Miracle-dz/UniFAR-FTUs huggingface dataset:
Mechanisms of inactivation of L-type calcium channels in human atrial myocytes.

We used whole cell patch-clamp and microfluorimetric (indo 1) techniques to measure Ca2+ current through L-type Ca2+ channels (I(Ca)) and Ca2+ transients in human atrial myocytes. During 1-s depolarizing pulses, I(Ca) inactivation was biexponential. The rate of rapid inactivation was slowed by ryanodine and was correlated with the rate of rise of cytoplasmic free Ca2+ concentration (r = 0.80, P < 0.01). Slower-phase I(Ca) inactivation was not affected by ryanodine but was accelerated by increasing the availability of Ca2+ to permeate the Ca2+ channel. Thus Ca2+ released from the sarcoplasmic reticulum (SR) was responsible for most I(Ca) inactivation during the first 50 ms of a depolarization to 0 mV, and thereafter inactivation by Ca2+ permeating the channel predominated. Pure voltage-dependent inactivation had a much slower time course of development (tau > 2 s) and played a smaller role than Ca2+-dependent mechanisms over a duration comparable to that of an action potential. We conclude that human atrial myocytes show both voltage- and Ca2+-dependent I(Ca) inactivation, that Ca2+-dependent mechanisms predominate over the time course of an action potential, and that although both Ca2+ released from the SR and Ca2+ permeating Ca2+ channels play a role, SR-released Ca2+ is particularly important in early, rapid I(Ca) inactivation, whereas Ca2+ permeating Ca2+ channels is more important in the slower phase of Ca2+-dependent inactivation.
Gastrointestinal disease outbreaks in cycling events: are preventive measures effective?

SUMMARY In 2009, following a bike race, a gastrointestinal illness outbreak affected many participants. A cohort study showed an attack rate of 16·3% with the main risk factor being mud splashes to the face. Considering these findings, in 2010 recommendations to participants in the bike race were issued and environmental control measures were implemented. In 2010, a retrospective cohort study using web-based questionnaires was conducted to measure the use of preventive measures and to assess risk factors associated with gastrointestinal illness. A 69% response rate was achieved and 11721 records analysed, with 572 (attack rate 4·9%) matching the case definition, i.e. participants reporting diarrhoea within 10 days of race. There was a clear increase in the use of mudguards (96·7% reported access to/receiving information on preventive measures) and a significant decrease in gastrointestinal illness. This may indicate that the measures have been effective and should be considered, both in terms of environmental control measures as well as individual measures.
No Impact of Deep Brain Stimulation on Fear-Potentiated Startle in Obsessive–Compulsive Disorder

Deep brain stimulation (DBS) of the ventral internal capsule is effective in treating therapy refractory obsessive–compulsive disorder (OCD). Given the close proximity of the stimulation site to the stria terminalis (BNST), we hypothesized that the striking decrease in anxiety symptoms following DBS could be the result of the modulation of contextual anxiety. However, the effect of DBS in this region on contextual anxiety is as of yet unknown. Thus, the current study investigated the effect of DBS on contextual anxiety in an experimental threat of shock paradigm. Eight patients with DBS treatment for severe OCD were tested in a double-blind crossover design with randomly assigned 2-week periods of active and sham stimulation. DBS resulted in significant decrease of obsessive–compulsive symptoms, anxiety, and depression. However, even though the threat manipulation resulted in a clear context-potentiated startle effect, none of the parameters derived from the startle recordings was modulated by the DBS. This suggests that DBS in the ventral internal capsule is effective in treating anxiety symptoms of OCD without modulating the startle circuitry. We hypothesize that the anxiety symptoms present in OCD are likely distinct from the pathological brain circuits in defensive states of other anxiety disorders.
White Matter Correlates of Musical Anhedonia: Implications for Evolution of Music

