The rockefeller university

A measurement of the J/psi and psi(2S) production cross sections in pp collisions at root s = 7 TeV with the CMS experiment at the LHC is presented. The data sample corresponds to an integrated luminosity of 37 pb(-1). Using a fit to the invariant mass and decay length distributions, production cross sections have been measured separately for prompt and non-prompt charmonium states, as a function of the meson transverse momentum in several rapidity ranges and integrated in the kinematical regions considered in this study. In addition, cross sections restricted to the acceptance of the CMS detector are given, which are not affected by the polarization of the charmonium states. The ratio of the differential production cross sections of the two states, where systematic uncertainties largely cancel, is also determined. The branching fraction of the inclusive B -> psi(2S)X decay is extracted from the ratio of the non-prompt cross sections to be: beta(B -> psi(2S)X) = (3.08 +/- 0.12 (stat.+ syst.) +/- 0.13 (theor.) +/- 0.42 (beta(PDG))) x 10(-3)

Na+/K+ pumps move net charge through the cell membrane by mediating unequal exchange of intracellular Na+ and extracellular K+. Most charge moves during transitions that release Na+ to the cell exterior. When pumps are constrained to bind and release only Na+, a membrane voltage-step redistributes pumps among conformations with zero, one, two or three bound Na+, thereby transiently generating current. By applying rapid voltage steps to squid giant axons, we previously identified three components in such transient currents, with distinct relaxation speeds: fast (which nearly parallels the voltage-jump time course), medium speed (tau(m) = 0.2-0.5 ms) and slow (tau(s) = 1-10 ms). Here we show that these three components are tightly correlated, both in their magnitudes and in the time courses of their changes. The correlations reveal the dynamics of the conformational rearrangements that release three Na+ to the exterior (or sequester them into their binding sites) one at a time, in an obligatorily sequential manner.

Bacteria are constantly challenged by bacteriophages (viruses that infect bacteria), the most abundant microorganism on earth. Bacteria have evolved a variety of immunity mechanisms to resist bacteriophage infection. In response, bacteriophages can evolve counter-resistance mechanisms and launch a 'virus versus host' evolutionary arms race. In this context, rapid evolution is fundamental for the survival of the bacterial cell. Programmed genetic variation mechanisms at loci involved in immunity against bacteriophages generate diversity at a much faster rate than random point mutation and enable bacteria to quickly adapt and repel infection. Diversity-generating retroelements (DGRs) and phase variation mechanisms enhance the generic (innate) immune response against bacteriophages. On the other hand, the integration of small bacteriophage sequences in CRISPR loci provide bacteria with a virus-specific and sequence-specific adaptive immune response. Therefore, although using different molecular mechanisms, both prokaryotes and higher organisms rely on programmed genetic variation to increase genetic diversity and fight rapidly evolving infectious agents.

The ear detects sounds so faint that they produce only atomic-scale displacements in the mechanoelectrical transducer, yet thermal noise causes fluctuations larger by an order of magnitude. Explaining how hearing can operate when the magnitude of the noise greatly exceeds that of the signal requires an understanding both of the transducer's micromechanics and of the associated noise. Using microrheology, we characterize the statistics of this noise; exploiting the fluctuation-dissipation theorem, we determine the associated micromechanics. The statistics reveal unusual Brownian motion in which the mean square displacement increases as a fractional power of time, indicating that the mechanisms governing energy dissipation are related to those of energy storage. This anomalous scaling contradicts the canonical model of mechanoelectrical transduction, but the results can be explained if the micromechanics incorporates viscoelasticity, a salient characteristic of biopolymers. We amend the canonical model and demonstrate several consequences of viscoelasticity for sensory coding.

We present a search for neutral Higgs bosons phi decaying into b (b) over bar, produced in association with b quarks in p (p) over bar collisions. This process could be observable in supersymmetric models with high values of tan beta. The event sample corresponds to 2.6 fb(-1) of integrated luminosity collected with the CDF II detector at the Fermilab Tevatron collider. We search for an enhancement in the mass of the two leading jets in events with three jets identified as coming from b quarks using a displaced vertex algorithm. A data-driven procedure is used to estimate the dijet mass spectrum of the nonresonant multijet background. The contributions of backgrounds and a possible Higgs boson signal are determined by a two-dimensional fit of the data, using the dijet mass together with an additional variable which is sensitive to the flavor composition of the three tagged jets. We set mass-dependent limits on sigma(p (p) over bar -> phi b) x B(phi -> b (b) over bar) which are applicable for a narrow scalar particle phi produced in association with b quarks. We also set limits on tan beta in supersymmetric Higgs models including the effects of the Higgs boson width.

