Miracle-dz/UniFAR-FTUs huggingface dataset:
Recombinant Adeno-Associated Virus Utilizes Cell-Specific Infectious Entry Mechanisms

ABSTRACT Understanding the entry and trafficking mechanism(s) of recombinant adeno-associated virus (rAAV) into host cells can lead to evolution in capsid and vector design and delivery methods, resulting in enhanced transduction and therapeutic gene expression. Variability of findings regarding the early entry pathway of rAAV supports the possibility that rAAV, like other viruses, can utilize more than one infectious entry pathway. We tested whether inhibition of macropinocytosis impacted rAAV transduction of HeLa cells compared to hepatocellular carcinoma cell lines. We found that macropinocytosis inhibitor cytochalasin D blocked rAAV transduction of HeLa cells (>2-fold) but enhanced (10-fold) transduction in HepG2 and Huh7 lines. Similar results were obtained with another macropinocytosis inhibitor, 5-(N-ethyl-N-isopropyl) amiloride (EIPA). The augmented transduction was due to neither viral binding nor promoter activity, affected multiple rAAV serotypes (rAAV2, rAAV2-R585E, and rAAV8), and influenced single-stranded and self-complementary virions to comparable extents. Follow-up studies using CDC42 inhibitor ML141 and p21-activated kinase 1 (PAK1) siRNA knockdown also resulted in enhanced HepG2 transduction. Microscopy revealed that macropinocytosis inhibition correlated with expedited nuclear entry of the rAAV virions into HepG2 cells. Enhancement of hepatocellular rAAV transduction extended to the mouse liver in vivo (4-fold enhancement) but inversely blocked heart tissue transduction (13-fold). This evidence of host cell-specific rAAV entry pathways confers a potent means for controlling and enhancing vector delivery and could help unify the divergent accounts of rAAV cellular entry mechanisms. IMPORTANCE There is a recognized need for improved rAAV vector targeting strategies that result in delivery of fewer total particles, averting untoward toxicity and/or an immune response against the vector. A critical step in rAAV transduction is entry and early trafficking through the host cellular machinery, the mechanisms of which are under continued study. However, should the early entry and trafficking mechanisms of rAAV differ across virus serotype or be dependent on host cell environment, this could expand our ability to target particular cells and tissue for selective transduction. Thus, the observation that inhibiting macropinocytosis leads to cell-specific enhancement or inhibition of rAAV transduction that extends to the organismic level exposes a new means of modulating vector targeting.
Why Does Trust Mediate the Effects of Ethical and Authentic Leadership in Korean Firms

Walumbwa et al. (2008) conducted research into the positive and direct effects of ethical and authentic leadership on organizational outcomes using a student sample in the United States. However, the study hypothesizes that in a non-American context within Korean firms, no direct relationship exists between the two leadership styles and organizational outcomes. This is due to the unique culture of Korea where trust is based on private networks such as regional, school, and blood ties. The results show that both leadership styles are only effective when they are mediated by followers’ trust. The results imply that the achievement of leadership requires more than the authenticity of the leader, rendering support for Eagly’s (2005) suggestion that authenticity is a relational concept.
Execution of benchmarking 2 D partitioning FPMs FuPerMod tool Process layout Benchmark code Load-balanced data partition

Heterogeneous systems composed of CPUs and accelerators sharing communication channels of different performance are getting mainstream in HPC but, at the same time, they show a complexity that makes it difficult to optimize the deployment of a data parallel application. Recent analytical tools such as Functional Performance Models, combined with advanced partitioning algorithms, manage to achieve a balanced configuration by distributing the workload unevenly, according to the performance of the different processing units. Unfortunately, such uneven distribution of the computation load leads to communication unbalances that, very often, render worthless the previous workload balancing efforts. Finding the optimal communication scheme without expensive testing on the executing platform requires an analytical approach to the estimation of the communication cost of different configurations of the application. With this goal in mind, we propose and discuss an extension of the τ–Lop communication performance model to cover heterogeneous architectures. In order to provide a quantitative assessment of this extended model, we conduct experiments with two representative computational kernels, the SUMMA algorithm and the 2D wave equation solver. The τ–Lop predictions are compared against the HLogGP model and the observed costs for a variety of configurations, hardware resources and problem sizes.
Protein folds and families: sequence and structure alignments

