gebhart/patrepeval huggingface dataset:
Promoter engineering: Recent advances in controlling transcription at the most fundamental level (2012)

Synthetic control of gene expression is critical for metabolic engineering efforts. Specifically, precise control of key pathway enzymes (heterologous or native) can help maximize product formation. The fundamental level of transcriptional control takes place at promoter elements that drive gene expression. Endogenous promoters are limited in that they do not fully sample the complete continuum of transcriptional control, and do not maximize the transcription levels achievable within an organism. To address this issue, several attempts at promoter engineering have shown great promise both in expanding the cell-wide transcriptional capacity of an organism and in enabling tunable levels of gene expression. Thus, this review highlights the recent advances and approaches for altering gene expression control at the promoter level. Furthermore, we propose that recent advances in the understanding of transcription factors and their DNA-binding sites will enable rational and predictive control of gene expression.
Thiazolidinediones and liver toxicity. (2001)

Thiazolidinediones or glitazones specifically target insulin resistance. They have proven efficacy for reducing plasma glucose levels of type 2 diabetic patients treated with diet alone, sulphonylureas, metformin or insulin. In addition, they may be associated to some improvement of cardiovascular risk profile. However, troglitazone, the first compound approved by the FDA in the US, proved to be hepatotoxic and was withdrawn from the market after the report of several dozens of deaths or cases of severe hepatic failure requiring liver transplantation. It remains unclear whether or not hepatotoxicity is a class effect or is related to the unique tocopherol side chain of troglitazone. Rosiglitazone and pioglitazone, two other glitazones, appear to have similar efficacy on blood glucose control of type 2 diabetic patients as compared to troglitazone. In controlled clinical trials, the incidence of significant increases in liver enzyme levels (ALT) was similar with rosiglitazone or pioglitazone as compared to placebo, whereas troglitazone was associated with a threefold greater incidence. In contrast to the numerous case reports of acute liver failure in patients receiving troglitzone, only two cases of severe reversible liver failure have been reported in patients treated with rosiglitazone, with a causal relationship remaining uncertain. Furthermore, no single case of severe hepatotoxicity has been reported yet with pioglitazone. While regular monitoring of liver enzymes is still recommended and more long-term data are desirable, current clinical evidence supports the conclusion that rosiglitazone and pioglitazone do not share the hepatotoxic profile of troglitazone.
Idebenone and Resveratrol Extend Lifespan and Improve Motor Function of HtrA2 Knockout Mice (2011)

Heterozygous loss-of-function mutation of the human gene for the mitochondrial protease HtrA2 has been associated with increased risk to develop mitochondrial dysfunction, a process known to contribute to neurodegenerative disorders such as Huntington's disease (HD) and Parkinson's disease (PD). Knockout of HtrA2 in mice also leads to mitochondrial dysfunction and to phenotypes that resemble those found in neurodegenerative disorders and, ultimately, lead to death of animals around postnatal day 30. Here, we show that Idebenone, a synthetic antioxidant of the coenzyme Q family, and Resveratrol, a bioactive compound extracted from grapes, are both able to ameliorate this phenotype. Feeding HtrA2 knockout mice with either compound extends lifespan and delays worsening of the motor phenotype. Experiments conducted in cell culture and on brain tissue of mice revealed that each compound has a different mechanism of action. While Idebenone acts by downregulating the integrated stress response, Resveratrol acts by attenuating apoptosis at the level of Bax. These activities can account for the delay in neuronal degeneration in the striata of these mice and illustrate the potential of these compounds as effective therapeutic approaches against neurodegenerative disorders such as HD or PD.
Tumor targets stimulate IL-2 activated killer cells to produce interferon-gamma and tumor necrosis factor. (1989)

