Miracle-dz/UniFAR-FTUs huggingface dataset:
Instructional objectives to core-gameplay: a serious game design technique

This paper explores a gap within the serious game design research. That gap is the ambiguity surrounding the process of aligning the instructional objectives of serious games with their core-gameplay i.e. the moment-to-moment activity that is the core of player interaction. A core-gameplay focused design framework is proposed that can work alongside existing, more broadly focused serious games design frameworks. The framework utilises an inquiry-based approach that allows the serious game designer to use key questions as a means to clearly outline instructional objectives with the core-gameplay. The use of this design framework is considered in the context of a small section of gameplay from an educational game currently in development. This demonstration of the framework brings shows how instructional objectives can be embedded into a serious games core-gameplay.
Analysis of 3GPP LTE-Advanced cell spectral efficiency

Multihop and multipoint transmissions are two of the main features towards an increased spectral efficiency for the LTE-Advanced mobile radio system. Fixed wireless relays with in-band backhauling are considered as a multihop technique in LTE-Advanced. Relays improve cell capacity and cell edge user performance depending on the deployment. In this paper, at first, results for the peak spectral efficiency of LTE-Advanced are presented and secondly, an analytical model to calculate the cell spectral efficiency of relay enhanced cell deployments in the context of the IMT-Advanced evaluation is presented. The developed model is applied to the LTE-Advanced system comparing different relay deployments with different frequency reuse schemes.
Morphological and Functional Characteristics of Patent Foramen Ovale and Their Embolic Implications

Background and Purpose Transesophageal echocardiography (TEE) has detected a high prevalence of patent foramen ovale (PFO) in stroke patients, but the clinical implications of the distinctive characteristics of this patency are still a matter of debate. Methods We studied 350 patients with acute ischemic stroke or transient ischemic attack (TIA) within 1 week of admission. Of these, 101 (29%) were identified by contrast TEE to have a PFO; 86 patients (25%) were cryptogenic stroke patients, and 163 were excluded because of the presence of a definite or possible arterial or clinical evidence of a source of emboli or small-vessel disease. Thirteen PFO subjects without a history of embolism were designated as the control group. All PFO and cryptogenic stroke patients were followed up by neurological visits. Results Compared with controls, PFO patients with acute stroke or TIA more frequently presented with a right-to-left shunt at rest and a higher membrane mobility (P <0.05). Patients with these characteristics were considered to be at high risk. During a median follow-up period of 31 months (range, 4 to 58 months), 8 PFO and 18 cryptogenic stroke patients experienced recurrent cerebrovascular events. The cumulative estimate of risk of cerebrovascular event recurrence at 3 years was 4.3% (95% confidence interval [CI], 0% to 10.2%) for “low-risk” PFO patients, 12.5% (95% CI, 0% to 26.1%) for “high-risk” PFO patients, and 16.3% (95% CI, 7.2% to 25.4%) for cryptogenic stroke patients (high-risk PFO versus low-risk PFO, P =0.05). Conclusions The association of right-to-left shunting at rest and high membrane mobility, as detected by contrast TEE, seems to identify PFO patients with cerebrovascular ischemic events who are at higher risk for recurrent brain embolism.
Nuclear Effects of G-Protein Receptor Kinase 5 on Histone Deacetylase 5–Regulated Gene Transcription in Heart Failure

