gebhart/patrepeval huggingface dataset:
Dengue/Dengue Hemorrhagic Fever: The Emergence of a Global Health Problem (1995)

Dengue and dengue hemorrhagic fever (DHF) are caused by one of four closely related but antigenically distinct virus serotypes (DEN-1 DEN-2 DEN- 3 and DEN-4) of the genus Flavivirus. Infection with one of these serotypes does not provide cross-protective immunity so persons living in a dengueendemic area can have four dengue infections during their lifetimes. Dengue is primarily an urban disease of the tropics and the viruses that cause it are maintained in a cycle that involves humans and Aedes aegypti a domestic day-biting mosquito that prefers to feed on humans. Infection with a dengue virus serotype can produce a spectrum of clinical illness ranging from a nonspecific viral syndrome to severe and fatal hemorrhagic disease. Important risk factors for DHF include the strain and serotype of the virus involved as well as the age immune status and genetic predisposition of the patient. The first reported epidemics of dengue fever occurred in 1779-1780 in Asia Africa and North America; the near simultaneous occurrence of outbreaks on three continents indicates that these viruses and their mosquito vector have had a worldwide distribution in the tropics for more than 200 years. During most of this time dengue fever was considered a benign nonfatal disease of visitors to the tropics. Generally there were long intervals (10-40 years) between major epidemics mainly because the viruses and their mosquito vector could only be transported between population centers by sailing vessels. (excerpt)
A study of mobile search queries in Japan (2007)

In this paper we study the characteristics of search queries on mobile phones in Japan, comparing them with previous results of generic search queries in Japan and mobile search queries in the USA. We confirm some results while find some interesting differences on the query distribution, use of the different script languages and query topics. 1.
PII-8Evaluation of gender-related differences in the prolongation of action potential duration during concomitant block of iKR and iKS (2006)

BACKGROUND/AIMS We previously reported that combined block of IKr and IKs induces potentiation of drug effects on cardiac repolarization. Furthermore, mechanisms responsible for gender-related differences in the risk of drug-induced proarrhythmia remain largely undefined. Therefore, the aim of the present study is to evaluate gender-related differences during the concomitant block of IKr and IKs. METHODS Hearts (n=32) from Hartley male and female guinea pigs were isolated and buffer-perfused in the Langendorff mode. After a 5 min perfusion with buffer, hearts were perfused sequentially with either[dofetilide 20 nM followed by a combination of dofetilide 20 nM and indapamide 66 μM] or[domperidone 100 nM followed by a combined perfusion of domperidone 100 nM and indapamide 66 μM]. RESULTS Dofetilide prolonged MAPD90 by 16.5±1.6 msec in male compared to 16.1±2.4 msec in female, while the dofetilide/indapamide combination induced a 36.3±1.5 msec MAPD90 prolongation in male and 35.9±3.7 msec in female (p>0.05). Similarly, domperidone prolonged MAPD90 by 16.5±1.6 msec in male and by 16.1±2.4 msec in female, while the domperidone/indapamide combination induced a 32.6±2.5 msec prolongation in male and 32.5±1.9 msec in female (p>0.05). CONCLUSION Prolongation of cardiac repolarization by combined IKr+IKs block did not show gender-related differences, suggesting that other factors remain to be assessed for a complete understanding of gender impact in drug-induced long QT syndrome. Clinical Pharmacology & Therapeutics (2005) 79, P37–P37; doi: 10.1016/j.clpt.2005.12.133
Hydropathic analysis of the free energy differences in anthracycline antibiotic binding to DNA (2003)

