Miracle-dz/UniFAR-FTUs huggingface dataset:
Population screening for carrier status: effects of test limitations on precision of carrier prevalence rates.

Because of genetic heterogeneity and ambiguity of test results, only rarely will carrier screening identify all carriers of a given autosomal recessive disorder. However, the fraction of carriers identified by the test can be estimated in a case frequency study. The population carrier rate then is the rate observed in a population screening study divided by the fraction of all defective alleles detected by the screening test, estimated in the case frequency study. For example, suppose 3% of a population are found to carry the delta F508 mutation for cystic fibrosis (CF) during population screening. If a case frequency study in this same population finds that 75% of the alleles of CF cases represent the delta F508 mutation, then the estimated population carrier rate is 4% (= .03/.75). The precision of this estimate involves the precision of both the fraction of carriers detected in the case frequency study and the proportion of carriers observed in the population screening study. Standard formulae for estimating the confidence interval and sample size consider only the variability in the population screening study. Since these formulae underestimate the true variability of the estimate of the population carrier rate, the sample size calculated for a population screening study is also underestimated. We present formulae which incorporate the variability in both factors, and illustrate the effect of this additional variability on confidence limits for estimates and sample size when planning a study.
The self‐reported quality of life of Lithuanian children with asthma was comparable to Western populations

Quality of life (QoL) has been widely researched among children with asthma in Western countries, but there is a lack of data from eastern Europe, where the prevalence is relatively low, but hospital admission rates are higher. We evaluated the overall level and major determinants of QoL in Lithuanian children aged 5–11 years with asthma.
Molecular Mechanism for a Role of SHP2 in Epidermal Growth Factor Receptor Signaling

ABSTRACT The Src homology 2-containing phosphotyrosine phosphatase (SHP2) is primarily a positive effector of receptor tyrosine kinase signaling. However, the molecular mechanism by which SHP2 effects its biological function is unknown. In this report, we provide evidence that defines the molecular mechanism and site of action of SHP2 in the epidermal growth factor-induced mitogenic pathway. We demonstrate that SHP2 acts upstream of Ras and functions by increasing the half-life of activated Ras (GTP-Ras) in the cell by interfering with the process of Ras inactivation catalyzed by Ras GTPase-activating protein (RasGAP). It does so by inhibition of tyrosine phosphorylation-dependent translocation of RasGAP to the plasma membrane, to its substrate (GTP-Ras) microdomain. Inhibition is achieved through the dephosphorylation of RasGAP binding sites at the level of the plasma membrane. We have identified Tyr992 of the epidermal growth factor receptor (EGFR) to be one such site, since its mutation to Phe renders the EGFR refractory to the effect of dominant-negative SHP2. To our knowledge, this is the first report to outline the site and molecular mechanism of action of SHP2 in EGFR signaling, which may also serve as a model to describe its role in other receptor tyrosine kinase signaling pathways.
DocuCompass: Effective exploration of document landscapes

The creation of interactive visualization to analyze text documents has gained an impressive momentum in recent years. This is not surprising in the light of massive and still increasing amounts of available digitized texts. Websites, social media, news wire, and digital libraries are just few examples of the diverse text sources whose visual analysis and exploration offers new opportunities to effectively mine and manage the information and knowledge hidden within them. A popular visualization method for large text collections is to represent each document by a glyph in 2D space. These landscapes can be the result of optimizing pairwise distances in 2D to represent document similarities, or they are provided directly as meta data, such as geo-locations. For well-defined information needs, suitable interaction methods are available for these spatializations. However, free exploration and navigation on a level of abstraction between a labeled document spatialization and reading single documents is largely unsupported. As a result, vital foraging steps for task-tailored actions, such as selecting subgroups of documents for detailed inspection, or subsequent sense-making steps are hampered. To fill in this gap, we propose DocuCompass, a focus+context approach based on the lens metaphor. It comprises multiple methods to characterize local groups of documents, and to efficiently guide exploration based on users' requirements. DocuCompass thus allows for effective interactive exploration of document landscapes without disrupting the mental map of users by changing the layout itself. We discuss the suitability of multiple navigation and characterization methods for different spatializations and texts. Finally, we provide insights generated through user feedback and discuss the effectiveness of our approach.
Reversible interruption of Giardia lamblia cyst wall protein transport in a novel regulated secretory pathway