Recent theoretical advances in the evolution of music posit that affective communication is an evolutionary function of music through which the mind and brain are transformed. A rigorous test of this view should entail examining the neuroanatomical mechanisms for affective communication of music, specifically by comparing individual differences in the general population with a special population who lacks specific affective responses to music. Here we compare white matter connectivity in BW, a case with severe musical anhedonia, with a large sample of control subjects who exhibit normal variability in reward sensitivity to music. We show for the first time that structural connectivity within the reward system can predict individual differences in musical reward in a large population, but specific patterns in connectivity between auditory and reward systems are special in an extreme case of specific musical anhedonia. Results support and extend the Mixed Origins of Music theory by identifying multiple neural pathways through which music might operate as an affective signaling system.
FITNESS COSTS OF INSECTICIDE RESISTANCE IN NATURAL BREEDING SITES OF THE MOSQUITO CULEX PIPIENS

Abstract Genetic changes conferring adaptation to a new environment may induce a fitness cost in the previous environment. Although this prediction has been verified in laboratory conditions, few studies have tried to document this cost directly in natural populations. Here, we evaluated the pleiotropic effects of insecticide resistance on putative fitness components of the mosquito Culex pipiens. Experiments using different larval densities were performed during the summer in two natural breeding sites. Two loci that possess alleles conferring organophosphate (OP) resistance were considered: ace-1 coding for an acetylcholinesterase (AChE1, the OP target) and Ester, a “super locus” including two closely linked loci coding for esterases A and B. Resistance ace-1 alleles coding for a modified AChE1 were associated with a longer development time and shorter wing length. The pleiotropic effects of two resistance alleles Ester1 and Ester4 coding for the overproduced esterases A1 and A4-B4, respectively, were more variable. Both A1 and A4-B4 reduced wing length, although only A1 was associated with a longer preimaginal stage. The fluctuating asymmetry (FA) of the wing did not respond to the presence or to the interaction of resistance alleles at the two loci at any of the density levels tested. Conversely, the FA of one wing section decreased when larval density increased. This may be the consequence of selection against less developmentally stable individuals. The results are discussed in relation to the local evolution of insecticide resistance genes.
Detecting community structure of networks using evolutionary coordination games

Community detection is a well-studied problem in network science. In this paper, a novel community detection algorithm based on evolutionary game dynamics is proposed, where individuals hold disperse opinions as their mixed strategies and play coordination games with their connected individuals in a network. Employing strategy updating processes among the population, the individuals finally fall into clusters of different opinionists which correspond to a community partition of the network. Using Zachary's karate club network as a benchmark test, the validity of the proposed community detection method is verified.
The 3D Structure of the Apical Complex and Association with the Flagellar Apparatus Revealed by Serial TEM Tomography in Psammosa pacifica, a Distant Relative of the Apicomplexa

The apical complex is one of the defining features of apicomplexan parasites, including the malaria parasite Plasmodium, where it mediates host penetration and invasion. The apical complex is also known in a few related lineages, including several non-parasitic heterotrophs, where it mediates feeding behaviour. The origin of the apical complex is unclear, and one reason for this is that in apicomplexans it exists in only part of the life cycle, and never simultaneously with other major cytoskeletal structures like flagella and basal bodies. Here, we used conventional TEM and serial TEM tomography to reconstruct the three dimensional structure of the apical complex in Psammosa pacifica, a predatory relative of apicomplexans and dinoflagellates that retains the archetype apical complex and the flagellar apparatus simultaneously. The P. pacifica apical complex is associated with the gullet and consists of the pseudoconoid, micronemes, and electron dense vesicles. The pseudoconoid is a convex sheet consisting of eight short microtubules, plus a band made up of microtubules that originate from the flagellar apparatus. The flagellar apparatus consists of three microtubular roots. One of the microtubular roots attached to the posterior basal body is connected to bypassing microtubular strands, which are themselves connected to the extension of the pseudoconoid. These complex connections where the apical complex is an extension of the flagellar apparatus, reflect the ancestral state of both, dating back to the common ancestor of apicaomplexans and dinoflagellates.
Genetic and epigenetic alterations in lung tumors from bitransgenic Ki‐rasG12C expressing mice

