Miracle-dz/UniFAR-FTUs huggingface dataset:
Variability in human drug metabolizing cytochrome P450 CYP2C9, CYP2C19 and CYP3A5 activities caused by genetic variations in cytochrome P450 oxidoreductase

A broad spectrum of human diseases are caused by mutations in the NADPH cytochrome P450 oxidoreductase (POR). Cytochrome P450 proteins perform several reactions, including the metabolism of steroids, drugs, and other xenobiotics. In 2004 the first human patients with defects in POR were reported, and over 250 variations in POR are known. Information about the effects of POR variants on drug metabolizing enzymes is limited and has not received much attention. By analyzing the POR sequences from genomics databases, we identified potentially disease-causing variations and characterized these by in vitro functional studies using recombinant proteins. Proteins were expressed in bacteria and purified for activity assays. Activities of cytochrome P450 enzymes were tested in vitro using liposomes prepared with lipids into which P450 and P450 reductase proteins were embedded. Here we are reporting the effect of POR variants on drug metabolizing enzymes CYP2C9, CYP2C19, and CYP3A5 which are responsible for the metabolism of many drugs. POR Variants A115V, T142A, A281T, P284L, A287P, and Y607C inhibited activities of all P450 proteins tested. Interestingly, the POR variant Q153R showed a reduction of 20-50% activities with CYP2C9 and CYP2C19 but had a 400% increased activity with CYP3A5. The A287P is most common POR mutation found in patients of European origin, and significantly inhibited drug metabolism activities which has important consequences for monitoring and treatment of patients. In vitro, functional assays using recombinant proteins provide a useful model for establishing the metabolic effect of genetic mutations. Our results indicate that detailed knowledge about POR variants is necessary for correct diagnosis and treatment options for persons with POR deficiency and the role of changes in drug metabolism and toxicology due to variations in POR needs to be addressed.
Semantic Mapping Based on Spatial Concepts for Grounding Words Related to Places in Daily Environments

An autonomous robot performing tasks in a human environment needs to recognize semantic information about places. Semantic mapping is a task in which suitable semantic information is assigned to an environmental map so that a robot can communicate with people and appropriately perform tasks requested by its users. We propose a novel statistical semantic mapping method called SpCoMapping, which integrates probabilistic spatial concept acquisition based on multimodal sensor information and a Markov random field applied for learning the arbitrary shape of a place on a map.SpCoMapping can connect multiple words to a place in a semantic mapping process using user utterances without pre-setting the list of place names. We also develop a nonparametric Bayesian extension of SpCoMapping that can automatically estimate an adequate number of categories. In the experiment in the simulation environments, we showed that the proposed method generated better semantic maps than previous semantic mapping methods; our semantic maps have categories and shapes similar to the ground truth provided by the user. In addition, we showed that SpCoMapping could generate appropriate semantic maps in a real-world environment.
Divisive Inhibition Prevails During Simultaneous Optogenetic Activation of All Interneuron Subtypes in Mouse Primary Visual Cortex

The mouse primary visual cortex (V1) has become an important brain area for exploring how neural circuits process information. Optogenetic tools have helped to outline the connectivity of a local V1 circuit comprising excitatory pyramidal neurons and several genetically-defined inhibitory interneuron subtypes that express parvalbumin, somatostatin, or vasoactive intestinal peptide. Optogenetic modulation of individual interneuron subtypes can alter the visual responsiveness of pyramidal neurons with distinct forms of inhibition and disinhibition. However, different interneuron subtypes have potentially opposing actions, and the potency of their effects relative to each other remains unclear. Therefore, in this study we simultaneously optogenetically activated all interneuron subtypes during visual processing to explore whether any single inhibitory effect would predominate. This aggregate interneuron activation consistently inhibited pyramidal neurons in a divisive manner, which was essentially identical to the pattern of inhibition produced by activating parvalbumin-expressing interneurons alone.
Agricultural Youth Injuries: A Review of 2015-2017 Cases from U.S. News Media Reports

