Miracle-dz/UniFAR-FTUs huggingface dataset:
Immune-Induced Evolutionary Selection Focused on a Single Reading Frame in Overlapping Hepatitis B Virus Proteins

ABSTRACT Viruses employ various means to evade immune detection. Reduction of CD8+ T cell epitopes is one of the common strategies used for this purpose. Hepatitis B virus (HBV), a member of the Hepadnaviridae family, has four open reading frames, with about 50% overlap between the genes they encode. We computed the CD8+ T cell epitope density within HBV proteins and the mutations within the epitopes. Our results suggest that HBV accumulates escape mutations that reduce the number of epitopes. These mutations are not equally distributed among genes and reading frames. While the highly expressed core and X proteins are selected to have low epitope density, polymerase, which is expressed at low levels, does not undergo the same selection. In overlapping regions, mutations in one protein-coding sequence also affect the other protein-coding sequence. We show that mutations lead to the removal of epitopes in X and surface proteins even at the expense of the addition of epitopes in polymerase. The total escape mutation rate for overlapping regions is lower than that for nonoverlapping regions. The lower epitope replacement rate for overlapping regions slows the evolutionary escape rate of these regions but leads to the accumulation of mutations more robust in the transfer between hosts, such as mutations preventing proteasomal cleavage into epitopes.
Comparative study of HEMTs for LNAs in Square Kilometre Array telescope

The paper focuses on a comparative study of transistors of different dimensions from nine prominent low noise HEMT processes around the world. The transistors include a combination of pHEMTs and mHEMTs based on GaAs and InP substrates with gate lengths ranging from 150nm to 70nm. The Square Kilometre Array telescope will require more than 30 million low noise amplifiers (LNA). Importance of power consumption and variation of ambient temperature of the amplifiers over time and also location are being recognised as two of the primary issues. Here a detailed comparative study of noise and gain indices of HEMTs of nine processes is presented with respect to power consumption. The variation of gain and minimum noise figure with respect to temperature from −50°C to 60°C is also analysed.
Implementation guidelines for a harmonised digital forensic investigation readiness process model

Digital forensic investigation readiness enables an organisation to prepare itself in order to perform a digital forensic investigation in a more efficient and effective manner. Benefits of achieving a high level of digital forensic investigation readiness include, but are not limited to, higher admissibility of digital evidence in a court of law, better utilisation of resources (including time and financial resources) and higher awareness of forensic investigation readiness. The problem that this paper addresses is that there is no harmonised digital forensic investigation readiness process model with appropriate implementation guidelines and, thus, there is a lack of an effective and standardised implementation of digital forensic investigation readiness measures within organisations. Valjarevic and Venter have, in their previous work, proposed a harmonised digital forensic investigation readiness process model. This paper proposes implementation guidelines for such a harmonised digital forensic investigation process model in order to help practitioners and researchers to successfully implement the proposed model. The authors believe that these guidelines will significantly help to properly and consistently implement digital forensic readiness measures in different organisations in a bid to achieve higher admissibility of digital evidence in a court of law, as well as more efficient and effective digital forensic investigations.
Reactive Oxygen Species Generation and Mitochondrial Dysfunction in the Apoptotic Response to Bortezomib, a Novel Proteasome Inhibitor, in Human H460 Non-small Cell Lung Cancer Cells*

