Conserved presence of G-quadruplex forming sequences in the Long Terminal Repeat Promoter of Lentiviruses

G-quadruplexes (G4s) are secondary structures of nucleic acids that epigenetically regulate cellular processes. In the human immunodeficiency lentivirus 1 (HIV-1), dynamic G4s are located in the unique viral LTR promoter. Folding of HIV-1 LTR G4s inhibits viral transcription; stabilization by G4 ligands intensifies this effect. Cellular proteins modulate viral transcription by inducing/unfolding LTR G4s. We here expanded our investigation on the presence of LTR G4s to all lentiviruses. G4s in the 5'-LTR U3 region were completely conserved in primate lentiviruses. A G4 was also present in a cattle-infecting lentivirus. All other non-primate lentiviruses displayed hints of less stable G4s. In primate lentiviruses, the possibility to fold into G4s was highly conserved among strains. LTR G4 sequences were very similar among phylogenetically related primate viruses, while they increasingly differed in viruses that diverged early from a common ancestor. A strong correlation between primate lentivirus LTR G4s and Sp1/NF\u3baB binding sites was found. All LTR G4s folded: their complexity was assessed by polymerase stop assay. Our data support a role of the lentiviruses 5'-LTR G4 region as control centre of viral transcription, where folding/unfolding of G4s and multiple recruitment of factors based on both sequence and structure may take place

Elastic and vibrational properties of alpha and beta-PbO

The structure, electronic and dynamic properties of the two layered alpha (litharge) and beta (massicot) phases of PbO have been studied by density functional methods. The role of London dispersion interactions as leading component of the total interaction energy between layers has been addressed by using the Grimme's approach, in which new parameters for Pb and O atoms have been developed. Both gradient corrected and hybrid functionals have been adopted using Gaussian-type basis sets of polarized triple zeta quality for O atoms and small core pseudo-potential for the Pb atoms. Basis set superposition error (BSSE) has been accounted for by the Boys-Bernardi correction to compute the interlayer separation. Cross check with calculations adopting plane waves that are BSSE free have also been performed for both structures and vibrational frequencies. With the new set of proposed Grimme's type parameters structures and dynamical parameters for both PbO phases are in good agreement with experimental data.Comment: 8 pages, 5 figure

Sagopilone (ZK-EPO, ZK 219477) for recurrent glioblastoma. A phase II multicenter trial by the European Organisation for Research and Treatment of Cancer (EORTC) Brain Tumor Group

Background: Sagopilone (ZK 219477), a lipophylic and synthetic analog of epothilone B, that crosses the blood-brain barrier has demonstrated preclinical activity in glioma models. Patients and methods: Patients with first recurrence/progression of glioblastoma were eligible for this early phase II and pharmacokinetic study exploring single-agent sagopilone (16 mg/m2 over 3 h every 21 days). Primary end point was a composite of either tumor response or being alive and progression free at 6 months. Overall survival, toxicity and safety and pharmacokinetics were secondary end points. Results: Thirty-eight (evaluable 37) patients were included. Treatment was well tolerated, and neuropathy occurred in 46% patients [mild (grade 1) : 32%]. No objective responses were seen. The progression-free survival (PFS) rate at 6 months was 6.7% [95% confidence interval (CI) 1.3-18.7], the median PFS was just over 6 weeks, and the median overall survival was 7.6 months (95% CI 5.3-12.3), with a 1-year survival rate of 31.6% (95% CI 17.7-46.4). Maximum plasma concentrations were reached at the end of the 3-h infusion, with rapid declines within 30 min after termination. Conclusions: No evidence of relevant clinical antitumor activity against recurrent glioblastoma could be detected. Sagopilone was well tolerated, and moderate-to-severe peripheral neuropathy was observed in despite prolonged administratio

