gebhart/patrepeval huggingface dataset:
cAMP-Dependent Signaling Pathways as Potential Targets for Inhibition of Plasmodium falciparum Blood Stages (2021)

We review the role of signaling pathways in regulation of the key processes of merozoite egress and red blood cell invasion by <i>Plasmodium falciparum</i> and, in particular, the importance of the second messengers, cAMP and Ca<sup>2+</sup>, and cyclic nucleotide dependent kinases. cAMP-dependent protein kinase (PKA) is comprised of cAMP-binding regulatory, and catalytic subunits. The less well conserved cAMP-binding pockets should make cAMP analogs attractive drug leads, but this approach is compromised by the poor membrane permeability of cyclic nucleotides. We discuss how the conserved nature of ATP-binding pockets makes ATP analogs inherently prone to off-target effects and how ATP analogs and genetic manipulation can be useful research tools to examine this. We suggest that targeting PKA interaction partners as well as substrates, or developing inhibitors based on PKA interaction sites or phosphorylation sites in PKA substrates, may provide viable alternative approaches for the development of anti-malarial drugs. Proximity of PKA to a substrate is necessary for substrate phosphorylation, but the <i>P. falciparum</i> genome encodes few recognizable A-kinase anchor proteins (AKAPs), suggesting the importance of PKA-regulatory subunit myristylation and membrane association in determining substrate preference. We also discuss how Pf14-3-3 assembles a phosphorylation-dependent signaling complex that includes PKA and calcium dependent protein kinase 1 (CDPK1) and how this complex may be critical for merozoite invasion, and a target to block parasite growth. We compare altered phosphorylation levels in intracellular and egressed merozoites to identify potential PKA substrates. Finally, as host PKA may have a critical role in supporting intracellular parasite development, we discuss its role at other stages of the life cycle, as well as in other apicomplexan infections. Throughout our review we propose possible new directions for the therapeutic exploitation of cAMP-PKA-signaling in malaria and other diseases caused by apicomplexan parasites.
A bottom-up complement to the logic-based top-down approach to the story arrangement test (2011)

Psychometric AI is a type of AI distinguished by the pursuit of intelligent systems able to excel on psychometrically validated human-level tests of cognitive abilities. We seek to build a system that solves a specific sub-test within Psychometric AI: the story arrangment test. Items in this test confront the test-taker with a set of jumbed snapshots (whether diagrammatic or otherwise) which must be ordered to tell a coherent story. We propose a dual-process system that combines bottom-up non- or sub-symbolic processing (e.g. neural network-based modelling) with top-down symbolic processing (e.g. deductive reasoning over declarative information represented as formulae in a logical system) for solving these tests of cognitive ability. The top-down process provides the benefits of a traceable proof, but requires a large amount of pre-existing knowledge. The bottom-up technique sacrifices provability and certainty on some problems for speed, but always yields some level of an answer to a given problem. This demonstrates a natural marriage between the two: the bottom-up approach seems especially powerful when used as a form of pre-processing in conjunction with a logic-based approach, because the latter approach would only need to consider a small number of possible orderings of snapshots.
Underestimation of Gleason score at prostate biopsy reflects sampling error in lower volume tumours (2011)

• Under-graded tumours are significantly smaller than tumours concordant for the higher grade, indicating that incomplete tumour sampling plays a significant role in Gleason score assignment error. • Surrogate measures of tumour volume may predict those at greatest risk of Gleason score upgrade.
Factors influencing the thermodynamics of molecular hydrogen oxidation addition to Vaska-type complexes (trans-Ir(PR3)2(CO)X): predictions from ab initio calculations and experimental verification (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTFactors influencing the thermodynamics of molecular hydrogen oxidation addition to Vaska-type complexes (trans-Ir(PR3)2(CO)X): predictions from ab initio calculations and experimental verificationFaraj Abu-Hasanayn, Karsten Krogh-Jespersen, and Alan S. GoldmanCite this: Inorg. Chem. 1993, 32, 5, 495–496Publication Date (Print):March 1, 1993Publication History Published online1 May 2002Published inissue 1 March 1993https://pubs.acs.org/doi/10.1021/ic00057a002https://doi.org/10.1021/ic00057a002research-articleACS PublicationsRequest reuse permissionsArticle Views288Altmetric-Citations27LEARN 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
Safety and efficacy of drug‐eluting stent for ST‐segment elevation myocardial infarction in an unselected consecutive cohort (2008)

