Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular Epidemiology of Influenza A/H3N2 Viruses Circulating in Mexico from 2003 to 2012

In this work, nineteen influenza A/H3N2 viruses isolated in Mexico between 2003 and 2012 were studied. Our findings show that different human A/H3N2 viral lineages co-circulate within a same season and can also persist locally in between different influenza seasons, increasing the chance for genetic reassortment events. A novel minor cluster was also identified, named here as Korea, that circulated worldwide during 2003. Frequently, phylogenetic characterization did not correlate with the determined antigenic identity, supporting the need for the use of molecular evolutionary tools additionally to antigenic data for the surveillance and characterization of viral diversity during each flu season. This work represents the first long-term molecular epidemiology study of influenza A/H3N2 viruses in Mexico based on the complete genomic sequences and contributes to the monitoring of evolutionary trends of A/H3N2 influenza viruses within North and Central America.
Nanocrystalline growth activation energy of alumina polymorphs synthesised by mechanochemical technique

Al2O3 nanopowders were synthesised via mechanochemical method using AlCl3 and CaO as raw materials. The effect of thermal treatment on the structural evolutions and morphological characteristics of the nanopowders was investigated using X-ray diffractometry, transmission electron microscopy, scanning electron microscopy, differential thermal analysis and Rietveld refinement. The results showed that the average crystallite size of Al2O3 was <100 nm up to ∼1200°C. The activation energy for Al2O3 nanocrystallite growth during calcinations was calculated to be ∼22 598 and 30 195 J mol−1 for η- and κ-alumina respectively, while for α-Al2O3, it was 8373 and 34 131 J mol−1 at temperatures up to 1200°C and >1200°C respectively. The mechanism of nanocrystalline growth of Al2O3 polymorphs during annealing is also discussed.
Reconfigurable Asynchronous Logic

Challenges in mapping asynchronous logic to a flexible substrate include developing a balance between circuit-level flexibility, mapping complexity, and logic overhead. We have developed a reconfigurable dataflow architecture that addresses these challenges, and have also created the necessary synthesis flow required to map designs to the architecture. The architecture exploits some of the unique features of asynchronous logic, and attains a performance that significantly exceeds previous asynchronous FPGAs
Virtual reality school for children with learning difficulties

This paper describes the process starting from the identification of educational needs of children with learning difficulties to the design of a fully interactive virtual school, where it is possible to learn about the physical and social world. The fundamentals of this design are the exclusive advantages that Real Time Graphics offer for developing tools in which children can learn while playing. This development has been done in the framework of a strongly-funded project by the Spanish Government. This ongoing project is in its final stage of development and will produce tools which are valid both for special and mainstream education, ready to be used and tested over final users.
Crack Growth Life Estimating for MSD Panel

The problem of multiple site damage (MSD) has got more attention in ageing structures. Cumulative effects of interacting cracks may significantly degrade the damage tolerance capacity of structures. Cracks caused by MSD are extremely difficult to detect and greatly reduce the residual strength, fatigue life and overall structural integrity of aircraft panels. This paper presents a simple numerical method, which use the principles of fracture mechanics and the computation results, to predict the fatigue crack growth life of MSD structure. Comparing with calculating crack growth life cycle by cycle, this method will save much time. To verify the validity of the proposed method, experiment was conducted and reported with simulation specimen of representative MSD structure with 5 details. The comparison between the calculated a-N curves and the crack growth lives and the test results shows that the prediction result with this fast method is acceptable. A discussion was carried out by numerical analysis; in with typical MSD structures with different initial crack length were adopted. Crack interaction effect was found obviously, but it occurred mainly in the last part of the crack growth lives. The relative size of MSD cracks depends significantly on the distribution of the initial cracks.
Comparison of Polymerase Chain Reaction and Virus Isolation for Detection of Epizootic Hemorrhagic Disease Virus in Clinical Samples from Naturally Infected Deer

