Increased Yield of ttbb at Hadron Colliders in Low-Energy Supersymmetry

Light bottom squarks and gluinos have been invoked to explain the b quark pair production excess at the Tevatron. We investigate the associated production of ttbb at hadron colliders in this scenario, and find that the rates for this process are enhanced over the Standard Model prediction. If light gluinos exist, it may be possible to detect them at the Tevatron, and they could easily be observed at the LHC.Comment: 5p, references added, version accepted to PR

Phenomenology of the Gowdy Universe on T3×RT^3 \times R

Numerical studies of the plane symmetric, vacuum Gowdy universe on $T^3 \times R$ yield strong support for the conjectured asymptotically velocity term dominated (AVTD) behavior of its evolution toward the singularity except, perhaps, at isolated spatial points. A generic solution is characterized by spiky features and apparent ``discontinuities'' in the wave amplitudes. It is shown that the nonlinear terms in the wave equations drive the system generically to the ``small velocity'' AVTD regime and that the spiky features are caused by the absence of these terms at isolated spatial points.Comment: 19 pages, 21 figures, uses Revtex, psfi

New Algorithm for Mixmaster Dynamics

We present a new numerical algorithm for evolving the Mixmaster spacetimes. By using symplectic integration techniques to take advantage of the exact Taub solution for the scattering between asymptotic Kasner regimes, we evolve these spacetimes with higher accuracy using much larger time steps than previously possible. The longer Mixmaster evolution thus allowed enables detailed comparison with the Belinskii, Khalatnikov, Lifshitz (BKL) approximate Mixmaster dynamics. In particular, we show that errors between the BKL prediction and the measured parameters early in the simulation can be eliminated by relaxing the BKL assumptions to yield an improved map. The improved map has different predictions for vacuum Bianchi Type IX and magnetic Bianchi Type VI$_0$ Mixmaster models which are clearly matched in the simulation.Comment: 12 pages, Revtex, 4 eps figure

Slow movement of a random walk on the range of a random walk in the presence of an external field

In this article, a localisation result is proved for the biased random walk on the range of a simple random walk in high dimensions (d \geq 5). This demonstrates that, unlike in the supercritical percolation setting, a slowdown effect occurs as soon a non-trivial bias is introduced. The proof applies a decomposition of the underlying simple random walk path at its cut-times to relate the associated biased random walk to a one-dimensional random walk in a random environment in Sinai's regime

Evidence that complement and coagulation proteins are mediating the clinical response to omega-3 fatty acids: A mass spectrometry-based investigation in subjects at clinical high-risk for psychosis

Preliminary evidence indicates beneficial effects of omega-3 polyunsaturated fatty acids (PUFAs) in early psychosis. The present study investigates the molecular mechanism of omega-3 PUFA-associated therapeutic effects in clinical high-risk (CHR) participants. Plasma samples of 126 CHR psychosis participants at baseline and 6-months follow-up were included. Plasma protein levels were quantified using mass spectrometry and erythrocyte omega-3 PUFA levels were quantified using gas chromatography. We examined the relationship between change in polyunsaturated PUFAs (between baseline and 6-month follow-up) and follow-up plasma proteins. Using mediation analysis, we investigated whether plasma proteins mediated the relationship between change in omega-3 PUFAs and clinical outcomes. A 6-months change in omega-3 PUFAs was associated with 24 plasma proteins at follow-up. Pathway analysis revealed the complement and coagulation pathway as the main biological pathway to be associated with change in omega-3 PUFAs. Moreover, complement and coagulation pathway proteins significantly mediated the relationship between change in omega-3 PUFAs and clinical outcome at follow-up. The inflammatory protein complement C5 and protein S100A9 negatively mediated the relationship between change in omega-3 PUFAs and positive symptom severity, while C5 positively mediated the relationship between change in omega-3 and functional outcome. The relationship between change in omega-3 PUFAs and cognition was positively mediated through coagulation factor V and complement protein C1QB. Our findings provide evidence for a longitudinal association of omega-3 PUFAs with complement and coagulation protein changes in the blood. Further, the results suggest that an increase in omega-3 PUFAs decreases symptom severity and improves cognition in the CHR state through modulating effects of complement and coagulation proteins

FOXD3 Regulates VISTA Expression in Melanoma.