ABSTRACT Background: The hazardous nature of the agricultural environment, reflected in the numerous injuries and deaths to children who live, work and play on farms, coupled with the lack of a comprehensive national surveillance system in the United States, highlights the need for making the best use of publicly available youth agricultural injury data. Objective: The purpose of this study was to describe a 3-year collection of youth agricultural injuries using the publicly available injury and fatality data from AgInjuryNews.org and present recommendations for future injury prevention strategies. Methods: Data were obtained from AgInjuryNews.org, a web-based collection of U.S. news reports of agricultural injuries. We analyzed cases from 2015 to 2017 for youth aged 0–17. We classified injuries as occupational and non-occupational related, based on the Farm and Agricultural Injury Classification (FAIC) code. Each case was also coded for source and event using the Occupational Injury and Illness Classification System (OIICS). Results: Of the 348 injury reports reviewed, 51% were fatal, and about one-third of the victims were 6 years old or younger. Most injuries were non-occupational, and the most frequent injury sources were vehicles (includes tractors and all-terrain vehicles) and machinery. Youth operators, extra riders, roadway operations, and unsupervised youth playing near or in a worksite were four key contributing factors associated with vehicle and machinery related injuries. Conclusions: This study reaffirms that youth agricultural-related injuries and fatalities are still a persistent problem in the United States. The hypothesis generating AgInjuryNews system can provide more current data than traditional surveillance datasets as a tool for understanding the sources of youth agricultural injuries, monitoring injury trends, and informing policy efforts and prevention strategies. Future studies should continue to explore and evaluate the comprehensiveness of this system’s data and the impact of its dissemination, as well as similar rural health informatics solutions for integration into sustainable interventions that can be customized and delivered domestically and abroad.
Tethering of Multi-Vesicular Bodies and the Tonoplast to the Plasma Membrane in Plants

Tethering of the plasma membrane (PM) and many organelles to the endoplasmic reticulum (ER) for communication and lipid exchange has been widely reported. However, despite growing interest in multi-vesicular bodies (MVBs) as possible sources of exosomes, tethering of MVBs to the PM has not been reported. Here we show that MVBs and the vacuolar membrane (tonoplast) could be tethered to the PM (PM-MVB/TP tethering) by artificial protein fusions or bimolecular fluorescence complementation (BiFC) complexes that contain a peripheral membrane protein that binds the PM and also a protein that binds MVBs or the tonoplast. PM-binding proteins capable of participating in PM-MVB/TP tethering included StRem1.3, BIK1, PBS1, CPK21, and the PtdIns(4)-binding proteins FAPP1 and Osh2. MVB/TP-binding proteins capable of participating in tethering included ARA6, ARA7, RHA1, RABG3f, and the PtdIns(3)P-binding proteins Vam7p and Hrs-2xFYVE. BiFC complexes or protein fusions capable of producing PM-MVB/TP tethering were visualized as large well-defined patches of fluorescence on the PM that could displace PM proteins such as AtFlotillin1 and also could displace cytoplasmic proteins such as soluble GFP. Furthermore, we identified paralogous ubiquitin E3 ligase proteins, SAUL1 (AtPUB44), and AtPUB43 that could produce PM-MVB/TP tethering. SAUL1 and AtPUB43 could produce tethering in uninfected tissue when paired with MVB-binding proteins or when their E3 ligase domain was deleted. When Nicotiana benthamiana leaf tissue was infected with Phytophthora capsici, full length SAUL1 and AtPUB43 localized in membrane patches consistent with PM-MVB/TP tethering. Our findings define new tools for studying PM-MVB/TP tethering and its possible role in plant defense. Significance Statement Although not previously observed, the tethering of multi-vesicular bodies to the plasma membrane is of interest due to the potential role of this process in producing exosomes in plants. Here we describe tools for observing and manipulating the tethering of multi-vesicular bodies and the tonoplast to the plant plasma membrane, and describe two plant proteins that may naturally regulate this process during infection.
Validation of HIV‐infected cohort identification using automated clinical data in the Department of Veterans Affairs

The US Department of Veterans Affairs (VA) is the largest integrated health care provider for HIV‐infected patients in the USA. VA data for HIV‐specific clinical and quality improvement research are an important resource. We sought to determine the accuracy of using the VA Corporate Data Warehouse (CDW), a fully automated medical records database for all VA users nationally, to identify HIV‐infected patients compared with a gold‐standard VA HIV Clinical Case Registry (CCR).
Prognostic Value of the Neo-Immunoscore in Renal Cell Carcinoma