Molecular models of six anthracycline antibiotics and their complexes with 32 distinct DNA octamer sequences were created and analyzed using HINT (Hydropathic INTeractions) to describe binding. The averaged binding scores were then used to calculate the free energies of binding for comparison with experimentally determined values. In parsing our results based on specific functional groups of doxorubicin, our calculations predict a free energy contribution of -3.6 +/- 1.1 kcal x mol(-1) (experimental -2.5 +/- 0.5 kcal x mol(-1)) from the groove binding daunosamine sugar. The net energetic contribution of removing the hydroxyl at position C9 is -0.7 +/- 0.7 kcal x mol(-1) (-1.1 +/- 0.5 kcal x mol(-1)). The energetic contribution of the 3' amino group in the daunosamine sugar (when replaced with a hydroxyl group) is -3.7 +/- 1.1 kcal x mol(-1) (-0.7 +/- 0.5 kcal x mol(-1)). We propose that this large discrepancy may be due to uncertainty in the exact protonation state of the amine. The energetic contribution of the hydroxyl group at C14 is +0.4 +/- 0.6 kcal x mol(-1) (-0.9 +/- 0.5 kcal x mol(-1)), largely due to unfavorable hydrophobic interactions between the hydroxyl oxygen and the methylene groups of the phosphate backbone of the DNA. Also, there appears to be considerable conformational uncertainty in this region. This computational procedure calibrates our methodology for future analyses where experimental data are unavailable.
Structure—Activity Relationship Studies of Ethyl 2‐[(3‐Methyl‐2,5‐dioxo(3‐pyrrolinyl))amino] ‐4‐(trifluoromethyl)pyrimidine‐5‐carboxylate: An Inhibitor of AP‐1 and NF‐ϰB Mediated Gene Expression. (2003)

Abstract For Abstract see ChemInform Abstract in Full Text.
RNAi inhibition of angiopoietin-like protein 3 (ANGPTL3) with ARO-ANG3 mimics the lipid and lipoprotein profile of familial combined hypolipidemia (2020)

Abstract Background Elevated LDL-C and triglyceride rich lipoproteins (TRLs) are independent risk factors for cardiovascular disease (CVD). Genetic deficiency of angiopoietin-like protein 3 (ANGPTL3) is associated with reduced circulating levels of LDL-C, triglycerides (TGs), VLDL-C, HDL-C and reduced CVD risk, with no described adverse phenotype. ARO-ANG3 is a RNA interference drug designed to silence expression of ANGPTL3. Single doses of ARO-ANG3 have been shown to reduce ANGPTL3, TGs, VLDL-C and LDL-C in healthy volunteers (HVs, AHA 2019). We report the effects of multiple doses of ARO-ANG3 in HVs with a focus on the duration of action. Methods ARO-ANG3 was administered subcutaneously to HVs on days 1 and 29 at doses of 100, 200 or 300 mg (n=4 per group). Measured parameters included ANGPTL3, LDL-C, TGs, VLDL-C and HDL-C. Follow up is ongoing. Results All HVs have received both doses and follow-up is currently through week 16 (12 weeks after second dose). Mean nadir for ANGPTL3 levels occurred 2 weeks after the second dose (−83–93%) with minimal change for 200 and 300 mg but 16% recovery for 100 mg at week 16. Mean TGs and VLDL-C reached nadir earlier (3 wks, −61–65%) without apparent dose response and minimal change for any dose at wk 16. LDL-C nadir occurred 4–6 wks after the second dose (−45–54%), again with minimal evidence for dose response or change through wk 16. HDL-C was reduced 14–37% at wk 16. ARO-ANG3 was well tolerated without serious or severe adverse events or dropouts related to drug. The most common adverse events have been headache and upper respiratory infections. Conclusions Genetic deficiency of ANGPTL3 is a cause of familial combined hypolipemia and is associated with a decreased risk of CVD. Using RNAi to selectively suppress ANGPTL3 production reproduces these genetic effects with a duration of at least 12 weeks following a second dose and with good tolerability over 16 wks. ANGPTL3 inhibition results in lowering of LDL-C and TRLs which may confer protection against CVD in patients with atherogenic mixed dyslipidemia. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Arrowhead Pharmaceuticals
Gender Dimorphism and Lack of Day/Night Variation or Effects of Energy Deprivation on Undercarboxylated Osteocalcin Levels in Humans (2013)

The hypothesis that ucOC plays a role in energy homeostasis or of leptin in regulating ucOC in humans is not supported.
Adobe PDF - MCT-07-0312--Suppl_Fig_S2.pdf from Exemestane's 17-hydroxylated metabolite exerts biological effects as an androgen (2023)

Adobe PDF - MCT-07-0312--Suppl_Fig_S2.pdf from Exemestane's 17-hydroxylated metabolite exerts biological effects as an androgen
Effect of Copper Line Geometry and Process Parameters on Interconnect Microstructure and Degradation Processes (2001)

