gebhart/patrepeval huggingface dataset:
Retinoid X Receptor Ligands with Anti-Type 2 Diabetic Activity (2016)

Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-dependent transcription factor that plays an important role in regulating glucose metabolism. Agonists of PPARγ, such as thiazolidinediones, have anti-hyperglycemic activity, and are therefore used to treat type 2 diabetes. However, the functional activity of PPARγ is manifested by heterodimers of PPARγ with retinoid X receptors (RXRs). Since RXR/PPARγ heterodimers can be activated not only by PPARγ agonists, but also by RXR agonists, RXR agonists are also attractive candidates for treatment of type 2 diabetes. However, RXR full agonists have side effects, such as triglyceride elevation and hypothyroidism. Therefore, RXR partial agonists have been developed as new anti-type 2 diabetes agent candidates with reduced side effects. In addition, RXR antagonists also show therapeutic potency in type 2 diabetes patients. Here, we review RXR full agonists, RXR antagonists, and RXR modulators (partial agonists) with reported anti-diabetic effects, and we discuss their potential suitability as anti-diabetic agents.
Broad-Host-Range cre-lox System for Antibiotic Marker Recycling in Gram-Negative Bacteria (2002)

Complete genome sequences are now available for many bacterial species that lack sophisticated genetic tools. We describe the development of a broad-host-range cre-lox system that allows antibiotic marker recycling in a variety of gram-negative bacteria. This system consists of an allelic exchange vector bearing a kanamycin cassette flanked by loxP sites and a tetracycline-resistant IncP plasmid that provides expression of the Cre recombinase. We demonstrate this system by generating unmarked deletions of genes in two different bacteria, Methylobacterium extorquens AM1 and Burkholderia fungorum LB400. This new antibiotic marker recycling system offers the possibility of creating unmarked mutants in a wide variety of gram-negative bacteria. Furthermore, marker recycling allows the generation of strains bearing multiple genetic manipulations in organisms for which few antibiotic markers are currently available.
Observation of dynamic nanostructural and nanochemical changes in ceria-based catalysts duringin-situreduction (2004)

Abstract We have studied the nanostructural and nanochemical changes occurring in pure ceria (CeO2) and CeO2–zirconia (ZrO2) catalysts during reduction. The reduction is carried out in an environmental transmission electron microscope in dry H2 at 2 Torr up to 800°C. We use in-situ electron-energy-loss spectroscopy to follow changes in the oxidation state of the Ce at close to the nanometre level. Our measurements show that reduction may or may not be accompanied by significant structural rearrangements in the material. In pure CeO2 and the mixed oxide, the reduced form can be composed of both crystalline and amorphous material. Our measurements confirm the formation of a superlattice formed due to the ordering of O vacancies in CeO2 during reduction. The mixed oxide material shows that O vacancy ordering occurs only over 2–3 nm domains. Acknowledgement We would like to thank Rhodia for samples and providing financial support to one of us (Z.C.K.).
Cytotoxic T-Lymphocyte Escape Does Not Always Explain the Transient Control of Simian Immunodeficiency Virus SIVmac239 Viremia in Adenovirus-Boosted and DNA-Primed Mamu-A*01-Positive Rhesus Macaques (2005)

Adenovirus 5 (Ad5) vectors show promise as human immunodeficiency virus vaccine candidates. Indian rhesus macaques vaccinated with Ad5-gag controlled simian-human immunodeficiency virus SHIV89.6P viral replication in the absence of Env immunogens that might elicit humoral immunity. Here we immunized 15 macaques using either a homologous Ad5-gag/Ad5-gag (Ad5/Ad5) or a heterologous DNA-gag/Ad5-gag (DNA/Ad5) prime-boost regimen and challenged them with a high dose of simian immunodeficiency virus SIVmac239. Macaques vaccinated with the DNA/Ad5 regimen experienced a brief viral load nadir of less than 10,000 viral copies per ml blood plasma that was not seen in Mamu-A*01-negative DNA/Ad5 vaccinees, Mamu-A*01-positive Ad5/Ad5 vaccinees, or vaccine-naive controls. Interestingly, most of these animals were not durably protected from disease progression when challenged with SIVmac239. To investigate the reasons underlying this short-lived vaccine effect, we investigated breadth of the T-cell response, immunogenetic background, and viral escape from CD8+ lymphocytes that recognize immunodominant T-cell epitopes. We show that these animals do not mount unusually broad cellular immune response, nor do they express unusual major histocompatibility complex class I alleles. Viral recrudescence occurred in four of the five Mamu-A*01-positive vaccinated macaques. However, only a single animal in this group demonstrated viral escape in the immunodominant Gag181-189 CM9 response. These results suggest that viral "breakthrough" in vaccinated animals and viral escape are not inextricably linked and underscore the need for additional research into the mechanisms of vaccine failure.
Sipuleucel-T immune parameters correlate with survival: an analysis of the randomized phase 3 clinical trials in men with castration-resistant prostate cancer (2012)

