Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterization of Quasispecies of Pandemic 2009 Influenza A Virus (A/H1N1/2009) by De Novo Sequencing Using a Next-Generation DNA Sequencer

Pandemic 2009 influenza A virus (A/H1N1/2009) has emerged globally. In this study, we performed a comprehensive detection of potential pathogens by de novo sequencing using a next-generation DNA sequencer on total RNAs extracted from an autopsy lung of a patient who died of viral pneumonia with A/H1N1/2009. Among a total of 9.4×106 40-mer short reads, more than 98% appeared to be human, while 0.85% were identified as A/H1N1/2009 (A/Nagano/RC1-L/2009(H1N1)). Suspected bacterial reads such as Streptococcus pneumoniae and other oral bacteria flora were very low at 0.005%, and a significant bacterial infection was not histologically observed. De novo assembly and read mapping analysis of A/Nagano/RC1-L/2009(H1N1) showed more than ×200 coverage on average, and revealed nucleotide heterogeneity on hemagglutinin as quasispecies, specifically at two amino acids (Gly172Glu and Gly239Asn of HA) located on the Sa and Ca2 antigenic sites, respectively. Gly239 and Asn239 on antigenic site Ca2 appeared to be minor amino acids compared with the highly distributed Asp239 in H1N1 HAs. This study demonstrated that de novo sequencing can comprehensively detect pathogens, and such in-depth investigation facilitates the identification of influenza A viral heterogeneity. To better characterize the A/H1N1/2009 virus, unbiased comprehensive techniques will be indispensable for the primary investigations of emerging infectious diseases.
Social media analysis for product safety using text mining and sentiment analysis

The growing incidents of counterfeiting and associated economic and health consequences necessitate the development of active surveillance systems capable of producing timely and reliable information for all stake holders in the anti-counterfeiting fight. User generated content from social media platforms can provide early clues about product allergies, adverse events and product counterfeiting. This paper reports a work in progress with contributions including: the development of a framework for gathering and analyzing the views and experiences of users of drug and cosmetic products using machine learning, text mining and sentiment analysis; the application of the proposed framework on Facebook comments and data from Twitter for brand analysis, and the description of how to develop a product safety lexicon and training data for modeling a machine learning classifier for drug and cosmetic product sentiment prediction. The initial brand and product comparison results signify the usefulness of text mining and sentiment analysis on social media data while the use of machine learning classifier for predicting the sentiment orientation provides a useful tool for users, product manufacturers, regulatory and enforcement agencies to monitor brand or product sentiment trends in order to act in the event of sudden or significant rise in negative sentiment.
Inhibition of Transporter-Mediated Hepatic Uptake as a Mechanism for Drug-Drug Interaction between Cerivastatin and Cyclosporin A

The mechanism involved in the clinically relevant drug-drug interaction (DDI) between cerivastatin (CER) and cyclosporin A (CsA) has not yet been clarified. In the present study, we examined the possible roles of transporter-mediated hepatic uptake in this DDI. The uptake of [14C]CER into human hepatocytes prepared from three different donors was examined. Kinetic analyses revealedK m values for the uptake of [14C]CER within the range of 3 to 18 μM, suggesting that more than 70% of the total uptake at therapeutic CER concentrations was accounted for by a saturable process, i.e., transporter-mediated uptake. This uptake was inhibited by CsA withK i values of 0.3 to 0.7 μM. The uptake of [14C]CER was also examined in human organic anion transporting polypeptide-2 (OATP2)-expressing Madin-Darby canine kidney cells (MDCKII). Saturable OATP2-mediated uptake of [14C]CER was observed and was also inhibited by CsA, with a K i value of 0.2 μM. These results suggest that the DDI between CER and CsA involves the inhibition of transporter-mediated uptake of CER and, at least in part, its OATP2-mediated uptake. The effect of CsA on the in vitro metabolism of [14C]CER was also examined. The metabolism of [14C]CER was inhibited by CsA with an IC50value of more than 30 μM. From these results, we conclude that the DDI between CER and CsA is mainly due to the inhibition of transporter (at least partly OATP2)-mediated uptake in the liver.
THE LYMPHATIC STATUS OF HAMSTER CHEEK POUCH TISSUE IN RELATION TO ITS PROPERTIES AS A GRAFT AND AS A GRAFT SITE