Dali and HSSP are derived databases organizing protein space in the structurally known regions. We use an automatic structure alignment program (Dali) for the classification of all known 3D structures based on all-against-all comparison of 3D structures in the Protein Data Bank. The HSSP database associates 1D sequences with known 3D structures using a position-weighted dynamic programming method for sequence profile alignment (MaxHom). As a result, the HSSP database not only provides aligned sequence families, but also implies secondary and tertiary structures covering 36% of all sequences in Swiss-Prot. The structure classification by Dali and the sequence families in HSSP can be browsed jointly from a web interface providing a rich network of links between neighbours in fold space, between domains and proteins, and between structures and sequences. In particular, this results in a database of explicit multiple alignments of protein families in the twilight zone of sequence similarity. The organization of protein structures and families provides a map of the currently known regions of the protein universe that is useful for the analysis of folding principles, for the evolutionary unification of protein families and for maximizing the information return from experimental structure determination. The databases are available from http://www.embl-ebi.ac. uk/dali/
PosterVote: expanding the action repertoire for local political activism

Online and digital technologies support and extend the action repertoires of localized social movements. In this paper we examine the ways by which digital technologies can support "on-the-ground" activist communities in the development of social movements. After identifying some of the challenges of deploying conventional voting and consultation technologies for activism, we examine situated political action in local communities through the design and deployment of a low-cost community voting prototype, PosterVote. We deploy PosterVote in two case studies with two local community organizations identifying the features that supported or hindered grassroots democratic practices. Through interviews with these communities, we explore the design of situated voting systems to support participation within an ecology of social action.
Allo-limbal transplantation in patients with limbal stem cell deficiency

AIM To report the outcome of a series of patients with stem cell deficiency who underwent allo-limbal transplantation and to describe a technique for this procedure. METHODS Six consecutive patients underwent allo-limbal stem cell transplantation. The primary diagnosis included alkali burn (n=2), trachoma (n=1), chronic rosacea blepharitis and keratoconjunctivitis (n=1), aniridia (n=1), and Stevens–Johnson syndrome (n=1). The limbal rim consisted of peripheral cornea and perilimbal sclera. FK-506 was used postoperatively for immunosuppression. RESULTS The length of follow up ranged from 3 to 24 months (mean follow up 11.8 (SD 9.3) months). The outcome was considered satisfactory in five of six cases. The corneal surface was completely epithelialised within 2 weeks, and there was a substantial improvement in vision and symptoms. One patient had recurrent epithelial defects related to eyelid abnormalities. No side effects associated with systemic immunosuppression were noted. CONCLUSION Allo-limbal transplantation, with systemic immunosuppression with FK-506 is useful in reconstruction of the ocular surface with improvement in vision in patients with severe stem cell deficiency.
Theory of Mind in Children with Traumatic Brain Injury – CORRIGENDUM

In the article ‘‘Theory of Mind in Children with Traumatic Brain Injury’’, by Dennis et al., 2012, the description of participants in the study was inaccurate as published. In the description of inclusion/exclusion criteria for the studies of social outcomes in children with TBI, all of our participants were at least 12 months post injury when they participated (not 6 months post injury as was written), and they were up to 63 months post-injury when they completed Visit 1 (not 48 months as written). The authors regret the error.
Two transpallidal pathways originating in the rat nucleus accumbens

