gebhart/patrepeval huggingface dataset:
A gene expression signature of RAS pathway dependence predicts response to PI3K and RAS pathway inhibitors and expands the population of RAS pathway activated tumors (2010)

These data demonstrate that the RAS pathway signature is superior to KRAS mutation status for the prediction of dependence on RAS signaling, can predict response to PI3K and RAS pathway inhibitors, and is likely to have the most clinical utility in lung and breast tumors.
Cyclic lactam .alpha.-melanotropin analogs of Ac-Nle4-cyclo[Asp5,D-Phe7,Lys10]-.alpha.-melanocyte-stimulating hormone-(4-10)-NH2 with bulky aromatic amino acids at position 7 show high antagonist potency and selectivity at specific melanocortin receptors (1995)

The cloning of the melanocyte-stimulating hormone (MSH) and adrenocorticotropic hormone (ACTH) receptors (MC1-R and MC2-R, respectively) recently has led to the identification of three additional melanocortin receptors, MC3-R, MC4-R, and MC5-R. The MC2 receptor primarily recognizes only ACTH peptides, but the other four receptors all recognize alpha-melanocyte-stimulating hormone (alpha-MSH) and potent alpha-MSH agonists such as [Nle4,D-Phe7]alpha-MSH-NH2 and Ac-Nle4-c[Asp5,D-Phe7,Lys10]alpha-MSH-(4-10)-NH2 as well as ACTH. The absence of any known physiological role for these new receptors, expressed both in the brain (MC3-R and MC4-R) and throughout a number of peripheral tissues (MC5-R), has necessitated as search for potent and receptor selective agonists and antagonists. We report here that analogues of the superpotent cyclic agonist analogue Ac-Nle4-c[Asp5,D-Phe7, Lys10]alpha-MSH-(4-10)-NH2, in which a bulky aromatic amino acid is substituted in the 7-position, can produce potent and selective antagonists for melanocortin receptors. Thus, the D-p-iodophenylalanine7-containing analogue Ac-Nle4-c[Asp5,D-Phe(pI)7,Lys10]alpha-MSH-(4-10)-NH2 is a potent antagonist (pA2 = 10.3) in the classical frog skin (Rana pipiens) assay (MC1-R), as is the D-2'-naphthylalanine7 (D-Nal(2)7)-containing analogue Ac-Nle4-c[Asp5,D-Nal(2)7,Lys10]alpha-MSH-(4-10)-NH2 (pA2 > 10.3). Interestingly, the D-p-chloro- and D-p-fluorophenylalanine7-containing analogues lacked antagonist activities at all melanotropin receptors, and both exhibited full agonist potency in the frog skin assay. The activity of these analogues also was examined at four mammalian melanocortin receptors. Interestingly, Ac-Nle4-c[Asp5,(D-Nal(2)7,Lys10] alpha-MSH-(4-10)-NH2 was found to be a potent antagonist of the MC4-R (pA2 = 9.3) with minimal agonist activity, a less potent antagonist of the MC3-R (pA2 = 8.3) with minimal agonist activity, and a full agonist of the MC1 and MC5 receptors. Surprisingly, Nle4-c[Asp5,D-Phe(pI)7,Lys10]alpha-MSH was found to be a potent agonist at the cloned human MC1-R (EC50 = 0.055 nM) and mouse MC1-R (EC50 = 0.19 nM) but had potent antagonist activities at the human MC4-R (pA2 = 9.7) and human MC3-R (pA2 = 8.3) with significant partial agonist activities (EC50 = 0.57 and 0.68 nM, respectively) as well. Thus, highly potent and receptor selective antagonist analogues can arise from substitution of the D-Phe7 residue with a bulky aromatic amino acid. These analogues can be used to help determine the functional roles of these receptors.
Electron microscopic evidence for in vivo extracellular localization of Yersinia pseudotuberculosis harboring the pYV plasmid (1990)

Electron microscopic evidence is presented that bacteria harboring the virulence plasmid pYV from Yersinia pseudotuberculosis are localized in extracellular sites during the course of infection in mice, often unambiguously undergoing active replication. Virulent pYV+ bacteria, often seen adherent to platelets, severely restricted granuloma formation, creating necrotic microabscesses poorly populated with inflammatory cells. This contrasts with granulomas produced by pYV- bacteria, which appear to be composed mainly of polymorphonuclear and mononuclear cells. Our results therefore strongly suggest that active replication of pYV+ bacteria predominantly, if not exclusively, occurs in vivo in extracellular sites.
MDM4 Overexpressed in Acute Myeloid Leukemia Patients with Complex Karyotype and Wild-Type TP53 (2014)

