Weak adhesion between deposited rough films:Relation to dispersion forces

Although the contact theory between rough surfaces is designed for adhesion energies ≳100mJ/m2, microsystems are controlled by much weaker adhesion ≲100μJ/m2, which is critical for their operation. The weakest adhesion is related to the omnipresent fluctuation-induced dispersion forces. We develop a theory for such a weak adhesion emphasizing that the adhesion energy as a function of the average distance separating the bodies is almost entirely defined by the dispersion interaction. This dependence can be evaluated using the Lifshitz theory, but the effects of contact interaction or plastic deformations give only small contribution to the adhesion. Such a behavior is explained by a specific roughness of the deposited thin films used in microtechnologies. The films deposited on cold substrates have a much larger number of high asperities than is predicted by the Gaussian distribution and the contact occurs over a few asperities with heights much larger than the root-mean-square roughness. Finally, we discuss application of the effect for more precise determination of the distance upon contact, which is crucial for precise measurements of the dispersion forces especially at short separations in the range 5<h<50nm

End invasion of peptide nucleic acids (PNAs) with mixed-base composition into linear DNA duplexes

Peptide nucleic acid (PNA) is a synthetic DNA mimic with valuable properties and a rapidly growing scope of applications. With the exception of recently introduced pseudocomplementary PNAs, binding of common PNA oligomers to target sites located inside linear double-stranded DNAs (dsDNAs) is essentially restricted to homopurine–homopyrimidine sequence motifs, which significantly hampers some of the PNA applications. Here, we suggest an approach to bypass this limitation of common PNAs. We demonstrate that PNA with mixed composition of ordinary nucleobases is capable of sequence-specific targeting of complementary dsDNA sites if they are located at the very termini of DNA duplex. We then show that such targeting makes it possible to perform capturing of designated dsDNA fragments via the DNA-bound biotinylated PNA as well as to signal the presence of a specific dsDNA sequence, in the case a PNA beacon is employed. We also examine the PNA–DNA conjugate and prove that it can initiate the primer-extension reaction starting from the duplex DNA termini when a DNA polymerase with the strand-displacement ability is used. We thus conclude that recognition of duplex DNA by mixed-base PNAs via the end invasion has a promising potential for site-specific and sequence-unrestricted DNA manipulation and detection.National Institutes of Health (CA74175, GM059173); Boston University (PIF and SPRING awards

End invasion of peptide nucleic acids (PNAs) with mixed-base composition into linear DNA duplexes

Peptide nucleic acid (PNA) is a synthetic DNA mimic with valuable properties and a rapidly growing scope of applications. With the exception of recently introduced pseudocomplementary PNAs, binding of common PNA oligomers to target sites located inside linear double-stranded DNAs (dsDNAs) is essentially restricted to homopurine–homopyrimidine sequence motifs, which significantly hampers some of the PNA applications. Here, we suggest an approach to bypass this limitation of common PNAs. We demonstrate that PNA with mixed composition of ordinary nucleobases is capable of sequence-specific targeting of complementary dsDNA sites if they are located at the very termini of DNA duplex. We then show that such targeting makes it possible to perform capturing of designated dsDNA fragments via the DNA-bound biotinylated PNA as well as to signal the presence of a specific dsDNA sequence, in the case a PNA beacon is employed. We also examine the PNA–DNA conjugate and prove that it can initiate the primer-extension reaction starting from the duplex DNA termini when a DNA polymerase with the strand-displacement ability is used. We thus conclude that recognition of duplex DNA by mixed-base PNAs via the end invasion has a promising potential for site-specific and sequence-unrestricted DNA manipulation and detection.National Institutes of Health (CA74175, GM059173); Boston University (PIF and SPRING awards

Prevention of post-transfusion hepatitis c transmission through donor blood and its components

The aim of organizational aspects of preventing the transmission of hepatitis C virus with donor blood and its components.Materials and methods. An activity of the blood service establishments in Russia for the prevention of HCV infection through transfusion of blood and its components on the basis of the analysis of sectoral statistical surveys was studied.Results. The frequency of detection of antibodies to hepatitis C virus in blood donors and its components during 2009–2013 decreased by more than 1,5 times. The percentage of donors who have identified markers of hepatitis C virus was significantly different in different regions: from 0,51% to 1,36%. The activity of the blood service implemented method of plasma quarantine resulting annually rejected from 0,32% to 0,23% as a result of the identified markers of HCV. Pathogen inactivated plasma volume increased in 3 times, the platelet concentrate in 3,2 times.Conclusion. To ensure the safety of donated blood and its components in the blood service effectively the modern technology use for to prevention transmission of the HCV: quarantine of plasma, donor selection and development, inactivation of pathogens. The degree of implementation in practice of nonpaid voluntary blood transfusions significantly increased and is characterized by regional features in recent years

