Intermediate-Mass Black Holes in Globular Clusters

There have been reports of possible detections of intermediate-mass black holes (IMBHs) in globular clusters (GCs). Empirically, there exists a tight correlation between the central supermassive black hole (SMBH) mass and the mean velocity dispersion of elliptical galaxies, "pseudobulges" and classical bulges of spiral galaxies. We explore such a possible correlation for IMBHs in spherical GCs. In our model of self-similar general polytropic quasi-static dynamic evolution of GCs, a criterion of forming an IMBH is proposed. The key result is M(BH) = L o^1/(1-n) where M(BH) is the IMBH mass, o is the GC mean stellar velocity, L is a coefficient, and 2/3 < n < 1

On Cyclic Edge-Connectivity of Fullerenes

A graph is said to be cyclic $k$-edge-connected, if at least $k$ edges must be removed to disconnect it into two components, each containing a cycle. Such a set of $k$ edges is called a cyclic-$k$-edge cutset and it is called a trivial cyclic-$k$-edge cutset if at least one of the resulting two components induces a single $k$-cycle. It is known that fullerenes, that is, 3-connected cubic planar graphs all of whose faces are pentagons and hexagons, are cyclic 5-edge-connected. In this article it is shown that a fullerene $F$ containing a nontrivial cyclic-5-edge cutset admits two antipodal pentacaps, that is, two antipodal pentagonal faces whose neighboring faces are also pentagonal. Moreover, it is shown that $F$ has a Hamilton cycle, and as a consequence at least $15\cdot 2^{\lfloor \frac{n}{20}\rfloor}$ perfect matchings, where $n$ is the order of $F$.Comment: 11 pages, 9 figure

MicroRNA regulation of endothelial homeostasis and commitment—implications for vascular regeneration strategies using stem cell therapies

Human embryonic (hESC) and induced pluripotent (hiPSC) stem cells have broad therapeutic potential in the treatment of a range of diseases, including those of the vascular system. Both hESCs and hiPSCs have the capacity for indefinite self-renewal, in addition to their ability to differentiate into any adult cell type. These cells could provide a potentially unlimited source of cells for transplantation and, therefore, provide novel treatments, e.g. in the production of endothelial cells for vascular regeneration. MicroRNAs are short, noncoding RNAs that act posttranscriptionally to control gene expression and thereby exert influence over a wide range of cellular processes, including maintenance of pluripotency and differentiation. Expression patterns of these small RNAs are tissue specific, and changes in microRNA levels have often been associated with disease states in humans, including vascular pathologies. Here, we review the roles of microRNAs in endothelial cell function and vascular disease, as well as their role in the differentiation of pluripotent stem cells to the vascular endothelial lineage. Furthermore, we discuss the therapeutic potential of stem cells and how knowledge and manipulation of microRNAs in stem cells may enhance their capacity for vascular regeneration

Impact of Vitamin D Supplementation on Arterial Vasomotion, Stiffness and Endothelial Biomarkers in Chronic Kidney Disease Patients

Background: Cardiovascular events are frequent and vascular endothelial function is abnormal in patients with chronic kidney disease (CKD). We demonstrated endothelial dysfunction with vitamin D deficiency in CKD patients; however the impact of cholecalciferol supplementation on vascular stiffness and vasomotor function, endothelial and bone biomarkers in CKD patients with low 25-hydroxy vitamin D [25(OH)D] is unknown, which this study investigated. Methods: We assessed non-diabetic patients with CKD stage 3/4, age 17–80 years and serum 25(OH)D ,75 nmol/L. Brachial artery Flow Mediated Dilation (FMD), Pulse Wave Velocity (PWV), Augmentation Index (AI) and circulating blood biomarkers were evaluated at baseline and at 16 weeks. Oral 300,000 units cholecalciferol was administered at baseline and 8-weeks. Results: Clinical characteristics of 26 patients were: age 50614 (mean61SD) years, eGFR 41611 ml/min/1.73 m2, males 73%, dyslipidaemia 36%, smokers 23% and hypertensives 87%. At 16-week serum 25(OH)D and calcium increased (43616 to 84629 nmol/L, p,0.001 and 2.3760.09 to 2.4260.09 mmol/L; p = 0.004, respectively) and parathyroid hormone decreased (10.868.6 to 7.464.4; p = 0.001). FMD improved from 3.163.3% to 6.163.7%, p = 0.001. Endothelial biomarker concentrations decreased: E-Selectin from 566662123 to 525662058 pg/mL; p = 0.032, ICAM-1, 3.4560.01 to 3.1061.04 ng/mL; p = 0.038 and VCAM-1, 54633 to 42633 ng/mL; p = 0.006. eGFR, BP, PWV, AI, hsCRP, von Willebrand factor and Fibroblast Growth Factor-23, remained unchanged. Conclusion: This study demonstrates for the first time improvement of endothelial vasomotor and secretory functions with vitamin D in CKD patients without significant adverse effects on arterial stiffness, serum calcium or FGF-23. Trial Registration: ClinicalTrials.gov NCT0200571

