925 research outputs found
Decoupling A and B model in open string theory -- Topological adventures in the world of tadpoles
In this paper we analyze the problem of tadpole cancellation in open
topological strings. We prove that the inclusion of unorientable worldsheet
diagrams guarantees a consistent decoupling of A and B model for open
superstring amplitudes at all genera. This is proven by direct microscopic
computation in Super Conformal Field Theory. For the B-model we explicitly
calculate one loop amplitudes in terms of analytic Ray-Singer torsions of
appropriate vector bundles and obtain that the decoupling corresponds to the
cancellation of D-brane and orientifold charges. Local tadpole cancellation on
the worldsheet then guarantees the decoupling at all loops. The holomorphic
anomaly equations for open topological strings at one loop are also obtained
and compared with the results of the Quillen formula
Deterministic and stochastic descriptions of gene expression dynamics
A key goal of systems biology is the predictive mathematical description of
gene regulatory circuits. Different approaches are used such as deterministic
and stochastic models, models that describe cell growth and division explicitly
or implicitly etc. Here we consider simple systems of unregulated
(constitutive) gene expression and compare different mathematical descriptions
systematically to obtain insight into the errors that are introduced by various
common approximations such as describing cell growth and division by an
effective protein degradation term. In particular, we show that the population
average of protein content of a cell exhibits a subtle dependence on the
dynamics of growth and division, the specific model for volume growth and the
age structure of the population. Nevertheless, the error made by models with
implicit cell growth and division is quite small. Furthermore, we compare
various models that are partially stochastic to investigate the impact of
different sources of (intrinsic) noise. This comparison indicates that
different sources of noise (protein synthesis, partitioning in cell division)
contribute comparable amounts of noise if protein synthesis is not or only
weakly bursty. If protein synthesis is very bursty, the burstiness is the
dominant noise source, independent of other details of the model. Finally, we
discuss two sources of extrinsic noise: cell-to-cell variations in protein
content due to cells being at different stages in the division cycles, which we
show to be small (for the protein concentration and, surprisingly, also for the
protein copy number per cell) and fluctuations in the growth rate, which can
have a significant impact.Comment: 23 pages, 5 figures; Journal of Statistical physics (2012
Risk of longer-term neurological conditions in the Deepwater Horizon Oil Spill Coast Guard Cohort Study – Five years of follow-up
Background: Long-term neurological health risks associated with oil spill cleanup exposures are largely unknown. We aimed to investigate risks of longer-term neurological conditions among U.S. Coast Guard (USCG) responders to the 2010 Deepwater Horizon (DWH) oil spill. Methods: We used data from active duty members of the DWH Oil Spill Coast Guard Cohort Study (N=45224). Self-reported oil spill exposures were ascertained from post-deployment surveys. Incident neurological outcomes were classified using International Classification of Diseases, 9th Revision, codes from military health encounter records up to 5.5 years post-DWH. We used Cox Proportional Hazards regression to calculate adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for various incident neurological diagnoses (2010–2015). Oil spill responder (n=5964) vs. non-responder (n= 39260) comparisons were adjusted for age, sex, and race, while within-responder comparisons were additionally adjusted for smoking. Results: Compared to those not responding to the spill, spill responders had reduced risks for headache (aHR=0.84, 95% CI: 0.74-0.96), syncope and collapse (aHR=0.74, 95% CI: 0.56-0.97), and disturbance of skin sensation (aHR=0.81, 95% CI: 0.68-0.96). Responders reporting ever (n=1068) vs. never (n=2424) crude oil inhalation exposure were at increased risk for several individual and grouped outcomes related to headaches and migraines (aHR range: 1.39-1.83). Crude oil inhalation exposure was also associated with elevated risks for an inflammatory nerve condition, mononeuritis of upper limb and mononeuritis multiplex (aHR=1.71, 95% CI: 1.04-2.83), and tinnitus (aHR=1.91, 95% CI: 1.23-2.96), a condition defined by ringing in one or both ears. Risk estimates for those neurological conditions were higher in magnitude among responders reporting exposure to both crude oil and oil dispersants than among those reporting crude oil only. Conclusion: In this large study of active duty USCG responders to the DWH disaster, self-reported spill cleanup exposures were associated with elevated risks for longer-term neurological conditions
