2,064 research outputs found
Screening disability insurance applications
This paper investigates the effects of stricter screening of disability insurance applications. A large-scale experiment was setup where in two of the 26 Dutch regions case workers of the disability insurance administration were instructed to screen applications more stringently. The empirical results show that stricter screening reduces long-term sickness absenteeism and disability insurance applications. We find evidence for direct effects of stricter screening on work resumption during the period of sickness absence and for self-screening by potential disability insurance applicants. Stricter screening seems to improve targeting efficiency, without inducing negative spillover effects to the inflow into unemployment insurance. The costs of stricter screening are only a small fraction of the monetary benefits.Disability insurance; experiment; policy evaluation; sickness absenteeism; self-screening
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Identification of unique reciprocal and non reciprocal cross packaging relationships between HIV-1, HIV-2 and SIV reveals an efficient SIV/HIV-2 lentiviral vector system with highly favourable features for in vivo testing and clinical usage.
BACKGROUND: Lentiviral vectors have shown immense promise as vehicles for gene delivery to non-dividing cells particularly to cells of the central nervous system (CNS). Improvements in the biosafety of viral vectors are paramount as lentiviral vectors move into human clinical trials. This study investigates the packaging relationship between gene transfer (vector) and Gag-Pol expression constructs of HIV-1, HIV-2 and SIV. Cross-packaged vectors expressing GFP were assessed for RNA packaging, viral vector titre and their ability to transduce rat primary glial cell cultures and human neural stem cells. RESULTS: HIV-1 Gag-Pol demonstrated the ability to cross package both HIV-2 and SIV gene transfer vectors. However both HIV-2 and SIV Gag-Pol showed a reduced ability to package HIV-1 vector RNA with no significant gene transfer to target cells. An unexpected packaging relationship was found to exist between HIV-2 and SIV with SIV Gag-Pol able to package HIV-2 vector RNA and transduce dividing SV2T cells and CNS cell cultures with an efficiency equivalent to the homologous HIV-1 vector however HIV-2 was unable to deliver SIV based vectors. CONCLUSION: This new non-reciprocal cross packaging relationship between SIV and HIV-2 provides a novel way of significantly increasing bio-safety with a reduced sequence homology between the HIV-2 gene transfer vector and the SIV Gag-Pol construct thus ensuring that vector RNA packaging is unidirectional.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are
The Wasteland of Random Supergravities
We show that in a general \cal{N} = 1 supergravity with N \gg 1 scalar
fields, an exponentially small fraction of the de Sitter critical points are
metastable vacua. Taking the superpotential and Kahler potential to be random
functions, we construct a random matrix model for the Hessian matrix, which is
well-approximated by the sum of a Wigner matrix and two Wishart matrices. We
compute the eigenvalue spectrum analytically from the free convolution of the
constituent spectra and find that in typical configurations, a significant
fraction of the eigenvalues are negative. Building on the Tracy-Widom law
governing fluctuations of extreme eigenvalues, we determine the probability P
of a large fluctuation in which all the eigenvalues become positive. Strong
eigenvalue repulsion makes this extremely unlikely: we find P \propto exp(-c
N^p), with c, p being constants. For generic critical points we find p \approx
1.5, while for approximately-supersymmetric critical points, p \approx 1.3. Our
results have significant implications for the counting of de Sitter vacua in
string theory, but the number of vacua remains vast.Comment: 39 pages, 9 figures; v2: fixed typos, added refs and clarification
Is Our Universe Natural?
It goes without saying that we are stuck with the universe we have.
Nevertheless, we would like to go beyond simply describing our observed
universe, and try to understand why it is that way rather than some other way.
Physicists and cosmologists have been exploring increasingly ambitious ideas
that attempt to explain why certain features of our universe aren't as
surprising as they might first appear.Comment: Invited review for Nature, 11 page
Gene and protein expression of glucose transporter 1 and glucose transporter 3 in human laryngeal cancer—the relationship with regulatory hypoxia-inducible factor-1α expression, tumor invasiveness, and patient prognosis
Increased glucose uptake mediated by glucose
transporters and reliance on glycolysis are common features
of malignant cells. Hypoxia-inducible factor-1α supports the
adaptation of hypoxic cells by inducing genes related to
glucose metabolism. The contribution of glucose transporter
(GLUT) and hypoxia-inducible factor-1α (HIF-1α) activity to
tumor behavior and their prognostic value in head and neck
cancers remains unclear. The aim of this study was to examine
the predictive value of GLUT1, GLUT3, and HIF-1α messenger
RNA (mRNA)/protein expression as markers of tumor
aggressiveness and prognosis in laryngeal cancer. The level of
hypoxia/metabolic marker genes was determined in 106 squamous
cell laryngeal cancer (SCC) and 73 noncancerous
matched mucosa (NCM) controls using quantitative realtime
PCR. The related protein levels were analyzed by
Western blot. Positive expression of SLC2A1, SLC2A3, and
HIF-1α genes was noted in 83.9, 82.1, and 71.7 % of SCC
specimens and in 34.4, 59.4, and 62.5 % of laryngeal cancer
samples. Higher levels of mRNA/protein for GLUT1 and
HIF-1α were noted in SCC compared to NCM (p<0.05).