Objective: This study evaluated the prognostic value of the newly-built Immunoscore (neo-Immunoscore) in patients with renal cell carcinoma (RCC). Methods: Eighty-two patients with RCC were enrolled in this study. Their 3- and 5-year survival rates and overall survival (OS) were evaluated. The clinicopathologic data of the 82 patients were collected and analyzed. CD3, CD4, CD8, CD45RO, Foxp3, tumor necrosis factor receptor type II (TNFR2), programmed death ligand-1 (PD-L1), CD68, programmed death-1 (PD-1), cytokeratin (CK), and indoleamine 2,3-dioxygenase (IDO) were separated into two panels and stained using multiplex fluorescent immunohistochemistry methods. An immunologic prediction model of RCC patients, the neo-Immunoscore (neo-IS), was constructed using a Cox regression model. For the prognostic prediction of RCC, the neo-IS with the immunoscore (IS) proposed by the Society for Immunotherapy of Cancer (SITC) were compared by receiver operator characteristic (ROC) curve analysis. Survivals between the neo-ISlow and neo-IShigh groups were analyzed using the Kaplan–Meier method. Multivariate Cox regression survival analysis was applied to analyze independent indicators. Results: The Cox regression model allowed the establishment of a neo-IS based on three features: CD3CT+, CD4+Foxp3+CD45ROCT+, and CD8+PD-1IM+. Compared to that of the IS proposed by the SITC, the neo-IS obtained a better prediction. The 3- and 5-year survival rates in neo-IShigh RCC patients were significantly higher than those in neo-ISlow RCC patients (94.7 vs. 77.4%, P = 0.035 and 94.7 vs. 64.5%, P = 0.002, respectively). The OS in the neo-ISlow group was significantly shorter than that in the neo-IShigh group (73 vs. 97 months, P = 0.000). In comparisons of the neo-IS with clinical pathological factors, we found that the risk stratification and neo-IS were independent factors for the prognosis of patients with RCC. Moreover, the OS rate of neo-IShigh RCC patients with low- and intermediate- risk was higher than that of neo-ISlow patients. Conclusion: The newly-constructed IS model more precisely predicted the survival of patients with RCC and may supplement the prognostic value of risk stratification.
The ZNF217 Biomarker Predicts Low- and High-Risk Oncotype DX® Recurrence Score in ER-Positive Invasive Breast Cancers

We assessed mRNA and protein expression levels of the ZN217 oncogene in 17 clinical FFPE ER-positive invasive breast cancer specimens with known (low or high) Oncotype DX® Recurrence Scores. This study shows that mRNA or nuclear protein levels of the ZNF217 significantly correlate with Oncotype DX® Recurrence Score.
Deuterated Polyunsaturated Fatty Acids Reduce Oxidative Stress and Extend the Lifespan of C. elegans

Chemically reinforced essential fatty acids (FAs) promise to fight numerous age-related diseases including Alzheimer’s, Friedreich’s ataxia and other neurological conditions. The reinforcement is achieved by substituting the atoms of hydrogen at the bis-allylic methylene of these essential FAs with the isotope deuterium. This substitution leads to a significantly slower oxidation due to the kinetic isotope effect, inhibiting membrane damage. The approach has the advantage of preventing the harmful accumulation of reactive oxygen species (ROS) by inhibiting the propagation of lipid peroxidation while antioxidants potentially neutralize beneficial oxidative species. Here, we developed a model system to mimic the human dietary requirement of omega-3 in Caenorhabditis elegans to study the role of deuterated polyunsaturated fatty acids (D-PUFAs). Deuterated trilinolenin [D-TG(54:9)] was sufficient to prevent the accumulation of lipid peroxides and to reduce the accumulation or ROS. Moreover, D-TG(54:9) significantly extended the lifespan of worms under normal and oxidative stress conditions. These findings demonstrate that D-PUFAs can be used as a food supplement to decelerate the aging process, resulting in extended lifespan.
INTERACTION BETWEEN HIV AWARENESS, KNOWLEDGE, SAFE SEX PRACTICE AND HIV PREVALENCE: EVIDENCE FROM BOTSWANA