Mutations in Ki‐ras occur in approximately 30–50% of patients with adenocarcinoma (AC) of the lung. We previously reported the development of a bitransgenic mouse model that expressed the human Ki‐rasG12C allele in a lung‐specific, tetracycline‐inducible manner and gave rise to benign lung tumors. In the current study, these benign tumors, which represent relatively early lesions in neoplastic progression, were analyzed for molecular alterations secondary to mutant Ki‐ras expression to determine the gene(s) that contribute to adenoma (AD) development. Tumors were removed following doxycycline (DOX) treatment for 9 and 12 mo and examined for alterations in cell‐cycle regulatory genes. Quantification of mRNA expression for cyclin D1, retinoblastoma, p16Ink4a, p19Arf, and survivin was carried out by real‐time PCR. All of the tumors examined exhibited a mean reduction of approximately fivefold for the retinoblastoma gene (P < 0.02). Increased expression of both p19Arf and survivin were detected in a majority of the tumors examined (P < 0.01 and 0.001, respectively), but no change in cyclin D1 RNA expression was observed. A subset of the lung tumors (8/28) displayed reduced levels of p16Ink4a expression (P = 0.02). Immunohistochemical analysis confirmed the upregulation of p19Arf and survivin in all 10 of the lung tumors examined. However, increased staining for cyclin D1 was observed in the tumor tissue. In addition, increased levels of activated p53 were found in lung tumor tissues stained with an anti‐phospho‐p53 antibody, while an absence of staining was observed with an anti‐phospho‐pRb antibody in both normal control and tumor tissue. Analysis of the methylation status of p16Ink4a by methylation‐specific PCR (MSP) demonstrated that seven of eight tumors exhibiting decreased expression of p16Ink4a had at least partial methylation of the promoter region. Single stranded conformational polymorphism (SSCP) analysis demonstrated that neither exons 1 or 2 of p16Ink4a nor exons 5–8 of p53 exhibited mutations. These data thus identify alterations in specific genes and pathways that combine with the mutation in Ki‐ras to promote the formation of benign lung tumors and suggest potential targets for the development of novel chemotherapeutic and chemopreventive agents during the early stages of lung tumor progression. © 2006 Wiley‐Liss, Inc.
Social presence in team-based digital games

This thesis explores the concept of social presence in team-based digital games, aiming to enlighten the core elements of social presence in this specific multi-user experience. The thesis achieves this exploration in three main ways, by using a novel approach to establish the core elements of social presence in team-based digital games, by developing a new measure for social presence specifically tailored for team-based digital games, and by exploring the effects of contextual gameplay factors on social presence in a large scale user study. The thesis documents the work carried out over the course of an Engineering Doctorate (EngD) sponsored by BAE Systems, who gave an industry perspective, helped to set the direction of the research and guide it throughout the program. The industry relevance to studying social presence in team-based digital games was the analogous nature of teambased games to virtual training technologies such as simulators and serious games, and the lack of understanding of social elements within these technologies. The research questions for this thesis were as follows: What is the nature of social presence in team-based digital games? How social presence is affected by sharing a team-based virtual environment with human or computer controlled entities? What other contextual elements encourage or reduce feelings of social presence? The first set of studies detailed in this thesis were a preliminary exploration of social presence in team-based digital games, a group of short user studies termed experiential vignettes, investigating the effect of agency on user experience. The experiential vignettes suggest that social presence is affected by a player’s perception of the other entities in the virtual environment, however the extent of the affect is highly dependent on task. These preliminary studies led to the development of a questionnaire designed to measure social presence in team-based digital games, the competitive and cooperative social presence questionnaire (CCPIG), developed and validated using user studies. The CCPIG was utilized and further validated in a large scale user study which aimed to explore the conceptual crossover between team trust and social presence, and how various contextual variables affected these concepts. This thesis shows that competitive and cooperative social presence are two distinct concepts, and that there is significant conceptual crossover between social presence and established notions of team trust. This thesis also shows that social presence is highly context dependent, affected by agency, familiarity with other players, team performance, and the nature of the game in which the experience occurs.
Safety in the workplace: The burden and pattern of markers of Hepatitis B virus infection in routine blood samples in haematology laboratory at Irrua, Edo, Nigeria

