Miracle-dz/UniFAR-FTUs huggingface dataset:
Transcriptional profiling of isogenic Friedreich ataxia neurons and effect of an HDAC inhibitor on disease signatures

Friedreich ataxia (FRDA) is a neurodegenerative disorder caused by transcriptional silencing of the frataxin (FXN) gene, resulting in loss of the essential mitochondrial protein frataxin. Based on the knowledge that a GAA·TTC repeat expansion in the first intron of FXN induces heterochromatin, we previously showed that 2-aminobenzamide–type histone deacetylase inhibitors (HDACi) increase FXN mRNA levels in induced pluripotent stem cell (iPSC)-derived FRDA neurons and in circulating lymphocytes from patients after HDACi oral administration. How the reduced expression of frataxin leads to neurological and other systemic symptoms in FRDA patients remains unclear. Similar to other triplet-repeat disorders, it is unknown why FRDA affects only specific cell types, primarily the large sensory neurons of the dorsal root ganglia and cardiomyocytes. The combination of iPSC technology and genome-editing techniques offers the unique possibility to address these questions in a relevant cell model of FRDA, obviating confounding effects of variable genetic backgrounds. Here, using “scarless” gene-editing methods, we created isogenic iPSC lines that differ only in the length of the GAA·TTC repeats. To uncover the gene expression signatures due to the GAA·TTC repeat expansion in FRDA neuronal cells and the effect of HDACi on these changes, we performed RNA-seq–based transcriptomic analysis of iPSC-derived central nervous system (CNS) and isogenic sensory neurons. We found that cellular pathways related to neuronal function, regulation of transcription, extracellular matrix organization, and apoptosis are affected by frataxin loss in neurons of the CNS and peripheral nervous system and that these changes are partially restored by HDACi treatment.
Applications of Chitin and Chitosan in Industry and Medical Science: A Review

Chitin can be extracted from the exoskeletons of crustaceans, insects and mollusks and the cell wall of microorganisms. It can be converted into chitosan by deacetylation process. Chitosan shows more versatility than chitin due to its solubility and reactive free amino group (-NH 2 ). This article helps to understand the importance and characteristics of chitin and chitosan by their various aspects such as properties and medical and industrial applications. Nepal Journal of Science and Technology Vol. 16, No.1 (2015) pp. 99-104
Distribution and identity of bacteria in subarctic permafrost thaw ponds.

Colored permafrost thaw ponds (thermokarst ponds), are abundant freshwater eco- systems in the subarctic. The ponds can emit significant levels of greenhouse gases, which are drivers of climate change, but little is known of their microbial communities. The ponds are verti- cally stratified for most of the year with suboxic to anoxic hypolimnia, suggesting varied habitats despite their shallow depths (1 to 4 m). Pelagic bacterial communities in 4 contrasting ponds near the coast of Hudson Bay, Quebec, Canada, were investigated by cloning and sequencing the 16S rRNA gene from environmental DNA. Surface and bottom water libraries yielded a total of 109 operational taxonomical units (defined as 97% sequence similarity) from 261 clones. The majority of clones had their closest matches to other environmental clones originating from freshwater environments, especially lakes. Proteobacteria accounted for the majority of sequences (33%), fol- lowed by Bacteroidetes (19%), Actinobacteria (13%), Chlorobi (10%), Verrucomicrobia (8%), and Cyanobacteria (7%). There were large differences in the assemblages inhabiting the different ponds and water layers. Bacteroidetes were predominant at the surface, while Chlorobi were found in bottom waters. Sequences with best matches to known methanotrophic bacteria re - presented up to 20% of all sequences. Methanotrophs included Methylobacter psychrophilus, Crenothrix polyspora, and Methylocystis parvus as closest matches. Ordination analysis clearly separated surface and bottom waters, where relatively large quantities of organic matter, low light availability, cool temperatures, and suboxic conditions selected for the distinct communities. The separation of surface waters of different ponds showed that bacterial communities could differ between superficially similar environments. This study illustrates the high diversity in bacterial assemblages occurring in ponds separated by a few meters, and thus, the potentially complex response of thaw pond systems to climate change.
Bioactive Cembrane-Based Diterpenoids from the Soft Coral Sinularia triangular

Chemical examination of the Taiwanese soft coral Sinularia triangular led to the isolation of five cembrane-based diterpenoids 1–5, including two new metabolites, triangulenes A (1) and B (2). The structures of the new metabolites were determined on the basis of extensive spectroscopic analysis, particularly mass spectroscopy and 2D NMR (1H–1H COSY, HMQC, HMBC, and NOESY) spectroscopy. Metabolites 3 and 5 exhibited moderate cytotoxicity to human tumor cell lines CCRF-CEM and DLD-1. Furthermore, 3–5 displayed significant in vitro anti-inflammatory activity in lipopolysaccharide-stimulated RAW264.7 macrophage cells by inhibiting the expression of the iNOS protein. Metabolites 4 and 5 also effectively reduced the expression of the COX-2 protein in the macrophages.
A spatial panel data version of the knowledge capital model

