7,427 research outputs found
Pricing and Welfare in Health Plan Choice
Prices in government and employer-sponsored health insurance markets only partially reflect insurers' expected costs of coverage for different enrollees. This can create inefficient distortions when consumers self-select into plans. We develop a simple model to study this problem and estimate it using new data on small employers. In the markets we observe, the welfare loss compared to the feasible efficient benchmark is around 2-11% of coverage costs. Three-quarters of this is due to restrictions on risk-rating employee contributions; the rest is due to inefficient contribution choices. Despite the inefficiency, we find substantial benefits from plan choice relative to single-insurer options.healthcare costs, health insurance, government-sponsered health insurance, employer-sponsored health insurance
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Being Different Yet Feeling Similar: The Influence Of Demographic Composition And Organizational Culture On Work Processes And Outcomes
Drawing from self-categorization theory, we tested hypotheses on the effects of an organization's demographic composition and cultural emphasis on work processes and outcomes. Using an organizational simulation, we found that the extent to which an organization emphasized individualistic or collectivistic values interacted with demographic composition to influence social interaction, conflict, productivity, and perceptions of creativity among 258 MBA students. Our findings suggest that the purported benefits of demographic diversity are more likely to emerge in organizations that, through their culture, make organizational membership salient and encourage people to categorize one another as having the organization's interests in common, rather than those that emphasize individualism and distinctiveness among members.(.)Managemen
Evidence that MEK1 positively promotes interhomologue double-strand break repair
During meiosis there is an imperative to create sufficient crossovers for homologue segregation. This can be achieved during repair of programmed DNA double-strand breaks (DSBs), which are biased towards using a homologue rather than sister chromatid as a repair template. Various proteins contribute to this bias, one of which is a meiosis specific kinase Mek1. It has been proposed that Mek1 establishes the bias by creating a barrier to sister chromatid repair, as distinct from enforcing strand invasion with the homologue. We looked for evidence that Mek1 positively stimulates strand invasion of the homologue. This was done by analysing repair of DSBs induced by the VMA1- derived endonuclease (VDE) and flanked by directly repeated sequences that can be used for intrachromatid single-strand annealing (SSA). SSA competes with interhomologue strand inva- sion significantly more successfully when Mek1 function is lost. We suggest the increase in intrachromosomal SSA reflects an opportunistic default repair pathway due to loss of a MEK1 stimulated bias for strand invasion of the homologous chromosome. Making use of an inhibitor sensitive mek1-as1 allele, we found that Mek1 function influences the repair pathway throughout the first 4-5 h of meiosis. Perhaps reflecting a particular need to create bias for successful interhomologue events before chromosome pairing is complete. Β© The Author(s) 2010. Published by Oxford University Pres
Positive regulation of meiotic DNA double-strand break formation by activation of the DNA damage checkpoint kinase Mec1(ATR)
During meiosis, formation and repair of programmed DNA double-strand breaks (DSBs) create genetic exchange between homologous chromosomes-a process that is critical for reductional meiotic chromosome segregation and the production of genetically diverse sexually reproducing populations. Meiotic DSB formation is a complex process, requiring numerous proteins, of which Spo11 is the evolutionarily conserved catalytic subunit. Precisely how Spo11 and its accessory proteins function or are regulated is unclear. Here, we use Saccharomyces cerevisiae to reveal that meiotic DSB formation is modulated by the Mec1(ATR) branch of the DNA damage signalling cascade, promoting DSB formation when Spo11-mediated catalysis is compromised. Activation of the positive feedback pathway correlates with the formation of single-stranded DNA (ssDNA) recombination intermediates and activation of the downstream kinase, Mek1. We show that the requirement for checkpoint activation can be rescued by prolonging meiotic prophase by deleting the NDT80 transcription factor, and that even transient prophase arrest caused by Ndt80 depletion is sufficient to restore meiotic spore viability in checkpoint mutants. Our observations are unexpected given recent reports that the complementary kinase pathway Tel1(ATM) acts to inhibit DSB formation. We propose that such antagonistic regulation of DSB formation by Mec1 and Tel1 creates a regulatory mechanism, where the absolute frequency of DSBs is maintained at a level optimal for genetic exchange and efficient chromosome segregation
Exoplanet Transmission Spectroscopy using KMOS
KMOS (K-Band Multi Object Spectrograph) is a novel integral field
spectrograph installed in the VLT's ANTU unit. The instrument offers an ability
to observe 24 2.8"2.8" sub-fields positionable within a 7.2' patrol
field, each sub-field producing a spectrum with a 1414-pixel spatial
resolution. The main science drivers for KMOS are the study of galaxies, star
formation, and molecular clouds, but its ability to simultaneously measure
spectra of multiple stars makes KMOS an interesting instrument for exoplanet
atmosphere characterization via transmission spectroscopy. We set to test
whether transmission spectroscopy is practical with KMOS, and what are the
conditions required to achieve the photometric precision needed, based on
observations of a partial transit of WASP-19b, and full transits of GJ 1214b
and HD 209458b. Our analysis uses the simultaneously observed comparison stars
to reduce the effects from instrumental and atmospheric sources, and Gaussian
processes to model the residual systematics. We show that KMOS can, in theory,
deliver the photometric precision required for transmission spectroscopy.
