gebhart/patrepeval huggingface dataset:
Enabling Large-Scale Pharmacogenetic Studies by High-Throughput Mutation Detection and Genotyping Technologies (2001)

Large-scale genotyping is crucial to the identification of the genetic make-ups that underlie the onset of diseases and individual variations in drug responses. Enabling technologies to identify genetic polymorphisms rapidly, accurately, and cost effectively will dramatically impact future drug and development processes.
Presence of ADP-Glucose Pyrophosphorylase in Shrunken-2 and Brittle-2 Mutants of Maize Endosperm (1969)

ADP-Glucose pyrophosphorylase activity has been detected in relatively low amounts in the embryos and endosperms of sh(2) and bt(2) mutant maize seeds. The total enzyme activities in sh(2) and bt(2) were about 12% and 17% respectively, of that found in starchy maize seeds (Dekalb 805). The ADP-glucose pyrophosphorylases from the starchy and mutant maize seeds were activated by 3-phosphoglycerate. However, the extent of the activation of the sh(2) enzyme was not as great as that observed with the bt(2) and Dekalb 805 enzymes. The low levels of ADP-glucose pyrophosphorylase activity in the maize mutants correlate well with the low levels of starch found in the endosperm of these mutants.
Cross‐presentation: underlying mechanisms and role in immune surveillance (2005)

It was originally thought that a cell's major histocompatibility complex (MHC) class I molecules presented peptides derived exclusively from proteins synthesized by the cell itself. However, in some circumstances, antigens from the extracellular environment can be presented on MHC class I molecules and stimulate CD8(+) T-cell immunity, a process termed cross-presentation. Cross-presentation was originally discovered as an obscure phenomenon in transplantation immunity. However, it is now clear that it is a major mechanism by which the immune system monitors tissues and phagocytes for the presence of foreign antigen. Cross-presentation is the only pathway by which the immune system can detect and respond to viral infections or mutations that exclusively occur in parenchymal cells rather than in bone marrow-derived antigen-presenting cells (APCs). Professional APCs, such as dendritic cells, are the principal cells endowed with the capacity to cross-present antigens. In this process, the APCs acquire proteins from other tissue cells through endocytic mechanisms, especially phagocytosis or macropinocytosis. The internalized antigen can then be processed through at least two different mechanisms. In one pathway, the antigen is transferred from the phagosome into the cytosol, where it is hydrolyzed by proteasomes into oligopeptides that are then transported by the transporter associated with antigen processing to MHC class I molecules in the endoplasmic reticulum or phagosomes. In a second pathway, the antigen is cleaved into peptides by endosomal proteases, particularly cathepsin S, and bound by class I molecules probably in the endocytic compartment itself. Depending on the nature of the antigen, one or both of these pathways can contribute to cross-presentation in vivo. The outcome of cross-presentation can be either tolerance or immunity. Which of these outcomes occurs is thought to depend on whether antigens are acquired by themselves alone, leading to tolerance, or with immunostimulatory signals, leading to immunity. One source of such signals is from dying cells that release immunostimulatory 'danger' signals that promote the generation of immunity to their cellular antigens. In addition to the critical role of cross-presentation in normal immune physiology, this pathway has considerable potential for being exploited for developing subunit vaccines that elicit both CD4(+) and CD8(+) T-cell immunity.
Block copolymers of styrene, isoprene, and ethylene oxide prepared by anionic polymerization. I. Synthesis and characterization (1978)

Abstract Anionic polymerization has been used as a technique for the synthesis of five‐block copolymers of polystyrene (PS), polyisoprene (PI), and poly(ethylene oxide) (PEO). Two types of such polymers, PEO‐PI‐PS‐PI‐PEO and PEO‐PS‐PI‐PS‐PEO with varying PEO block length, have been prepared, using potassium naphthalene as the initiator and tetrahydrofuran as the solvent. The polymers were purified by extraction with ethyl acetate, diethyl ether, and water. After the addition of each monomer, a sample from the living polymer solution was taken and analyzed by spectroscopy (infared (IR) and proton magnetic resonance (PMR)), osmometry, and gel‐permeation chromatography (GPC) to obtain information about composition, molecular weight and molecular weight distribution of the intermediate polymers. The five‐block copolymers have also been characterized by the same techniques and by elemental analysis.
Marked Reduction of Ventricular Defibrillation Threshold by Application of an Auxiliary Shock to a Catheter Electrode in the Left Posterior Coronary Vein of Dogs (2000)