This paper attempts to analyze the impact of knowledge and knowledge spillovers on regional total factor productivity (TFP) in Europe. Regional patent stocks are used as a proxy for knowledge, and TFP is measured in terms of a superlative index. We follow Fischer et. al (2008) by using a spatial-spillover model and a data set covering 203 regions for six time periods. In order to estimate the impact of knowledge stocks we use a spatial autoregressive model with random effects, which allows for three kinds of spatial dependence: Spatial correlation in the innovations, the exogenous and the endogenous variables. The results suggest that there is a significant positive impact of knowledge on regional TFP levels, and that knowledge spills over to neighboring regions. These spillovers decay exponentially with distance at a rate of 8%. Using Monte Carlo simulations we calculate the distribution of direct and indirect effects. The average elasticity of a region's TFP with respect to its own knowledge stock is 0.2 and highly significant. The average effect of all other regions' TFP is about 50% higher, which confirms that the cross-country externalities are important in the measuring of the impact.
miRDeep-P2: accurate and fast analysis of the microRNA transcriptome in plants

Motivation Two major challenges arise when employing next generation sequencing (NGS) methods to comprehensively identify microRNAs (miRNAs) in plants: 1) how to minimize the false-positive inheritable to computational predictions; 2) how to minimize the computational time required for analyzing the miRNA transcriptome in plants with complex and large genomes. Results We updated miRDeep-P to miRDeep-P2 (miRDP2) by employing a new filtering strategy and overhauling the algorithm. miRDP2 has been tested against miRNA transcriptomes in plants with increasing genome sizes that included Arabidopsis, rice, tomato, maize and wheat. Compared with miRDeep-P and several other computational tools, miRDP2 processes NGS data with superior speed. By incorporating newly updated plant miRNA annotation criteria and developing a new scoring system, the accuracy of miRDP2 outperformed other programs. Taken together, our results demonstrate miRDP2 as a fast and accurate tool for analyzing the miRNA transcriptome in plants. Availability The miRDP2 are freely available from https://sourceforge.net/projects/mirdp2/. Supplementary information Supplementary data are available at Bioinformatics online.
Arctic curves for paths with arbitrary starting points: a tangent method approach

We use the tangent method of Colomo and Sportiello to investigate the arctic curve in a model of non-intersecting lattice paths with arbitrary fixed starting points aligned along some boundary and whose distribution is characterized by some arbitrary piecewise differentiable function. We find that the arctic curve has a simple explicit parametric representation depending of this function, providing us with a simple transform that maps the arbitrary boundary condition to the arctic curve location. We discuss generic starting point distributions as well as particular freezing ones which create additional frozen domains adjacent to the boundary, hence new portions for the arctic curve. A number of examples are presented, corresponding to both generic and freezing distributions. Our results corroborate already known expressions obtained by more involved methods based on bulk correlations, hence providing more evidence to the validity of the tangent method.
Diagnostic leukapheresis for CTC analysis in breast cancer patients: CTC frequency, clinical experiences and recommendations for standardized reporting

Diagnostic leukapheresis (DLA) is based on continuous centrifugation that collects mononuclear cells from peripheral blood with a density of 1.055–1.08 g/ml. As epithelial cells have a similar density, DLA cocollects circulating tumor cell (CTCs) along with the targeted mononuclear cells. Here, we report on our single center experience applying DLA in 40 nonmetastatic and metastatic breast cancer patients and its impact on CTC detection. We found that the use of just 5% of the DLA product (corresponding to a median peripheral blood volume of around 60 ml) in the CellSearch® assay already leads to a significant increase in CTC detection frequency and yield. The implementation of the method was unproblematic, and we did not observe any adverse events in our patient cohort. Extrapolating the CTC counts in the DLA samples to the whole DLA product indicated that enormous CTC numbers could be harvested by this approach (around 205x more CTCs than in the 7.5 ml blood sample in M1 patients). In conclusion, DLA is a clinically safe method to collect CTCs from liters of blood enabling a real liquid biopsy. Yet, further technical developments are required to process whole DLA products and exploit the full potential of this approach. As it is foreseeable that DLA will be used by several groups, and hopefully ultimately brought to the patients in a routine setting, we discuss recommendations on the minimum of required information for reporting on DLAs to allow comparison across different approaches. © 2018 International Society for Advancement of Cytometry
Topology Optimization of Dual Octagonal Array antenna for low frequency applications