We compared our recently reported reverse transcriptase polymerase chain reaction (PCR)-based assay for detection of epizootic hemorrhagic disease virus (EHDV) in clinical samples with different virus isolation (VI) procedures. Thirty-six blood samples and 1 spleen sample from deer were assessed by the EHDV PCR assay and VI in baby hamster kidney (BHK)-21 cells and embryonated chicken eggs (ECE). The EHDV PCR assay detected EHDV RNA from 6 blood samples obtained from deer during 1988–1989 outbreaks of epizootic hemorrhagic disease and from the spleen and blood samples of a deer with clinical hemorrhagic disease in 1992. The 6 blood samples from the 1988–1989 outbreaks and the spleen sample from the 1992 case were VI positive on BHK-21 cell culture. The blood from the same deer with the PCR- and VI-positive spleen was VI negative in BHK-21 cells and ECE. All EHDV isolates were identified as EHDV serotype 2 by a plaque inhibition test. The results of this study indicate that the sensitivity of the previously described EHDV PCR assay is comparable to or greater than that of the VI method in BHK-21 cell culture or ECE. The EHDV PCR assays could provide a superior diagnostic alternative to the current cumbersome and time-consuming VI procedures.
Biomimetic Materials for Bone Tissue Engineering – State of the Art and Future Trends

Bone tissue engineering is extremely promising for regenerating large bone defects in orthopedic or maxillofacial surgery. It consists of harvesting, culturing and differentiating human mesenchymal stem cells in combination with scaffolds. Different cell sources, such as bone marrow or adipose tissue, have been studied. Biomaterials resembling bone extracellular matrix have been used for scaffolding cells. However, these macroporous calcium phosphate ceramics or biodegradable polymers are two dimensional structures at the cellular level and have low osteogenesis properties in vivo. In this paper, several biomimetic approaches involving hydrogels or particles for 3‐dimensional (3D) cell cultures are reviewed. High numbers of cells for low amounts of material induced abundant extracellular matrix formation in vitro and relatively large amounts of bone tissue formation in vivo. In addition, the 3D culture of several cell populations should make it easier for bone tissue constructs to vascularize, thus lifting the limits of current clinical applications.
AXL-Mediated Productive Infection of Human Endothelial Cells by Zika Virus.

RATIONALE The mosquito-borne Zika virus (ZIKV) is now recognized as a blood-borne pathogen, raising an important question about how the virus gets into human bloodstream. The imminent threat of the ZIKV epidemic to the global blood supply also demands novel therapeutics to stop virus transmission though transfusion. OBJECTIVE We intend to characterize ZIKV tropism for human endothelial cells (ECs) and provide potential targets for intervention. METHODS AND RESULTS We conducted immunostaining, plaque assay, and quantitative reverse transcription-polymerase chain reaction of ZIKV RNA to evaluate the possible infection of ECs by ZIKV. Both the African and the South American ZIKV strains readily infect human umbilical vein endothelial cells and human ECs derived from aortic and coronary artery, as well as the saphenous vein. Infected ECs released infectious progeny virus. Compared with the African strains, South American ZIKV isolates replicate faster in ECs and are partially cytopathic, suggesting enhanced virulence of these isolates. Flow cytometric analyses showed that the susceptibility of ECs positively correlated with the cell surface levels of tyrosine-protein kinase receptor UFO (AXL) receptor tyrosine kinase. Gain- and loss-of-function studies further revealed that AXL is required for ZIKV entry at a postbinding step. Finally, small-molecule inhibitors of the AXL kinase significantly reduced ZIKA infection of ECs. CONCLUSIONS We identified EC as a key cell type for ZIKV infection. These data support the view of hematogenous dissemination of ZIKV and implicate AXL as a new target for antiviral therapy.
Chronic Administration of Ghrelin Improves Left Ventricular Dysfunction and Attenuates Development of Cardiac Cachexia in Rats With Heart Failure