Immune checkpoint inhibitors have improved patient survival in melanoma, but the innate resistance of many patients necessitates the investigation of alternative immune targets. Many immune checkpoint proteins lack proper characterization, including V-domain Ig suppressor of T cell activation (VISTA). VISTA expression on immune cells can suppress T cell activity; however, few studies have investigated its expression and regulation in cancer cells. In this study, we observe that VISTA is expressed in melanoma patient samples and cell lines. Tumor cell-specific expression of VISTA promotes tumor onset in vivo, associated with increased intratumoral T regulatory cells, and enhanced PDL-1 expression on tumor-infiltrating macrophages. VISTA transcript levels are regulated by the stemness factor Forkhead box D3 (FOXD3). BRAF inhibition upregulates FOXD3 and reduces VISTA expression. Overall, this study demonstrates melanoma cell expression of VISTA and its regulation by FOXD3, contributing to the rationale for therapeutic strategies that combine targeted inhibitors with immune checkpoint blockade

Design and Implementation of Collaborative Research Approaches

This poster reviews the collarborative research approaches that NASA has been designing and implementing for the Integrated Vehicle Health Management (IVHM) Project. The inputs for the technical plan are reviewed, the Research Test and Integration Plan (RTIP) WIKI, is used to create and propose a multi-themed and multi-partner research testing opportunities. The outputs are testing opportunities

Concurrent MEK targeted therapy prevents MAPK pathway reactivation during BRAFV600E targeted inhibition in a novel syngeneic murine glioma model.

Inhibitors of BRAFV600E kinase are currently under investigations in preclinical and clinical studies involving BRAFV600E glioma. Studies demonstrated clinical response to such individualized therapy in the majority of patients whereas in some patients tumors continue to grow despite treatment. To study resistance mechanisms, which include feedback activation of mitogen-activated protein kinase (MAPK) signaling in melanoma, we developed a luciferase-modified cell line (2341luc) from a BrafV600E mutant and Cdkn2a- deficient murine high-grade glioma, and analyzed its molecular responses to BRAFV600E- and MAPK kinase (MEK)-targeted inhibition. Immunocompetent, syngeneic FVB/N mice with intracranial grafts of 2341luc were tested for effects of BRAFV600E and MEK inhibitor treatments, with bioluminescence imaging up to 14-days after start of treatment and survival analysis as primary indicators of inhibitor activity. Intracranial injected tumor cells consistently generated high-grade glioma-like tumors in syngeneic mice. Intraperitoneal daily delivery of BRAFV600E inhibitor dabrafenib only transiently suppressed MAPK signaling, and rather increased Akt signaling and failed to extend survival for mice with intracranial 2341luc tumor. MEK inhibitor trametinib delivered by oral gavage daily suppressed MAPK pathway more effectively and had a more durable anti-growth effect than dabrafenib as well as a significant survival benefit. Compared with either agent alone, combined BRAFV600E and MEK inhibitor treatment was more effective in reducing tumor growth and extending animal subject survival, as corresponding to sustained MAPK pathway inhibition. Results derived from the 2341luc engraftment model application have clinical implications for the management of BRAFV600E glioma

De novo design of bioactive protein switches.

Allosteric regulation of protein function is widespread in biology, but is challenging for de novo protein design as it requires the explicit design of multiple states with comparable free energies. Here we explore the possibility of designing switchable protein systems de novo, through the modulation of competing inter- and intramolecular interactions. We design a static, five-helix 'cage' with a single interface that can interact either intramolecularly with a terminal 'latch' helix or intermolecularly with a peptide 'key'. Encoded on the latch are functional motifs for binding, degradation or nuclear export that function only when the key displaces the latch from the cage. We describe orthogonal cage-key systems that function in vitro, in yeast and in mammalian cells with up to 40-fold activation of function by key. The ability to design switchable protein functions that are controlled by induced conformational change is a milestone for de novo protein design, and opens up new avenues for synthetic biology and cell engineering

Resolution of the clinical features of tyrosinemia following orthotopic liver transplantation for hepatoma

The clinical history before transplantation and subsequent clinical and biochemical course of 3 children and one adult with hereditary tyrosinemia treated by orthotopic hepatic transplantation is described. All four patients are now free of their previous dietary restrictions and appear to be cured of both their metabolic disease and their hepatic neoplasm. © 1986 Elsevier Science Publishers B.V. All rights reserved