DES are safe and effective in the treatment of STEMI in an unselected cohort; 90.9% of patients are free of MACE at 12 months post discharge.
Word-parallel coprocessor architecture for digital nearest Euclidean distance search (2013)

The reported digital, word-parallel and scalable coprocessor architecture for nearest Euclidean distance (ED) search is based on mapping the distance into time domain onto an equivalent clock number. Area-efficient sequential square calculation and a minimization algorithm of the clock number necessary for the search are applied for practical efficiency. Experimental concept verification was done with an 180nm CMOS design implementing 32 reference vectors with 16 components and 8 bit per component. The fabricated test chips achieved 1.19μs average search time, 5.77 μs worst-case search time and low power dissipation of 8.75mW at 47MHz and Vdd=1.8V for code-book-based picture compression. To our best knowledge this is the first report of practical, word-parallel, digital nearest ED-search architecture. In comparison to previous digital-analog ASIC and GPU implementations, factors 1.8 and 4.5·10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">5</sup> smaller power delay products per 1NN search are realized, respectively.
Effects of long-acting GIP, xenin and oxyntomodulin peptide analogues on alpha-cell transdifferentiation in insulin-deficient diabetic Glu (2019)

Enzyme-resistant long-acting forms of the gut-derived peptide hormones, glucose-dependent insulinotropic polypeptide (GIP), xenin and oxyntomodulin (Oxm) have been generated, and exert beneficial effects on diabetes control and pancreatic islet architecture. The current study has employed alpha-cell lineage tracing in Glu ;ROSA26-eYFP transgenic mice to investigate the extent to which these positive pancreatic effects are associated with alpha- to beta-cell transdifferentiation. Twice-daily administration of (D-Ala )GIP, xenin-25[Lys PAL] or (D-Ser )-Oxm[Lys PAL] for 10 days to streptozotocin (STZ)-induced diabetic mice did not affect body weight, food intake or blood glucose levels, but (D-Ser )-Oxm[Lys PAL] reduced (P
Major gene expression changes and epigenetic remodelling in Nile tilapia muscle after just one generation of domestication (2020)

The historically recent domestication of fishes has been essential to meet the protein demands of a growing human population. Selection for traits of interest during domestication is a complex process whose epigenetic basis is poorly understood. Cytosine hydroxymethylation is increasingly recognized as an important DNA modification involved in epigenetic regulation. In the present study, we investigated if hydroxymethylation plays a role in fish domestication and demonstrated for the first time at a genome-wide level and single nucleotide resolution that the muscle hydroxymethylome changes after a single generation of Nile tilapia (<i>Oreochromis niloticus</i>, Linnaeus) domestication. The overall decrease in hydroxymethylcytosine levels was accompanied by the downregulation of 2015 genes in fish reared in captivity compared to their wild progenitors. In contrast, several myogenic and metabolic genes that can affect growth potential were upregulated. There were 126 differentially hydroxymethylated cytosines between groups, which were not due to genetic variation; they were associated with genes involved in immune-, growth- and neuronal-related pathways. Taken together, our data unveil a new role for DNA hydroxymethylation in epigenetic regulation of fish domestication with impact in aquaculture and implications in artificial selection, environmental adaptation and genome evolution.
Attenuated Expression of A20 Markedly Increases the Efficacy of Double-Stranded RNA-Activated Dendritic Cells As an Anti-Cancer Vaccine (2009)