Bortezomib, a proteasome inhibitor, shows substantial anti-tumor activity in a variety of tumor cell lines, is in phase I, II, and III clinical trials and has recently been approved for the treatment of patients with multiple myeloma. The sequence of events leading to apoptosis following proteasome inhibition by bortezomib is unclear. Bortezomib effects on components of the mitochondrial apoptotic pathway were examined: generation of reactive oxygen species (ROS), alteration in the mitochondrial membrane potential (Δψm), and release of cytochrome c from mitochondria. With human H460 lung cancer cells, bortezomib exposure at 0.1 μm showed induction of apoptotic cell death starting at 24 h, with increasing effects after 48–72 h of treatment. After 3–6 h, an elevation in ROS generation, an increase in Δψm, and the release of cytochrome c into the cytosol, were observed in a time-dependent manner. Co-incubation with rotenone and antimycin A, inhibitors of mitochondrial electron transport chain complexes I and III, or with cyclosporine A, an inhibitor of mitochondrial permeability transition pore, resulted in inhibition of bortezomib-induced ROS generation, increase in Δψm, and cytochrome c release. Tiron, an antioxidant agent, blocked the bortezomib-induced ROS production, Δψm increase, and cytochrome c release. Tiron treatment also protected against the bortezomib-induced PARP protein cleavage and cell death. Benzyloxycarbonyl-VAD-fluoromethyl ketone, an inhibitor of pan-caspase, did not alter the bortezomib-induced ROS generation and increase in Δψm, although it prevented bortezomib-induced poly(ADP-ribose) polymerase cleavage and apoptotic death. In PC-3 prostate carcinoma cells (with overexpression of Bcl-2), a reduction of bortezomib-induced ROS generation, Δψm increase was correlated with cellular resistance to bortezomib and the attenuation of drug-induced apoptosis. The transient transfection of wild type p53 in p53 null H358 cells caused stimulation of the bortezomib-induced apoptosis but failed to enhance ROS generation and Δψm increase. Thus ROS generation plays a critical role in the initiation of the bortezomib-induced apoptotic cascade by mediation of the disruption of Δψm and the release of cytochrome c from mitochondria.
Is Preferential Attachment the 2nd Law of Thermodynamics in Disguise?

Barab\'asi-Albert's `Scale Free' model is the accepted theory of the evolution of real world networks. Careful comparison of the theory with a wide range of real world graphs, however, has identified shortcomings in the predictions of the theory when compared to the data. In particular, the exponent $\gamma$ of the power law distribution of degree is predicted by the model to be identically 3, whereas the data has values of $\gamma$ between 1.2 and 2.9. The degree distribution data also tends to fall off at high degrees, which indicates the existence of maximal node degrees for many networks. In this paper we propose a simple extension to the `Scale Free' model, which offers far better agreement with the experimental data. This improvement is satisfying, but the model still does not explain why the attachment probabilities should favor high degree nodes, or indeed how constraints arrive in non-physical networks. Using recent advances in the analysis of the entropy of graphs at the node level we propose a first principles derivation for the `Scale Free' and `constraints' model from thermodynamic principles, and demonstrate that both preferential attachment and constraints are simply a natural consequence of the 2nd law of thermodynamics.
Learning Model Rules From High-Speed Data Streams

Decision rules are one of the most expressive languages for machine learning. In this paper we present Adaptive Model Rules (AMRules), the first streaming rule learning algorithm for regression problems. In AMRules the antecedent of a rule is a conjunction of conditions on the attribute values, and the consequent is a linear combination of attribute values. Each rule in AMRules uses a Page-Hinkley test to detect changes in the process generating data and react to changes by pruning the rule set. In the experimental section we report the results of AMRules on benchmark regression problems, and compare the performance of our algorithm with other streaming regression algorithms.
Does Applicability Domain Exist in Microarray-Based Genomic Research?

Constructing an accurate predictive model for clinical decision-making on the basis of a relatively small number of tumor samples with high-dimensional microarray data remains a very challenging problem. The validity of such models has been seriously questioned due to their failure in clinical validation using independent samples. Besides the statistical issues such as selection bias, some studies further implied the probable reason was improper sample selection that did not resemble the genomic space defined by the training population. Assuming that predictions would be more reliable for interpolation than extrapolation, we set to investigate the impact of applicability domain (AD) on model performance in microarray-based genomic research by evaluating and comparing model performance for samples with different extrapolation degrees. We found that the issue of applicability domain may not exist in microarray-based genomic research for clinical applications. Therefore, it is not practicable to improve model validity based on applicability domain.
Negative Views of Parents and Struggles with God: An Exploration of Two Mediators

