Miracle-dz/UniFAR-FTUs huggingface dataset:
A Novel Substrate-Based HIV-1 Protease Inhibitor Drug Resistance Mechanism

Background HIV protease inhibitor (PI) therapy results in the rapid selection of drug resistant viral variants harbouring one or two substitutions in the viral protease. To combat PI resistance development, two approaches have been developed. The first is to increase the level of PI in the plasma of the patient, and the second is to develop novel PI with high potency against the known PI-resistant HIV protease variants. Both approaches share the requirement for a considerable increase in the number of protease mutations to lead to clinical resistance, thereby increasing the genetic barrier. We investigated whether HIV could yet again find a way to become less susceptible to these novel inhibitors. Methods and Findings We have performed in vitro selection experiments using a novel PI with an increased genetic barrier (RO033-4649) and demonstrated selection of three viruses 4- to 8-fold resistant to all PI compared to wild type. These PI-resistant viruses did not have a single substitution in the viral protease. Full genomic sequencing revealed the presence of NC/p1 cleavage site substitutions in the viral Gag polyprotein (K436E and/or I437T/V) in all three resistant viruses. These changes, when introduced in a reference strain, conferred PI resistance. The mechanism leading to PI resistance is enhancement of the processing efficiency of the altered substrate by wild-type protease. Analysis of genotypic and phenotypic resistance profiles of 28,000 clinical isolates demonstrated the presence of these NC/p1 cleavage site mutations in some clinical samples (codon 431 substitutions in 13%, codon 436 substitutions in 8%, and codon 437 substitutions in 10%). Moreover, these cleavage site substitutions were highly significantly associated with reduced susceptibility to PI in clinical isolates lacking primary protease mutations. Furthermore, we used data from a clinical trial (NARVAL, ANRS 088) to demonstrate that these NC/p1 cleavage site changes are associated with virological failure during PI therapy. Conclusions HIV can use an alternative mechanism to become resistant to PI by changing the substrate instead of the protease. Further studies are required to determine to what extent cleavage site mutations may explain virological failure during PI therapy.
The Association between Urine Albumin to Creatinine Ratio and Osteoporosis in Postmenopausal Women with Type 2 Diabetes

Background Osteoporosis is a progressive bone disease that is characterized by a decrease in bone mass density and destruction of microstructure, which can lead to an increased risk of fracture. Although many studies have been published about the relationship between end-stage renal disease and osteoporosis, research on the relationship between proteinuria and the prevalence of osteoporosis is still lacking. Methods We assessed 91 postmenopausal women with type 2 diabetes who visited our hospital from January 2009 to January 2012. Results Among 91 patients, the prevalence of osteoporosis and osteopenia was 35.2% (32 cases) and 32.9% (30 cases) according to bone mineral density. The patients with microalbuminuria and macroalbuminuria (urine albumin-to-creatinine ratio [UACR] ≥ 30) had a significantly higher incidence of osteoporosis compared to subjects with normoalbuminuria (P<0.05). Conclusions This study indicates that UACR may be a useful biomarker for increased risk of osteoporosis in postmenopausal women with type 2 diabetes who have been linked to higher UACR levels.
Design, validation, and reliability of an observational instrument for ball possessions in rugby union

The purpose of this paper was to design and validate an observational instrument to analyse ball possessions in rugby union. The instrument design and validation was done in six stages. The first and second stages had the objective of designing the observational instrument, a category system. In the third and fourth stages, the content validity was established and calculated. In the fifth stage, the instrument’s reliability was tested. In the sixth stage, the observers used and applied the designed instrument. The number of experts that participated in the present study was 56 coaches. The final instrument included 99 behaviours for observation. Sixty were related to the initial phase, 14 were related to the game phase, and 25 were related to the end phase. Since all variables had an Aikeńs V greater than 0.85, they were pertinent. This instrument design is valid and reliable for describing ball possessions in rugby and also for differentiating winning and losing technical and tactical performances. It allows for the analysis of the performance of rugby teams from a technical and tactical perspective.
A comparison of lookahead and algorithmic blocking techniques for parallel matrix factorization

