Miracle-dz/UniFAR-FTUs huggingface dataset:
A Chemoproteomics Approach Towards the Discovery of Novel Anti-Cancer Covalent Ligands and Targets

Author(s): Roberts, Allison Marie | Advisor(s): Nomura, Daniel K | Abstract: While many disease-modifying protein targets have been discovered, most of these targets have remained untranslated as they are considered to be difficult to target with small-molecule drugs. In fact, most of the proteome is devoid of pharmacological tools, greatly hindering both basic and translational research efforts. Studies have demonstrated that the development of high-quality chemical tools for proteins of interest catalyze research into the function and therapeutic exploitation of those proteins, thus correlating the development of chemical tools for specific proteins with their associated research activity.1 In fact, only 2% of all predicted human gene products are currently targeted with small-molecule drugs and only 10-15% of all human genes are thought to be ‘druggable,’ with only a 25% overlap between druggable protein targets and known disease-modifying targets.2 Therefore, it is crucial to develop novel approaches and pharmacological tools that garter the entire proteome if we hope to accelerate drug discovery efforts towards curing complex diseases.The use of reactivity-based chemoproteomic probes and isoTOP-ABPP platforms has afforded the discovery of numerous sites within proteins that may represent a variety of functions such catalytic activity, protein- protein interactions, and allosteric regulation.3–6 In this dissertation, I present evidence of how chemical genetics and chemoproteomics approaches can be coupled to not only identify novel anti-cancer protein targets, but also covalent small molecule compounds that can inhibit or impair said targets. I also demonstrate how chemoproteomics as a whole allows for the target identification of almost any small molecule of interest, therefore accelerating drug discovery platforms by identify lead targets and the general promiscuity of a lead ligand. Overall, I provide work that details how we have identified novel sites within protein targets that can be drugged, as well as novel protein targets themselves. This work demonstrates how chemoproteomic platforms, when applied to multiple drug discovery platforms, allows for the rapid identification of novel anti-cancer covalent compounds, and their targets, ultimately providing an approach that can have a large impact on the fight to cure cancer.
Historical and projected trends in near-surface temperature indices for 22 locations in South Africa

Motivated by the risks posed by global warming, historical trends and future projections of near-surface temperature in South Africa have been investigated in a number of previous studies. These studies included the assessment of trends in average temperatures as well as extremes. In this study, historical trends in near-surface minimum and maximum temperatures as well as extreme temperature indices in South Africa were critically investigated by comparing quality-controlled station observations with downscaled model projections. Because climate models are the only means of generating future global warming projections, this critical point comparison between observed and downscaled model simulated time series can provide valuable information regarding the interpretation of model-generated projections. Over the historical 1951–2005 period, both observed data and downscaled model projections were compared at 22 point locations in South Africa. An analysis of model projection trends was conducted over the period 2006–2095. The results from the historical analysis show that model outputs tend to simulate the historical trends well for annual means of daily maximum and minimum temperatures. However, noteworthy discrepancies exist in the assessment of temperature extremes. While both the historical model simulations and observations show a general warming trend in the extreme indices, the observational data show appreciably more spatial and temporal variability. On the other hand, model projections for the period 2006–2095 show that for the medium-to-low concentration Representative Concentration Pathway (RCP) 4.5, the projected decrease in cold nights is not as strong as is the case for the historically observed trends. However, the upward trends in warm nights for both the RCP4.5 and the high concentration RCP8.5 pathways are noticeably stronger than the historically observed trends. For cool days, future projections are comparable to the historically observed trends, but for hot days noticeably higher. Decreases in cold spells and increases in warm spells are expected to continue in future, with relatively strong positive trends on a regional basis. It is shown that projected trends are not expected to be constant into the future, in particular trends generated from the RCP8.5 pathway that show a strong increase in warming towards the end of the projection period. Significance: Comparison between the observed and simulated trends emphasises the necessity to assess the reliability of the output of climate models which have a bearing on the credibility of projections. The limitation of the models to adequately simulate the climate extremes, renders the projections conservative.
Recent Advances in Studies of Molecular Hydrogen against Sepsis

