Miracle-dz/UniFAR-FTUs huggingface dataset:
Fgfr3 mutation disrupts chondrogenesis and bone ossification in zebrafish model mimicking CATSHL syndrome partially via enhanced Wnt/β-catenin signaling

CATSHL syndrome, characterized by camptodactyly, tall stature and hearing loss, is caused by loss-of-function mutations of fibroblast growth factor receptors 3 (FGFR3) gene. Most manifestations of patients with CATSHL syndrome start to develop in the embryonic stage, such as skeletal overgrowth, craniofacial abnormalities, however, the pathogenesis of these phenotypes especially the early maldevelopment remains incompletely understood. Furthermore, there are no effective therapeutic targets for this skeleton dysplasia. Methods: We generated fgfr3 knockout zebrafish by CRISPR/Cas9 technology to study the developmental mechanisms and therapeutic targets of CATSHL syndrome. Several zebrafish transgenic lines labeling osteoblasts and chondrocytes, and live Alizarin red staining were used to analyze the dynamical skeleton development in fgfr3 mutants. Western blotting, whole mount in situ hybridization, Edu labeling based cell proliferation assay and Wnt/β-catenin signaling antagonist were used to explore the potential mechanisms and therapeutic targets. Results: We found that fgfr3 mutant zebrafish, staring from early development stage, showed craniofacial bone malformation with microcephaly and delayed closure of cranial sutures, chondroma-like lesion and abnormal development of auditory sensory organs, partially resembling the clinical manifestations of patients with CATSHL syndrome. Further studies showed that fgfr3 regulates the patterning and shaping of pharyngeal arches and the timely ossification of craniofacial skeleton. The abnormal development of pharyngeal arch cartilage is related to the augmented hypertrophy and disordered arrangement of chondrocytes, while decreased proliferation, differentiation and mineralization of osteoblasts may be involved in the delayed maturation of skull bones. Furthermore, we revealed that deficiency of fgfr3 leads to enhanced IHH signaling and up-regulated canonical Wnt/β-catenin signaling, and pharmacological inhibition of Wnt/β-catenin could partially alleviate the phenotypes of fgfr3 mutants. Conclusions: Our study further reveals some novel phenotypes and underlying developmental mechanism of CATSHL syndrome, which deepens our understanding of the pathogenesis of CATSHL and the role of fgfr3 in skeleton development. Our findings provide evidence that modulation of Wnt/β-catenin activity could be a potential therapy for CATSHL syndrome and related skeleton diseases.
Review of Various Algorithms in Graph Mining Based on Search Strategies

-Graph mining is an active research area during these days. Graphs have become significant in the modeling of complicated structures such as circuit images, chemical compounds, protein structures, biological networks, social networks, web workflows and XML documents. A common framework is necessary to study various graph mining algorithms and their applications. In this paper, we present a review study of various algorithms based on their graph representation, subgraph generation
Mitodepressive Effect of Four Food Additives Using the Allium Cepa Assay

The mitodepressive effect of potassium bromate, sodium benzoate, sodium bicarbonate and ammonium bicarbonate were determined using the Allium cepa Linn. (the common onion) assay. This model was used to determine the effects of these additives on the mean root length, mitotic index and chromosomal aberrations of onion bulbs using 0.25, 0.5 and 1% (w/v) of each food additive. All additives showed a concentration-dependent toxicity on the roots, interfering with mitotic cell division and causing chromosomal aberrations. _____________________________________________________________________________________________________________
DSAGEN: Synthesizing Programmable Spatial Accelerators

Domain-specific hardware accelerators can provide orders of magnitude speedup and energy efficiency over general purpose processors. However, they require extensive manual effort in hardware design and software stack development. Automated ASIC generation (eg. HLS) can be insufficient, because the hardware becomes inflexible. An ideal accelerator generation framework would be automatable, enable deep specialization to the domain, and maintain a uniform programming interface. Our insight is that many prior accelerator architectures can be approximated by composing a small number of hardware primitives, specifically those from spatial architectures. With careful design, a compiler can understand how to use available primitives, with modular and composable transformations, to take advantage of the features of a given program. This suggests a paradigm where accelerators can be generated by searching within such a rich accelerator design space, guided by the affinity of input programs for hardware primitives and their interactions. We use this approach to develop the DSAGEN framework, which automates the hardware/software co-design process for reconfigurable accelerators. For several existing accelerators, our evaluation demonstrates that the compiler can achieve 89% of the performance of manually tuned versions. For automated design space exploration, we target multiple sets of workloads which prior accelerators are design for; the generated hardware has mean 1.3× perf2/mm2 over prior programmable accelerators.
Expression of β1, β3, β4, and β5 Integrins by Human Lung Carcinoma Cells of Different Histotypes

