Nearly every massive galaxy harbors a supermassive black hole (SMBH) in its nucleus. SMBH masses are millions to billions of solar mass, and they correlate with properties of spheroids of their host ...galaxies. While the SMBH growth channels, mergers, and gas accretion are well established, their origin remains uncertain: they could have emerged either from massive "seeds" (105-106 M ) formed by direct collapse of gas clouds in the early universe or from smaller (100 M ) BHs, end products of first stars. The latter channel would leave behind numerous intermediate-mass BHs (IMBHs, 102-105 M ). Although many IMBH candidates have been identified, none are accepted as definitive; thus, their very existence is still debated. Using data mining in wide-field sky surveys and applying dedicated analysis to archival and follow-up optical spectra, we identified a sample of 305 IMBH candidates having masses 3 × 10 4 M < M BH < 2 × 10 5 M , which reside in galaxy centers and are accreting gas that creates characteristic signatures of a type I active galactic nucleus (AGN). We confirmed the AGN nature of 10 sources (including five previously known objects that validate our method) by detecting the X-ray emission from their accretion disks, thus defining the first bona fide sample of IMBHs in galactic nuclei. All IMBH host galaxies possess small bulges and sit on the low-mass extension of the M BH - M bulge scaling relation, suggesting that they must have experienced very few if any major mergers over their lifetime. The very existence of nuclear IMBHs supports the stellar-mass seed scenario of the massive BH formation.
Well-ordered graphite films with a thickness of a few graphene layers have been grown on Ni substrates by chemical vapor deposition (CVD) from a mixture of hydrogen and methane activated by a DC ...discharge. According to Auger, Raman and scanning tunneling microscopy (STM) data the CVD graphite film thickness is about 1.5
±
0.5
nm. The graphene layers were perfectly adhered to the substrate surface except for upthrusted ridges of a few tens of nanometers in height. STM has revealed an atomically smooth surface with the atomic arrangement typical of graphite between the ridges. A difference in the thermal expansion coefficients of nickel and graphite is considered as a reason for the ridge formation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Recombinant adeno-associated virus 2 (AAV2) vectors are in use in several Phase I/II clinical trials, but relatively large vector doses are needed to achieve therapeutic benefits. Large vector doses ...also trigger an immune response as a significant fraction of the vectors fails to traffic efficiently to the nucleus and is targeted for degradation by the host cell proteasome machinery. We have reported that epidermal growth factor receptor protein tyrosine kinase (EGFR-PTK) signaling negatively affects transduction by AAV2 vectors by impairing nuclear transport of the vectors. We have also observed that EGFR-PTK can phosphorylate AAV2 capsids at tyrosine residues. Tyrosine-phosphorylated AAV2 vectors enter cells efficiently but fail to transduce effectively, in part because of ubiquitination of AAV capsids followed by proteasome-mediated degradation. We reasoned that mutations of the surface-exposed tyrosine residues might allow the vectors to evade phosphorylation and subsequent ubiquitination and, thus, prevent proteasome-mediated degradation. Here, we document that site-directed mutagenesis of surface-exposed tyrosine residues leads to production of vectors that transduce HeLa cells almost equal to10-fold more efficiently in vitro and murine hepatocytes nearly 30-fold more efficiently in vivo at a log lower vector dose. Therapeutic levels of human Factor IX (F.IX) are also produced at an almost equal to10-fold reduced vector dose. The increased transduction efficiency of tyrosine-mutant vectors is due to lack of capsid ubiquitination and improved intracellular trafficking to the nucleus. These studies have led to the development of AAV vectors that are capable of high-efficiency transduction at lower doses, which has important implications in their use in human gene therapy.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Darcy’s law (which states that a fluid flow rate is directly proportional to the pressure gradient) is shown to be accurate in a rather narrow range of flow velocities. Numerous studies show that at ...low pressure gradients gas slippage effect occurs, which gives overestimated flow rates compared to Darcy’s law. At higher flow rates, Darcy’s law is usually replaced by the Forchheimer equation which accounts for inertial forces including a quadratic term in the flow rate. Darcy’s and Forchheimer’s laws and the problem of detecting transitions between their ranges of applicability are discussed in this study. Analysis of experimental data shows that deviation from Darcy’s law is governed by the Forchheimer number, which is defined by the authors as a product of tortuosity and Reynolds number. The use of the Forchheimer number and semi-analytical approaches enables us to describe non-Darcy flow as a simple universal equation valid for any flow geometry. Comparison of the experimental data with predictions based on a semi-analytical model shows excellent agreement for a wide range of reservoir properties.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Recombinant adeno-associated viral (rAAV) vectors based on serotype 2 are currently being evaluated most extensively in animals and human clinical trials. rAAV vectors constructed from other AAV ...serotypes (serotypes 1, 3, 4, 5, and 6) can transduce certain tissues more efficiently and with different specificity than rAAV2 vectors in animal models. Here, we describe reagents and methods for the production and purification of AAV2 inverted terminal repeat-containing vectors pseudotyped with AAV1 or AAV5 capsids. To facilitate pseudotyping, AAV2
rep/AAV1
cap and AAV2
rep/AAV5
cap helper plasmids were constructed in an adenoviral plasmid backbone. The resultant plasmids, pXYZ1 and pXYZ5, were used to produce rAAV1 and rAAV5 vectors, respectively, by transient transfection. Since neither AAV5 nor AAV1 binds to the heparin affinity chromatography resin used to purify rAAV2 vectors, purification protocols were developed based on anion-exchange chromatography. The purified vector stocks are 99% pure with titers of 1×10
12 to 1×10
13
vector genomes/ml.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The aim was to establish the prevalence of chronic venous disease (CVD) and its risk factors in the general population.
