Shape-selective recognition of DNA abasic sites by metallohelices : inhibition of human AP endonuclease 1

Loss of a base in DNA leading to creation of an abasic (AP) site leaving a deoxyribose residue in the strand, is a frequent lesion that may occur spontaneously or under the action of various physical and chemical agents. Progress in the understanding of the chemistry and enzymology of abasic DNA largely relies upon the study of AP sites in synthetic duplexes. We report here on interactions of diastereomerically pure metallo–helical ‘flexicate’ complexes, bimetallic triple-stranded ferro-helicates [Fe2(NN-NN)3]4+ incorporating the common NN–NN bis(bidentate) helicand, with short DNA duplexes containing AP sites in different sequence contexts. The results show that the flexicates bind to AP sites in DNA duplexes in a shape-selective manner. They preferentially bind to AP sites flanked by purines on both sides and their binding is enhanced when a pyrimidine is placed in opposite orientation to the lesion. Notably, the Λ-enantiomer binds to all tested AP sites with higher affinity than the Δ-enantiomer. In addition, the binding of the flexicates to AP sites inhibits the activity of human AP endonuclease 1, which is as a valid anticancer drug target. Hence, this finding indicates the potential of utilizing well-defined metallo–helical complexes for cancer chemotherapy

Iron(II) supramolecular helicates interfere with the HIV-1 Tat–TAR RNA interaction critical for viral replication

The interaction between the HIV-1 transactivator protein Tat and TAR (transactivation responsive region) RNA, plays a critical role in HIV-1 transcription. Iron(II) supramolecular helicates were evaluated for their in vitro activity to inhibit Tat–TAR RNA interaction using UV melting studies, electrophoretic mobility shift assay, and RNase A footprinting. The results demonstrate that iron(II) supramolecular helicates inhibit Tat-TAR interaction at nanomolar concentrations by binding to TAR RNA. These studies provide a new insight into the biological potential of metallosupramolecular helicates

Privacy-preserving security solution for cloud services

AbstractWe propose a novel privacy-preserving security solution for cloud services. Our solution is based on an efficient non-bilinear group signature scheme providing the anonymous access to cloud services and shared storage servers. The novel solution offers anonymous authenticationfor registered users. Thus, users' personal attributes (age, valid registration, successful payment) can be proven without revealing users' identity, and users can use cloud services without any threat of profiling their behavior. However, if a user breaks provider's rules, his access right is revoked. Our solution provides anonymous access, unlinkability and the confidentiality of transmitted data. We implement our solution as a proof of concept applicationand present the experimental results. Further, we analyzecurrent privacy preserving solutions for cloud services and group signature schemes as basic parts of privacy enhancing solutions in cloud services. We compare the performance of our solution with the related solutionsand schemes

Numerical realization of spatial model of system building-base-ground

For example, a typical brick building is considered in the process of modeling and calculation of loaded deformed condition of the space system building-base-ground. The numerical implementation of the nonlinear problem in view of the structural destruction of materials by finite element method is in accordance with the developed algorithm. Crack propagation is presented in pattern and contour plots of stress and displacement, resulting from the calculation

PALLADIUM BASED CONTACTS TO GaAs AND InP

Au(85nm)/Pd(55nm) and Pd(55nm) metallizations were deposited on GaAs(lOO) and InP(100) substrates. The samples were heat treated in a scanning electron microscope (SEM) equipped with a quadrupole mass spectrometer. The simultaneous observation of the volatile component loss (in situ) by Evolved Gas Analysis (EGA) and the change in surface morphology by SEM during the heart treatment using a heating rate of 30°C/min were carried out. The interaction of the metallization with compound semiconductor substrates was observed after the heat treatment by transmission electron microscopy (TEM) using samples prepared by cross-sectional technique. In the course of the present work a large volatile component (arsenic and phosphorus) loss was observed for the samples coated by single layer metallization (at 410° C for Pd/GaAs and at 580°C for Pd/InP) and two peaks were registered in the case of Au/Pd metallization. In the latter case the cause of the second evaporation peak is the interaction between diffused gold and compound semiconductor. The SEM images of the surfaces demonstrate a significant change of the surface morphology at the singularities of the EGA curves. The grains grown into the semiconductors are shown by the cross-sectional images of the heat treated samples

Intra-aneurysm sac pressure measurements after endovascular aneurysm repair: differences between shrinking, unchanged, and expanding aneurysms with and without endoleaks