Background—Ghrelin is a novel growth hormone (GH)–releasing peptide that may also induce vasodilation and stimulate feeding through GH-independent mechanisms. We investigated whether ghrelin improves left ventricular (LV) dysfunction and attenuates cardiac cachexia in rats with chronic heart failure (CHF). Methods and Results—Ligation of the left coronary artery or sham operation was performed; 4 weeks after surgery, rat ghrelin (100 &mgr;g/kg SC BID) or saline was administered for 3 weeks. Echocardiography and cardiac catheterization were performed. Serum GH and insulin-like growth factor-1 were significantly higher in both CHF and sham rats treated with ghrelin than in those given placebo (P <0.05 for both). CHF rats given placebo showed an impaired increase in body weight compared with sham rats given placebo (P <0.05). CHF rats treated with ghrelin, however, showed a significantly greater increase in body weight than those given placebo (+10% versus +3%, P <0.05). They showed significantly higher cardiac output (315±49 versus 266±31 mL · min−1 · kg−1, P <0.05) and LV dP/dtmax (5738±908 versus 4363±973 mm Hg/s, P <0.05) than CHF rats given placebo. Ghrelin increased diastolic thickness of the noninfarcted posterior wall, inhibited LV enlargement, and increased LV fractional shortening in CHF rats (from 15±3% to 19±3%, P <0.05). Conclusions—Chronic subcutaneous administration of ghrelin improved LV dysfunction and attenuated the development of LV remodeling and cardiac cachexia in rats with CHF.
PLCγ2 and PKC Are Important to Myeloid Lineage Commitment Triggered by M‐SCF and G‐CSF

Myeloid differentiation is a complex process whereby mature granulocytes or monocytes/macrophages are derived from a common myeloid progenitor through the coordinated action of hematopoietic cytokines. In this study, we explored the role of the Ca2+i signaling transduction pathway in the commitment of hematopoietic stem/progenitor cells to either the monocytic or granulocytic lineage in response to macrophage colony‐stimulating factor (M‐CSF) and granulocyte colony‐stimulating factor (G‐CSF). M‐CSF and G‐CSF induce cell expansion and monocyte or granulocyte differentiation, respectively, without affecting the percentage of hematopoietic progenitor cells. Colony‐forming units (CFUs) and flow cytometry demonstrated the involvement of phospholipase Cγ (PLCγ) and protein kinase C (PKC) in monocyte/granulocyte commitment. In addition, using flow cytometry and RNA interference, we identified PLCγ2 as the PLCγ isoform that participates in this cell expansion and differentiation. Differences in signaling elicited by M‐CSF and G‐CSF were observed. The M‐CSF‐related effects were associated with the activation of ERK1/2 and nuclear factor of activated T‐cells (NFAT); the inhibition of both molecules reduced the number of colonies in a CFU assay. In contrast, using flow cytometry and confocal evaluation, we demonstrated that G‐CSF activated Jak‐1 and STAT‐3. Additionally, the effects induced by G‐CSF were also related with the participation of Ca2+ calmodulin kinase II and the transcription factor PU.1. STAT‐3 activation and the increase of PU.1 expression were sensitive to PLC inhibition by U73122. These data show that PLCγ2 and PKC are important upstream signals that regulate myelopoiesis through cytokines, and differences in M‐CSF and G‐CSF downstream signaling were identified. J. Cell. Biochem. 115: 42–51, 2014. © 2013 Wiley Periodicals, Inc.
Learning Contextually Informed Representations for Linear-Time Discourse Parsing

Recent advances in RST discourse parsing have focused on two modeling paradigms: (a) high order parsers which jointly predict the tree structure of the discourse and the relations it encodes; or (b) linear-time parsers which are efficient but mostly based on local features. In this work, we propose a linear-time parser with a novel way of representing discourse constituents based on neural networks which takes into account global contextual information and is able to capture long-distance dependencies. Experimental results show that our parser obtains state-of-the art performance on benchmark datasets, while being efficient (with time complexity linear in the number of sentences in the document) and requiring minimal feature engineering.
Wide-Band Sensing and Optimization for Cognitive Radio Networks With Noise Variance Uncertainty

This paper considers wide-band spectrum sensing and optimization for cognitive radio (CR) networks with noise variance uncertainty. It is assumed that the considered wide-band contains one or more white sub-bands. Under this assumption, we consider throughput maximization of the CR network while appropriately protecting the primary network. We address this problem as follows. First, we propose novel ratio based test statistics for detecting the edges of each sub-band. Second, we employ simple energy comparison approach to choose one reference white sub-band. Third, we propose novel generalized energy detector (GED) for examining each of the remaining sub-bands by exploiting the noise information of the reference white sub-band. Finally, we optimize the sensing time (To) to maximize the CR network throughput using the detection and false alarm probabilities of the GED. The proposed GED does not suffer from signal to noise ratio (SNR) wall and outperforms the existing signal detectors. Moreover, the relationship between the proposed GED and conventional energy detector (CED) is quantified analytically. We show that the optimal To depends on the noise variance information. In particular, with 10TV bands, SNR = -20 dB and 2s frame duration, we found that the optimal To is 28.5 ms (50.6 ms) with perfect (imperfect) noise variance scenario.
Test strategies for cost-sensitive decision trees