To survive in the environment and infect a new host, Giardia lamblia secretes an extracellular cyst wall using a poorly understood pathway. The two cyst wall proteins (CWPs) form disulphide‐bonded heterodimers and are exported via novel encystation‐specific secretory vesicles (ESVs). Exposure of eukaryotic cells to dithiothreitol (DTT) blocks the formation of disulphide bonds in nascent proteins that accumulate in the endoplasmic reticulum (ER) and induces an unfolded protein response (UPR). Proteins that have exited the ER are not susceptible. Exposure to DTT inhibits ESV formation by > 85%. Addition of DTT to encysting cells causes rapid (t1/2 < 10 min), reversible disappearance of ESVs, correlated with reduction of CWPs to monomers and reformation of CWP oligomers upon removal of DTT. Neither CWPs nor ESVs are affected by mercaptoethanesulphonic acid, a strong reducing agent that does not penetrate cells. DTT does not inhibit the overall protein secretory pathway, and recovery does not require new protein synthesis. We found evidence of protein disulphide isomerases in the ESV and the surface of encysting cells, in which they may catalyse initial CWP folding and recovery from DTT. This is the first suggestion of non‐CWP proteins in ESVs and of enzymes on the giardial surface. DTT treatment did not stimulate a UPR, suggesting that Giardia may have diverged before the advent of this conserved form of ER quality control.
Gaussian Filter in CRF Based Semantic Segmentation

Artificial intelligence is making great changes in academy and industry with the fast development of deep learning, which is a branch of machine learning and statistical learning. Fully convolutional network [1] is the standard model for semantic segmentation. Conditional random fields coded as CNN [2] or RNN [3] and connected with FCN has been successfully applied in object detection [4]. In this paper, we introduce a multi-resolution neural network for FCN and apply Gaussian filter to the extended CRF kernel neighborhood and the label image to reduce the oscillating effect of CRF neural network segmentation, thus achieve higher precision and faster training speed.
A Campus Community-based Mobility Model for Routing in Opportunistic Networks

Mobility models are invaluable for determining the performance of routing protocols in opportunistic networks. The movement of nodes has a significant influence on the topological structure and data transmission in networks. In this paper, we propose a new mobility model called the campus-based community mobility model (CBCNM) that closely reflects the daily life pattern of students on a real campus. Consequent on a discovery that the pause time of nodes in their community follows a power law distribution, instead of a classical exponential distribution, we abstract the semi-Markov model from the movement of the campus nodes and analyze its rationality. Then, using the semi-Markov algorithm to switch the movement of the nodes between communities, we infer the steady-state probability of node distribution at random time points. We verified the proposed CBCNM via numerical simulations and compared all the parameters with real data in several aspects, including the nodes’ contact and inter-contact times. The results obtained indicate that the CBCNM is highly adaptive to an actual campus scenario. Further, the model is shown to have better data transmission network performance than conventional models under various routing strategies.
Predictors of Caregiver and Family Functioning Following Traumatic Brain Injury: Social Support Moderates Caregiver Distress

Objective:This study examined predictors of family dysfunction and caregiver distress among 60 pairs of persons who sustained a traumatic brain injury and their caregivers. Design:A cross-sectional design that used hierarchical multiple regression analyses evaluated the relative influences of time since injury, awareness of deficit, and neurobehavioral and neuropsychological functioning of the person with injury, and caregiver perceived social support. Results:The predictor model accounted for 52% of the variance in family dysfunction and 39% in caregiver psychological distress. Neurobehavioral disturbance in the person with injury was the strongest predictor of caregiver distress. Social support showed a direct and linear relationship to family functioning, and it was the strongest predictor of family functioning. Social support was a powerful moderator of caregiver psychological distress. In the absence of adequate social support, caregiver distress increased with longer time after injury, cognitive dysfunction, and unawareness of deficit in care recipients, whereas these characteristics were not associated with distress among caregivers with adequate social support. Conclusions:Rehabilitation professionals should stress the importance of caregivers and families of persons with TBI seeking and obtaining adequate social support.
Force Balance along Isunnguata Sermia, West Greenland

Ice flows when gravity acts on gradients in surface elevation, producing driving stresses. In the Isunnguata Sermia and Russel Glacier catchments of western Greenland, a 50% decline in driving stress along a flow line is juxtaposed with increasing surface flow speed. Here, these circumstances are investigated using modern observational data sources and an analysis of the balance of forces. Stress gradients in the ice mass and basal drag which resist the local driving stress are computed in order to investigate the underlying processes influencing the velocity and stress regimes. Our results show that the largest resistive stress gradients along the flowline result from increasing surface velocity. However, the longitudinal coupling stresses fail to exceed 15 kPa, or 20% of the local driving stress. Consequently, computed basal drag declines in proportion to the driving stress. In the absence of significant resistive stress gradients, other mechanisms are therefore necessary to explain the observed velocity increase despite declining driving stress. In the study area, the observed velocity - driving stress feature occurs at the long-term mean position of the equilibrium line of surface mass balance. We hypothesize that this position approximates the inland limit where surface meltwater penetrates the bed, and that the increased surface velocity reflects enhanced basal motion associated with seasonal meltwater perturbations.
Impact of Fixed and Non-Fixed Foot Orthoses on Fatigue of Lower Limb Muscles