Sipuleucel-T broadly engages the immune system by activating APCs ex vivo and inducing long-lived immune responses in vivo. These data indicate antigen-specific immune activation as a mechanism by which sipuleucel-T prolongs OS.
Glycopeptide Synthesis by an .alpha.-Amino Acid N-Carboxyanhydride (NCA) Method: Ring-Opening Polymerization of a Sugar-Substituted NCA (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTGlycopeptide Synthesis by an .alpha.-Amino Acid N-Carboxyanhydride (NCA) Method: Ring-Opening Polymerization of a Sugar-Substituted NCAKeigo Aoi, Kaname Tsutsumiuchi, and Masahiko OkadaCite this: Macromolecules 1994, 27, 3, 875–877Publication Date (Print):January 1, 1994Publication History Published online1 May 2002Published inissue 1 January 1994https://pubs.acs.org/doi/10.1021/ma00081a040https://doi.org/10.1021/ma00081a040research-articleACS PublicationsRequest reuse permissionsArticle Views1340Altmetric-Citations130LEARN 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
The Interactive Demonstration of Interactional Competence in the ITA TEACH Test (2014)

This paper reports on a work-in-progress that examines a high-stakes teaching and oral language performance assessment known as the TEACH test, in which international teaching assistant (ITA) candidates are required to demonstrate their competency in a panel-rated teaching simulation. This study draws upon the analytic tools of Conversation Analysis to examine 29 videotaped TEACH tests recorded at a large Research 1 (R1) university in the eastern United States with the objective of providing a more in-depth understanding of the demands placed on test-takers and raters. The initial analysis shows how prospective ITAs manage questions that engender problematic responses, and how audience participation can be supportive of the demonstration of competence. In the conclusion, directions for future work are discussed.
Effects of exogenous ketone supplementation on blood ketone, glucose, triglyceride, and lipoprotein levels in Sprague–Dawley rats (2016)

This study demonstrates the efficacy and tolerability of oral exogenous ketone supplementation in inducing nutritional ketosis independent of dietary restriction.
Identification, isolation, and overexpression of the gene encoding the psi subunit of DNA polymerase III holoenzyme (1993)

The gene encoding the psi subunit of DNA polymerase III holoenzyme, holD, was identified and isolated by an approach in which peptide sequence data were used to obtain a DNA hybridization probe. The gene, which maps to 99.3 centisomes, was sequenced and found to be identical to a previously uncharacterized open reading frame that overlaps the 5' end of rimI by 29 bases, contains 411 bp, and is predicted to encode a protein of 15,174 Da. When expressed in a plasmid that also expressed holC, holD directed expression of the psi subunit to about 3% of total soluble protein.
Studies on Enzyme-Cleavable Dialkoxymethyl-cycloSaligenyl-2′,3′-dideoxy-2′,3′-didehydrothymidine Monophosphates (2008)

Recently we reported on conceptually new enzymatically activated cycloSal-pronucleotides. Now, we developed this concept further with new compounds of this type. The basic idea is fast intracellular cleavage of a functionalized group at the cycloSal residue that results in a rapid delivery of the nucleotide and thus an intracellular enrichment of the nucleotide. The introduction of a higher alkylated acylal group, the di- iso-butyryloxymethyl group, to the aromatic ring led to the expected higher stability of these prodrugs against enzymatic cleavage but also entailed surprisingly a decrease in hydrolysis stabilities and solubility problems. For some compounds, a separation of the two diastereomeric forms ( R P or S P) was achieved. By X-ray structure analysis, the absolute configuration at the P-atom was assigned. For all separated diastereomers the ( S P) form showed better antiviral activity than the ( R P) form.
The Keap1-Nrf2 pathway: Mechanisms of activation and dysregulation in cancer (2013)