ПРОФИЛАКТИКА ПОСТТРАНСФУЗИОННОГО ВИРУСНОГО ГЕПАТИТА С ПРИ ПЕРЕЛИВАНИИ ДОНОРСКОЙ КРОВИ И ЕЕ КОМПОНЕНТОВ

The aim of organizational aspects of preventing the transmission of hepatitis C virus with donor blood and its components.Materials and methods. An activity of the blood service establishments in Russia for the prevention of HCV infection through transfusion of blood and its components on the basis of the analysis of sectoral statistical surveys was studied.Results. The frequency of detection of antibodies to hepatitis C virus in blood donors and its components during 2009–2013 decreased by more than 1,5 times. The percentage of donors who have identified markers of hepatitis C virus was significantly different in different regions: from 0,51% to 1,36%. The activity of the blood service implemented method of plasma quarantine resulting annually rejected from 0,32% to 0,23% as a result of the identified markers of HCV. Pathogen inactivated plasma volume increased in 3 times, the platelet concentrate in 3,2 times.Conclusion. To ensure the safety of donated blood and its components in the blood service effectively the modern technology use for to prevention transmission of the HCV: quarantine of plasma, donor selection and development, inactivation of pathogens. The degree of implementation in practice of nonpaid voluntary blood transfusions significantly increased and is characterized by regional features in recent years .Цель. Исследование организационных аспектов профилактики передачи вирусного гепатита С с донорской кровью и ее компонентами.Материалы и методы. Проведено изучение деятельности учреждений службы крови России по предупреждению инфицирования ВГС при переливании донорской крови и ее компонентов на основе анализа отраслевых статистических наблюдений.Результаты. Частота выявления антител к вирусному гепатиту С у доноров крови и ее компонентов в течение 2009–2013 гг. снизилась более чем в 1,5 раз. Процентное число доноров, у которых выявлены маркеры вируса гепатита С, существенно отличалось в различных регионах: от 0,51% до 1,36%. В деятельность службы крови внедрен метод карантинизации плазмы, в результате чего ежегодно бракуется от 0,32% до 0,23% вследствие выявленных маркеров ВГС. Объем патогенинактивированной плазмы увеличился в 3 раза, тромбоцитного концентрата – в 3,2 раза.Заключение. Для обеспечения безопасности донорской крови и ее компонентов в службе крови эффективно применяются современные технологии профилактики передачи ВГС: карантинизация плазмы, отбор доноров и развитие безвозмездного добровольного донорства, инактивация патогенов. Cтепень их внедрения в трансфузиологическую практику в последние годы существенно повышается и характеризуется региональными особенностями

X-ray Spectral Survey with XMM--Newton of a Complete Sample of Nearby Seyfert Galaxies

Results obtained from an X-ray spectral survey of nearby Seyfert galaxies using XMM--Newton are reported. The sample was optically selected, well defined, complete in B mag, and distance limited: it consists of the nearest (D<22 Mpc) 27 Seyfert galaxies (9 of type 1, 18 of type 2) taken from the Ho et al. (1997) sample. This is one of the largest atlases of hard X-ray spectra of low-L active galaxies ever assembled. All nuclear sources except two Sey 2s are detected between 2-10 keV, half for the first time ever, and average spectra are obtained for all of them. Nuclear luminosities reach values down to 10**38 erg/s. The shape of the distribution of X-ray parameters is affected by the presence of Compton-thick objects (> 30% among type 2s). The latter have been identified either directly from their intense FeK line and flat X-ray spectra, or indirectly with flux diagnostic diagrams which use isotropic indicators. After taking into account these highly absorbed sources, we find that (i) the intrinsic X-ray spectral properties (i.e., spectral shapes and luminosities above 2 keV) are consistent between type 1 and type 2 Sey, as expected from ``unified models'', (ii) Sey galaxies as a whole are distributed fairly continuously over the entire range of Nh, between 10**20 and 10**25 cm**-2, and (iii) while Sey 1s tend to have lower Nh and Sey 2s tend to have the highest, we find 30% and 10% exceptions, respectively. Overall the sample well represents the average intrinsic X-ray spectral properties of nearby AGN, including a proper estimate of the distribution of their absorbing columns. Finally, we conclude that, with the exception of a few cases, the present study agrees with predictions of unified models of Sey galaxies, and extends their validity down to very low luminosities.Comment: 23 pages, 4 tables, 4 figures, 2 Appendices with 27 source spectra and notes, to be published in the Astronomy & Astrophysics Journa