Hepatitis B virus [HBV] infection is a worldwide problem resulting in many deaths yearly from cirrhosis and liver cancer. Regrettably also, healthcare workers get exposed to blood-borne pathogens, including hepatitis B virus at work. HBV infection in immuno-competent hosts results in acute fulminant illness which may be fatal, partially resolved to become chronic, or completely resolved. HBV immunization in the country cover neonates and health workers leaving many people uncovered. Lack of monitoring and confirmation of successful HBV immunization in heath workers reduces coverage in this group leaving many susceptible to HBV infection at work. We aimed to determine the magnitude of this risk for occupational exposure to HBV infection. We therefore analyzed sixty nine routine blood samples coming to our Haematology laboratory at Irrua, Edo, Nigeria, using the five parameter hepatitis B virus kit manufactured by Micropoint Diagnostics USA. Results showed that HBsAg, Ant-HBs, HBeAg, Anti-HBe and Anti-HBc were reactive in 11.6%, 23%, 1.4%, 7% and 7% of our study samples indicating that the burden of HBV infectivity is high. We recommend active monitoring and routine confirmation of successful HBV immunization in health workers with expansion of the program to cover more of our population. Keywords: Chronic HBV Infection, Occupational exposure, Immunization, Management of Chronic HBV infection
A discrete universal denoiser and its application to binary images

This paper describes a discrete universal denoiser for two dimensional data and also presents an experimental results of its application to noisy binary images. A discrete universal denoiser (DUDE) is introduced for recovering a signal with finite-valued components corrupted by finite-valued, uncorrelated noise. The DUDE is asymptotically optimal and universal, in the sense of asymptotically achieving, without access to any information on the statistics of the clean signal, the same performance as the best denoiser that does have access to such information. It is also practical, and can be implemented in low complexity.
Dorsal Parietal Area 5 Encodes Immediate Reach in Sequential Arm Movements

To generate a coherent action sequence, it is essential to integrate all component movements beforehand, and such sequence-related information has been observed in numerous brain regions. However, this high-level sequential plan encompassing multiple motor elements in parallel ultimately must be decomposed into serial motor commands to be executed by the musculoskeletal system. In the present study, we recorded single-neuron activity from dorsal parietal area 5 (area 5d) while monkeys performed a double-reach task, and found that area 5d conveys the immediate upcoming reach, but not the subsequent movement, as opposed to the entire movement sequence being encoded as in other cortical sensorimotor areas. The elementary movement coded in area 5d suggests that unfolding of the motor sequence begins in the parietal-frontal cortex, instead of being exclusively implemented by downstream subcortical and spinal circuits.
Pharmacokinetics and absolute bioavailability of mepolizumab following administration at subcutaneous and intramuscular sites

This study characterized the pharmacokinetics (PK) of mepolizumab, after a single intravenous (IV), subcutaneous (SC), or intramuscular (IM) dose in healthy adults and determined the absolute bioavailability of SC and IM mepolizumab delivered at different anatomical regions. Sixty healthy subjects were randomly assigned to receive a single dose of either mepolizumab 250 mg by IV, SC injection (upper arm, abdomen, or thigh); or IM injection (thigh). Following IV administration, the mean maximum observed plasma mepolizumab concentration (Cmax) and the mean area under the concentration versus time curves from time zero to infinity (AUC(0‐∞)) were 109 ± 17 µg/mL and 1,557 ± 250 µg d/mL, respectively. After SC administration, the mean (±SD) values of Cmax and AUC(0‐∞) were 34.1–38.2 ± 7.3–12.1 µg/mL and 1,110–1,238 ± 228–372 µg d/mL, respectively. Following IM administration, the mean values of Cmax and AUC(0‐∞) were 46.9 ± 10.6 µg/mL and 1,395 ± 348 µg d/mL. The median terminal half‐life was similar for SC, IM and IV administration (17.9–20.4, 19.2, and 18.5 days, respectively). The overall mean bioavailability of SC mepolizumab was 64–75%, and absorption was relatively similar for the three SC injection sites. Mepolizumab 250 mg was generally well tolerated in this study. These results support flexibility in the SC injection site for mepolizumab.
DYNAMIC PARAMETER SIMILITUDE FOR CONCRETE MODELS

