297 research outputs found
Dynamical energy analysis on mesh grids: a new tool for describing the vibro-acoustic response of complex mechanical structures
We present a new approach for modelling noise and vibration in complex mechanical structures in the mid-to-high frequency regime. It is based on a dynamical energy analysis (DEA) formulation which extends standard techniques such as statistical energy analysis (SEA) towards non-diffusive wave fields. DEA takes into account the full directionality of the wave field and makes sub-structuring obsolete. It can thus be implemented on mesh grids commonly used, for example, in the finite element method (FEM). The resulting mesh based formulation of DEA can be implemented very efficiently using discrete flow mapping (DFM) as detailed in [1] and described here for applications in vibro-acoustics
Blood RNA analysis can increase clinical diagnostic rate and resolve variants of uncertain significance
Purpose
Diagnosis of genetic disorders is hampered by large numbers of variants of uncertain significance (VUSs) identified through next-generation sequencing. Many such variants may disrupt normal RNA splicing. We examined effects on splicing of a large cohort of clinically identified variants and compared performance of bioinformatic splicing prediction tools commonly used in diagnostic laboratories.
Methods
Two hundred fifty-seven variants (coding and noncoding) were referred for analysis across three laboratories. Blood RNA samples underwent targeted reverse transcription polymerase chain reaction (RT-PCR) analysis with Sanger sequencing of PCR products and agarose gel electrophoresis. Seventeen samples also underwent transcriptome-wide RNA sequencing with targeted splicing analysis based on Sashimi plot visualization. Bioinformatic splicing predictions were obtained using Alamut, HSF 3.1, and SpliceAI software.
Results
Eighty-five variants (33%) were associated with abnormal splicing. The most frequent abnormality was upstream exon skipping (39/85 variants), which was most often associated with splice donor region variants. SpliceAI had greatest accuracy in predicting splicing abnormalities (0.91) and outperformed other tools in sensitivity and specificity.
Conclusion
Splicing analysis of blood RNA identifies diagnostically important splicing abnormalities and clarifies functional effects of a significant proportion of VUSs. Bioinformatic predictions are improving but still make significant errors. RNA analysis should therefore be routinely considered in genetic disease diagnostics
The origins and development of Zuwīla, Libyan Sahara: an archaeological and historical overview of an ancient oasis town and caravan centre
Zuwīla in southwestern Libya (Fazzān) was one of the most important early Islamic centres in the Central Sahara, but the archaeological correlates of the written sources for it have been little explored. This paper brings together for the first time a detailed consideration of the relevant historical and archaeological data, together with new AMS radiocarbon dates from several key monuments. The origins of the settlement at Zuwīla were pre-Islamic, but the town gained greater prominence in the early centuries of Arab rule of the Maghrib, culminating with the establishment of an Ibāḍī state ruled by the dynasty of the Banū Khaṭṭāb, with Zuwīla its capital. The historical sources and the accounts of early European travellers are discussed and archaeological work at Zuwīla is described (including the new radiocarbon dates). A short gazetteer of archaeological monuments is provided as an appendix. Comparisons and contrasts are also drawn between Zuwīla and other oases of the ash-Sharqiyāt region of Fazzān. The final section of the paper presents a series of models based on the available evidence, tracing the evolution and decline of this remarkable site
Climate change research and action must look beyond 2100
Anthropogenic activity is changing Earth's climate and ecosystems in ways that are potentially dangerous and disruptive to humans. Greenhouse gas concentrations in the atmosphere continue to rise, ensuring that these changes will be felt for centuries beyond 2100, the current benchmark for projection. Estimating the effects of past, current, and potential future emissions to only 2100 is therefore short-sighted. Critical problems for food production and climate-forced human migration are projected to arise well before 2100, raising questions regarding the habitability of some regions of the Earth after the turn of the century. To highlight the need for more distant horizon scanning, we model climate change to 2500 under a suite of emission scenarios and quantify associated projections of crop viability and heat stress. Together, our projections show global climate impacts increase significantly after 2100 without rapid mitigation. As a result, we argue that projections of climate and its effects on human well-being and associated governance and policy must be framed beyond 2100
Measurement of the Mass Splittings between the States
We present new measurements of photon energies and branching fractions for
the radiative transitions: Upsilon(2S)->gamma+chi_b(J=0,1,2). The masses of the
chi_b states are determined from the measured radiative photon energies. The
ratio of mass splittings between the chi_b substates,
r==(M[J=2]-M[J=1])/(M[J=1]-M[J=0]) with M the chi_b mass, provides information
on the nature of the bbbar confining potential. We find
r(1P)=0.54+/-0.02+/-0.02. This value is in conflict with the previous world
average, but more consistent with the theoretical expectation that r(1P)<r(2P);
i.e., that this mass splittings ratio is smaller for the chi_b(1P) triplet than
for the chi_b(2P) triplet.Comment: 11 page postscript file, postscript file also available through
http://w4.lns.cornell.edu/public/CLN
Solar parameters for modeling interplanetary background
The goal of the Fully Online Datacenter of Ultraviolet Emissions (FONDUE)
Working Team of the International Space Science Institute in Bern, Switzerland,
was to establish a common calibration of various UV and EUV heliospheric
observations, both spectroscopic and photometric. Realization of this goal
required an up-to-date model of spatial distribution of neutral interstellar
hydrogen in the heliosphere, and to that end, a credible model of the radiation
pressure and ionization processes was needed. This chapter describes the solar
factors shaping the distribution of neutral interstellar H in the heliosphere.