c-MET Protects Breast Cancer Cells from Apoptosis Induced by Sodium Butyrate

Sodium Butyrate (NaBu) is regarded as a potential reagent for cancer therapy. In this study, a specific breast cancer cell population that is resistant NaBu treatment was identified. These cells possess cancer stem cell characters, such as the capability of sphere formation in vitro and high tumor incident rate (85%) in mouse model. Forty percent of the NaBu resistant cells express the cancer stem cells marker, the CD133, whereas only 10% intact cells present the CD133 antigen. Furthermore, the endogenous expressing c-MET contributes to the survival of cancer stem cell population from the treatment of NaBu. The CD133+ group also presents a higher level of c-MET. A combination treatment of MET siRNA and NaBu efficiently prohibited the breast cancer progression, and the incident rate of the tumor decrease to 18%. This study may help to develop a new and alternative strategy for breast cancer therapy

MYB suppresses differentiation and apoptosis of human breast cancer cells

Introduction: MYB is highly expressed in estrogen receptor positive (ER + ve) breast tumours and tumour cell lines. We recently demonstrated that MYB is essential for the proliferation of ER + ve breast cancer cells, and have now investigated its role in mammary epithelial differentiation.Methods: MCF-7 breast cancer cells were treated with sodium butyrate, vitamin E succinate or 12-O-tetradecanoylphorbol-13-acetate to induce differentiation as measured by Nile Red staining of lipid droplets and β-casein expression. The non-tumorigenic murine mammary epithelial cell (MEC) line, HC11, was induced to differentiate with lactogenic hormones. MYB levels were manipulated by inducible lentiviral shRNA-mediated knockdown and retroviral overexpression.Results: We found that MYB expression decreases following chemically-induced differentiation of the human breast cancer cell line MCF-7, and hormonally-induced differentiation of a non-tumorigenic murine mammary epithelial cell (MEC) line, HC11. We also found that shRNA-mediated MYB knockdown initiated differentiation of breast cancer cells, and greatly sensitised them to the differentiative and pro-apoptotic effects of differentiation-inducing agents (DIAs). Sensitisation to the pro-apoptotic effects DIAs is mediated by decreased expression of BCL2, which we show here is a direct MYB target in breast cancer cells. Conversely, enforced expression of MYB resulted in the cells remaining in an undifferentiated state, with concomitant suppression of apoptosis, in the presence of DIAs.Conclusions: Taken together, these data imply that MYB function is critical in regulating the balance between proliferation, differentiation, and apoptosis in MECs. Moreover, our findings suggest MYB may be a viable therapeutic target in breast cancer and suggest specific approaches for exploiting this possibility

The SARS-Unique Domain (SUD) of SARS Coronavirus Contains Two Macrodomains That Bind G-Quadruplexes

Since the outbreak of severe acute respiratory syndrome (SARS) in 2003, the three-dimensional structures of several of the replicase/transcriptase components of SARS coronavirus (SARS-CoV), the non-structural proteins (Nsps), have been determined. However, within the large Nsp3 (1922 amino-acid residues), the structure and function of the so-called SARS-unique domain (SUD) have remained elusive. SUD occurs only in SARS-CoV and the highly related viruses found in certain bats, but is absent from all other coronaviruses. Therefore, it has been speculated that it may be involved in the extreme pathogenicity of SARS-CoV, compared to other coronaviruses, most of which cause only mild infections in humans. In order to help elucidate the function of the SUD, we have determined crystal structures of fragment 389–652 (“SUDcore”) of Nsp3, which comprises 264 of the 338 residues of the domain. Both the monoclinic and triclinic crystal forms (2.2 and 2.8 Å resolution, respectively) revealed that SUDcore forms a homodimer. Each monomer consists of two subdomains, SUD-N and SUD-M, with a macrodomain fold similar to the SARS-CoV X-domain. However, in contrast to the latter, SUD fails to bind ADP-ribose, as determined by zone-interference gel electrophoresis. Instead, the entire SUDcore as well as its individual subdomains interact with oligonucleotides known to form G-quadruplexes. This includes oligodeoxy- as well as oligoribonucleotides. Mutations of selected lysine residues on the surface of the SUD-N subdomain lead to reduction of G-quadruplex binding, whereas mutations in the SUD-M subdomain abolish it. As there is no evidence for Nsp3 entering the nucleus of the host cell, the SARS-CoV genomic RNA or host-cell mRNA containing long G-stretches may be targets of SUD. The SARS-CoV genome is devoid of G-stretches longer than 5–6 nucleotides, but more extended G-stretches are found in the 3′-nontranslated regions of mRNAs coding for certain host-cell proteins involved in apoptosis or signal transduction, and have been shown to bind to SUD in vitro. Therefore, SUD may be involved in controlling the host cell's response to the viral infection. Possible interference with poly(ADP-ribose) polymerase-like domains is also discussed