SLC2A1 was found to have a positive relationship with grade,
tumor front grading (TFG) score, and depth and mode of
invasion (p<0.05). SLC2A3 was related to grade and invasion
type (p<0.05). There were also relationships of HIF-1α with
pTNM, TFG scale, invasion depth and mode, tumor recurrences,
and overall survival (p<0.05). In addition, more advanced
tumors were found to be more likely to demonstrate
positive expression of these proteins. In conclusion, the
hypoxia/metabolic markers studied could be used as molecular
markers of tumor invasiveness in laryngeal cancer.This work was supported, in part, by the statutory
fund of the Department of Cytobiochemistry, University of Łódź, Poland
(506/811), and by grant fromtheNational Science Council, Poland (N403
043 32/2326)
The Ctf18 RFC-like complex positions yeast telomeres but does not specify their replication time
Peer reviewedPreprin
A Comprehensive Workflow for General-Purpose Neural Modeling with Highly Configurable Neuromorphic Hardware Systems
In this paper we present a methodological framework that meets novel
requirements emerging from upcoming types of accelerated and highly
configurable neuromorphic hardware systems. We describe in detail a device with
45 million programmable and dynamic synapses that is currently under
development, and we sketch the conceptual challenges that arise from taking
this platform into operation. More specifically, we aim at the establishment of
this neuromorphic system as a flexible and neuroscientifically valuable
modeling tool that can be used by non-hardware-experts. We consider various
functional aspects to be crucial for this purpose, and we introduce a
consistent workflow with detailed descriptions of all involved modules that
implement the suggested steps: The integration of the hardware interface into
the simulator-independent model description language PyNN; a fully automated
translation between the PyNN domain and appropriate hardware configurations; an
executable specification of the future neuromorphic system that can be
seamlessly integrated into this biology-to-hardware mapping process as a test
bench for all software layers and possible hardware design modifications; an
evaluation scheme that deploys models from a dedicated benchmark library,
compares the results generated by virtual or prototype hardware devices with
reference software simulations and analyzes the differences. The integration of
these components into one hardware-software workflow provides an ecosystem for
ongoing preparative studies that support the hardware design process and
represents the basis for the maturity of the model-to-hardware mapping
software. The functionality and flexibility of the latter is proven with a
variety of experimental results
Comparison of the CDC Backpack aspirator and the Prokopack aspirator for sampling indoor- and outdoor-resting mosquitoes in southern Tanzania.
BACKGROUND\ud
\ud
Resting mosquitoes can easily be collected using an aspirating device. The most commonly used mechanical aspirator is the CDC Backpack aspirator. Recently, a simple, and low-cost aspirator called the Prokopack has been devised and proved to have comparable performance. The following study evaluates the Prokopack aspirator compared to the CDC backpack aspirator when sampling resting mosquitoes in rural Tanzania.\ud
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METHODS\ud
\ud
Mosquitoes were sampled in- and outdoors of 48 typical rural African households using both aspirators. The aspirators were rotated between collectors and households in a randomized, Latin Square design. Outdoor collections were performed using artificial resting places (large barrel and car tyre), underneath the outdoor kitchen (kibanda) roof and from a drop-net. Data were analysed with generalized linear models.\ud
\ud
RESULTS\ud
\ud
The number of mosquitoes collected using the CDC Backpack and the Prokopack aspirator were not significantly different both in- and outdoors (indoors p = 0.735; large barrel p = 0.867; car tyre p = 0.418; kibanda p = 0.519). The Prokopack was superior for sampling of drop-nets due to its smaller size. The number mosquitoes collected per technician was more consistent when using the Prokopack aspirator. The Prokopack was more user-friendly: technicians preferred using the it over the CDC backpack aspirator as it weighs considerably less, retains its charge for longer and is easier to manoeuvre.\ud
\ud
CONCLUSIONS\ud
\ud
The Prokopack proved in the field to be more advantageous than the CDC Backpack aspirator. It can be self assembled using simple, low-cost and easily attainable materials. This device is a useful tool for researchers or vector-control surveillance programs operating in rural Africa, as it is far simpler and quicker than traditional means of sampling resting mosquitoes. Further longitudinal evaluations of the Prokopack aspirator versus the gold standard pyrethrum spray catch for indoor resting catches are recommended
Toward Human-Carnivore Coexistence: Understanding Tolerance for Tigers in Bangladesh
Fostering local community tolerance for endangered carnivores, such as tigers (Panthera tigris), is a core component of many conservation strategies. Identification of antecedents of tolerance will facilitate the development of effective tolerance-building conservation action and secure local community support for, and involvement in, conservation initiatives. We use a stated preference approach for measuring tolerance, based on the ‘Wildlife Stakeholder Acceptance Capacity’ concept, to explore villagers’ tolerance levels for tigers in the Bangladesh Sundarbans, an area where, at the time of the research, human-tiger conflict was severe. We apply structural equation modeling to test an a priori defined theoretical model of tolerance and identify the experiential and psychological basis of tolerance in this community. Our results indicate that beliefs about tigers and about the perceived current tiger population trend are predictors of tolerance for tigers. Positive beliefs about tigers and a belief that the tiger population is not currently increasing are both associated with greater stated tolerance for the species. Contrary to commonly-held notions, negative experiences with tigers do not directly affect tolerance levels; instead, their effect is mediated by villagers’ beliefs about tigers and risk perceptions concerning human-tiger conflict incidents. These findings highlight a need to explore and understand the socio-psychological factors that encourage tolerance towards endangered species. Our research also demonstrates the applicability of this approach to tolerance research to a wide range of socio-economic and cultural contexts and reveals its capacity to enhance carnivore conservation efforts worldwide
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