In this paper, we analyse and compare the techniques of algorithmic blocking and (storage blocking with) lookahead for distributed memory LU, LLT and QR factorizations. Concepts and some useful properties of a simpli ed model of lookahead are explored, including the minimal degree of lookahead required for optimal performance. Issues in the implementation of lookahead are discussed, which are more involved for the cases of LLT and QR factorizations. It is also explained how hybrid algorithmic blocking and lookahead techniques can be implemented. Implications for parallel linear algebra library design are also discussed. Results are given on the Fujitsu AP1000 and AP+ multicomputers, which have relatively high communication to computation to speeds. The results indicate that both methods are superior to storage blocking (without lookahead). They also indicate that for such machines, the hybrid method is optimal for smaller matrices, due to savings in communication startups. For larger matrices, algorithmic blocking gave the best performance, due to its better load balancing properties. An exception was LLT for the AP+, where lookahead alone gave comparable or better performance for larger matrix sizes as well. Performance models, predicting the minimummatrix size where lookahead becomes e ective, indicate this trend can be expected for machines with lower communication to computation speeds, but that the range for where lookahead is superior is extended.
VRSync: Characterizing and eliminating synchronization-induced voltage emergencies in many-core processors

Power consumption is a primary concern for microprocessor designers. Lowering the supply voltage of processors is one of the most effective techniques for improving their energy efficiency. Unfortunately, low-voltage operation faces multiple challenges going forward. One such challenge is increased sensitivity to voltage fluctuations, which can trigger so-called “voltage emergencies” that can lead to errors. These fluctuations are caused by abrupt changes in power demand, triggered by processor activity variation as a function of workload. This paper examines the effects of voltage fluctuations on future many-core processors. With the increase in the number of cores in a chip, the effects of chip-wide activity fluctuation - such as that caused by global synchronization in multithreaded applications - overshadow the effects of core-level workload variability. Starting from this observation, we developed VRSync, a novel synchronization methodology that uses emergency-aware scheduling policies that reduce the slope of load fluctuations, eliminating emergencies. We show that VRSync is very effective at eliminating emergencies, allowing voltage guardbands to be significantly lowered, which reduces energy consumption by an average of 33%.
Establishment of HSV1 Latency in Immunodeficient Mice Facilitates Efficient In Vivo Reactivation

The establishment of latent infections in sensory neurons is a remarkably effective immune evasion strategy that accounts for the widespread dissemination of life long Herpes Simplex Virus type 1 (HSV1) infections in humans. Periodic reactivation of latent virus results in asymptomatic shedding and transmission of HSV1 or recurrent disease that is usually mild but can be severe. An in-depth understanding of the mechanisms regulating the maintenance of latency and reactivation are essential for developing new approaches to block reactivation. However, the lack of a reliable mouse model that supports efficient in vivo reactivation (IVR) resulting in production of infectious HSV1 and/or disease has hampered progress. Since HSV1 reactivation is enhanced in immunosuppressed hosts, we exploited the antiviral and immunomodulatory activities of IVIG (intravenous immunoglobulins) to promote survival of latently infected immunodeficient Rag mice. Latently infected Rag mice derived by high dose (HD), but not low dose (LD), HSV1 inoculation exhibited spontaneous reactivation. Following hyperthermia stress (HS), the majority of HD inoculated mice developed HSV1 encephalitis (HSE) rapidly and synchronously, whereas for LD inoculated mice reactivated HSV1 persisted only transiently in trigeminal ganglia (Tg). T cells, but not B cells, were required to suppress spontaneous reactivation in HD inoculated latently infected mice. Transfer of HSV1 memory but not OVA specific or naïve T cells prior to HS blocked IVR, revealing the utility of this powerful Rag latency model for studying immune mechanisms involved in control of reactivation. Crossing Rag mice to various knockout strains and infecting them with wild type or mutant HSV1 strains is expected to provide novel insights into the role of specific cellular and viral genes in reactivation, thereby facilitating identification of new targets with the potential to block reactivation.
Selection of 3′-Template Bases and Initiating Nucleotides by Hepatitis C Virus NS5B RNA-Dependent RNA Polymerase

ABSTRACT De novo RNA synthesis by hepatitis C virus (HCV) nonstructural protein 5B (NS5B) RNA-dependent RNA polymerase has been investigated using short RNA templates. Various templates including those derived from the HCV genome were evaluated by examining the early steps of de novo RNA synthesis. NS5B was shown to be able to produce an initiation dinucleotide product from templates as short as 4-mer and from the 3′-terminal sequences of both plus and minus strands of the HCV RNA genome. GMP, GDP, and guanosine were able to act as an initiating nucleotide in de novo RNA synthesis, indicating that the triphosphate moiety is not absolutely required by an initiating nucleotide. Significant amounts of the initiation product accumulated in de novo synthesis, and elongation from the dinucleotide was observed when large amounts of dinucleotide were available. This result suggests that NS5B, a template, and incoming nucleotides are able to form an initiation complex that aborts frequently by releasing the dinucleotide product before transition to an elongation complex. The transition is rate limiting. Furthermore, we discovered that the secondary structure of a template was not essential for de novo initiation and that 3′-terminal bases of a template conferred specificity in selection of an initiation site. Initiation can occur at the +1, +2, or +3 position numbered from the 3′ end of a template depending on base composition. Pyrimidine bases at any of the three positions are able to serve as an initiation site, while purine bases at the +2 and +3 positions do not support initiation. This result implies that HCV possesses an intrinsic ability to ensure that de novo synthesis is initiated from the +1 position and to maintain the integrity of the 3′ end of its genome. This assay system should be an important tool for investigating the detailed mechanism of de novo initiation by HCV NS5B as well as other viral RNA polymerases.
Leadership, learning and human resource management The meanings of social entrepreneurship today

