Miracle-dz/UniFAR-FTUs huggingface dataset:
Barth Syndrome: From Mitochondrial Dysfunctions Associated with Aberrant Production of Reactive Oxygen Species to Pluripotent Stem Cell Studies

Mutations in the gene encoding the enzyme tafazzin, TAZ, cause Barth syndrome (BTHS). Individuals with this X-linked multisystem disorder present cardiomyopathy (CM) (often dilated), skeletal muscle weakness, neutropenia, growth retardation, and 3-methylglutaconic aciduria. Biopsies of the heart, liver and skeletal muscle of patients have revealed mitochondrial malformations and dysfunctions. It is the purpose of this review to summarize recent results of studies on various animal or cell models of Barth syndrome, which have characterized biochemically the strong cellular defects associated with TAZ mutations. Tafazzin is a mitochondrial phospholipidlysophospholipid transacylase that shuttles acyl groups between phospholipids and regulates the remodeling of cardiolipin (CL), a unique inner mitochondrial membrane phospholipid dimer consisting of two phosphatidyl residues linked by a glycerol bridge. After their biosynthesis, the acyl chains of CLs may be modified in remodeling processes involving up to three different enzymes. Their characteristic acyl chain composition depends on the function of tafazzin, although the enzyme itself surprisingly lacks acyl specificity. CLs are crucial for correct mitochondrial structure and function. In addition to their function in the basic mitochondrial function of ATP production, CLs play essential roles in cardiac function, apoptosis, autophagy, cell cycle regulation and Fe-S cluster biosynthesis. Recent developments in tafazzin research have provided strong insights into the link between mitochondrial dysfunction and the production of reactive oxygen species (ROS). An important tool has been the generation of BTHS-specific induced pluripotent stem cells (iPSCs) from BTHS patients. In a complementary approach, disease-specific mutations have been introduced into wild-type iPSC lines enabling direct comparison with isogenic controls. iPSC-derived cardiomyocytes were then characterized using biochemical and classical bioenergetic approaches. The cells are tested in a “heart-on-chip” assay to model the pathophysiology in vitro, to characterize the underlying mechanism of BTHS deriving from TAZ mutations, mitochondrial deficiencies and ROS production and leading to tissue defects, and to evaluate potential therapies with the use of mitochondrially targeted antioxidants.
Seasonal habitat use by Elephants (Loxodonta africana) in the Mole National Park of Ghana

Abstract To avoid unnecessary waste of limited resources and to help prioritize areas for conservation efforts, this study aimed to provide information on habitat use by elephants between the wet and dry seasons in the Mole National Park (MNP) of Ghana. We compiled coordinates of 516 locations of elephants’ encounters, 256 for dry season and 260 for wet season. Using nine predictor variables, we modeled the probability of elephant's distribution in MNP. We threshold the models to “suitable” and “nonsuitable” regions of habitat use using the equal training sensitivity and specificity values of 0.177 and 0.181 for the dry and wet seasons, respectively. Accuracy assessment of our models revealed a sensitivity score of 0.909 and 0.974, and a specificity of 0.579 and 0.753 for the dry and wet seasons, respectively. A TSS of 0.488 was also recorded for the dry season and 0.727 for the wet season indicating a good model agreement. Our model predicts habitat use to be confined to the southern portion of MNP due to elevation difference and a relatively steep slope that separates the northern regions of the park from the south. Regions of habitat use for the wet season were 856 km2 and reduced significantly to 547.68 km2 in the dry season. We observed significant overlap (327.24 km2) in habitat use regions between the wet and dry seasons (Schoener's D = 0.922 and Hellinger's‐based I = 0.991). DEM, proximity to waterholes, and saltlicks were identified as the key variables that contributed to the prediction. We recommend construction of temporal camps in regions of habitat use that are far from the headquarters area for effective management of elephants. Also, an increase in water point's density around the headquarters areas and selected dry areas of the park will further decrease elephant's range and hence a relatively less resource use in monitoring and patrols.
A Burst-Mode Digital Receiver With Programmable Input Jitter Filtering for Energy Proportional Links

