Miracle-dz/UniFAR-FTUs huggingface dataset:
Symptom and activities of daily living trajectory in multiple sclerosis: a 10-year study.

BACKGROUND Symptom control in chronic illness is not merely a matter of medical management as the patient and family must rely on their own judgment, wisdom, and ingenuity for controlling symptoms. The absence in the literature regarding the effects of multiple sclerosis (MS) as perceived by afflicted people and their family members led to the 10-year longitudinal study. OBJECTIVES To study patient self-report data to determine whether particular interventions may be needed to enhance the individual's comfort and functional levels. METHODS The chronic illness trajectory of three groups of people with MS (< or =5 years of diagnosis, n=49; >5 to 10 years, n=36; and >10 years, n=68) was examined over a 10-year period. Serial self-assessments of the subjects' prevalence of MS-related symptoms (motor, brain stem, sensory, elimination, mental/emotional) and level of activities of daily living (ADL) functioning (fine and gross motor activities, sensory/communication, socializing/recreation, intimacy) were obtained annually. Profiles illustrating the subject's symptom and ADL pattern were also returned annually to each subject. RESULTS Using 10-year average scores, study findings indicated no group differences relative to symptoms but showed significant group differences in all ADL functions. Separate group within-year (1, 3, 5, 7, 10) comparisons reflected significant increases in motor, brain stem, and elimination symptoms together with a decline in all ADL functions for specific groups. CONCLUSIONS Medical data suggest, on average, a continuous downward trajectory beginning in the first years of illness or at approximately 36 to 37 years of age. In contrast, in this research, patient self-reports of fine and gross motor ADL, a correlate of neurologically based disability evaluations, reflect that relatively major decline begins after 5 years post-diagnosis and after age 40 for subjects recruited primarily from nonclinical sites.
The Phox Homology (PX) Domain-dependent, 3-Phosphoinositide-mediated Association of Sorting Nexin-1 with an Early Sorting Endosomal Compartment Is Required for Its Ability to Regulate Epidermal Growth Factor Receptor Degradation*

Recent studies have shown that phox homology (PX) domains act as phosphoinositide-binding motifs. The majority of PX domains studied show binding to phosphatidylinositol 3-monophosphate (PtdIns(3)P), an association that allows the host protein to localize to membranes of the endocytic pathway. One issue, however, is whether PX domains may have alternative phosphoinositide binding specificities that could target their host protein to distinct subcellular compartments or allow their allosteric regulation by phosphoinositides other than PtdIns(3)P. It has been reported that the PX domain of sorting nexin 1 (SNX1) specifically binds phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) (Zhong, Q., Lazar, C. S., Tronchere, H., Sato, T., Meerloo, T., Yeo, M., Songyang, Z., Emr, S. D., and Gill, G. N. (2002)Proc. Natl. Acad. Sci. U. S. A. 99, 6767–6772). In the present study, we have shown that whereas SNX1 binds PtdIns(3,4,5)P3 in protein:lipid overlay assays, in liposomes-based assays, binding is observed to PtdIns(3)P and phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2) but not to PtdIns(3,4,5)P3. To address the significance of PtdIns(3,4,5)P3 binding, we examined the subcellular localization of SNX1 under conditions in which plasma membrane PtdIns(3,4,5)P3 levels were significantly elevated. Under these conditions, we failed to observe association of SNX1 with this membrane. However, consistent with the binding to PtdIns(3)P and PtdIns(3,5)P2 being of more physiological significance was the observation that the association of SNX1 with an early endosomal compartment was dependent on a 3-phosphoinositide-binding PX domain and the presence of PtdIns(3)P on this compartment. Finally, we have shown that the PX domain-dependent/early endosomal association of SNX1 is important for its ability to regulate the targeting of internalized epidermal growth factor receptor for lysosomal degradation.
The Design and Implementation of Typed Scheme: From Scripts to Programs

When scripts in untyped languages grow into large programs, maintaining them becomes difficult. A lack of explicit type annotations in typical scripting languages forces programmers to must (re)discover critical pieces of design information every time they wish to change a program. This analysis step both slows down the maintenance process and may even introduce mistakes due to the violation of undiscovered invariants. This paper presents Typed Scheme, an explicitly typed extension of PLT Scheme, an untyped scripting language. Its type system is based on the novel notion of occurrence typing, which we formalize and mechanically prove sound. The implementation of Typed Scheme additionally borrows elements from a range of approaches, including recursive types, true unions and subtyping, plus polymorphism combined with a modicum of local inference. The formulation of occurrence typing naturally leads to a simple and expressive version of predicates to describe refinement types. A Typed Scheme program can use these refinement types to keep track of arbitrary classes of values via the type system. Further, we show how the Typed Scheme type system, in conjunction with simple recursive types, is able to encode refinements of existing datatypes, thus expressing both proposed variations of refinement types.
Perspective: how to make microarray, serial analysis of gene expression, and proteomic relevant to day-to-day endocrine problems and physiological systems.