A20 is a zinc finger protein with ubiquitin-modifying activity. A20 has been described as negatively regulating signaling induced by the TNF receptor and TLR family in a number of cell types, including mouse bone marrow-derived dendritic cells (DCs). However, the expression and effect of A20 in activated human monocyte-derived DCs have not been previously evaluated. We report that DCs activated with the TLR3 ligand poly(I:C) up-regulate A20. Down-regulating A20 demonstrated its role in the functional activation of DCs. A20 down-regulated DCs showed higher activation of the transcription factors NF-kappaB and activator protein-1, which resulted in increased and sustained production of IL-6, IL-10, and IL-12p70. We additionally silenced the immunosuppressive cytokine IL-10 and demonstrated that IL-10 inhibits T cell proliferation. We further demonstrated that A20 down-regulated DCs skew naive CD4+ T cells toward IFN-gamma producing Th1 cells, a process which is dependent on IL-12p70 and which is unaffected by IL-10. Furthermore, A20 and/or IL-10 down-regulated DCs had an enhanced capacity to prime Melan-A/MART-1 specific CD8+ T cells. Finally, we demonstrated that potent T cell stimulatory DCs are generated by the simultaneous delivery of poly(I:C12U), A20, or A20/IL-10 small interfering RNA and Ag-encoding mRNA, introducing a one step approach to improve DC-based vaccines. Together these findings demonstrate that A20 negatively regulates NF-kappaB and activator protein-1 in DCs and that down-regulation of A20 results in DCs with enhanced T cell stimulatory capacity.
Combination Effect of Photodynamic and Sonodynamic Therapy on Experimental Skin Squamous Cell Carcinoma in C3H/HeN Mice (2000)

We studied a combination of photodynamic therapy (PDT) and sonodynamic therapy (SDT) for improving tumoricidal effects in a transplantable mouse squamous cell carcinoma (SCC) model. Two sensitizers were utilized: the pheophorbide-a derivative PH-1126, which is a newly developed photosensitizer, and the gallium porphyrin analogue ATX-70, a commonly used sonosensitizer. Mice were injected with either PH-1126 or ATX-70 i.p. at doses of 5 or 10 mg/kg.bw. At 24 (ATX-70) or 36 hr (PH-1126) (time of optimum drug concentration in the tumor) after injection, SCCs underwent laser light irradiation (88 J/cm2 of 575 nm for ATX-70; 44J/cm2 of 650 nm for PH-1126) (PDT), ultrasound irradiation (0.51 W/cm2 at 1.0 MHz for 10 minutes) (SDT), or a combination of the two treatments. The combination of PDT and SDT using either PH-1126 or ATX-70 as a sensitizer resulted in significantly improved inhibition of tumor growth (92-98%) (additive effect) as compared to either single treatment (27-77%). The combination using PH-1126 resulted in 25% of the treated mice being tumor free at 20 days after treatment. Moreover, the median survival period (from irradiation to death) of PDT + SDT-treated mice (> 120 days) was significantly greater than that in single treatment groups (77-95 days). Histological changes revealed that combination therapy could induce tumor necrosis 2-3 times as deep as in either of the single modalities. The combination of PDT and SDT could be very useful for treatment of non-superficial or nodular tumors.
Involvement of Arabidopsis HOS15 in histone deacetylation and cold tolerance (2008)

Histone modification in chromatin is one of the key control points in gene regulation in eukaryotic cells. Protein complexes composed of histone acetyltransferase or deacetylase, WD40 repeat protein, and many other components have been implicated in this process. Here, we report the identification and functional characterization of HOS15, a WD40-repeat protein crucial for repression of genes associated with abiotic stress tolerance through histone deacetylation in Arabidopsis. HOS15 shares high sequence similarity with human transducin-beta like protein (TBL), a component of a repressor protein complex involved in histone deacetylation. Mutation of the HOS15 gene renders mutant plants hypersensitive to freezing temperatures. HOS15 is localized in the nucleus and specifically interacts with histone H4. The level of acetylated histone H4 is higher in the hos15 mutant than in WT plants. Moreover, the stress inducible RD29A promoter is hyperinduced and associated with a substantially higher level of acetylated histone H4 in the hos15 mutant under cold stress conditions. Our results suggest a critical role for gene activation/repression by histone acetylation/deacetylation in plant acclimation and tolerance to cold stress.
Intermetallic Platinum Alloy Nanoparticles and Single Atoms Hybrid Electrocatalysts for Proton Exchange Membrane Fuel Cells (2021)

Abstract Proton exchange membrane fuel cell converts hydrogen and oxygen into electricity with zero emission 1 . The high cost and low durability of Pt-based electrocatalysts for oxygen reduction reaction hinder its wide applications 2,3 . The development of non-precious metal electrocatalysts also reaches the bottleneck because of the low activity and durability 4,5 . Here we rationally design a hybrid electrocatalyst consisting of atomically dispersed Pt and Fe single atoms and intermetallic PtFe alloy nanoparticles. The Pt mass activity of the hybrid catalyst is 3.5 times higher than that of commercial Pt/C in a fuel cell. More importantly, the fuel cell with an ultra-low Pt loading in the cathode (0.015 mg Pt cm -2 ) shows unprecedented durability, with 93.6% activity retention after 100,000 cycles and no noticeable current drop at 0.6 V for at least 206 h. These results highlight the importance of the synergistic effects among active sites in hybrid electrocatalysts and provide an alternative way to design more active and durable low-Pt electrocatalysts for electrochemical devices.
Analysis of time-resolved scattering from macroscale bacterial colonies (2008)

We investigate the relationship of incubation time and forward-scattering signature for bacterial colonies grown on solid nutrient surfaces. The aim of this research is to understand the colony growth characteristics and the corresponding evolution of the scattering patterns for a variety of pathogenic bacteria relevant to food safety. In particular, we characterized time-varying macroscopic and microscopic morphological properties of the growing colonies and modeled their optical properties in terms of two-dimensional (2-D) amplitude and phase modulation distributions. These distributions, in turn, serve as input to scalar diffraction theory, which is, in turn, used to predict forward-scattering signatures. For the present work, three different species of Listeria were considered: Listeria innocua, Listeria ivanovii, and Listeria monocytogenes. The baseline experiments involved the growth of cultures on brain heart infusion (BHI) agar and the capture of scatter images every 6 h over a total incubation period of 42 h. The micro- and macroscopic morphologies of the colonies were studied by phase contrast microscopy. Growth curves, represented by colony diameter as a function of time, were compared with the measured time-evolution of the scattering signatures.
Screen-Printed Dense Yttria-Stabilized-Zirconia Electrolytes for Anode-Supported Solid Oxide Fuel Cells. (2006)

Further cost reductions are necessary for the commercialization of solid oxide fuel cells (SOFCs). The economically sensible methods of screen-printing and tape casting were used to fabricate green films that were subsequently sintered producing 5 cm x 5 cm planar Yittria- stabilized-Zirconia (YSZ)-based SOFCs. An anode-interlayer was also included in the cell design that increased interfacial bonding between the electrolyte and anode. The SOFCs were characterized using scanning electron microscopy and pressure drop measurements. The YSZ electrolytes were gas- tight and dense. These cells showed a maximum power density of 0.14 W/cm2 when tested using a methane-water vapor fuel source at 800{degree sign}C.
Hypospadias and increased risk for neurodevelopmental disorders (2014)

This is the first study to identify an increased risk for neurodevelopmental disorders in patients with hypospadias, as well as an increased risk for ASD in their brothers, suggesting a common familial (genetic and/or environmental) liability.
History of coarrays and SPMD parallelism in Fortran (2020)

The coarray programming model is an expression of the Single-Program-Multiple-Data (SPMD) programming model through the simple device of adding a codimension to the Fortran language. A data object declared with a codimension is a coarray object. Codimensions express the idea that some objects are located in local memory while others are located in remote memory. Coarray syntax obeys most of the same rules for normal array syntax. It is familiar to the Fortran programmer so the use of coarray syntax is natural and intuitive. Although the basic idea is quite simple, inserting it into the language definition turned out to be difficult. In addition, the process was complicated by rapidly changing hardware and heated arguments over whether parallelism should be supported best as an interface to language-independent libraries, as a set of directives superimposed on languages, or as a set of specific extensions to existing languages. In this paper, we review both the early history of coarrays and also their development into a part of Fortran 2008 and eventually into a larger part of Fortran 2018. Coarrays have been used, for example, in weather forecasting and in neural networks and deep learning.
Increased Plasma Glucose and Insulin Responses to High-Carbohydrate Feedings in Normal Subjects (1974)

