Miracle-dz/UniFAR-FTUs huggingface dataset:
Malignant hyperthermia susceptibility arising from altered resting coupling between the skeletal muscle L-type Ca2+ channel and the type 1 ryanodine receptor

Malignant hyperthermia (MH) susceptibility is a dominantly inherited disorder in which volatile anesthetics trigger aberrant Ca2+ release in skeletal muscle and a potentially fatal rise in perioperative body temperature. Mutations causing MH susceptibility have been identified in two proteins critical for excitation–contraction (EC) coupling, the type 1 ryanodine receptor (RyR1) and CaV1.1, the principal subunit of the L-type Ca2+ channel. All of the mutations that have been characterized previously augment EC coupling and/or increase the rate of L-type Ca2+ entry. The CaV1.1 mutation R174W associated with MH susceptibility occurs at the innermost basic residue of the IS4 voltage-sensing helix, a residue conserved among all CaV channels [Carpenter D, et al. (2009) BMC Med Genet 10:104–115. ]. To define the functional consequences of this mutation, we expressed it in dysgenic (CaV1.1 null) myotubes. Unlike previously described MH-linked mutations in CaV1.1, R174W ablated the L-type current and had no effect on EC coupling. Nonetheless, R174W increased sensitivity of Ca2+ release to caffeine (used for MH diagnostic in vitro testing) and to volatile anesthetics. Moreover, in CaV1.1 R174W-expressing myotubes, resting myoplasmic Ca2+ levels were elevated, and sarcoplasmic reticulum (SR) stores were partially depleted, compared with myotubes expressing wild-type CaV1.1. Our results indicate that CaV1.1 functions not only to activate RyR1 during EC coupling, but also to suppress resting RyR1-mediated Ca2+ leak from the SR, and that perturbation of CaV1.1 negative regulation of RyR1 leak identifies a unique mechanism that can sensitize muscle cells to MH triggers.
Influence of Tear Film and Contact Lens Osmolality on Ocular Comfort in Contact Lens Wear

Purpose. To evaluate a novel method to measure the osmolality of worn contact lenses and assess the impact of contact lens and tear film osmolality on comfort during short-term wear. Methods. A new method to measure contact lens osmolality was validated by testing for repeatability and by evaluating independence of lens material, power, and osmolality value of the lens. This method was then used in a clinical study. Nine different lens types were each worn by 15 subjects. Osmolality, tear film, and ocular surface parameters were tested for their association to comfort using linear mixed model. Results. The method to measure contact lens osmolality was independent of lens material (p = 0.911), power (p = 0.826), and osmolality value of the lens (p = 0.858). No differences in contact lens osmolalities between two different days were observed (p > 0.05). Comfort after 6 h of lens wear was associated with the osmolality of the worn lens (p = 0.006, r = −0.41) but not with tear osmolality after lens wear (p = 0.993). Comfort was associated with conjunctival indentation (p = 0.002, r = −0.37). Osmolality of worn lenses significantly correlated with tear film break-up time (p = 0.003, r = −0.22), lens water content (p < 0.001, r = −0.58), conjunctival indentation (p < 0.001, r = 0.45), and ocular sensitivity (p < 0.05) after 6 h lens wear. Conclusion. This newly developed method to measure contact lens osmolality was repeatable and independent of lens material, power, and osmolality value of the contact lens. Although no association between tear film osmolality and ocular comfort after 6 h of lens wear could be demonstrated, contact lens osmolality was associated with comfort and ocular surface characteristics, and may provide the link between symptoms and clinical observations.
Measuring Success in Family Businesses: The Concept of Configurational Fit

The problems associated with measuring success in small businesses are primarily caused by a lack of comparable data due to the ambiguity of “success” and by subjective biases. Success evaluation is dominated by the estimates of business owners, who tend to overestimate overall success and internal strengths. However, reliable success measurement instruments would be useful for small business owners/managers as well as small business policymakers. The main purposes of this article are to compare various measures of success, to explore the differences in their outcomes, and to analyze whether a model of success measurement using configurational fit can be used to overcome subjective biases. The study is based on a recent survey of 103 small family-owned businesses in the eastern Austrian border region. Our analysis of the data confirmed the existence of the measurement problems mentioned above. Although some individual indicators show significant biases as well as effects due to company age, size, and industry, the aggregated indicator based on the concept of configurational fit seems to be an appropriate means of overcoming most of these drawbacks.
(1, k)‐Coloring of Graphs with Girth at Least Five on a Surface