Macromolecular assemblies can be intrinsically refractive to classical structural analysis, due to their size, complexity, plasticity and dynamic nature. One such assembly is the nuclear pore complex (NPC). The NPC is formed from similar to 450 copies of 30 different proteins, called nucleoporins, and is the sole mediator of exchange between the nucleus and the cytoplasm in eukaryotic cells. Despite significant progress, it has become increasingly clear that new approaches, integrating different sources of structural and functional data, will be needed to understand the functional biology of the NPC. Here, we discuss the latest approaches trying to address this challenge.

Hair cells in the auditory, vestibular, and lateral-line systems of vertebrates receive inputs through a remarkable variety of accessory structures that impose complex mechanical loads on the mechanoreceptive hair bundles. Although the physiological and morphological properties of the hair bundles in each organ are specialized for detecting the relevant inputs, we propose that the mechanical load on the bundles also adjusts their responsiveness to external signals. We use a parsimonious description of active hair-bundle motility to show how the mechanical environment can regulate a bundle's innate behavior and response to input. We find that an unloaded hair bundle can behave very differently from one subjected to a mechanical load. Depending on how it is loaded, a hair bundle can function as a switch, active oscillator, quiescent resonator, or low-pass filter. Moreover, a bundle displays a sharply tuned, nonlinear, and sensitive response for some loading conditions and an untuned or weakly tuned, linear, and insensitive response under other circumstances. Our simple characterization of active hair-bundle motility explains qualitatively most of the observed features of bundle motion from different organs and organisms. The predictions stemming from this description provide insight into the operation of hair bundles in a variety of contexts.

Current vaccines primarily work by inducing protective antibodies. However, in many infections like HIV, malaria and tuberculosis as well as cancers, there remains a need for durable and protective T-cell immunity. Here, we summarize our efforts to develop a safe T-cell-based protein vaccine that exploits the pivotal role of dendritic cells (DC) in initiating adaptive immunity. Focusing on HIV, gag-p24 protein antigen is introduced into a monoclonal antibody (mAb) that efficiently and specifically targets the DEC-205 antigen uptake receptor on DC. When administered together with synthetic double-stranded RNA, polyriboinosinic: polyribocytidylic acid (poly IC) or its analogue poly IC stabilized with carboxymethylcellulose and poly-L-lysine (poly ICLC), as adjuvant, HIV gag-p24 within anti-DEC-205 mAb is highly immunogenic in mice, rhesus macaques, and in ongoing research, healthy human volunteers. Human subjects form both T- and B-cell responses to DC-targeted protein. Thus, DC-targeted protein vaccines are a potential new vaccine platform, either alone or in combination with highly attenuated viral vectors, to induce integrated immune responses against microbial or cancer antigens, with improved ease of manufacturing and clinical use.

Polycomb repressive complexes (PRCs) play key roles in developmental epigenetic regulation. Yet the mechanisms that target PRCs to specific loci in mammalian cells remain incompletely understood. In this study we show that Bmi1, a core component of Polycomb Repressive Complex 1 (PRC1), binds directly to the Runx1/CBF beta transcription factor complex. Genome-wide studies in megakaryocytic cells demonstrate significant chromatin occupancy overlap between the PRC1 core component Ring1b and Runx1/CBF beta and functional regulation of a considerable fraction of commonly bound genes. Bmi1/Ring1b and Runx1/CBF beta deficiencies generate partial phenocopies of one another in vivo. We also show that Ring1b occupies key Runx1 binding sites in primary murine thymocytes and that this occurs via PRC2-independent mechanisms. Genetic depletion of Runx1 results in reduced Ring1b binding at these sites in vivo. These findings provide evidence for site-specific PRC1 chromatin recruitment by core binding transcription factors in mammalian cells.