Lymphokine-activated killer (LAK) cells are cytotoxic for a variety of autologous and allogeneic tumor cells as well as modified autologous cells. It is assumed that LAK cells lyse their targets solely by direct cell to cell contact, possibly involving the degranulation and exocytosis of pore-forming elements, similar to that observed with cytotoxic T lymphocytes and NK cells. Reported here are studies demonstrating that LAK cells release factor(s) that are cytotoxic for a human breast carcinoma cell line, MCF-7, when stimulated with tumor cells. The factor(s) are slow acting and maximum cytotoxicity is observed only in a 72-h cytotoxic assay. The ability of LAK cells to secrete cytotoxic factor(s) is dependent on both the ratio of LAK cells to stimulating tumor cells as well as the length of their coincubation. A number of similarly slow acting cytokines that are cytostatic and/or cytotoxic for tumor cells have been described. We tested the ability of specific polyclonal antibodies directed against TNF, IFN-alpha, IFN-beta, and IFN-gamma to neutralize the cytotoxic supernatant activity. Only antibodies specific for IFN-gamma and TNF were neutralizing. We measured the amounts of IFN-gamma and TNF in the cytotoxic supernatants and determined that increased amounts of IFN-gamma and TNF were released after LAK cell-tumor cell interactions compared to supernatants of LAK cells alone or tumor cell alone. Comparable concentrations of human rIFN-gamma and rTNF resulted in similar levels (50 to 90%) of MCF-7 cell cytotoxicity as those observed with the stimulated LAK cell supernatants. We thus concluded that the majority of the cytotoxic activity released by LAK cells when stimulated with tumor cells was attributed to the synergistic activities of IFN-gamma and TNF. The significance of these observations in relation to the possible mechanisms by which LAK cells mediate cytolysis is discussed.
An endogenously synthesized decamer peptide efficiently primes cytotoxic T cells specific for the HIV‐1 envelope glycoprotein (1993)

The immunodominant H-2Dd-restricted cytotoxic T lymphocyte (CTL) response to the HIV-1 gp160 envelope glycoprotein maps to a single determinant in the V3 loop, designated p18. Using a series of peptides synthesized on pins we have determined that the minimal core sequence of this determinant required for CTL recognition comprises 8 amino acids (residues 320-327). However, 9mer and 10mer peptides containing this core sequence were more effective than the 8mer peptide at sensitizing Dd-expressing target cells. To analyze the antigenicity of endogenously synthesized p18, minigenes encoding a 10-amino acid determinant (residues 318-327) and a 67-amino acid peptide (residues 281-348; containing the V3 loop) were expressed using vaccinia virus (Vac) recombinants. Both peptides were as effective as wild-type gp160 in their ability to sensitize target cells for lysis by gp160-specific CTL. Immunization of BALB/c mice with Vac recombinants encoding both gp160 peptides elicited gp160-specific CTL. These data demonstrate that both the V3 loop itself and a 10-residue epitope are sufficient to prime CTL in vivo and strongly support the potential use of minigene-encoded CTL epitopes for recombinant vaccines designed to induce protective T cell-mediated immunity against HIV-1.
Human transcriptome array for high-throughput clinical studies (2011)

A 6.9 million-feature oligonucleotide array of the human transcriptome [Glue Grant human transcriptome (GG-H array)] has been developed for high-throughput and cost-effective analyses in clinical studies. This array allows comprehensive examination of gene expression and genome-wide identification of alternative splicing as well as detection of coding SNPs and noncoding transcripts. The performance of the array was examined and compared with mRNA sequencing (RNA-Seq) results over multiple independent replicates of liver and muscle samples. Compared with RNA-Seq of 46 million uniquely mappable reads per replicate, the GG-H array is highly reproducible in estimating gene and exon abundance. Although both platforms detect similar expression changes at the gene level, the GG-H array is more sensitive at the exon level. Deeper sequencing is required to adequately cover low-abundance transcripts. The array has been implemented in a multicenter clinical program and has generated high-quality, reproducible data. Considering the clinical trial requirements of cost, sample availability, and throughput, the GG-H array has a wide range of applications. An emerging approach for large-scale clinical genomic studies is to first use RNA-Seq to the sufficient depth for the discovery of transcriptome elements relevant to the disease process followed by high-throughput and reliable screening of these elements on thousands of patient samples using custom-designed arrays.
Interface and execution models in the Fluke kernel (1999)