A full-rate burst-mode receiver that achieves fast on/off operation needed for energy-proportional links is presented. By injecting input data edges into the oscillator embedded in a classical Type-II digital clock and data recovery (CDR) circuit, the proposed receiver achieves instantaneous phase-locking and input jitter filtering simultaneously. In other words, the proposed CDR combines the advantages of conventional feed-forward and feedback architectures to achieve energy-proportional operation. By controlling the number of data edges injected into the oscillator, both the jitter transfer bandwidth and the jitter tolerance corner are accurately controlled. The feedback loop also corrects for any frequency error and helps improve CDR's immunity to oscillator frequency drift during the power-on and -off states. This also improves CDR's tolerance to consecutive identical digits present in the input data. Fabricated in a 90 nm CMOS process, the prototype receiver instantaneously locks onto the very first data edge and consumes 6.1 mW at 2.2 Gb/s. Owing to its short power-on time, the receiver's energy efficiency varies only from 2.77 pJ/bit to 3.87 pJ/bit when the effective data rate is varied from 0.44 Gb/s to 2.2 Gb/s. Input sensitivity of the receiver is 36 mV for a BER of 10-12.
Evaluation of a Unique Interprofessional Education Program Involving Medical and Pharmacy Students

Objective. To measure changes in interprofessional competencies among pharmacy and medical students following a half-day event focusing on interprofessional learning. Methods. There were 118 pharmacy students and 28 medical students who participated in the Healthcare Interprofessional Education Day (HIPED) which consisted of three stations (communication, patient interviewing, and prescribing) in which pharmacy and medical students had to work collaboratively. The standardized Interprofessional Collaborative Competency Attainment Survey (ICCAS) was used to evaluate the effectiveness of the program. Results. There were 133 surveys completed for a response rate of 91%. All 20 items measured by the ICCAS showed a significant improvement. The strongest effect sizes were in the collaboration, roles & responsibilities, and collaborative practice/family-centered approach categories. The least robust effects were in the conflict management/resolution category. Conclusion. The HIPED activity was an effective IPE experience. The strong and consistent improvement in all ICCAS scores suggest a framework for pharmacy and medical school training to move from siloed educational experiences to synergistic learning opportunities.
Seamless surface mappings

We introduce a method for computing seamless bijective mappings between two surface-meshes that interpolates a given set of correspondences. A common approach for computing a map between surfaces is to cut the surfaces to disks, flatten them to the plane, and extract the mapping from the flattenings by composing one flattening with the inverse of the other. So far, a significant drawback in this class of techniques is that the choice of cuts introduces a bias in the computation of the map that often causes visible artifacts and wrong correspondences. In this paper we develop a surface mapping technique that is indifferent to the particular cut choice. This is achieved by a novel type of surface flattenings that encodes this cut-invariance, and when optimized with a suitable energy functional results in a seamless surface-to-surface map. We show the algorithm enables producing high-quality seamless bijective maps for pairs of surfaces with a wide range of shape variability and from a small number of prescribed correspondences. We also used this framework to produce three-way, consistent and seamless mappings for triplets of surfaces.
Participation Changes in Sexual Functioning after Mild Stroke

The purpose of this study was to explore the extent to which people with mild stroke experience changes in participation in sexual activity post stroke. A cross-sectional study was completed with adults 6 to 18 months post mild stroke (N = 13); a brief case study was also done with one of the participants. Participants completed an assessment battery over the telephone that included the modified Quality of Sexual Function scale, the Stroke Impact Scale (SIS), and the Patient Health Questionnaire-9. The sample reported mild problems with sexual dysfunction (mean = 10.77, SD = 4.09). Sexual dysfunction post stroke was highly correlated (r = −0.372 to −0.875) with all of the domains on the SIS. Several participants in this study reported that they would have liked more information about sexual functioning post stroke. These findings suggest that individuals with mild stroke are experiencing decreased participation in sexual activities post stroke and would like more information from the health care community on the potential for sexual changes.
Time of Day Affects Episodic Memory in Older Adults