In medical diagnosis, doctors must often determine what medical tests (e.g., X-ray and blood tests) should be ordered for a patient to minimize the total cost of medical tests and misdiagnosis. In this paper, we design cost-sensitive machine learning algorithms to model this learning and diagnosis process. Medical tests are like attributes in machine learning whose values may be obtained at a cost (attribute cost), and misdiagnoses are like misclassifications which may also incur a cost (misclassification cost). We first propose a lazy decision tree learning algorithm that minimizes the sum of attribute costs and misclassification costs. Then, we design several novel "test strategies" that can request to obtain values of unknown attributes at a cost (similar to doctors' ordering of medical tests at a cost) in order to minimize the total cost for test examples (new patients). These test strategies correspond to different situations in real-world diagnoses. We empirically evaluate these test strategies, and show that they are effective and outperform previous methods. Our results can be readily applied to real-world diagnosis tasks. A case study on heart disease is given throughout the paper
A Chemogenomic Screening of Sulfanilamide-Hypersensitive Saccharomyces cerevisiae Mutants Uncovers ABZ2, the Gene Encoding a Fungal Aminodeoxychorismate Lyase

ABSTRACT Large-scale phenotypic analyses have proved to be useful strategies in providing functional clues about the uncharacterized yeast genes. We used here a chemogenomic profiling of yeast deletion collections to identify the core of cellular processes challenged by treatment with the p-aminobenzoate/folate antimetabolite sulfanilamide. In addition to sulfanilamide-hypersensitive mutants whose deleted genes can be categorized into a number of groups, including one-carbon related metabolism, vacuole biogenesis and vesicular transport, DNA metabolic and cell cycle processes, and lipid and amino acid metabolism, two uncharacterized open reading frames (YHI9 and YMR289w) were also identified. A detailed characterization of YMR289w revealed that this gene was required for growth in media lacking p-aminobenzoic or folic acid and encoded a 4-amino-4-deoxychorismate lyase, which is the last of the three enzymatic activities required for p-aminobenzoic acid biosynthesis. In light of these results, YMR289w was designated ABZ2, in accordance with the accepted nomenclature. ABZ2 was able to rescue the p-aminobenzoate auxotrophy of an Escherichia coli pabC mutant, thus demonstrating that ABZ2 and pabC are functional homologues. Phylogenetic analyses revealed that Abz2p is the founder member of a new group of fungal 4-amino-4-deoxychorismate lyases that have no significant homology to its bacterial or plant counterparts. Abz2p appeared to form homodimers and dimerization was indispensable for its catalytic activity.
Modulation of Membrane Lipid Composition and Homeostasis in Salmon Hepatocytes Exposed to Hypoxia and Perfluorooctane Sulfonamide, Given Singly or in Combination

The relative importance of environmental hypoxia due to global climate change on organismal ability to adapt to chemical insult and/or mechanisms of these responses is not well understood. Therefore, we have studied the effects of combined exposure to perfluorooctane sulfonamide (PFOSA) and chemically induced hypoxia on membrane lipid profile and homeostasis. Primary salmon hepatocytes were exposed to PFOSA at 0, 25 and 50 µM singly or in combination with either cobalt chloride (CoCl2: 0 and 150 µM) or deferroxamine (DFO: 0 and 100 µM) for 24 and 48 h. CoCl2 and DFO were used to induce cellular hypoxia because these two chemicals have been commonly used in animal experiments for this purpose and have been shown to increase hypoxia-inducible factor 1-alpha (HIF-1α) and vascular endothelial growth factor (VEGF) levels. Fatty acid (FA) profiles were determined by GC-MS, while gene expression patterns were determined by quantitative PCR. Hypoxic condition was confirmed with time-related increases of HIF-1α mRNA levels in CoCl2 and DFO exposed cells. In general, significant alterations of genes involved in lipid homeostasis were predominantly observed after 48 h exposure. Gene expression analysis showed that biological responses related to peroxisome proliferation (peroxisome proliferator-activated receptors (PPARs) and acyl coenzyme A (ACOX)) and FA desaturation (Δ5- and Δ6-desaturases: FAD5 and FAD6, respectively) and elongation (FAE) were elevated slightly by single exposure (i.e. either PFOSA, CoCl2 or DFO exposure alone), and these responses were potentiated in combined exposure conditions. Principal component analysis (PCA) showed a clustering of peroxisome proliferation responses at transcript levels and FA desaturation against membrane FAs levels whose changes were explained by PFOSA and chemically induced hypoxia exposures. Overall, our data show that most of the observed responses were stronger in combined stressor exposure conditions, compared to individual stressor exposure. In general, our data show that hypoxia may, singly or in combination with PFOSA produce deleterious health, physiological and developmental consequences through the alteration of membrane lipid profile in organisms.
PIK3CA Mutations Frequently Coexist with EGFR/KRAS Mutations in Non-Small Cell Lung Cancer and Suggest Poor Prognosis in EGFR/KRAS Wildtype Subgroup