A graph is (d1,.,dr) ‐colorable if its vertex set can be partitioned into r sets V1,. ,Vr so that the maximum degree of the graph induced by Vi is at most di for each i∈{1,. ,r} . For a given pair (g,d1) , the question of determining the minimum d2=d2(g,d1) such that planar graphs with girth at least g are (d1,d2) ‐colorable has attracted much interest. The finiteness of d2(g,d1) was known for all cases except when (g,d1)=(5,1) . Montassier and Ochem explicitly asked if d2(5, 1) is finite. We answer this question in the affirmative with d2(5,1)≤10 ; namely, we prove that all planar graphs with girth at least five are (1, 10)‐colorable. Moreover, our proof extends to the statement that for any surface S of Euler genus γ, there exists a K=K(γ) where graphs with girth at least five that are embeddable on S are (1, K)‐colorable. On the other hand, there is no finite k where planar graphs (and thus embeddable on any surface) with girth at least five are (0, k)‐colorable.
A peptide panel investigation reveals the acceptor specificity of O‐GlcNAc transferase

O‐linked β‐N‐acetylglucosaminylation (O‐GlcNAcylation) is widely distributed on nucleocytoplasmic proteins and participates in various physiological processes. But O‐GlcNAc status on numerous proteins remains unknown. To better understand this modification, computational analysis combined with experimental study was performed in this work. Structural analysis of many O‐GlcNAcylation sites indicated that the modification occurred predominantly in a random coil region. Frequency analysis on many O‐GlcNAcylated peptides revealed a signature sequence, PPVS/TSATT, around the modification site (underlined, position 0). Based on the sequence, a peptide panel was designed to investigate key positions affecting O‐GlcNAcylation of peptides and their amino acid preference. It was indicated that 3 positions (–2, –1, and +2) had an important role for this modification, where the presence of uncharged amino acids with small side chains could confer high reactivity. The amino acid preference at key positions was further investigated on bovine crystalline αvia site‐directed mutagenesis. The preferred amino acids were Pro > Ala > Gly at position – 2, Ala > Thr > Val > Lys > Pro at position –1, and Ala > Gly > Arg > Glu at position +2. Altogether, these findings suggested that a substrate (peptide or protein) with Pro, Ala at position –2, and/or Val, Ala, Thr, Ser at position –1, and/or Ala, Ser, Pro, Thr, Gly at position +2 would have more chances for O‐GlcNAcylation. To test the rule, 2 O‐GlcNAcylation sites on sOGT (S52 and T449) were predicted and confirmed by Western blot. The present work systematically investigated the sequence signature for O‐GlcNAcylation. The result will contribute to predicting the O‐GlcNAc status of a protein and further functional studies. —Liu, X. , Li, L. , Wang, Y. , Yan, H. , Ma, X. , Wang, P. G. , Zhang, L. A peptide panel investigation reveals the acceptor specificity of O‐GlcNAc transferase. FASEB J. 28, 3362–3372 (2014). www.fasebj. org
Major intraoperative complications during video-assisted thoracoscopic anatomical lung resections: an intention-to-treat analysis.

