4,133 research outputs found

    Iterated conditional expectations

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    AbstractConsider the probability space ([0,1),B,λ), where B is the Borel σ-algebra on [0,1) and λ the Lebesgue measure. Let f=1[0,1/2) and g=1[1/2,1). Then for any ε>0 there exists a finite sequence of sub-σ-algebras Gj⊂B (j=1,…,N), such that putting f0=f and fj=E(fj−1|Gj), j=1,…,N, we have ‖fN−g‖∞<ε; here E(⋅|Gj) denotes the operator of conditional expectation given σ-algebra Gj. This is a particular case of a surprising result by Cherny and Grigoriev (2007) [1] in which f and g are arbitrary equidistributed bounded random variables on a nonatomic probability space. The proof given in Cherny and Grigoriev (2007) [1] is very complicated. The purpose of this note is to give a straightforward analytic proof of the above mentioned result, motivated by a simple geometric idea, and then show that the general result is implied by its special case

    A Human BRCA2 Complex Containing a Structural DNA Binding Component Influences Cell Cycle Progression

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    AbstractGermline mutations of the human BRCA2 gene confer susceptibility to breast cancer. Although the function of the BRCA2 protein remains to be determined, murine cells homozygous for BRCA2 inactivation display chromosomal aberrations. We have isolated a 2 MDa BRCA2-containing complex and identified a structural DNA binding component, designated as BR CA2-A ssociated F actor 35 (BRAF35). BRAF35 contains a nonspecific DNA binding HMG domain and a kinesin-like coiled coil domain. Similar to BRCA2, BRAF35 mRNA expression levels in mouse embryos are highest in proliferating tissues with high mitotic index. Strikingly, nuclear staining revealed a close association of BRAF35/BRCA2 complex with condensed chromatin coincident with histone H3 phosphorylation. Importantly, antibody microinjection experiments suggest a role for BRCA2/BRAF35 complex in modulation of cell cycle progression

    Rossby wave dynamics of the North Pacific extra-tropical response to El Niño: importance of the basic state in coupled GCMs

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    The extra-tropical response to El Nino in a "low" horizontal resolution coupled climate model, typical of the Intergovernmental Panel on Climate Change fourth assessment report simulations, is shown to have serious systematic errors. A high resolution configuration of the same model has a much improved response that is similar to observations. The errors in the low resolution model are traced to an incorrect representation of the atmospheric teleconnection mechanism that controls the extra-tropical sea surface temperatures (SSTs) during El Nino. This is due to an unrealistic atmospheric mean state, which changes the propagation characteristics of Rossby waves. These erroneous upper tropospheric circulation anomalies then induce erroneous surface circulation features over the North Pacific. The associated surface wind speed and direction errors create erroneous surface flux and upwelling anomalies which finally lead to the incorrect extra-tropical SST response to El Nino in the low resolution model. This highlights the sensitivity of the climate response to a single link in a chain of complex climatic processes. The correct representation of these processes in the high resolution model indicates the importance of horizontal resolution in resolving such processes

    Locked and Unlocked Chains of Planar Shapes

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    We extend linkage unfolding results from the well-studied case of polygonal linkages to the more general case of linkages of polygons. More precisely, we consider chains of nonoverlapping rigid planar shapes (Jordan regions) that are hinged together sequentially at rotatable joints. Our goal is to characterize the families of planar shapes that admit locked chains, where some configurations cannot be reached by continuous reconfiguration without self-intersection, and which families of planar shapes guarantee universal foldability, where every chain is guaranteed to have a connected configuration space. Previously, only obtuse triangles were known to admit locked shapes, and only line segments were known to guarantee universal foldability. We show that a surprisingly general family of planar shapes, called slender adornments, guarantees universal foldability: roughly, the distance from each edge along the path along the boundary of the slender adornment to each hinge should be monotone. In contrast, we show that isosceles triangles with any desired apex angle less than 90 degrees admit locked chains, which is precisely the threshold beyond which the inward-normal property no longer holds.Comment: 23 pages, 25 figures, Latex; full journal version with all proof details. (Fixed crash-induced bugs in the abstract.

    Combinations of β-lactam or aminoglycoside antibiotics with plectasin are synergistic against methicillin-sensitive and methicillin-resistant Staphylococcus aureus.