Abstract Structural and functional analyses of several integrin heterodimers were performed in non-small-cell lung cancer (NSCLC) and small cell lung cancer (SCLC) cell lines. The expression of β1, β3, β4, and β5 heterodimers was evaluated at protein and mRNA levels. By flow cytometry and immunoprecipitation experiments we demonstrate that NSCLC cells (A549 adenocarcinoma and DG3 large cell carcinoma) coexpress integrin heterodimers composed of β1, β3, β4, and β5 subunits, whereas SCLC cells (AE2 and H69) express only β1 integrin heterodimers. Northern blot experiments confirmed immunochemical analysis: SCLC cells in contrast to NSCLC cells express only the mRNA coding for the β1 subunit. These data indicate that in lung carcinoma cells the diversity in the integrin repertoire depends upon differential gene expression. The functionality of integrin receptors has been studied using antibody blocking experiments. Data reported demonstrate that the α6β1 integrin is a laminin receptor in either SCLC or NSCLC cells. An antibody to the β4 subunit partially inhibits the adhesion of adenocarcinoma cells to laminin but does not block laminin adhesion of large cell carcinoma cells, even though α6β4 complexes are expressed on both cell types. Two antisera to vitronectin receptors inhibit the adhesion of NSCLC cells to both vitronectin and fibronectin. The same antisera inhibit the adhesion of SCLC cells only to laminin, indicating that the αvβ1 integrin might function in these cells as laminin receptor.
Occurrence of Corynespora cassiicola isolates resistant to boscalid on cucumber in Ibaraki Prefecture, Japan

A total of 651 isolates of cucumber corynespora leaf spot fungus (Corynespora cassiicola) collected from cucumber in Japan, either with (438 isolates) or without (213 isolates) a prior history of boscalid use, were tested for their sensitivity to boscalid by using a mycelial growth inhibition method on YBA agar medium. Additionally, seven isolates of C. cassiicola obtained from tomato, soybean, eggplant (aubergine) and cowpea in different locations in Japan were tested before boscalid registration. Minimum inhibitory concentration (MIC) and 50% effective concentration (EC50) values for 220 isolates from crops without a prior history of boscalid use ranged from 0·5 to 7·5 μg mL−1 and from 0·04 to 0·59 μg mL−1, respectively. Two hundred and fourteen out of 438 isolates collected from ten cucumber greenhouses in Ibaraki Prefecture, Japan, which received boscalid spray applications showed boscalid resistance, with MIC values higher than 30 μg mL−1. Moreover, resistant isolates were divided into two groups: a moderately resistant (MR) group consisting of 189 isolates with EC50 values ranging from 1·1 to 6·3 μg mL−1, and a very highly resistant (VHR) group consisting of 25 isolates with EC50 values higher than 24·8 μg mL−1. MR isolates were detected from all ten greenhouses, but VHR isolates were detected from only three. As a result of fungus inoculation tests which used potted cucumber plants, control failures of boscalid were observed against resistant isolates. Efficacy of boscalid was remarkably low against VHR isolates in particular. This is the first known report on boscalid resistance in Japan.
A fabrication-oriented remeshing method for auxetic pattern extraction

We propose a method for extracting auxetic patterns from meshes for fabrication by modifying the existing mesh primitives directly and fully automatically. This direct approach is novel in the sense that most of the fabricationoriented surface tiling methods introduce additional primitives, such as curve networks in an interactive semiautomatic framework. Our method is based on a remeshing procedure that converts a given quad mesh with arbitrary topology into our desired structure that is ready to be fabricated. The main advantages of establishing auxetic patterns on meshes are the achieved flexibility using cheap inflexible materials as well as less material usage and fabrication time, as demonstrated in our results.
THE FLUCTUATION ANALYSIS OF CONFORMATIONAL MOBILITY FOR PYRIDOXINE DERIVATIVES IN THE ACTIVE SITE OF ACETYLCHOLINESTERASE