The recent mapping of the human genome has opened the way to novel technologies for identifying new genes or clustering regulated genes and proteins in a tissueand cellspecific manner. Microarray and serial analysis of gene expression (SAGE) are quite powerful in this regard, and they generate on a day-to-day basis data banks of gene profile from cells or tissues of animals challenged with different compounds including hormones. Here we review these techniques with their strengths and limits in physiological systems with a particular emphasis on the endocrine system. We also present new developing techniques in proteomic, especially for the analysis of functional proteins and proteinprotein interaction. Although we are still at the embryonic stage of the proteomic area, there is no doubt that the current ongoing work will have a great impact in endocrinology. There are also serious drawbacks that have to be taken into consideration to prevent generating data that may either be nonphysiological or difficult to interpret, the most critical one being the experimental design. Since the crystallization of the first hormone—adrenalin—by Takamine and Aldrich at the beginning of the twentieth century, modern endocrinology kept growing to comprise various fields of research, namely cytology, cellular biology, and more recently molecular biology and genetic. During the past two decades, large-scale sequencing efforts including the Human Genome Project (1) generated initial large-scale databases, and numerous new genes were discovered, some of them encoding proteins with a function still remaining to be unraveled. Recent progress in biotechnology, more particularly in gene expression microarray and SAGE technologies gave us new tools for identifying gene functions and much more (see Table 1). Actually, microarray and SAGE experiments allow us to test the expression of thousands of genes simultaneously and to identify automatically the genes of interest. In the same way, based on the last developments in the technologies of protein separation, quantification, and identification, protein expression profiles are now available with proteomics. Because proteins are final posttranslational products from mRNA, proteomics will give us access to a new database with particular biological significance. Today, in the scientific literature, the number and diversity of data generated from microarray experiments are impressive and there are already numerous reports covering the whole biomedical community. In the field of endocrinology, analysis of both gene and protein expression will be quite powerful tools to study the regulation of physiological mechanisms triggered or inhibited by hormones. Here we review how to make DNA microarrays, SAGE, and proteomics relevant in modern endocrinology.
Do hemodialysis patients prefer renal-specific or standard oral nutritional supplements?

OBJECTIVE We investigated whether hemodialysis (HD) patients prefer standard or renal-specific oral nutritional supplements (ONS). DESIGN Standard ONS Fortisip (Nutricia Clinical Care, Wiltshire, Trowbridge, UK) and renal ONS Renilon (Nutricia Clinical Care) and Nepro (Abbott Laboratories, Ltd., Maidenhead, Berkshire, UK) were compared using single-blind taste tests and face-to-face, interviewer-administered questionnaires. SETTING This study took place in our HD unit in September 2007. PATIENTS There were 40 patients, including 24 males, 14 smokers, and 26 Caucasians, aged <30 years (n = 6), 31 to 50 years (n = 13), 51 to 70 years (n = 12), and >70 years (n = 9). INTERVENTION Patients ranked ONS taste on a Likert scale (1 to 5), and compared flavor options, phosphate-binder requirements, and fluid contribution. MAIN OUTCOME MEASURE Which factors influenced a patient's choice of ONS? RESULTS Gender, smoking status, ethnicity, and age influenced patients' choices. The taste of Fortisip and Nepro was liked by 58% (n = 23), versus 28% liking Renilon (n = 11). Renilon was disliked by 35% (n = 14), Nepro was disliked by 30% (n = 12), and Fortisip was disliked by 25% (n = 10). The favorite taste was Fortisip, in 52% (n = 21). However, 21% (n = 4) who preferred the taste of renal ONS would not choose them long-term because of their limited flavor ranges. The lack of phosphate binders with Renilon was a deciding factor in 27% (n = 19/33). The low fluid contribution of renal ONS influenced the choice of 43% (n = 12/28). All factors considered, standard ONS remained most popular for patients aged >70 years. However, in all other subgroups, and particularly males and non-Caucasians, renal ONS became more popular. Many patients (23%; n = 9) would sacrifice taste for the benefits of renal ONS. CONCLUSIONS Renal ONS are more popular in HD patients because of their low fluid contribution and phosphate-binder requirements, which can influence preference over taste. Patients need information to make informed choices.
Listening, corporeality and presence.

