Cancer Molecular Analysis Project: Weaving a rich cancer research tapestry

AbstractThe Cancer Molecular Analysis Project (CMAP) of the NCI is integrating diverse cancer research data to elucidate fundamental etiologic processes, enable development of novel therapeutic approaches, and facilitate the bridging of basic and clinical science

The impact of phonological versus semantic repetition training on generalisation in chronic stroke aphasia reflects differences in dorsal pathway connectivity

It has been suggested that neuroimaging can be used to inform therapeutic intervention. The current study aimed to determine whether an individual would benefit more from training engaging their intact or their damaged neural pathway. Two males with chronic stroke aphasia participated, with DM showing milder disruption of connectivity along the dorsal language pathway relative to JS, according to distortion corrected diffusion-weighted magnetic resonance imaging. Each patient received two blocks of six repetition training sessions over two weeks, one of which was "phonological" and the other "semantic" in nature. Both phonological and semantic training produced significant gains for both patients for trained items. For the untrained control items, significant gains were specific to training type for each patient. Only phonological training elicited significant generalisation for DM, which was greater than that seen for JS. Conversely, only semantic training elicited significant generalisation for JS, which was greater than that seen for DM. This double dissociation in generalisation effects suggests that a restitutive approach is more effective for patients with milder damage while a compensatory approach may be more effective for those with more severe damage. These results indicate the utility of neuroimaging to optimise relearning strategies and promote generalisation to untrained items

Decays of ℓ=1\ell=1 Baryons --- Quark Model versus Large-NcN_c

We study nonleptonic decays of the orbitally excited, \su6 \rep{70}-plet baryons in order to test the hypothesis that the successes of the nonrelativistic quark model have a natural explanation in the large-$N_c$ limit of QCD. By working in a Hartree approximation, we isolate a specific set of operators that contribute to the observed s- and d-wave decays in leading order in $1/N_c$. We fit our results to the current experimental decay data, and make predictions for a number of allowed but unobserved modes. Our tentative conclusion is that there is more to the nonrelativistic quark model of baryons than large-$N_c$.Comment: LaTeX 49pp. (38 pp. landscape), PicTex, PrePicTex, PostPicTex required for 3 figures, Harvard Preprint HUTP-94/A008. (Two additional operators are included, but conclusions are unchanged.

Partisan Asymmetries in Online Political Activity

We examine partisan differences in the behavior, communication patterns and social interactions of more than 18,000 politically-active Twitter users to produce evidence that points to changing levels of partisan engagement with the American online political landscape. Analysis of a network defined by the communication activity of these users in proximity to the 2010 midterm congressional elections reveals a highly segregated, well clustered partisan community structure. Using cluster membership as a high-fidelity (87% accuracy) proxy for political affiliation, we characterize a wide range of differences in the behavior, communication and social connectivity of left- and right-leaning Twitter users. We find that in contrast to the online political dynamics of the 2008 campaign, right-leaning Twitter users exhibit greater levels of political activity, a more tightly interconnected social structure, and a communication network topology that facilitates the rapid and broad dissemination of political information.Comment: 17 pages, 10 figures, 6 table

T Cell Activation and Senescence Predict Subclinical Carotid Artery Disease in HIV-Infected Women

Background. Individuals infected with human immunodeficiency virus (HIV) have increased risk of cardiovascular events. It is unknown whether T cell activation and senescence, 2 immunologic sequelae of HIV infection, are associated with vascular disease among HIV-infected adults

Viable Supersymmetric Models with an Inverted Scalar Mass Hierarchy at the GUT Scale

Supersymmetric models with an inverted mass hierarchy (IMH: multi-TeV first and second generation matter scalars, and sub-TeV third generation and Higgs scalars) have been proposed to ameliorate phenomenological problems arising from flavor changing neutral currents (FCNCs) and CP violating processes, while satisfying conditions of naturalness. Models with an IMH already in place at the GUT scale have been shown to be constrained in that for many model parameter choices, the top squark squared mass is driven to negative values. We delineate regions of parameter space where viable models with a GUT scale IMH can be generated. We find that larger values of GUT scale first and second generation scalar masses act to suppress third generation scalars, leading to acceptable solutions if GUT scale gaugino masses are large enough. We show examples of viable models and comment on their characteristic features. For example, in these models the gluino mass is bounded from below, and effectively decouples, whilst third generation scalars remain at sub-TeV levels. While possibly fulfilling criteria of naturalness, these models present challenges for detection at future pp and e^+e^- collider experiments.Comment: 16 page REVTEX file with 6 PS figure

Inhibition of cytochrome P450 2D6 metabolism of hydrocodone to hydromorphone does not importantly affect abuse liability

