The rockefeller university

An updated measurement of the single top quark production cross section is presented using the full data set collected by the Collider Detector at Fermilab (CDF), corresponding to 9.5 fb(-1) of integrated luminosity from proton-antiproton collisions at 1.96 TeV center-of-mass energy. The events selected contain an imbalance in the total transverse momentum, jets identified as containing b quarks, and no identified leptons. The sum of the s- and t-channel single top quark cross sections is measured to be 3.53(-1.16)(+1.25) pb and a lower limit on the magnitude of the top-to-bottom quark coupling, vertical bar V-tb vertical bar of 0.63, is obtained at the 95% credibility level. These measurements are combined with previously reported CDF results obtained from events with an imbalance in total transverse momentum, jets identified as originating from b quarks, and one identified lepton. The combined cross section is measured to be 3.02(-0.48)(+0.49) pb and a lower limit on vertical bar V-tb vertical bar of 0.84 is obtained at the 95% credibility level.

VRC01-class broadly neutralizing HIV-1 antibodies protect animals from experimental infection and could contribute to an effective vaccine response. Their predicted germline forms (gl) bind Env inefficiently, which may explain why they are not elicited by HIV-1 Env-immunization. Here we show that an optimized Env immunogen can engage multiple glVRC01-class antibodies. Furthermore, this immunogen activates naive B cells expressing the human germline heavy chain of 3BNC60, paired with endogenous mouse light chains in vivo. To address whether it activates B cells expressing the fully humanized gl3BNC60 B-cell receptor (BCR), we immunized mice carrying both the heavy and light chains of gl3BNC60. B cells expressing this BCR display an autoreactive phenotype and fail to respond efficiently to soluble forms of the optimized immunogen, unless it is highly multimerized. Thus, specifically designed Env immunogens can activate naive B cells expressing human BCRs corresponding to precursors of broadly neutralizing HIV-1 antibodies even when the B cells display an autoreactive phenotype.

A search for pair production of first and second generation leptoquarks is performed in final states containing either two charged leptons and two jets, or one charged lepton, one neutrino and two jets, using proton-proton collision data at root s = 8 TeV. The data, corresponding to an integrated luminosity of 19.7 fb(-1), were recorded with the CMS detector at the LHC. First-generation scalar leptoquarks with masses less than 1010 (850) GeV are excluded for beta = 1.0 (0.5), where beta is the branching fraction of a leptoquark decaying to a charged lepton and a quark. Similarly, second-generation scalar leptoquarks with masses less than 1080 (760) GeV are excluded for beta = 1.0 (0.5). Mass limits are also set for vector leptoquark production scenarios with anomalous vector couplings, and for R-parity violating supersymmetric scenarios of top squark pair production resulting in similar final-state signatures. These are the most stringent limits placed on the masses of vector leptoquarks and RPV top squarks to date.

We investigate the motion of a single particle moving on a two-dimensional square lattice whose sites are occupied by right and left rotators. These left and right rotators deterministically rotate the particle's velocity to the right or left, respectively and flip orientation from right to left or from left to right after scattering the particle. We study three types of configurations of left and right rotators, which we think of as types ofmedia, through with the particle moves. These are completely random (CR), random periodic (RP), and completely periodic (CP) configurations. For CR configurations the particle's dynamics depends on the ratio r of right to left scatterers in the following way. For small r similar or equal to 0, when the configuration is nearly homogeneous, the particle subdiffuses with an exponent of 2/3, similar to the diffusion of a macromolecule in a crowded environment. Also, the particle's trajectory has a fractal dimension of d(f) similar or equal to 4/3, comparable to that of a self-avoiding walk. As the ratio increases to r similar or equal to 1, the particle's dynamics transitions from subdiffusion to anomalous diffusion with a fractal dimension of d(f) similar or equal to 7/4, similar to that of a percolating cluster in 2-d. In RP configurations, which are more structured than CR configurations but also randomly generated, we find that the particle has the same statistic as in the CR case. In contrast, CP configurations, which are highly structured, typically will cause the particle to go through a transient stage of subdiffusion, which then abruptly changes to propagation. Interestingly, the subdiffusive stage has an exponent of approximately 2/3 and a fractal dimension of d(f) similar or equal to 4/3, similar to the case of CR and RP configurations for small r.