Objectives: Efficient antenna design for use in communication systems is altering the face of the antenna modeling. The ever-increasing demand for portable and efficient antennas is making researchers to develop innovative models [1] using advanced antenna modeling tools that comply with industrial needs and standards. Methods/Statistical Analysis: Antennas with lower operating frequencies have the major constraints on its size, efficiency and gain. Study on matching techniques, feeding techniques was also to be considered. Findings: Micro strip patch antennas offers considerable amount of radiation, low cost when fabricated on FR4, light weight and are conformable to suite any application. This paper projects the design, simulation and testing of a dual octagonal patch, the topology algorithm [3] is used to optimize the size and shape of the patch where octagons are spaced in the form of an array to address optimization on size and fits into wireless applications. Application/Improvements: The proposed model is tested in the standard antenna test bench comprising of microwave integrated circuit analyzer receiver MIC10kit and found to operate at a resonant frequency of 1.8 GHz with good radiation characteristics.
GLOBALIZATION, THE VOLATILITY OF INTERMEDIATE GOODS PRICES, AND ECONOMIC GROWTH

We set up a dynamic stochastic model of a stylized economy comprising a final output sector (with traditional and modern firms) and an intermediate goods sector. It is shown that market integration reduces the volatility of the rate of return to capital invested in modern firms. The induced portfolio decisions of households lead to a reallocation of capital from traditional to modern firms. Despite the presence of a reverse precautionary saving channel, the growth rate unambiguously increases because of the reallocation of capital. Empirical estimates for OECD countries support the theoretical results.
Social Determinants of Intention to Dope in Sports Clubs and Institutions

Doping is the use of drug for the purpose of improving performance in general and sports performance in particular. Rejection or acceptance of the use of banned substances by athletes is determined by internal factors that are subjective and external or social. Against this background, the present study examined social risk factors as determinants of intention (temptation) to use banned substances and explored the willingness of athletes at the national level, to report the use of substances that enhance performance. The survey method was a self-report questionnaire based on the Romanian National Anti-Doping Agency (NADA) model of approaching risk factors associated with the use of prohibited substances, collection of demographic data and use of the Performance Enhancement Attitude Scale (PEAS). The subjects were 171 athletes (mean age = 19.75, std. error = 0.103) and 30 coaches in sporting institutions and universities. The results reveal a complex distribution of environment-specific social-proximity influences of athletes, including the family, social class or professional institution, leisure group, sports team, sports clubs and social representation. The rate of prevalence for performance-enhancing drugs (PED) was 1.23% to 12.0% for NADA (p < 0.05) and 1.1% to 15.0% for the PEAS (p < 0.001) and fall into ranges reported by recent studies (1.2% to 25.8%). The approach used took into account the assumption that doping is a rational behavior and intentional. As such, it provides points of intervention that influence decision-making. The findings reveal the need to consider the contribution of several social support factors that contribute to the trend abuse drugs that increase performance.
U.S.-India Cooperation on Demand-Side Management (DSM): Expanding Maharashtra and Delhi Programs to National Level

The Indian government has promoted energy efficiency through initiatives such as equipment labels, outreach activities, and voluntary building codes. Occasionally, it has implemented DSM pilot programs. Beginning in December 2007, Lawrence Berkeley National Laboratory in collaboration with the California Public Utilities Commission and the California Energy Commission signed three agreements to promote DSM programs in two states, Maharashtra and Delhi, and at the national level. In December 2009, the Indian government announced that the National Mission on Enhanced Energy Efficiency (NMEEE) will be implemented from April 1, 2010. Four key approaches are envisioned under NMEEE – creation of market for tradable energy savings certificates for large industrial customers, market transformation, creation of financing platform to facilitate ESCO activity, and development of broader economic framework (e.g. tax incentives, public procurement, etc.) to support EE. In this paper, we focus on the market transformation approach included in the NMEEE. We discuss how the NMEEE can foster ongoing EE activities in India – for example, DSM programs initiated by regulatory commissions, administered by utilities, and funded by ratepayers. We provide an overview of the existing institutions, legal and regulatory framework, availability and capability of EE workforce, and the financial infrastructure that can support EE. Based on our experience in India in design and implementation of DSM programs, we identify missing elements that are necessary for delivering EE and achieving the potential estimated in the NMEEE. We present a critical review of previous EE initiatives in India. Finally, for Indian policymakers, we suggest a road-map that incorporates the NMEEE and would be critical for rapidly achieving all cost-effective CO2 reductions through EE.
Inventory Management in Construction Operations Involving on-site Fabrication of Raw Materials