Sepsis is a syndrome comprised of a series of life-threatening organ dysfunctions caused by a maladjusted body response to infection with no effective treatment. Molecular hydrogen is a new type of antioxidant with strong free radical scavenging ability, which has been demonstrated to be effective for treating various diseases, such as infection, trauma, poisoning, organ ischemia-reperfusion, metabolic diseases, and tumors. Molecular hydrogen exerts multiple biological effects involving anti-inflammation, anti-oxidation, anti-apoptosis, anti-shock, and autophagy regulation, which may attenuate the organ and barrier damage caused by sepsis. However, the underlying molecular mechanisms remain elusive, but are likely related to the signaling pathways involved. This review focuses on the research progress and potential mechanisms of molecular hydrogen against sepsis to provide a theoretical basis for clinical treatment.
Aetio-Prevalence Study on Bovine Sub Clinical Mastitis in Lactating Jersey Cross-Bred Cows

Subclinical Mastitis is a common problem hindering the production growth in dairy farming. Dairy cattle are highly susceptible to mastitis because of increased metabolic stress to mammary gland (Radositits, et al., 2006). It has been found that despite implementation of recommended control measures for control of mastitis, the menace of mastitis still continues to haunt the dairy enterprise. Annual losses in the dairy industry due to mastitis have been approximately 2 billion dollars in USA and 526 million dollars in India due to subclinical (Varshney and Naresh, 2004). ) According to Sheare and Harris (2003), subclinical mastitis is important due to the fact that it is 15 to 40 times more prevalent than the clinical form (for every clinical case of mastitis there will be 15-40 sub clinical cases), it usually precedes the clinical form, is of longer duration, difficult to detect, adversely affects milk quality and production and constitutes a reservoir of microorganisms that lead to infection of other animals within the herd (Khan et al., 2006). Unlike coagulase-positive Staphylococcus aureus, coagulase-negative staphylococci are of low virulence, and are rarely associated with clinical disease, although they frequently produce an International Journal of Current Microbiology and Applied Sciences ISSN: 2319-7706 Volume 6 Number 10 (2017) pp. 3354-3357 Journal homepage: http://www.ijcmas. com
The transcriptional regulator SpfB negatively regulates DNA phosphorothioate modification in Pseudomonas fluorescens Pf0-1

Objective DNA phosphorothioate (PT) modification, in which the sulfur replaces a nonbridging oxygen, occurs naturally in diverse bacteria, archaea and human pathogens as a new kind of epigenetic modification. However, the regulatory mechanism of PT modification has not been fully characterized. In this study, the regulatory mechanism of spfB on DNA phosphorothioate (PT) modification in Pseudomonas fluorescens Pf0-1 was demonstrated. Methods Firstly, the spfB genetic interruption and complementary strains were constructed by homologous recombination and then tested the modification frequency in these strains by iodine cleavage. The operons within spf gene cluster were grouped by RT-PCR and the transcriptional level was analyzed in the ΔspfB mutant by quantitative real-time PCR. Finally, the possible regulatory region of SpfB on the spf operon was characterized by EMSA and DNase I footprinting assay. Results The inactivation of spfB led to more dispersed small fragments in genomic DNA of ΔspfB mutant and its complementation obviously restored the phenotype of wild type strain. Genes in spf gene cluster were assigned into one co-transcription unit, and the disruption of spfB directly up-regulated the transcription of the operon. In vitro SpfB directly protected two separate sequences within the spf promoter region from DNase I cleavage, and each protected sequence contained a direct repeat (5'-TGTTTGT-3'). Conclusion SpfB in Pseudomonas fluorescens Pf0-1 was a negative regulator in DNA phosphorothioate modification.
A Soft-Switching Non-Inverting Buck–Boost Converter With Efficiency and Performance Improvement