We have defined and implemented a kernel API that makes every exported operation fully interruptible and restartable, thereby appearing atomic to the user. To achieve interruptibility, all possible kernel states in which a thread may become blocked for a long time are represented as kernel system calls, without requiring the kernel to retain any unexposable internal state. Since all kernel operations appear atomic, services such as transparent checkpointing and process migration that need access to the complete and consistent state of a process can be implemented by ordinary user-mode processes. Atomic operations also enable applications to provide reliability in a more straightforward manner. This API also allows us to explore novel kernel implementation techniques and to evaluate existing techniques. The Fluke kernel's single source implements either the process or the interrupt execution model on both uniprocessors and multiprocessors, depending on a configuration option affecting a small amount of code. We report preliminary measurements comparing fully, partially and non-preemptible configurations of both process and interrupt model implementations. We find that the interrupt model has a modest performance advantage in some benchmarks, maximum preemption latency varies nearly three orders of magnitude, average preemption latency varies by a factor of six, and memory use favors the interrupt model as expected, but not by a large amount. We find that the overhead for restarting the most costly kernel operation ranges from 2-8% of the cost of the operation.
Vapor Adsorption in Thin Silicalite-1 Films Studied by Spectroscopic Ellipsometry (1998)

Thin films of silicalite-1 grown on silicon substrates were studied by spectroscopic ellipsometry. Analysis of spectra using an optical model consisting of a single porous layer on silicon yielded average film thicknesses of 84 and 223 nm for films synthesized for 10 and 30 h. Void fraction for the films was 0.32−0.33. Vapor adsorption from a nitrogen carrier gas at room temperature was monitored by ellipsometry. Isotherms for different adsorbates were obtained by analysis of spectra taken at different vapor concentrations using an optical model where the void volume was filled with both nitrogen and condensed vapors. Quantification of the condensed vapor amount was based on the changes in refractive index when adsorbates replaced nitrogen in the pores. Adsorbate volumes for water, toluene, 1-propanol, and hexane were 0.12, 0.12, 0.15, and 0.17 cm3 liquid g-1 film, respectively.
Potent HIV-1 protease inhibitors: stereoselective synthesis of a dipeptide mimic (1993)

The synthesis of a differentially protected dipeptide mimic 10 in enantiomerically pure form is described. The key step involves the epimerization of the C-2 center of the lactone 4, hydrolysis and protection of the resulting hydroxy acid, followed by Curtius rearrangement to introduce the urethane functionality. The scope and versatility of this isostere has been demonstrated by its conversion to potent HIV-1 protease inhibitors with nanomolar potencies. Also, established through the synthesis of compound 13 and 14, the 3<i>S</i> hydroxyl configuration of the dipeptide isostere 1 is the preferred configuration for its potency. The present synthesis is efficient and provides an access to other dipeptide mimics with a great deal of structural diversity.
At smile på operationsbordet—den biopolitiske entreprenør (2003)

I denne artikel søges en affirmativ læsning af Empire, idet fokus er på arbejderens potentiale som biopolitisk arbejder, hvilket munder ud i en diagrammatisering af arbejderen som en potentiel biopolitisk entreprenør. Idet forestillingen og erfaringen af krise gøres til en metodisk pointe, viser analysen nødvendigheden af at vende tilbage til selve produktionens center: ikke blot produktionen af varer, men også af værdier, affekter og sociale relationer, i alt: politik. Det forsøges vist, hvorledes produktion af subjektivitet ikke blot er en teknologi for undertrykkelse, men samtidigt det sted, hvorfra en ny modstand kan tænkes, hvorved den politiske problemstilling bliver etisk. En lille pige, der skal gennemføre en vanskelig operation uden bedøvelse, bliver underholdt af hospitalsklovner, der på denne måde understøtter barnets modstand mod nutiden og viser en ny rolle for kreative og affektive aktører på markedet. Det er en modstandsform, der er immanent markedets logik og kapitalens dynamiske aksiomatik, idet disse aktører arbejder med at værksætte både vare og værdi, innovation og mening. Herved bliver modstandsbegrebet—der i Empire kan forekomme noget abstrakt, ikke mindst på grund af et ikke helt afklaret begreb om ‘multituden’ -til en kategori for alle, idet vi alle i neoliberalismen må være en bliven-arbejder. Her kan så selvet—nu som social realitet snarere end terapeutisk vare eller bourgeois dannelsesideal—forbindes til det absolutte ydre via Foucaults genfundne hellenistiske begreb om enkrateia, en produktiv og fri selvrelation. Dette fremtræder mangfoldige steder i vores samtid, hvilket afsluttende søges vist empirisk: Den biopolitiske entreprenør forbinder overalt forandringens projekt i en ‘kærlighedens praksis’.
Participation of the Intron in the Reaction Catalyzed by the Xenopus tRNA Splicing Endonuclease (1992)

