Miracle-dz/UniFAR-FTUs huggingface dataset:
TRIM25 Enhances the Antiviral Action of Zinc-Finger Antiviral Protein (ZAP)

The host factor and interferon (IFN)-stimulated gene (ISG) product, zinc-finger antiviral protein (ZAP), inhibits a number of diverse viruses by usurping and intersecting with multiple cellular pathways. To elucidate its antiviral mechanism, we perform a loss-of-function genome-wide RNAi screen to identify cellular cofactors required for ZAP antiviral activity against the prototype alphavirus, Sindbis virus (SINV). In order to exclude off-target effects, we carry out stringent confirmatory assays to verify the top hits. Important ZAP-liaising partners identified include proteins involved in membrane ion permeability, type I IFN signaling, and post-translational protein modification. The factor contributing most to the antiviral function of ZAP is TRIM25, an E3 ubiquitin and ISG15 ligase. We demonstrate here that TRIM25 interacts with ZAP through the SPRY domain, and TRIM25 mutants lacking the RING or coiled coil domain fail to stimulate ZAP’s antiviral activity, suggesting that both TRIM25 ligase activity and its ability to form oligomers are critical for its cofactor function. TRIM25 increases the modification of both the short and long ZAP isoforms by K48- and K63-linked polyubiquitin, although ubiquitination of ZAP does not directly affect its antiviral activity. However, TRIM25 is critical for ZAP’s ability to inhibit translation of the incoming SINV genome. Taken together, these data uncover TRIM25 as a bona fide ZAP cofactor that leads to increased ZAP modification enhancing its translational inhibition activity.
Experimental approaches to lymphocyte migration in dermatology in vitro and in vivo

Abstract: Lymphocyte trafficking through the dermal compartment is part of the physiological surveillance process of the adaptive immune system. On the other hand, persistent or recurrent lymphocyte infiltrates are hallmarks of both types of chronic inflammatory skin diseases, Th1‐type such as psoriasis or Th2/allergic‐type like atopic dermatitis. A better understanding of the mechanisms underlying lymphocyte movements is one of the key prerequisites for developing more effective therapies. In this review, we introduce a range of simple‐to‐sophisticated experimental in vitro and in vivo approaches to analyze lymphocyte migration. These methods start from static in vitro adhesion and chemotaxis assays, include dynamic endothelial flow chamber, intravital dual photon, and transcutaneous live‐video microscopy, and finally encompass specific genetically deficient or engineered animal models. Discussing pros and cons of these assay systems hopefully generates both state‐of‐the‐art knowledge about the factors involved in most common chronic skin diseases as well as an improved understanding of the limitations and chances of new biologic pharmaceuticals that are currently introduced into clinical practice.
LMI-based adaptive fuzzy integral sliding mode control of mismatched uncertain systems

LMI-based adaptive fuzzy integral sliding mode control of mismatched uncertain systems Integral sliding mode design is considered for a class of uncertain systems in the presence of mismatched uncertainties in both state and input matrices, as well as norm-bounded nonlinearities and external disturbances. A sufficient condition for the robust stability of the sliding manifold is derived by means of linear matrix inequalities. The initial existence of the sliding mode is guaranteed by the proposed control law. The improvement of the proposed control scheme performances, such as chattering elimination and estimation of norm bounds of uncertainties, is then considered with the application of an adaptive fuzzy integral sliding mode control law. The validity and efficiency of the proposed approaches are investigated through a sixth order uncertain mechanical system.
Assay Sensitivity and the Epistemic Contexts of Clinical Trials

This article examines the concept of assay sensitivity in clinical research. Defined as the ability of a clinical trial to distinguish between an effective and ineffective treatment, the need for assay sensitivity has been taken to support the claim that placebos are methodologically superior to active control treatments. The demands of doing good clinical science must trump the physician-researcher’s ethical duty to provide all trial participants with nothing less than competent medical care. We argue that this supposed implication of assay sensitivity rests on (1) collapsing the distinction between biological efficacy and clinical effectiveness, and (2) conflating the epistemic contexts of a trial-as-designed and a trial-as-executed. Once these errors are corrected, it becomes clear that placebos grant no epistemological advantage over active controls, and there is therefore no longer a tension between the epistemic and ethical demands of research. We suggest that the legitimate worries behind assay sensitivity can be better understood as the need for researchers to articulate their experimental heuristics and to demonstrate a robust pattern of evidence across a series of trials.
Dynamical friction in constant density cores: a failure of the Chandrasekhar formula