Acetylcholinesterase (AChE) is the main enzyme of the nervous system that is responsible for the regulation of a nerve impulse transfer by a rapid hydrolysis of the neurotransmitter acetylcholine. The most important aspect in the studies related to AChE is the issue of specific interaction with ligands for its activity regulation. In most cases it is necessary for AChE site-specific inhibitors design for development of potential new drugs for the treatment of neurodegenerative diseases with more efficiency and less side effects. Currently the methods of molecular modeling are widely used for new drugs design. In this study AChE structure of 2JEY mouse served as biological target. The derivatives of pyridoxine were used as ligands, with anticholinesterase effect shown in vivo. Moreover the position of these ligands in AChE active center during docking was similar to AChE inhibitors used in medicine (proserin, physostigmine). A combination of molecular docking and Molecular Dynamics methods allowed us to estimate the drug potential of inhibitors more efficiently. The study was carried out using the following software packages: AutoDock.1. 5.6 (Vina application) and NAMD 2.8 with AMBER 99 force field. The result showed that the ligand position in the active cavity of an enzyme may vary significantly even for related compounds and these positions depend on ligand modification. The analysis of molecular dynamics revealed that the ligand mobility and respective inhibitory activity depend on an inhibitor size and on ligand affinity to AChE. The number of interatomic interactions between molecules and probabilities of their interactions in an active site of the enzyme were used for analysis. It was shown that the molecules with a high affinity for the enzyme active cavity not always will be able to get into active cavity by reason of their size. The hydrophobic interactions of ligands with uncharged amino acid residues allows them to bind more efficiently to the active center of AChE. Thus the structural R.Kh. Ayupov* et al. International Journal Of Pharmacy & Technology IJPT| June-2016 | Vol. 8 | Issue No.2 | 14539-14547 Page 14540 features of the ligand exactly define long-term anticholinesterase effect.
Role of non-wood forest products for local livelihoods in countries with transition and market economies: case studies in Ukraine and Sweden

Abstract The role of non-wood forest products (NWFPs) in local economies differ in time and space. We analysed Ukrainian and Swedish national policies and management rules related to the use of NWFPs, and described how different forest stakeholders utilised NWFPs in rural areas in Ukraine and Sweden. In total we interviewed 114 local forest stakeholders in one rural region's settlements in both countries. The topics for the field study were (1) the reasons and amounts of NWFPs harvested by different forest user categories; (2) traditional practices of NWFP use, including harvesting methods and (3) how these practices have changed over the past decades. At the national level, both countries allowed the utilisation of most NWFPs, did not regulate the use, and did not include NWFPs into forest management plans. In both case studies, historical use of NWFPs was intensive. This use remained important in Ukraine, but not in Sweden. Due to difficult economic transition in Ukraine, use of NWFPs by locals has increased. While hunting as a tradition was more popular in the Swedish case study, recreational use of forest was popular in both case studies. Finally, we discuss the role of NWFPs in countries with transition and market economies, and the extent to which the countries support sustainable use of NWFPs.
NEGATED ITEMSETS OBTAINING METHODS FROM TREE-STRUCTURED STREAM DATA

With the rapid development of Internet of Things technologies, millions of physical objects communicate each other and produce huge volumes of data. The IoT revolution comes great opportunities and changes the world completely, but also increases the difficulty of data usage. Along with fusing the cutting-edge technologies, the challenge is the development of software and analytical systems that turn the deluge of massive data produced by different applications over sensor networks and internets into valuable and useful information. One of the popular method is to discover interesting relations between data. However, finding hidden information from xml-based data is not easy task to do. To make matter worse, it is much more difficult if the discovering relation is for between non-exiting parts of data. In this paper, we are trying to figure out how efficiently find out the important non-existing data parts from xml-based data and provide some definitions with adjusted formulas tailored to our target data along with an framed algorithm.
Targeting of Formyl Peptide Receptor 2 for in vivo imaging of acute vascular inflammation

