Miracle-dz/UniFAR-FTUs huggingface dataset:
Directed evolution, natural products for cancer chemotherapy, and micro‐biosensing robots

a Planta, 14071, Cordoba, Spain. apart from the time saving facet of this methodology, this protocol can also avoid bias as a result of multiple steps and the limitations of cloning mutants by traditional methods (restriction enzymes and ligation); thus broaden- ing the range of potential candidates. Bacteria from the genus Streptomyces produce more than 70% of commercially available antibiotics, plus many other metabolites of therapeutic interest such as anti- tumour agents or immunosuppressive drugs. The produc- tion of these compounds is tightly controlled by means of g-butyrolactones; microbial hormones that are also involved in the regulation of other processes such as morphological differentiation or pathogenesis. The article presented by D'Alia and co-workers focuses on the regu- lation of these hormones by the ScbA regulator, a homo- logue of the A-factor biosynthesis afsA gene from Streptomyces coelicolor (D'Alia et al., 2011). For this purpose, they studied the differences in transcript levels between the wild-type strain and a DscbA mutant using global microarray analysis, and the results were con- firmed by more accurate qRT-PCR. The authors show that ScbA not only controls antibiotic production but also inter- feres with intracellular iron levels modulating siderophore desferrioxamine E biosynthesis. Interestingly, this study also shows that in the scbA mutant genes coding for enzymes related to primary metabolism are upregulated just before antibiotic production, placing butanolides upfront of general metabolic regulation in S. coelicolor. When S. coelicolor A3(2) grows under nutrient limited conditions, it triggers a gamut of nutrient-stress responses, mediated by a number of global regulators including PhoP, GlnR, AfsR and others. The action of these regulators is also integrated at the molecular level to control secondary metabolite biosynthesis and differen- tiation. As a result of the potential uses of these microbes in biotechnology, nutritional control has received relevant attention in the field and, in this issue, Martin and col- leagues (2011) describe how phosphate control of primary and secondary metabolism in Streptomyces species is mediated by the two-component regulatory system PhoR- PhoP. PhoP controls secondary metabolism by binding to the PHO box in the afsS promoter. They illustrate that this PHO Box overlaps with the AfsR binding site (D'Alia et al.,
Crafting Papers on Machine Learning

This essay gives advice to authors of papers on machine learning, although much of it car-ries over to other computational disciplines. The issues covered include the material that should appear in a well-balanced paper, factors that arise in di(cid:11)erent approaches to evaluation, and ways to improve a submission's ability to communicate ideas to its readers.
Statistical issues in the analysis of DNA Copy Number Variations

Approaches to assess copy number variation have advanced rapidly and are being incorporated into genetic studies. While the technology exists for CNV genotyping, a further understanding and discussion of how to use the CNV data for association analyses is warranted. We present the options available for processing and analysing CNV data. We break these steps down into choice of genotyping platform, normalisation of the array data, calling algorithm, and statistical analysis.
Alcohol consumption and health among elders.

PURPOSE This article estimates the effects of alcohol consumption on self-reported overall health status, injuries, heart problems, emergency room use, and hospitalizations among persons older than the age of 65. DESIGN AND METHODS We analyzed data from the first wave of the National Epidemiologic Survey on Alcohol and Related Conditions, a nationally representative study. We used multivariate regression and instrumental variables methods to study the associations between alcohol consumption (current drinking, binge drinking, and average number of drinks consumed) and several indicators of health status and health care utilization. RESULTS Alcohol consumption by women was associated with better self-perceived health status, improved cardiovascular health, and lower rates of hospitalizations. We detected no significant negative or positive associations for older men. IMPLICATIONS These findings suggest that light to moderate alcohol use by older women may have beneficial health effects. Experimental trials, however, are needed to more rigorously assess the potential benefits of alcohol use by elders due to the inherent biases of observational studies.
Photoreceptor cell fate specification in vertebrates