CK2 phosphorylation-dependent interaction between aprataxin and MDC1 in the DNA damage response

Aprataxin, defective in the neurodegenerative disorder ataxia oculomotor apraxia type 1, resolves abortive DNA ligation intermediates during DNA repair. Here, we demonstrate that aprataxin localizes at sites of DNA damage induced by high LET radiation and binds to mediator of DNA-damage checkpoint protein 1 (MDC1/NFBD1) through a phosphorylation-dependent interaction. This interaction is mediated via the aprataxin FHA domain and multiple casein kinase 2 di-phosphorylated S-D-T-D motifs in MDC1. X-ray structural and mutagenic analysis of aprataxin FHA domain, combined with modelling of the pSDpTD peptide interaction suggest an unusual FHA binding mechanism mediated by a cluster of basic residues at and around the canonical pT-docking site. Mutation of aprataxin FHA Arg29 prevented its interaction with MDC1 and recruitment to sites of DNA damage. These results indicate that aprataxin is involved not only in single strand break repair but also in the processing of a subset of double strand breaks presumably through its interaction with MDC1

CK2 phosphorylation-dependent interaction between aprataxin and MDC1 in the DNA damage response

Aprataxin, defective in the neurodegenerative disorder ataxia oculomotor apraxia type 1, resolves abortive DNA ligation intermediates during DNA repair. Here, we demonstrate that aprataxin localizes at sites of DNA damage induced by high LET radiation and binds to mediator of DNA-damage checkpoint protein 1 (MDC1/NFBD1) through a phosphorylation-dependent interaction. This interaction is mediated via the aprataxin FHA domain and multiple casein kinase 2 di-phosphorylated S-D-T-D motifs in MDC1. X-ray structural and mutagenic analysis of aprataxin FHA domain, combined with modelling of the pSDpTD peptide interaction suggest an unusual FHA binding mechanism mediated by a cluster of basic residues at and around the canonical pT-docking site. Mutation of aprataxin FHA Arg29 prevented its interaction with MDC1 and recruitment to sites of DNA damage. These results indicate that aprataxin is involved not only in single strand break repair but also in the processing of a subset of double strand breaks presumably through its interaction with MDC1

The effect of boron addition on the atomic structure and microwave magnetic properties of FeGaB thin films

Varying amounts of boron were added to the host FeGa alloy to investigate its impact upon local atomic structure and magnetic and microwave properties. The impact of B upon the local atomic structure in FeGaB films was investigated by extended x-ray absorption fine structure ͑EXAFS͒ analysis. The EXAFS fitting results revealed a contraction of lattice parameters with the introduction of B. The Debye-Waller factor determined from EXAFS fitting increases as a function of boron addition and abruptly changes during the structural evolution from crystalline to amorphous that occurs near 9% B. Upon the onset of this transition the static and microwave magnetic properties became exceptionally soft, with values of coercivity and ferromagnetic linewidth reducing to less than 1 Oe and 25 Oe, respectively

Bottom stress generation and sediment transport over the shelf and slope off of Lake Superior's Keweenaw peninsula

Author Posting. © American Geophysical Union, 2004. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 109 (2004): C10S04, doi:10.1029/2003JC001997.Data from near-bottom instruments reveal that the mechanisms responsible for generating bottom stresses and resuspending sediment over the shelf and slope off of Lake Superior's Keweenaw peninsula exhibit distinct seasonal variations. Notably, near-bottom flows over the slope are persistently weak (<10 cm s−1) during summer but frequently attain high speeds, in excess of 20 cm s−1, in autumn and winter. During the intense storms of autumn and winter the generation of bottom stress is enhanced by the action of near-bottom orbital velocities due to surface waves. Even at 90-m depth, orbital velocities can increase bottom stress by a factor of up to 20% during storms. Where the seasonal thermocline intersects the lake floor, bottom stress is also considerably enhanced, often by more than a factor of 2, by high-frequency motions in the internal wave band. Over the Keweenaw slope, sediment resuspension is largely confined to autumn and winter episodes of high bottom stress. Our analysis indicates that this resuspended material tends to be carried offshore, a phenomenon that is partly due to the coincidence of the direction of the buoyancy-driven component of the Keweenaw Current with downwelling favorable alongshore winds. As a result of this coincidence, currents and bottom stresses tend to be greater during periods of downwelling, as opposed to upwelling, circulation. A potential challenge to modeling storm-driven resuspension in the study region is indicated by observations that the minimum stress required for resuspension may vary significantly with time over the autumn and winter.The work described was part of the Keweenaw Interdisciplinary Transport Experiment in Superior funded by the National Science Foundation through grants 9712889 to J. Churchill and A.Williams and 9712871 to E. Ralph