Background— G-protein receptor kinases (GRKs) modulate cardiac &bgr;-adrenergic signaling. GRK5 is upregulated in heart failure, and a gain-of-function polymorphism substituting leucine for wild-type glutamine at amino acid 41 (GRK5-Leu41) is associated with improved outcomes in heart failure and hypertension. GRK5 is distinguished by partial nuclear localization and class II histone deacetylases (HDAC) kinase activity that is postulated to regulate G&agr;q-stimulated cardiac gene expression. Methods and Results— We used in vitro tissue culture and in vivo mouse compound genetic models to examine the effects of GRK5 on HDAC phosphorylation, nucleo-cytoplasmic HDAC transport, and G&agr;q-dependent transcriptional regulation. In vitro, GRK5 stimulated HDAC5 nuclear export only in the context of G&agr;q signaling stimulated by angiotensin II. GRK5-Gln41 and Leu41 were similar inducers of HDAC5 nucleo-cytoplasmic shuttling. In vivo, GRK5-Gln41 and-Leu41 partitioned equally to nuclear and nonnuclear myocardial fractions. GRK5 increased cardiac HDAC5 phosphorylation and reversed the increase in nuclear HDAC5 content seen with cardiomyocyte-autonomous G&agr;q overexpression. Deep RNA sequencing showed few changes in gene expression induced by GRK5 overexpression or ablation alone, but GRK5 overexpression normalized steady-state expression levels of 48% (96 of 200) of all G&agr;q down-regulated mRNAs. Conclusions— GRK5 is a transcriptional modifier of a subset of G&agr;q-downregulated genes, acting in opposition to the pathological effects of G&agr;q and normalizing levels of these transcripts. This transcriptional coregulator effect may act in concert with &bgr;-adrenergic receptor desensitization to protect against heart failure decompensation.
Primary assessment of a self-adhesive gutta-percha material.

AIM To evaluate a prototype gutta-percha material (Bio-Gutta), which is claimed to work without sealer because of its incorporated ultrafine bioactive glass particles, in terms of its induction of pH and calcium phosphate (CaP) precipitates, and its self-adhesiveness in root canals. METHODOLOGY Bio-Gutta was compared with conventional gutta-percha (GP, composition: 70 wt% ZnO, 30 wt% polyisoprene). Test and control materials (N = 3) were immersed in phosphate-buffered saline (PBS) at 37 °C for 30 days. The pH in the solution was monitored. Apparent CaP formation was assessed using scanning electron microscopy (SEM). The root canals of 33 single-rooted teeth were filled by vertical compaction of heated Bio-Gutta, 33 control canals were filled with vertically compacted GP without sealer. Push-out bond strengths associated with the filling materials in root cross-sections from middle root thirds was determined 1, 8, and 30 days after root filling (N = 11 per group). These values were compared between groups using one-way anova (α < 0.05). RESULTS Bio-Gutta induced a high pH in the PBS solution, which plateaued at values between 11.4 and 11.8. Apparent CaP crystals covered the Bio-Gutta material after 30 days of immersion in PBS, whilst no such structures were observed on GP. Both materials under investigation had similar initial push-out bond strength values (P > 0.05). The adherence of Bio-Gutta increased from day 1 to 8 and was significantly higher than that of conventional GP at 8 and 30 days (P < 0.05). CONCLUSIONS The experimental gutta-percha material under investigation was alkaline and caused CaP precipitates on its surface. It improved its adherence to the root canal wall within 1 week.
Cell-mediated Immunity in Patients Positive for Hepatitis-associated Antigen

Cell-mediated immunity to antigens prepared from both serum and liver of patients positive for hepatitis-associated antigen (H.A.A.) was measured by using the leucocyte migration test. Altogether, 43 patients with H.A. A. -positive acute and chronic liver disease, eight with serum antibody to H.A. A. , and 13 controls were studied. The cell-mediated immunity detected was specific for H.A. A. or other antigenic determinants of the associated infective agent and could be found only in patients with evidence of previous contact with H.A. A. Cell-mediated immunity to the H.A. A. -positive test antigens was found in all but one of the patients with acute hepatitis, in about half of the patients with chronic aggressive hepatitis or cirrhosis, rarely in those with chronic persistent hepatitis, and in none of the apparently healthy carriers. Our results support the hypothesis that the cellular immune response plays an important part in the clearance of the infective agent from H.A. A. -positive patients and in the pathogenesis of the associated liver cell injury.
Dynamic Histone H3 Acetylation and Methylation at Human Cytomegalovirus Promoters during Replication in Fibroblasts