Photoreceptors – the light-sensitive cells in the vertebrate retina – have been extremely well-characterized with regards to their biochemistry, cell biology and physiology. They therefore provide an excellent model for exploring the factors and mechanisms that drive neural progenitors into a differentiated cell fate in the nervous system. As a result, great progress in understanding the transcriptional network that controls photoreceptor specification and differentiation has been made over the last 20 years. This progress has also enabled the production of photoreceptors from pluripotent stem cells, thereby aiding the development of regenerative medical approaches to eye disease. In this Review, we outline the signaling and transcription factors that drive vertebrate photoreceptor development and discuss how these function together in gene regulatory networks to control photoreceptor cell fate specification. Summary: This Review discusses recent progress in the understanding of the mechanisms of photoreceptor specification from neural progenitors and their implications for the treatment of retinal diseases.
Research on technological innovation network of multinational corporations based on complex network

Along with the development of globalization, the process of multinational companies' technological innovation becomes increasingly complex. This paper systematically expounds related theories of multinational corporations' technological innovation and complex networks, and points out that multinational companies' technological innovation is the formation process of a complex network, and describes BA scale-free network model in detail, which is introduced into technological innovation networks of multinational corporations. Finally, the corresponding results are obtained by means of in-depth analysis of technological innovation networks' elements of multinational companies, BA scale-free effect, searching of key nodes and natural language description of building process.
A coupled geomorphic and ecological model of tidal marsh evolution

The evolution of tidal marsh platforms and interwoven channel networks cannot be addressed without treating the two-way interactions that link biological and physical processes. We have developed a 3D model of tidal marsh accretion and channel network development that couples physical sediment transport processes with vegetation biomass productivity. Tidal flow tends to cause erosion, whereas vegetation biomass, a function of bed surface depth below high tide, influences the rate of sediment deposition and slope-driven transport processes such as creek bank slumping. With a steady, moderate rise in sea level, the model builds a marsh platform and channel network with accretion rates everywhere equal to the rate of sea-level rise, meaning water depths and biological productivity remain temporally constant. An increase in the rate of sea-level rise, or a reduction in sediment supply, causes marsh-surface depths, biomass productivity, and deposition rates to increase while simultaneously causing the channel network to expand. Vegetation on the marsh platform can promote a metastable equilibrium where the platform maintains elevation relative to a rapidly rising sea level, although disturbance to vegetation could cause irreversible loss of marsh habitat.
Application of big-data in healthcare analytics — Prospects and challenges

Big-Data has opened up enormous opportunities for a variety of industries. Our ability to process large amounts of data, particularly a plethora of types of data, within a unified processing platform has been extremely useful in pushing the boundaries of what can be achieved from our computational models and how we can apply that to solve real life problems. This paper enumerates the main areas where Big-Data has been applied so far and points out areas within healthcare analytics where the same level of success can be gained through adoption of this technology.
PD-1 immune checkpoint blockade may be viable for the prevention and treatment of elderly patients with POCD [Letter]