Acute myeloid leukemia patients with complex karyotype (CK-AML) account for approximately 10-15% of adult AML cases, and are often associated with a poor prognosis. Except for about 70% of CK-AML patients with biallelic inactivation of TP53, the leukemogenic mechanism in the nearly 30% of CK-AML patients with wild-type TP53 has remained elusive. In this study, 15 cases with complex karyotype and wild-type TP53 were screened out of 140 de novo AML patients and the expression levels of MDM4, a main negative regulator of p53-signaling pathway, were detected. We ruled out mutations in genes associated with a poor prognosis of CK-AML, including RUNX1 or FLT3-ITD. The mRNA expression levels of the full-length of MDM4 (MDM4FL) and short isoform MDM4 (MDM4S) were elevated in CK-AML relative to normal karyotype AML (NK-AML) patients. We also explored the impact of MDM4 overexpression on the cell cycle, cell proliferation and the spindle checkpoint of HepG2 cells, which is a human cancer cell line with normal MDM4 and TP53 expression. The mitotic index and the expression of p21, BubR1 and Securin were all reduced following Nocodazole treatment. Moreover, karyotype analysis showed that MDM4 overexpression might lead to aneuploidy or polyploidy. These results suggest that MDM4 overexpression is related to CK-AML with wild-type TP53 and might play a pathogenic role by inhibiting p53-signal pathway.
The Caenorhabditis elegans unc-13 gene product is a phospholipid-dependent high-affinity phorbol ester receptor (1992)

The Caenorhabditis elegans unc-13 mutant is a member of a class of mutants that have un-coordinated movement. Mutations of the unc-13 gene cause diverse defects in C. elegans, including abnormal neuronal connections and modified synaptic transmission in the nervous system. unc-13 cDNA encodes a protein (UNC-13) of 1734 amino acid residues with a predicted molecular mass of 198 kDa and sequence identity to the C1/C2 regions but not to the catalytic domain of the ubiquitously expressed protein kinase C family [Maruyama & Brenner (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 5729-5733]. To characterize the phorbol ester binding site of the UNC-13 protein, cDNA encoding the C1/C2-like regions (amino acid residues 546-940) was expressed in Escherichia coli and the 43 kDa recombinant protein was purified. Phorbol ester binding to the 43 kDa protein was zinc- and phospholipid-dependent, stereospecific and of high affinity (Kd 67 nM). UNC-13 specific antisera detected a protein of approx. 190 kDa in wild-type (N2) but not in mutant (e1019) C. elegans cell extracts. We conclude that UNC-13 represents a novel class of phorbol ester receptor.
Electroluminescence and electrical transport in poly(3-octylthiophene) diodes (1992)

We report visible light emission from diodes made from poly(3-octylthiophene). Use of a soluble derivative of polythiophene allows fabrication of the light emitting diodes by casting the polymer film from solution with no subsequent processing or heat treatment required. The devices emit dim red-orange light with relatively low external quantum efficiencies, below 2.5×10−5 photons per electron at room temperature. Electrical characterization reveals diode behavior with rectification ratios greater than 102. The temperature dependence indicates that tunneling phenomena dominate the charge injection.
Affinity between Metal–Organic Frameworks and Polyimides in Asymmetric Mixed Matrix Membranes for Gas Separations (2012)

A series of flat-sheet asymmetric mixed matrix membranes (MMMs) have been fabricated with MOF-5, Cu3(BTC)2, and MIL-53(Al) as fillers and PI polymer as a matrix through the dry–wet phase inversion method. After the surface modification by coating a PAA solution (15% wt) on the top of the obtained membrane, a thin defect-free selective skin in the MMM is obtained. The permeance of various gases such as H2, He, CH4, N2, and CO2 and their gas pair selectivity have been investigated, respectively. The results show that Cu3(BTC)2/PI MMM possesses the best gas separation performance with H2 permeance of 0.44 GPU and H2/CH4 selectivity of 100. In addition, the mechanism of MOF fillers in MMMs has been further revealed by the interaction analysis between MOF fillers and PI chains.
Exploiting the Natural Diversity in Adenovirus Tropism for Therapy and Prevention of Disease (2002)