The striatopallidal projection originating in the nucleus accumbens was investigated by using anterograde transport of PHA‐L in combination with peptide immunohistochemistry in order to localize the injection sites and transported lectin with respect to neurochemically defined subterritories in the nucleus accumbens and subcommissural ventral pallidum. The results reported here supplement our previous observations, which indicated that the subcommissural ventral pallidum of the rat comprises two immunohistochemically defined subterritories (Zahm and Heimer, '88: J. Comp. Neurol., 272:516–535) which give rise to dichotomous downstream projection systems (Zahm, '89: Neuroscience, 30:33–50). The present data indicate that the neurotensin immunoreactivity‐rich ventromedial district of ventral pallidum receives its accumbal input almost exclusively from the shell district of the nucleus accumbens. The accumbal core, alternatively, projects to the dorsolateral ventral pallidal subterritory that lacks appreciable neurotensin immunoreactivity and in many other respects more resembles the adjoining striatopallidal components of the caudate‐putamen. In addition to direct topographic relationships in the frontal plane among the accumbal injection sites and ventral pallidal terminations, it was observed that more caudally placed core injections resulted in patches of striatopallidal terminations that were more caudally located in ventral pallidum. Shell injections, in contrast, produced columns of terminations that extended continuously from the rostralmost level that they appeared to the caudal end of ventromedial ventral pallidum. The accumbal shell, its exclusive projection to the ventromedial subterritory in the subcommissural ventral pallidum, and the previously reported, almost exclusive projection of that pallidal subdistrict to the mesencephalic ventral tegmental area are discussed in terms of a number of other neurochemical and hodological features that serve to distinguish them sufficiently to suggest that they represent a uniquely specialized part of the basal ganglia.
Novel IRF6 Mutations Detected in Orofacial Cleft Patients by Targeted Massively Parallel Sequencing

Common variants in interferon regulatory factor 6 (IRF6) have been associated with nonsyndromic cleft lip with or without cleft palate (NSCL/P) as well as with tooth agenesis (TA). These variants contribute a small risk towards the 2 congenital conditions and explain only a small percentage of heritability. On the other hand, many IRF6 mutations are known to be a monogenic cause of disease for syndromic orofacial clefting (OFC). We hypothesize that IRF6 mutations in some rare instances could also cause nonsyndromic OFC. To find novel rare variants in IRF6 responsible for nonsyndromic OFC and TA, we performed targeted multiplex sequencing using molecular inversion probes (MIPs) in 1,072 OFC patients, 67 TA patients, and 706 controls. We identified 3 potentially pathogenic de novo mutations in OFC patients. In addition, 3 rare missense variants were identified, for which pathogenicity could not unequivocally be shown, as all variants were either inherited from an unaffected parent or the parental DNA was not available. Retrospective investigation of the patients with these variants revealed the presence of lip pits in one of the patients with a de novo mutation suggesting a Van der Woude syndrome (VWS) phenotype, whereas, in other patients, no lip pits were identified.
Propagation-based social-aware multimedia content distribution

Online social networks have reshaped how multimedia contents are generated, distributed, and consumed on today's Internet. Given the massive number of user-generated contents shared in online social networks, users are moving to directly access these contents in their preferred social network services. It is intriguing to study the service provision of social contents for global users with satisfactory quality of experience. In this article, we conduct large-scale measurement of a real-world online social network system to study the social content propagation. We have observed important propagation patterns, including social locality, geographical locality, and temporal locality. Motivated by the measurement insights, we propose a propagation-based social-aware delivery framework using a hybrid edge-cloud and peer-assisted architecture. We also design replication strategies for the architecture based on three propagation predictors designed by jointly considering user, content, and context information. In particular, we design a propagation region predictor and a global audience predictor to guide how the edge-cloud servers backup the contents, and a local audience predictor to guide how peers cache the contents for their friends. Our trace-driven experiments further demonstrate the effectiveness and superiority of our design.
Maternal antibody decay and antibody‐mediated immune responses in chicken pullets fed prebiotics and synbiotics