Department of Anesthesiology, Qilu Hospital of Shandong University (Qingdao), Qingdao 266035, People’s Republic of China Dear Editor Recently, we read with great interest the well-written review article published in the November 8, 2018 edition of the Clinical Interventions in Aging by Kotekar and colleagues titled “Postoperative cognitive dysfunction – current preventive strategies”. The article elegantly addressed the current preventive strategies for postoperative cognitive dysfunction (POCD). The authors concluded that the best preventive strategies for POCD may involve early recognition and management of potential perioperative risk factors, such as intraoperative anesthetic monitoring of the depth of anesthesia, Enhanced Recovery After Surgery and a multidisciplinary collaboration. Furthermore, the authors proposed that pharmacological interventions may be effective preventative and therapeutic strategies to attenuate POCD. We appreciate the efforts of the authors and would like to present our opinion on the review. POCD is a highly prevalent condition with significant impact on the prognosis of elderly patients undergoing an operation, experiencing problems with memory, concentration, information processing, language comprehension, and social integration that can last for months or may even be permanent. Chronic neuroinflammation and accompanying accumulation of amyloid-β (Aβ) and phosphorylation of tau protein secondary to surgery and anesthesia are strongly implicated in the pathophysiology of POCD. The exact cascade by which surgical stress and anesthesia induce neuroinflammation in association with POCD remains unknown. Boosting degenerative systemic immune response in elderly patients may be a potential pharmacological strategy in treating POCD. Although previous studies have highlighted the role of the systemic immune response in inducing neuroinflammation, these results still did not show a significant association between systemic immune response and neuroinflammation. A famous study revealed that surgery-induced neuroinflammation was associated with infiltration of peripheral macrophages. POCD is commonly observed in perioperative care in elderly patients; therefore, a limitation of this study is that they did not use aged mice as an experimental animal model of POCD. Furthermore, elderly individuals more frequently present a degenerative systemic immune system and resident microglial priming in the aging brain, rather than the migration of peripheral macrophages, may have an important role in cognitive deficits after surgery. Normal microglia respond to and degrade Aβ by phagocytosis; however, primed microglia become more proinflammatory and less phagocytic. Current antiCorrespondence: Jianjun Li Department of Anesthesiology, Qilu Hospital of Shandong University (Qingdao), No.758 Hefei Road, Qingdao, People’s Republic of China Tel +86 532 6685 0629 Fax +86 532 6685 0629 Email Ljj9573@163.com Clinical Interventions in Aging Dovepress open access to scientific and medical research
Oligosaccharides Profile and Prebiotic Potential of Gembolo Tuber (Dioscorea bulbifera)

Indonesia has many potential tubers that not yet utilized, whereas the tubers can be utilized in functional food. Dioscorea bulbifera contains oligosaccharides which can be used as functional food prebiotics based. This research aim was to analyze the content of oligosaccharides from Dioscorea bulbifera tuber flour and its prebiotics potential. The extraction of oligosaccharides from Dioscorea bulbifera flour was done using ethanol 70% and analyze the content of oligosaccharides using HPLC (High-Performance Liquid Chromatography). The inoculum of colonic microbial used from volunteer infants aged less than 6 months and only consume breast milk. The prebiotic index was determined by enumerating the growth of total bacteria, microbial probiotics (Bifidobacteria and Lactobacillus) and microbial pathogens (Bacteroids and Clostridium) in anaerobic conditions at 0, 24 and 48 hours. The results showed that oligosaccharides profile of Dioscorea bulbifera flour were Inulin 0.76; Raffinose 0.07; and Lactulose 0.09% b/v. The prebiotics index value of oligosaccharide of extracts of Dioscorea bulbifera flour at 48th hour is 1.2045. It can be concluded that the oligosaccharide from Dioscorea bulbifera tuber flour has potential as a prebiotic.
Are Women at Greater Risk for PTSD than Men

Differences between the sexes regarding the prevalence, psychopathology and natural history of psychiatric disorders have become the focus of an increasingly large number of epidemiological, biological and psychological studies. A fundamental understanding of sex differences may lead to a better understanding of the underlying mechanisms of diseases, as well as their expression and risks.
Data Analysis Based on Functional Dependencies

We present a novel approach to the design of schemas appropriate for data analysis; we call such schemas “analysis contexts”. Roughly speaking, an analysis context is a set of paths with common origin, in which the nodes are attributes and the edges are functional dependencies. Our main contributions are (a) an algorithm for generating all analysis contexts embodied in a set of attributes and a set of functional dependencies over the attributes, (b) a functional language in which analysis queries can be formulated within a context, (c) a formal approach to query optimization, and (d) an algorithm for mapping an analysis context and its associated functional language to a relational star schema for the efficient evaluation of analysis queries. Altogether, our main contribution is the proposal of a schema design method for analytic processing that parallels (and complements) the schema design process in transactional databases.
A Rapid Screening for Cytochrome P450 Catalysis on New Chemical Entities

