81 research outputs found
Genetics of diabetic microvascular disease
Publisher Copyright: © 2020 John Wiley & Sons, Inc.Diabetic microvascular complications, affecting the kidneys, retina, and the nervous system, are a heavy burden for both the diabetic individual and society. The complications seem to cluster in families suggesting a genetic component in their pathogenesis. However, the actual genetic factors have long remained unknown. During the past few years, major advances have been made with large-scale genetic studies that have identified common genetic risk factors, e.g. in the AFF3 and CNKSR3 gene loci affecting the risk of diabetic kidney disease (DKD) end-stage renal disease. There is increasing evidence that genetic factors affecting kidney disease in non-diabetic individuals also affect the risk in individuals with type 2 diabetes (T2D), while less evidence is found for individuals with type 1 diabetes (T1D). While genetic explorations for diabetic retinopathy remain limited in sample size, a recent genome-wide association study (GWAS) identified variants associated with retinopathy on the GRB2 gene. Nevertheless, the field is still lacking strong validated genetic markers. In the future, better phenotyping, larger studies, and exploration of the rare variation are essential to identify the genetic causes behind diabetic microvascular complications, and to understand the interplay between genes and environment.Peer reviewe
Semileptonic form factors - a model-independent approach
We demonstrate that the B->D(*) l nu form factors can be accurately predicted
given the slope parameter rho^2 of the Isgur-Wise function. Only weak
assumptions, consistent with lattice results, on the wavefunction for the light
degrees of freedom are required to establish this result. We observe that the
QCD and 1/m_Q corrections can be systematically represented by an effective
Isgur-Wise function of shifted slope. This greatly simplifies the analysis of
semileptonic B decay. We also investigate what the available semileptonic data
can tell us about lattice QCD and Heavy Quark Effective Theory. A rigorous
identity relating the form factor slope difference rho_D^2-rho_A1^2 to a
combination of form factor intercepts is found. The identity provides a means
of checking theoretically evaluated intercepts with experiment.Comment: 18 pages, Revtex, 4 postscript figures, uses epsfig.st
Lymphocytic choriomeningitis arenavirus requires cellular COPI and AP-4 complexes for efficient virion production
Lymphocytic choriomeningitis virus (LCMV) is a bisegmented negative-sense RNA virus classified within the Arenaviridae family of the Bunyavirales order. LCMV is associated with fatal disease in immunocompromized populations, and as the prototypical arenavirus, acts as a model for the many serious human pathogens within this group. Here, we examined the dependence of LCMV multiplication on cellular trafficking components using a recombinant LCMV expressing enhanced green fluorescent protein in conjunction with a curated siRNA library. The screen revealed a requirement for subunits of both the coat protein 1 (COPI) coatomer and adapter protein 4 (AP-4) complexes. By rescuing a recombinant LCMV harboring a FLAG-tagged glycoprotein (GP-1) envelope spike (rLCMV-GP1-FLAG), we showed infection resulted in marked co-localization of individual COPI and AP-4 components with both LCMV nucleoprotein (NP) and GP-1, consistent with their involvement in viral processes. To further investigate the role of both COPI and AP-4 complexes during LCMV infection, we utilized the ARF-I inhibitor brefeldin A (BFA) that prevents complex formation. Within a single 12-h cycle of virus multiplication, BFA pre-treatment caused no significant change in LCMV-specific RNA synthesis, alongside no significant change in LCMV NP expression, as measured by BFA time-of-addition experiments. In contrast, BFA addition resulted in a significant drop in released virus titers, approaching 50-fold over the same 12-h period, rising to over 600-fold over 24 h. Taken together, these findings suggest COPI and AP-4 complexes are important host cell factors required for the formation and release of infectious LCMV
Supernova Neutrinos, Neutrino Oscillations, and the Mass of the Progenitor Star
We investigate the initial progenitor mass dependence of the early-phase
neutrino signal from supernovae taking neutrino oscillations into account. The
early-phase analysis has advantages in that it is not affected by the time
evolution of the density structure of the star due to shock propagation or
whether the remnant is a neutron star or a black hole. The initial mass affects
the evolution of the massive star and its presupernova structure, which is
important for two reasons when considering the neutrino signal. First, the
density profile of the mantle affects the dynamics of neutrino oscillation in
supernova. Second, the final iron core structure determines the features of the
neutrino burst, i.e., the luminosity and the average energy. We find that both
effects are rather small. This is desirable when we try to extract information
on neutrino parameters from future supernova-neutrino observations. Although
the uncertainty due to the progenitor mass is not small for intermediate
(), we
can, nevertheless, determine the character of the mass hierarchy and whether
is very large or very small.Comment: 8 pages, 15 figure
Cavity-enhanced direct frequency comb spectroscopy
Cavity-enhanced direct frequency comb spectroscopy combines broad spectral
bandwidth, high spectral resolution, precise frequency calibration, and
ultrahigh detection sensitivity, all in one experimental platform based on an
optical frequency comb interacting with a high-finesse optical cavity. Precise
control of the optical frequency comb allows highly efficient, coherent
coupling of individual comb components with corresponding resonant modes of the
high-finesse cavity. The long cavity lifetime dramatically enhances the
effective interaction between the light field and intracavity matter,
increasing the sensitivity for measurement of optical losses by a factor that