Our research focuses on the two types of foot orthoses (fixed and non-fixed types) used by cerebral stroke patients for foot drop treatment. The aim is to investigate their impact on the fatigue of the main muscles of the lower limbs. Using electromyography signals, we measured the activities of different muscles, including biceps femoris, rectus femoris, tibialis anterior, and gastrocnemius. Then the impact of the two types of orthoses was compared. Results show for the non-fixed ankle foot orthoses (AFO), the amplitude indicators of the calf muscle are larger than the fixed one. The reduced frequency difference for the non-fixed AFO was greater than for the fixed AFO. Also, the laboratory parameters of the thigh muscle were similar between the stationary and non-stationary one. We conclude: when wearing non-fixed orthoses, the shank muscles receive recovery and the cooperation between the thigh and shank muscles improves. Also, it is noticeable that long-time walking rehabilitation training in orthoses can result in fatigue. When wearing fixed orthoses, the activity of the shank muscle is not obvious, and the participation of thigh muscles does not differ a lot from that in the non-fixed type. The activity level is significantly different compared with the situation in which there is no orthoses limiting the ankle movements. The cooperation of thigh and shank muscles is relatively poor during walking, and the thigh muscles tend to develop fatigue over time.
Dental fear, communication, and behavioural management problems in children referred for dental problems.

BACKGROUND Knowledge about the influence of the interaction between child, parent, and dentist and the referral pattern is very limited. AIM This study intended to assess to what extent the pathways of Rachman could clarify why a child is being referred to a specialist in paediatric dentistry and if other aspects in the interaction between child, parent, and dentist play a role in the referral. DESIGN The referral letters of 500 children referred to a Special Dental Care Centre in Amsterdam were examined. All parents filled out the Children's Fear Survey Schedule-Dental Subscale, on behalf of the child. Information about interaction and the referral was collected from the referral letter and a semistructured interview with the parent and dentist separately. RESULTS Eighty pairs of parents and dentists of referred children participated in a semistructured interview. Child factors seem to contribute the most to the referral. For the cause of referral the pathways of Rachman and communication were often combined. CONCLUSIONS Apart from fear acquisition, as implied in Rachman's pathways, the interaction between child, dentist, and parent also contributes to the referral of a child to a specialist clinic in paediatric dentistry.
The electrical breakdown of thin dielectric elastomers: thermal effects

Dielectric elastomers are being developed for use in actuators, sensors and generators to be used in various applications, such as artificial eye lids, pressure sensors and human motion energy generators. In order to obtain maximum efficiency, the devices are operated at high electrical fields. This increases the likelihood for electrical breakdown significantly. Hence, for many applications the performance of the dielectric elastomers is limited by this risk of failure, which is triggered by several factors. Amongst others thermal effects may strongly influence the electrical breakdown strength. In this study, we model the electrothermal breakdown in thin PDMS based dielectric elastomers in order to evaluate the thermal mechanisms behind the electrical failures. The objective is to predict the operation range of PDMS based dielectric elastomers with respect to the temperature at given electric field. We performed numerical analysis with a quasi-steady state approximation to predict thermal runaway of dielectric elastomer films. We also studied experimentally the effect of temperature on dielectric properties of different PDMS dielectric elastomers. Different films with different percentages of silica and permittivity enhancing filler were selected for the measurements. From the modeling based on the fitting of experimental data, it is found that the electrothermal breakdown of the materials is strongly influenced by the increase in both dielectric permittivity and conductivity.
Evaluating the effectiveness of clinical decision support systems: the case of multimorbidity care

General Practitioners (GPs) and healthcare systems, worldwide, are overwhelmed by the growing number of patients with multimorbidity, particularly in light of the additional complexity and costs involved in treating these patients. While it has been proven that clinical decision support systems (CDSS) play a key role in supporting healthcare decisions, there is little research into their role in the case of multimorbidity. This study examines practice systems currently used in Ireland and evaluates their effectiveness in such circumstances. The findings uncover a number of deficiencies, including: (1) the lack of provision of integrated medical guidelines for multiple chronic diseases within the CDSS, (2) the inability to centralise the patient rather than the disease, (3) the difficulty in seamlessly integrating CDSS into the patient consultation, and (4) the lack of adequate training of GPs on how best to use CDSS in multimorbidity decision making. The study underlines the need for further research into CDSS and multimorbidity, and highlights some of the key issues that must be addressed in order to improve how CDSS support the care of multimorbid patients.
Specific excretion of Serratia marcescens protease through the outer membrane of Escherichia coli

