An Approximation Scheme for Reflected Stochastic Differential Equations

In this paper we consider the Stratonovich reflected stochastic differential equation $dX_t=\sigma(X_t)\circ dW_t+b(X_t)dt+dL_t$ in a bounded domain \O which satisfies conditions, introduced by Lions and Sznitman, which are specified below. Letting $W^N_t$ be the $N$-dyadic piecewise linear interpolation of $W_t$ what we show is that one can solve the reflected ordinary differential equation $\dot X^N_t=\sigma(X^N_t)\dot W^N_t+b(X^N_t)+\dot L^N_t$ and that the distribution of the pair $(X^N_t,L^N_t)$ converges weakly to that of $(X_t,L_t)$. Hence, what we prove is a distributional version for reflected diffusions of the famous result of Wong and Zakai. Perhaps the most valuable contribution made by our procedure derives from the representation of $\dot X^N_t$ in terms of a projection of $\dot W_t^N$. In particular, we apply our result in hand to derive some geometric properties of coupled reflected Brownian motion in certain domains, especially those properties which have been used in recent work on the "hot spots" conjecture for special domain.Comment: 26 pages, 4 figure

Upregulation of Id1 by Epstein-Barr Virus-encoded LMP1 confers resistance to TGFβ-mediated growth inhibition

BACKGROUND: Epstein-Barr virus (EBV)-encoded LMP1 protein is commonly expressed in nasopharyngeal carcinoma (NPC). LMP1 is a prime candidate for driving tumourigenesis given its ability to activate multiple signalling pathways and to alter the expression and activity of variety of downstream targets. Resistance to TGFβ-mediated cytostasis is one of the growth transforming effects of LMP1. Of the downstream targets manipulated by LMP1, the induction of Id1 and inactivation of Foxo3a appear particularly relevant to LMP1-mediated effects. Id1, a HLH protein is implicated in cell transformation and plays a role in cell proliferation, whilst Foxo3a, a transcription factor controls cell integrity and homeostasis by regulating apoptosis. The mechanism(s) by which LMP1 induces these effects have not been fully characterised. RESULTS: In this study, we demonstrate that the ability of LMP1 to induce the phosphorylation and inactivation of Foxo3a is linked to the upregulation of Id1. Furthermore, we show that the induction of Id1 is essential for the transforming function of LMP1 as over-expression of Id1 increases cell proliferation, attenuates TGFβ-SMAD-mediated transcription and renders cells refractory to TGFβ-mediated cytostasis. Id1 silencing in LMP1-expressing epithelial cells abolishes the inhibitory effect of LMP1 on TGFβ-mediated cell growth arrest and reduces the ability of LMP1 to attenuate SMAD transcriptional activity. In response to TGFβ stimulation, LMP1 does not abolish SMAD phosphorylation but inhibits p21 protein expression. In addition, we found the induction of Id1 in LMP1-expressing cells upon stimulation by TGFβ. We provide evidence that LMP1 suppresses the transcriptional repressor ATF3, possibly leading to the TGFβ-induced Id1 upregulation. CONCLUSION: The current data provide novel information regarding the mechanisms by which LMP1 suppresses TGFβ-induced cytostasis, highlighting the importance of Id1 in LMP1 mediated cell transformatio

The Transmembrane Domains of the EBV-Encoded Latent Membrane Protein 1 (LMP1) Variant CAO Regulate Enhanced Signalling Activity

AbstractSequence variants of the Epstein–Barr virus (EBV)-encoded latent membrane protein-1 (LMP1) have been reported in association with EBV-linked malignancies but little is known about their effects on signalling pathways and phenotype. We have examined the ability of the nasopharyngeal carcinoma (NPC)-derived variant, CAO-LMP1 to activate the transcription factors NF-κB and AP-1 in epithelial cells. In this study, transient expression of CAO-LMP1 was found to activate higher levels of NF-κB and AP-1 than the prototype B95.8-LMP1 in human embryonic kidney (HEK) 293 cells and SV40-transformed keratinocytes (SVK). In addition, pulse–chase analysis revealed that CAO-LMP1 has a longer half-life than B95.8-LMP1. Chimera studies localised these phenomena to the transmembrane domains of CAO-LMP1, suggesting that this enhanced signalling capacity may be a consequence of its prolonged half-life. The ability of CAO-LMP1 to activate higher levels of NF-κB and AP-1 may contribute to its potent transforming properties