There are usually plenty of material inventories in a construction site. More inventories can meet unexpected demands, and also they may have an economical advantage by avoiding a probable escalation of raw material costs. On the other hand, these inventories also cause negative aspects to increase costs for storing redundant inventory as well as decreasing construction productivity. Therefore, a proper method of deciding an optimal level of material inventories while considering dynamic variations of resources under uncertainty is very crucial for the economical efficiency of construction projects. This research presents a stochastic modelling method for construction operations, particularly targeting a work process involving on-site fabrication of raw materials like iron-rebar process (delivery, cut and assembly, and placement). To develop the model, we apply the concept of factory physics to depict the overall components of a system. Then, an optimal inventory management model is devised to support purchase decisions where users can make timely actions on how much to order and when to buy raw materials. Also, optimal time lag, which minimizes the storage time for pre-assembled materials, is obtained. To verify this method, a real case is applied to elicit an optimal amount of inventory and time lag. It is found that average values as well as variability of inventory level decreased significantly so as to minimize economic costs related to inventory management under uncertain project condition.
Benchmark Data for Mobile App Traffic Research

Mobile app traffic classification aims to automatically map mobile packets into apps. It has become an active task in mobile traffic engineering, and numerous algorithms have been proposed for this task, including machine learning, deep packet inspection methods. However, existing works mainly evaluate their methods on their own collected mobile traffic traces. There is no public benchmark data. The results in existing papers cannot be directly compared. This largely limits the development of mobile app traffic classification methods. This paper describes our Mobile Traffic Data(MTD): Android app traffic flow sample sets with ground truth. The goal of MTD is to advance the state-of-arts in mobile app traffic classification. For building MTD, we collected and annotated more than ten thousands of traffic flows using Mobilegt system. The popularity used flow features were also extracted to build flow samples for mobile traffic classification using machine learning. MTD sets have been shared in public. In addition, this paper provides the performance analysis of typical machine learning techniques on MTD, which can be served as the baseline results on this benchmark data.
Chure forestry conservation and management plan: A case study of Arghakhanchi district, Nepal

Chure Region has a distinct geographical and bio-physical specificities lying on the foothill of Himalaya. It is the youngest mountain of the world, and suffers from mass erosion, landslides and other environmental externalities which make the region vulnerable. Resource depletion, for example deforestation, due to natural as well as human induced factors in the Chure Region has accelerated; and livelihood opportunities have been retreating. Degradation of watershed, lowering the underground water and disturbing the ecological niche in and around the region makes the region more sensitive and fragile. Ecological balance and conservation of natural resources of the Chure Region, therefore, is very urgent. For the betterment of the people and resources of the Chure, Bhabar and Terai regions, there is need to design the work plan for conservation and development. The Government of Nepal, at present, has also given greater emphasis to the protection of Chure through initiation of ‘Rastrapati Chure Conservation Program since 2009 in the field of conservation and management of the resources in the Chure Region. The present paper is an attempt to identify the problems and issues of Chure forest conservation and to prepare conservation and management plan using qualitative as well as quantitative methods of analysis. The paper has pointed out that the ecological, geographical and bio-physical conditions of the Chure Region have rapidly degraded since the last 32 years. Increasing landslides and flooding; and human intervention makes Chure more fragile and weakest zone where lack of/inadequate livelihood assets and food insecurity are noted. However, Chure Region has many opportunities of employment and income generation through establishment of environmental friendly green enterprises. Thus, the paper concludes an urgent need to formulate short-term to long-term strategies with policy priorities actions and result-oriented efforts. The policies and strategies should be related to establish Chure as a rich bio-diversity zone, with hazardless and improved livelihoods. Key words: Chure, forestry, forestry conservation, forest management, Nepal, land use.
Basal insulin therapy: Unmet medical needs in Asia and the new insulin glargine in diabetes treatment

Diabetes remains a global epidemic and a tremendous health challenge, especially in the Asian population. Dramatic increases in the prevalence of diabetes across different countries or areas in Asia have been reported in recent epidemiological studies. Although clinical guidelines have strengthened appropriate antihyperglycemic medications and lifestyle modifications for optimal diabetes management, inadequate glycemic control still occurs in many patients with an increased risk of developing microvascular and macrovascular complications. Insulin administration is the main therapy for diabetes in response to the inability to secrete insulin, and is recommended in current guidelines to treat patients with type 2 diabetes after failure of oral antidiabetic drugs. Clinical studies have shown that long‐acting insulin analogs improve basal glycemic control with reduced risk of hypoglycemia. In the present review, we discuss previous challenges with basal insulin therapy in Asia, the pharmacological development of insulin analogs to overcome the unmet medical needs and recent clinical studies of the new ultra‐long‐acting insulin analog, insulin glargine U300. Furthermore, relevant findings of current real‐world evidence are also included for the comparison of the efficacy and safety of different insulin formulations. Based on the accumulating evidence showing a low incidence of hypoglycemia and technical benefits of dose titration, treatment with glargine U300 can be a promising strategy for Asian diabetes patients to achieve glycemic targets with favorable safety.