Mutations in the gene encoding IFT dynein complex component WDR34 cause jeune asphyxiating thoracic dystrophy

Bidirectional (anterograde and retrograde) motor-based intraflagellar transport (IFT) governs cargo transport and delivery processes that are essential for primary cilia growth and maintenance and for hedgehog signaling functions. The IFT dynein-2 motor complex that regulates ciliary retrograde protein transport contains a heavy chain dynein ATPase/motor subunit, DYNC2H1, along with other less well functionally defined subunits. Deficiency of IFT proteins, including DYNC2H1, underlies a spectrum of skeletal ciliopathies. Here, by using exome sequencing and a targeted next-generation sequencing panel, we identified a total of 11 mutations in WDR34 in 9 families with the clinical diagnosis of Jeune syndrome (asphyxiating thoracic dystrophy). WDR34 encodes a WD40 repeat-containing protein orthologous to Chlamydomonas FAP133, a dynein intermediate chain associated with the retrograde intraflagellar transport motor. Three-dimensional protein modeling suggests that the identified mutations all affect residues critical for WDR34 protein-protein interactions. We find that WDR34 concentrates around the centrioles and basal bodies in mammalian cells, also showing axonemal staining. WDR34 coimmunoprecipitates with the dynein-1 light chain DYNLL1 in vitro, and mining of proteomics data suggests that WDR34 could represent a previously unrecognized link between the cytoplasmic dynein-1 and IFT dynein-2 motors. Together, these data show that WDR34 is critical for ciliary functions essential to normal development and survival, most probably as a previously unrecognized component of the mammalian dynein-IFT machinery.

The influence of critical infrastructure interdependencies on post-disaster reconstruction: Elements of infrastructure interdependency that impede the post-disaster recovery effort

The importance of developing effective disaster management strategies has significantly grown as the world continues to be confronted with unprecedented disastrous events. Factors such as climate instability, recent urbanization along with rapid population growth in many cities around the world have unwittingly exacerbated the risks of potential disasters, leaving a large number of people and infrastructure exposed to new forms of threats from natural disasters such as flooding, cyclones, and earthquakes. With disasters on the rise, effective recovery planning of the built environment is becoming imperative as it is not only closely related to the well-being and essential functioning of society, but it also requires significant financial commitment. In the built environment context, post-disaster reconstruction focuses essentially on the repair and reconstruction of physical infrastructures. The reconstruction and rehabilitation efforts are generally performed in the form of collaborative partnerships that involve multiple organisations, enabling the restoration of interdependencies that exist between infrastructure systems such as energy, water (including wastewater), transport, and telecommunication systems. These interdependencies are major determinants of vulnerabilities and risks encountered by critical infrastructures and therefore have significant implications for post-disaster recovery. When disrupted by natural disasters, such interdependencies have the potential to promote the propagation of failures between critical infrastructures at various levels, and thus can have dire consequences on reconstruction activities. This paper outlines the results of a pilot study on how elements of infrastructure interdependencies have the potential to impede the post-disaster recovery effort. Using a set of unstructured interview questionnaires, plausible arguments provided by seven respondents revealed that during post-disaster recovery, critical infrastructures are mutually dependent on each other’s uninterrupted availability, both physically and through a host of information and communication technologies. Major disruption to their physical and cyber interdependencies could lead to cascading failures, which could delay the recovery effort. Thus, the existing interrelationship between critical infrastructures requires that the entire interconnected network be considered when managing reconstruction activities during the post-disaster recovery period.