ABSTRACT Enzymatic conversion of hydrocodone to hydromorphone is catalyzed by cytochrome P450 2D6, which is inactive in about 7% of Caucasians [poor metabolizers (PMs)] and can be inhibited by quinidine pretreatment in the remainder [extensive metabolizers (EMs)]. If hydromorphone, having a substantially higher -receptor affinity than hydrocodone, contributes importantly to the physiological and subjective effects of oral hydrocodone, then PMs should be less responsive to the same doses, and quinidine pretreatment should cause EMs to temporarily respond as PMs. Seventeen EMs and 8 PMs who previously responded positively to hydromorphone s.c. received placebo and hydrocodone (10 mg, 15 mg and 22.5 mg p.o.) and were retested with their favorite dose after placebo or quinidine (100 mg) pretreatment; physiological and subjective measures were collected at base line and four times after drug administration, and urine was collected for 8 hr. EMs and PMs were equally responsive to oral hydrocodone, and quinidine had no consistent effect on their responses, even though quinidine abolished the pre-existing metabolic differences in hydromorphone production, as measured in urine. These data suggest only a small role of hydromorphone in eliciting abuserelated responses to oral hydrocodone. The genetic polymorphism of the drug-metabolizing enzyme CYP2D6 results in phenotypic differences in the pharmacokinetics of many drugs One drug for which there is evidence of phenotypic differences in response is codeine, which is O-demethylated by CYP2D6 to form morphine Hydrocodone differs structurally from codeine in that the C6-position is occupied by a keto-group, and thus the drug does not undergo the extensive conjugation (Ͼ60%) that codeine undergoe

The Reach of the Fermilab Tevatron and CERN LHC for Gaugino Mediated SUSY Breaking Models

In supersymmetric models with gaugino mediated SUSY breaking (inoMSB), it is assumed that SUSY breaking on a hidden brane is communicated to the visible brane via gauge superfields which propagate in the bulk. This leads to GUT models where the common gaugino mass $m_{1/2}$ is the only soft SUSY breaking term to receive contributions at tree level. To obtain a viable phenomenology, it is assumed that the gaugino mass is induced at some scale $M_c$ beyond the GUT scale, and that additional renormalization group running takes place between $M_c$ and $M_{GUT}$ as in a SUSY GUT. We assume an SU(5) SUSY GUT above the GUT scale, and compute the SUSY particle spectrum expected in models with inoMSB. We use the Monte Carlo program ISAJET to simulate signals within the inoMSB model, and compute the SUSY reach including cuts and triggers approriate to Fermilab Tevatron and CERN LHC experiments. We find no reach for SUSY by the Tevatron collider in the trilepton channel. %either with or without %identified tau leptons. At the CERN LHC, values of $m_{1/2}=1000$ (1160) GeV can be probed with 10 (100) fb$^{-1}$ of integrated luminosity, corresponding to a reach in terms of $m_{\tg}$ of 2150 (2500) GeV. The inoMSB model and mSUGRA can likely only be differentiated at a linear $e^+e^-$ collider with sufficient energy to produce sleptons and charginos.Comment: 17 page revtex file with 9 PS figure

Analytical and computational study of magnetization switching in kinetic Ising systems with demagnetizing fields

An important aspect of real ferromagnetic particles is the demagnetizing field resulting from magnetostatic dipole-dipole interaction, which causes large particles to break up into domains. Sufficiently small particles, however, remain single-domain in equilibrium. This makes such small particles of particular interest as materials for high-density magnetic recording media. In this paper we use analytic arguments and Monte Carlo simulations to study the effect of the demagnetizing field on the dynamics of magnetization switching in two-dimensional, single-domain, kinetic Ising systems. For systems in the ``Stochastic Region,'' where magnetization switching is on average effected by the nucleation and growth of fewer than two well-defined critical droplets, the simulation results can be explained by the dynamics of a simple model in which the free energy is a function only of magnetization. In the ``Multi-Droplet Region,'' a generalization of Avrami's Law involving a magnetization-dependent effective magnetic field gives good agreement with our simulations.Comment: 29 pages, REVTeX 3.0, 10 figures, 2 more figures by request. Submitted Phys. Rev.

Gaugino Anomaly Mediated SUSY Breaking: phenomenology and prospects for the LHC

We examine the supersymmetry phenomenology of a novel scenario of supersymmetry (SUSY) breaking which we call Gaugino Anomaly Mediation, or inoAMSB. This is suggested by recent work on the phenomenology of flux compactified type IIB string theory. The essential features of this scenario are that the gaugino masses are of the anomaly-mediated SUSY breaking (AMSB) form, while scalar and trilinear soft SUSY breaking terms are highly suppressed. Renormalization group effects yield an allowable sparticle mass spectrum, while at the same time avoiding charged LSPs; the latter are common in models with negligible soft scalar masses, such as no-scale or gaugino mediation models. Since scalar and trilinear soft terms are highly suppressed, the SUSY induced flavor and CP-violating processes are also suppressed. The lightest SUSY particle is the neutral wino, while the heaviest is the gluino. In this model, there should be a strong multi-jet +etmiss signal from squark pair production at the LHC. We find a 100 fb^{-1} reach of LHC out to m_{3/2}\sim 118 TeV, corresponding to a gluino mass of \sim 2.6 TeV. A double mass edge from the opposite-sign/same flavor dilepton invariant mass distribution should be visible at LHC; this, along with the presence of short-- but visible-- highly ionizing tracks from quasi-stable charginos, should provide a smoking gun signature for inoAMSB.Comment: 30 pages including 14 .eps figure