Presented are the solar Lyman-alpha flux and the solar Lyman-alpha resonant
radiation pressure force acting on neutral H atoms in the heliosphere, solar
EUV radiation and the photoionization of heliospheric hydrogen, and their
evolution in time and the still hypothetical variation with heliolatitude.
Further, solar wind and its evolution with solar activity is presented in the
context of the charge exchange ionization of heliospheric hydrogen, and in the
context of dynamic pressure variations. Also the electron ionization and its
variation with time, heliolatitude, and solar distance is presented. After a
review of all of those topics, we present an interim model of solar wind and
the other solar factors based on up-to-date in situ and remote sensing
observations of solar wind. Results of this effort will further be utilised to
improve on the model of solar wind evolution, which will be an invaluable asset
in all heliospheric measurements, including, among others, the observations of
Energetic Neutral Atoms by the Interstellar Boundary Explorer (IBEX).Comment: Chapter 2 in the planned "Cross-Calibration of Past and Present Far
UV Spectra of Solar System Objects and the Heliosphere", ISSI Scientific
Report No 12, ed. R.M. Bonnet, E. Quemerais, M. Snow, Springe
Weird exoskeletons: propositional politics and the making of home in underground Bucharest
The article explores the politics of life underground in Bucharest, Romania. It focuses on a tunnel passing under Bucharest's central train station, where a community of drug users and so‐called ‘homeless’ have made a long‐standing home, using a space that many others considered uninhabitable. Relying on extensive ethnographic observations and interviews undertaken within the tunnels, the article traces and illustrates the socio‐material entanglements characterizing life underground. It frames this assemblage of bodies, veins, syringes, substances and various relationships of power and affect, as a ‘propositional politics’ of home and life at the margins. Such a politics speaks of drug addiction and extreme marginalization, but also of a sense of belonging, reciprocal trust and care. In tracing such a politics, the article does not aim to romanticize the status of home in the underground or to treat it as the marginal antithesis of normative homeliness, but to reveal the ways in which an affirmative, self‐grounding politics of home emerges from the immanence of tunnel life within the fabric of the city. As such, the article contributes to debates around homing practices in conditions of uninhabitability and proposes a radical approach to the politics of life at the margins in the contemporary urban
Common variants near MC4R are associated with fat mass, weight and risk of obesity.
To identify common variants influencing body mass index (BMI), we analyzed genome-wide association data from 16,876 individuals of European descent. After previously reported variants in FTO, the strongest association signal (rs17782313, P = 2.9 x 10(-6)) mapped 188 kb downstream of MC4R (melanocortin-4 receptor), mutations of which are the leading cause of monogenic severe childhood-onset obesity. We confirmed the BMI association in 60,352 adults (per-allele effect = 0.05 Z-score units; P = 2.8 x 10(-15)) and 5,988 children aged 7-11 (0.13 Z-score units; P = 1.5 x 10(-8)). In case-control analyses (n = 10,583), the odds for severe childhood obesity reached 1.30 (P = 8.0 x 10(-11)). Furthermore, we observed overtransmission of the risk allele to obese offspring in 660 families (P (pedigree disequilibrium test average; PDT-avg) = 2.4 x 10(-4)). The SNP location and patterns of phenotypic associations are consistent with effects mediated through altered MC4R function. Our findings establish that common variants near MC4R influence fat mass, weight and obesity risk at the population level and reinforce the need for large-scale data integration to identify variants influencing continuous biomedical traits
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