An alternative approach to describing agility in sports through establishment of a relationship between velocity and radius of curvature

Agility is an essential part of many athletic activities. Currently, agility drill duration is the sole criterion used for evaluation of agility performance. The relationship between drill duration and factors such as acceleration, deceleration and change of direction, however, has not been fully explored. This paper provides a mathematical description of the relationship between velocity and radius of curvatures in an agility drill through implementation of a power law (PL). Two groups of skilled and unskilled participants performed a cyclic forward/backward shuttle agility test. Kinematic data was recorded using motion capture system at a sampling rate of 200 Hz. The logarithmic relationship between tangential velocity and radius of curvature of participant trajectories in both groups was established using the PL. The slope of the regression line was found to be 0.26 and 0.36, for the skilled and unskilled groups, respectively. The magnitudes of regression line slope for both groups were approximately 0.3 which is close to the expected 1/3 value. Results are an indication of how the PL could be implemented in an agility drill thus opening the way for establishment of a more representative measure of agility performance instead of drill duration.

Systematic literature review of incidence rates of low-speed vehicle run-over incidents in children

Aim: To systematically review the literature investigating the incidence of fatal and or nonfatal low-speed vehicle run-over (LSVRO) incidents in children aged 0–15 years. Methods: The following databases were searched using specific search terms, from their date of conception up to June 2011: Cochrane Library, Medline, CINAHL, Embase, AMI, Sociological Abstracts, ERIC, PsycArticles, PsycInfo, Urban Studies and Planning; Australian Criminology Database; Dissertations and Thesis; Academic Research Library; Social Services Abstracts; Family and Society; Scopus; and Web of Science. A total of 128 articles were identified in the databases (33 found by hand searching). The title and abstract of these were read, and 102 were removed because they were not primary research articles relating to LSVRO-type injuries. Twenty-six articles were assessed against the inclusion (reporting population level incidence rates) and exclusion criteria, 19 of which were excluded, leaving a total of five articles for inclusion in the review. Findings: Five studies were identified that met the inclusion criteria. The incidence rate in nonfatal LSVRO events varied in the range of 7.09 to 14.79 per 100,000 and from 0.63 to 3.2 per 100,000 in fatal events. Discussion: Using International Classification of Diseases codes for classifying fatal or nonfatal LSVRO incidents is problematic as there is no specific code for LSVRO. The current body of research is void of a comprehensive secular population data analysis. Only with an improved spectrum of incidence rates will appropriate evaluation of this problem be possible, and this will inform nursing prevention interventions. The effect of LSVRO incidents is clearly understudied. More research is required to address incidence rates in relation to culture, environment, risk factors, car design, and injury characteristics. Conclusions: Thevlack of nursing research or policy around this area of injury, most often to children, indicates a field of inquiry and policy development that needs attention.

Estimation of the time of a linear trend in monitoring survival time

Change point estimation is recognized as an essential tool of root cause analyses within quality control programs as it enables clinical experts to search for potential causes of change in hospital outcomes more effectively. In this paper, we consider estimation of the time when a linear trend disturbance has occurred in survival time following an in-control clinical intervention in the presence of variable patient mix. To model the process and change point, a linear trend in the survival time of patients who underwent cardiac surgery is formulated using hierarchical models in a Bayesian framework. The data are right censored since the monitoring is conducted over a limited follow-up period. We capture the effect of risk factors prior to the surgery using a Weibull accelerated failure time regression model. We use Markov Chain Monte Carlo to obtain posterior distributions of the change point parameters including the location and the slope size of the trend and also corresponding probabilistic intervals and inferences. The performance of the Bayesian estimator is investigated through simulations and the result shows that precise estimates can be obtained when they are used in conjunction with the risk-adjusted survival time cumulative sum control chart (CUSUM) control charts for different trend scenarios. In comparison with the alternatives, step change point model and built-in CUSUM estimator, more accurate and precise estimates are obtained by the proposed Bayesian estimator over linear trends. These superiorities are enhanced when probability quantification, flexibility and generalizability of the Bayesian change point detection model are also considered.