This was a population based, cross sectional study. In total, 703 residents ...aged > 18 years from the rural community of Kryukovo (Central Russia) were enrolled. Medical history was taken and clinical examination performed, documenting venous signs/symptoms. The CEAP classification of the most affected limb was used. Duplex ultrasound was performed to register morphological changes and reflux in deep and superficial veins.
There were 63% women and 37% men (mean age 53.5 years). CVD was found in 69.3%. Of all participants 4.7% were C0S and 34.3% were C1. Chronic venous insufficiency (C3–C6) was found in 8.2% and venous ulcers (C5–C6) in 1.1%. Venous pain, heaviness, fatigue, itching, and the sensation of swelling were documented in 14.8%, 36.3%, 32.8%, 7.0% and 29.1% of patients respectively. Family history was the significant risk factor for both CVD (hazard ratio HR 1.3) and primary varicose vein disease (HR 1.6; p < .01). Female sex was a risk factor only for CVD (HR 1.3; p < .01) but not for varicose veins. Age was a risk factor for CVD (HR 1.01) and for varicose veins (HR 1.02; p < .01). For women, number of births (HR 1.05; p < .05) and menopause (HR 1.3; p < .01) were risk factors for CVD. Menopause was a risk factor for varicose veins (HR 2.0; p < .05).
This study provides data on the prevalence of CVD, venous abnormalities and risk factors in Russia. The results contribute to already established data, giving a more complete outlook on the global prevalence of CVD.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Neutron stars are thought to be born rapidly rotating and then exhibit a phase of rotation-powered pulsations as they slow down to 1-10 s periods. The significant population of millisecond pulsars ...observed in our Galaxy is explained by the recycling concept: during an epoch of accretion from a donor star in a binary system, the neutron star is spun up to millisecond periods. However, only a few pulsars are observed during this recycling process, with relatively high rotational frequencies. Here we report the detection of an X-ray pulsar with in the globular cluster B091D in the Andromeda galaxy, the slowest pulsar ever found in a globular cluster. This bright (up to 30% of the Eddington luminosity) spinning-up pulsar, persistent over the 12 years of observations, must have started accreting less than 1 Myr ago and has not yet had time to accelerate to hundreds of Hertz. The neutron star in this unique wide binary with an orbital period in a 12 Gyr old, metal-rich star cluster accretes from a low-mass, slightly evolved post-main-sequence companion. We argue that we are witnessing a binary formed at a relatively recent epoch by getting a ∼0.8 star in a dynamical interaction-a viable scenario in a massive, dense globular cluster like B091D with high global and specific stellar encounter rates. This intensively accreting non-recycled X-ray pulsar therefore provides a long-sought missing piece in the standard pulsar recycling picture.
Two metal–organic frameworks (MOFs), UiO-66 and UiO-66-NH2, were considered as containers for bioactive chemicals. We provide a synthesis technique, which allowed the production of these materials ...suitable for biomedical applications. Both MOFs were characterized as single-phase porous materials composed of nanoparticles (30–65 nm) with a ζ-potential of more than 40 mV in water suspension. D,L-Leucine was applied as a model molecule, which allowed us to trace the mechanism of the loading process. We showed that after synthesis, amino groups of UiO-66-NH2 are coordinated with solvent residuals. It results in a similar route of leucine loading in UiO-66 and UiO-66-NH2 samples. Using joint data of thermogravimetric analysis and calorimetry, infrared spectroscopy, and nitrogen adsorption, we revealed that methyl groups of leucine molecules are responsible for bonding of an MOF matrix. We proposed the formation of bonds between CH3 groups and benzene rings of linkers via CH−π interaction. We also assessed the toxicity of the synthesized MOFs toward HeLa cells at 50 μg/mL after 24 h incubation and revealed no negative effects on the viability of the cells, prompting further biomedical research in the areas of small-molecule delivery and cell signaling and metabolism modulation.
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IJS, KILJ, NUK, PNG, UL, UM
We describe a new method for the deposition of protective ceramic-based coatings. The novelty of the method lies in the unique interaction of the electron beam with a dielectric target, in which ions ...in the beam-produced plasma neutralize the target surface charge build-up. This effect is brought about by the use of our novel forevacuum-pressure, plasma-cathode electron beam source, which can produce energetic, focused electron beams, with associated beam-produced plasmas, in the previously inaccessible pressure range of 1–100Pa. The work described here demonstrates the evaporation of aluminum oxide ceramic by electron beam bombardment and the subsequent deposition of an alumina coating. A significant increase in the microhardness of the ceramic-coated Ti substrate and a uniform depth-distribution of the elemental composition has been determined. The approach described here opens up new opportunities for the deposition of coatings in various fields of industry.
•A method for deposition of ceramic coating by e-beam evaporation of ceramic using fore-vacuum electron source is shown.•We employed this method for deposition of alumina-oxide coating on titan sample.•Surface hardness of Ti sample is increased in 3 times after deposition of coating with a uniform elemental composition.•Composition of beam plasma with gas and evaporated particle ions was investigated using modified analyzer RGA-100.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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