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    Bacterial infections remain the leading killer worldwide which is worsened by the continuous emergence of antibiotic resistance. In particular, methicillin-sensitive (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) are prevalent and the latter can be difficult to treat. The traditional strategy of novel therapeutic drug development inevitably leads to emergence of resistant strains, rendering the new drugs ineffective. Therefore, rejuvenating the therapeutic potentials of existing antibiotics offers an attractive novel strategy. Plectasin, a defensin antimicrobial peptide, potentiates the activities of other antibiotics such as β-lactams, aminoglycosides and glycopeptides against MSSA and MRSA. We performed in vitro and in vivo investigations to test against genetically diverse clinical isolates of MSSA (n = 101) and MRSA (n = 115). Minimum inhibitory concentrations (MIC) were determined by the broth microdilution method. The effects of combining plectasin with β-lactams, aminoglycosides and glycopeptides were examined using the chequerboard method and time kill curves. A murine neutropenic thigh model and a murine peritoneal infection model were used to test the effect of combination in vivo. Determined by factional inhibitory concentration index (FICI), plectasin in combination with aminoglycosides (gentamicin, neomycin or amikacin) displayed synergistic effects in 76-78% of MSSA and MRSA. A similar synergistic response was observed when plectasin was combined with β-lactams (penicillin, amoxicillin or flucloxacillin) in 87-89% of MSSA and MRSA. Interestingly, no such interaction was observed when plectasin was paired with vancomycin. Time kill analysis also demonstrated significant synergistic activities when plectasin was combined with amoxicillin, gentamicin or neomycin. In the murine models, plectasin at doses as low as 8 mg/kg augmented the activities of amoxicillin and gentamicin in successful treatment of MSSA and MRSA infections. We demonstrated that plectasin strongly rejuvenates the therapeutic potencies of existing antibiotics in vitro and in vivo. This is a novel strategy that can have major clinical implications in our fight against bacterial infections

    2013 Update in addiction medicine for the generalist.

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    Increasingly, patients with unhealthy alcohol and other drug use are being seen in primary care and other non-specialty addiction settings. Primary care providers are well positioned to screen, assess, and treat patients with alcohol and other drug use because this use, and substance use disorders, may contribute to a host of medical and mental health harms. We sought to identify and examine important recent advances in addiction medicine in the medical literature that have implications for the care of patients in primary care or other generalist settings. To accomplish this aim, we selected articles in the field of addiction medicine, critically appraised and summarized the manuscripts, and highlighted their implications for generalist practice. During an initial review, we identified articles through an electronic Medline search (limited to human studies and in English) using search terms for alcohol and other drugs of abuse published from January 2010 to January 2012. After this initial review, we searched for other literature in web-based or journal resources for potential articles of interest. From the list of articles identified in these initial reviews, each of the six authors independently selected articles for more intensive review and identified the ones they found to have a potential impact on generalist practice. The identified articles were then ranked by the number of authors who selected each article. Through a consensus process over 4 meetings, the authors reached agreement on the articles with implications for practice for generalist clinicians that warranted inclusion for discussion. The authors then grouped the articles into five categories: 1) screening and brief interventions in outpatient settings, 2) identification and management of substance use among inpatients, 3) medical complications of substance use, 4) use of pharmacotherapy for addiction treatment in primary care and its complications, and 5) integration of addiction treatment and medical care. The authors discuss each selected articles' merits, limitations, conclusions, and implication to advancing addiction screening, assessment, and treatment of addiction in generalist physician practice environments

    Charmless Hadronic Two-Body B Meson Decays

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    We report the results of a study of two-body B meson decays to the complete set of K pi, pi pi, and K K final states. The study is performed on a data sample of 31.7 +/- 0.3 million B B-bar events recorded on the Upsilon(4S) resonance by the Belle experiment at KEKB. We observe significant signals in all K pi final states and in the pi+ pi- and pi+ pi0 final states. We set limits on the pi0 pi0 and K K final states. A search is performed for partial-rate asymmetries between conjugate states for flavor-specific final states.Comment: Submitted to PR

    Improved annotation of 3' untranslated regions and complex loci by combination of strand-specific direct RNA sequencing, RNA-seq and ESTs

