Ideal Linear Chain Polymers with Fixed Angular Momentum

The statistical mechanics of a linear non-interacting polymer chain with a large number of monomers is considered with fixed angular momentum. The radius of gyration for a linear polymer is derived exactly by functional integration. This result is then compared to simulations done with a large number of non-interacting rigid links at fixed angular momentum. The simulation agrees with the theory up to finite size corrections. The simulations are also used to investigate the anisotropic nature of a spinning polymer. We find universal scaling of the polymer size along the direction of the angular momentum, as a function of rescaled angular momentum.Comment: 7 pages, 3 figure

Towards More Precise Photometric Redshifts: Calibration Via CCD Photometry

We present the initial results from a deep, multi-band photometric survey of selected high Galactic latitude redshift fields. Previous work using the photographic data of Koo and Kron demonstrated that the distribution of galaxies in the multi-dimensional flux space U B R I is nearly planar. The position of a galaxy within this plane is determined by its redshift, luminosity and spectral type. Using recently acquired deep CCD photometry in existing, published redshift fields, we have redetermined the distribution of galaxies in this four-dimensional magnitude space. Furthermore, from our CCD photometry and the published redshifts, we have quantified the photometric-redshift relation within the standard AB magnitude system. This empirical relation has a measured dispersion of approximately 0.02 for z < 0.4. With this work we are reaching the asymptotic intrinsic dispersions that were predicted from simulated distributions of galaxy colors.Comment: submitted to the Astrophysical Journal Letter

SECOND INTERNATIONAL SYMPOSIUM ON RANAVIRUSES:: A NORTH AMERICAN HERPETOLOGICAL PERSPECTIVE

Ranaviruses are large double stranded DNA viruses of poikilothermic vertebrates including amphibians, reptiles and fish. In North America, ranaviral disease and ranavirus-related die-off events have been documented in all three classes. Ranaviruses are found worldwide, appear to be emerging in some regions, and are increasingly recognized as a threat to many species

Topology and Organization of the Salmonella typhimurium Type III Secretion Needle Complex Components

The correct organization of single subunits of multi-protein machines in a three dimensional context is critical for their functionality. Type III secretion systems (T3SS) are molecular machines with the capacity to deliver bacterial effector proteins into host cells and are fundamental for the biology of many pathogenic or symbiotic bacteria. A central component of T3SSs is the needle complex, a multiprotein structure that mediates the passage of effector proteins through the bacterial envelope. We have used cryo electron microscopy combined with bacterial genetics, site-specific labeling, mutational analysis, chemical derivatization and high-resolution mass spectrometry to generate an experimentally validated topographic map of a Salmonella typhimurium T3SS needle complex. This study provides insights into the organization of this evolutionary highly conserved nanomachinery and is the basis for further functional analysis

Discovery Of Isoxazole Analogues Of Sazetidine-A As Selective α4β2-Nicotinic Acetylcholine Receptor Partial Agonists For The Treatment Of Depression

Depression, a common neurological condition, is one of the leading causes of disability and suicide worldwide. Standard treatment, targeting monoamine transporters selective for the neurotransmitters serotonin and noradrenaline, is not able to help many patients that are poor responders. This study advances the development of sazetidine-A analogues that interact with α4β2 nicotinic acetylcholine receptors (nAChRs) as partial agonists and that possess favorable antidepressant profiles. The resulting compounds that are highly selective for the α4β2 subtype of nAChR over α3β4-nAChRs are partial agonists at the α4β2 subtype and have excellent antidepressant behavioral profiles as measured by the mouse forced swim test. Preliminary absorption, distribution, metabolism, excretion, and toxicity (ADMET) studies for one promising ligand revealed an excellent plasma protein binding (PPB) profile, low CYP450-related metabolism, and low cardiovascular toxicity, suggesting it is a promising lead as well as a drug candidate to be advanced through the drug discovery pipeline. © 2011 American Chemical Society

Somatic mutations and clonal dynamics in healthy and cirrhotic human liver.

The most common causes of chronic liver disease are excess alcohol intake, viral hepatitis and non-alcoholic fatty liver disease, with the clinical spectrum ranging in severity from hepatic inflammation to cirrhosis, liver failure or hepatocellular carcinoma (HCC). The genome of HCC exhibits diverse mutational signatures, resulting in recurrent mutations across more than 30 cancer genes1-7. Stem cells from normal livers have a low mutational burden and limited diversity of signatures8, which suggests that the complexity of HCC arises during the progression to chronic liver disease and subsequent malignant transformation. Here, by sequencing whole genomes of 482 microdissections of 100-500 hepatocytes from 5 normal and 9 cirrhotic livers, we show that cirrhotic liver has a higher mutational burden than normal liver. Although rare in normal hepatocytes, structural variants, including chromothripsis, were prominent in cirrhosis. Driver mutations, such as point mutations and structural variants, affected 1-5% of clones. Clonal expansions of millimetres in diameter occurred in cirrhosis, with clones sequestered by the bands of fibrosis that surround regenerative nodules. Some mutational signatures were universal and equally active in both non-malignant hepatocytes and HCCs; some were substantially more active in HCCs than chronic liver disease; and others-arising from exogenous exposures-were present in a subset of patients. The activity of exogenous signatures between adjacent cirrhotic nodules varied by up to tenfold within each patient, as a result of clone-specific and microenvironmental forces. Synchronous HCCs exhibited the same mutational signatures as background cirrhotic liver, but with higher burden. Somatic mutations chronicle the exposures, toxicity, regeneration and clonal structure of liver tissue as it progresses from health to disease.This work was supported by a Wellcome Trust and Cancer Research UK (CRUK) Grand Challenge Award (C98/A24032). P.J.C. is a Wellcome Trust Senior Clinical Fellow (WT088340MA); S.F.B. was supported by the Swiss National Science Foundation (P2SKP3-171753 and P400PB-180790); M.A.S. is supported by a Rubicon fellowship from NWO (019.153LW.038); the Cambridge Human Research Tissue Bank is supported by the NIHR Cambridge Biomedical Research Centre; and M.H. is supported by a CRUK Clinician Scientist Fellowship (C52489/A19924)