The use of sound to create or enhance the sense of presence is well recognized and the measurements of which have focused on hearing, e.g. “were you able to identify a particular sound? ”, “how well could you localize the sounds”. To this treatment of audition we now add, listening. Listening is active, directed, intentional hearing. This aspect of the phenomenology of sound - listening - has received relatively little attention from the presence community. Focusing on listening has one further consequence - it underlines the corporeality of the listener. Listening is not merely ego-centric it is body-centric. Hearing, in contrast, is allo-centric – “The sounds appears to be coming from over there”. We suggest that an exploration of the nature of listening in virtual environments may contribute to the understanding of presence and its relation to corporeality. A classification scheme is proposed and applied to an empirical study of listening in real and simulated environments.
Improving performance on switchboard by combining hybrid HME/HMM and mixture of Gaussians acoustic models

This paper presents results of our e(cid:11)orts on combining standard mixture of Gaussians acoustic modeling [10] with a context-dependent hybrid connectionist HME/HMM architecture [3, 4] for the Switchboard corpus. Using a score normalization scheme which is independent of the stream’s modeling paradigm and adaptive methods for combining multiple probability distributions, we achieve a relative decrease in word error rate of 3.5% and 9.3%, compared to each of the single stream systems. As opposed to multiple acoustic streams based on mixture of Gaussians, the integration of hybrid NN/HMM based modeling appears to be advantageous since the differences in modeling techniques and training algorithms allow to capture di(cid:11)erent aspects of the speech signal. Small dependence among emission probability estimates is considered essential for potential gains in interpolated systems.
Extracellular α-Galactosidase from Trichoderma sp. (WF-3): Optimization of Enzyme Production and Biochemical Characterization

Trichoderma spp. have been reported earlier for their excellent capacity of secreting extracellular α-galactosidase. This communication focuses on the optimization of culture conditions for optimal production of enzyme and its characterization. The evaluation of the effects of different enzyme assay parameters such as stability, pH, temperature, substrate concentrations, and incubation time on enzyme activity has been made. The most suitable buffer for enzyme assay was found to be citrate phosphate buffer (50 mM, pH 6.0) for optimal enzyme activity. This enzyme was fairly stable at higher temperature as it exhibited 72% activity at 60°C. The enzyme when incubated at room temperature up to two hours did not show any significant loss in activity. It followed Michaelis-Menten curve and showed direct relationship with varying substrate concentrations. Higher substrate concentration was not inhibitory to enzyme activity. The apparent Michaelis-Menten constant (K m), maximum rate of reaction (V max), K cat, and catalytic efficiency values for this enzyme were calculated from the Lineweaver-Burk double reciprocal plot and were found to be 0.5 mM, 10 mM/s, 1.30 U mg−1, and 2.33 U mg−1 mM−1, respectively. This information would be helpful in understanding the biophysical and biochemical characteristics of extracellular α-galactosidase from other microbial sources.
A Comparative Performance Analysis of Remote GPU Virtualization over Three Generations of GPUs

The use of Graphics Processing Units (GPUs) has become a very popular way to accelerate the execution of many applications. However, GPUs are not exempt from side effects. For instance, GPUs are expensive devices which additionally consume a non-negligible amount of energy even when they are not performing any computation. Furthermore, most applications present low GPU utilization. To address these concerns, the use of GPU virtualization has been proposed. In particular, remote GPU virtualization is a promising technology that allows applications to transparently leverage GPUs installed in any node of the cluster. In this paper the remote GPU virtualization mechanism is comparatively analyzed across three different generations of GPUs. The goal of this study is to analyze how the performance of the remote GPU virtualization technique is impacted by the underlying hardware. To that end, the Tesla K20, Tesla K40 and Tesla P100 GPUs along with FDR and EDR InfiniBand fabrics are used in the study. The analysis is performed in the context of the rCUDA middleware. It is clearly shown that the GPU virtualization middleware requires a comprehensive design of its communication layer, which should be perfectly adapted to every hardware generation in order to avoid a reduction in performance.
Impact of Federal drug law enforcement on the supply of heroin in Australia.