OBJECTIVES A multicentre evaluation of the frequency and nature of major intraoperative complications during video-assisted thoracoscopic (VATS) anatomical resections. METHODS Six European centres submitted their series of consecutive anatomical lung resections with the intention to treat by VATS. Conversions to thoracotomy, vascular injuries and major intraoperative complications were studied in relation to surgeons' experience. Major complications included immediate life-threatening complications (i.e. blood loss of more than 2 l), injury to proximal airway or other organs or those leading to unplanned additional anatomical resections. All cases were discussed by a panel and recommendations were drafted. RESULTS A total of 3076 patients were registered. Most resections (90%, n = 2763) were performed for bronchial carcinoma. There were 3 intraoperative deaths, including 1 after conversion for technical reasons. In-hospital mortality was 1.4% (n = 43). Conversion to open thoracotomy was observed in 5.5% (n = 170), of whom 21.8% (n = 37) were for oncological reasons, 29.4% (n = 50) for technical reasons and 48.8% (n = 83) for complications. Vascular injuries were reported in 2.9% (n = 88) patients and led to conversion in 2.2% (n = 70). In 1.5% (n = 46), major intraoperative complications were identified. These consisted of erroneous transection of bronchovascular structures (n = 9); injuries to gastrointestinal organs (n = 5) or proximal airway (n = 6); complications requiring additional unplanned major surgery (n = 9) or immediate life-threatening complications (n = 17). Twenty-three percent of the in-hospital mortalities (n = 10/43) were related to major intraoperative complications. Eight pneumonectomies (five intraoperative and three postoperative at 0.3%) were a consequence of a major complication. Surgeon's experience was related to non-oncological conversions, but not to vascular injuries or major complications in a multivariable logistic regression analysis. CONCLUSION Major intraoperative complications during VATS anatomical lung resections are infrequent, seem not to be related to surgical experience but have an important impact on patient outcome. Constant awareness and a structured plan of action are of paramount importance to prevent them.
Tapering Strategies to Enhance Maximal Strength

II ATTESTATION OF AUTHORSHIP . VII ACKNOWLEDGEMENTS . VIII CO-AUTHORED PUBLICATIONS . IX LIST OF FIGURES . X LIST OF TABLES . XI LIST OF ABBREVIATIONS . XII CHAPTER ONE .
Binaural Speech Intelligibility and Interaural Cross-Correlation Under Disturbing Noise and Reverberation

Subjective tests were carried out in order to investigate speech intelligibility, and the possible relative improvements that can be obtained in practical applications to acoustic communication systems, for different forms of presentation through headphones: monaural, monophonic, binaural at 0o (in front of the listener) and binaural at ±30o (right or left, relative to the listener), played back undisturbed, and also with the addition of extreme levels of disturbing noise and reverberation, with a signal to noise ratio of
A revisited phylogeography of Nautilus pompilius

Abstract The cephalopod genus Nautilus is considered a “living fossil” with a contested number of extant and extinct species, and a benthic lifestyle that limits movement of animals between isolated seamounts and landmasses in the Indo‐Pacific. Nautiluses are fished for their shells, most heavily in the Philippines, and these fisheries have little monitoring or regulation. Here, we evaluate the hypothesis that multiple species of Nautilus (e.g., N. belauensis, N. repertus and N. stenomphalus) are in fact one species with a diverse phenotypic and geologic range. Using mitochondrial markers, we show that nautiluses from the Philippines, eastern Australia (Great Barrier Reef), Vanuatu, American Samoa, and Fiji fall into distinct geographical clades. For phylogenetic analysis of species complexes across the range of nautilus, we included sequences of Nautilus pompilius and other Nautilus species from GenBank from localities sampled in this study and others. We found that specimens from Western Australia cluster with samples from the Philippines, suggesting that interbreeding may be occurring between those locations, or that there is limited genetic drift due to large effective population sizes. Intriguingly, our data also show that nautilus identified in other studies as N. belauensis, N. stenomphalus, or N. repertus are likely N. pompilius displaying a diversity of morphological characters, suggesting that there is significant phenotypic plasticity within N. pompilius.
Frequency, severity, and evolution of split family alliances: How observable are they?