Using analytic calculations and N-body simulations we show that in constant density (harmonic) cores, sinking satellites undergo an initial phase of very rapid (super-Chandrasekhar) dynamical friction, after which they experience no dynamical friction at all. For density profiles with a central power law profile, ρ∝r−α, the infalling satellite heats the background and causes α to decrease. For α < 0.5 initially, the satellite generates a small central constant density core and stalls as in the α= 0 case. We discuss some astrophysical applications of our results to decaying satellite orbits, galactic bars and mergers of supermassive black hole binaries. In a companion paper we show that a central constant density core can provide a natural solution to the timing problem for Fornax's globular clusters.
Software Engineering Formal and Practical on Formality on Practicality the Approachused in the Book Reader Background Using the Book in Courses Online Supplemental Material Faculty Colleagues Who Have Taught Me Much about Software Engineering Include

Preface This book is a comprehensive study of software engineering, with emphasis on the practical application of formal methods. While formal methods are an important part of software engineering, theya re by no means the whole picture. Indeed, manya spects of software development involvep rinciples of aesthetics and human communication that cannot be readily formalized. Since this text provides a comprehensive treatment of the field, both formal and non-formal aspects are fully covered. Throughout the coverage, the book integrates formal methods into the major phases of software development, to provide a foundation for the development process. From the author'sp erspective,t he use of formal methods has been significantly neglected in most software engineering texts as well as in industrial practice. In general, far too manysoftware engineers view formal methods as impractical and largely irrelevant to their regular activities. This is a rather unusual viewwhen one compares software engineering to other science and engineering disciplines. In almost all such disciplines, formal mathematical analysis is a common practice. One cause for lack of rigor in software engineering is that formal reasoning can be hard. When giventhe chance, human nature will steer us awayf rom hard tasks. The civil engineer,f or example, might liket o draws ome simple pictures and perform some informal analysis when designing a bridge, without devoting endless hours to formal modeling. Fortunately,t he competent civil engineer knows that informal analysis is not sufficient, and that a bridge may well collapse if a careful mathematical specification is not developed. The civil engineer learns this as part of basic training and the practice of civil engineering demands that formal analysis is an integral part of the job. Likethe civil engineer,the software engineer should learn that careful formal reasoning can be an integral part of building complexs oftware systems. In current practice, informal analysis and design are frequently considered adequate for software engineering projects. Furthermore, most software engineers are not trained in formal methods, nor does the practice of software engineering require the same degree of mathematical rigor as is required in other branches of engineering. This author firmly believest hat as software engineering matures into a genuine engineering discipline, acceptance and use of formal methods will be an important part of its maturation. Ak ey distinction between this text and most others is that here formal methods are considered to be an integral part of software development, rather than an alternate …
SAVANT: aggregated feedback and accountability framework for named data networking

Content providers (i.e., entities that own or are licensed to sell or distribute content e.g., BBC, Netflix) are looking for more efficient, secure, cheaper, accountable and scalable mechanisms for the delivery of content to end-users. The Information Centric Networking (ICN) paradigm offers solutions to some of these challenges by decoupling a user's trust in content from where it is obtained by enabling the content to self-verify (i.e., the user can establish integrity, trust and provenance in content received from trusted or untrusted infrastructure). However, there are still associated challenges with using ICN architectures related to content feedback and accountability. In this paper, we propose an ICN architecture extension for content feedback and accountability called the Savant framework, which we apply to the Named Data Networking (NDN) architecture.
Examining the Family Context and Relations with Attitudes to School and Scholastic Competence

The importance of family relations in children's adjustment has been established, but questions remain about the contexts that account for these associations. Examining children's reactions to family stress holds promise for advancing our understanding of the relations between attachment and school-related outcomes. The present study examined children's attachment, basal cortisol, and emotional reactions in 235 community families, to understand contributions to children's attitudes to school and scholastic competence. Children's attachment security and normative basal cortisol both contributed to positive school outcomes, while insecurity in the context of low or high cortisol and emotional distress related negatively. Findings highlight the importance of examining stress in family contexts to advance the understanding of children's school functioning, with implications for school mental health interventions.
ADtrees for Fast Counting and for Fast Learning of Association Rules

