T-cell cytotoxicity in the absence of viral protein synthesis in target cells

CYTOTOXIC T cells lyse only those virus infected target cells in vitro which express, in addition to the viral antigen(s), those K or D region products of the major histocompati-bility complex (MHC) which were present during anti-viral sensitisation in vivo. This 'associative recogniton' by cytotoxic T cells could reflect the interaction of two T-cell receptors with specificity for target K or D gene products and independently for the viral antigen, or one receptor with specificity for virally altered K or D region products (see ref. 1 and refs therein). There are various ways that the MHC antigens could be altered, including 'modification from within', where the virus modifies host protein synthesis by interfering with transcription2, translation or post-translational glycosylation; or 'modification from without' where enzymic or chemical alteration of cell membrane proteins are induced by virus activity at the cell surface. In this report we show that inactivated Sendai virus or isolated Sendai virus envelopes can serve to modify a cell and make it a specific target for Sendai-immune T-cell killing, thus excluding the possibility of 'modification from within' in this system

Solitonic supersymmetry restoration

Q-balls are a possible feature of any model with a conserved, global U(1) symmetry and no massless, charged scalars. It is shown that for a broad class of models of metastable supersymmetry breaking they are extremely influential on the vacuum lifetime and make seemingly viable vacua catastrophically short lived. A net charge asymmetry is not required as there is often a significant range of parameter space where statistical fluctuations alone are sufficient. This effect is examined for two supersymmetry breaking scenarios. It is found that models of minimal gauge mediation (which necessarily have a messenger number U(1)) undergo a rapid, supersymmetry restoring phase transition unless the messenger mass is greater than 10^8 GeV. Similarly the ISS model, in the context of direct mediation, quickly decays unless the perturbative superpotential coupling is greater than the Standard Model gauge couplings.Comment: 17 pages, 3 figures, minor comments added, accepted for publication in JHE

Generalized nonreciprocity in an optomechanical circuit via synthetic magnetism and reservoir engineering

Synthetic magnetism has been used to control charge neutral excitations for applications ranging from classical beam steering to quantum simulation. In optomechanics, radiation-pressure-induced parametric coupling between optical (photon) and mechanical (phonon) excitations may be used to break time-reversal symmetry, providing the prerequisite for synthetic magnetism. Here we design and fabricate a silicon optomechanical circuit with both optical and mechanical connectivity between two optomechanical cavities. Driving the two cavities with phase-correlated laser light results in a synthetic magnetic flux, which in combination with dissipative coupling to the mechanical bath, leads to nonreciprocal transport of photons with 35dB of isolation. Additionally, optical pumping with blue-detuned light manifests as a particle non-conserving interaction between photons and phonons, resulting in directional optical amplification of 12dB in the isolator through direction. These results indicate the feasibility of utilizing optomechanical circuits to create a more general class of nonreciprocal optical devices, and further, to enable novel topological phases for both light and sound on a microchip.Comment: 18 pages, 8 figures, 4 appendice

Revising the WHO verbal autopsy instrument to facilitate routine cause-of-death monitoring.

OBJECTIVE: Verbal autopsy (VA) is a systematic approach for determining causes of death (CoD) in populations without routine medical certification. It has mainly been used in research contexts and involved relatively lengthy interviews. Our objective here is to describe the process used to shorten, simplify, and standardise the VA process to make it feasible for application on a larger scale such as in routine civil registration and vital statistics (CRVS) systems. METHODS: A literature review of existing VA instruments was undertaken. The World Health Organization (WHO) then facilitated an international consultation process to review experiences with existing VA instruments, including those from WHO, the Demographic Evaluation of Populations and their Health in Developing Countries (INDEPTH) Network, InterVA, and the Population Health Metrics Research Consortium (PHMRC). In an expert meeting, consideration was given to formulating a workable VA CoD list [with mapping to the International Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) CoD] and to the viability and utility of existing VA interview questions, with a view to undertaking systematic simplification. FINDINGS: A revised VA CoD list was compiled enabling mapping of all ICD-10 CoD onto 62 VA cause categories, chosen on the grounds of public health significance as well as potential for ascertainment from VA. A set of 221 indicators for inclusion in the revised VA instrument was developed on the basis of accumulated experience, with appropriate skip patterns for various population sub-groups. The duration of a VA interview was reduced by about 40% with this new approach. CONCLUSIONS: The revised VA instrument resulting from this consultation process is presented here as a means of making it available for widespread use and evaluation. It is envisaged that this will be used in conjunction with automated models for assigning CoD from VA data, rather than involving physicians

Aspects of Non-minimal Gauge Mediation

A large class of non-minimal gauge mediation models, such as (semi-)direct gauge mediation, predict a hierarchy between the masses of the supersymmetric standard model gauginos and those of scalar particles. We perform a comprehensive study of these non-minimal gauge mediation models, including mass calculations in semi-direct gauge mediation, to illustrate these features, and discuss the phenomenology of the models. We point out that the cosmological gravitino problem places stringent constraints on mass splittings, when the Bino is the NLSP. However, the GUT relation of the gaugino masses is broken unlike the case of minimal gauge mediation, and an NLSP other than the Bino (especially the gluino NLSP) becomes possible, relaxing the cosmological constraints. We also discuss the collider signals of the models.Comment: 56 pages, 8 figures; v2:minor corrections, references added; v3:minor correction

Extracellular Heat Shock Protein (Hsp)70 and Hsp90α Assist in Matrix Metalloproteinase-2 Activation and Breast Cancer Cell Migration and Invasion