The Ursinus Weekly, January 14, 1957

McClure releases statement on new funds for UC • UC evaluation to be held in Feb. • Committee begins work on Campus Chest plans • Y to hear speaker Wed. • WSGA plans forum on student government • Frosh to present Show boat on January 18 • Canterbury Club hears Busler, plans Communion • Two brothers of APE announce engagements • Two Deltas engaged New Year\u27s to Ursinus women • Symons accepts state post in administrative dept. • Twelve Ursinus seniors to be included in 1957 Who\u27s who • Washington trip planned by WRC • MSGA council discusses plans for second semester • Chi Alpha to hear views on evangelism tonight • KDK drive yields 300 lbs. of clothing for Hungary • Two Sig Rho-ers pinned • Reese - Ruth engagement • Noted showman to talk at Feb. Forum • Editorial: Some comments on culture • Da Nighta afta Chrismist • Letters to the editor • Love conquereth all • American theatre: Sophistication or drama • Drexel, Delaware hand J.V. cagers first two defeats • Badminton belles begin practice • Bailey gains new post in E.C.A.C. • Heavyweight forfeit gives Fords 18-18 tie with Bruin matmen Sat. • Losing streak goes to 7 as cagers lose to Drexel, Hens • Finals schedule to be published January 21 • Herman - Eggenhofer engagement • Shelly - Frank engagementhttps://digitalcommons.ursinus.edu/weekly/1419/thumbnail.jp

A New Perspective on Cosmic Coincidence Problems

Cosmological data suggest that we live in an interesting period in the history of the universe when \rho_\Lambda \sim \rho_M \sim \rho_R. The occurence of any epoch with such a "triple coincidence" is puzzling, while the question of why we happen to live during this special epoch is the "Why now?" problem. We introduce a framework which makes the triple coincidence inevitable; furthermore, the ``Why now?'' problem is transformed and greatly ameliorated. The framework assumes that the only relevant mass scales are the electroweak scale, M_{EW}, and the Planck scale, M_{Pl}, and requires \rho_\Lambda^{1/4} \sim M_{EW}^2/M_{Pl} parametrically. Assuming that the true vacuum energy vanishes, we present a simple model where a false vacuum energy yields a cosmological constant of this form.Comment: 5 pages, 1 figure, uses psfig. Refs added, slightly enhance

Activated lymphocyte recruitment into the tumor microenvironment following preoperative sipuleucel-T for localized prostate cancer.

BackgroundSipuleucel-T is a US Food and Drug Administration-approved immunotherapy for asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC). Its mechanism of action is not fully understood. This prospective trial evaluated the direct immune effects of systemically administered sipuleucel-T on prostatic cancer tissue in the preoperative setting.MethodsPatients with untreated localized prostate cancer were treated on an open-label Phase II study of sipuleucel-T prior to planned radical prostatectomy (RP). Immune infiltrates in RP specimens (posttreatment) and in paired pretreatment biopsies were evaluated by immunohistochemistry (IHC). Correlations between circulating immune response and IHC were assessed using Spearman rank order.ResultsOf the 42 enrolled patients, 37 were evaluable. Adverse events were primarily transient, mild-to-moderate and infusion related. Patients developed T cell proliferation and interferon-γ responses detectable in the blood following treatment. Furthermore, a greater-than-three-fold increase in infiltrating CD3(+), CD4(+) FOXP3(-), and CD8(+) T cells was observed in the RP tissues compared with the pretreatment biopsy (binomial proportions: all P < .001). This level of T cell infiltration was observed at the tumor interface, and was not seen in a control group consisting of 12 concurrent patients who did not receive any neoadjuvant treatment prior to RP. The majority of infiltrating T cells were PD-1(+) and Ki-67(+), consistent with activated T cells. Importantly, the magnitude of the circulating immune response did not directly correlate with T cell infiltration within the prostate based upon Spearman's rank order correlation.ConclusionsThis study is the first to demonstrate a local immune effect from the administration of sipuleucel-T. Neoadjuvant sipuleucel-T elicits both a systemic antigen-specific T cell response and the recruitment of activated effector T cells into the prostate tumor microenvironment