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Soft X-Ray Magnetic Imaging of Focused Ion Beam Lithographically Patterned Fe Thin Films
We illustrate the potential of modifying the magnetic behavior and structural properties of ferromagnetic thin films using focused ion beam 'direct-write' lithography. Patterns inspired by the split-ring resonators often used as components in meta-materials were defined upon 15 nm Fe films using a 30 keV Ga{sup +} focused ion beam at a dose of 2 x 10{sup 16} ions cm{sup -2}. Structural, chemical and magnetic changes to the Fe were studied using transmission soft X-ray microscopy at the ALS, Berkeley CA. X-ray absorption spectra showed a 23% reduction in the thickness of the film in the Ga irradiated areas, but no change to the chemical environment of Fe was evident. X-ray images of the magnetic reversal process show domain wall pinning around the implanted areas, resulting in an overall increase in the coercivity of the film. Transmission electron microscopy showed significant grain growth in the implanted regions
Height and risk of death among men and women: aetiological implications of associations with cardiorespiratory disease and cancer mortality
OBJECTIVES: Height is inversely associated with cardiovascular disease mortality risk and has shown variable associations with cancer incidence and mortality. The interpretation of findings from previous studies has been constrained by data limitations. Associations between height and specific causes of death were investigated in a large general population cohort of men and women from the West of Scotland.
DESIGN: Prospective observational study.
SETTING: Renfrew and Paisley, in the West of Scotland.
SUBJECTS: 7052 men and 8354 women aged 45-64 were recruited into a study in Renfrew and Paisley, in the West of Scotland, between 1972 and 1976. Detailed assessments of cardiovascular disease risk factors, morbidity and socioeconomic circumstances were made at baseline.
MAIN OUTCOME MEASURES: Deaths during 20 years of follow up classified into specific causes.
RESULTS: Over the follow up period 3347 men and 2638 women died. Height is inversely associated with all cause, coronary heart disease, stroke, and respiratory disease mortality among men and women. Adjustment for socioeconomic position and cardiovascular risk factors had little influence on these associations. Height is strongly associated with forced expiratory volume in one second (FEV1) and adjustment for FEV1 considerably attenuated the association between height and cardiorespiratory mortality. Smoking related cancer mortality is not associated with height. The risk of deaths from cancer unrelated to smoking tended to increase with height, particularly for haematopoietic, colorectal and prostate cancers. Stomach cancer mortality was inversely associated with height. Adjustment for socioeconomic position had little influence on these associations.
CONCLUSION: Height serves partly as an indicator of socioeconomic circumstances and nutritional status in childhood and this may underlie the inverse associations between height and adulthood cardiorespiratory mortality. Much of the association between height and cardiorespiratory mortality was accounted for by lung function, which is also partly determined by exposures acting in childhood. The inverse association between height and stomach cancer mortality probably reflects Helicobacter pylori infection in childhood resulting inor being associated withshorter height. The positive associations between height and several cancers unrelated to smoking could reflect the influence of calorie intake during childhood on the risk of these cancers
Isometric Sliced Inverse Regression for Nonlinear Manifolds Learning
[[abstract]]Sliced inverse regression (SIR) was developed to find effective linear dimension-reduction directions for exploring the intrinsic structure of the high-dimensional data. In this study, we present isometric SIR for nonlinear dimension reduction, which is a hybrid of the SIR method using the geodesic distance approximation. First, the proposed method computes the isometric distance between data points; the resulting distance matrix is then sliced according to K-means clustering results, and the classical SIR algorithm is applied. We show that the isometric SIR (ISOSIR) can reveal the geometric structure of a nonlinear manifold dataset (e.g., the Swiss roll). We report and discuss this novel method in comparison to several existing dimension-reduction techniques for data visualization and classification problems. The results show that ISOSIR is a promising nonlinear feature extractor for classification applications.[[incitationindex]]SCI[[booktype]]紙本[[booktype]]電子