ABSTRACT Human cytomegalovirus DNA is packaged in virions without histones but associates with histones upon reaching the nucleus of an infected cell. Since transcription is modulated by the interplay of histone modifications, we used chromatin immunoprecipitation to detect acetylation and methylation of histone H3 at viral promoters at different times during the viral replication cycle. Histone H3 at immediate-early promoters is acetylated at the start of infection, while it is initially methylated at early and late promoters. Acetylation at immediate-early promoters is dynamic, with a high level of activating modifications at 3 and 6 h postinfection (hpi), followed by a marked reduction at 12 hpi. All viral promoters, as well as nonpromoter regions, are modified with activating acetylations at 24 to 72 hpi. The transient reduction in histone H3 acetylation at the major immediate-early promoter depends on the cis-repressive sequence to which the UL122-coded IE2 protein binds. A mutant virus lacking this element exhibited decreased IE2 binding at the major immediate-early promoter and failed to show reduced acetylation of histone H3 residing at this promoter at 12 hpi. Our results demonstrate that cytomegalovirus chromatin undergoes dynamic, promoter-specific histone modifications early in the infectious cycle, after which the entire chromosome becomes highly acetylated.
Climate Change Vulnerability of Native and Alien Freshwater Fishes of California: A Systematic Assessment Approach

Freshwater fishes are highly vulnerable to human-caused climate change. Because quantitative data on status and trends are unavailable for most fish species, a systematic assessment approach that incorporates expert knowledge was developed to determine status and future vulnerability to climate change of freshwater fishes in California, USA. The method uses expert knowledge, supported by literature reviews of status and biology of the fishes, to score ten metrics for both (1) current status of each species (baseline vulnerability to extinction) and (2) likely future impacts of climate change (vulnerability to extinction). Baseline and climate change vulnerability scores were derived for 121 native and 43 alien fish species. The two scores were highly correlated and were concordant among different scorers. Native species had both greater baseline and greater climate change vulnerability than did alien species. Fifty percent of California’s native fish fauna was assessed as having critical or high baseline vulnerability to extinction whereas all alien species were classified as being less or least vulnerable. For vulnerability to climate change, 82% of native species were classified as highly vulnerable, compared with only 19% for aliens. Predicted climate change effects on freshwater environments will dramatically change the fish fauna of California. Most native fishes will suffer population declines and become more restricted in their distributions; some will likely be driven to extinction. Fishes requiring cold water (<22°C) are particularly likely to go extinct. In contrast, most alien fishes will thrive, with some species increasing in abundance and range. However, a few alien species will likewise be negatively affected through loss of aquatic habitats during severe droughts and physiologically stressful conditions present in most waterways during summer. Our method has high utility for predicting vulnerability to climate change of diverse fish species. It should be useful for setting conservation priorities in many different regions.
Twenty-five years of sport performance research in the Journal of Sports Sciences

Abstract In this historical review covering the past 25 years, we reflect on the content of manuscripts relevant to the Sport Performance section of the Journal of Sports Sciences. Due to the wide diversity of sport performance research, the remit of the Sport Performance section has been broad and includes mathematical and statistical evaluation of competitive sports performances, match- and notation-analysis, talent identification, training and selection or team organization. In addition, due to the academic interests of its section editors, they adopted a quality-assurance role for the Sport Performance section, invariably communicated through key editorials that subsequently shaped the editorial policy of the Journal. Key high-impact manuscripts are discussed, providing readers with some insight into what might lead an article to become a citation “classic”. Finally, landmark articles in the areas of “science and football” and “notation analysis” are highlighted, providing further insight into how such articles have contributed to the development of sport performance research in general and the Journal of Sports Sciences in particular.
Distinct Roles of Different Presynaptic and Postsynaptic NCAM Isoforms in Early Motoneuron–Myotube Interactions Required for Functional Synapse Formation