Abstract The atomic transport processes which could cause degradation mechanisms in Cu interconnects are described. The influence of interconnect line width, barrier type and anneal process on the microstructure and reliability of the inlaid Cu lines are discussed. Grain size and texture measurements have been performed at blanket films and at arrays of Cu lines using advanced analytical techniques. The median grain size decreases with decreasing line width, and it can be influenced by heat treatments. The crystallographic texture is predominantly {111} out-of-plane with sidewall-oriented grains in narrow Cu lines. The grains have an in-plane preferred orientation with the 〈110〉 direction parallel to the sidewall normal. The Cu texture is influenced by barrier structure and thickness.
Genome-wide contribution of common short-tandem repeats to Parkinson’s disease genetic risk (2022)

Parkinson's disease is a complex neurodegenerative disorder with a strong genetic component, for which most known disease-associated variants are single nucleotide polymorphisms (SNPs) and small insertions and deletions (indels). DNA repetitive elements account for >50% of the human genome; however, little is known of their contribution to Parkinson's disease aetiology. While select short tandem repeats (STRs) within candidate genes have been studied in Parkinson's disease, their genome-wide contribution remains unknown. Here we present the first genome-wide association study of STRs in Parkinson's disease. Through a meta-analysis of 16 imputed genome-wide association study cohorts from the International Parkinson's Disease Genomic Consortium (IPDGC), totalling 39 087 individuals (16 642 cases and 22 445 controls of European ancestry), we identified 34 genome-wide significant STR loci (P < 5.34 × 10-6), with the strongest signal located in KANSL1 [chr17:44 205 351:[T]11, P = 3 × 10-39, odds ratio = 1.31 (95% confidence interval = 1.26-1.36)]. Conditional-joint analyses suggested that four significant STRs mapping nearby NDUFAF2, TRIML2, MIRNA-129-1 and NCOR1 were independent from known risk SNPs. Including STRs in heritability estimates increased the variance explained by SNPs alone. Gene expression analysis of STRs (eSTRs) in RNA sequencing data from 13 brain regions identified significant associations of STRs influencing the expression of multiple genes, including known Parkinson's disease genes. Further functional annotation of candidate STRs revealed that significant eSTRs within NUDFAF2 and ZSWIM7 overlap with regulatory features and are associated with change in the expression levels of nearby genes. Here, we show that STRs at known and novel candidate loci contribute to Parkinson's disease risk and have functional effects in disease-relevant tissues and pathways, supporting previously reported disease-associated genes and giving further evidence for their functional prioritization. These data represent a valuable resource for researchers currently dissecting Parkinson's disease risk loci.
PWE-157 Two Dimensional Mapping of Mutant Clones in Human Colonic Crypts Reveal Stem Cell Dynamics and Migration Patterns (2013)

Introduction Deficiency in the enzyme cytochrome C oxidase (CCO) has proven to be a versatile marker of clonal population in human tissues. CCO is encoded entirely by the mitochondrial DNA (mtDNA) and deficiency in CCO expression is usually attributable to mutation in the mtDNA. CCO-deficient cells are easily detectable by two-colour enzyme histochemistry. This staining provides means to identify clonal patches of CCO-deficient cells. Subsequent sequencing of mtDNA from individual cells within the patch and revealing the same somatic mutation in each cell confirms the clonality of a patch. In the human intestine, crypts are composed of a population of a contiguous CCO-deficient mtDNA-mutated cells, and also non-mutant CCO-proficient cells are frequently observed: from the small clones occupying only a few cell positions on the crypt circumference (partially-mutated crypts), to crypts composed only CCO-deficient cells (wholly-mutated crypts). Patches of adjacent and clonal CCO-deficient crypts are also observed. Larger patches are more common in older patients indicating that CCO-deficient crypts continue to divide in the ageing colon. Methods To study stem cells dynamics within intestinal crypts, we aim to characterise the shape and the size of clones in partially CCO-deficient crypts, by combining the two-colour enzyme histochemical staining with image analysis and computer reconstruction. Multiple serial sections in the transverse plain were taken through frozen samples. Digital images were then taken of each serial section and used to create a ‘crypt map’ using in-house analytical software. A crypt map is a representation of the whole 3D tubular crypt unfurled and laid flat with colour enhancement post-processing. Results Our results in normal and diseased human colon show that clone size can be approximated by the percentage of the crypt circumference measured from crypt transverse sections and occupied by a CCO-deficient clone. Conclusion We envisage that analysis of such clonal distributions in the context of a branching process model could be used to determine the patterns of stem cell division within the human colon. Disclosure of Interest None Declared.
Supplementary Data from Loss of Epigenetic Regulation Disrupts Lineage Integrity, Induces Aberrant Alveogenesis, and Promotes Breast Cancer (2023)

Supplementary Data from Loss of Epigenetic Regulation Disrupts Lineage Integrity, Induces Aberrant Alveogenesis, and Promotes Breast Cancer
Simultaneous analysis of endogenous DNA adducts in chronic lymphocytic leukemia patients (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

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Oxidized bases represent DNA lesions induced by hydroxyl radicals, hydrogen peroxide, superoxide, peroxynitrite, singlet oxygen or one-electron oxidation reactions. A number of modified nucleosides, including diastereomeric forms, have been characterized in detailed model studies. Despite the abundance of DNA adducts resulting from oxidative damage, the analysis of these adducts is not always simple, because of the potential artifactual oxidation of the overwhelmingly larger concentrations of normal bases during sample preparation and analysis. The compound most commonly investigated in studies of oxidative stress is 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-HOdG), and, depending on the analytical method used, the literature reports quite widely varying amounts of this oxidative modification. By optimization of our previously published method we are now able not only to determine the genomic methylation level but also to quantitate various biomarkers of oxidative stress in a single analytical run. The method involves hydrolyzing DNA to modified and unmodified 2′-deoxynucleoside-3′-monophosphates, labeling the nucleotides with BODIPY® FL EDA as fluorescence marker, micellar electrokinetic chromatography and laser-induced-fluorescence detection (CE-LIF). It has been validated to a reproducible, high-throughput method which in epidemiological studies allows the quantification of adducts with low standard deviations. In the ongoing investigation presented here, we have so far analyzed N6-etheno-2’-deoxyadenosine-3′-monophosphate (etheno-dAMP), 2′-deoxyuridine-3′-monophosphate (dUMP), 2′-deoxyinosine-3′-monophosphate (dIMP), 5,6-dihydro-5,6-dihydroxy-2′-deoxy-thymidine-3′-monophosphate (dTgMP) and 5-methyl-2′-deoxycytidine-3′-monophosphate (5mdCMP) in DNA samples from CLL patients. The quantification of the first four was enabled by the addition of standards synthesized by members of our group. The strategy developed for synthesizing 2′-desoxynucleoside-3′-monophosphates will make it possible for us to prepare other DNA adducts, which could also be used as standards in 32P postlabeling.
CRISPR/Cas9-mediated targeted mutagenesis in grape (2017)

RNA-guided genome editing using the CRISPR/Cas9 CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated protein 9) system has been applied successfully in several plant species. However, to date, there are few reports on the use of any of the current genome editing approaches in grape-an important fruit crop with a large market not only for table grapes but also for wine. Here, we report successful targeted mutagenesis in grape (Vitis vinifera L., cv. Neo Muscat) using the CRISPR/Cas9 system. When a Cas9 expression construct was transformed to embryonic calli along with a synthetic sgRNA expression construct targeting the Vitis vinifera phytoene desaturase (VvPDS) gene, regenerated plants with albino leaves were obtained. DNA sequencing confirmed that the VvPDS gene was mutated at the target site in regenerated grape plants. Interestingly, the ratio of mutated cells was higher in lower, older, leaves compared to that in newly appearing upper leaves. This result might suggest either that the proportion of targeted mutagenized cells is higher in older leaves due to the repeated induction of DNA double strand breaks (DSBs), or that the efficiency of precise DSBs repair in cells of old grape leaves is decreased.
COMPOSITUM 1 contributes to the architectural simplification of barley inflorescence via meristem identity signals (2020)

Grasses have varying inflorescence shapes; however, little is known about the genetic mechanisms specifying such shapes among tribes. Here, we identify the grass-specific TCP transcription factor COMPOSITUM 1 (COM1) expressing in inflorescence meristematic boundaries of different grasses. COM1 specifies branch-inhibition in barley (Triticeae) versus branch-formation in non-Triticeae grasses. Analyses of cell size, cell walls and transcripts reveal barley COM1 regulates cell growth, thereby affecting cell wall properties and signaling specifically in meristematic boundaries to establish identity of adjacent meristems. COM1 acts upstream of the boundary gene Liguleless1 and confers meristem identity partially independent of the COM2 pathway. Furthermore, COM1 is subject to purifying natural selection, thereby contributing to specification of the spike inflorescence shape. This meristem identity pathway has conceptual implications for both inflorescence evolution and molecular breeding in Triticeae.
Microfabrication Technology of Biodegradable Polymers for Interconnecting Microstructures (2006)