Purpose PIK3CA gene encoding a catalytic subunit of the phosphatidylinositol-3-kinase (PI3K) is mutated and/or amplified in various neoplasia, including lung cancer. Here we investigated PIK3CA gene alterations, the expression of core components of PI3K pathway, and evaluated their clinical importance in non-small cell lung cancer (NSCLC). Materials and methods Oncogenic mutations/rearrangements in PIK3CA, EGFR, KRAS, HER2, BRAF, AKT1 and ALK genes were detected in tumors from 1117 patients with NSCLC. PIK3CA gene copy number was examined by fluorescent in situ hybridization and the expression of PI3K p110 subunit alpha (PI3K p110α), p-Akt, mTOR, PTEN was determined by immunohistochemistry in PIK3CA mutant cases and 108 patients without PIK3CA mutation. Results PIK3CA mutation was found in 3.9% of squamous cell carcinoma and 2.7% of adenocarcinoma. Among 34 PIK3CA mutant cases, 17 tumors harbored concurrent EGFR mutations and 4 had KRAS mutations. PIK3CA mutation was significantly associated with high expression of PI3K p110α (p<0.0001), p-Akt (p = 0.024) and mTOR (p = 0.001), but not correlated with PIK3CA amplification (p = 0.463). Patients with single PIK3CA mutation had shorter overall survival than those with PIK3CA-EGFR/KRAS co-mutation or wildtype PIK3CA (p = 0.004). A significantly worse survival was also found in patients with PIK3CA mutations than those without PIK3CA mutations in the EGFR/KRAS wildtype subgroup (p = 0.043) Conclusions PIK3CA mutations frequently coexist with EGFR/KRAS mutations. The poor prognosis of patients with single PIK3CA mutation in NSCLC and the prognostic value of PIK3CA mutation in EGFR/KRAS wildtype subgroup suggest the distinct mutation status of PIK3CA gene should be determined for individual therapeutic strategies in NSCLC.
Scientific Discovery by Machine Intelligence: A New Avenue for Drug Research

The majority of big data is unstructured and of this majority the largest chunk is text. While data mining techniques are well developed and standardized for structured, numerical data, the realm of unstructured data is still largely unexplored. The general focus lies on information extraction, which attempts to retrieve known information from text. The Holy Grail, however is knowledge discovery, where machines are expected to unearth entirely new facts and relations that were not previously known by any human expert. Indeed, understanding the meaning of text is often considered as one of the main characteristics of human intelligence. The ultimate goal of semantic artificial intelligence is to devise software that can understand the meaning of free text, at least in the practical sense of providing new, actionable information condensed out of a body of documents. As a stepping stone on the road to this vision I will introduce a totally new approach to drug research, namely that of identifying relevant information by employing a self-organizing semantic engine to text mine large repositories of biomedical research papers, a technique pioneered by Merck with the InfoCodex software. I will describe the methodology and a first successful experiment for the discovery of new biomarkers and phenotypes for diabetes and obesity on the basis of PubMed abstracts, public clinical trials and Merck internal documents. The reported approach shows much promise and has potential to impact fundamentally pharmaceutical research as a way to shorten time-to-market of novel drugs, and for early recognition of dead ends.