ABSTRACT The neuropsychological test scores of 2,030 cognitively normal older adults were examined to evaluate performance patterns as they related to time of day (TOD) at which testing was initiated. Multiple regression analyses were used to examine the association of TOD with scores on seven neuropsychological tests used in the clinical evaluation of dementia. Episodic memory performance was significantly related to TOD, while memory span and verbal fluency were not. Best performance occurred during early morning hours and late afternoon; worst performance occurred mid-day (i.e., noon). These findings may have implications for clinical assessment, the design of research on dementia, and the daily functioning of older adults.
Digital Elevation Model (DEM) generation using airborne SAR interferometry (InSAR)

Information about the shape of the Earth’s surface is important in many applications as it helps users to visualize and analyze geographic problems accurately in 3D. This paper focuses on the InSAR technique of generating Digital Elevation Models (DEM) by using InSAR data acquired from an airborne platform. The data cover a study area of 4 km x 3 km located in Thetford Forest, East Anglia, United Kingdom. They were collected by an experimental SAR sensor (E-SAR) carried onboard a DLR aircraft as part of the UK’s first SHAC campaign in July 2000. This study demonstrates that DEM generated from airborne InSAR data are highly correlated with ground topography. Ground elevations in the test area were measured using the Global Positioning System (GPS) and Total Station techniques. It was found that the RMS error of the InSAR-derived DEM was less than 2.0m. The possibility of generating topographic elevations for under forest cover was also examined. Ground elevations were derived from the Ordnance Survey (GB) 1:10000 digital contour map, while the UK Forestry Commission’s tree height model was used to estimate tree heights. It was thus possible to estimate the penetration depth of the radar signal into the canopy. It was found that penetration depth increases with the age of the trees.
The Likelihood of Preventing Respiratory Exacerbations in Children and Adolescents with either Chronic Suppurative Lung Disease or Bronchiectasis

Chronic suppurative lung disease (CSLD) and bronchiectasis in children and adolescents are important causes of respiratory morbidity and reduced quality of life (QoL), also leading to subsequent premature death during adulthood. Acute respiratory exacerbations in pediatric CSLD and bronchiectasis are important markers of disease control clinically, given that they impact upon QoL and increase health-care-associated costs and can adversely affect future lung functioning. Preventing exacerbations in this population is, therefore, likely to have significant individual, familial, societal, and health-sector benefits. In this review, we focus on therapeutic interventions, such as drugs (antibiotics, mucolytics, hyperosmolar agents, bronchodilators, corticosteroids, non-steroidal anti-inflammatory agents), vaccines and physiotherapy, and care-planning, such as post-hospitalization management and health promotion strategies, including exercise, diet, and reducing exposure to environmental toxicants. The review identified a conspicuous lack of moderate or high-quality evidence for preventing respiratory exacerbations in children and adolescents with CSLD or bronchiectasis. Given the short- and long-term impact of exacerbations upon individuals, their families, and society as a whole, large studies addressing interventions at the primary and tertiary prevention phases are required. This research must include children and adolescents in both developing and developed countries and address long-term health outcomes.
Demographic Factors and Playing Variables in Online Computer Gaming

Despite the growing popularity of online game playing, there has been no primary survey of its players. Therefore, an online questionnaire survey was used to examine basic demographic factors of online computer game players who played the popular online game Everquest (i.e., gender, age, marital status, nationality, education level, occupation). The survey also examined playing frequency (i.e., amount of time spent playing the game a week), playing history (i.e., how long they had been playing the game, who they played the game with, whether they had ever gender swapped their game character), the favorite and least favorite aspects of playing the game, and what they sacrifice (if anything) to play the game. Results showed that 81% of online game players were male, and that the mean age of players was 27.9 years of age. For many players, the social aspects of the game were the most important factor in playing. A small minority of players appear to play excessively (over 80 h a week), and results suggest that a small minority sacrifice important activities in order to play (e.g., sleep, time with family and/or partner, work, or schooling).
Age‐related brain structural alterations in children with specific language impairment

