Polynuclear growth on a flat substrate and edge scaling of GOE eigenvalues

We consider the polynuclear growth (PNG) model in 1+1 dimension with flat initial condition and no extra constraints. Through the Robinson-Schensted-Knuth (RSK) construction, one obtains the multilayer PNG model, which consists of a stack of non-intersecting lines, the top one being the PNG height. The statistics of the lines is translation invariant and at a fixed position the lines define a point process. We prove that for large times the edge of this point process, suitably scaled, has a limit. This limit is a Pfaffian point process and identical to the one obtained from the edge scaling of Gaussian orthogonal ensemble (GOE) of random matrices. Our results give further insight to the universality structure within the KPZ class of 1+1 dimensional growth models.Comment: 40 pages, 6 figures, LaTeX; Section 4 is substantially modifie

Localization of ampa-selective excitatory amino acid receptor subunits in identified populations of striatal neurons

Two-color immunofluorescence histochemistry and immunohistochemistry in combination with retrograde tract-tracing techniques were used to examine the relationship of [alpha]-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA)-selective glutamate receptor subunits (GluR1, GluR2/3/4c and GluR4) to identified populations of striatal projection neurons and interneurons. The majority of striatonigral and striatopallidal neurons were double-labeled for GluR2/3/4c. These findings were confirmed using calbindin to label matrix projection neurons. In contrast, immunostaining of the GluR1 subunit was not observed to co-localize with any striatal projection neurons. Striatal interneurons immunostained for parvalbumin were also labeled by antibodies directed against the GluRl subunit. Approximately 50% of parvalbumin neurons also contained GluR2/3/4c. Somatostatin immunoreactivity did not co-localize with either the GluR1 or GluR2/3/4c subunits. GluR4-immunoreactive neurons were not observed in striatum.This study demonstrates that AMPA-selective glutamate receptors are differentially localized on subpopulations of striatal neurons and interneurons. These findings suggest that discrete striatal neuron populations may express different AMPA receptor subunit combinations which may account for their functional specificity.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31419/1/0000336.pd

EXCEDE Technology Development III: First Vacuum Tests

This paper is the third in the series on the technology development for the EXCEDE (EXoplanetary Circumstellar Environments and Disk Explorer) mission concept, which in 2011 was selected by NASA's Explorer program for technology development (Category III). EXCEDE is a 0.7m space telescope concept designed to achieve raw contrasts of 1e6 at an inner working angle of 1.2 l/D and 1e7 at 2 l/D and beyond. This will allow it to directly detect and spatially resolve low surface brightness circumstellar debris disks as well as image giant planets as close as in the habitable zones of their host stars. In addition to doing fundamental science on debris disks, EXCEDE will also serve as a technological and scientific precursor for any future exo-Earth imaging mission. EXCEDE uses a Starlight Suppression System (SSS) based on the PIAA coronagraph, enabling aggressive performance. We report on our continuing progress of developing the SSS for EXCEDE, and in particular (a) the reconfiguration of our system into a more flight-like layout, with an upstream deformable mirror and an inverse PIAA system, as well as a LOWFS, and (b) testing this system in a vacuum chamber, including IWA, contrast, and stability performance. The results achieved so far are 2.9e-7 contrast between 1.2-2.0 l/D and 9.7e-8 contrast between 2.0-6.0 l/D in monochromatic light; as well as 1.4e-6 between 2.0-6.0 l/D in a 10% band, all with a PIAA coronagraph operating at an inner working angle of 1.2 l/D. This constitutes better contrast than EXCEDE requirements (in those regions) in monochromatic light, and progress towards requirements in broadband light. Even though this technology development is primarily targeted towards EXCEDE, it is also germane to any exoplanet direct imaging space-based telescopes because of the many challenges common to different coronagraph architectures and mission requirements.Comment: 12 pages, 12 figures, to be published in proceedings of SPIE Astronomical Telescopes + Instrumentation (2014

Spectroscopy of Broad Line Blazars from 1LAC

We report on optical spectroscopy of 165 Flat Spectrum Radio Quasars (FSRQs) in the Fermi 1LAC sample, which have helped allow a nearly complete study of this population. Fermi FSRQ show significant evidence for non-thermal emission even in the optical; the degree depends on the gamma-ray hardness. They also have smaller virial estimates of hole mass than the optical quasar sample. This appears to be largely due to a preferred (axial) view of the gamma-ray FSRQ and non-isotropic (H/R ~ 0.4) distribution of broad-line velocities. Even after correction for this bias, the Fermi FSRQ show higher mean Eddington ratios than the optical population. A comparison of optical spectral properties with Owens Valley Radio Observatory radio flare activity shows no strong correlation.Comment: Accepted for publication in Ap