Event-related alpha suppression in response to facial motion

This article has been made available through the Brunel Open Access Publishing Fund.While biological motion refers to both face and body movements, little is known about the visual perception of facial motion. We therefore examined alpha wave suppression as a reduction in power is thought to reflect visual activity, in addition to attentional reorienting and memory processes. Nineteen neurologically healthy adults were tested on their ability to discriminate between successive facial motion captures. These animations exhibited both rigid and non-rigid facial motion, as well as speech expressions. The structural and surface appearance of these facial animations did not differ, thus participants decisions were based solely on differences in facial movements. Upright, orientation-inverted and luminance-inverted facial stimuli were compared. At occipital and parieto-occipital regions, upright facial motion evoked a transient increase in alpha which was then followed by a significant reduction. This finding is discussed in terms of neural efficiency, gating mechanisms and neural synchronization. Moreover, there was no difference in the amount of alpha suppression evoked by each facial stimulus at occipital regions, suggesting early visual processing remains unaffected by manipulation paradigms. However, upright facial motion evoked greater suppression at parieto-occipital sites, and did so in the shortest latency. Increased activity within this region may reflect higher attentional reorienting to natural facial motion but also involvement of areas associated with the visual control of body effectors. © 2014 Girges et al

Growth and Structure of Ultrathin Iron Silicate and Iron Germanate Films

The growth and structure of two-dimensional iron silicate and iron germanate films on Ru(0001) are studied. We investigate in detail the temperature-dependent film formation of ultrathin layers of iron silicate and iron germanate. These two-dimensional films can be seen as model systems for more complex catalytically active structures, such as zeolites, which can be used as selective catalysts or molecular sieves. The experimental methods of XPS, LEED, LEEM, LEEM-IV, and XPEEM are applied for correlated chemical and physical characterization in situ and in real time, and DFT is applied for theoretical consideration. We show that both systems can be considered as two-layered systems, with a monolayer of iron oxide at the Ru interface and a monolayer of silica or germania on top, respectively. The Fe-Fe distance in the iron oxide layer is influenced by the Si-O-Si or Ge-O-Ge bond length, in agreement with those of unstrained silicates or germanates. Moreover, iron silicate can be prepared using different preparation methods. The actual loading of Fe atoms is three per unit cell for FeGeOx and only two for FeSiOx

Hydrogen-doped Brookite TiO2 Nanobullets Array as a Novel Photoanode for Efficient Solar Water Splitting

As a representative photocatalyst for photoelectrochemical solar water splitting, TiO2 has been intensively studied but most researches have focused on the rutile and anatsase phases because brookite, another important crystalline polymorph of TiO2, rarely exists in nature and is difficult to synthesize. In this work, hydrogen doped brookite (H:brookite) nanobullet arrays were synthesized via a well-designed solution reaction for the first time. H:brookite shows highly improved PEC properties with excellent stability, enhanced photocurrent, and significantly high Faradaic efficiency for overall solar water splitting. To support the experimental data, ab initio density functional theory calculations were also conducted. At the interstitial doping site that has minimum formation energy, the hydrogen atoms act as shallow donors and exist as H+. which has the minimum formation energy among three states of hydrogen (H+. H0, and H-). The calculated density of states of H:brookite shows a narrowed bandgap and an increased electron density compared to the pristine brookite. The combined experimental and theoretical results provide frameworks for the exploration of the PEC properties of doped brookite and extend our knowledge regarding the undiscovered properties of brookite of TiO2.ope

Improving Matrix-vector Multiplication via Lossless Grammar-Compressed Matrices

As nowadays Machine Learning (ML) techniques are generating huge data collections, the problem of how to efficiently engineer their storage and operations is becoming of paramount importance. In this article we propose a new lossless compression scheme for real-valued matrices which achieves efficient performance in terms of compression ratio and time for linear-algebra operations. Ex- periments show that, as a compressor, our tool is clearly superior to gzip and it is usually within 20% of xz in terms of compression ratio. In addition, our compressed format supports matrix-vector multiplications in time and space proportional to the size of the compressed representation, unlike gzip and xz that require the full decompression of the compressed matrix. To our knowledge our lossless compressor is the first one achieving time and space com- plexities which match the theoretical limit expressed by the k-th order statistical entropy of the input. To achieve further time/space reductions, we propose column- reordering algorithms hinging on a novel column-similarity score. Our experiments on various data sets of ML matrices show that our column reordering can yield a further reduction of up to 16% in the peak memory usage during matrix-vector multiplication. Finally, we compare our proposal against the state-of-the-art Compressed Linear Algebra (CLA) approach showing that ours runs always at least twice faster (in a multi-thread setting), and achieves better compressed space occupancy and peak memory usage. This experimentally confirms the provably effective theoretical bounds we show for our compressed-matrix approach