Plasma glucose and insulin responses to two different diets were measured in 20 adult nondiabetic men. The diets were isocaloric, and differed in amount of calories as fat and carbohydrate. One diet contained 42% fat and 43% carbohydrate, while the other contained 30% fat and 55% carbohydrate. On the fourth clay of each dietary period plasma glucose and insulin levels were measured before the noon feeding, and hourly for the next 3 hr. The low-fat–high-carbohydrate diet led to postprandial increases in plasma glucose and insulin concentrations. The increase in plasma glucose response was relatively modest, but the high-carbohydrate diet resulted in an approximate 40% increase in plasma insulin response. Since ingestion of a low-fat-high-carbohydrate diet led to increases in glucose and insulin levels, the advisability of recommending such diets as general prophylaxis against the development of atherosclerotic heart disease must be reconsidered in this light.
SY40-2 * PHOSPHODIESTERASE TYPE 7: A NOVEL TARGET FOR SMOKING CESSATION -PRECLINICAL EVIDENCE- (2014)

The nucleotide phosphodiesterase (PDE) type 7 family includes two members, PDE7A and PDE7B, which are cyclic-AMP-specific PDEs expressed in brain dopaminergic regions linked to addiction, such as the nucleus accumbens (NAc) and ventral tegmental area (VTA). Here we assessed the role of PDE7 in addiction by evaluating selective PDE7 inhibitors (PDE7i) OMS182399 and OMS182401 in rat models of nicotine self-administration and relapse to drug seeking. Our results showed that PDE7 inhibition by OMS182399 or OMS182401 significantly reduced fixed-ratio 3 (FR-3) and progressive ratio (PR) nicotine self-administration. In preclinical model of relapse we found that OMS182399 and OMS182401 also attenuated cue- and yohimbine-induced reinstatement of nicotine seeking. Food self-administration was not modified either drug. In rats implanted bilaterally with intracranial cannulas aimed at the VTA, we found that site specific injection of OMS182399 or OMS182401 into this brain area significantly reduced nicotine self-administration under both FR-3 and PR schedule of reinforcement suggesting a role of corticomesolimbic dapaminergic circuitries in PDE7i effects. Biochemical analysis in different brain areas has been conducted to shed light on the mechanism of action of PDE7i. These findings suggest that PDE7 could be a novel therapeutic target for nicotine addiction.
A Mobile Head-Mounted Display for Action Sports (2012)

We describe a highly portable head-mounted display designed for use in action sports such as skiing and snowboarding. The low field-of-view, monocular display is designed to keep distraction to a minimum and not impede the mobility of the wearer. Implications of the location of the monocular display are discussed. The driving electronics and power source are small enough so that no tethering is needed, all electronics are attached to the display.
Echinatin induces reactive oxygen species‐mediated apoptosis via JNK/p38 MAPK signaling pathway in colorectal cancer cells (2022)

Colorectal cancer (CRC) is a very common and deadly cancer worldwide, and oxaliplatin is used as first-line chemotherapy. However, resistance usually develops, limiting treatment. Echinatin (Ech) is the main component of licorice and exhibits various therapeutic effects on inflammation-mediated diseases and cancer, ischemia/reperfusion, and liver injuries. The present study elucidated the underlying molecular mechanism of Ech-induced apoptosis in both oxaliplatin-sensitive (HT116 and HT29) and -resistant (HCT116-OxR and HT29-OxR) CRC cells. To evaluate the antiproliferative activities of Ech, we performed MTT and soft agar assays. Ech reduced viability, colony size, and numbers of CRC cells. The underlying molecular mechanisms were explored by various flow cytometry analyses. Ech-induced annexin-V stained cells, reactive oxygen species (ROS) generation, cell cycle arrest, JNK/p38 MAPK activation, endoplasmic reticulum (ER) stress, mitochondrial membrane potential depolarization, and multi-caspase activity. In addition apoptosis-, cell cycle-, and ER stress-related protein levels were confirmed by western blotting. Moreover, we verified ROS-mediated cell death by treatment with inhibitors such as N-acetyl-L-cysteine, SP600125, and SB203580. Taken together, Ech exhibits anticancer activity in oxaliplatin-sensitive and -resistant CRCs by inducing ROS-mediated apoptosis through the JNK/p38 MAPK signaling pathway. This is the first study to show that Ech has the potential to treat drug-resistant CRC, providing new directions for therapeutic strategies targeting drug-resistant CRC.