Since targeting of recombinant adenovirus vectors to defined cell types in vivo is a major challenge in gene therapy and vaccinology, we explored the natural diversity in human adenovirus tissue tropism. Hereto, we constructed a library of Ad5 vectors carrying fibers from other human serotypes. From this library, we identified vectors that efficiently infect human cells that are important for diverse gene therapy approaches and for induction of immunity. For several medical applications (prenatal diagnosis, artificial bone, vaccination, and cardiovascular disease), we demonstrate the applicability of these novel vectors. In addition, screening cell types derived from different species revealed that cellular receptors for human subgroup B adenoviruses are not conserved between rodents and primates. These results provide a rationale for utilizing elements of human adenovirus serotypes to generate chimeric vectors that improve our knowledge concerning adenovirus biology and widen the therapeutic window for vaccination and many different gene transfer applications.
Anti‐proliferative effects of γ‐tocotrienol on mammary tumour cells are associated with suppression of cell cycle progression (2009)

Treatment with 4 micromgamma-tocotrienol significantly inhibited +SA cell proliferation over a 4-day culture period. Moreover, this treatment resulted in a relatively large reduction in cyclin D1, cyclin dependent kinase (CDK)4, CDK2 and CDK6 levels, between 4 and 24 h after EGF exposure. Tocotrienol treatment also resulted in a relatively large increase in CDK inhibitor (CKI) p27, prior to and after EGF exposure, but had little effect on levels of CKIs, p21 and p15. Tocotrienol treatment also induced a large relative reduction in retinoblastoma (Rb) protein phosphorylation at ser780 and ser807/811. These findings strongly suggest that anti-proliferative effects of gamma-tocotrienol are associated with reduction in cell cycle progression from G(1) to S, as evidenced by increased p27 levels, and a corresponding decrease in cyclin D1, CDK2, CDK4, CDK6 and phosphorylated Rb levels.
The Expression of MicroRNA miR-107 Decreases Early in Alzheimer's Disease and May Accelerate Disease Progression through Regulation of β-Site Amyloid Precursor Protein-Cleaving Enzyme 1 (2008)

MicroRNAs (miRNAs) are small regulatory RNAs that participate in posttranscriptional gene regulation in a sequence-specific manner. However, little is understood about the role(s) of miRNAs in Alzheimer's disease (AD). We used miRNA expression microarrays on RNA extracted from human brain tissue from the University of Kentucky Alzheimer's Disease Center Brain Bank with near-optimal clinicopathological correlation. Cases were separated into four groups: elderly nondemented with negligible AD-type pathology, nondemented with incipient AD pathology, mild cognitive impairment (MCI) with moderate AD pathology, and AD. Among the AD-related miRNA expression changes, miR-107 was exceptional because miR-107 levels decreased significantly even in patients with the earliest stages of pathology. In situ hybridization with cross-comparison to neuropathology demonstrated that particular cerebral cortical laminas involved by AD pathology exhibit diminished neuronal miR-107 expression. Computational analysis predicted that the 3'-untranslated region (UTR) of beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1) mRNA is targeted multiply by miR-107. From the same RNA material analyzed on miRNA microarrays, mRNA expression profiling was performed using Affymetrix Exon Array microarrays on nondemented, MCI, and AD patients. BACE1 mRNA levels tended to increase as miR-107 levels decreased in the progression of AD. Cell culture reporter assays performed with a subset of the predicted miR-107 binding sites indicate the presence of at least one physiological miR-107 miRNA recognition sequence in the 3'-UTR of BACE1 mRNA. Together, the coordinated application of miRNA profiling, Affymetrix microarrays, new bioinformatics predictions, in situ hybridization, and biochemical validation indicate that miR-107 may be involved in accelerated disease progression through regulation of BACE1.
Tantalum Carbide or Niobium Carbide Catalyzed Oxidation of Sulfides with Hydrogen Peroxide: Highly Efficient and Chemoselective Syntheses of Sulfoxides and Sulfones (2010)