Introns have generally been assumed to be passive in the transfer RNA splicing reaction. Experiments have now been done showing that the endonuclease is able to cut a precursor provided that a base in the single-stranded loop of the intron can pair with the base of the 5' exon situated at the position that immediately follows the anticodon stem (position 33 in the yeast tRNA isoacceptor pre-tRNA(Leu)3, position 32 in yeast pre-tRNA(Phe)). The elucidation of the role of the intron reveals that in addition to the conserved bases, there are positions in the mature domain which, although not necessarily occupied by the same base in all pre-tRNA's, nevertheless have a fundamental role in the splicing reaction. These positions are termed cardinal positions.
Nuclear Magnetic Resonance ofXe129in Solid and Liquid Xenon (1963)

Self-diffusion coefficients, resonance shifts, and nuclear spin-spin relaxation times are reported for ${\mathrm{Xe}}^{129}$ in solid and liquid xenon. In the solid, the ${T}_{2}$ data indicate $D=({{7.3}_{\ensuremath{-}0.2}}^{+0.4})\mathrm{exp}[\ensuremath{-}\frac{(7400\ifmmode\pm\else\textpm\fi{}50}{\mathrm{RT}}]$ ${\mathrm{cm}}^{2}$/sec. In the liquid, direct external gradient-diffusion measurements yield $D=({{2.3}_{\ensuremath{-}0.7}}^{+0.8})\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}3} \mathrm{exp}\ifmmode\times\else\texttimes\fi{}[\ensuremath{-}\frac{(1400\ifmmode\pm\else\textpm\fi{}150)}{\mathrm{RT}}]$ ${\mathrm{cm}}^{2}$/sec. Density-dependent resonance shifts are found to occur in both the liquid and the solid.
Synthesis of 1-fluorocycloalkenes (1971)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of 1-fluorocycloalkenesDonald R. Strobach and G. A. Boswell Jr.Cite this: J. Org. Chem. 1971, 36, 6, 818–820Publication Date (Print):March 1, 1971Publication History Published online1 May 2002Published inissue 1 March 1971https://pubs.acs.org/doi/10.1021/jo00805a019https://doi.org/10.1021/jo00805a019research-articleACS PublicationsRequest reuse permissionsArticle Views436Altmetric-Citations43LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Induced Pluripotent Stem Cells (iPSC) from Cord Blood CD133+ Cells Using Oct4 and Sox2 (2011)

Induced pluripotent stem cells (iPSCs) provide an invaluable resource for regenerative medicine to repair tissues damaged through disease or injury. Although human iPSCs have been generated using different type of somatic cells, such as skin fibroblasts and keratinocytes, neural stem cells, hepatocytes, and blood cells, it is still under debate on what is the best source for generating iPSCs. In this chapter, we discuss how to generate human iPSCs from cord blood (CB) CD133+ cells using only two transcription factors OCT4 and SOX2. The methods for establishment and maintenance of CB-derived iPS (CB-iPS) cells are similar, with some modifications, to those for human iPSCs derived from fibroblasts. In particular, this protocol includes a detailed procedure to isolate CB CD133+ cells from both fresh and frozen CB and a procedure to optimize retroviral infection to generate iPSCs from these cells. In addition, we describe methods for the characterization of CB-iPS cells, such as embryoid bodies formation and teratoma differentiation, to validate their pluripotent phenotype.
Erythropoietin Therapy Improves Graft Patency with No Increased Incidence of Thrombosis or Thrombophlebitis (1998)

Primary and secondary AV fistula patency rates were improved by 10% with rHuEPO. rHuEPO did not increase DVT.
Antiproteases in herpetic keratitis. (1986)

