Vaccines and Immunotherapeutics for the Treatment of Malignant Disease

The employment of the immune system to treat malignant disease represents an active area of biomedical research. The specificity of the immune response and potential for establishing long-term tumor immunity compels researchers to continue investigations into immunotherapeutic approaches for cancer. A number of immunotherapeutic strategies have arisen for the treatment of malignant disease, including various vaccination schemes, cytokine therapy, adoptive cellular therapy, and monoclonal antibody therapy. This paper describes each of these strategies and discusses some of the associated successes and limitations. Emphasis is placed on the integration of techniques to promote optimal scenarios for eliminating cancer

The Reddest Quasars

In a survey of quasar candidates selected by matching the FIRST and 2MASS catalogs, we have found two extraordinarily red quasars. FIRST J013435.7-093102 is a 1 Jy source at z=2.216 and has B-K > 10, while FIRST J073820.1+275045 is a 2.5 mJy source at z=1.985 with B-K = 8.4. FIRST J073820.1+275045 has strong absorption lines of MgII and CIV in the rest frame of the quasar and is highly polarized in the rest frame ultraviolet, strongly favoring the interpretation that its red spectral energy distribution is caused by dust reddening local to the quasar. FIRST J073820.1+275045 is thus one of the few low radio-luminosity, highly dust-reddened quasars known. The available observational evidence for FIRST J013435.7-093102 leads us to conclude that it too is reddened by dust. We show that FIRST J013435.7-093102 is gravitationally lensed, increasing the number of known lensed, extremely dust-reddened quasars to at least three, including MG0414-0534 and PKS1830-211. We discuss the implications of whether these objects are reddened by dust in the host or lensing galaxies. If reddened by their local environment, then we estimate that between 10 and 20% of the radio-loud quasar population is reddened by dust in the host galaxy. The discovery of FIRST J073820.1+275045 and objects now emerging from X-ray surveys suggests the existence of an analogous radio-quiet red quasar population. Such objects will be entirely missed by standard radio or optical quasar surveys. If dust in the lensing galaxies is primarily responsible for the extreme redness of the lensed quasars, then an untold number of gravitationally lensed quasars are being overlooked.Comment: AASTEX 24 pp., 7 figs; accepted by ApJ. See also the preprint astro-ph/0107435 by Winn et al., who independently discovered that J013435.7-093102 is gravitationally lense

MRC2014: Extensions to the MRC format header for electron cryo-microscopy and tomography

Open Access funded by Medical Research CouncilThe MRC binary file format is widely used in the three-dimensional electron microscopy field for storing image and volume data. Files contain a header which describes the kind of data held, together with other important metadata. In response to advances in electron microscopy techniques, a number of variants to the file format have emerged which contain useful additional data, but which limit interoperability between different software packages. Following extensive discussions, the authors, who represent leading software packages in the field, propose a set of extensions to the MRC format standard designed to accommodate these variants, while restoring interoperability. The MRC format is equivalent to the map format used in the CCP4 suite for macromolecular crystallography, and the proposal also maintains interoperability with crystallography software. This Technical Note describes the proposed extensions, and serves as a reference for the standard.We thank Chris Booth and Steffen Meyer from Gatan Inc. for clarifying the format definition used by Digital Micrograph. Acknowledgement for support from National Institute of Health, USA includes: NIGMS grant P41GM103310 (AC and SD), NIBIB grant 5R01-EB005027 (DM), and R01GM080139 (SJL). RH and MW would like to thank the UK Medical Research Council for the award of Partnership Grant MR/J000825/1 to support the establishment of CCP-EM. RH and JS are also supported by MRC grant U105184322

Detection of CI in absorption towards PKS 1830-211 with the eSMA

We report the first science observations and results obtained with the "extended" SMA (eSMA), which is composed of the SMA (Submillimeter Array), JCMT (James Clerk Maxwell Telescope) and CSO (Caltech Submillimeter Observatory). Redshifted absorptions at z=0.886 of CI (^3P_1 - ^3P_0) were observed with the eSMA with an angular resolution of 0.55"x0.22" at 1.1 mm toward the southwestern image of the remarkable lensed quasar PKS 1830-211, but not toward the northeastern component at a separation of ~1". Additionally, SMA observations of CO, 13CO and C18O (all J=4-3) were obtained toward this object: CO was also detected toward the SW component, but none of the isotopologues were. This is the first time [CI] is detected in this object, allowing the first direct determination of relative abundances of neutral atomic carbon to CO in the molecular clouds of a spiral galaxy at z>0.1. The [CI] and CO profiles can be decomposed into two and three velocity components respectively. We derive C/CO column density ratios ranging from <0.5 (representative of dense cores) to ~2.5 (close to translucent clouds values). This could indicate that we are seeing environments with different physical conditions or that we are witnessing chemical evolution of regions where C has not completely been converted into CO.Comment: 6 pages using emulateapj, 3 tables, 2 figures ; accepted for publication in ApJ

Inbreeding shapes the evolution of marine invertebrates

Inbreeding is a potent evolutionary force shaping the distribution of genetic variation within and among populations of plants and animals. Yet, our understanding of the forces shaping the expression and evolution of nonrandom mating in general, and inbreeding in particular, remains remarkably incomplete. Most research on plant mating systems focuses on self-fertilization and its consequences for automatic selection, inbreeding depression, purging, and reproductive assurance, whereas studies of animal mating systems have often assumed that inbreeding is rare, and that natural selection favors traits that promote outbreeding. Given that many sessile and sedentary marine invertebrates and marine macroalgae share key life history features with seed plants (e.g., low mobility, modular construction, and the release of gametes into the environment), their mating systems may be similar. Here, we show that published estimates of inbreeding coefficients (FIS) for sessile and sedentary marine organisms are similar and at least as high as noted in terrestrial seed plants. We also found that variation in FIS within invertebrates is related to the potential to self-fertilize, disperse, and choose mates. The similarity of FIS for these organismal groups suggests that inbreeding could play a larger role in the evolution of sessile and sedentary marine organisms than is currently recognized. Specifically, associations between traits of marine invertebrates and FIS suggest that inbreeding could drive evolutionary transitions between hermaphroditism and separate sexes, direct development and multiphasic life cycles, and external and internal fertilization