is on the order of the cavity finesse. The use of low-dispersion mirrors
permits almost the entire spectral bandwidth of the frequency comb to be
employed for detection, covering a range of ~10% of the actual optical
frequency. The light transmitted from the cavity is spectrally resolved to
provide a multitude of detection channels with spectral resolutions ranging
from a several gigahertz to hundreds of kilohertz. In this review we will
discuss the principle of cavity-enhanced direct frequency comb spectroscopy and
the various implementations of such systems. In particular, we discuss several
types of UV, optical, and IR frequency comb sources and optical cavity designs
that can be used for specific spectroscopic applications. We present several
cavity-comb coupling methods to take advantage of the broad spectral bandwidth
and narrow spectral components of a frequency comb. Finally, we present a
series of experimental measurements on trace gas detections, human breath
analysis, and characterization of cold molecular beams.Comment: 36 pages, 27 figure
Advances, gaps and way forward in provision of climate services over the Greater Horn of Africa
The Greater Horn of Africa is prone to extreme climatic conditions, thus, making climate services increasingly important in supporting decision-making processes across a range of climate sensitive sectors. This study aims to provide a comprehensive review of the recent advances, gaps and challenges in the provision of climate services over the region, for each of the components of the Global Framework for Climate Services. The study explores various milestones that have been achieved toward climate service delivery. The achievements include improvement of station network coverage, and enhancing the capacity of member states to utilize various tools in data analysis and generate routine climate products. The advancement in science, and availability of High-Performance Computing has made it possible for forecast information to be provided from nowcasting to seasonal timescales. Moreover, operationalizing of the objective forecasting method for monthly and seasonal forecasts has made it possible to translate tercile forecasts for applications models. Additionally, innovative approaches to user engagement through co-production, communication channels, user-friendly interfaces, and dissemination of climate information have also been developed. Despite the significant progress that has been made in the provision of climate services, there are still many challenges and gaps that need to be overcome in order to ensure that these services are effectively meeting the needs of users. The research of the science underpinning climate variability, capacity building and stakeholder engagement, as well as improved data management and quality control processes are some of the gaps that exist over the region. Additionally, communication and dissemination of climate information, including timely warnings and risk communication, require improvement to reach diverse user groups effectively. Addressing these challenges will require strengthened partnerships, increased investment in capacity building, enhanced collaboration between the climate information producers and stakeholders, and the development of user-friendly climate products. Bridging these gaps will foster greater resilience to climate-related hazards and disasters in the Greater Horn of Africa and support sustainable development in the region
A baby steps/giant steps Monte Carlo algorithm for computing roadmaps in smooth compact real hypersurfaces
International audienceWe consider the problem of constructing roadmaps of real algebraic sets. The problem was introduced by Canny to answer connectivity questions and solve motion planning problems. Given polynomial equations with rational coefficients, of degree in variables, Canny's algorithm has a Monte Carlo cost of operations in ; a deterministic version runs in time . The next improvement was due to Basu, Pollack and Roy, with an algorithm of deterministic cost for the more general problem of computing roadmaps of semi-algebraic sets ( is the dimension of an associated object). We give a Monte Carlo algorithm of complexity for the problem of computing a roadmap of a compact hypersurface of degree in variables; we also have to assume that has a finite number of singular points. Even under these extra assumptions, no previous algorithm featured a cost better than
Age at first birth in women is genetically associated with increased risk of schizophrenia
Prof. Paunio on PGC:n jäsenPrevious studies have shown an increased risk for mental health problems in children born to both younger and older parents compared to children of average-aged parents. We previously used a novel design to reveal a latent mechanism of genetic association between schizophrenia and age at first birth in women (AFB). Here, we use independent data from the UK Biobank (N = 38,892) to replicate the finding of an association between predicted genetic risk of schizophrenia and AFB in women, and to estimate the genetic correlation between schizophrenia and AFB in women stratified into younger and older groups. We find evidence for an association between predicted genetic risk of schizophrenia and AFB in women (P-value = 1.12E-05), and we show genetic heterogeneity between younger and older AFB groups (P-value = 3.45E-03). The genetic correlation between schizophrenia and AFB in the younger AFB group is -0.16 (SE = 0.04) while that between schizophrenia and AFB in the older AFB group is 0.14 (SE = 0.08). Our results suggest that early, and perhaps also late, age at first birth in women is associated with increased genetic risk for schizophrenia in the UK Biobank sample. These findings contribute new insights into factors contributing to the complex bio-social risk architecture underpinning the association between parental age and offspring mental health.Peer reviewe
Mouse Chromosome 11
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46996/1/335_2004_Article_BF00648429.pd
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