Ability of commonly used prediction equations to predict resting energy expenditure in children with inflammatory bowel disease

Background: Paediatric onset inflammatory bowel disease (IBD) may cause alterations in energy requirements and invalidate the use of standard prediction equations. Our aim was to evaluate four commonly used prediction equations for resting energy expenditure (REE) in children with IBD. Methods: Sixty-three children had repeated measurements of REE as part of a longitudinal research study yielding a total of 243 measurements. These were compared with predicted REE from Schofield, Oxford, FAO/WHO/UNU, and Harris-Benedict equations using the Bland-Altman method. Results: Mean (±SD) age of the patients was 14.2 (2.4) years. Mean measured REE was 1566 (336) kcal per day compared with 1491 (236), 1441 (255), 1481 (232), and 1435 (212) kcal per day calculated from Schofield, Oxford, FAO/WHO/UNU, and Harris-Benedict, respectively. While the Schofield equation demonstrated the least difference between measured and predicted REE, it, along with the other equations tested, did not perform uniformly across all subjects, indicating greater errors at either end of the spectrum of energy expenditure. Smaller differences were found for all prediction equations for Crohn's disease compared with ulcerative colitis. Conclusions: Of the commonly used equations, the equation of Schofield should be used in pediatric patients with IBD when measured values are not able to be obtained. (Inflamm Bowel Dis 2010;) Copyright © 2010 Crohn's & Colitis Foundation of America, Inc.

Will algorithmic playlist curation be the end of music stardom?

It is 2015 and there are no indications that the relentless digital transformation of the music economy is about to slow down. Rather, the music economy continues to rapidly reinvent itself and industry powers, positions and practices that were redefined only a few years ago are being questioned once again. This paper examines the most recent changes of the music economy as it moves from a product-based towards an access-based logic. The paper starts out by recognising the essential role of technology in the evolution of the music economy. It then moves on to a discussion about the rise of so-called access-based music business models and points out some of the controversies and debates that are associated with these models and online services. With this as a background the paper explores how access-based music services and the algorithmically curated playlists developed by these services transform the relationship between artists, music and fans and challenges the music industrial power relationships and established industry practices once again.

Influence of LRP5 polymorphisms on normal variation in BMD

Genetic studies based on cohorts with rare and extreme bone phenotypes have shown that the LRP5 gene is an important genetic modulator of BMD. Using family-based and case-control approaches, this study examines the role of the LRP5 gene in determining normal population variation of BMD and describes significant association and suggestive linkage between LRP5 gene polymorphisms and BMD in >900 individuals with a broad range of BMD. Introduction: Osteoporosis is a common, highly heritable condition determined by complex interactions of genetic and environmental etiologies. Genetic factors alone can account for 50-80% of the interindividual variation in BMD. Mutations in the LRP5 gene on chromosome 11q12-13 have been associated with rare syndromes characterized by extremely low or high BMD, but little is known about the contribution of this gene to the development of osteoporosis and determination of BMD in a normal population. Materials and Methods: To examine the entire spectrum of low to high BMD, 152 osteoporotic probands, their families (597 individuals), and 160 women with elevated BMD (T score > 2.5) were recruited. BMD at the lumbar spine, femoral neck, and hip were measured in each subject using DXA. Results: PAGE sequencing of the LRP5 gene revealed 10 single nucleotide polymorphisms (SNPs), 8 of which had allele frequencies of >5%, in exons 8, 9, 10, 15, and 18 and in introns 6, 7, and 21. Within families, a strong association was observed between an SNP at nucleotide C171346A in intron 21 and total hip BMD (p < 1 × 10-5 in men only, p = 0.0019 in both men and women). This association was also observed in comparisons of osteoporotic probands and unrelated elevated BMD in women (p = 0.03), along with associations with markers in exons 8 (C135242T, p = 0.007) and 9 (C141759T, p = 0.02). Haplotypes composed of two to three of the SNPs G121513A, C135242T, G138351A, and C141759T were strongly associated with BMD when comparing osteoporotic probands and high BMD cases (p < 0.003). An SNP at nucleotide C165215T in exon 18 was linked to BMD at the lumbar spine, femoral neck, and total hip (parametric LOD scores = 2.8, 2.5, and 2.2 and nonparametric LOD scores = 0.3, 1.1, and 2.2, respectively) but was not genetically associated with BMD variation. Conclusion: These results show that common LRP5 polymorphisms contribute to the determination of BMD in the general population.