This letter proposed a new soft-switching non-inverting buck–boost converter (NIBBC) by introducing the magnetic coupling effect to an existing soft-switching dc/dc converter. The new NIBBC obtains two superiorities: one magnetic core is removed to improve the efficiency; the magnetic coupling effect can give an adjustable soft-switching range. Operating principles and converter characteristics of the new NIBBC are presented. An experimental prototype of the new NIBBC is built, and switching waveforms and the efficiency are measured. Experimental results show that the new NIBBC can obtain soft-switching conditions and has efficiency improvement comparing to hard-switching converter and another soft-switching dc/dc converter.
Design science in operations management: conceptual foundations and literature analysis

Goal: The aim of this paper is to show that design science and design science research may contribute as a methodological approach in the context of operations management. Design/methodology/approach: A systematic literature review was conducted to identify articles that have applied design science and design science research in operations management studies. Results: The findings show that the concepts of design science and design science research are relevant and can be applied to conduct more relevant research. Moreover, this paper presents appropriate steps for conducting design science research and provides a summary of the main studies conducted in operations management until the present time. Some drivers are also suggested for advancing research in design science and design science research in operations management. Limitations of the investigation: The main limitation of this paper is the lack of an empirical approach. Practical implication: This paper can contribute to other researchers in the sense of presenting a methodological approach that can help reducing the gap that exists between the research that is developed by academics and what is necessary to support practitioners in organizations, mainly in operations management problems. Originality/value: Publications that discuss research in the area of operations management generally consider the aims and practices determined by traditional sciences (natural and social) as a reference. Thus, it is important to explain the core concepts and foundations, as well as presenting the papers, which have already been developed using design science research in operations management, is necessary for advancing the discussion regarding the use of this method in this area.
Effect of vanadium pentoxide concentration in ZnO/V2O5 nanostructured composite thin films for toluene detection

ZnO/V2O5 nanocomposite thin films were synthesised by the spray pyrolysis technique with optimised deposition parameters by varying the concentration of vanadium pentoxide. The X-ray diffraction results showed that the ZnO/V2O5 nanocomposite thin films have a Wurtzite-type hexagonal ZnO structure. We attained crystal phases at all concentrations. These results indicated that the two crystal phases of pure zinc oxide and vanadium pentoxide exist together within the composite thin film matrix. The morphology was investigated with field emission scanning electron microscopy and transmission electron microscopy (TEM). The microstructures of the deposited thin films were confirmed by Raman spectroscopy. The optical characterizations of the prepared samples were investigated by using a UV-vis spectrophotometer. X-ray photoelectron spectroscopy (XPS) was carried out to confirm the oxidation states of the elements existing on the surface of the composite thin films. The gas-sensing properties of the composite thin films towards toluene gas were studied at the temperature of 27 °C. The sensing mechanism for toluene gas was reported; the response and recovery times were determined from the transient response curve and were found to be 24 s and 28 s, respectively, for the optimised composite film.
Direct Growth of Substrate-Adhered Graphene on Flexible Polymer Substrates for Soft Electronics

This article describes a novel method of growing graphene directly on a flexible substrate at low temperatures using plasma-enhanced chemical vapor deposition with a solid aromatic hydrocarbon source, 1,2,3,4-tetraphenylnaphthalene (TPN), which acts as the feedstock for graphene growth. TPN is embedded with copper ions that are reduced under the growth conditions to copper nanoparticles that catalyze the graphene growth and then evaporate to leave pristine graphene. Strong covalent bonds between the TPN film and the flexible substrate, prepared by depositing an aluminum oxide (Al2O3) layer on a colorless polyimide layer, are generated by exposing the TPN film to ultraviolet/ozone. The TPN/substrate interfacial adhesive bonds impede the sublimation of TPN from the flexible substrate at the growth temperature, and TPN can convert directly to graphene. The synthesized substrate-adhered graphene shows excellent bending stability, with small electrical resistance changes (the resistance R during bending over i.
Facteurs associés à l’exposition élevée aux médicaments psychotropes identifiés lors d’une étude épidémiologique montréalaise