The oxidation of sulfides with 30% hydrogen peroxide catalyzed by tantalum carbide provided the corresponding sulfoxides in high yields. The reaction of sulfides with 30% hydrogen peroxide catalyzed by niobium carbide efficiently afforded the corresponding sulfones. These catalysts can easily be recovered from the reaction mixture and may be repeatedly used as catalysts for the oxidation without losing their activity.
Lactobacillus bulgaricus asparagine synthetase and asparaginyl-tRNA synthetase: coregulation by transcription antitermination? (1996)

Genes encoding the ammonia-dependent asparagine synthetase (asnA) and asparaginyl-tRNA synthetase (asnS) have been cloned from Lactobacillus bulgaricus ATCC 11842. The nucleotide sequence suggests that asnA and asnS are organized as one operon and regulated by the tRNA-directed transcription antitermination mechanism (T. M. Henkin, Mol. Microbiol. 13:381-387, 1994).
Pathologic Predictors of Microsatellite Instability in Colorectal Cancer (2008)

Identification of microsatellite unstable (MSI-H) colorectal cancers (CRCs) is important not only for the identification of hereditary nonpolyposis colorectal cancer syndrome but also because MSI-H CRCs have a better prognosis and may respond differently to 5-fluorouracil-based chemotherapy. We present 2 nearly equivalent logistic regression models for clinical use that predict microsatellite instability based on the review of 1649 CRCs from patients of all ages collected in a population-based case control study in northern Israel. One hundred ninety-eight of these 1649 tumors demonstrated a high degree of microsatellite instability (12%). Multivariate analysis found that >2 tumor-infiltrating lymphocyte (TIL) cells per high-powered field, the lack of dirty necrosis, the presence of a Crohn-like reaction, right-sided location, any mucinous differentiation (mucinous or focally mucinous) and well or poor differentiation, and age less than 50 were all independent predictors of MSI-H. We developed 2 logistic regression models that differ only by the statistical approach used to analyze the number of TIL cells per high-powered field, where the slightly more accurate (and complex) model uses the log of the total number of TIL cells. The simpler clinical model uses a cut-off of 2>TIL cells per high-powered field. The accuracy of both models is high, with an 85.4% versus 85.0% probability of correctly classifying tumors as MSI-H. By employing the simpler model, pathologists can predict the likelihood of microsatellite instability by compiling the MSI probability score (Table 4 and Fig. 1) from simple histologic and clinical data available during sign-out. Our model shows that approximately 43% of CRCs have a MSI probability score of 1 or less and hence have little likelihood (<3%) of being MSI-H. Although this model is not perfect in predicting microsatellite instability, its use could improve the efficiency of expensive diagnostic testing.
A Comparative Study of n+/p Junction Formation for Deep Submicron Elevated Source/Drain Metal Oxide Semiconductor Field Effect Transistors (1997)

Ultrashallow elevated n+/p junctions (∼75 nm) incorporating selectively deposited epitaxial silicon layers were fabricated. The undoped epi layers (∼100 nm) were deposited on exposed diffusion areas in an Advanced Semiconductor Material Epsilon I system specifically designed for low thermal budget single‐wafer processing. Shallow junctions (∼75 nm) were formed by ion implantation (As, 4 × 1015/cm2, 80 keV) into undoped epi layers and out‐diffusion into the underlying substrate. Alternatively, an ion implanted (As, 4 × 1015/cm2, 60 keV) elevated layer was utilized to contact a shallow junction, which was formed (As, 1.5 × 1015/cm2, 15 keV) before the epi deposition. All junctions were annealed at 950°C for 10 s. Nonsilicided elevated junctions and conventional nonelevated (As, 1.5 × 1015/cm2, 15 keV) ones displayed very similar junction characteristics. Silicided nonelevated ultrashallow junctions, however, showed large reverse leakage current due to the substrate consumption. Both silicided elevated (post‐epi and pre‐epi) junctions exhibited excellent forward characteristics and low reverse leakage current. The difference in the reverse leakage characteristics of these two elevated junctions was attributed to the epi faceting formed at the sidewall edge of localized oxidation of silicon isolation. Deep submicron n = channel metal oxide semiconductor field effect transistors incorporating these junctions were also fabricated and electrically tested. Both elevated source/drain (S/D) devices show superior current driving capability compared to nonelevated ones as a result of much reduced parasitic resistance from contact source/drain junctions.
Dactylocyclines: novel tetracycline glycosides active against tetracycline-resistant bacteria (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDactylocyclines: novel tetracycline glycosides active against tetracycline-resistant bacteriaAdrienne A. Tymiak, Carol Aklonis, Mark S. Bolgar, Alicia D. Kahle, Donald R. Kirsch, Joseph O'Sullivan, Michael A. Porubcan, Pacifico Principe, William H. Trejo, and Cite this: J. Org. Chem. 1993, 58, 3, 535–537Publication Date (Print):January 1, 1993Publication History Published online1 May 2002Published inissue 1 January 1993https://pubs.acs.org/doi/10.1021/jo00055a002https://doi.org/10.1021/jo00055a002research-articleACS PublicationsRequest reuse permissionsArticle Views611Altmetric-Citations28LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Distribution and regulation of cyclooxygenase‐2 in carrageenan‐induced inflammation (1999)