However, this is shown to require a) pre-imaging to ensure accurate centering
and b) a very stable night with optimal observing conditions (seeing
0.8"). Combining these two factors with the need to observe several
transits, each with a sufficient out-of-transit baseline (and with the fact
that similar or better precision can be reached with telescopes and instruments
with smaller pressure,) we conclude that transmission spectroscopy is not the
optimal science case to take advantage of the abilities offered by KMOS and
VLT.Comment: 11 pages, accepted to MNRA
Spatially selecting single cell for lysis using light induced electric fields
An optoelectronic tweezing (OET) device, within an integrated microfluidic channel, is used to precisely select single cells for lysis among dense populations. Cells to be lysed are exposed to higher electrical fields than their neighbours by illuminating a photoconductive film underneath them. Using beam spot sizes as low as 2.5 ΞΌm, 100% lysis efficiency is reached in <1 min allowing the targeted lysis of cells
PyMT-Maclow: A novel, inducible, murine model for determining the role of CD68 positive cells in breast tumor development
CD68+ tumor-associated macrophages (TAMs) are pro-tumorigenic, pro-angiogenic and are associated with decreased survival rates in patients with cancer, including breast cancer. Non-specific models of macrophage ablation reduce the number of TAMs and limit the development of mammary tumors. However, the lack of specificity and side effects associated with these models compromise their reliability. We hypothesized that specific and controlled macrophage depletion would provide precise data on the effects of reducing TAM numbers on tumor development. In this study, the MacLow mouse model of doxycycline-inducible and selective CD68+ macrophage depletion was crossed with the murine mammary tumor virus (MMTV)-Polyoma virus middle T antigen (PyMT) mouse model of spontaneous ductal breast adenocarcinoma to generate the PyMT-MacLow line. In doxycycline-treated PyMT-MacLow mice, macrophage numbers were decreased in areas surrounding tumors by 43%. Reducing the number of macrophages by this level delayed tumor progression, generated less proliferative tumors, decreased the vascularization of carcinomas and down-regulated the expression of many pro-angiogenic genes. These results demonstrate that depleting CD68+ macrophages in an inducible and selective manner delays the development of mammary tumors and that the PyMT-MacLow model is a useful and unique tool for studying the role of TAMs in breast cancer
Improvement and further development of SSM/I overland parameter algorithms using the WetNet workstation
Since the launch of the DMSP Special Sensor Microwave/Imager (SSM/I), several algorithms have been developed to retrieve overland parameters. These include the present operational algorithms resulting from the Navy calibration/validation effort such as land surface type (Neale et al. 1990), land surface temperature (McFarland et al. 1990), surface moisture (McFarland and Neale, 1991) and snow parameters (McFarland and Neale, 1991). In addition, other work has been done including the classification of snow cover and precipitation using the SSM/I (Grody, 1991). Due to the empirical nature of most of the above mentioned algorithms, further research is warranted and improvements can probably be obtained through a combination of radiative transfer modelling to study the physical processes governing the microwave emissions at the SSM/I frequencies, and the incorporation of additional ground truth data and special cases into the regression data sets. We have proposed specifically to improve the retrieval of surface moisture and snow parameters using the WetNet SSM/I data sets along with ground truth information namely climatic variables from the NOAA cooperative network of weather stations as well as imagery from other satellite sensors such as the AVHRR and Thematic Mapper. In the case of surface moisture retrievals the characterization of vegetation density is of primary concern. The higher spatial resolution satellite imagery collected at concurrent periods will be used to characterize vegetation types and amounts which, along with radiative transfer modelling should lead to more physically based retrievals. Snow parameter retrieval algorithm improvement will initially concentrate on the classification of snowpacks (dry snow, wet snow, refrozen snow) and later on specific products such as snow water equivalent. Significant accomplishments in the past year are presented
Use of optoelectronic tweezers in manufacturing β accurate solder bead positioning
In this work, we analyze the use of optoelectronic tweezers (OETs) to manipulate 45βΞΌm diameter Sn62Pb36Ag2 solder beads with light-induced dielectrophoresis force and we demonstrate high positioning accuracy. It was found that the positional deviation of the solder beads increases with the increase of the trap size. To clarify the underlying mechanism, simulations based on the integration of the Maxwell stress tensor were used to study the force profiles of OET traps with different sizes. It was found that the solder beads felt a 0.1 nN static friction or stiction force due to electrical forces pulling them towards the surface and that this force is not dependent on the size of the trap. The stiction limits the positioning accuracy; however, we show that by choosing a trap that is just larger than the solder bead sub-micron positional accuracy can be achieved
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A nucleotide resolution map of Top2-linked DNA breaks in the yeast and human genome
DNA topoisomerases are required to resolve DNA topological stress. Despite this essential role, abortive topoisomerase activity generates aberrant protein-linked DNA breaks, jeopardising genome stability. Here, to understand the genomic distribution and mechanisms underpinning topoisomerase-induced DNA breaks, we map Top2 DNA cleavage with strand-specific nucleotide resolution across the S. cerevisiae and human genomesβand use the meiotic Spo11 protein to validate the broad applicability of this method to explore the role of diverse topoisomerase family members. Our data characterises Mre11-dependent repair in yeast and defines two strikingly different fractions of Top2 activity in humans: tightly localised CTCF-proximal, and broadly distributed transcription-proximal, the latter correlated with gene length and expression. Moreover, single nucleotide accuracy reveals the influence primary DNA sequence has upon Top2 cleavageβdistinguishing sites likely to form canonical DNA double-strand breaks (DSBs) from those predisposed to form strand-biased DNA single-strand breaks (SSBs) induced by etoposide (VP16) in vivo
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