PREDICTION OF YELLOW STARTHISTLE SURVIVAL AND MOVEMENT OVER TIME AND SPACE

Yellow starthistle is a noxious weed that has become a serious plant pest with devastating impact on ranching operation and natural resources in western states. Early detection of yellow starthistle and predicting its spread has important managerial implications and greatly reduce the economic losses due to this weed. The dispersal of yellow starthistle consists of two main components, plant survival and seed movement. Resources and direct factors relating to these components are not typically available or are difficult to obtain. Alternatively, topographic factors, such as slope, aspect and elevation, are readily available and can be related to plant survival and seed movement. In this study, several GIS network models incorporating these topographic factors are considered for the prediction of yellow starthistle spread. The models differed in their assessment of the costs of movement derived from these factors. Models were evaluated based on their predictive ability and residual analysis. The optimal model gave an accurate estimate of the dispersal boundary for the study area. Further validation of the estimated model using an independent data set from a larger area also verified its predictive capability

Prototype Cryospheric Experimental Synthetic Aperture Radiometer (CESAR)

Present satellite microwave radiometers typically have a coarse spatial resolution of several kilometers or more. This is only adequate only over homogenous areas. Significantly enhanced spatial resolution is critically important to reduce the uncertainty of estimated cryospheric parameters in heterogeneous and climatically-sensitive areas. Examples include: (1) dynamic sea ice areas with frequent lead and polynya developments and variable ice thicknesses, (2) mountainous areas that require improved retrieval of snow water equivalent, and (3) melting outlet glacier or ice shelf areas along the coast of Greenland and Antarctica. For these situations and many others, an Earth surface spot size of no more than 100 m is necessary to retrieve the information needed for significant new scientific progress, including the synthesis of field observations with satellite observations with high confidence

A screen for nuclear transcripts identifies two linked noncoding RNAs associated with SC35 splicing domains

BACKGROUND: Noncoding RNA species play a diverse set of roles in the eukaryotic cell. While much recent attention has focused on smaller RNA species, larger noncoding transcripts are also thought to be highly abundant in mammalian cells. To search for large noncoding RNAs that might control gene expression or mRNA metabolism, we used Affymetrix expression arrays to identify polyadenylated RNA transcripts displaying nuclear enrichment. RESULTS: This screen identified no more than three transcripts; XIST, and two unique noncoding nuclear enriched abundant transcripts (NEAT) RNAs strikingly located less than 70 kb apart on human chromosome 11: NEAT1, a noncoding RNA from the locus encoding for TncRNA, and NEAT2 (also known as MALAT-1). While the two NEAT transcripts share no significant homology with each other, each is conserved within the mammalian lineage, suggesting significant function for these noncoding RNAs. NEAT2 is extraordinarily well conserved for a noncoding RNA, more so than even XIST. Bioinformatic analyses of publicly available mouse transcriptome data support our findings from human cells as they confirm that the murine homologs of these noncoding RNAs are also nuclear enriched. RNA FISH analyses suggest that these noncoding RNAs function in mRNA metabolism as they demonstrate an intimate association of these RNA species with SC35 nuclear speckles in both human and mouse cells. These studies show that one of these transcripts, NEAT1 localizes to the periphery of such domains, whereas the neighboring transcript, NEAT2, is part of the long-sought polyadenylated component of nuclear speckles. CONCLUSION: Our genome-wide screens in two mammalian species reveal no more than three abundant large non-coding polyadenylated RNAs in the nucleus; the canonical large noncoding RNA XIST and NEAT1 and NEAT2. The function of these noncoding RNAs in mRNA metabolism is suggested by their high levels of conservation and their intimate association with SC35 splicing domains in multiple mammalian species