Hamster cheek pouch skin, transplanted to the side of an isogenic host's chest wall, retains its immunologically privileged status as evidenced by the prolonged survival of inlaid homografts of ordinary skin. Various findings sustain the premise that exemption from rejection by otherwise susceptible homografts in both intact pouch tissue and in established pouch skin isografts is due to an impediment in the afferent pathway of the immunologic reflex, i.e., to deficient lymphatic drainage. Although lymphatics were not apparent when dye was injected into pouch skin grafts or into grafts of ordinary skin sustained by them, lymph vessels were readily and consistently revealed by dye injected into intact trunk skin or established isografts of trunk skin. When suspensions of viable lymph node cells from specifically sensitized parental strain donors were injected superficially into either the intact skin or established grafts of normal skin on F1 hybrid hamsters, a striking hypertrophy of the regional lymph nodes occurred, due to graft-versus-host reactivity. However, similar cell suspensions inoculated into intact pouch tissue or into pouch skin grafts on F1 hamsters incited no regional lymphadenopathy, indicating the lack of appropriate pathways to the nodes. When skin homografts were inlaid eccentrically into pouch skin isografts, so that they were in contact with host skin at one edge, rejection occurred. Furthermore, rejection of long-established intrapouch skin homografts resulted if the hosts received: (a) small homografts of ordinary skin transplanted to conventional beds; (b) suspensions of donor strain pouch skin epidermal cells, injected intracutaneously; (c) lymph node cells from specifically sensitized donors of the same strain, i.e. adoptive immunization; or, (d) if a portion of the target homograft's perimeter was surgically approximated to body skin. Treatment of normal hamsters with two closely spaced pulses of ALS, although only marginally effective in prolonging the lives of homografts of trunk skin, enabled pouch skin homografts to survive for very long periods. The influence of this brief treatment with immunosuppressant was still demonstrable if challenge of hosts with the weakly immunogenic pouch skin homografts was delayed for 100 days.
Pressure-Discharge Law of Local Tanks Connected to a Water Distribution Network: Experimental and Mathematical Results

In many Mediterranean countries, users store water resources in private tanks, which are typically located on rooftops. These local reservoirs are generally connected directly to the water distribution network (WDN). This installation scheme causes a disconnection of the WDN from the users, and thus, the users’ water supply is no longer linked to their consumption, which changes the network operating conditions from the designed conditions. For WDNs characterized by the presence of several private tanks, specific models have to be developed to correctly simulate the operation of the WDN while accounting for reservoirs located between the hydraulic network and users. Some mathematical models that are able to reproduce the tank emptying/filling cycles have already been developed, which combine a tank continuity equation with a float valve emitter law. In the present work, a new emitter law is proposed that improves the predictability of actual models. The new formulation takes into account the variation of the emitter coefficient and of the discharge area during the phases of the filling process of private tanks. Specifically, hyperbolic tangent laws were adopted. A comparison between the proposed mathematical model and the experimental data demonstrated the ability of the new law to estimate the flow discharging into private tanks independently of the float valve branch and of the pressure in the network. The developed model can easily be implemented in hydrodynamic models to take private tanks into account.
Agent-based software engineering

The technology of intelligent agents and multi-agent systems is expected to alter radically the way in which complex, distributed, open systems are conceptualised and implemented. The paper considers the problem of building a multi-agent system as a software engineering enterprise. Three issues are focused on: how agents might be specified; how these specifications might be refined or otherwise transformed into efficient implementations: and how implemented agents and multi-agent systems might subsequently be verified, to show that they are correct with respect to their specifications. These issues are discussed with reference to a number of case studies. The paper concludes by setting out some issues and open problems for future research.
vav, a novel human oncogene derived from a locus ubiquitously expressed in hematopoietic cells.

A novel human oncogene, designated vav, was generated by a genetic rearrangement during gene transfer assays. The vav oncogene directs the synthesis of a 3.0 kb mRNA from which we isolated a 2.8 kb‐long complementary DNA copy. Nucleotide sequence analysis of this vav oncogene cDNA clone revealed that its 5′ 167 bp were derived from pSV2neo DNA cotransfected as a selectable marker during gene transfer. The remaining 2597 bp were unrelated to genes included in current data banks, indicating that the vav oncogene is likely to be derived from a novel human locus. The vav oncogene cDNA clone encompasses a 2391 bp long open reading frame (ORF) capable of directing the synthesis of a 797 amino acid long polypeptide. The predicted vav oncogene protein sequence exhibits several motifs reminiscent of transcriptional factors. They include a highly acidic amino‐terminal region separated from two putative nuclear localization signals by a proline‐rich sequence, presumably a hinge region. In addition, we identified two zinc‐finger‐like domains, one of which conforms to the canonical pattern Cys‐X2‐Cys‐X13‐Cys‐X2‐Cys previously found to confer trans‐activating activity to the adenovirus E1A protein. Transcription of its normal allele, the vav proto‐oncogene, has been exclusively observed in cells of hematopoietic origin, including those of erythroid, lymphoid and myeloid lineages. These findings raise the possibility that this novel locus might play an important role in hematopoiesis.
Performance analysis of MIMO maximum likelihood receivers with channel correlation, colored Gaussian noise, and linear prefiltering

We present an analytical performance evaluation of a Rayleigh fading MIMO link with matrix transmit prefiltering, channel correlation at transmitter and receiver, and spatially colored Gaussian noise for arbitrary two-dimensional signal constellations based on a tight union bound of the pairwise error probabilities. Asymptotic results for the high SNR region allow a simple characterization of the correlation effects and a quantification of the SNR penalty. It is shown that the diversity level of ML detection is unaffected by fading correlation and demonstrated that the effects of transmit and receive correlation may be assessed independently with the standard simplified channel model. Prefiltering algorithms based on long-term stable channel correlation characteristics are derived using the framework at hand. Simulations results illustrate the effectiveness of transmit prefilter designs based on the performance bound.
Roles of Long and Short Replication Initiation Proteins in the Fate of IncP-1 Plasmids

ABSTRACT Broad-host-range IncP-1 plasmids generally encode two replication initiation proteins, TrfA1 and TrfA2. TrfA2 is produced from an internal translational start site within trfA1. While TrfA1 was previously shown to be essential for replication in Pseudomonas aeruginosa, its role in other bacteria within its broad host range has not been established. To address the role of TrfA1 and TrfA2 in other hosts, efficiency of transformation, plasmid copy number (PCN), and plasmid stability were first compared between a mini-IncP-1β plasmid and its trfA1 frameshift variant in four phylogenetically distant hosts: Escherichia coli, Pseudomonas putida, Sphingobium japonicum, and Cupriavidus necator. TrfA2 was sufficient for replication in these hosts, but the presence of TrfA1 enhanced transformation efficiency and PCN. However, TrfA1 did not contribute to, and even negatively affected, long-term plasmid persistence. When trfA genes were cloned under a constitutive promoter in the chromosomes of the four hosts, strains expressing either both TrfA1 and TrfA2 or TrfA1 alone, again, generally elicited a higher PCN of an IncP1-β replicon than strains expressing TrfA2 alone. When a single species of TrfA was produced at different concentrations in E. coli cells, TrfA1 maintained a 3- to 4-fold higher PCN than TrfA2 at the same TrfA concentrations, indicating that replication mediated by TrfA1 is more efficient than that by TrfA2. These results suggest that the broad-host-range properties of IncP-1 plasmids are essentially conferred by TrfA2 and the intact replication origin alone but that TrfA1 is nonetheless important to efficiently establish plasmid replication upon transfer into a broad range of hosts.
Arousal Effect of Caffeine Depends on Adenosine A2A Receptors in the Shell of the Nucleus Accumbens