Summary This paper makes methodological and empirical contributions to the study of HIV in the context of Botswana, a country with high HIV prevalence. Comparable evidence is presented from India to put the Botswana results in perspective. The results point to the strong role played by affluence and education in increasing HIV knowledge, promoting safe sex and reducing HIV prevalence. The study presents African evidence on the role played by the empowerment of women in promoting safe sex practices such as condom use. The lack of significant association between HIV prevalence and safe sex practice points to the danger of HIV-infected individuals spreading the disease through multiple sex partners and unprotected sex. This danger is underlined by the finding that females with multiple sex partners are at higher risk of being infected with HIV. These results take on special policy significance in the context of Botswana, where the issue of multiple sex partners has not been adequately addressed in the programme to contain the spread of HIV.
High Speed Generator for Gas Microturbine Installations

The article deals with the development issues of high speed generator designed to the gas microturbine installation. A review of existing technical solutions for the development of high-speed generators is presented. The conclusion about the need to use of the induction electric machine with a massive rotor as an electric generator is made on the basis of preliminary calculations. The variants with threeand fivephase stator windings are considered. The calculation results of the magnetic field distribution, of the generated electromagnetic moment and losses in the rotor are given for these variants. The application of a five-phase stator winding which allows reducing the current of semiconductor devices of the power electronic converter controlling the high-speed power generator operation is justified.
An experimental study on the effect of using gasto-liquid ( GTL ) fuel on diesel engine performance and emissions

GTL; Diesel; Engine; Emission Abstract Gas to Liquid (GTL) fuel is considered one of the most propitious clean alternative fuels for the diesel engines. The aim of this study was to experimentally compare the performance and emissions of a diesel engine fueled by GTL fuel, diesel, and a blend of GTL and diesel fuels with a mixing ratio of 1:1 by volume (G50) at various engine load and speed conditions. Although using the GTL and G50 fuels decreased slightly the engine maximum power compared to the diesel fuel, both the engine brake thermal efficiency and engine brake specific fuel consumption were improved. In addition, using the GTL and G50 fuels as alternatives to the diesel resulted in a significant decrease in engine CO, NOx, and SO2 emissions. 2016 Faculty of Engineering, Alexandria University. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Performance Analysis Of Low-power , Short-range Wireless Transceivers 2004

To address the various emerging standards like Bluetooth, Home RF, Wi-fi (IEEE 802.11), ZigBee etc., in the field of wireless communications, different transceivers have been designed to operate at various frequencies such as 450 MHz, 902-920 MHz, 2.4 GHz, all part of designated ISM band. Though, the wireless systems have become more reliable, compact and easy to develop than before, a detailed performance analysis and characterization of the devices should be done. This report details the performance analysis and characterization of a popular binary FSK transceiver TRF6901 from Texas Instruments. The performance analysis of the device is done with respect to the TRF/MSP430 demonstration and development kit.
Fallover of Ribulose 1,5-Bisphosphate Carboxylase/Oxygenase Activity : Decarbamylation of Catalytic Sites Depends on pH.

Loss of ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco) activity during CO(2) fixation, called fallover, occurred with or without loss of activator CO(2) from catalytic sites depending on pH. At pH 7.5, but not at pH 8.5, the fraction of Rubisco sites that were carbamylated decreased during fallover. Inhibitors which formed during fallover were identified following NaBH(4) reduction and separation of the products by high performance anion-exchange chromatography and pulsed amperometric detection. They were xylulose 1,5-bisphosphate (XuBP) and 3-ketoarabinitol 1,5-bisphosphate. During fallover at pH 8.5, 3-ketoarabinitol-P(2) was the only inhibitor binding to Rubisco and this binding was at carbamylated sites, although both inhibitors were made. At pH 7.5, both inhibitors were bound to catalytic sites of Rubisco with XuBP bound tightly to decarbamylated sites, whereas 3-ketoarabinitol-P(2) bound to carbamylated sites. The pH during fallover also influenced the ratio of 3-ketoarabinitol-P(2) to XuBP formed. When fallover occurred at pH 7.5, both the formation of XuBP and its binding affinity to decarbamylated Rubisco sites were increased compared with those at pH 8.5. 3-Ketoribitol-P(2) was not found at either pH.
DESIGN OF ROBUST CONTROLLERS FOR UNCERTAIN PIECEWISE LINEAR SYSTEMS