B-cell lymphoma 10 (BCL10) is not essential for actin polymerisation after Fc gamma R stimulation in human fibroblasts. (C) 2016 Elsevier Inc. All rights reserved.

Adult organisms rely on tissue stem cells for maintenance and repair. During homeostasis, the concerted action of local niche signals and epigenetic regulators establish stable gene expression patterns to ensure that stem cells are not lost over time. However, stem cells also provide host tissues with a remarkable plasticity to respond to perturbations. How adult stem cells choose and acquire new fates is unknown, but the genome-wide mapping of epigenetic landscapes suggests a critical role for chromatin remodeling in these processes. Here, we explore the emerging role of chromatin modifiers and pioneer transcription factors in adult stem cell fate decisions and plasticity, which ensure that selective lineage choices are only made when environmentally cued.

Metformin, a drug prescribed to treat type-2 diabetes, exhibits anti-cancer effects in a portion of patients, but the direct molecular and genetic interactions leading to this pleiotropic effect have not yet been fully explored. To repurpose metformin as a precision anti-cancer therapy, we have developed a novel structural systems pharmacology approach to elucidate metformin's molecular basis and genetic biomarkers of action. We integrated structural proteome-scale drug target identification with network biology analysis by combining structural genomic, functional genomic, and interactomic data. Through searching the human structural proteome, we identified twenty putative metformin binding targets and their interaction models. We experimentally verified the interactions between metformin and our topranked kinase targets. Notably, kinases, particularly SGK1 and EGFR were identified as key molecular targets of metformin. Subsequently, we linked these putative binding targets to genes that do not directly bind to metformin but whose expressions are altered by metformin through protein-protein interactions, and identified network biomarkers of phenotypic response of metformin. The molecular targets and the key nodes in genetic networks are largely consistent with the existing experimental evidence. Their interactions can be affected by the observed cancer mutations. This study will shed new light into repurposing metformin for safe, effective, personalized therapies.

Tornadoes cause loss of life and damage to property each year in the United States and around the world. The largest impacts come from 'outbreaks' consisting of multiple tornadoes closely spaced in time. Here we find an upward trend in the annual mean number of tornadoes per US tornado outbreak for the period 1954-2014. Moreover, the variance of this quantity is increasing more than four times as fast as the mean. The mean and variance of the number of tornadoes per outbreak vary according to Taylor's power law of fluctuation scaling (TL), with parameters that are consistent with multiplicative growth. Tornado-related atmospheric proxies show similar power-law scaling and multiplicative growth. Path-length-integrated tornado outbreak intensity also follows TL, but with parameters consistent with sampling variability. The observed TL power-law scaling of outbreak severity means that extreme outbreaks are more frequent than would be expected if mean and variance were independent or linearly related.

Type III-A CRISPR-Cas systems defend prokaryotes against viral infection using CRISPR RNA (crRNA)-guided nucleases that perform co-transcriptional cleavage of the viral target DNA and its transcripts. Whereas DNA cleavage is essential for immunity, the function of RNA targeting is unknown. Here, we show that transcription-dependent targeting results in a sharp increase of viral genomes in the host cell when the target is located in a late-expressed phage gene. In this targeting condition, mutations in the active sites of the type III-A RNases Csm3 and Csm6 lead to the accumulation of the target phage mRNA and abrogate immunity. Csm6 is also required to provide defense in the presence of mutated phage targets, when DNA cleavage efficiency is reduced. Our results show that the degradation of phage transcripts by CRISPR-associated RNases ensures robust immunity in situations that lead to a slow clearance of the target DNA.