity, while suppressive cytokines are not.
Microfluidic Control Using Colloidal Devices (2002)

By manipulating colloidal microspheres within customized channels, we have created micrometer-scale fluid pumps and particulate valves. We describe two positive-displacement designs, a gear and a peristaltic pump, both of which are about the size of a human red blood cell. Two colloidal valve designs are also demonstrated, one actuated and one passive, for the direction of cells or small particles. The use of colloids as both valves and pumps will allow device integration at a density far beyond what is currently achievable by other approaches and may provide a link between fluid manipulation at the macro- and nanoscale.
Cellular uptake of Antennapedia Penetratin peptides is a two-step process in which phase transfer precedes a tryptophan-dependent translocation (2003)

Several homeodomains and homeodomain-containing proteins enter live cells through a receptor- and energy-independent mechanism. Translocation through biological membranes is conferred by the third alpha-helix of the homeodomain, also known as Penetratin. Biophysical studies demonstrate that entry of Penetratin into cells requires its binding to surface lipids but that binding and translocation are differentially affected by modifications of some physico-chemical properties of the peptide, like helical amphipathicity or net charge. This suggests that the plasma membrane lipid composition affects the internalization of Penetratin and that internalization requires both lipid binding and other specific properties. Using a phase transfer assay, it is shown that negatively charged lipids promote the transfer of Penetratin from a hydrophilic into a hydrophobic environment, probably through charge neutralization. Accordingly, transfer into a hydrophobic milieu can also be obtained in the absence of negatively charged lipids, by the addition of DNA oligonucleotides. Strikingly, phase transfer by charge neutralization was also observed with a variant peptide of same charge and hydrophobicity in which the tryptophan at position 6 was replaced by a phenylalanine. However, Penetratin, but not its mutant version, is internalized by live cells. This underscores that charge neutralization and phase transfer represent only a first step in the internalization process and that further crossing of a biological membrane necessitates the critical tryptophan residue at position 6.
Oxime conjugation in protein chemistry: from carbonyl incorporation to nucleophilic catalysis (2016)

Use of oxime forming reactions has become a widely applied strategy for peptide and protein bioconjugation. The efficiency of the reaction and robust stability of the oxime product has led to the development of a growing list of methods to introduce the required ketone or aldehyde functionality site specifically into proteins. Early methods focused on site-specific oxidation of an N-terminal serine or threonine and more recently transamination methods have been developed to convert a broader set of N-terminal amino acids into a ketone or aldehyde. More recently, site-specific modification of protein has been attained through engineering enzymes involved in posttranslational modifications in order to accommodate aldehyde-containing substrates. Similarly, a growing list of unnatural amino acids can be introduced through development of selective amino-acyl tRNA synthetase/tRNA pairs combined with codon reassignment. In the case of glycoproteins, glycans can be selectively modified chemically or enzymatically to introduce aldehyde functional groups. Finally, the total chemical synthesis of proteins complements these biological and chemoenzymatic approaches. Once introduced, the oxime ligation of these aldehyde and ketone groups can be catalyzed by aniline or a variety of aniline derivatives to tune the activity, pH preference, stability and solubility of the catalyst. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.
Characterization of Human Expired Air: A Promising Investigative and Diagnostic Technique (1977)

Expired air samples have been collected from a carefully selected population of normal healthy human subjects under controlled experimental conditions. The samples were concentrated and analyzed by quantitative, reproducible and sensitive techniques which resulted in well-defined composite compositional and occurrence profiles of the organic constituents present in normal expired air. The composite profiles provide valuable baseline information upon which suitable correlation studies may be advanced toward the use of human expired air for diagnostic purposes.
Smooth Muscle Cells, But Not Myocytes, of Host Origin in Transplanted Human Hearts (2002)

Vascular smooth muscle cells of infiltrating host cell origin can be found in human cardiac allografts. However, unlike prior reports, we found no evidence that chimerism is present in cardiac myocytes.
Dietary Fatty Acids and Cardiovascular Health – An Ongoing Controversy (2011)

No abstract available.
Structural Integrity of the Uncinate Fasciculus and Resting State Functional Connectivity of the Ventral Prefrontal Cortex in Late Life Depression (2011)

These results support the notion that resting state functional connectivity reflects structural integrity, since the ventral PFC is structurally connected to temporal regions by the UF. Future studies should include larger samples of patients and healthy comparison subjects in which both resting state and task-based functional connectivity are examined.
How to exchange (secret) keys (1983)

A protocol is presented whereby two adversaries may exchange secrets, although neither trusts the other. The secrets are the prime factors of their publicly announced composite numbers. The two adversaries can exchange their secrets bit by bit, but each fears the other will cheat by sending "junk" bits. To solve this problem we show how each of the two can prove, for each bit delivered, that the bit is good.