Could a negative view of one's mother or father be related to struggles with God? If so, what mediating variables might explain this connection? We conducted two studies to examine these questions, one with a broad-based internet sample (n = 471) and one with undergraduates (n = 236). Both studies confirmed that seeing one's mother or father as cruel was associated with two types of divine struggle: anger toward God and concern about God's anger or disapproval toward the self. A cruel God concept largely mediated the link with divine struggle in Study 1. In Study 2, a multiple mediation procedure identified two distinct mediators: not only a cruel God concept but also a sense of instability or anxiety about abandonment in one's perceived bond with God. These results complement other theoretical and empirical work that connects experiences with parents with perceptions and emotions regarding God.
GLAP: A G LOBAL LOOPBACK ANOMALY PREVENTION MECHANISM FOR MULTI -LEVEL DISTRIBUTED TRANSACTIONS

The multi-level/hierarchical distributed transaction execution model is currently the model specified in the database standards and practiced in the implementations of commercial database management systems. In this model, a transaction may execute more than one subtransaction with different origins at a participating site, causing the same transaction to appear more than once at the participating site. This system state is well recognized in the literature and is commonly known as a “loopback”. When a loopback occurs at a site, certain types of anomalies may arise. The effects of these anomalies on the system behaviour vary depending on the type of the anomaly. In an extreme case, a loopback anomaly may lead to non-serializable executions of transactions, sacrificing the consistency of the entire distributed database system. Thus, it is imperative to characterize the different types of loopback anomalies and to provide a practical and efficient solution to those that are most devastating on the system behaviour. This is the focus of this article.
Epidemiology of hip and knee pain and its impact on overall health status in older adults.

OBJECTIVES To obtain prevalence rates of hip and knee pain in elderly people and compare combinations of symptoms with overall health status. METHODS We performed a cross-sectional postal survey of a random sample of 5500 Oxfordshire residents aged 65 yr and older. Prevalence estimates were based on the screening question: 'During the past 12 months, have you had pain in or around either of your hip/knee joints on most days for one month or longer? ' Overall health status was assessed with the SF-36 questionnaire. RESULTS The response rate was 66.3% (3341/5039 eligible people), and was highest (approximately reverse similar 72%) for the 65-74 yr age-group. The percentage reporting hip pain was 19.2% [95% confidence interval (CI) 17.9-20.6], and 32.6% (95% CI 31.0-34.3) reported knee pain. The percentage reporting hip and knee pain was 11.3%, and 40.7% reported hip or knee pain. Less than half (48%) of the symptomatic respondents had unilateral problems affecting one hip or knee joint only. SF-36 scores worsened as the number of symptomatic hip and knee joints increased (P<0.001 for physical function, physical role limitation and bodily pain). CONCLUSIONS Patterns of hip and knee symptoms are complex in older people. Amongst the symptomatic, most have more than one hip/knee affected. This has implications for treatment and health status measurement. In the absence of hip and knee symptoms, general health status scores of elderly people are similar to those of people aged under 65 yr.
Construction of Mycobacterium tuberculosis cdd knockout and evaluation of invasion and growth in macrophages

Cytidine deaminase (MtCDA), encoded by cdd gene (Rv3315c), is the only enzyme identified in nucleotide biosynthesis pathway of Mycobacterium tuberculosis that is able to recycle cytidine and deoxycytidine. An M. tuberculosis knockout strain for cdd gene was obtained by allelic replacement. Evaluation of mRNA expression validated cdd deletion and showed the absence of polar effect. MudPIT LC-MS/MS data indicated thymidine phosphorylase expression was decreased in knockout and complemented strains. The cdd disruption does not affect M. tuberculosis growth both in Mid- dlebrook 7H9 and in RAW 264.7 cells, which indicates that cdd is not important for macrophage invasion and virulence.
UsingWeb Services for Configuration and Deployment according to the CDDLM Standard