Proteolytic enzyme inhibitors are capable of preventing decomposition of the collagen structures of the corneal stroma, and also have a regulating influence on various aspects of the inflammatory process. The content of proteolytic enzymes (alpha 1-antitrypsin and alpha 2-macroglobulin) was studied in the tears and the blood serum of patients with herpes viral keratitis, as well as in the blood serum of rabbits with experimentally-induced ophthalmoherpes. Herpetic keratitis was attended by significant changes in the content of proteolysis inhibitors, as well as in the peripheral blood neutral proteases activity, this presumably serving as a nonspecific blood protective reaction to the inflammation. In the tears of patients suffering from herpetic keratitis the inhibitors are expended for binding activated proteases in the cornea. Local application to rabbits of protein preparations with an inhibitory effect (contrykal, gordox) at the acute period of the experimentally-induced ophthalmoherpes produced a marked antiphlogistic effect.
The GenBank genetic sequence databank (1986)

The GenBank Genetic Sequence Data Bank contains over 5700 entries for DNA and RNA sequences that have been reported since 1967. This paper briefly describes the contents of the database, the forms in which the database is distributed, and the services we offer to scientists who use the GenBank database.
Molecular pharmacology regulation and function of mammalian melatonin receptors (2003)

Melatonin (5-methoxy-N-acetyltryptamine), dubbed the hormone of darkness, is released following a circadian rhythm with high levels at night. It provides circadian and seasonal timing cues through activation of G protein-coupled receptors (GPCRs) in target tissues (1). The discovery of selective melatonin receptor ligands and the creation of mice with targeted disruption of melatonin receptor genes are valuable tools to investigate the localization and functional roles of the receptors in native systems. Here we describe the pharmacological characteristics of melatonin receptor ligands and their various efficacies (agonist, antagonist, or inverse agonist), which can vary depending on tissue and cellular milieu. We also review melatonin-mediated responses through activation of melatonin receptors (MT1, MT2, and MT3) highlighting their involvement in modulation of CNS, hypothalamic-hypophyseal-gonadal axis, cardiovascular, and immune functions. For example, activation of the MT1 melatonin receptor inhibits neuronal firing rate in the suprachiasmatic nucleus (SCN) and prolactin secretion from the pars tuberalis and induces vasoconstriction. Activation of the MT2 melatonin receptor phase shifts circadian rhythms generated within the SCN, inhibits dopamine release in the retina, induces vasodilation, enhances splenocyte proliferation and inhibits leukocyte rolling in the microvasculature. Activation of the MT3 melatonin receptor reduces intraocular pressure and inhibits leukotriene B4-induced leukocyte adhesion. We conclude that an accurate characterization of melatonin receptors mediating specific functions in native tissues can only be made using receptor specific ligands, with the understanding that receptor ligands may change efficacy in both native tissues and heterologous expression systems.
Mode of interaction between platelet factor 4 and heparin (1993)

Platelet factor 4 (PF4) is a platelet-derived protein capable of binding to, and thus neutralizing, the biological activities of heparin and heparan sulphate. The mode of binding of PF4 to heparin was investigated in a comparative study also involving antithrombin (AT; previously shown to selectively bind a specific oligosaccharide sequence) and fibronectin (FN; non-specific electrostatic interaction). Heparin-derived saccharides were incubated with each of the three proteins, followed by separation of free and protein-bound carbohydrate on a nitrocellulose filter. The interaction systems involved either (i) competition for the protein ligand between 3H-labelled heparin and unlabelled, size-fractionated heparin oligosaccharides (isolated after deaminative cleavage with HNO2) or (ii) direct binding of 3H-labelled oligosaccharides. Species smaller than octasaccharides were unable to bind AT, whereas binding to FN and PF4 increased continuously throughout the series, with increasing size of the oligosaccharides. Further separation by anion-exchange chromatography showed that the PF4-binding and FN-binding octasaccharides represented essentially all components present in the initial octasaccharide fraction, the proportion of binding species increasing with charge (hence with the degree of sulphation). The AT-binding octasaccharides, on the other hand, selectively represented only a few of the total octasaccharide components, without any correlation to overall charge. These results indicate that the binding of PF4 to heparin occurs by relatively non-specific electrostatic interactions. The methodology delineated here may be generally useful in assessing specificity in glycosaminoglycan-protein interactions.