Addition of an AS from the posterior cardiac vein before an endocardial PS reduces DFT energy by more than 50%. Such DFT reduction could improve therapeutic safety margin or permit reduction in volume of implantable cardioverter defibrillators.
The Dipole Moment of ms-Tetraphenylporphine (1942)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Dipole Moment of ms-TetraphenylporphineW. D. KumlerCite this: J. Am. Chem. Soc. 1942, 64, 12, 2993–2994Publication Date (Print):December 1, 1942Publication History Published online1 May 2002Published inissue 1 December 1942https://pubs.acs.org/doi/10.1021/ja01264a079https://doi.org/10.1021/ja01264a079research-articleACS PublicationsRequest reuse permissionsArticle Views33Altmetric-Citations3LEARN 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
Extrinsic regulation of satellite cell specification (2010)

Cellular commitment during vertebrate embryogenesis is controlled by an interplay of intrinsic regulators and morphogenetic signals. These mechanisms recruit a subset of cells in the developing organism to become the ancestors of skeletal muscle. Signals that control progression through the myogenic lineage converge on a battery of hierarchically organized transcription factors which modulate the cells to either remain in a primitive state or allow their commitment and differentiation into skeletal muscle fibers. A small population of cells will retain a largely unspecified state throughout development. Such stem cells, in conjunction with more committed myogenic progenitors, form a heterogeneous population that colonizes adult skeletal muscle as satellite cells. The satellite cell pool is responsible for the remarkable regenerative capacity of skeletal muscle. Similar to their counterparts during embryonic development, satellite cells are capable of self-renewal and can give rise to myogenic progeny. Impaired satellite cell homeostasis has been associated with numerous muscular disorders. Due to intense research efforts in the past two decades, the complex biology of muscle stem cells has now revealed some of its secrets and new avenues for the development of therapeutic molecules have emerged. In the present review we focus on the extrinsic mechanisms that control self-renewal, specification and differentiation of satellite cells and their significance for the development of biologic drugs.
Green Resin from Forestry Waste Residue “Karanja (Pongamia pinnata) Seed Cake” for Biobased Composite Structures (2014)

A nonedible protein was extracted from defatted karanja (Pongamia pinnata) seedcake, so far considered as forestry waste residue after oil extraction. High average molecular weight and availability of reactive amino groups of karanja protein (KP), which can be cross-linked, provide the basis to form strong polymeric material. Green thermoset resin was developed from KP using a natural α,β-unsaturated aldehyde “cinnamaldehyde”. In addition, a natural plasticizer (sorbitol) was used to reduce the brittleness of the resin. Mechanical and physical properties were characterized by solution casting resin films. The cross-linking and plasticizer content were optimized to get the best overall performance. A combination of 5% plasticizer content and 12% cross-linking resulted in best mechanical properties. The modified KP resin provides a green, sustainable, and biobased alternative to not only the petroleum-based resins but also to the edible protein-based resins such as soy protein. The KP resin would be inexpensive and useful to fabricate biobased green composite structures.
Novel late-onset Alzheimer disease loci variants associate with brain gene expression (2012)

CLU and MS4A4A eSNPs may at least partly explain the LOAD risk association at these loci. CLU and ABCA7 may harbor additional strong eSNPs. These results have implications in the search for functional variants at the novel LOAD risk loci.
Epstein-Barr Virus IL-10 Engages IL-10R1 by a Two-step Mechanism Leading to Altered Signaling Properties (2012)

Background: ebvIL-10 is a viral mimic of human . Results: ebvIL-10 assembles the ebvIL-10IL-10R1 complex in a two-step process that alters its signaling properties relative to hIL-10. Conclusion: Distinct receptor engagement by ebvIL-10 enhances its bioactivity on cells with high IL-10R1 levels. Significance: Elucidating differences in hIL-10 and ebvIL-10 function is critical to understand EBV immune evasion.
Mutation of a mutL Homolog in Hereditary Colon Cancer (1994)