Abstract Split alliances (within-family differences in the emotional bond with the therapist) were studied in 19 U.S. and 21 Spanish families using the System for Observing Family Therapy Alliances (SOFTA; Friedlander, Escudero, & Heatherington, 2006). Examining individual family members’ scores on the corresponding self-report and observational Emotional Connection to the Therapist SOFTA scales, the authors identified mild, moderate, and severe split alliances. In both samples, self-reported splits occurred frequently and with almost all of the therapists. Although clients’ observed interactions with the therapist often mirrored their self-reports, family members’ perceptions of the therapeutic bond were generally more discrepant than their behavior suggested. The majority of families that dropped out had a moderately or severely split alliance in at least one session.
Enhanced adenoviral gene delivery to motor and dorsal root ganglion neurons following injection into demyelinated peripheral nerves

Injection of viral vectors into peripheral nerves may transfer specific genes into their dorsal root ganglion (DRG) neurons and motoneurons. However, myelin sheaths of peripheral axons block the entry of viral particles into nerves. We studied whether mild, transient peripheral nerve demyelination prior to intraneural viral vector injection would enhance gene transfer to target DRG neurons and motoneurons. The right sciatic nerve of C57BL/6 mice was focally demyelinated with 1% lysolecithin, and the left sciatic nerve was similarly injected with saline (control). Five days after demyelination, 0.5 μl of Ad5‐GFP was injected into both sciatic nerves at the site of previous injection. The effectiveness of gene transfer was evaluated by counting GFP+ neurons in the DRGs and ventral horns. After peripheral nerve demyelination, there was a fivefold increase in the number of infected DRG neurons and almost a 15‐fold increase in the number of infected motoneurons compared with the control, nondemyelinated side. Focal demyelination reduced the myelin sheath barrier, allowing greater virus–axon contact. Increased CXADR expression on the demyelinated axons facilitated axoplasmic viral entry. No animals sustained any prolonged neurological deficits. Increased gene delivery into DRG neurons and motoneurons may provide effective treatment for amyotrophic lateral sclerosis, pain, and spinal cord injury. © 2010 Wiley‐Liss, Inc.
Sustainable hybrid composites of recycled polypropylene and construction debris

We prepared composites of recycled polypropylene and construction debris aiming to obtain a sustainable hybrid material, with prospective application in the construction industry. We varied the amount of debris in 0, 1, 2, 3 and 7 m/m/% and the compounded materials were analysed by scanning electron microscopy, thermogravimetry/derivative thermogravimetry, differential scanning calorimetry, Fourier-transform infrared spectroscopy, melt flow rate, wide angle X-ray diffractometry, nuclear magnetic resonance relaxation time and dynamic mechanical analysis. The melt flow rate varied non-linearly according to the debris content. The thermal stability of recycled polypropylene was slightly improved due to the presence of debris particles. The degree of crystallinity of the recycled polypropylene also showed a non-linear change, and we noticed some transcrystallization phenomenon in the polymeric matrix. The glass transition temperature decreased for all composites, denoting an increase in the segmental mobility of the polymeric chains. Considering the domains curves of the nuclear magnetic resonance, there was some interaction between polymer and debris particles, mainly ascribed to the nanometric portion of the hybrid debris particles. We concluded that this hybrid composite may become of great interest to the construction industry, used as replacement for closing boards.
Pathological and microbiological investigations into cases of bacterial chondronecrosis and osteomyelitis in broiler poultry

ABSTRACT Bacterial chondronecrosis and osteomyelitis (BCO) is increasingly recognized as a major cause of lameness in commercial broilers chickens worldwide, but the pathogenesis of the condition is incompletely understood. This was a longitudinal study of 20 commercial broiler farms in Victoria, Australia, to investigate the aetiology and pathology of BCO. Thorough postmortem examination was performed on culled and dead birds (n = 325) from 20 different flocks at either 1 week, 4 weeks or 5 weeks of age and samples were analysed by conventional bacteriology, molecular identification of infectious organisms detected, serology and histopathology. BCO occurs throughout the life of broiler flocks at a very high rate, with lesions detected in 28% (95% CI 23–34%) of the mortalities and culls. The condition occurs with similar prevalence in both the femur and tibiotarsus. BCO is an infectious process that appears to result from bacteraemia and haematological spread of bacterial pathogens, especially Escherichia coli, to the bones, with 65.3% bacterial isolates from histologically confirmed BCO identified as E. coli, 11.5% as Staphylococcus and the remainder composed of mixed infections or a range of other minor isolates. We observed that almost all E. coli isolated from cases of BCO are avian pathogenic E. coli, suggesting that preventative measures should be directed at this organism.
Gyrokinetic electron acceleration in the force-free corona with anomalous resistivity