This paper reports the results of a series of experimental modal analyses that were performed to examine the similitude of the dynamic parameters of reinforced concrete replica models. Also reported are the similitude requirements for damping forces that were developed as part of this study. The similitude analysis shows that both material properties and system geometry must be considered when scaling the damping forces. Results of the experiments show that the modal frequencies and the mode shapes of a prototype structure can be accurately predicted from tests on scale-model structures. Variations in equivalent viscous damping ratios identified on models and prototype were greater than variations for the other measured dynamic parameters. However, all damping ratios were less than 2 percent of critical, and the observed variations would not significantly alter the dynamic response of the structures.
Instance-Optimal Geometric Algorithms

We prove the existence of an algorithm $A$ for computing 2-d or 3-dconvex hulls that is optimal for {\em every point set\/} in the following sense: %for every set $S$ of $n$ points and for every algorithm $A'$ in a certain class $\A$, the running time of $A$ on the worst permutation of $S$ for $A$ is at most a constant factor times the running time of $A'$ on the worst permutation of $S$ for $A'$. %In fact, we can establish a stronger property: for every $S$ and $A'$, the running time of $A$ on $S$ is at most a constant factor times the average running time of $A'$ over all permutations of $S$. %We call algorithms satisfying these properties {\em instance-optimal\/} in the {\em order-oblivious\/} and {\em random-order\/} setting. %Such instance-optimal algorithms simultaneously subsume output-sensitive algorithms and distribution-dependent average-case algorithms, and all algorithms that do not take advantage of the order of the input or that assume the input is given in a random order. The class $\A$ under consideration consists of all algorithms in a decision tree model where the tests involve only {\em multilinear\/}functions with a constant number of arguments. %To establish an instance-specific lower bound, we deviate from traditional Ben--Or-style proofs and adopt an interesting adversary argument. %For 2-d convex hulls, we prove that a version of the well known algorithm by Kirkpatrick and Seidel (1986) or Chan, Snoeyink, and Yap(1995) already attains this lower bound. For 3-d convex hulls, we propose a new algorithm. We further obtain instance-optimal results for a few other standard problems in computational geometry, such as maxima in 2-d and 3-d, orthogonal line segment intersection in 2-d, %finding bichromatic $L_\infty$-close pairs in 2-d, off-line orthogonal range searching in 2-d, %off-line dominance reporting in 2-d and 3-d, off-line halfspace range reporting in 2-d and 3-d, and off-line point location in 2-d. The theory we develop also neatly reveals connections to entropy-dependent data structures, and yields as a byproduct new expected-case results, e.g., for on-line orthogonal range counting in 2-d.
Informatics Tools and Medical Communication: Patient Perspectives of "Knowledge Coupling" in Primary Care

The use of various "informatics tools" for routine patient care promises to radically alter the ways whereby medical knowledge and information are processed and applied. In so doing, it can also change the nature of the information exchange and relational communication that occurs between patients and caregivers. This investigation examines how patients view "knowledge coupling" (KC) tools as they are routinely used in a "coupler-centered" family practice (CCP). How do patients view these tools as influencing information exchange and their relationship with caregivers? Based upon close- and open-ended questions of a random sample of patients in the CCP, this study found that most respondents viewed KC informatics tools as elevating the information exchange that occurs between patients and caregivers-increasing the extent to which patients are "heard and understood" by caregivers and come to "know and understand" what is ailing them. Many respondents report being empowered by the use of the tools, and having greater confidence in the care and advice caregivers offer. A few others, however, suggest diminished confidence in care and a more "impersonal" environment, resulting specifically from the use of the computer in the office. The article concludes by suggesting ways whereby such deficiencies might be remedied.