Some cases of hereditary nonpolyposis colorectal cancer (HNPCC) are due to alterations in a mutS-related mismatch repair gene. A search of a large database of expressed sequence tags derived from random complementary DNA clones revealed three additional human mismatch repair genes, all related to the bacterial mutL gene. One of these genes (hMLH1) resides on chromosome 3p21, within 1 centimorgan of markers previously linked to cancer susceptibility in HNPCC kindreds. Mutations of hMLH1 that would disrupt the gene product were identified in such kindreds, demonstrating that this gene is responsible for the disease. These results suggest that defects in any of several mismatch repair genes can cause HNPCC.
Serum Cytokine Profiling as a Diagnostic and Prognostic Tool in Ovarian Cancer: A Potential Role for Interleukin 7 (2007)

IL-7 levels were found to be strongly associated with ovarian cancer and could be used in combination with CA-125 to distinguish between malignant and benign ovarian tumors.
ERYTHROMYCIN DERIVATIVES ABT 229 AND GM 611 ACT ON MOTILIN RECEPTORS IN THE RABBIT DUODENUM (1999)

1. The present study was undertaken to determine whether the macrolide antibiotic erythromycin, its stable motilide derivatives ABT 229 and GM 611 and motilin act at the same receptors on intestinal muscle 2. Each compound contracted the longitudinal muscle of the rabbit duodenum in a concentration-dependent manner that was unaffected by 1 mumol/L tetrodotoxin. The potency order (pEC50 values in brackets) was motilin (8.4), ABT 229 (7.6), GM 611 (7.5) and erythromycin (6.0). 3. The motilin receptor antagonists GM 109 and [phe3, leu13]-motilin, both shifted the concentration-response curves for each agonist to the right, but did not affect concentration-response relationships for the muscarinic agonist carbachol. Schild regression analysis yielded similar pA2 values for GM 109 (in the range 7.2-7.5) for all agonists. This analysis was not done for [phe3, leu13]motilin, which was a non-competitive antagonist and partial agonist. 4. It is concluded that erythromycin, the motilides and motilin act at the same (motilin) receptor on rabbit duodenal muscle and do not have any detectable actions at other receptors in this preparation.
Inhibition of macrophage activation and tumor growth in animals by DHMEQ, an NF-kappaB inhibitor (2005)

4685 [Introduction] Solid tumors are often associated with the presence of a large number of macrophages. These tumor-associated macrophages may enhance the growth of tumors, since activated macrophages secrete various growth factors and cytokines following activation of transcription factors such as NF-kappaB. Therefore, inhibition of macrophage activation may suppress tumor growth in animals. In the course of our search for NF-kappaB inhibitors, we have designed new ones of low molecular weight based on the structure of epoxyquinomicin C, a compound isolated from Amicolatopsis . One of the designed compounds, dehydroxymethylepoxyquinomicin (DHMEQ), inhibited TNF-alpha-induced activation of NF-kappaB. In the present research we looked into the effect of DHMEQ on the macrophage activities such as nitrogen monoxide (NO) production, secretion of cytokines, and phagocytosis. We also examined the antitumor effect of DHMEQ on breast carcinomas in mice. [Experimental procedures] We employed cells of the mouse macrophage-like cell line RAW264.7. Cytokines secreted into culture medium were measured by specific enzyme-linked immunosorbent assays. Phagocytosis was visualized by use of fluorescently labeled Escherichia coli and microspheres. [Summary] DHMEQ inhibited the lipopolysaccharide (LPS)-induced NF-kappaB activation without inhibiting the degradation of IkappaB. It also inhibited the inducible NO synthase expression and NO production. DHMEQ was shown to inhibit LPS-induced secretion of interleukin-1beta (IL-1beta), IL-6, IL-10, IL-12, and TNF-alpha without any toxicity. Moreover, the drug inhibited LPS-induced phagocytosis of fluorescently labeled Escherichia coli or microspheres by RAW264.7 cells. It also inhibited IL-1beta-induced phagocytosis of Escherichia coli, and we obtained the first evidence for the involvement of NF-kappaB in the regulation of phagocytosis by use of this inhibitor. Finally, the intraperitoneal administration of DHMEQ suppressed the growth of breast carcinomas MDA-MB-231 and MCF-7 in SCID mice, again with no signs of toxicity. [Conclusions] DHMEQ inhibited NO production, cytokine secretion, and phagocytosis in mouse macrophage-like cells. It also inhibited the growth of breast carcinomas in mice without toxicity. Previously DHMEQ showed antitumor activity toward prostate carcinoma and other tumor models in animals. It is possible that inhibition of macrophage activation may have contributed to the inhibition of tumor growth in these tumor models.
Combining the FLT3 Inhibitor PKC412 and the Triterpenoid CDDO-Me Synergistically Induces Apoptosis in Acute Myeloid Leukemia with the Internal Tandem Duplication Mutation (2010)