As Web services and service oriented architectures are adopted, it is increasingly important to have standard and interoperable means to deploy and configure Web services. Within the Global Grid Forum, HP, NEC, and Softricity have been developing a standard for configuration description, deployment, and lifecycle management (CDDLM). In order to prove its feasibility, reference implementations are being developed. This paper describes an independent reference implementation of CDDLM and the experience in using Web Services for deployment in a standardized manner. Our main contributions are: the lessons learned in implementing this WS-based standard and an architecture for implementing CDDLM
Cyclooxygenase-2 Promotes Human Cholangiocarcinoma Growth

The expression of cyclooxygenase-2 (COX-2) is increased in human cholangiocarcinoma. However, the biologic function and molecular mechanisms of COX-2 in the control of cholangiocarcinoma cell growth have not been well established. This study was designed to examine the direct effect of COX-2 and its inhibitor celecoxib on the growth of human intrahepatic cholangiocarcinoma cells. Overexpression of COX-2 or treatment with prostaglandin E2 (PGE2) enhanced human cholangiocarcinoma cell growth, whereas antisense depletion of COX-2 in these cells decreased PGE2 production and inhibited growth. These findings demonstrate a direct role of COX-2-mediated PGE2 in the growth regulation of human cholangiocarcinoma cells. Furthermore, the COX-2 inhibitor celecoxib induced a dose-dependent inhibition of cell growth, cell cycle arrest at the G1-S checkpoint, and induction of cyclin-dependent kinase inhibitors p21waf1/cip1 and p27kip1. However, the high concentration of celecoxib (50 μm) required for inhibition of growth, the incomplete protection of celecoxib-induced inhibition of cell growth by PGE2 or COX-2 overexpression, and the fact that overexpression or antisense depletion of COX-2 failed to alter the level of p21waf1/cip1 and p27kip1 indicate the existence of a COX-2-independent mechanism in celecoxib-induced inhibition of cholangiocarcinoma cell growth.
Type I Interferon as a Link Between Innate and Adaptive Immunity through Dendritic Cell Stimulation

Type I interferon (IFN-α/β) is expressed rapidly after infection and plays a key role in innate defense against pathogens. Recent studies have shown that a connection exists between IFN-α/β and antigen-presenting dendritic cells (DCs) at two levels. Firstly, a specific DC precursor, the plasmacytoid pre-DC (p-preDC), was identified as a cell type able to secrete very high amounts of IFN-α/β following stimulation with infectious agents. Secondly, IFN-α/β has been shown to act as a differentiation/maturation factor for DCs. These findings will be discussed in association with evidence indicating that IFN-α/β can enhance and modulate immune responses in vivo. Taken together, the available data suggest that IFN-α/β serves as a link between the innate response to infection and the adaptive immune response.
Role of regulatory T cells in gastrointestinal inflammatory disease

Regulatory T cells curb unwanted immune responses and regulate responses to microflora and it is now clear that regulatory T cells play an important role in a number of chronic inflammatory diseases of the gut. First, regulatory T cells are crucial in controlling immune responses to gastric autoantigens and thus preventing autoimmune gastritis and pernicious anemia. Second, regulatory T cells may modulate the response to Helicobacter pylori, thus affecting the ability of the immune system to clear the pathogen and mediate damage to the gastric mucosa. Finally, regulatory T cells play an important role in preventing damaging inflammatory responses to commensal organisms in the lower gut, thus guarding against inflammatory bowel diseases. In the present review, we examine the actions of regulatory T cells in the gut and conclude that further understanding of regulatory T cell biology may lead to new therapeutic approaches to chronic gastrointestinal disease.
HIV Risk-Reduction Counseling and Testing on Behavior Change of MSM