This work presents the validation of a rapid screening procedure for the catalysis of cytochrome P450 on new chemical entities. The assay is tested on the prototypical, catalytically self-sufficient and soluble cytochrome P450 BM3 from Bacillus megaterium that shares a high degree of homology with mammalian counterparts. The so-called alkali assay developed in our laboratory is validated here also by product formation and molecular modeling on a number of derivatives sharing the molecular scaffold of the 1,2,5-oxadiazole ring, a class of molecules very different from the long-chain fatty acids known to be oxidized by cytochrome P450 BM3. The alkali assay reveals the ability of this cytochrome to oxidize NADPH in the presence of nine out of thirteen 1,2,5-oxadiazole derivatives tested. The enzyme shows high affinity and coupling efficiencies when incubated with four 1,2,5-oxadiazole derivatives. The presence of oxidation products deriving from catalysis was also confirmed by high-performance liquid chromatography (HPLC). Molecular docking suggests that a key factor for the 1,2,5-oxadiazole derivatives to enter the active site and induce catalysis is the presence of the –SO2 moiety bridging the 1,2,5-oxadiazole and phenyl rings. These data indicate that the alkali assay is able to quickly and cheaply detect the recognition of new substrates by cytochrome P450. The assay is not intended to substitute HPLC–mass spectrometry analysis, but it is a preliminary screening that allows elimination of obvious nonsubstrates from the start.
Effect of antitubercular treatment on serum electrolyte and bicarbonate among pulmonary tuberculosis patients in tertiary care Hospital: An observational study

Introduction: Tuberculosis is mainly associated with diarrhea, vomiting and profuse sweating leading to dehydration, electrolyte imbalance and acid base derangements. Treatment with anti tubercular drugs reduces the symptoms and balances the electrolytes. Hence, this study was carried out to assess the electrolyte imbalance among tuberculosis patients and to know the effect of anti tubercular treatment. This study was carried out to study the electrolyte imbalance among newly diagnosed tuberculosis patients and to know the effect of treatment with anti tubercular drugs in improving the electrolyte balance at BRIMS teaching Hospital Bidar. Materials and Methods: This was observational study conducted in pulmonary Medicine OPD of Bidar Institute of Medical Sciences teaching hospital Bidar. 50 participants were enrolled in our study and assessed for demographic data, serum electrolytes and bicarbonate levels and compared with Tuberculosis patients before and after treatment. Results: The electrolyte imbalance in terms of decrease in sodium, potassium chloride and bicarbonate values was significantly associate (p Conclusion: In our study, after treatment with antitubercular drugs, electrolyte levels returned to normal. Because of the high incidence of the electrolyte disturbances in tuberculosis patients, close monitoring and aggressive management are mandatory. Keywords: Mycobacterium tuberculosis, Electrolytes, Cytochemical changes, Antitubercular drugs.
Two components of cardiac delayed rectifier K+ current. Differential sensitivity to block by class III antiarrhythmic agents

An envelope of tails test was used to show that the delayed rectifier K+ current (IK) of guinea pig ventricular myocytes results from the activation of two outward K+ currents. One current was specifically blocked by the benzenesulfonamide antiarrhythmic agent, E-4031 (IC50 = 397 nM). The drug-sensitive current, "IKr" exhibits prominent rectification and activates very rapidly relative to the slowly activating drug-insensitive current, "IKs. " IKs was characterized by a delayed onset of activation that occurs over a voltage range typical of the classically described cardiac IK. Fully activated IKs, measured as tail current after 7.5-s test pulses, was 11.4 times larger than the fully activated IKr. IKr was also blocked by d-sotalol (100 microM), a less potent benzenesulfonamide Class III antiarrhythmic agent. The activation curve of IKr had a steep slope (+7.5 mV) and a negative half- point (-21.5 mV) relative to the activation curve of IKs (slope = +12.7 mV, half-point = +15.7 mV). The reversal potential (Erev) of IKr (-93 mV) was similar to EK (-94 mV for [K+]o = 4 mM), whereas Erev of IKs was -77 mV. The time constants for activation and deactivation of IKr made up a bell-shaped function of membrane potential, peaking between - 30 and -40 mV (170 ms). The slope conductance of the linear portion of the fully activated IKr-V relation was 22.5 S/F. Inward rectification of this relation occurred at potentials greater than -50 mV, resulting in a voltage-dependent decrease in peak IKr at test potentials greater than 0 mV. Peak IKr at 0 mV averaged 0.8 pA/pF (n = 21). Although the magnitude of IKr was small relative to fully activated IKs, the two currents were of similar magnitude when measured during a relatively short pulse protocol (225 ms) at membrane potentials (-20 to +20 mV) typical of the plateau phase of cardiac action potentials.
Uniformity of sunscreen product application: a problem in testing, a problem for consumers