L’article examine les associations entre l’exposition elevee aux medicaments psychotropes, la presence d’un diagnostic de trouble mental et les caracteristiques sociodemographiques chez la population adulte. Un questionnaire a ete passe par entrevue aupres de 2433 personnes de 15 ans et plus dans le cadre de l’enquete ZEPSOM (zone epidemiologique du sud-ouest de Montreal). Les determinants de leur consommation de psychotropes ont fait l’objet d’analyses bivariees et de regression logistique multivariee. Une association bivariee significative a ete observee entre la consommation de somniferes, d’anxiolytiques et d’antidepresseurs et etre plus âge, etre une femme, vivre seul, avoir un niveau d’instruction et de revenu faible, de ne pas avoir occupe un emploi au cours des 12 mois precedant l’enquete et presenter un trouble mental. Une exposition elevee aux differents medicaments psychotropes (trois ou plus) a ete rapportee chez 3,1 % des repondants. Toutes choses etant egales, elle augmente avec l’âge, le fait de vivre seul, ne pas avoir occupe d’emploi au cours de la derniere annee et de presenter un trouble mental. Les resultats suggerent la necessite de considerer l’isolement social et la prevalence des troubles mentaux pour contextualiser l’exposition elevee aux medicaments psychotropes puisque la polypharmacie peut presenter des risques importants si elle ne s’inscrit pas dans la logique d’un protocole d’intervention clinique coherent.
Investigation of the protective and treatment effects of vinpocetine in myocardial infarctional with isoprotenol in rats

As aim of this study, the knowledge of whether vinpocetine (VINPO) is cardioprotective or not following isoprotenol (ISO) induced cardiac ischemia in rats. In myocard infarction, the one of the responsible mechanisms of injury is oxidative damage and inflammmation. The effect of Vinpo which is the potent antioxidant and anti inflammatory agent aimed to reveal as the biochemical, electrophysiological, and histopathologic parameters. In this study, thirty- two Wistar-Albino male rats (in the estimated weight of 250-400gm.) were divided into four groups, each consisting of eight rats. The group 1 named as sham, no any drug used in this group. Group 2 named as iso group, only isoprotenol was adminestered, the group 3 named as vinpo and iso group, here initially vinpocetine then isopretenol were used, and the group 4 named as iso and vinpo, here initially isoprotenol then vinpocetine were used. For the rats in group 2, in first and second day isoprotenol adminestered at a dose of 120mg/kg using an intraperitoneal injection. At third and fourth day no any drug used. And at fifth day the experiment terminated. For the rats in group 3, at the first and second day Vinponcetine adminestered at adose of 20 mg/kg using an intraperitoneal injection, after 30 minute isoprotenol administered at adose of 120mg/kg using an intraperitoneal injection. At third and fourth day no any drug was used. And at fifth day experiment was terminated. Lastly for the rats in group4, first and second day isoprotenol administered at adose of 120mg/kg using an intraperitoneal injection, at third and fourth day vinpocetine adminestered at adose of 20 mg/kg using an intraperitoneal injection, and at fifth day experiment terminated. Prior to termination of experiment the pulse rate and ECG changes were recorded. After completion of experiment protocols blood samples and cardiac tissue samples were recieved. For the knowledge of effects of vinpocetine experimental miyocardial ischemia induced in rats, and the serum myoglobulin, total creatine kinase (CK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), alanin aminotransferase (ALT), measured. In myocardial tissue as an antioxidative system and an oxidative stres markers; malonylaldehate (MDA), Superoxidedismutase (SOD), Catalase (CAT), Glutathionperoxidase (GPx), GSH, Total oxidant status (TOS),Total antioxidant status(TAS),Oxidative stres index (OSI) studied. As a result, Vinpocetin showed positive impact on cardiac functions. With all of these for the best clear results, advanced studies are needed.
Analysis of a Sedan Car Seat Vibration