Ownership and control in a competitive industry
We study a differentiated product market in which an investor initially owns a controlling stake in one of two competing firms and may acquire a non-controlling or a controlling stake in a competitor, either directly using her own assets, or indirectly via the controlled firm. While industry profits are maximized within a symmetric two product monopoly, the investor attains this only in exceptional cases. Instead, she sometimes acquires a noncontrolling stake. Or she invests asymmetrically rather than pursuing a full takeover if she acquires a controlling one. Generally, she invests indirectly if she only wants to affect the product market outcome, and directly if acquiring shares is profitable per se. --differentiated products,separation of ownership and control,private benefits of control
RAS/MAPK activation is associated with reduced Tumor-infiltrating lymphocytes in Triple-Negative Breast Cancer: Therapeutic Cooperation Between MEK and PD-1/PD-L1 Immune Checkpoint Inhibitors
PURPOSE:
Tumor-infiltrating lymphocytes (TIL) in the residual disease (RD) of triple-negative breast cancers (TNBC) after neoadjuvant chemotherapy (NAC) are associated with improved survival, but insight into tumor cell-autonomous molecular pathways affecting these features are lacking.
EXPERIMENTAL DESIGN:
We analyzed TILs in the RD of clinically and molecularly characterized TNBCs after NAC and explored therapeutic strategies targeting combinations of MEK inhibitors with PD-1/PD-L1-targeted immunotherapy in mouse models of breast cancer.
RESULTS:
Presence of TILs in the RD was significantly associated with improved prognosis. Genetic or transcriptomic alterations in Ras-MAPK signaling were significantly correlated with lower TILs. MEK inhibition upregulated cell surface MHC expression and PD-L1 in TNBC cells both in vivo and in vitro. Moreover, combined MEK and PD-L1/PD-1 inhibition enhanced antitumor immune responses in mouse models of breast cancer.
CONCLUSIONS:
These data suggest the possibility that Ras-MAPK pathway activation promotes immune-evasion in TNBC, and support clinical trials combining MEK- and PD-L1-targeted therapies. Furthermore, Ras/MAPK activation and MHC expression may be predictive biomarkers of response to immune checkpoint inhibitors
Equine infectious anemia : prevalence in working equids of livestock herds, in Minas Gerais, Brazil
Estimaram-se, no estado de Minas Gerais, a prevalência e a distribuição espacial da anemia infecciosa eqüina (AIE) em propriedades com eqüídeos de serviço. As amostras de sangue, de 6540 eqüídeos de 1940 rebanhos foram coletadas no período de setembro de 2003 a março de 2004, nos 853 municípios do estado. Utilizaram-se dois testes de laboratório em seqüência: ELISA, usando-se antígeno recombinante gp90, e imunodifusão em gel de ágar (IDGA). As prevalências foram de 5,3% [IC=4,3 a 6,3%] para rebanhos e de 3,1% [IC=2,2 a 3,9%] para animais. O estado de Minas Gerais foi considerado área endêmica para AIE. As mais altas prevalências para rebanhos e para animais foram encontradas na região Norte/Noroeste, seguida pela região Vale do Mucuri/Jequitinhonha. ___________________________________________________________________________________________________________ ABSTRACTThe prevalence and spatial distribution of equine infectious anemia (EIA) were estimated in livestock herds where equids were used as draft power and for transportation in the State of Minas Gerais, Brazil. Serum samples were collected from September/2003 to March/2004 in 853 municipalities of the state. The sample comprised 6,540 equids from 1,940 herds. Two laboratorial tests were performed in sequence: ELISA using a recombinant gp90 protein, following by the AGID. The prevalence in the herds was estimated in 5.3% [CI = 4.3 to 6.3%], and 3.1% [CI = 2.2 to 3.9%] of the animals tested were positive. Minas Gerais was considered an endemic region for EIA. The highest prevalence for herds and animals was found in North/Northwest region (strata) followed by Vale do Mucuri/Jequitinhonha region
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