The neural cell adhesion molecule (NCAM) is expressed both presynaptically and postsynaptically during neuromuscular junction formation. Genetic deletion in mice of all three isoforms (180, 140, and 120 kDa), or just the 180 isoform, suggested that different isoforms played distinct roles in synaptic maturation. Here we characterized in mice of either sex the earliest adhesive contacts between the growth cones of motoneurons and myotubes and their subsequent maturation into functional synapses in cocultures of motoneurons and myotubes, which expressed their normal complement of NCAM isoforms, or were lacking all isoforms either presynaptically or postsynaptically. Growth cone contact with +/+ mouse myotubes resulted in immediate adhesive contacts and the rapid downregulation of growth cone motility. When contacting NCAM−/− myotubes, growth cones touched and retracted/collapsed multiple times and failed to form stable contacts, even after 10 h. Exogenous expression in myotubes of either the 180 or 140 isoform, but not the 120 kDa isoform, rescued the rapid formation of stable contacts, the accumulation of presynaptic and postsynaptic molecules, and functional transmission. When NCAM was absent only in motoneurons, growth cones did not retract upon myotube contact, but, since their motility was not downregulated, they grew off the ends of the myotubes, failing to form synapses. The agrin receptor Lrp4 was strongly downregulated in NCAM-negative myotubes, and motoneuron growth cones did not make stable contacts with Lrp4-negative myotubes. These studies have identified novel roles for presynaptic and postsynaptic NCAM in mediating early cell–cell interactions required for synapse formation. SIGNIFICANCE STATEMENT Although many molecular signals needed to form the functionally effective neuromuscular synapses required for normal movement have been described, the earliest signals that let motoneuron growth cones make stable adhesive contacts with myotubes and cease motility are not well understood. Using dynamic imaging of motoneuron–myotube cocultures, we show that NCAM is required on both the growth cone and myotube and that different NCAM isoforms mediate initial adhesion and the downregulation of growth cone motility. The agrin receptor Lrp4 was also essential for initial adhesive contacts and was downregulated on NCAM−/− myotubes. Our identification of novel roles for NCAM and Lrp4 and possible interactions between them in transforming motile growth cones into stable contacts opens interesting new avenues for exploration.
Programming Directives for Elastic Computing

Enabling and controlling the elasticity of cloud computing applications is challenging. The developer must deal with daunting tasks using low-level code to implement strategies trading off costs versus quality of service. Programming directives can substantially reduce this overhead by delegating control of elasticity to middleware systems while allowing developers to focus on defining suitable strategies. This Web extra lists example directives in the Simple-Yet-Beautiful Language (SYBL).
Hyperspectral image classification using a spectral–spatial random walker method

ABSTRACT This article proposes a spectral–spatial method for classification of hyperspectral images (HSIs) by modifying traditional random walker (RW). The proposed method consists of suggesting two main modifications. First, to construct a spatial edge weighting function, low-frequency edge weighting function is proposed. In this function, the detail weights are removed. Second, to enhance the classification accuracy, a fusion of spectral and spatial Laplacian matrix in RW is suggested. This fusion can improve the classification performances compared to traditional RW using only spatial Laplacian matrix. In comparison with some of the state-of-the-art RW and spectral–spatial classifier methods, the experimental results of the proposed method (spectral–spatial RW) show that the proposed method significantly increases the classification accuracy of HSI.
Computing the Diameters of Huge Social Networks

The diameter of a graph is the maximum distance among all pairs of nodes. Determining the diameter of a graph in the tradition way costs O(mn) time, where n is the number of nodes and m is the number of edges. A social network can be modelled as a graph. With the rapid expansion of social networks, the number of nodes in a social network could be hundreds of millions. In this paper, we propose a new approach for computing the diameters of large undirected unweighted graphs. The worst case time complexity is still O(mn). In practice, especially for social network graphs, the running time is O(m). Our approach is based on BFS to select a proper node as the starting node of a BFS process is the most important issue when computing the diameter. We show how to choose the good nodes with small cost.
Excessive Sympathetic Activation in Heart Failure With Obesity and Metabolic Syndrome: Characteristics and Mechanisms