Statistical analysis of the position of the monsoon trough

Using surface charts at 0330GMT, the movement df the monsoon trough during the months June to September 1990 al two fixed longitudes, namely 79 degrees E and 85 degrees E, is studied. The probability distribution of trough position shows that the median, mean and mode occur at progressively more northern latitudes, especially at 85 degrees E, with a pronounced mode that is close to the northern-most limit reached by the trough. A spectral analysis of the fluctuating latitudinal position of the trough is carried out using FFT and the Maximum Entropy Method (MEM). Both methods show significant peaks around 7.5 and 2.6 days, and a less significant one around 40-50 days. The two peaks at the shorter period are more prominent at the eastern longitude. MEM shows an additional peak around 15 days. A study of the weather systems that occurred during the season shows them to have a duration around 3 days and an interval between systems of around 9 days, suggesting a possible correlation with the dominant short periods observed in the spectrum of trough position.

Anomalous thermal dynamics of Bragg gratings inscribed in germanosilicate optical fiber

An interesting, periodic appearance of a new peak has been observed in the reflected spectrum of a Fiber Bragg Grating (FBG) inscribed in a germanosilicate fiber during thermal treatment. The new peak occurs on the longer wavelength side of the spectrum during heating and on the shorter wavelength side during cooling, following an identical reverse dynamics. Comparison with a commercial grating with 99.9% reflectivity shows a similar decay dynamics. It is proposed that the distortion due to simultaneous erasure and thermal expansion of the index modulation profile may be responsible for the observed anomaly. The reported results help us in understanding the thermal behavior of FBGs and provide additional insights into the mechanisms responsible for the photosensitivity in germanosilicate fibers.

Synthesis, crystal structure and DNA cleavage activity of (aqua)bis(dipyridophenazine)copper(II) complex

A copper(II) complex of dipyridophenazine, viz., [Cu(dppz)(2)(H2O)](ClO4)(2) (I), has been prepared and structurally characterized by X-ray crystallography. The crystal structure of the complex shows a five-coordinate structure in which two N,N-donor dipyridophenazine (dppz) and one aqua ligand bind to the copper(II) center giving Cu-O and Cu-N bond distances in the range of 1.981(6) to 2.043(6) angstrom. The ESI-MS spectrum of 1 in MeCN shows a peak at m/z value of 313 (100%) indicating the dissociation of the aqua ligand in the solution phase. The complex is one-electron paramagnetic (mu(eff), 1.86 mu(B)). It displays a quasi-reversible Cu(II)/Cu(I) redox process at 0.096 V. The complex is an avid binder to CT DNA giving a binding constant value of 3.5 x 10(5) M-1. It shows significant hydrolytic cleavage of supercoiled pUC19 DNA in dark ill the absence of any external agents. The complex exhibits chemical nuclease activity oil treatment with 3-mercaptopropionic acid as a reducing agent forming hydroxyl radicals. Complex 1 is a model synthetic nuclease and hydrolase showing both modes of DNA cleavage under different reaction conditions. The DNA cleavage activity of 1 is significantly better than its phen analogue but similar to that of the bis-dpq complex.