Inflammatory conditions are associated with a variety of diseases and can significantly contribute to their pathophysiology. Neutrophils are recognised as key players in driving vascular inflammation and promoting inflammation resolution. As a result, neutrophils, and specifically their surface formyl peptide receptors (FPRs), are attractive targets for non-invasive visualization of inflammatory disease states and studying mechanistic details of the process. Methods: A small-molecule Formyl Peptide Receptor 2 (FPR2/ALX)-targeted compound was combined with two rhodamine-derived fluorescent tags to form firstly, a targeted probe (Rho-pip-C1) and secondly a targeted, pH-responsive probe (Rho-NH-C1) for in vivo applications. We tested internalization, toxicity and functional interactions with neutrophils in vitro for both compounds, as well as the fluorescence switching response of Rho-NH-C1 to neutrophil activation. Finally, in vivo imaging (fluorescent intravital microscopy [IVM]) and therapeutic efficacy studies were performed in an inflammatory mouse model. Results: In vitro studies showed that the compounds bound to human neutrophils via FPR2/ALX without causing internalization at relevant concentrations. Additionally, the compounds did not cause toxicity or affect neutrophil functional responses (e.g. chemotaxis or transmigration). In vivo studies using IVM showed Rho-pip-C1 bound to activated neutrophils in a model of vascular inflammation. The pH-sensitive (“switchable”) version termed Rho-NH-C1 validated these findings, showing fluorescent activity only in inflammatory conditions. Conclusions: These results indicate a viable design of fluorescent probes that have the ability to detect inflammatory events by targeting activated neutrophils.
DETERMINATION OF INITIAL CENTROID IN K-MEANS USING PCA FACTOR SCORES

Clustering is considered as the task of dividing a dataset, such that elements within each subset are similar between them and are dissimilar to elements belonging to other subsets. One of the most commonly and widely used is K-Means clustering because of its simplicity and performance. The initial centroids for clustering are generated randomly before clustering. If the dataset used is large, then the performance of K-Means will be reduced and also the time complexity will be increased. To overcome this problem, this paper focuses on determining the initial cluster centroids for K-Means. For this purpose, PCA factor score initialization is used in this paper. The experimental results show that the proposed technique provides better clustering and also decreases the time complexity.
A Specialized Architecture for Object Serialization with Applications to Big Data Analytics

Object serialization and deserialization (S/D) is an essential feature for efficient communication between distributed computing nodes with potentially non-uniform execution environments. S/D operations are widely used in big data analytics frameworks for remote procedure calls and massive data transfers like shuffles. However, frequent S/D operations incur significant performance and energy overheads as they must traverse and process a large object graph. Prior approaches improve S/D throughput by effectively hiding disk or network I/O latency with computation, increasing compression ratio, and/or application-specific customization. However, inherent dependencies in the existing (de)serialization formats and algorithms eventually become the major performance bottleneck. Thus, we propose Cereal, a specialized hardware accelerator for memory object serialization. By co-designing the serialization format with hardware architecture, Cereal effectively utilizes abundant parallelism in the S/D process to deliver high throughput. Cereal also employs an efficient object packing scheme to compress metadata such as object reference offsets and a space-efficient bitmap representation for the object layout. Our evaluation of Cereal using both a cycle-level simulator and synthesizable Chisel RTL demonstrates that Cereal delivers 43.4× higher average S/D throughput than 88 other S/D libraries on Java Serialization Benchmark Suite. For six Spark applications Cereal achieves 7.97× and 4.81× speedups on average for S/D operations over Java built-in serializer and Kryo, respectively, while saving S/D energy by 227.75× and 136.28×.
Heterogenous Job Separations and the Balassa-Samuelson Effect