Congestive heart failure is characterized by sympathetic activation, which has also been described in the metabolic syndrome. No information exists, however, as to whether the sympathostimulating effects of these 2 conditions summate when heart failure is complicated by the metabolic syndrome, leading to an exceedingly high adrenergic drive. This is clinically relevant, because in heart failure sympathetic activation is closely related to mortality. We studied 48 control subjects (age: 58.4±1.6 years, mean±SEM) and 89 age-matched heart failure patients (New York Heart Association class II), of whom 47 were without and 42 were with metabolic syndrome. Measurements included blood pressure (Finapres), heart rate (ECG), and sympathetic nerve traffic (microneurography) at rest and during baroreceptor manipulation. Waist circumference, blood pressure, and metabolic variables were greater in heart failure with metabolic syndrome than in heart failure without metabolic syndrome and in control subjects. Left ventricular ejection fraction and end-diastolic diameter were similarly altered in the 2 heart failure groups. Compared with control subjects, sympathetic nerve activity was greater in heart failure patients without metabolic syndrome (64.7±3.2 versus 45.8±2.9 bursts/100 heartbeats; P<0.01), a further pronounced increase being detected in those with metabolic syndrome (80.9±3.2 bursts/100 heartbeats; P<0.01). In the multivariate analysis, waist circumference and body mass index were the variables most closely related to sympathetic activation. Compared with control subjects, baroreflex responses were significantly attenuated in the 2 heart failure groups, the impairment being more marked in the group with than without metabolic syndrome. Thus, obesity and metabolic syndrome potentiate the sympathetic activation characterizing heart failure. This potentiation is likely to mainly depend on metabolic and baroreflex mechanisms.
THE EFFECT OF A COMPETITIVE COLLEGIATE FOOTBALL SEASON ON POWER PERFORMANCE AND MUSCLE OXYGEN RECOVERY KINETICS

Ten intercollegiate football players were tested within 3 days prior to (T1) and the day following the end (T2) of football preseason training camp and during weeks 7 (T3) and 11 (T4) of the competitive season. During each testing session, subjects performed a 30-second Wingate anaerobic power test. Near-infrared continuous wave spectroscopy was used to measure muscle deoxygenation during exercise. No changes in any power performance measures were seen during the competitive football season. A significant (p < 0.05) decrease in the extent of deoxygenation during exercise was observed between T2 (72.6 ± 19.4%) and T4 (50.2 ± 14.2%). A 30 and 29% difference (p < 0.05) in the onset of reoxygenation was observed between T1 and T3 and T4, respectively. A 51% decrease (p < 0.05) in halftime recovery was observed between T2 and T3. Results indicate that the extent of muscle deoxygenation is reduced during high-intensity exercise and that muscle oxygen recovery kinetics improves over the duration of a competitive season of football.
Automatic amortised analysis of dynamic memory allocation for lazy functional programs

This paper describes the first successful attempt, of which we are aware, to define an automatic, type-based static analysis of resource bounds for lazy functional programs. Our analysis uses the automatic amortisation approach developed by Hofmann and Jost, which was previously restricted to eager evaluation. In this paper, we extend this work to a lazy setting by capturing the costs of unevaluated expressions in type annotations and by amortising the payment of these costs using a notion of lazy potential. We present our analysis as a proof system for predicting heap allocations of a minimal functional language (including higher-order functions and recursive data types) and define a formal cost model based on Launchbury's natural semantics for lazy evaluation. We prove the soundness of our analysis with respect to the cost model. Our approach is illustrated by a number of representative and non-trivial examples that have been analysed using a prototype implementation of our analysis.
Surgical Management of Skull Base Meningiomas – An Overview

Meningiomas as extra axial tumours, developing from arachnoid cap cells may occur from all dural structures, cranial and spinal and rarely outside of these structures (Whittle et al. 2004). The skull base is an area with multiple neural structures as well as brain supplying adjacent arteries and veins. Meningiomas, growing on or within the skull can thus be very challenging for the neurosurgeon. In consequence, complete tumour removal without neural impairment is not always possible (Seifert 2010; Yasargil 1980) and surgery in this area, especially in petro-clival meningiomas, hazardous. Advances in microsurgical technique, development of new approaches and advancement of adjuvant therapies allow for reducing or removing meningiomas as well as a sufficient control of residual or recurrent tumours.
An OAEP Variant With a Tight Security Proof

We introduce the OAEP encoding method, which is an adaptation of the OAEP encoding method, replacing the last step of the encoding operation with an application of a block cipher such as AES. We demonstrate that if f is a one-way trapdoor function that is hard to invert, then OAEP combined with f is secure against an INDCCA2 adversary in the random oracle model. Moreover, the security reduction is tight; an adversary against f -OAEP can be extended to an f -inverter with a running time linear in the number of oracle queries. 1