71 research outputs found

    The third way to 3D gravity

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    Consistency of Einstein’s gravitational field equation [Formula: see text] imposes a “conservation condition” on the [Formula: see text]-tensor that is satisfied by (i) matter stress tensors, as a consequence of the matter equations of motion and (ii) identically by certain other tensors, such as the metric tensor. However, there is a third way, overlooked until now because it implies a “nongeometrical” action: one not constructed from the metric and its derivatives alone. The new possibility is exemplified by the 3D “minimal massive gravity” model, which resolves the “bulk versus boundary” unitarity problem of topologically massive gravity with Anti-de Sitter asymptotics. Although all known examples of the third way are in three spacetime dimensions, the idea is general and could, in principle, apply to higher dimensional theories. AJR is supported by a grant from the London Mathematical Society, and he would also like to thank the University of Groningen for hospitality during the writing of this essay.This is the author accepted manuscript. The final version is available from World Scientific via http://dx.doi.org/10.1142/S021827181544015

    Surgical management of vesicoureteral reflux in children

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    Vesicoureteral reflux (VUR) is the most common uropathy affecting children. Compared to children without VUR, those with VUR have a higher rate of pyelonephritis and renal scarring following urinary tract infection (UTI). Options for treatment include observation with or without antibiotic prophylaxis and surgical repair. Surgical intervention may be necessary in patients with persistent reflux, renal scarring, and recurrent or breakthrough febrile UTI. Both open and endoscopic approaches to reflux correction are successful and reduce the occurrence of febrile UTI. Estimated success rates of open and endoscopic reflux correction are 98.1% (95% CI 95.1, 99.1) and 83.0% (95% CI 69.1, 91.4), respectively. Factors that affect the success of endoscopic injection include pre-operative reflux grade and presence of functional or anatomic bladder abnormalities including voiding dysfunction and duplicated collecting systems. Few studies have evaluated the long-term outcomes of endoscopic injection, and with variable results. In patients treated endoscopically, recurrent febrile UTI occurred in 0–21%, new renal damage in 9–12%, and recurrent reflux in 17–47.6% of treated ureters with at least 1 year follow-up. These studies highlight the need for standardized outcome reporting and longer follow-up after endoscopic treatment

    Atomic Resolution Cryo-EM Structure Of A Nativelike CENP-A Nucleosome Aided By An Antibody Fragment

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    Genomic DNA in eukaryotes is organized into chromatin through association with core histones to form nucleosomes, each distinguished by their DNA sequences and histone variants. Here, we used a single-chain antibody fragment (scFv) derived from the anti-nucleosome antibody mAb PL2-6 to stabilize human CENP-A nucleosome containing a native α-satellite DNA and solved its structure by the cryo-electron microscopy (cryo-EM) to 2.6 Å resolution. In comparison, the corresponding cryo-EM structure of the free CENP-A nucleosome could only reach 3.4 Å resolution. We find that scFv binds to a conserved acidic patch on the histone H2A-H2B dimer without perturbing the nucleosome structure. Our results provide an atomic resolution cryo-EM structure of a nucleosome and insight into the structure and function of the CENP-A nucleosome. The scFv approach is applicable to the structural determination of other native-like nucleosomes with distinct DNA sequences

    LEDGF/p75 Proteins with Alternative Chromatin Tethers Are Functional HIV-1 Cofactors

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    LEDGF/p75 can tether over-expressed lentiviral integrase proteins to chromatin but how this underlies its integration cofactor role for these retroviruses is unclear. While a single integrase binding domain (IBD) binds integrase, a complex N-terminal domain ensemble (NDE) interacts with unknown chromatin ligands. Whether integration requires chromatin tethering per se, specific NDE-chromatin ligand interactions or other emergent properties of LEDGF/p75 has been elusive. Here we replaced the NDE with strongly divergent chromatin-binding modules. The chimeras rescued integrase tethering and HIV-1 integration in LEDGF/p75-deficient cells. Furthermore, chromatin ligands could reside inside or outside the nucleosome core, and could be protein or DNA. Remarkably, a short Kaposi's sarcoma virus peptide that binds the histone 2A/B dimer converted GFP-IBD from an integration blocker to an integration cofactor that rescues over two logs of infectivity. NDE mutants were corroborative. Chromatin tethering per se is a basic HIV-1 requirement and this rather than engagement of particular chromatin ligands is important for the LEDGF/p75 cofactor mechanism

    Histone H1 Subtypes Differentially Modulate Chromatin Condensation without Preventing ATP-Dependent Remodeling by SWI/SNF or NURF

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    Although ubiquitously present in chromatin, the function of the linker histone subtypes is partly unknown and contradictory studies on their properties have been published. To explore whether the various H1 subtypes have a differential role in the organization and dynamics of chromatin we have incorporated all of the somatic human H1 subtypes into minichromosomes and compared their influence on nucleosome spacing, chromatin compaction and ATP-dependent remodeling. H1 subtypes exhibit different affinities for chromatin and different abilities to promote chromatin condensation, as studied with the Atomic Force Microscope. According to this criterion, H1 subtypes can be classified as weak condensers (H1.1 and H1.2), intermediate condensers (H1.3) and strong condensers (H1.0, H1.4, H1.5 and H1x). The variable C-terminal domain is required for nucleosome spacing by H1.4 and is likely responsible for the chromatin condensation properties of the various subtypes, as shown using chimeras between H1.4 and H1.2. In contrast to previous reports with isolated nucleosomes or linear nucleosomal arrays, linker histones at a ratio of one per nucleosome do not preclude remodeling of minichromosomes by yeast SWI/SNF or Drosophila NURF. We hypothesize that the linker histone subtypes are differential organizers of chromatin, rather than general repressors

    Mode of socio-economic development and occupational structure: the case of contemporary Russia

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    The given paper assumes the existence of a correlation between the occupational structure and the mode of social and economic development of a country. It is shown that the modern stage of development in advanced economies could be described by the post-industrial phase with (a) the specific proportions in the occupational structure (predominance of professional managers and technical experts); (b) particular nature of work and the corresponding extent of labor division according to specialization and qualification (highly skilled labor with broad specialization and a new criterion of creativity included within qualifications). Within the certain historical framework these indicators, combined onto the entire scheme, produce the criteria to distinct different types of socio-economic development and arrange them in consistent order. The analysis of occupational structure of Russian population shows that the reforms of 1990s have facilitated the process of deindustrialization alongside with the growth of semi- and low-skilled jobs. According to the scheme, Russia seems to have reached the stage of the development that is similar to one of the 1950–1960s in the USA and the Europe
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