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    The reference annotations made for a genome sequence provide the framework for all subsequent analyses of the genome. Correct annotation is particularly important when interpreting the results of RNA-seq experiments where short sequence reads are mapped against the genome and assigned to genes according to the annotation. Inconsistencies in annotations between the reference and the experimental system can lead to incorrect interpretation of the effect on RNA expression of an experimental treatment or mutation in the system under study. Until recently, the genome-wide annotation of 3-prime untranslated regions received less attention than coding regions and the delineation of intron/exon boundaries. In this paper, data produced for samples in Human, Chicken and A. thaliana by the novel single-molecule, strand-specific, Direct RNA Sequencing technology from Helicos Biosciences which locates 3-prime polyadenylation sites to within +/- 2 nt, were combined with archival EST and RNA-Seq data. Nine examples are illustrated where this combination of data allowed: (1) gene and 3-prime UTR re-annotation (including extension of one 3-prime UTR by 5.9 kb); (2) disentangling of gene expression in complex regions; (3) clearer interpretation of small RNA expression and (4) identification of novel genes. While the specific examples displayed here may become obsolete as genome sequences and their annotations are refined, the principles laid out in this paper will be of general use both to those annotating genomes and those seeking to interpret existing publically available annotations in the context of their own experimental dataComment: 44 pages, 9 figure

    Determination of |Vcb| using the semileptonic decay \bar{B}^0 --> D^{*+}e^-\bar{\nu}

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    We present a measurement of the Cabibbo-Kobayashi-Maskawa (CKM) matrix element |Vcb| using a 10.2 fb^{-1} data sample recorded at the \Upsilon(4S) resonance with the Belle detector at the KEKB asymmetric e^+e^- storage ring. By extrapolating the differential decay width of the \bar{B}^0 --> D^{*+}e^-\bar{\nu} decay to the kinematic limit at which the D^{*+} is at rest with respect to the \bar{B}^0, we extract the product of |Vcb| with the normalization of the decay form factor F(1), |Vcb |F(1)= (3.54+/-0.19+/-0.18)x10^{-2}, where the first error is statistical and the second is systematic. A value of |Vcb| = (3.88+/-0.21+/-0.20+/-0.19)x10^{-2} is obtained using a theoretical calculation of F(1), where the third error is due to the theoretical uncertainty in the value of F(1). The branching fraction B(\bar{B}^0 --> D^{*+}e^-\bar{\nu}) is measured to be (4.59+/-0.23+/-0.40)x10^{-2}.Comment: 20 pages, 6 figures, elsart.cls, submitted to PL

    The Radio - X-ray relation as a star formation indicator: Results from the VLA--E-CDFS Survey

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    In order to trace the instantaneous star formation rate at high redshift, and hence help understanding the relation between the different emission mechanisms related to star formation, we combine the recent 4 Ms Chandra X-ray data and the deep VLA radio data in the Extended Chandra Deep Field South region. We find 268 sources detected both in the X-ray and radio band. The availability of redshifts for 95\sim 95 of the sources in our sample allows us to derive reliable luminosity estimates and the intrinsic properties from X-ray analysis for the majority of the objects. With the aim of selecting sources powered by star formation in both bands, we adopt classification criteria based on X-ray and radio data, exploiting the X-ray spectral features and time variability, taking advantage of observations scattered across more than ten years. We identify 43 objects consistent with being powered by star formation. We also add another 111 and 70 star forming candidates detected only in the radio or X-ray band, respectively. We find a clear linear correlation between radio and X-ray luminosity in star forming galaxies over three orders of magnitude and up to z1.5z \sim 1.5. We also measure a significant scatter of the order of 0.4 dex, higher than that observed at low redshift, implying an intrinsic scatter component. The correlation is consistent with that measured locally, and no evolution with redshift is observed. Using a locally calibrated relation between the SFR and the radio luminosity, we investigate the L_X(2-10keV)-SFR relation at high redshift. The comparison of the star formation rate measured in our sample with some theoretical models for the Milky Way and M31, two typical spiral galaxies, indicates that, with current data, we can trace typical spirals only at z<0.2, and strong starburst galaxies with star-formation rates as high as 100Myr1\sim 100 M_\odot yr^{-1}, up to z1.5z\sim 1.5.Comment: 21 pages, 10 figures, 5 table
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