Previous neuroimaging studies have suggested that children with specific language impairment (SLI) may show subtle anatomical alterations in specific brain regions. We aimed to characterize structural abnormalities in children with SLI using a voxel‐wise analysis over the whole brain. Subjects covered a wide age range (5–17 years) in order to assess the dynamic nature of the disorder across childhood. Three‐dimensional MRIs were collected from 36 children with SLI and from a comparable group of healthy controls. Global gray and white matter measurements were obtained for each subject, and voxel‐based morphometry (VBM) was used to evaluate between‐group differences in regional brain anatomy. Possible age‐related changes were assessed in separate analyses of younger (below 11 years of age) and older children. SLI patients showed larger global gray and white matter volumes, particularly in the younger subgroup. Voxel‐wise analyses of the whole sample showed two regions of increased gray matter volume in SLI: the right perisylvian region and the occipital petalia. Age‐group analyses suggested a more extended pattern of volume increases in the younger subjects, which included entorhinal, temporopolar, caudate nucleus, motor‐precentral and precuneus gray matter, and white matter of the frontal and temporal lobes. Our results suggest that in the SLI brain there are enduring anatomical alterations that exist across a wide age range, as well as a distributed pattern of abnormalities that appear to normalize with development. They also suggest that the neuroanatomical basis of SLI may be better characterized by considering the dynamic course of the disorder throughout childhood. Hum Brain Mapp 2009. © 2008 Wiley‐Liss, Inc.
A simulation study on the effects of dendritic morphology on layer V prefrontal pyramidal cell firing behavior

Pyramidal cells, the most abundant neurons in neocortex, exhibit significant structural variability across different brain areas and layers in different species. Moreover, in response to a somatic step current, these cells display a range of firing behaviors, the most common being (1) repetitive action potentials (Regular Spiking—RS), and (2) an initial cluster of 2–5 action potentials with short interspike interval (ISIs) followed by single spikes (Intrinsic Bursting—IB). A correlation between firing behavior and dendritic morphology has recently been reported. In this work we use computational modeling to investigate quantitatively the effects of the basal dendritic tree morphology on the firing behavior of 112 three-dimensional reconstructions of layer V PFC rat pyramidal cells. Particularly, we focus on how different morphological (diameter, total length, volume, and branch number) and passive [Mean Electrotonic Path length (MEP)] features of basal dendritic trees shape somatic firing when the spatial distribution of ionic mechanisms in the basal dendritic trees is uniform or non-uniform. Our results suggest that total length, volume and branch number are the best morphological parameters to discriminate the cells as RS or IB, regardless of the distribution of ionic mechanisms in basal trees. The discriminatory power of total length, volume, and branch number remains high in the presence of different apical dendrites. These results suggest that morphological variations in the basal dendritic trees of layer V pyramidal neurons in the PFC influence their firing patterns in a predictive manner and may in turn influence the information processing capabilities of these neurons.
Heparanase-mediated Loss of Nuclear Syndecan-1 Enhances Histone Acetyltransferase (HAT) Activity to Promote Expression of Genes That Drive an Aggressive Tumor Phenotype*