A roadmap of strain in doped anatase TiO2

Anatase titanium oxide is important for its high chemical stability and photocatalytic properties, however, the latter are plagued by its large band gap that limits its activity to only a small percentage of the solar spectrum. In that respect, straining the material can reduce its band gap increasing the photocatalytic activity of titanium oxide. We apply density functional theory with the introduction of the Hubbard + U model, to investigate the impact of stress on the electronic structure of anatase in conjunction with defect engineering by intrinsic defects (oxygen/titanium vacancies and interstitials), metallic dopants (iron, chromium) and non-metallic dopants (carbon, nitrogen). Here we show that both biaxial and uniaxial strain can reduce the band gap of undoped anatase with the use of biaxial strain being marginally more beneficial reducing the band gap up to 2.96 eV at a tensile stress of 8 GPa. Biaxial tensile stress in parallel with doping results in reduction of the band gap but also in the introduction of states deep inside the band gap mainly for interstitially doped anatase. Dopants in substitutional positions show reduced deep level traps. Chromium-doped anatase at a tensile stress of 8 GPa shows the most significant reduction of the band gap as the band gap reaches 2.4 eV

Adult Neural Stem Cell Regulation by Small Non-coding RNAs: Physiological Significance and Pathological Implications

The adult neurogenic niches are complex multicellular systems, receiving regulatory input from a multitude of intracellular, juxtacrine, and paracrine signals and biological pathways. Within the niches, adult neural stem cells (aNSCs) generate astrocytic and neuronal progeny, with the latter predominating in physiological conditions. The new neurons generated from this neurogenic process are functionally linked to memory, cognition, and mood regulation, while much less is known about the functional contribution of aNSC-derived newborn astrocytes and adult-born oligodendrocytes. Accumulating evidence suggests that the deregulation of aNSCs and their progeny can impact, or can be impacted by, aging and several brain pathologies, including neurodevelopmental and mood disorders, neurodegenerative diseases, and also by insults, such as epileptic seizures, stroke, or traumatic brain injury. Hence, understanding the regulatory underpinnings of aNSC activation, differentiation, and fate commitment could help identify novel therapeutic avenues for a series of pathological conditions. Over the last two decades, small non-coding RNAs (sncRNAs) have emerged as key regulators of NSC fate determination in the adult neurogenic niches. In this review, we synthesize prior knowledge on how sncRNAs, such as microRNAs (miRNAs) and piwi-interacting RNAs (piRNAs), may impact NSC fate determination in the adult brain and we critically assess the functional significance of these events. We discuss the concepts that emerge from these examples and how they could be used to provide a framework for considering aNSC (de)regulation in the pathogenesis and treatment of neurological diseases

Using Cross-Impact Analysis for Probabilistic Risk Assessment

Cross-impact analysis is widely employed to inform management and policy decisions based on the formulation of scenarios which are defined as combinations of outcomes of relevant uncertainty factors. In this paper, we argue that the use of non-probabilistic variants of cross-impact analysis is problematic in the context of risk assessment where the aim usually is to produce conservative risk estimates which may exceed but are not smaller than the actual risk level. Then, building on the characterization of probabilistic dependencies, we develop an approach to probabilistic cross-impact analysis which (i) admits several kinds of probabilistic statements about the outcomes of relevant uncertainty factors and their dependencies; (ii) maps such statements into constraints on the joint probability distribution over all possible scenarios; (iii) provides support for preserving the consistency of elicited statements; and (iv) uses mathematical optimization to compute lower and upper bounds on the overall risk level. This approach{which is illustrated with an example from the context of nuclear waste repositories{is useful in that it retains the informativeness of cross-impact statements while ensuring that these statements are interpreted within the coherent framework of probability theory