The problem of discovering association rules in large databases has received considerable research attention. Much research has examined the exhaustive discovery of all association rules involving positive binary literals (e.g. Agrawal et al. 1996). Other research has concerned finding complex association rules for high-arity attributes such as CN2 (Clark and Niblett 1989). Complex association rules are capable of representing concepts such as "Purchased-Chips=True and PurchasedSoda=False and Area=NorthEast and CustomerType=Occasional ⇒ AgeRange=Young", but their generality comes with severe computational penalties (intractable numbers of preconditions can have large support). Here, we introduce new algorithms by which a sparse data structure called the ADtree, introduced in (Moore and Lee 1997), can accelerate the finding of complex association rules from large datasets. The ADtree uses the algebra of probability tables to cache a dataset's sufficient statistics within a tractable amount of memory. We first introduce a new ADtree algorithm for quickly counting the number of records that match a precondition. We then show how this can be used in accelerating exhaustive search for rules, and for accelerating CN2-type algorithms. Results are presented on a variety of datasets involving many records and attributes. Even taking the costs of initially building the ADtree into account, the computational speedups can be dramatic.
Proteomic changes in renal cancer and co‐ordinate demonstration of both the glycolytic and mitochondrial aspects of the Warburg effect

Renal cell carcinoma (RCC) is the tenth most common cancer although the incidence is increasing. The main clinical problems stem from the relatively late presentation of many patients due to the often asymptomatic nature of the illness, and the relative insensitivity of metastatic disease to conventional chemotherapy and radiotherapy. Despite increasing knowledge of some of the genetic changes underlying sporadic renal cancer such as those involving the Von Hippel Lindau (VHL) gene, many of the underlying pathophysiological changes are ill‐defined and there remains a need for the identification of disease markers for use in diagnosis and prognosis or as potential therapeutic targets. This study has used a proteomic approach, based on two‐dimensional gel electrophoresis and mass spectrometry, to compare the protein profiles of conventional RCC tissue with patient‐matched normal kidney cortex. Sequencing of 32 protein spots with significantly increased expression in RCC samples (≥ 4/6 patients) and 41 proteins whose levels decreased (6/6 patients) confirmed several previously known RCC‐associated changes such as increases in Mn‐superoxide dismutase, lactate dehydrogenase‐A, aldolase A and C, pyruvate kinase M2, and thymidine phosphorylase. Additionally, several previously unknown changes were identified, including increased expression of three members of the annexin family and increased levels of the actin depolymerisation factor cofilin. The Warburg effect was also demonstrated with the identification of increases in proteins involved in the majority of steps in the glycolytic pathway and decreases in the gluconeogenic reactions, together with a parallel decrease in several mitochondrial enzymes. A number of the alterations seen were further confirmed in additional samples by immunohistochemistry, Western blotting, and laser capture microdissection.
Group Testing Algorithms: Bounds and Simulations

We consider the problem of nonadaptive noiseless group testing of N items of which K are defective. We describe four detection algorithms, the COMP algorithm of Chan et al., two new algorithms, DD and SCOMP, which require stronger evidence to declare an item defective, and an essentially optimal but computationally difficult algorithm called SSS. We consider an important class of designs for the group testing problem, namely those in which the test structure is given via a Bernoulli random process. In this class of Bernoulli designs, by considering the asymptotic rate of these algorithms, we show that DD outperforms COMP, that DD is essentially optimal in regimes where K ≥ √N, and that no algorithm can perform as well as the best nonrandom adaptive algorithms when K > N0.35. In simulations, we see that DD and SCOMP far outperform COMP, with SCOMP very close to the optimal SSS, especially in cases with larger K.
Changes in Properties of Auditory Nerve Synapses following Conductive Hearing Loss