1 We characterized the regulation of cyclooxygenase-2 (COX-2) at the mRNA, protein and mediator level in two rat models of acute inflammation, carrageenan-induced paw oedema and mechanical hyperalgesia. 2 Carrageenan was injected in the hind paw of rat at low (paw oedema) and high doses (hyperalgesia). COX-2 and prostaglandin E2 (PGE2) levels were measured by RT-PCR and immunological assays. We also determined the distribution of COX-2 by immunohistochemistry. 3 The injection of carrageenan produced a significant and parallel induction of both COX-2 and PGE2. This induction was significantly higher in hyperalgesia than in paw oedema. This was probably due to the 9 fold higher concentration of carrageenan used to provoke hyperalgesia. 4 Immunohistochemical examination showed COX-2 immunoreactivity in the epidermis, skeletal muscle and inflammatory cells of rats experiencing hyperalgesia. In paw oedema however, only the epidermis showed positive COX-2 immunoreactivity. 5 Pretreatment with indomethacin completely abolished the induction of COX-2 in paw oedema but not in hyperalgesia. 6 These results suggest that multiple mechanisms regulate COX-2 induction especially in the more severe model. In carrageenan-induced paw oedema, prostanoid production have been linked through the expression of the COX-2 gene which suggest the presence of a positive feedback loop mechanism.
Procathepsins L and D are membrane-bound in acidic microsomal vesicles (1991)

Procathepsins L and D, the proenzyme forms of two lysosomal proteases, are shown to bind to mouse fibroblast microsomal membranes at acidic pH. The propeptide of procathepsin L is necessary for membrane association because the mature forms of this lysosomal protein did not bind to the membranes. Both proenzymes were eluted from the membranes by increasing either the pH or the ionic strength of the buffer, so they are peripheral proteins that interact ionically with the membranes. The proenzymes were not eluted from the membranes with 50 mM mannose or 10 mM mannose 6-phosphate, which suggests that carbohydrate does not mediate membrane binding. Membrane binding is probably a specific, protein-mediated interaction since treatment of the microsomes with trypsin reduced by half the amount of procathepsin L which bound to the membranes, and binding of procathepsin L to the membranes was saturable. One or more "lysosomal proenzyme receptors" capable of binding to lysosomal proenzymes at acidic pH could complement the mannose 6-phosphate receptor system in prelysosomes and sort certain lysosomal proenzymes to lysosomes.
W. J. M. Rankine and the Rise of Thermodynamics (1981)

In the history of thermodynamics, two dates stand out as especially important: 1824, when Sadi Carnot's brilliant memoir Réflexions sur la puissance motrice du feu appeared in print; and 1850, when Rudolf Clausius published his similarly titled paper ‘Ueber die bewegende Kraft der Wärme’. In this paper Clausius narrowly beat the Scottish physicist William Thomson to the solution of a puzzle which had been highlighted in the latter's recent publications: how could Carnot's theory, with all its intellectual attractions, be reconciled with the newly discovered principle of the inter-convertibility of heat and work? Clausius's solution (as is well known) was to replace Carnot's axiom of heat conservation, with the axiom now known as the second law of thermodynamics.
Disease phenotype and genotype are associated with shifts in intestinal-associated microbiota in inflammatory bowel diseases (2010)

These results support the concept that disease phenotype and genotype are associated with compositional changes in intestinal-associated microbiota.