Aims. We numerically explore electron acceleration and coronal heating by dissipative electric fields. Methods. Electrons are traced in linear force-free magnetic fields extrapolated from SOHO/MDI magnetograms, endowed with anomalous resistivity (η) in localized dissipation regions where the magnetic twist ∇× ˆ exceeds a given threshold. Associated with η> 0 is a parallel electric field E = ηj that can accelerate runaway electrons. In order to gain observational predictions, we inject electrons inside the dissipation regions and follow them for several seconds in real time. Results. Precipitating electrons that leave the simulation system at height z = 0 are associated with hard X rays, and electrons that escape at height z ∼ 3 × 10 4 km are associated with normal-drifting type IIIs at the local plasma frequency. A third, trapped population is related to gyrosynchrotron emission. Time profiles and spectra of all three emissions are calculated, and their dependence on the geometric model parameters and on η is explored. It is found that precipitation generally precedes escape by fractions of a second and that the electrons perform many visits to the dissipation regions before leaving the simulation system. The electrons impacting z = 0 reach higher energies than the escaping ones, and non-Maxwellian tails are observed at energies above the largest potential drop across a single dissipation region. Impact maps at z = 0 show the tendency of the electrons to arrive at the borders of sunspots of one polarity. Conclusions. Although the magnetograms used here belong to non-flaring times, so that the simulations refer to nanoflares and “quiescent” coronal heating, it is conjectured that the same process, on a larger scale, is responsible for solar flares.
Towards Adaptive Smoothed Aggregation (AlphaSA) for Nonsymmetric Problems

Applying smoothed aggregation (SA) multigrid to solve a nonsymmetric linear system, $A\mathbf{x} =\mathbf{b}$, is often impeded by the lack of a minimization principle that can be used as a basis for the coarse-grid correction process. This paper proposes a Petrov-Galerkin (PG) approach based on applying SA to either of two symmetric positive definite (SPD) matrices, $\sqrt{A^{t}A}$ or $\sqrt{AA^{t}}$. These matrices, however, are typically full and difficult to compute, so it is not computationally efficient to use them directly to form a coarse-grid correction. The proposed approach approximates these coarse-grid corrections by using SA to accurately approximate the right and left singular vectors of $A$ that correspond to the lowest singular value. These left and right singular vectors are used to construct the restriction and interpolation operators, respectively. A preliminary two-level convergence theory is presented, suggesting that more relaxation should be applied than for an SPD problem. Additionally, a nonsymmetric version of adaptive SA ($\alpha$SA) is given that automatically constructs SA multigrid hierarchies using a stationary relaxation process on all levels. Numerical results are reported for convection-diffusion problems in two dimensions with varying amounts of convection for constant, variable, and recirculating convection fields. The results suggest that the proposed approach is algorithmically scalable for problems coming from these nonsymmetric scalar PDEs (with the exception of recirculating flow). This paper serves as a first step for nonsymmetric $\alpha$SA. The long-term goal of this effort is to develop nonsymmetric $\alpha$SA for systems of PDEs, where the SA framework has proven to be well suited for adaptivity in SPD problems.
Severe Fever with Thrombocytopenia Syndrome

A 73-year-old Japanese man was referred to Hiroshima Prefectural Hospital with a 6-day history of fever. Nine days prior to admission, he had received a tick bite on his right knee while picking bamboo shoots. Three days after the bite, he developed a fever with shaking chills. Minocycline was prescribed at a local clinic, but his symptoms did not resolve. On admission, his consciousness was unclear. Petechiae were observed on his right lower limb (Picture 1). The tick bite site had formed an obscure eschar (Picture 2). His platelet count was 110×10/μL. The patient was suspected of having severe fever with thrombocytopenia syndrome (SFTS), and was treated with supportive measures. SFTS viral nucleic acid was detected through a polymerase chain reaction in his serum sample. The petechiae disappeared on the 12th day of admission (Picture 3), but the eschar remained at that time (Picture 4). The patient thereafter suc-