AIMS To conduct an empirical investigation of the efficacy of law enforcement in reducing heroin supply in Australia. Specifically, this paper addresses the question of whether heroin purity levels in the Australian Capital Territory (ACT) could be predicted by heroin seizures at the national level by the Australian Federal Police (AFP) in the preceding year. DESIGN We considered two forms of evidence. First, a Bayesian Markov Chain Monte Carlo (MCMC) change-point model was used to discover (a) if there was a substantial increase in heroin seizures by the AFP, (b) when the increase began and (c) whether it occurred after increased funding to the Australian Federal Police for the purpose of drug law enforcement. Second, standard time-series methods were used to ascertain whether fluctuations in heroin seizure weights or the frequency of large-scale seizures after the aforementioned changes in seizure levels predicted fluctuations in heroin purity levels in the ACT after autocorrelation had been removed from the purity series. FINDINGS A Bayesian MCMC change-point model supported the hypothesis that heroin seizures rapidly increased about a year before the estimated decline in heroin purity and after the increased funding of AFP. The autoregression models suggested that 10-20% of the variance in the residuals of the heroin purity series was predicted by appropriately lagged residuals of the seizure-number and log-weight series, after autocorrelation had been removed. CONCLUSION The overall results are consistent with the hypothesis that large-scale heroin seizures by the AFP reduce street-level heroin supply a year or so later, although the short-term dynamics suggest an 'opponent' response to residual fluctuations in seizures. To our knowledge, this is first time a connection has been identified between large-scale heroin seizures and street-level supply.
Generating Random Networks Without Short Cycles

Random graph generation is an important tool for studying large complex networks. Despite abundance of random graph models, constructing models with application-driven constraints is poorly understood. In order to advance state-of-the-art in this area, we focus on random graphs without short cycles as a stylized family of graphs, and propose the RandGraph algorithm for randomly generating them. For any constant k, when m=O(n^{1+1/[2k(k+3)]}), RandGraph generates an asymptotically uniform random graph with n vertices, m edges, and no cycle of length at most k using O(n^2m) operations. We also characterize the approximation error for finite values of n. To the best of our knowledge, this is the first polynomial-time algorithm for the problem. RandGraph works by sequentially adding $m$ edges to an empty graph with n vertices. Recently, such sequential algorithms have been successful for random sampling problems. Our main contributions to this line of research includes introducing a new approach for sequentially approximating edge-specific probabilities at each step of the algorithm, and providing a new method for analyzing such algorithms.
From false belief to friendship: commentary on Fink, Begeer, Peterson, Slaughter, and de Rosnay.

Fink, Begeer, Peterson, Slaughter, and de Rosnay (Brit. J. Dev. Psychol, 2015; 33, 1-17) represent a welcome contribution in providing empirical evidence of the link from false belief understanding at Time 1 to mutual friendship 2 years later, controlling for several other possible contributors. This opens a new and important line of inquiry into the practical significance of a Theory of Mind. As is typical of pioneering research, further study is needed to address some issues; here, we point out some of these issues and then briefly discuss the broader implications of Fink et al.'s findings.
Stress and immunity in humans: a meta‐analytic review.

&NA; This article presents a meta‐analysis of the literature on stress and immunity in humans. The primary analyses include all relevant studies irrespective of the measure or manipulation of stress. The results of these analyses show substantial evidence for a relation between stress and decreases in functional immune measures (proliferative response to mitogens and natural killer cell activity). Stress is also related to numbers and percent of circulating white blood cells, immunoglobulin levels, and antibody titers to herpesviruses. Subsequent analyses suggest that objective stressful events are related to larger immune changes than subjective self‐reports of stress, that immune response varies with stressor duration, and that interpersonal events are related to different immune outcomes than nonsocial events. We discuss the way neuroendocrine mechanisms and health practices might explain immune alteration following stress, and outline issues that need to be investigated in this area.
Commonsense Conceptions of Emergent Processes: Why Some Misconceptions Are Robust

This article offers a plausible domain-general explanation for why some concepts of processes are resistant to instructional remediation although other, apparently similar concepts are more easily understood. The explanation assumes that processes may differ in ontological ways: that some processes (such as the apparent flow in diffusion of dye in water) are emergent and other processes (such as the flow of blood in human circulation) are direct. Although precise definition of the two kinds of processes are probably impossible, attributes of direct and emergent processes are described that distinguish them in a domain-general way. Circulation and diffusion, which are used as examples of direct and emergent processes, are associated with different kinds of misconceptions. The claim is that students' misconceptions for direct kinds of processes, such as blood circulation, are of the same ontological kind as the correct conception, suggesting that misconceptions of direct processes may be nonrobust. However, students' misconceptions of emergent processes are robust because they misinterpret emergent processes as a kind of commonsense direct processes. To correct such a misconception requires a re-representation or a conceptual shift across ontological kinds. Therefore, misconceptions of emergent processes are robust because such a shift requires that students know about the emergent kind and can overcome their (perhaps even innate) predisposition to conceive of all processes as a direct kind. Such a domain-general explanation suggests that teaching students the causal structure underlying emergent processes may enable them to recognize and understand a variety of emergent processes for which they have robust misconceptions, such as concepts of electricity, heat and temperature, and evolution.