AbstractPurpose – Aims to explore the historical development and current usages of the concept of socialentrepreneurship.Design/methodology/approach – The paper ﬁrst examines the socio-political conditions leading tobusiness repositioning in the traditionally governmental role of catering to the ﬁnancial needs of civilsociety.It then reviews severalmodelsof socialentrepreneurship andtheleaders whohave emergedassocial entrepreneurs within those frameworks.Findings – In discussion the paper questions some of the motives of social entrepreneurs and warnsagainst uncritical acceptance of a blurring of the boundaries between sectors of society.Research limitations/implications – This is a theoretical paper. Follow-up research will examine indetail case studies of social entrepreneurship.Originality/value – Social entrepreneurship is a new and rapidly rising ﬁeld of practice that is, as yet,under-researched. This paper synthesizes the limited yet diverse current literature on socialentrepreneurship. It also offers a critical perspective that needs to be taken into account before thepractice is accepted as a common-sense salve to social difﬁculties. Keywords Entrepreneurialism, Privatization, LeadershipPaper type General review
Evaluating anticipatory grief as a moderator of life and marital satisfaction for spousal caregivers of individuals with dementia

ABSTRACT It is important to understand the role that anticipatory grief may have in moderating the interaction between relationship quality and marital and life satisfaction to help improve the awareness among professionals when identifying challenges individuals may experience while providing care to their romantic partner. This awareness may then lead to new ways of providing education or intervention to caregivers that may result in higher quality of care to individuals with dementia. The purpose of this study was to provide increasing awareness by evaluating the moderating role of anticipatory grief between perceptions of the relationship and marriage and life satisfaction. The sample of this study consisted of 90 spousal caregivers of individuals with dementia. Multiple regression was used and it was found that attachment and perceived closeness significantly predict satisfaction with life and marriage. Tests of moderation did not demonstrate that anticipatory grief served as a moderator for marital satisfaction or life satisfaction. The findings from the study provide information related to informing and structuring interventions and psychoeducation activities for spousal caregivers.
The Word Frequency Effect in Word Processing: An Updated Review

The word frequency effect refers to the observation that high-frequency words are processed more efficiently than low-frequency words. Although the effect was first described over 80 years ago, in recent years it has been investigated in more detail. It has become clear that considerable quality differences exist between frequency estimates and that we need a new standardized frequency measure that does not mislead users. Research also points to consistent individual differences in the word frequency effect, meaning that the effect will be present at different word frequency ranges for people with different degrees of language exposure. Finally, a few ongoing developments point to the importance of semantic diversity rather than mere differences in the number of times words have been encountered and to the importance of taking into account word prevalence in addition to word frequency.
Nonlinear control of a nonholonomic free joint manipulator with the averaging method

In our previous work, we analyzed nonlinear behaviours of a 2DOF free-joint manipulator with a periodic input and developed a positioning of the both joints by modulating the amplitude of the input. The strategy was effective but very heuristic and cannot be applied to other systems. In this paper, we apply the averaging method to the system and derive its behaviour from the averaged system. We also discuss its feedback control and design a feedback stabilization to a desired manifold. Even though its concept is the same as in Suzuki et al. (1996), the control strategy is analytically constructed. The feedback control is designed by a Lyapunov function for the averaged system and it is also effective for the real system.
Synaptobrevin I mediates exocytosis of CGRP from sensory neurons and inhibition by botulinum toxins reflects their anti-nociceptive potential