Caffeine, the most widely used psychoactive compound, is an adenosine receptor antagonist. It promotes wakefulness by blocking adenosine A2A receptors (A2ARs) in the brain, but the specific neurons on which caffeine acts to produce arousal have not been identified. Using selective gene deletion strategies based on the Cre/loxP technology in mice and focal RNA interference to silence the expression of A2ARs in rats by local infection with adeno-associated virus carrying short-hairpin RNA, we report that the A2ARs in the shell region of the nucleus accumbens (NAc) are responsible for the effect of caffeine on wakefulness. Caffeine-induced arousal was not affected in rats when A2ARs were focally removed from the NAc core or other A2AR-positive areas of the basal ganglia. Our observations suggest that caffeine promotes arousal by activating pathways that traditionally have been associated with motivational and motor responses in the brain.
Extracellular myocilin affects activity of human trabecular meshwork cells

The trabecular meshwork (TM), a specialized eye tissue, is a major site for regulation of the aqueous humor outflow. Malfunctioning of this tissue is believed to be responsible for development of glaucoma, a blinding disease. Myocilin is a gene linked to the most common form of glaucoma. The protein product has been localized to both intra and extracellular sites, but its function still remains unclear. This study was to determine whether extracellular myocilin presented in the matrix affects adhesion, morphology, and migratory and phagocytic activities of human TM cells in culture. Cell adhesion assays indicated that TM cells, while adhering readily on fibronectin, failed to attach on recombinant myocilin purified from bacterial cultures. Adhesion on fibronectin was also compromised by myocilin in a dose dependent manner. Myocilin in addition triggered TM cells to assume a stellate appearance with broad cell bodies and microspikes. Loss of actin stress fibers and focal adhesions was observed. TM cell migration on fibronectin/myocilin to scratched wounds was reduced compared to fibronectin controls. Myocilin, however, had little impact on phagocytic activities of TM cells. Cell attachment on fibronectin and migration of corneal fibroblasts, a control cell type, were not altered by myocilin. These results demonstrate that extracellular myocilin elicits anti‐adhesive and counter‐migratory effects on TM cells. Myocilin in the matrix of tissues could be exerting a similar influence on TM cells in vivo, impacting the flexibility and resilience required for maintenance of the normal aqueous outflow. © 2004 Wiley‐Liss, Inc.
Regulation of Energy Stores and Feeding by Neuronal and Peripheral CREB Activity in Drosophila

The cAMP-responsive transcription factor CREB functions in adipose tissue and liver to regulate glycogen and lipid metabolism in mammals. While Drosophila has a homolog of mammalian CREB, dCREB2, its role in energy metabolism is not fully understood. Using tissue-specific expression of a dominant-negative form of CREB (DN-CREB), we have examined the effect of blocking CREB activity in neurons and in the fat body, the primary energy storage depot with functions of adipose tissue and the liver in flies, on energy balance, stress resistance and feeding behavior. We found that disruption of CREB function in neurons reduced glycogen and lipid stores and increased sensitivity to starvation. Expression of DN-CREB in the fat body also reduced glycogen levels, while it did not affect starvation sensitivity, presumably due to increased lipid levels in these flies. Interestingly, blocking CREB activity in the fat body increased food intake. These flies did not show a significant change in overall body size, suggesting that disruption of CREB activity in the fat body caused an obese-like phenotype. Using a transgenic CRE-luciferase reporter, we further demonstrated that disruption of the adipokinetic hormone receptor, which is functionally related to mammalian glucagon and β-adrenergic signaling, in the fat body reduced CRE-mediated transcription in flies. This study demonstrates that CREB activity in either neuronal or peripheral tissues regulates energy balance in Drosophila, and that the key signaling pathway regulating CREB activity in peripheral tissue is evolutionarily conserved.
Significant variations in Weber fraction for changes in inter-onset interval of a click train over the range of intervals between 5 and 300 ms