We incorporate different sectoral job separation rates into a two-sector small open economy model to investigate the Balassa-Samuelson (B-S) effect. While labour is mobile, unemployment occurs due to search frictions. In addition, unequal separation rates give rise to compensating wage differentials. When productivity grows in the tradeables sector, labour moves from the tradeables sector to the nontradeables sector if tradeables and nontradeables are complements in consumption. Nevertheless, unemployment always falls due to the positive income effect. We also find that the effect of productivity growth in the tradeables sector on the real exchange rate is reduced by almost 38 per cent when separation rates differ across sectors and tradeables and nontradeables are complements. Overall, an overvaluation of the real exchange rate in the basic B-S model can be explained by heterogeneous
HDAC6-specific inhibitor suppresses Th17 cell function via the HIF-1α pathway in acute lung allograft rejection in mice

Background: Previous animal experiments and clinical studies indicated the critical role of Th17 cells in lung transplant rejection. Therefore, the downregulation of Th17 cell function in lung transplant recipients is of great interest. Methods: We established an orthotopic mouse lung transplantation model to investigate the role of histone deacetylase 6-specific inhibitor (HDAC6i), Tubastatin A, in the suppression of Th17 cells and attenuation of pathologic lesions in lung allografts. Moreover, mechanism studies were conducted in vitro. Results: Tubastatin A downregulated Th17 cell function in acute lung allograft rejection, prolonged the survival of lung allografts, and attenuated acute rejection by suppressing Th17 cell accumulation. Consistently, exogenous IL-17A supplementation eliminated the protective effect of Tubastatin A. Also, hypoxia-inducible factor-1α (HIF-1α) was overexpressed in a lung transplantation mouse model. HIF-1α deficiency suppressed Th17 cell function and attenuated lung allograft rejection by downregulating retinoic acid-related orphan receptor γt (ROR γt) expression. We showed that HDAC6i downregulated HIF-1α transcriptional activity under Th17-skewing conditions in vitro and promoted HIF-1α protein degradation in lung allografts. HDAC6i did not affect the suppression of HIF-1α-/- naïve CD4+ T cell differentiation into Th17 cell and attenuation of acute lung allograft rejection in HIF-1α-deficient recipient mice. Conclusion: These findings suggest that Tubastatin A downregulates Th17 cell function and suppresses acute lung allograft rejection, at least partially, via the HIF-1α/ RORγt pathway.
IMPROVED ERROR REDUCED EXTREME LEARNING MACHINE (IERELM) CLASSIFIER FOR BIG DATA ANALYTICS

Nowadays the term ‘Big Data Analytics’ has been talked everywhere due to the advancement of information technology, evolution of computer applications, mobile communications and much more. This paves the way for doing lot of research in this big data arena. It is common to known that classification is one among the thrust research dimension in the field of big data particularly in the field of data analytics. Machine learning algorithms have lot of scope on analytics; particularly extreme learning machine is a kind of feed-forward neural network that is commonly applied for performing classification task. This machine learning ELM algorithm has single layer hidden nodes with randomly assigned weights for connecting with hidden layer. It is to be noted that feed-forward neural networks in extreme learning machine are poor in updating the weights that leads to performance degradation. Computational complexity is certainly more when applying ELM for big data analytics. This part of doctoral research work inclines high motivation for improving the performance of ELM in terms of reducing the error and we named it as Improved Error Reduced ELM shortly coined as IERELM. The performance of the proposed IERELM mechanism is applied for performing the classification task in KDD Cup 99 multivariate dataset that contains 40,00,020 instances with 42 attributes. Obtained results portrays that the proposed IERELM performs better in terms of detection rate, false alarm rate and elapsed time to perform classification.
“Guidelines for Assessing Cultural Disparity in e-Learning”

Education is an important component of any nation’s development process (UNDP, 2001). With the expansion of educational technologies, more developing countries are experimenting with such technologies and related programs to expand educational opportunities for their populations. However, stakeholders in educational programs have expressed concern that levels of access in developing countries to information and communication technologies (ICTs), the foundation of educational technologies, could generate inequitable educational opportunities (Burbules & Callister, 2000; Haywood, 1995; Lax, 2001; Lelliott, Pendlebury, & Enslin, 2000; McLoughlin, 2000; Rosen, 1998). In addition, targeted learners may experience inequitable learning outcomes if they are expected to use educational ICTs produced in another culture or country (DeFillippi, 2001; Henderson, 1996; Lu, Walker, & Huang, 1999; McLoughlin, 1999). Several factors can generate or exacerbate these cultural disparities: