Collapse of a semiflexible polymer in poor solvent

We investigate the dynamics and the pathways of the collapse of a single, semiflexible polymer in a poor solvent via 3-D Brownian Dynamics simulations. Earlier work indicates that the condensation of semiflexible polymers generically proceeds via a cascade through metastable racquet-shaped, long-lived intermediates towards the stable torus state. We investigate the rate of decay of uncollapsed states, analyze the preferential pathways of condensation, and describe likelihood and lifespan of the different metastable states. The simulation are performed with a bead-stiff spring model with excluded volume interaction and exponentially decaying attractive potential. The semiflexible chain collapse is studied as functions of the three relevant length scales of the phenomenon, i.e., the total chain length $L$, the persistence length $L_p$ and the condensation length $L_0 = \sqrt{k_B T L_p/u_0}$, where $u_0$ is a measure of the attractive potential per unit length. Two dimensionless ratios, $L/L_p$ and $L_0/L_p$, suffice to describe the decay rate of uncollapsed states, which appears to scale as $(L/L_p)^{1/3} (L_0/L_p)$. The condensation sequence is described in terms of the time series of the well separated energy levels associated with each metastable collapsed state. The collapsed states are described quantitatively through the spatial correlation of tangent vectors along the chain. We also compare the results obtained with a locally inextensible bead-rod chain and with a phantom bead-spring model. Finally, we show preliminary results on the effects of steady shear flow on the kinetics of collapse.Comment: 9 pages, 8 figure

Minimal Mass Matrices for Dirac Neutrinos

We consider the possibility of neutrinos being Dirac particles and study minimal mass matrices with as much zero entries as possible. We find that up to 5 zero entries are allowed. Those matrices predict one vanishing mass state, CP conservation and U_{e3} either zero or proportional to R, where R is the ratio of the solar and atmospheric \Delta m^2. Matrices containing 4 zeros can be classified in categories predicting U_{e3} = 0, U_{e3} \neq 0 but no CP violation or |U_{e3}| \neq 0 and possible CP violation. Some cases allow to set constraints on the neutrino masses. The characteristic value of U_{e3} capable of distinguishing some of the cases with non-trivial phenomenological consequences is about R/2 \sin 2 \theta_{12}. Matrices containing 3 and less zero entries imply (with a few exceptions) no correlation for the observables. We outline models leading to the textures based on the Froggatt-Nielsen mechanism or the non-Abelian discrete symmetry D_4 \times Z_2.Comment: 32 pages, 3 figures. Comments and references added. To appear in JHE

Developing a core outcome set for future infertility research : An international consensus development study