It is a common psychophysical experience that a train of clicks faster than ca. 30/s is heard as one steady sound, whereas temporal patterns occurring on a slower time scale are perceptually resolved as individual auditory events. This phenomenon suggests the existence of two different neural mechanisms for processing of auditory sequences with fast and slow repetition rates. To test this hypothesis we used Weber’s law, which is known to be valid for perception of time intervals. Discrimination thresholds and Weber fractions (WFs) for 12 base inter-click intervals (ICIs) between 5 and 300 ms were measured from 10 normal hearing subjects by using an “up–down staircase” algorithm. The mean WF, which is supposed to be constant for any perceptual mechanism according to Weber’s law, displayed significant variation with click rate. WFs decreased sharply from an average value of around 5% at repetition rates below 20 Hz to about 0.5% at rates above 67 Hz. Parallel to this steep transition, subjects reported that at rates below 20 Hz they perceived periodicity as a fast tapping rhythm, whereas at rates above 50 Hz the perceived quality was a pitch. Such a dramatic change in WF indicated the existence of two separate mechanisms for processing the click rate for long and short ICIs, based on temporal and spectral features, respectively. A range of rates between 20 and 33 Hz, in which the rate discrimination threshold was maximum, appears to be a region where both of the presumed time and pitch mechanisms are relatively insensitive to rate alterations. Based on this finding, we speculate that the interval-based perception mechanism ceases to function at around 20 Hz and the spectrum-based mechanism takes over at around 33 Hz; leaving a transitional gap in between, where neither of the two mechanisms is as sensitive. Another notable finding was a significant drop in WF for ICI = 100 ms, suggesting a connection of time perception to the electroencephalography alpha rhythm.
Condition based maintenance model for a production deteriorating system

This paper addresses a condition based maintenance model taking into account both maintenance cost and production capacity aspects for a single unit production system whose condition is monitored by inspection relying on an aperiodic inspection schedule. In order to assess the performance of the proposed maintenance policy, maintenance cost per unit of product is introduced and calculated analytically. A numerical example of a multi state production system is finally introduced to illustrate the performance of the proposed policy, as well as the advantages of proposed evaluation approach.
Verification and Analysis of Self-Checking Properties through ATPG

Present and future semiconductor technologies are characterized by increasing parameters variations as well as an increasing susceptibility to external disturbances. Transient errors during system operation are no longer restricted to memories but also affect random logic, and a robust design becomes mandatory to ensure a reliable system operation. Self-checking circuits rely on redundancy to detect and compensate errors online. However, during synthesis and optimization self-checking properties can be destroyed. This paper shows how automatic test pattern generation (ATPG) can be used to analyze self-checking properties. As a result the properties are either verified or the fault detection profile provided by ATPG can be used to increase the error detection or fault tolerance capabilities of the design. Experimental data are shown for several self-checking arithmetic circuits.
Comparative evaluation of orthodontic bracket base shapes on shear bond strength and adhesive remnant index: An in vitro study

Background The objective of this study was to evaluate the effect of orthodontic bracket base shape on shear bond strength and adhesive remnant index. Material and Methods In this in vitro study using 140 bovine incisors, shear bond strength (SBS) of brackets with different base shapes (rectangle, flower, round, heart, diamond, star, and football) were measured with an Instron testing machine and tested until bond failure. Adhesive Remnant Index (ARI) scoring was evaluated after debonding to evaluate the location of bond failure. Descriptive and one-way ANOVA post-hoc Tukey statistical analyses were performed with a statistical significance set at p≤0.05. Results Statistically significant difference in mean SBS in Newtons was observed for multiple base shapes (p<0.05). The highest mean SBS (N ± SD) was observed in football and flower base shapes (73.83 N ± 53.46; 65.82 N ± 37.89 respectively); the lowest mean was observed with diamond and heart shapes (30.51 N ± 11.73; 33.28 N ± 16.89 respectively). When reported in Megaspascals, statistically significant difference was observed for rectangle base shape (3.54 MPa ± 2.69) when compared to all other base shapes. Conclusions Bracket base shape has an effect on SBS. Higher SBS (N) for rectangle, flower, and football base shape indicates even stress distributions throughout the bracket base. Base shape with a pronounced converging tip over the axial plane may contribute to the reduction in SBS due to increased peak stress concentration resulting in bond failure. Key words:Shaped brackets, Shear bond strength, Adhesive remnant index, WildSmiles®.