Mutations of the FLT3 receptor tyrosine kinase consisting of internal tandem duplications (ITD) have been detected in blasts from 20% to 30% of patients with acute myeloid leukemia (AML) and are associated with a poor prognosis. FLT3/ITD results in constitutive autophosphorylation of the receptor and factor-independent survival in leukemia cell lines. The C-28 methyl ester of the oleane triterpenoid (CDDO-Me) is a multifunctional molecule that induces apoptosis of human myeloid leukemia cells. Here, we report that CDDO-Me blocks targeting of NFkappaB to the nucleus by inhibiting IkappaB kinase beta-mediated phosphorylation of IkappaBalpha. Moreover, CDDO-Me blocked constitutive activation of the signal transducer and activator of transcription 3. We report the potent and selective antiproliferative effects of CDDO-Me on FLT3/ITD-positive myeloid leukemia cell lines and primary AML cells. The present studies show that CDDO-Me treatment results in caspase-3-mediated induction of apoptosis of FLT3/ITD-expressing cells and its antiproliferative effects are synergistic with PKC412, a FLT3-tyrosine kinase inhibitor currently in clinical trials. Taken together, our studies indicate that CDDO-Me greatly enhanced the efficacy of the FLT3 inhibitor PKC412, suggesting that combining two separate pathway inhibitors might be a viable therapeutic strategy for AML associated with a FLT3/ITD mutation.
Mechanisms of action of human interferons. Induction of 2'5'-oligo(A) polymerase. (1980)

Interferons induce an enzymatic activity that polymerizes ATP into 2'5'-oligoadenylate. This enzyme, designated 2'5'-oligo(A) polymerase, is induced in HeLa cells by type I interferon with a faster kinetics than by type II (immune) interferon. Cells treated with type I interferon in the presence of cycloheximide show elevated levels of polymerase when the inhibitor or protein synthesis is removed and actinomycin D is added to the cultures to prevent further synthesis of mRNA. This suggests that, in the presence of cycloheximide, interferon can activate transcription of mRNA for the 2'5'-oligo(A) polymerase, which is subsequently translated upon removal of this inhibitor. In contrast, cells treated with type II interferon in the same way do not show increased levels of polymerase. This indicates that type II interferon cannot activate transcription of a stable mRNA for the polymerase when protein synthesis is inhibited. This observation and the different kinetics of induction of 2'5'-oligo(A) polymerase suggest major differences in the mechanism of action of the different types of interferon, with type I being a "direct" inducer of the polymerase and type II an "indirect" inducer. The commitment of HeLa cells to the induction of 2'5'-oligo(A) polymerase declines if the cells are exposed to type I interferon in the presence of an inhibitor of RNA synthesis. This suggests that transcription of specific mRNAs is transiently activated by interferon and that repeated interaction of interferon with its receptor may be required for prolonged transcription of the mRNA for 2'5'-oligo(A) polymerase.
Abstract 5540: Preclinical investigation of the novel histone deacetylase (HDAC) inhibitor AR-42 in the treatment of cancer-induced cachexia (2014)