HIV and AIDS incidence in China is high among men who have sex with men (MSM) and ours was one of few studies in China to evaluate the role of HIV risk reduction counseling and testing. Respondent-driven sampling (RDS) was used to recruit 430 MSM. Participants were followed up at 6, 12 and 18 months to evaluate behavioral changes after counseling to reduce risk behaviors. At baseline, HIV prevalence was 4.7%, whereas HIV incidence was 5.2 per 100 person-years. The incidence was 3.8 during six to 12 months, and 1.1 during 12 to 18 months. During the study period, the reported unprotected anal intercourse (UAI) significantly decreased from 60.9% to 42.9%. The proportion of participants who had one or no partner significantly increased from 40.9% to 48.0%. The study also found that some risk behaviors decreased between baseline and 12 months, followed by a slight increase between 12 and 18 months. Reductions in UAI can be achieved through counseling and testing, but may wane over time. Future programs should consider HIV risk-reduction counseling and testing for interventions in MSM in China.
Towards Privacy-preserving Attribute Aggregation in Federated eID Systems

In: S. España, M. Ivanović, M. Savić (eds.): Proceedings of the CAiSE’16 Forum at the 28th International Conference on Advanced Information Systems Engineering, Ljubljana, Slovenia, 13-17.6. 2016, published at http://ceur-ws.org Abstract. During the past years, achieving interoperability, i.e. creating identity federations, between different eID systems has gained relevance. A key problem of identity federations is the missing harmonization between different attribute providers (APs). In closed eID systems, ontologies allow a higher degree of automation in the process of aligning and aggregating attributes from different APs. This approach does not work for identity federations, as each eID system uses its own ontology to represent attributes. Moreover, providing attributes to intermediate entities required to align and aggregate attributes potentially violates privacy rules. To tackle these problems, we propose the use of combined ontology alignment approaches and locality-sensitive hashing (LSH) functions. We assess existing implementations of these concepts by means of criteria that are specific for identity federations. Obtained results show that suitable implementations of these concepts exist and that they can be used to achieve interoperability between eID systems on attribute level.
Overexpression of AtCPS and AtKS in Arabidopsis Confers Increased ent-Kaurene Production But No Increase in Bioactive Gibberellins1

The plant growth hormone gibberellin (GA) is important for many aspects of plant growth and development. Although most genes encoding enzymes at each step of the GA biosynthetic pathway have been cloned, their regulation is less well understood. To assess how up-regulation of early steps affects the biosynthetic pathway overall, we have examined transgenic Arabidopsis plants that overexpress either AtCPS or AtKS or both. These genes encode the enzymes ent-copalyl diphosphate synthase (CPS) and ent-kaurene synthase, which catalyze the first two committed steps in GA biosynthesis. We find that both CPS and CPS/ent-kaurene synthase overexpressors have greatly increased levels of the early intermediates ent-kaurene and ent-kaurenoic acid, but a lesser increase of later metabolites. These overexpression lines do not exhibit any GA overdose morphology and have wild-type levels of bioactive GAs. Our data show that CPS is limiting for ent-kaurene production and suggest that conversion of ent-kaurenoic acid to GA12 by ent-kaurenoic acid oxidase may be an important rate-limiting step for production of bioactive GA. These results demonstrate the ability of plants to maintain GA homeostasis despite large changes in accumulation of early intermediates in the biosynthetic pathway.
The associated nontargets effect: Evidence of nontarget processing at and beyond the level of letter recognition

In four visual search tasks participants were asked to make a target response if either of two targets was present and to make a nontarget response if neither target was present. Some target-absent displays included only nontarget stimuli or features that never occurred in the same displays as targets, whereas other target-absent displays included nontarget stimuli or features that did sometimes occur with targets. Nontarget responses were reliably faster in the former case than in the latter. This “associated nontargets effect” indicates that nontargets are not simply classified as nontargets but in addition are discriminated from one another. Current visual search models may underestimate the degree to which nontargets are processed during search.