The Keap1-Nrf2 pathway is the major regulator of cytoprotective responses to oxidative and electrophilic stress. Although cell signaling pathways triggered by the transcription factor Nrf2 prevent cancer initiation and progression in normal and premalignant tissues, in fully malignant cells Nrf2 activity provides growth advantage by increasing cancer chemoresistance and enhancing tumor cell growth. In this graphical review, we provide an overview of the Keap1-Nrf2 pathway and its dysregulation in cancer cells. We also briefly summarize the consequences of constitutive Nrf2 activation in cancer cells and how this can be exploited in cancer gene therapy.
The C Terminus of Component C2II of Clostridium botulinum C2 Toxin Is Essential for Receptor Binding (2000)

The binary Clostridium botulinum C2 toxin consists of two separate proteins, the binding component C2II (80.5 kDa) and the actin-ADP-ribosylating enzyme component C2I (49.4 kDa). For its cytotoxic action, C2II binds to a cell membrane receptor and induces cell entry of C2I via receptor-mediated endocytosis. Here we studied the structure-function relationship of C2II by constructing truncated C2II proteins and producing polyclonal antisera against selective regions of C2II. An antibody raised against the C terminus (amino acids 592 to 721) of C2II inhibited binding of C2II to cells. The antibody prevented pore formation by C2II oligomers in artificial membranes but did not influence the properties of existing channels. To further define the region responsible for receptor binding, we constructed proteins with deletions in C2II; specifically, they lacked amino acid residues 592 to 721 and the 7 C-terminal amino acid residues. The truncated proteins still formed sodium dodecyl sulfate-stable oligomers but were unable to bind to cells. Our data indicate that the C terminus of C2II mediates binding of the protein to cells and that the 7 C-terminal amino acids are structurally important for receptor binding.
Adoptive T‐cell therapy for cancer: The era of engineered T cells (2015)

Tumors originate from a number of genetic events that deregulate homeostatic mechanisms controlling normal cell behavior. The immune system, devoted to patrol the organism against pathogenic events, can identify transformed cells, and in several cases cause their elimination. It is however clear that several mechanisms encompassing both central and peripheral tolerance limit antitumor immunity, often resulting into progressive diseases. Adoptive T-cell therapy with either allogeneic or autologous T cells can transfer therapeutic immunity. To date, genetic engineering of T cells appears to be a powerful tool for shaping tumor immunity. In this review, we discuss the most recent achievements in the areas of suicide gene therapy, and TCR-modified T cells and chimeric antigen receptor gene-modified T cells. We provide an overview of current strategies aimed at improving the safety and efficacy of these approaches, with an outlook on prospective developments.
Animal models of Duchenne muscular dystrophy: from basic mechanisms to gene therapy (2015)

Duchenne muscular dystrophy (DMD) is a progressive muscle-wasting disorder. It is caused by loss-of-function mutations in the dystrophin gene. Currently, there is no cure. A highly promising therapeutic strategy is to replace or repair the defective dystrophin gene by gene therapy. Numerous animal models of DMD have been developed over the last 30 years, ranging from invertebrate to large mammalian models. mdx mice are the most commonly employed models in DMD research and have been used to lay the groundwork for DMD gene therapy. After ~30 years of development, the field has reached the stage at which the results in mdx mice can be validated and scaled-up in symptomatic large animals. The canine DMD (cDMD) model will be excellent for these studies. In this article, we review the animal models for DMD, the pros and cons of each model system, and the history and progress of preclinical DMD gene therapy research in the animal models. We also discuss the current and emerging challenges in this field and ways to address these challenges using animal models, in particular cDMD dogs.
Modification of Collagen IV by Glucose or Methylglyoxal Alters Distinct Mesangial Cell Functions (2009)