Global biogeography of mating system variation in seed plants

Latitudinal gradients in biotic interactions have been suggested as causes of global patterns of biodiversity and phenotypic variation. Plant biologists have long speculated that outcrossing mating systems are more common at low than high latitudes owing to a greater predictability of plant&ndash;pollinator interactions in the tropics; however, these ideas have not previously been tested. Here, we present the first global biogeographic analysis of plant mating systems based on 624 published studies from 492 taxa. We found a weak decline in outcrossing rate towards higher latitudes and among some biomes, but no biogeographic patterns in the frequency of self-incompatibility. Incorporating life history and growth form into biogeographic analyses reduced or eliminated the importance of latitude and biome in predicting outcrossing or self-incompatibility. Our results suggest that biogeographic patterns in mating system are more likely a reflection of the frequency of life forms across latitudes rather than the strength of plant&ndash;pollinator interactions

The Sloan Digital Sky Survey Quasar Lens Search. IV. Statistical Lens Sample from the Fifth Data Release

We present the second report of our systematic search for strongly lensed quasars from the data of the Sloan Digital Sky Survey (SDSS). From extensive follow-up observations of 136 candidate objects, we find 36 lenses in the full sample of 77,429 spectroscopically confirmed quasars in the SDSS Data Release 5. We then define a complete sample of 19 lenses, including 11 from our previous search in the SDSS Data Release 3, from the sample of 36,287 quasars with i<19.1 in the redshift range 0.6<z<2.2, where we require the lenses to have image separations of 1"<\theta<20" and i-band magnitude differences between the two images smaller than 1.25 mag. Among the 19 lensed quasars, 3 have quadruple-image configurations, while the remaining 16 show double images. This lens sample constrains the cosmological constant to be \Omega_\Lambda=0.84^{+0.06}_{-0.08}(stat.)^{+0.09}_{-0.07}(syst.) assuming a flat universe, which is in good agreement with other cosmological observations. We also report the discoveries of 7 binary quasars with separations ranging from 1.1" to 16.6", which are identified in the course of our lens survey. This study concludes the construction of our statistical lens sample in the full SDSS-I data set.Comment: 37 pages, 2 figures and 5 tables, accepted to A

Functionals of the Brownian motion, localization and metric graphs

We review several results related to the problem of a quantum particle in a random environment. In an introductory part, we recall how several functionals of the Brownian motion arise in the study of electronic transport in weakly disordered metals (weak localization). Two aspects of the physics of the one-dimensional strong localization are reviewed : some properties of the scattering by a random potential (time delay distribution) and a study of the spectrum of a random potential on a bounded domain (the extreme value statistics of the eigenvalues). Then we mention several results concerning the diffusion on graphs, and more generally the spectral properties of the Schr\"odinger operator on graphs. The interest of spectral determinants as generating functions characterizing the diffusion on graphs is illustrated. Finally, we consider a two-dimensional model of a charged particle coupled to the random magnetic field due to magnetic vortices. We recall the connection between spectral properties of this model and winding functionals of the planar Brownian motion.Comment: Review article. 50 pages, 21 eps figures. Version 2: section 5.5 and conclusion added. Several references adde

\u3ci\u3eFundulus\u3c/i\u3e as the premier teleost model in environmental biology: Opportunities for new insights using genomics

A strong foundation of basic and applied research documents that the estuarine fish Fundulus heteroclitus and related species are unique laboratory and field models for understanding how individuals and populations interact with their environment. In this paper we summarize an extensive body of work examining the adaptive responses of Fundulus species to environmental conditions, and describe how this research has contributed importantly to our understanding of physiology, gene regulation, toxicology, and ecological and evolutionary genetics of teleosts and other vertebrates. These explorations have reached a critical juncture at which advancement is hindered by the lack of genomic resources for these species. We suggest that a more complete genomics toolbox for F. heteroclitus and related species will permit researchers to exploit the power of this model organism to rapidly advance our understanding of fundamental biological and pathological mechanisms among vertebrates, as well as ecological strategies and evolutionary processes common to all living organisms

Status of Muon Collider Research and Development and Future Plans

The status of the research on muon colliders is discussed and plans are outlined for future theoretical and experimental studies. Besides continued work on the parameters of a 3-4 and 0.5 TeV center-of-mass (CoM) energy collider, many studies are now concentrating on a machine near 0.1 TeV (CoM) that could be a factory for the s-channel production of Higgs particles. We discuss the research on the various components in such muon colliders, starting from the proton accelerator needed to generate pions from a heavy-Z target and proceeding through the phase rotation and decay ($\pi \to \mu \nu_{\mu}$) channel, muon cooling, acceleration, storage in a collider ring and the collider detector. We also present theoretical and experimental R & D plans for the next several years that should lead to a better understanding of the design and feasibility issues for all of the components. This report is an update of the progress on the R & D since the Feasibility Study of Muon Colliders presented at the Snowmass'96 Workshop [R. B. Palmer, A. Sessler and A. Tollestrup, Proceedings of the 1996 DPF/DPB Summer Study on High-Energy Physics (Stanford Linear Accelerator Center, Menlo Park, CA, 1997)].Comment: 95 pages, 75 figures. Submitted to Physical Review Special Topics, Accelerators and Beam