Heparanase acts as a master regulator of the aggressive tumor phenotype in part by enhancing expression of proteins known to drive tumor progression (e.g. VEGF, MMP-9, hepatocyte growth factor (HGF), and RANKL). However, the mechanism whereby this enzyme regulates gene expression remains unknown. We previously reported that elevation of heparanase levels in myeloma cells causes a dramatic reduction in the amount of syndecan-1 in the nucleus. Because syndecan-1 has heparan sulfate chains and because exogenous heparan sulfate has been shown to inhibit the activity of histone acetyltransferase (HAT) enzymes in vitro, we hypothesized that the reduction in nuclear syndecan-1 in cells expressing high levels of heparanase would result in increased HAT activity leading to stimulation of protein transcription. We found that myeloma cells or tumors expressing high levels of heparanase and low levels of nuclear syndecan-1 had significantly higher levels of HAT activity when compared with cells or tumors expressing low levels of heparanase. High levels of HAT activity in heparanase-high cells were blocked by SST0001, an inhibitor of heparanase. Restoration of high syndecan-1 levels in heparanase-high cells diminished nuclear HAT activity, establishing syndecan-1 as a potent inhibitor of HAT. Exposure of heparanase-high cells to anacardic acid, an inhibitor of HAT activity, significantly suppressed their expression of VEGF and MMP-9, two genes known to be up-regulated following elevation of heparanase. These results reveal a novel mechanistic pathway driven by heparanase expression, which leads to decreased nuclear syndecan-1, increased HAT activity, and up-regulation of transcription of multiple genes that drive an aggressive tumor phenotype.
Who is more likely to use doctor-rating websites, and why? A cross-sectional study in London

Objectives To explore the extent to which doctor-rating websites are known and used among a sample of respondents from London. To understand the main predictors of what makes people willing to use doctor-rating websites. Design A cross-sectional study. Setting The Borough of Hammersmith and Fulham, London, England. Participants 200 individuals from the borough. Main outcome measures The likelihood of being aware of doctor-rating websites and the intention to use doctor-rating websites. Results The use and awareness of doctor-rating websites are still quite limited. White British subjects, as well as respondents with higher income are less likely to use doctor-rating websites. Aspects of the doctor–patient relationship also play a key role in explaining intention to use the websites. The doctor has both a ‘complementary’ and ‘substitute’ role with respect to Internet information. Conclusions Online rating websites can play a major role in supporting patients’ informed decisions on which healthcare providers to seek advice from, thus potentially fostering patients’ choice in healthcare. Subjects who seek and provide feedback on doctor-ranking websites, though, are unlikely to be representative of the overall patients’ pool. In particular, they tend to over-represent opinions from non-White British, medium–low-income patients who are not satisfied with their choice of the healthcare treatments and the level of information provided by their GP. Accounting for differences in the users’ characteristics is important when interpreting results from doctor-rating sites.
Sparse and robust kernel methods

Statistical inference inescapably involves dealing with uncertainty, whether “out there” in the real world, or in the parameters of a hypothetical model. A powerful framework built upon the foundation of Bayes’ theorem provides a set of mathematically sound rules for manipulating a probabilistic representation of belief in the light of new evidence. The Gaussian process (GP) is a widely extensible class of models to which all the mechanics of Bayesian inference may be applied: uncertainties are propagated into predictions for “error bars”, and the evidence framework can be employed as a principled method for learning parameters higher in the model hierarchy. This thesis explores methods that allow the wider application of GPs by addressing issues of complexity and robustness. Computationally, the GP becomes unwieldy for modelling relationships between more than a few hundred points due to the cubic scaling of inference and quadratic scaling of prediction times. A generic algorithm is presented, applicable to any sampling distribution, that reduces these costs to O(NM2) and O(M2) for N data points, using a small “active set” of size M . Supervised dimensionality reduction is investigated as a possible source of further advantage, and the model is evaluated for the common task of binary classification. For the convenience of a fully tractable GP inference problem, it is often assumed that data have been corrupted with independent and identically distributed Gaussian noise. In domains of heavy-tailed or heteroscedastic corruptions this assumption is inappropriate. A new noise model is presented in which fluctuations in sample variance are achieved by using a second GP to partition softly between two noise regimes. This design permits an efficient deterministic inference, avoiding the need for slow stochastic sampling of the posterior. The faithfulness of the result using an approximate posterior is compared to that returned by Monte Carlo integration. The model is further shown to come from a certain class of GP mixtures; applications of the design to classification and more general regression and mixture modelling tasks are discussed, in each of which the benefit of deterministic inference is retained.