Diabetic nephropathy (DN) affects both glomerular cells and the extracellular matrix (ECM), yet the pathogenic mechanisms involving cell-matrix interactions are poorly understood. Glycation alters integrin-dependent cell-ECM interactions, and perturbation of these interactions results in severe renal pathology in diabetic animals. Here, we investigated how chemical modifications of the ECM by hyperglycemia and carbonyl stress, two major features of the diabetic milieu, affect mesangial cell functions. Incubation of collagen IV with pathophysiological levels of either the carbonyl compound methylglyoxal (MGO) or glucose resulted in modification of arginine or lysine residues, respectively. Mouse mesangial cells plated on MGO-modified collagen IV showed decreased adhesion and migration. Cells plated on glucose-modified collagen IV showed reduced proliferation and migration and increased collagen IV production. Inhibiting glucose-mediated oxidative modification of collagen IV lysine residues rescued the alterations in cell growth, migration, and collagen synthesis. We propose that diabetic ECM affects mesangial cell functions via two distinct mechanisms: modification of arginine residues by MGO inhibits cell adhesion, whereas oxidative modification of lysine residues by glucose inhibits cell proliferation and increases collagen IV production. These mechanisms may contribute to mesangial cell hypertrophy and matrix expansion in DN.
Sterol composition of 19 vegetable oils (1973)

Abstract The unsaponifiables from 19 vegetable oils were divided into a sterol and three other fractions by thin‐layer chromatography. All except olive and palm kernel oils gave the sterol fraction in a large quantity. Compositions of the sterol fractions were determined by gas liquid chromatography. Identification of each sterol was carried out by gas liquid chromatography and combined gas chromatograph‐mass spectrometry. Campesterol, stigmasterol and β‐sitosterol were present in all oils, and a minor amount of cholesterol in majority of the oils. Brassicasterol occurrence was widespread but its content was extremely small in oils other than rapeseed oil. Other sterols, presumably δ 7 ‐stigmastenol and δ 5 ‐ and δ 7 ‐avenasterol were detected in most of the oils.
PUVA‐induced lymphocyte apoptosis: Mechanism of action in psoriasis (1999)

Psoralen plus ultraviolet A (PUVA), utilizing oral 8-methoxypsoralen (8-MOP), is a widely utilized and effective treatment for psoriasis vulgaris. Previous studies have suggested that PUVA's mechanism of action in psoriasis is a result of its direct lymphotoxic effects. Trimethylpsoralen (TMP), a potentially safer compound, has been found to be effective in psoriasis during bath water delivery. In this study we examined the relative antilymphocytic effects of TMP and 8-MOP through both flow cytometry and tissue analysis on lesional skin during clinical treatment. Based on FACS analysis on phytohemagglutinin-activated lymphocytes, we found TMP to be nearly 10,000 fold more lymphotoxic compared to 8-MOP. In addition, lymphocytes treated with 8-MOP or TMP with UVA displayed DNA degradation patterns typical of apoptotic cell death. These findings were consistent with our investigation of treated psoriatic skin, with virtual elimination of epidermal CD3+ T-cells following bath water treatment with TMP or 8-MOP. These results support the theory that the therapeutic effects of PUVA stem from its toxic effects on activated lymphocytes. If further investigation supports TMP's lack of carcinogenicity, this potent lymphotoxic treatment may prove to be one of the safest and most effective treatments for psoriasis.
Characteristics and device design of sub-100 nm strained Si N- and PMOSFETs (2003)

Current drive enhancements were demonstrated in the strained-Si PMOSFETs with sub-100 nm physical gate lengths for the first time, as well as in the NMOSFETs with well-controlled threshold voltage V/sub T/ and overlap capacitance C/sub OV/ characteristics for L/sub poly/ and L/sub eff/ below 80 nm and 60 nm. A 110% enhancement in the electron mobility was observed in the strained Si devices with 1.2% tensile strain (28% Ge content in the relaxed SiGe buffer), along with a 45% increase in the peak hole mobility.
Valence and patterning of aromatic residues determine the phase behavior of prion-like domains (2020)

Prion-like domains (PLDs) can drive liquid-liquid phase separation (LLPS) in cells. Using an integrative biophysical approach that includes nuclear magnetic resonance spectroscopy, small-angle x-ray scattering, and multiscale simulations, we have uncovered sequence features that determine the overall phase behavior of PLDs. We show that the numbers (valence) of aromatic residues in PLDs determine the extent of temperature-dependent compaction of individual molecules in dilute solutions. The valence of aromatic residues also determines full binodals that quantify concentrations of PLDs within coexisting dilute and dense phases as a function of temperature. We also show that uniform patterning of aromatic residues is a sequence feature that promotes LLPS while inhibiting aggregation. Our findings lead to the development of a numerical stickers-and-spacers model that enables predictions of full binodals of PLDs from their sequences.
A widely tunable narrow linewidth semiconductor fiber ring laser (1998)