Ride comfort in vehicle transportation is quite complex, and it depends on various dynamic performance criteria and subjective perception from the car passengers. Vibration discomfort from various factors such as vehicle conditions, the speed of the vehicle, road surface condition, vehicle load, and operating condition can lead to poor ride comfort. Driver seat will be the main part of a car that needed to get a dynamic comfort. Comfort and safety are major factors that need to be considered. To ensure the safety for passenger, the driver must feel comfortable while driving. The objective of this project is to analyze the vibration at the seat of a Proton Wira at different speeds, different loads and different road surfaces. In this project, use six different speeds. Vibration data from two types of road and three different loads are collected using two accelerometers sensor that place on driver seat and seat frame. The rough surface will cause a car to generate more vibration. The results for frequency and time responses show that the vibration increases at the dirt road.
Sistema informatizado de workflow no atendimento ao consumidor: estudo em uma operadora de saúde suplementar

In Brazil, health insurance carriers need to have efficient customer service channels. A workflow system can assist in managing service channels. Hence, there is a need to understand how the implementation of a workflow system helps improve the productivity and central quality of customer service of health insurance carriers. This study aims to describe the stages of implementation of a computerized system for workflow at a health insurance provider. The results showed that this system enabled the monitoring of real-time operations, the reduction of costs, a decrease in customer complaints, the definition of performance indicators, and the ease of generating reports and retrieving documents. The study contributed to broadening the understanding of the application of computerized workflow systems in the context of health insurance carriers and to demonstrate how this system helps to improve productivity and service quality in customer service.
Primary and secondary sources of ambient formaldehyde in the Yangtze River Delta based on Ozone Mapping and Profiler Suite (OMPS) observations

Abstract. Formaldehyde (HCHO) in the ambient air not only causes cancer but is also an ideal indicator of volatile organic compounds (VOCs), which are major precursors of ozone (O3) and secondary organic aerosol (SOA) near the surface. It is meaningful to differentiate between the direct emission and the secondary formation of HCHO for HCHO pollution control and sensitivity studies of O3 production. However, understanding of the sources of HCHO is still poor in China, due to the scarcity of field measurements (both spatially and temporally). In this study, tropospheric HCHO vertical column densities (VCDs) in the Yangtze River Delta (YRD), East China, where HCHO pollution is serious, were retrieved from the Ozone Mapping and Profiler Suite (OMPS) onboard the Suomi National Polar-orbiting Partnership (Suomi-NPP) satellite from 2014 to 2017; these retrievals showed good agreement with the tropospheric HCHO columns measured using ground-based high-resolution Fourier transform infrared spectrometry (FTS) with a correlation coefficient (R) of 0.78. Based on these results, the cancer risk was estimated both nationwide and in the YRD region. It was calculated that at least 7840 people in the YRD region would develop cancer in their lives due to outdoor HCHO exposure, which comprised 23.4 % of total national cancer risk. Furthermore, the contributions of primary and secondary sources were apportioned, in addition to primary and secondary tracers from surface observations. Overall, the HCHO from secondary formation contributed most to ambient HCHO and can be regarded as the indicator of VOC reactivity in Hangzhou and in urban areas of Nanjing and Shanghai from 2015 to 2017, due to the strong correlation between total HCHO and secondary HCHO. At industrial sites in Nanjing, primary emissions more strongly influenced ambient HCHO concentrations in 2015 and showed an obvious decreasing trend. Seasonally, HCHO from secondary formation reached a maximum in summer and a minimum in winter. In the spring, summer, and autumn, secondary formation had a significant effect on the variation of ambient HCHO in urban regions of Nanjing, Hangzhou, and Shanghai, whereas in the winter the contribution from secondary formation became less significant. A more thorough understanding of the variation of the primary and secondary contributions of ambient HCHO is needed to develop a better knowledge regarding the role of HCHO in atmospheric chemistry and to formulate effective control measures to decrease HCHO pollution and the associated cancer risk.