AbstractObjectiveOur objective was to study intra-aneurysm pressure after endovascular aneurysm repair (EVAR) in shrinking, unchanged, and expanding abdominal aortic aneurysms (AAAs) with and without endoleaks.MethodsDirect intra-aneurysm sac pressure measurement (DISP) by percutaneous translumbar puncture of the AAA under fluoroscopic guidance was performed 46 times during the follow-up of 37 patients (30 men; median age, 73 years [range, 58-82 years]; AAA diameter: median, 60 mm [range, 48-84 mm]). Three patients were included in two different groups because DISP was performed more than once with different indications. Tip-pressure sensors mounted on 0.014-inch guidewires were used for simultaneous measurement of systemic and AAA sac pressures. Mean pressure index (MPI) was calculated as the percentage of mean intra-aneurysm pressure relative to the simultaneous mean intra-aortic pressure.ResultsMedian MPI was 19% in shrinking (11 patients), 30% in unchanged (10 patients), and 59% in expanding (9 patients) aneurysms without endoleaks. Pulse pressure was also higher in expanding (10 mm Hg) compared with shrinking (2 mm Hg; P < .0001) AAAs. Four of the nine patients with expanding AAAs underwent five repeated DISPs later in the follow-up, and MPIs were consistently elevated. Seven of the 10 patients with unchanged AAAs without endoleaks underwent further computed tomography follow-up after DISP; 2 expanded (MPI, 47%-63%), 4 shrank (MPI, 21%-30%), and 1 remained unchanged (MPI, 14%). Type II endoleaks (6 patients, 7 DISPs) were associated with wide range of MPI (22%-92%). Successful endoleak embolization (n = 4) resulted in pressure reduction.ConclusionsIntra-aneurysm sac pressure measurement is an important adjunctive for EVAR evaluation, possibly allowing early detection of failures. High pressure is associated with AAA expansion and low pressure with shrinkage. Type II endoleaks can be responsible for AAA pressurization, and successful embolization appears to result in pressure reduction

LARS-like symptoms in the general population may suggest the significance of postoperative functional problems and emotional implications of rectal surgery

Background & Aim. Sphincter-saving rectal surgery is prone to cause changes in bowel function associated with Low Anterior Resection Syndrome (LARS). Our aim was to assess LARS-like symptoms within a population of 50-80-year old in order to understand the functional disturbances and emotional impact of LARS. Materials and methods: We used a questionnaire to evaluate LARS with the following categories of symptoms: flatulence control, anal incontinence, frequency, clustering and urgency of the stools, and the psycho-emotional impact created by the presence of these symptoms. We calculated the severity of LARS on 343 responders. Results. The average age of the responders (57.4% females) was 60 years. Overall, 48.1% of those questioned had no LARS-associated symptoms, while the rest presented either minor (39.9%) or major (12%) LARS-like symptomatology according to the assessment scale. Women have a higher relative risk (1.32) of having minor or major LARS. The frequency of stools did not correlate with the overall LARS score. The psycho-emotional impact was mostly influenced by the presence of incontinence (p=0.001) and urgency (p=0.05). Discussions. The study highlights the need to integrate the initial status of patients into the overall quantification of the effects of surgery on the quality of life. Age does not influence the prevalence of LARS, but symptoms seem more prevalent in women. The psycho-emotional impact is relevant to the general population, so explanations given during the informed consent and accurate description of potential consequences of surgical intervention increase compliance to ensure better post-operative control of the symptomatology. Conclusions. Deriving a normative LARS-like score may alter the interpretation and discussion of LARS scores for future rectal cancer patients, and it also provides a better understanding of the emotional impact of such symptoms on certain population subsets or cultural groups

About the psychological peculiarities of parents oriented on early development of children

The early development of the child for the modern parent becomes the norm of life, the rejection of which can cost the adult condemnation and censure from the immediate environment. There is a natural growth of expectations, fears and anxiety about the correctness of the educational strategy, self-assessment as a parent. In this regard, the study of factors contributing to the desire of parents to facilitate the development of children becomes particularly relevant. The aim of the study is a comparative study of the psychological characteristics of parents focused on the early development of children and parents who do not share the ideas of early development of children.Целью исследования является сравнительное изучение психологических особенностей родителей, ориентированных на раннее развитие детей, и родителей, не разделяющих идей раннего развития детей

DNA binding of dinuclear iron(II) metallosupramolecular cylinders. DNA unwinding and sequence preference

[Fe2L3]4+ (L = C25H20N4) is a synthetic tetracationic supramolecular cylinder (with a triple helical architecture) that targets the major groove of DNA and can bind to DNA Y-shaped junctions. To explore the DNA-binding mode of [Fe2L3]4+, we examine herein the interactions of pure enantiomers of this cylinder with DNA by biochemical and molecular biology methods. The results have revealed that, in addition to the previously reported bending of DNA, the enantiomers extensively unwind DNA, with the M enantiomer being the more efficient at unwinding, and exhibit preferential binding to regular alternating purine–pyrimidine sequences, with the M enantiomer showing a greater preference. Also, interestingly, the DNA binding of bulky cylinders [Fe2(L-CF3)3]4+ and [Fe2(L-Ph)3]4+ results in no DNA unwinding and also no sequence preference of their DNA binding was observed. The observation of sequence-preference in the binding of these supramolecular cylinders suggests that a concept based on the use of metallosupramolecular cylinders might result in molecular designs that recognize the genetic code in a sequence-dependent manner with a potential ability to affect the processing of the genetic code