A DNA fragment of Serratia marcescens directing an extracellular serine protease (Mr, 41,000) was cloned in Escherichia coli. The cloned fragment caused specific excretion of the protease into the extracellular medium through the outer membrane of E. coli host cells in parallel with their growth. No excretion of the periplasmic enzymes of host cells occurred. The cloned fragment contained a single open reading frame of 3,135 base pairs coding a protein of 1,045 amino acids (Mr 112,000). Comparison of the 5' nucleotide sequence with the N-terminal amino acid sequence of the protease indicated the presence of a typical signal sequence. The C-terminal amino acid of the enzyme was found at position 408, as deduced from the nucleotide sequence. Artificial frameshift mutations introduced into the coding sequence for the assumed distal polypeptide after the C terminus of the protease caused complete loss of the enzyme production. It was concluded that the Serratia serine protease is produced as a 112-kilodalton proenzyme and that its N-terminal signal peptide and a large C-terminal part are processed to cause excretion of the mature protease through the outer membrane of E. coli cells.
Emerging drugs for bipolar disorder

Bipolar disorder is a relatively common condition characterised by recurrent episodes of mania and depression, and associated with high levels of morbidity and mortality. Although there have been substantial advances in the pharmacotherapeutics of this condition over the last 10 – 15 years, the benefits have been predominantly in terms of tolerability and safety, with no new treatments being demonstrated to be more effective than lithium – the prototype mood stabiliser. This article reviews current and emerging medications for bipolar disorder. Most of the emerging treatments in pharmaceutical industry developmental programmes are new or modified anticonvulsants or atypical antipsychotics. A number of possible future directions and challenges for the field are discussed. The treatment of bipolar disorder is unlikely to advance substantially until the causative pathogenetic molecular processes are elucidated.
Conformational Changes That Effect Oligomerization and Initiate Pore Formation Are Triggered throughout Perfringolysin O upon Binding to Cholesterol*

Pore formation by the cholesterol-dependent cytolysins (CDCs) requires the presence of cholesterol in the target membrane. Cholesterol was long thought to be the cellular receptor for these toxins, but not all CDCs require cholesterol for binding. Intermedilysin, secreted by Streptococcus intermedius, only binds to membranes containing the human protein CD59 but forms pores only if the membrane contains sufficient cholesterol. In contrast, perfringolysin O (PFO), secreted by Clostridium perfringens, only binds to membranes containing substantial amounts of cholesterol. Given that different steps in the assembly of various CDC pores require cholesterol, here we have analyzed to what extent cholesterol molecules, by themselves, can modulate the conformational changes associated with PFO oligomerization and pore formation. PFO binds to cholesterol when dispersed in aqueous solution, and this binding triggers the distant rearrangement of a β-strand that exposes an oligomerization interface. Moreover, upon binding to cholesterol, PFO forms a prepore complex, unfolds two amphipathic transmembrane β-hairpins, and positions their nonpolar surfaces so they associate with the hydrophobic cholesterol surface. The interaction of PFO with cholesterol is therefore sufficient to initiate an irreversible sequence of coupled conformational changes that extend throughout the toxin molecule.
Convex combination of direct frequency estimators

Direct frequency estimator (DFE) has recently been proposed for unbiased frequency estimation of a real tone in white noise. This paper proposes to improve the performance of the DFE using a convex combination of two DFEs. Each DFE is adapted independently to retain its performance advantage, and the estimation results are then adaptively combined for optimal performance. The convex combination scheme offers improved tracking and accuracy. Simulations show that the proposed estimator performs better than the conventional DFE.
Cumulative effects of sleep restriction on daytime sleepiness.

Sleep and daytime sleepiness were evaluated in 10 young adult subjects to determine whether restricting nocturnal step by a constant amount produces cumulative impairment. Subjects were studied for 12 consecutive days, including 3 baseline days with a 10-hr time in bed, 7 days with sleep restricted to 5 hrs, and 2 recovery days. In 5 subjects, recovery included a 10-hr time in bed; in the remaining subject, recovery induced a 5-hr time in bed with a 1-hr daytime nap. Sleepiness was measured using two self-rating scales and the multiple sleep latency test. During sleep restriction, nocturnal stage 2 and REM sleep were reduced and slow wave sleep was unaffected. Stanford Sleepiness Scales showed an immediate increase in daytime sleepiness that reached a plateau after 4 days. An analog sleepiness rating scale showed increased sleepiness after 2 restricted nights and leveled off after the fourth restricted night. The multiple sleep latency tests showed no effect of sleep restriction until the second day, followed by a progressive increase in sleepiness that persisted through the seventh sleep restriction day. During the recovery period, daytime sleepiness returned to basal values on all three measures following one full night of sleep; with a daytime nap, no further cumulative effects of sleep restriction were seen.
Hyperoxia during one lung ventilation: Inflammatory and oxidative responses

It is common practice during one lung ventilation (OLV) to use 100% oxygen, although this may cause hyperoxia‐ and oxidative stress‐related lung injury. We hypothesized that lower oxygen (FiO2) during OLV will result in less inflammatory and oxidative lung injury and improved lung function.