Abstract Background: Cachexia occurs in more than 50% of cancer patients. Cachexia is characterized by severe loss of weight and skeletal muscle that is not reversed by nutritional support, and contributes significantly to morbidity and mortality. The development of effective therapies for cancer cachexia is clearly warranted. AR-42 is a novel class I/IIB HDAC inhibitor that was developed in our laboratories and currently in Phase I/IB trials at The Ohio State University. Here, we report the anti-cachectic activity of AR-42 in two murine models of cancer cachexia. Methods: Experiments were conducted using the colon-26 adenocarcinoma (C-26) and Lewis lung carcinoma (LLC) tumor mice models of cancer cachexia. AR-42 was administered by oral gavage at 50 mg/kg every other day starting at day 6 after tumor cell inoculation. Serum samples (n = 3) and muscle tissues (n = 8) from each group were sent for RNAseq and small RNAseq (OSU), cytokine/chemokine profiling assays [Eve Technologies, Alberta, Canada] and metabolomic analyses [Metabolon, Research Triangle Park, NC]. Results: In the C-26 model, AR-42 significantly attenuated cachexia-induced losses of skeletal muscle mass and body weight, with minimal effects on C-26 tumor growth, and prolonged survival time relative to mice treated with vehicle only or with other HDAC inhibitors (vorinostat and romidepsin). Metabolomic and gene expression analyses revealed that the effects of AR-42 were associated with its ability to maintain metabolic and gene expression profiles in skeletal muscle to levels comparable to those in muscle from tumor-free mice. Analysis of RNAseq data of relevant genes suggests that AR-42 modulates major pathways involved in muscle wasting, mitochondrial function, lipolysis, and cytoskeletal integrity. The main mechanism of action is thought to be through down-regulating FOXO1 (&amp;gt; 5-fold) leading to suppression of MuRF1 and Atrogin-1. Additional mechanistic validation is underway and full results will be available at the meeting. AR-42-induced abrogation of cachexia and rescue of muscle weight was additionally confirmed in the LLC model. Conclusion: Our results suggest AR-42 induces unique protective effects on cancer-induced muscle wasting and lipolysis, and our findings support further evaluation of AR-42 as a potential treatment for cancer cachexia. Citation Format: Yu-Chou Tseng, Samuel Kulp, I-Lu Lai, Wei He, Ralf Bundschuh, David Frankhouser, Pearlly Yan, Denis Guttridge, Guido Marcucci, Ching-Shih Chen, Tanios Bekaii-Saab. Preclinical investigation of the novel histone deacetylase (HDAC) inhibitor AR-42 in the treatment of cancer-induced cachexia. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5540. doi:10.1158/1538-7445.AM2014-5540
The Role of Angiotensin II in Vascular Smooth Muscle Cell Growth (1992)

One of the major consequences of hypertension is an increase in the thickness of the arterial medial smooth muscle cell layer. This has been shown in both large and medium size resistance vessels caused by smooth muscle cell hypertrophy. Both in vivo and in vitro data suggest that the vasoconstrictor peptide angiotensin II (Ang II) may play an important role in the development of the smooth muscle hypertrophy. We have demonstrated that Ang II, when added to quiescence cultures of vascular smooth muscle cells, results in the rapid induction of the early growth response genes c-fos, c-myc, and c-jun. This is due to new transcription as demonstrated by nuclear runoff transcription assay, but is not dependent on new protein synthesis, as it is not blocked by the addition of cycloheximide. The effect is due, however, to an increase in intracellular calcium, suggesting that any vasoconstrictor which results in an increase in intracellular calcium may act in this manner. Following the induction of the early growth response genes there is delayed induction of the platelet derived growth factor A-chain gene. Data from our laboratory and from that of others has shown in preliminary studies that blockade of either the Ang II-induced increases in c-fos or in the platelet-derived growth factor A-chain increases smooth muscle cell protein synthesis. This suggests that Ang II and other vasoconstrictors may play an important role in vascular smooth muscle growth, in hypertension and also in atherosclerosis and following balloon injury of the arterial wall.(ABSTRACT TRUNCATED AT 250 WORDS)
Fabrication of an artificial 3-dimensional vascular network using sacrificial sugar structures (2009)

Using sacrificial sugar structures, we have formed a 3D fluidic vascular network in a polymeric matrix. Melt-spun sugar fibers (cotton candy) were used to form channels with diameters and densities similar to those of capillaries. To interface to macroscopic fluidic systems, larger sacrificial sugar structures were used to form an artificial inlet and outlet. To verify that the channel network supported flow, we used video fluorescence microscopy to image both 2 µm fluorescent polystyrene spheres in an aqueous solution and fluorescently labeled blood. This fabrication process may be applied to a wide range of polymeric materials and is rapid, inexpensive, and highly scalable.