A systematic method to design robust digital controllers for uncertain piecewise linear systems with structured parametric uncertainties is presented in this paper. This method consists of decomposing the uncertainties of the original system such that it can be rewritten as a set of local linear models with additional disturbed inputs. For this representation of the uncertain system, a continuous-time robust controller is designed as the solution of a linear matrix inequality problem with pole placement restrictions. The robust digital controller is obtained as the digital redesign of the continuous-time robust controller in the state-matching sense. Numerical solution of the tracking problem for the uncertain chaotic Chua’s circuit is used to illustrate the effectiveness of the proposed method.
Targets of Online Hate Speech in Context. A Comparative Digital Social Science Analysis of Comments on Public Facebook Pages from Romania and Hungary

1 Online hate speech, especially on social media platforms, is the subject of both policy and political debate in Europe and globally – from the fragmentation of network publics to echo chambers and bubble phenomena, from networked outrage to networked populism, from trolls and bullies to propaganda and non–linear cyberwarfare. Both researchers and Facebook Community Standards see the identification of the potential targets of hateful or antagonistic speech as key to classifying and distinguishing the latter from arguments that represent political viewpoints protected by freedom of expression rights. This research is an exploratory analysis of mentions of targets of hate speech in comments in the context of 106 public Facebook pages in Romanian and Hungarian from January 2015 to December 2017. A total of 1.8 million comments were collected through API interrogation and analyzed using a text–mining niche–dictionaries approach and co–occurrence analysis to reveal connections to events on the media and political agenda and discursive patterns. Findings indicate that in both countries the most prominent targets mentioned are connected to current events on the political and media agenda, that targets are most frequently mentioned in contexts created by politicians and news media, and that discursive patterns in both countries involve the proliferation of similar stereotypes about certain target groups.
ABLATION OF C/C COMPOSITES: ROUGHNESS AND REACTIVITY

Introduction Several forms of carbon-based materials are used as ablative thermal protection parts in systems designed to withstand extreme temperatures and heat fluxes: Thermal Protection Systems (TPS) for atmospheric reentry of objects from space, nozzles and divergents in rocket engines, internal walls of Tokamak reactors, etc . Under such conditions, the material surface recedes under ablation and acquires a specific roughness. An important issue in designing those systems and parts is the knowledge of the effective heat and mass transfer between the material and its surrounding environment. To this point of view, the material roughness plays a very important role: first, it reveals the material heterogeneity; second, it is able to promote a change in the transfer efficiency by acting on the local turbulence. As a matter of fact, the material heterogeneity, i.e. the spatial organization of the different forms of carbon contained in it, also acts strongly on the effective response of the material to the external solicitations. This works deals principally with ablation from a material point of view [1] and focuses on roughness and effective reactivity.
Relationship between Brand Experience, Brand Personality, Consumer Satisfaction, and Consumer Loyalty of DSSMF Brand

PT XYZ is one of the market leaders of Indonesia’s tobacco market with domination in almost all segments of cigarette. However, PT XYZ is still considered unsuccessful in capturing the market of Full Flavor Machine Made Cigarette (known as SKM FF). This is proven by insignificant performance of DSSMF as PT XYZ’s product under SKM FF segment, especially in Javanese market. This research is aimed to analyze the relationship of brand experience, brand personality, consumer satisfaction, and consumer loyalty of DSSMF. Furthermore, this research attempts to examine the role of brand personality as mediating variable between DSSMF brand experience and consumer loyalty. This research used simple random sampling method. Moreover simple and multiple linear regressions were used as themethods of data-analysis. In gathering the data, the writers used online questionnaire with DSSMF consumers domiciled in Java as the targeted respondents and successfully gathered 94 respondents. These research findings indicate that consumer satisfaction is the only variable significantly impacting DSSMF consumer loyalty. Brand experience and brand personality variables are found to be insignificant to consumer loyalty of DSSMF. Consequently, brand personality is proven not to be the mediating variable between brand experience and consumer loyalty of DSSMF. Keywords: Brand experience, brand personality, consumer satisfaction, consumer loyalty.