Auditory activity plays an important role in the development of the auditory system. Decreased activity can result from conductive hearing loss (CHL) associated with otitis media, which may lead to long-term perceptual deficits. The effects of CHL have been mainly studied at later stages of the auditory pathway, but early stages remain less examined. However, changes in early stages could be important because they would affect how information about sounds is conveyed to higher-order areas for further processing and localization. We examined the effects of CHL at auditory nerve synapses onto bushy cells in the mouse anteroventral cochlear nucleus following occlusion of the ear canal. These synapses, called endbulbs of Held, normally show strong depression in voltage-clamp recordings in brain slices. After 1 week of CHL, endbulbs showed even greater depression, reflecting higher release probability. We observed no differences in quantal size between control and occluded mice. We confirmed these observations using mean-variance analysis and the integration method, which also revealed that the number of release sites decreased after occlusion. Consistent with this, synaptic puncta immunopositive for VGLUT1 decreased in area after occlusion. The level of depression and number of release sites both showed recovery after returning to normal conditions. Finally, bushy cells fired fewer action potentials in response to evoked synaptic activity after occlusion, likely because of increased depression and decreased input resistance. These effects appear to reflect a homeostatic, adaptive response of auditory nerve synapses to reduced activity. These effects may have important implications for perceptual changes following CHL. SIGNIFICANCE STATEMENT Normal hearing is important to everyday life, but abnormal auditory experience during development can lead to processing disorders. For example, otitis media reduces sound to the ear, which can cause long-lasting deficits in language skills and verbal production, but the location of the problem is unknown. Here, we show that occluding the ear causes synapses at the very first stage of the auditory pathway to modify their properties, by decreasing in size and increasing the likelihood of releasing neurotransmitter. This causes synapses to deplete faster, which reduces fidelity at central targets of the auditory nerve, which could affect perception. Temporary hearing loss could cause similar changes at later stages of the auditory pathway, which could contribute to disorders in behavior.
Responses to televised alcohol associated with drinking 10‐17‐year‐olds advertisem ents behaviour of

A im s. To examine the nature of the relationships between 10-17-year-old New Zealanders' responses to alcohol advertisements and their drinking behaviour and future drinking expectations, with consideration also being given to the role of positive and negative beliefs about drinking . D esign. Survey involving 500 face-to-face interviews, with selection based on random cluster sampling . Setting. In respondents' homes in New Zealand's three largest urban areas . Participants. Ten-17-year-old New Zealanders . M easurem ents. Response to specific alcohol advertisements was measured by recalled exposure (how often they recalled having seen the advertisements) and liking (a measure of positive response) . Findings. An exploratory structural equation model provided tentative support for the theory-based hypothesis that positive responses to beer advertisements increased the frequency of current drinking and expected future drinking, among this age group. There was no evidence for the hypothesized reciprocal effects; the frequency of drinking (including non-drinking) did not significantly affect the respondent's liking of beer advertisements. There was also no support for a hypothesis that linking of the beer advertisements was a product of a general liking for alcohol. Many of the young people themselves felt that alcohol advertising encouraged teenagers to drink. This was especially the case among 10-13-year-old males, who were the most likely to accept the portrayals in alcohol advertising as realistic . C onclusions. Although there are limitations on the confidence with which conclusions can be drawn, the findings are consistent with qualitative and quantitative research and different theoretical perspectives on advertising processes which suggest alcohol advertising is likely to have some influence on young people .
Influence of teacher characteristics on students' academic achievement among secondary schools

The purpose of this study was to establish the relationship between teacher characteristics and students’ academic achievement. The study was guided by Education Production Function theory (EPF) which connects student academic achievement to teacher characteristics. The study was conducted in Nandi District, Kenya and the target population comprised of teachers of all 26 public secondary schools. The study applied a causal comparative research design. A questionnaire was used for data collection. Data was analyzed using descriptive and inferential statistical techniques. The study findings suggest that there was no significant relationship between teacher qualification and student academic achievement.
Expanded Parts Model for Human Attribute and Action Recognition in Still Images

We propose a new model for recognizing human attributes (e.g. wearing a suit, sitting, short hair) and actions (e.g. running, riding a horse) in still images. The proposed model relies on a collection of part templates which are learnt discriminatively to explain specific scale-space locations in the images (in human centric coordinates). It avoids the limitations of highly structured models, which consist of a few (i.e. a mixture of) 'average' templates. To learn our model, we propose an algorithm which automatically mines out parts and learns corresponding discriminative templates with their respective locations from a large number of candidate parts. We validate the method on recent challenging datasets: (i) Willow 7 actions [7], (ii) 27 Human Attributes (HAT) [25], and (iii) Stanford 40 actions [37]. We obtain convincing qualitative and state-of-the-art quantitative results on the three datasets.
Systematic overweighting of early items in serial cue integration

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Playful Supervised Smart Spaces (P3S) -- A Framework for Designing, Implementing and Deploying Multisensory Play Experiences for Children with Special Needs

Our research explores novel forms of smart spaces that support full body interaction with smart objects instrumented with audio, light, and motion sensors and actuators, virtual worlds on medium-large displays, and smart lights, and are integrated with cloud services for remote supervision and analysis of user behaviour. In this paper, we present the architecture and coordination infrastructure created in the Playful Supervised Smart Space (P3S) project, as well as initial designs for the Smart Object and Smart Space Gateway Components.