A microtechnology for synthetic biodegradable polymers has been developed to fabricate three-dimensionally (3-D) shaped and microstructured multilayer constructs for biomedical applications. A unique micromolding method is proposed to create deep and interconnecting microstructures which facilitate cellular scale interconnection across the layers for cell-to-cell communication and the supply of nutrients and oxygen. A geometrical condition and molding setup for interconnecting microstructuring are described and demonstrated experimentally. Furthermore, various types of synthetic biodegradable polymers are explored and compared with regard to the behavior during the proposed process. Considering the thermal instability of synthetic biodegradable polymers, it is also confirmed that the proposed process does not affect the property of the polymers. Finally, microfabricated 3-D multilayer constructs is presented to demonstrate the feasibility of the technology as a unique scaffolding method
N-arachidonoyl dopamine is a possible factor of the rate of tentacle formation in freshwater hydra regeneration (2008)

The effect of N-arachidonoyl dopamine, haloperidol, and their mixture on the rate of tentacle formation was studied during regeneration of the gastral and basal fragments of freshwater hydra. Some concentrations of haloperidol inhibited the tentacle formation, which was more pronounced in the basal fragment. N-arachidonoyl dopamine accelerated the tentacle formation in both fragments, particularly, in the basal one (an inversion of the natural difference in the rate of tentacle formation between the gastral and basal fragments). After the exposure to the mixture of these drugs, the effects of each of them were observed. Mass spectrometry assay has demonstrated endogenous N-arachidonoyl dopamine in the intact hydra homogenate. The possible involvement of this acyl-neurotransmitter in the regulation of the rate of tentacle formation in regenerating hydra is discussed.
Nucleation rate and glide velocity of misfit dislocations in Si1−<i>x</i>Ge<i>x</i>/(100) Si heterostructures (1990)

Expressions are presented for the rate of strain relaxation, misfit dislocation nucleation, and propagation in strained Si1−xGex/(100)Si heterostructures. Independent measurements of misfit dislocation nucleation and 60° type a/2 〈110〉 dislocation glide velocity in the temperature range 450–1000 °C have led to a model which characterizes the kinetics of strain relaxation for 0&amp;lt;x&amp;lt;0.25. The generalized force or effective stress τeff, which drives strain relaxation, is defined for an arbitrary strain profile and strained-layer geometry. New experimental data for misfit dislocation glide velocity (V in cm s−1) have been fitted to a semi-empirical relation found to be appropriate for all Si1−xGex/(100)Si heterostructures, V=(4±2)⋅1013(τeff /μ)2 exp−[(2.25±0.05)/kT]. An analogous expression for the nucleation rate of new misfit dislocation segments was determined from experimental data, dN(t)/dt=BN0(τeff /μ)2.5 exp−[2.5±0.2)/kT], where N0 is the density of heterogeneous nuclei and B is a material constant ∼1018 s−1 for Si1−xGex. These expressions are combined in a kinetic model which is then used to predict the rate of strain relaxation in Si1−xGex/Si heterostructures.
Supplementary Table S1: NGS-Cancer Panel from Genomic and Immunological Tumor Profiling Identifies Targetable Pathways and Extensive CD8&lt;sup&gt;+&lt;/sup&gt;/PDL1&lt;sup&gt;+&lt;/sup&gt; Immune Infiltration in Inflammatory Breast Cancer Tumors (2023)

&lt;p&gt;NGS-Cancer Panel Gene list&lt;/p&gt;
Identification of a HAD superfamily phosphatase, HdpA, involved in 1,3‐dihydroxyacetone production during sugar catabolism in <i>Corynebacterium glutamicum</i> (2012)

Corynebacterium glutamicum produces 1,3-dihydroxyacetone (DHA) as metabolite of sugar catabolism but the responsible enzyme is yet to be identified. Using a transposon mutant library, the gene hdpA (cgR_2128) was shown to encode a haloacid dehalogenase superfamily member that catalyzes dephosphorylation of dihydroxyacetone phosphate to produce DHA. Inactivation of hdpA led to a drastic decrease in DHA production from each of glucose, fructose, and sucrose, indicating that HdpA is the main enzyme responsible for DHA production from sugars in C. glutamicum. Confirmation of DHA production via dihydroxyacetone phosphatase finally confirms a long-speculated route through which bacteria produce DHA.