We have demonstrated a novel approach to obtain a 0.1-nm line width laser with 38-dB sidemode suppression by utilizing a 1.3-μm semiconductor optical amplifier in a fiber unidirectional ring that consists of a linear polarizer and polarization controllers. The laser has a low-threshold current of 22.5 mA as well as a wide tuning range of 28 nm. The new approach is applicable to the 1.55-μm region as well. It is expected that nanosecond wavelength tuning speed is feasible using this approach in conjunction with fast electrooptic polarization controllers, short cavities and low-cavity losses."
Melatonin protects SH‐SY5Y neuroblastoma cells from calyculin A‐induced neurofilament impairment and neurotoxicity (2004)

Abstract: Hyperphosphorylation of cytoskeletal proteins seen in Alzheimer's disease is most probably the result of an imbalanced regulation in protein kinases and protein phosphatases (PP) in the affected neurons. Previous studies have revealed that PP‐2A and PP‐1 play important roles in the pathogenesis. Employing human neuroblastoma cells, we found that 10 n m calyculin A (CA), a selective inhibitor of PP‐2A and PP‐1, significantly increased phosphorylation and accumulation of neurofilament (NF) in the cells. Levels of NF‐M (middle chain) and NF‐L (light chain) mRNA decreased after CA treatment. Additionally, CA led to a decreased cell viability determined by MTT and crystal violet assay. Melatonin efficiently protects the cell from CA‐induced alterations in NF hyperphosphorylation and accumulation, suppressed NF gene expression as well as decreased cell viability. It is concluded that inhibition of PP‐2A/PP‐1 by CA induces abnormalities in NF metabolism and cell survival, and melatonin efficiently arrests the lesions.
Clostridium difficile toxin a therapy for hct 116 human colon cancer in nude mice (1994)

Clostridium difficile toxin A was evaluated for an antitumor effect in vivo on HCT 116 human colon carcinoma cells growing subcutaneously in nude mice. A mean reduction in tumor volume of at least 65%, by measurement in three dimensions, was observed in mice who received two 9- to 13-day courses of daily intraperitoneal injections of toxin A as compared to mice receiving diluent alone. Reversible adverse effects of toxin A were noted in some animals, consisting primarily of liver toxicity and skin rash. HCT 116 cells in toxin A-treated mice grew as flattened tumors with ulcerated centers compared to rounded tumors without ulceration in controls. Histologic examination of tumors from representative mice revealed that two thirds of the tumor in a treated mouse was necrotic compared to only one third in a control, suggesting greater antitumor efficacy of toxin A than estimated by tumor measurements alone.
Geminale Vinyldiazide, VI. 4,5‐Dihydro‐1H‐tetrazol‐5‐ylidene aus 3,3‐Diazido‐2‐cyanacrylsäureestern und Hydrazinen, Hydraziden sowie O‐substituierten Hydroxylaminen (1989)

Abstract Bei der Umsetzung der geminalen Vinyldiazide 6 und 7 bei –30°C mit Phenylhydrazin ( 8a ), den Hydraziden 8b , c sowie O ‐Benzylhydroxylamin ( 8d ) entstehen primär die Vinylazide 9 und 10 ( 9a , b sind isolierbar). Anschließender 1,5′‐Ringschluß (aufeinanderfolgende Vinylazid‐Iminoazid‐Isomerisierung, Iminoazid‐Tetrazol‐Isomerisierung und Tautomerie) liefert die 4,5‐Dihydro‐1 H ‐tetrazol‐5‐ylidene 15 und 16 . Mit Triethylamin bildet 15a das Ammonium‐Salz 17 . Setzt man das geminale Vinyldiazid 6 nicht bei –30°C sondern bei 20°C mit den Hydraziden 20a , b (= 8b , c ) um, dann entstehen an Stelle von 15b , c die 5‐Amino‐1,2,4‐triazole 23a , b .