Background/Aims: Testing of sunscreen products requires application of uniform films of product of defined thickness to test volunteers. In spite of the seeming importance of product application to defining sunscreen efficacy, there have been few studies determining how well uniformity is achieved. The purpose of this work was to evaluate the uniformity of sunscreen products of different sun protection factors (SPFs) and vehicles on a variety of substrates by in vitro testing techniques. The results of a variety of testing strategies are reported.
Semi-automated evaluation of Ki-67 index in invasive ductal carcinoma of the breast

A significant factor that affects the value of the Ki-67 proliferation index (IK) is the interpretation and implementation approach. This method is based on visual or automated methods to count tumor nuclei labeled with Ki-67 antigen, and is prone to errors. Detection of Ki-67 is a useful tool in breast cancer and contributes to its molecular classification. The current study proposes a method for the quantification of Ki-67-positive tumor nuclei, which allows for the determination of the exact IK value that is required for tumor stratification based on the proliferation rate. The IK was assessed in 81 successive cases of diagnosed invasive ductal breast carcinoma using a semi-automated method that accurately identifies positive tumor cell nuclei. This method prevents the inclusion of other possible positive cells, including lymphoid, normal epithelia and hyperplastic. In small specimens with increased cell density, where the nucleus/cytoplasm ratio is markedly in favor of the nucleus and the distance between nuclei is small, the method allows precise quantification of the nuclei, even when the limits between nuclei are difficult to identify. In addition, images may be stored in a database, including the assessments, and easily accessed when required. We hypothesize that the semi-automated method for counting nuclei offers the most accurate method of assessing the IK and avoids counting errors that may occur through other methods.
Structure and functional implications of WYL-domain-containing transcription factor PafBC involved in the mycobacterial DNA damage response

In mycobacteria, transcriptional activator PafBC is responsible for upregulating the majority of genes induced by DNA damage. Understanding the mechanism of PafBC activation is impeded by a lack of structural information on this transcription factor that contains a widespread, but poorly understood WYL domain frequently encountered in bacterial transcription factors. Here, we determined the crystal structure of Arthrobacter aurescens PafBC. The protein consists of two modules, each harboring an N-terminal helix-turn-helix DNA binding domain followed by a central WYL and a C-terminal extension (WCX) domain. The WYL domains exhibit Sm-folds, while the WCX domains adopt ferredoxin-like folds, both characteristic for RNA binding proteins. Our results suggest a mechanism of regulation in which WYL domain-containing transcription factors may be activated by binding RNA molecules. Using an in vivo mutational screen in Mycobacterium smegmatis, we identify potential co-activator binding sites on PafBC.
Investigation of the Association between GFPT2 Gene Polymorphism and Risk of Type 2 Diabetes

Accepted: 26 Oct, 2016 Abstract Background and Objectives: Type 2 diabetes is one of the most common metabolic diseases and a complex disorder with a strong genetic predisposition, which significantly affects mortality. A series of factors, such as environmental factors and genetic background are involved in the disease. Recently, a new gene associated with type 2 diabetes has been discovered, which is called GFPT2 and is located on the long arm of chromosome 5. Various mutations can alter GFPT2 function and provide risk for diabetes. In this study, the association of GFPT2 gene polymorphism and the risk of type 2 diabetes, was investigated.