A combined experimental and theoretical study of the charge-transfer compound between C60Br8 and tetrathiafulvalene

C60Br8, unlike C60Br6 and C60Cl6, forms a solid charge-transfer compound with tetrathiafulvalene (TTF), the composition being C60Br8(TTF)(8). The unique complex-forming property of C60Br8 can be understood on the basis of the electronic structures of the halogenated derivatives of C-60. Molecular orbital calculations show that the low LUMO energy of C60Br8 compared with the other halogen derivatives renders the formation of the complex with TTF favourable, the four virtual LUMOs being able to accept 8 electrons. The Raman spectrum of C60Br8(TTF)(8) shows a marked softening of the bands (-46 cm(-1) on average) with respect to C60Br8 suggesting that indeed 8 electrons are transferred per C60Br8 molecule, one from each TTF molecule. The complex is weakly paramagnetic and shows a magnetic transition around 80 K.

B- and T-cell epitopes of tropomyosin, the major shrimp allergen

Seafood allergy is often encountered on ingestion of crustaceans such as shrimp, lobster, crab, and crayfish (1). On eating cooked shrimp, sensitive individuals experience a wide spectrum of reactions ranging from abdominal discomfort to anaphylaxis. The presence of cross-reacting heat-stable allergens in crustacean food was first recognized by Hoffman et al. (2) and Lehrer et al. (3). Subsequently, the major allergen was isolated and characterized from the shrimp species Paneaus indicus (Pen i 1) (4) and I? aztecm (Pen a 1) (5). Pen i 1 (originally designated Sa-TI) and Pen a 1, with mol. mass of 34 and 36 kDa, respectively, contain 301 and 312 amino-acid residues with a predominance of gluta- mate/glutamine and asparatate/asparagine.

Assembly of sol-gel-grown $Li _{(x)} CoO_{2}$ nanocrystals through electromagnetic irradiation

We report the fabrication of assembled nanostructures from the pre-synthesized nanocrystals building blocks through optical means of exciton formation and dissociation. We demonstrate that Li (x) CoO2 nanocrystals assemble to an acicular architecture, upon prolonged exposure to ultraviolet-visible radiation emitted from a 125 W mercury vapor lamp, through intermediate excitation of excitons. The results obtained in the present study clearly show how nanocrystals of various materials with band gaps appropriate for excitations of excitons at given optical wavelengths can be assembled to unusual nanoarchitectures through illumination with incoherent light sources. The disappearance of exciton bands due to Li (x) CoO2 phase in the optical spectrum of the irradiated film comprising acicular structure is consistent with the proposed mechanism of exciton dissociation in the observed light-induced assembly process. The assembly process occurs through attractive Coulomb interactions between charged dots created upon exciton dissociation. Our work presents a new type of nanocrystal assembly process that is driven by light and exciton directed.

The complementation of yeast with human or Plasmodium falciparum Hsp90 confers differential inhibitor sensitivities

Developing novel drugs against the unicellular parasite Plasmodium is complicated by the paucity of simple screening systems. Heat-shock proteins are an essential class of proteins for the parasite's cyclical life style between different cellular milieus and temperatures. The molecular chaperone Hsp90 assists a large variety of proteins, but its supporting functions for many proteins that are important for cancer have made it into a well-studied drug target. With a better understanding of the differences between Hsp90 of the malarial parasite and Hsp90 of its human host, new therapeutic options might become available. We have generated a set of isogenic strains of the budding yeast Saccharomyces cerevisiae where the essential yeast Hsp90 proteins have been replaced with either of the two human cytosolic isoforms Hsp90 alpha or Hsp90 beta, or with Hsp90 from Plasmodium falciparum (Pf). All strains express large amounts of the Flag-tagged Hsp90 proteins and are viable. Even though the strain with Pf Hsp90 grows more poorly, it provides a tool to reconstitute additional aspects of the parasite Hsp90 complex and its interactions with substrates in yeast as a living test tube. Upon exposure of the set of Hsp90 test strains to the two Hsp90 inhibitors radicicol (Rd) and geldanamycin (GA), we found that the strain with Pf Hsp90 is relatively more sensitive to GA than to Rd compared to the strains with human Hsp90's. This indicates that this set of yeast strains could be used to screen for new Pf Hsp90 inhibitors with a wider therapeutic window.