&NA; Three experiments were conducted to evaluate the effect of yeast‐derived carbohydrates (YDC), and a blend of probiotics and YDC (synbiotic, SNB) on serum IgG concentration, maternal‐derived antibody (MDA) decay, and specific antibody‐mediated immune response in chick pullets following immunization with T‐cell dependent antigens. A total of 300 day‐old pullet chicks were randomly assigned to 3 dietary treatments including: a basal diet (Control), and diets containing YDC, and SNB (Lactobacillus acidophilus, L. casei, Streptococcus faecium, and Bacillus subtilis, and YDC). In experiment one, on d 1 and wk 3, 4, 5, and 6, blood samples were collected and serum were analyzed by ELISA for total IgG (Y), and MDA against Newcastle disease virus (NDV) and infectious bursal disease virus (IBDV). The second experiment examined the specific antibody against infectious bronchitis virus (IBV) in pullet chicks following vaccination against IBV at d 1. Finally, in experiment 3, on d 21 and 28 posthatch, 10 birds per treatment were immunized intramuscularly with both sheep red blood cells (SRBC) and bovine serum albumin (BSA), and 11 after immunization serum samples were analyzed by hemagglutination assay for antibody response to SRBC, and by ELISA for serum IgM and IgG response to BSA. The results demonstrated that diet containing SNB increased serum IgG at wk 3 posthatch. However, the decay rate of MDA against NDV and IBDV were not affected by dietary treatments. Birds fed YDC showed higher specific antibody response against IBV in wk 4, while both diets containing YDC and SNB decreased antibody response to IBV in wk 6. In addition, specific antibody response against SRBC and BSA was not affected by diets. In conclusion, supplementation of diet with SNB improved humoral immunity by increasing IgG concentration in serum, and modulated the adaptive antibody‐mediated immune response against IBV.
Vitamin E derivative packs anticancer punch.

WHILE VITAMIN E’S ANTIOXIdant properties suggest that it may provide potential health benefits, there are conflicting findings about the medicinal value of vitamin E supplementation beyond the recommended daily allowance. Scientists have found, for example, that the nutrient has potential to benefit the immune system and prevent various diseases, but taking high doses also increase risks for bleeding problems. Now, in new work that has yielded information adding weight to the positive side of vitamin E’s balance sheet, researchers have discovered how a derivative of vitamin E can kill cancer cells and have used the information to make the derivative better (Shiau CW et al. J Biol Chem. 2006; 281:11819-11825). “We found a mode of mechanism for this [killing], and based on this, we were able to improve the potency and make the derivative a stronger agent,” said principal investigator Ching-Shih Chen, PhD, of The Ohio State University, in Columbus. The findings could be useful for the treatment of cancer and could offer insights into ways to improve the effectiveness of therapeutic agents in general.
Feedback inhibition of action potential discharge by endogenous adenosine enhancement of the medium afterhyperpolarization

Phasic activity in supraoptic nucleus vasopressin neurones is characterized by alternating periods of activity (bursts) and silence. During bursts, activation of a medium afterhyperpolarization induces spike frequency adaptation. Antagonism of A1 adenosine receptors within the supraoptic nucleus decreases spike frequency adaptation and prolongs phasic bursts in vivo, indicating that endogenous adenosine contributes to spike frequency adaptation. Here we used sharp electrode intracellular recordings from supraoptic nucleus neurones in hypothalamic explants to show that endogenous adenosine increases medium afterhyperpolarization amplitude to enhance spike frequency adaptation during phasic bursts. Superfusion of the A1 receptor antagonist 8‐cyclopentyl‐1,3‐dimethylxanthine (CPT, 10 μm) increased intraburst firing rate of phasic neurones (by 2.0 ± 0.7 spikes s−1, P= 0.03) and burst duration (by 141 ± 113 s, P= 0.03). The CPT‐induced increase in intraburst firing rate developed over the first few seconds of firing and persisted thereafter. In a separate series of experiments, CPT reduced the amplitude of the medium afterhyperpolarization evoked by a 1 s 20 Hz spike train (by 0.8 ± 0.3 mV, P < 0.001) in supraoptic nucleus neurones; this inhibition was not prevented by 3 mm CsCl (0.8 ± 0.1 mV decrease, P < 0.01) to block the afterdepolarization (which overlaps temporally with the medium afterhyperpolarization). In the presence of apamin to block the medium afterhyperpolarization, CPT did not alter afterdepolarization amplitude. Taken together, these data show that endogenous adenosine enhances medium afterhyperpolarization amplitude to contribute to spike frequency adaptation in phasic supraoptic nucleus neurones.
A HYBRID GENETIC ALGORITHM FOR OPTICAL ORTHOGONAL CODE CONSTRUCTION