STUDY QUESTION: Can a core outcome set to standardize outcome selection, collection and reporting across future infertility research be developed? SUMMARY ANSWER: A minimum data set, known as a core outcome set, has been developed for randomized controlled trials (RCTs) and systematic reviews evaluating potential treatments for infertility. WHAT IS KNOWN ALREADY: Complex issues, including a failure to consider the perspectives of people with fertility problems when selecting outcomes, variations in outcome definitions and the selective reporting of outcomes on the basis of statistical analysis, make the results of infertility research difficult to interpret. STUDY DESIGN, SIZE, DURATION: A three-round Delphi survey (372 participants from 41 countries) and consensus development workshop (30 participants from 27 countries). PARTICIPANTS/MATERIALS, SETTING, METHODS: Healthcare professionals, researchers and people with fertility problems were brought together in an open and transparent process using formal consensus science methods. MAIN RESULTS AND THE ROLE OF CHANCE: The core outcome set consists of: viable intrauterine pregnancy confirmed by ultrasound (accounting for singleton, twin and higher multiple pregnancy); pregnancy loss (accounting for ectopic pregnancy, miscarriage, stillbirth and termination of pregnancy); live birth; gestational age at delivery; birthweight; neonatal mortality; and major congenital anomaly. Time to pregnancy leading to live birth should be reported when applicable. LIMITATIONS, REASONS FOR CAUTION: We used consensus development methods which have inherent limitations, including the representativeness of the participant sample, Delphi survey attrition and an arbitrary consensus threshold. WIDER IMPLICATIONS OF THE FINDINGS: Embedding the core outcome set within RCTs and systematic reviews should ensure the comprehensive selection, collection and reporting of core outcomes. Research funding bodies, the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) statement, and over 80 specialty journals, including the Cochrane Gynaecology and Fertility Group, Fertility and Sterility and Human Reproduction, have committed to implementing this core outcome set. STUDY FUNDING/COMPETING INTEREST(S): This research was funded by the Catalyst Fund, Royal Society of New Zealand, Auckland Medical Research Fund and Maurice and Phyllis Paykel Trust. The funder had no role in the design and conduct of the study, the collection, management, analysis or interpretation of data, or manuscript preparation. B.W.J.M. is supported by a National Health and Medical Research Council Practitioner Fellowship (GNT1082548). S.B. was supported by University of Auckland Foundation Seelye Travelling Fellowship. S.B. reports being the Editor-in-Chief of Human Reproduction Open and an editor of the Cochrane Gynaecology and Fertility group. J.L.H.E. reports being the Editor Emeritus of Human Reproduction. J.M.L.K. reports research sponsorship from Ferring and Theramex. R.S.L. reports consultancy fees from Abbvie, Bayer, Ferring, Fractyl, Insud Pharma and Kindex and research sponsorship from Guerbet and Hass Avocado Board. B.W.J.M. reports consultancy fees from Guerbet, iGenomix, Merck, Merck KGaA and ObsEva. C.N. reports being the Co Editor-in-Chief of Fertility and Sterility and Section Editor of the Journal of Urology, research sponsorship from Ferring, and retains a financial interest in NexHand. A.S. reports consultancy fees from Guerbet. E.H.Y.N. reports research sponsorship from Merck. N.L.V. reports consultancy and conference fees from Ferring, Merck and Merck Sharp and Dohme. The remaining authors declare no competing interests in relation to the work presented. All authors have completed the disclosure form

Genome-wide survival study identifies a novel synaptic locus and polygenic score for cognitive progression in Parkinson's disease

A key driver of patients' well-being and clinical trials for Parkinson's disease (PD) is the course that the disease takes over time (progression and prognosis). To assess how genetic variation influences the progression of PD over time to dementia, a major determinant for quality of life, we performed a longitudinal genome-wide survival study of 11.2 million variants in 3,821 patients with PD over 31,053 visits. We discover RIMS2 as a progression locus and confirm this in a replicate population (hazard ratio (HR) = 4.77, P = 2.78 x 10(-11)), identify suggestive evidence for TMEM108 (HR = 2.86, P = 2.09 x 10(-8)) and WWOX (HR = 2.12, P = 2.37 x 10(-8)) as progression loci, and confirm associations for GBA (HR = 1.93, P = 0.0002) and APOE (HR = 1.48, P = 0.001). Polygenic progression scores exhibit a substantial aggregate association with dementia risk, while polygenic susceptibility scores are not predictive. This study identifies a novel synaptic locus and polygenic score for cognitive disease progression in PD and proposes diverging genetic architectures of progression and susceptibility.A genome-wide survival study identifies variants at RIMS2 associated with progression of Parkinson's disease to dementia and highlights divergence in the genetic architecture of disease onset and progression.Neurological Motor Disorder

Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria

Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria

Virtual water trade a quantification of virtual water flows between nations in relation to international crop trade

The water that is used in the production process of an agricultural or industrial product is called the 'virtual water' contained in the product. A water-scarce country might wish to import products that require a lot of water in their production (water-intensive products) and export products or services that require less water (waterextensive products). This implies net import of ‘virtual water’ (as opposed to import of real water, which is generally too expensive) and will relieve the pressure on the nation’s own water resources. Until date little is known on the actual volumes of virtual water trade flows between countries. The objective of this study is to quantify the volumes of all virtual water trade flows between nations in the period 1995-1999 and to put the virtual water trade balances of nations within the context of national water needs and water availability. The study has been limited to the quantification of virtual water trade flows related to international crop trade. The basic approach has been to multiply international crop trade flows (ton/yr) by their associated virtual water content (m3/ton). The required crop trade data have been taken from the United Nations Statistics Division in New York. The required data on virtual water content of crops originating from different countries have been estimated on the basis of various FAO databases (CropWat, ClimWat, FAOSTAT). The calculations show that the global volume of crop-related virtual water trade between nations was 695 Gm3/yr in average over the period 1995-1999. For comparison: the total water use by crops in the world has been estimated at 5400 Gm3/yr (Rockström and Gordon, 2001). This means that 13% of the water used for crop production in the world is not used for domestic consumption but for export (in virtual form). This is the global percentage; the situation strongly varies between countries. Considering the period 1995-1999, the countries with largest net virtual water export are: United States, Canada, Thailand, Argentina, and India. The countries with largest net virtual water import in the same period are: Sri Lanka, Japan, the Netherlands, the Republic of Korea, and China. For each nation of the world a ‘water footprint’ has been calculated (a term chosen on the analogy of the ‘ecological footprint’). The water footprint, equal to the sum of the domestic water use and net virtual water import, is proposed here as a measure of a nation’s actual appropriation of the global water resources. It gives a more complete picture than if one looks at domestic water use only, as is being done until date. In addition to the water footprint, indicators are proposed for a nation’s ‘water self-sufficiency’ and a nation’s ‘water dependency’. In studying global virtual water trade flows, it is recommended to start working on other products than crops as well, for instance livestock products such as meat. Another next step is to start interpreting the data and to study how governments can deliberately interfere in the current national virtual water trade balances in order to achieve higher global water use efficiency

Globalisation of water resources: Global virtual water flows in relation to international crop trade

The water that is used in the production process of a commodity is called the ‘virtual water’ contained in the commodity. International trade of commodities brings along international flows of virtual water. The objective of this paper is to quantify the volumes of virtual water flows between nations in the period 1995–1999 insofar related to international crop trade and to analyse national virtual water balances in relation to national water needs and water availability. The basic approach is to multiply international crop trade flows (ton/yr) by their associated virtual water content (m3 ton−1). The calculations show that the global volume of crop-related international virtual water flows between nations was 695 Gm3 yr−1 in average over the period 1995–1999. For comparison: the total water use by crops in the world has been estimated at 5400 Gm3 yr−1. This means that 13% of the water used for crop production in the world is not used for domestic consumption but for export (in virtual form). This is a conservative estimate because only a limited number of crops––although the most important ones––have been taken into account and because crop products (such as cotton clothes) have been excluded from the study. The countries with the largest net virtual water export are United States, Canada, Thailand, Argentina and India. The largest net import appears to be in Japan, the Netherlands, the Republic of Korea, China and Indonesia.\ud \u

Evidence for distinct human auditory cortex regions for sound location versus identity processing

Neurophysiological animal models suggest that anterior auditory cortex (AC) areas process sound identity information, whereas posterior ACs specialize in sound location processing. In humans, inconsistent neuroimaging results and insufficient causal evidence have challenged the existence of such parallel AC organization. Here we transiently inhibit bilateral anterior or posterior AC areas using MRI-guided paired-pulse transcranial magnetic stimulation (TMS) while subjects listen to Reference/Probe sound pairs and perform either sound location or identity discrimination tasks. The targeting of TMS pulses, delivered 55–145 ms after Probes, is confirmed with individual-level cortical electric-field estimates. Our data show that TMS to posterior AC regions delays reaction times (RT) significantly more during sound location than identity discrimination, whereas TMS to anterior AC regions delays RTs significantly more during sound identity than location discrimination. This double dissociation provides direct causal support for parallel processing of sound identity features in anterior AC and sound location in posterior AC.Peer reviewe

A novel high-k gate dielectric HfLaO for next generation CMOS technology

10.1109/ICSICT.2006.306255ICSICT-2006: 2006 8th International Conference on Solid-State and Integrated Circuit Technology, Proceedings372-37