Calcitonin-gene-related peptide (CGRP), a potent vasodilator that mediates inflammatory pain, is elevated in migraine; nevertheless, little is known about its release from sensory neurons. In this study, CGRP was found to occur in the majority of neurons from rat trigeminal ganglia, together with the three exocytotic SNAREs [SNAP25, syntaxin 1 and the synaptobrevin (Sbr, also known as VAMP) isoforms] and synaptotagmin. Ca2+-dependent CGRP release was evoked with K+-depolarisation and, to lower levels, by capsaicin or bradykinin from neurons that contain the vanilloid receptor 1 and/or bradykinin receptor 2. Botulinum neurotoxin (BoNT) type A cleaved SNAP25 and inhibited release triggered by K+ > bradykinin >> capsaicin. Unlike BoNT type D, BoNT type B did not affect exocytosis, even though the neurons possess its receptor and Sbr II and Sbr III got proteolysed (I is resistant in rat) but, in mouse neurons, it additionally cleaved Sbr I and blocked transmitter release. Sbr I and II were found in CGRP-containing vesicles, and each was shown to separately form a SNARE complex. These new findings, together with punctate staining of Sbr I and CGRP in neurites, implicate isoform Sbr I in exocytosis from large dense-core vesicles together with SNAP25 (also, probably, syntaxin 1 because BoNT type C1 caused partial cleavage and inhibition); this differs from Sbr-II-dependent release of transmitters from small synaptic vesicles. Such use of particular Sbr isoform(s) by different neurons raises the functional implications for other cells previously unrecognised.
Compression noise based video forgery detection

Intelligent video editing techniques can be used to tamper videos such as surveillance camera videos, defeating their potential to be used as evidence in a court of law. In this paper, we propose a technique to detect forgery in MPEG videos by analyzing the frame's compression noise characteristics. The compression noise is extracted from spatial domain by using a modified Huber Markov Random Field (HMRF) as a prior for image. The transition probability matrices of the extracted noise are used as features to classify a given video as single compressed or double compressed. The experiment is conducted on different YUV sequences with different scale factors. The efficiency of our classification is observed to be higher relative to the state of the art detection algorithms.
Histomorphometric Evaluation of Superovulation Effect on Follicular Development after Autologous Ovarian Transplantation in Mice

The effect of superovulation by pregnant mare serum gonadotropin (PMSG) on autologous transplanted ovaries in the lumbar muscles of mice was histomorphometrically evaluated using the indices of number and volume of different kind of follicles and volume of corpora lutea, ovary, and stroma. Angiogenesis was observed after mouse ovarian transplantation on days 14 and 21 after ovarian grafting. After transplantation, the total number and volume of primary and secondary follicles reduced, while PMSG superovulation increased the total number and total volume of tertiary follicles and also the ovarian volume after transplantation. Transplantation increased the average size of primary, secondary, and tertiary follicles. Therefore, primary and secondary follicles can survive after autologous transplantation but their reservations diminished by increasing the time of transplantation. However, number of tertiary follicles and their response to superovulation increased over time after transplantation.
A COMPREHENSIVE ANALYSIS OF ATTACKS ON ONLINE PAYMENT SCHEMES

When payments are to be made over the Internet, security becomes critical. The online banking system has become the preferred target of some attackers. To maintain the clients’ trust and confidence in the security of the services, the financial institutions and related research workers must identify how the attackers damage the user’s account and develop methods to enhance the security of the system. Based on analyzing the basic processes of online payment and the mode of attacks, the security and general prevention techniques are discussed. A complete analysis of the attack process in the transactions is given. In addition, some secure schemes and corresponding system design strategies against aggressive behaviors are proposed. This analysis and schemes are intended to be useful for commercial banks to adopt or to improve their online banking systems.
Effects of creative dance on proprioception, rhythm and balance of preschool children

ABSTRACT The purpose of this study was to investigate the effects of creative dance on proprioception, rhythm and static balance in preschool children. The treatment group consisted of 32 preschool children which took part in a creative dance programme that lasted 2 months (twice a week), while the control group (30 preschool children) participated in an unstructured free-play setting. Prior to and after the intervention, children were assessed for proprioception (Active-Reproduction Test), rhythm (K-Rhythm Test) and balancing on one foot. The results showed that the treatment group performed significantly better on the proprioception and rhythm post-test measures compared to the control group. No significant differences were found for static balance. It may be concluded that creative dance can positively affect proprioception and rhythmic synchronization in preschool children. Considering the importance of these factors for children’s motor development, it is suggested that creative dance should be included in early childhood curricula.
Image Retrieval Using Landmark Indexing for Indoor Navigation

A novel approach is proposed for real-time retrieval of images from a large database of overlapping images of an indoor environment. The procedure extracts visual features from images using selected computer vision techniques, and processes the extracted features to create a reduced list of features annotated with the frame numbers they appear in. This method is named landmark indexing. Unlike some state-of-the-art approaches, the proposed method does not need to consider large image adjacency graphs because the overlap of the images in the map sufficiently increases information gain, and mapping of similar features to the same landmark reduces the search space to improve search efficiency. Empirical evidence from experiments on real datasets shows better performance and accuracy than other approaches. Experiments are further performed by integrating the image retrieval technique into a 3D real-time navigation system. This system is tested in several indoor environments and all experiments show highly accurate localization results.