Optical orthogonal codes (OOCs) are used to uniquely identify stations within an optical code division multiple access (CDMA) local area network (LAN). Previous efforts in constructing OOCs have focused on the use of deterministic techniques, which relied heavily on the use of Galois fields. These techniques severely restrict the availability of the resulting OOCs. This paper considers an evolutionary approach by proposing a hybrid genetic algorithm (hGA) as a flexible technique to construct OOCs. This hGA uses the simulated annealing (SA) method to generate its initial population. The effectiveness of the proposed hGA for OOC construction is demonstrated in two stages. First, we show that the SA-generated initial population is better than the randomly generated initial population in terms of fitness. Due to this, the hGA is able to converge on average two times faster compared to the use of the GA-only scheme. Second, we compare the code availability and performance of the hGA-constructed OOCs (hGA OOCs) against that of three other OOCs. Through these comparisons, we show why the proposed hGA is a more flexible technique for constructing OOCs with higher availability and better performance.
An algorithm for reactive batch sequencing

The specifics of process manufacturing have a great influence on a production management and the focus of production scheduling is to maintain stable production within given constraints. The paper presents a dedicated online algorithm that has been developed with the intention of predicting the adequate starting time for a single new batch in a system consisting of two chemical reactors sharing a common discharge vessel. The validation of the achieved results, derived from the algorithm testing, shows that the proposed algorithm can significantly contribute to more stable production and can efficiently deal with the no-wait constraints and the non-uniformity of batch durations of the real case study process
A Price-Based Negotiation Mechanism for Distributed Collaborative Design

With an increased focus on collaborative design for success in global markets, there is a need for a negotiation mechanism for designs distributed over autonomous stakeholders. This paper utilizes the unit price of the design variables as a medium for negotiation between autonomous and self-interested design participants represented by design agents (DAs). An artificial agent - the facilitator agent (FA), maximizes the overall utility of the design as a function of the prices of the design variables, and guides the design toward global feasibility. By relating the FA's price space to the DAs' design space through price-variable curves, a negotiation platform is developed and tested.
Sensor based coaching for a fit and healthy society

With decreasing strenuosity and increasing sedentariness in today's life styles, combined with excessive food intake, the modern society is at a brink of major health concerns like obesity, diabetes and high blood pressure. An ageing society increases this further with millions worldwide forecasted to suffer from the health issues. The biggest challenge thus faced by the health industry is how to motivate people to not only start, but also stick to a healthy life style, including sufficient physical exercise or sports. Our research explores capturing and analyzing physical, psychological, and social health variables via smart phones, and providing feedback to improve adherence to a healthy life style. We also make the feedback personalized and real-time.
Managing and Analysing Software Product Line Requirements

Modelling software product line (SPL) features plays a crucial role to a successful development of SPL. Feature diagram is one of the widely used notations to model SPL variants. However, there is a lack of precisely defined formal notations for representing and verifying such models. This paper presents an approach that we adopt to model SPL variants by using UML and subsequently verify them by using first-order logic. UML provides an overall modelling view of the system. First-order logic provides a precise and rigorous interpretation of the feature diagrams. We model variants and their dependencies by using propositional connectives and build logical expressions. These expressions are then validated by the Alloy verification tool. The analysis and verification process is illustrated by using Computer Aided Dispatch (CAD) system.