Breast cancer is second only to lung cancer in cancer-related deaths in women, and the majority of these deaths are caused by metastases. Obtaining a better understanding of migration and invasion, two early steps in metastasis, is critical for the development of treatments that inhibit breast cancer metastasis. In a functional proteomic screen for proteins required for invasion, extracellular heat shock protein 90 alpha (Hsp90α) was identified and shown to activate matrix metalloproteinase 2 (MMP-2). The mechanism of MMP-2 activation by Hsp90α is unknown. Intracellular Hsp90α commonly functions with a complex of co-chaperones, leading to our hypothesis that Hsp90α functions similarly outside of the cell. In this study, we show that a complex of co-chaperones outside of breast cancer cells assists Hsp90α mediated activation of MMP-2. We demonstrate that the co-chaperones Hsp70, Hop, Hsp40, and p23 are present outside of breast cancer cells and co-immunoprecipitate with Hsp90α in vitro and in breast cancer conditioned media. These co-chaperones also increase the association of Hsp90α and MMP-2 in vitro. This co-chaperone complex enhances Hsp90α-mediated activation of MMP-2 in vitro, while inhibition of Hsp70 in conditioned media reduces this activation and decreases cancer cell migration and invasion. Together, these findings support a model in which MMP-2 activation by an extracellular co-chaperone complex mediated by Hsp90α increases breast cancer cell migration and invasion. Our studies provide insight into a novel pathway for MMP-2 activation and suggest Hsp70 as an additional extracellular target for anti-metastatic drug development

Azimuthal anisotropy and correlations at large transverse momenta in p+pp+p and Au+Au collisions at sNN\sqrt{s_{_{NN}}}= 200 GeV

Results on high transverse momentum charged particle emission with respect to the reaction plane are presented for Au+Au collisions at $\sqrt{s_{_{NN}}}$= 200 GeV. Two- and four-particle correlations results are presented as well as a comparison of azimuthal correlations in Au+Au collisions to those in $p+p$ at the same energy. Elliptic anisotropy, $v_2$, is found to reach its maximum at $p_t \sim 3$ GeV/c, then decrease slowly and remain significant up to $p_t\approx 7$ -- 10 GeV/c. Stronger suppression is found in the back-to-back high-$p_t$ particle correlations for particles emitted out-of-plane compared to those emitted in-plane. The centrality dependence of $v_2$ at intermediate $p_t$ is compared to simple models based on jet quenching.Comment: 4 figures. Published version as PRL 93, 252301 (2004

Azimuthal anisotropy in Au+Au collisions at sqrtsNN = 200 GeV

The results from the STAR Collaboration on directed flow (v_1), elliptic flow (v_2), and the fourth harmonic (v_4) in the anisotropic azimuthal distribution of particles from Au+Au collisions at sqrtsNN = 200 GeV are summarized and compared with results from other experiments and theoretical models. Results for identified particles are presented and fit with a Blast Wave model. Different anisotropic flow analysis methods are compared and nonflow effects are extracted from the data. For v_2, scaling with the number of constituent quarks and parton coalescence is discussed. For v_4, scaling with v_2^2 and quark coalescence is discussed.Comment: 26 pages. As accepted by Phys. Rev. C. Text rearranged, figures modified, but data the same. However, in Fig. 35 the hydro calculations are corrected in this version. The data tables are available at http://www.star.bnl.gov/central/publications/ by searching for "flow" and then this pape

Rapidity and Centrality Dependence of Proton and Anti-proton Production from Au+Au Collisions at sqrt(sNN) = 130GeV

We report on the rapidity and centrality dependence of proton and anti-proton transverse mass distributions from Au+Au collisions at sqrt(sNN) = 130GeV as measured by the STAR experiment at RHIC. Our results are from the rapidity and transverse momentum range of |y|<0.5 and 0.35 <p_t<1.00GeV/c. For both protons and anti-protons, transverse mass distributions become more convex from peripheral to central collisions demonstrating characteristics of collective expansion. The measured rapidity distributions and the mean transverse momenta versus rapidity are flat within |y|<0.5. Comparisons of our data with results from model calculations indicate that in order to obtain a consistent picture of the proton(anti-proton) yields and transverse mass distributions the possibility of pre-hadronic collective expansion may have to be taken into account.Comment: 4 pages, 3 figures, 1 table, submitted to PR

How well do adolescents recall use of mobile telephones? Results of a validation study

<p>Abstract</p> <p>Background</p> <p>In the last decade mobile telephone use has become more widespread among children. Concerns expressed about possible health risks have led to epidemiological studies investigating adverse health outcomes associated with mobile telephone use. Most epidemiological studies have relied on self reported questionnaire responses to determine individual exposure. We sought to validate the accuracy of self reported adolescent mobile telephone use.</p> <p>Methods</p> <p>Participants were recruited from year 7 secondary school students in Melbourne, Australia. Adolescent recall of mobile telephone use was assessed using a self administered questionnaire which asked about number and average duration of calls per week. Validation of self reports was undertaken using Software Modified Phones (SMPs) which logged exposure details such as number and duration of calls.</p> <p>Results</p> <p>A total of 59 adolescents participated (39% boys, 61% girls). Overall a modest but significant rank correlation was found between self and validated number of voice calls (ρ = 0.3, P = 0.04) with a sensitivity of 57% and specificity of 66%. Agreement between SMP measured and self reported duration of calls was poorer (ρ = 0.1, P = 0.37). Participants whose parents belonged to the 4^thsocioeconomic stratum recalled mobile phone use better than others (ρ = 0.6, P = 0.01).</p> <p>Conclusion</p> <p>Adolescent recall of mobile telephone use was only modestly accurate. Caution is warranted in interpreting results of epidemiological studies investigating health effects of mobile phone use in this age group.</p