Guillain-Barré Syndrome, Influenza Vaccination, and Antecedent Respiratory and Gastrointestinal Infections: A Case-Centered Analysis in the Vaccine Safety Datalink, 2009–2011

Background: Guillain-Barré Syndrome (GBS) can be triggered by gastrointestinal or respiratory infections, including influenza. During the 2009 influenza A (H1N1) pandemic in the United States, monovalent inactivated influenza vaccine (MIV) availability coincided with high rates of wildtype influenza infections. Several prior studies suggested an elevated GBS risk following MIV, but adjustment for antecedent infection was limited. Methods: We identified patients enrolled in health plans participating in the Vaccine Safety Datalink and diagnosed with GBS from July 2009 through June 2011. Medical records of GBS cases with 2009–10 MIV, 2010–11 trivalent inactivated influenza vaccine (TIV), and/or a medically-attended respiratory or gastrointestinal infection in the 1 through 141 days prior to GBS diagnosis were reviewed and classified according to Brighton Collaboration criteria for diagnostic certainty. Using a case-centered design, logistic regression models adjusted for patient-level time-varying sources of confounding, including seasonal vaccinations and infections in GBS cases and population-level controls. Results: Eighteen confirmed GBS cases received vaccination in the 6 weeks preceding onset, among 1.27 million 2009–10 MIV recipients and 2.80 million 2010–11 TIV recipients. Forty-four confirmed GBS cases had infection in the 6 weeks preceding onset, among 3.77 million patients diagnosed with medically-attended infection. The observed-versus-expected odds that 2009–10 MIV/2010–11 TIV was received in the 6 weeks preceding GBS onset was odds ratio = 1.54, 95% confidence interval (CI), 0.59–3.99; risk difference = 0.93 per million doses, 95% CI, −0.71–5.16. The association between GBS and medically-attended infection was: odds ratio = 7.73, 95% CI, 3.60–16.61; risk difference = 11.62 per million infected patients, 95% CI, 4.49–26.94. These findings were consistent in sensitivity analyses using alternative infection definitions and risk intervals for prior vaccination shorter than 6 weeks. Conclusions: After adjusting for antecedent infections, we found no evidence for an elevated GBS risk following 2009–10 MIV/2010–11 TIV influenza vaccines. However, the association between GBS and antecedent infection was strongly elevated

Novel Role of Prostate Apoptosis Response-4 Tumor Suppressor in B-Cell Chronic Lymphocytic Leukemia

Prostate apoptosis response-4 (Par-4), a proapoptotic tumor suppressor protein, is downregulated in many cancers including renal cell carcinoma, glioblastoma, endometrial, and breast cancer. Par-4 induces apoptosis selectively in various types of cancer cells but not normal cells. We found that chronic lymphocytic leukemia (CLL) cells from human patients and from Eµ-Tcl1 mice constitutively express Par-4 in greater amounts than normal B-1 or B-2 cells. Interestingly, knockdown of Par-4 in human CLL-derived Mec-1 cells results in a robust increase in p21/WAF1 expression and decreased growth due to delayed G1-to-S cell-cycle transition. Lack of Par-4 also increased the expression of p21 and delayed CLL growth in Eμ-Tcl1 mice. Par-4 expression in CLL cells required constitutively active B-cell receptor (BCR) signaling, as inhibition of BCR signaling with US Food and Drug Administration (FDA)–approved drugs caused a decrease in Par-4 messenger RNA and protein, and an increase in apoptosis. In particular, activities of Lyn, a Src family kinase, spleen tyrosine kinase, and Bruton tyrosine kinase are required for Par-4 expression in CLL cells, suggesting a novel regulation of Par-4 through BCR signaling. Together, these results suggest that Par-4 may play a novel progrowth rather than proapoptotic role in CLL and could be targeted to enhance the therapeutic effects of BCR-signaling inhibitors

Author Correction: A consensus-based transparency checklist.

An amendment to this paper has been published and can be accessed via a link at the top of the paper

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A>T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations