The SKA and "High-Resolution" Science

"High-resolution", or "long-baseline", science with the SKA and its precursors covers a broad range of topics in astrophysics. In several research areas, the coupling between improved brightness sensitivity of the SKA and a sub-arcsecond resolution would uncover truly unique avenues and opportunities for studying extreme states of matter, vicinity of compact relativistic objects, and complex processes in astrophysical plasmas. At the same time, long baselines would secure excellent positional and astrometric measurements with the SKA and critically enhance SKA image fidelity at all scales. The latter aspect may also have a substantial impact on the survey speed of the SKA, thus affecting several key science projects of the instrument.Comment: JENAM-2010: Invited talk at JENAM session S7: The Square Kilometre Array: Paving the way for the new 21st century radio astronomy paradigm; 9 page

Theoretical Analysis of the Stress Induced B-Z Transition in Superhelical DNA

We present a method to calculate the propensities of regions within a DNA molecule to transition from B-form to Z-form under negative superhelical stresses. We use statistical mechanics to analyze the competition that occurs among all susceptible Z-forming regions at thermodynamic equilibrium in a superhelically stressed DNA of specified sequence. This method, which we call SIBZ, is similar to the SIDD algorithm that was previously developed to analyze superhelical duplex destabilization. A state of the system is determined by assigning to each base pair either the B- or the Z-conformation, accounting for the dinucleotide repeat unit of Z-DNA. The free energy of a state is comprised of the nucleation energy, the sequence-dependent B-Z transition energy, and the energy associated with the residual superhelicity remaining after the change of twist due to transition. Using this information, SIBZ calculates the equilibrium B-Z transition probability of each base pair in the sequence. This can be done at any physiologically reasonable level of negative superhelicity. We use SIBZ to analyze a variety of representative genomic DNA sequences. We show that the dominant Z-DNA forming regions in a sequence can compete in highly complex ways as the superhelicity level changes. Despite having no tunable parameters, the predictions of SIBZ agree precisely with experimental results, both for the onset of transition in plasmids containing introduced Z-forming sequences and for the locations of Z-forming regions in genomic sequences. We calculate the transition profiles of 5 kb regions taken from each of 12,841 mouse genes and centered on the transcription start site (TSS). We find a substantial increase in the frequency of Z-forming regions immediately upstream from the TSS. The approach developed here has the potential to illuminate the occurrence of Z-form regions in vivo, and the possible roles this transition may play in biological processes

Theoretical Analysis of Competing Conformational Transitions in Superhelical DNA

We develop a statistical mechanical model to analyze the competitive behavior of transitions to multiple alternate conformations in a negatively supercoiled DNA molecule of kilobase length and specified base sequence. Since DNA superhelicity topologically couples together the transition behaviors of all base pairs, a unified model is required to analyze all the transitions to which the DNA sequence is susceptible. Here we present a first model of this type. Our numerical approach generalizes the strategy of previously developed algorithms, which studied superhelical transitions to a single alternate conformation. We apply our multi-state model to study the competition between strand separation and B-Z transitions in superhelical DNA. We show this competition to be highly sensitive to temperature and to the imposed level of supercoiling. Comparison of our results with experimental data shows that, when the energetics appropriate to the experimental conditions are used, the competition between these two transitions is accurately captured by our algorithm. We analyze the superhelical competition between B-Z transitions and denaturation around the c-myc oncogene, where both transitions are known to occur when this gene is transcribing. We apply our model to explore the correlation between stress-induced transitions and transcriptional activity in various organisms. In higher eukaryotes we find a strong enhancement of Z-forming regions immediately 5′ to their transcription start sites (TSS), and a depletion of strand separating sites in a broad region around the TSS. The opposite patterns occur around transcript end locations. We also show that susceptibility to each type of transition is different in eukaryotes and prokaryotes. By analyzing a set of untranscribed pseudogenes we show that the Z-susceptibility just downstream of the TSS is not preserved, suggesting it may be under selection pressure

Hybrid silicon nanostructures with conductive ligands and their microscopic conductivities

Silicon nanoparticles (SiNPs) functionalized with conjugated molecules promise a potential pathway to generate a new category of thermoelectric materials. While the thermoelectric performance of materials based on phenyl-acetylene capped SiNPs has been proven, their low conductivity is still a problem for their general application. A muon study of phenyl-acetylene capped SiNPs has been recently carried out using the HiFi spectrometer at the Rutherford Appleton Laboratory, measuring the ALC spectra as a function of temperature. The results show a reduction in the measured line width of the resonance above room temperature, suggesting an activated behaviour for this system. This study shows that the muon study could be a powerful method to investigate microscopic conductivity of hybrid thermoelectric materials

Can Oxygen Set Thermal Limits in an Insect and Drive Gigantism?

Contains fulltext : 111575.pdf (publisher's version ) (Open Access

Parainfluenza virus infection associated with posterior reversible encephalopathy syndrome: a case report

<p>Abstract</p> <p>Introduction</p> <p>Posterior reversible encephalopathy syndrome is a clinical and radiological entity. The most accepted theory of posterior reversible encephalopathy syndrome is a loss of autoregulation in cerebral blood flow with a subsequent increase in vascular permeability and leakage of blood plasma and erythrocytes, producing vasogenic edema. In infection-associated posterior reversible encephalopathy syndrome, a clinical pattern consistent with systemic inflammatory response syndrome develops. Parainfluenza virus has not been reported in the medical literature to be associated with posterior reversible encephalopathy syndrome.</p> <p>Case presentation</p> <p>We report herein the case of a 54-year-old Caucasian woman with posterior reversible encephalopathy syndrome associated with parainfluenza virus infection who presented with generalized headache, blurring of vision, new-onset seizure and flu-like symptoms.</p> <p>Conclusion</p> <p>Infection-associated posterior reversible encephalopathy syndrome as well as hypertension-associated posterior reversible encephalopathy syndrome favor the contribution of endothelial dysfunction to the pathophysiology of this clinicoradiological syndrome. In view of the reversible nature of this clinical entity, it is important that all physicians are well aware of posterior reversible encephalopathy syndrome in patients presenting with headache and seizure activity. A detailed clinical assessment leading to the recognition of precipitant factors in posterior reversible encephalopathy syndrome is paramount.</p

Three-dimensional modelling identifies novel genetic dependencies associated with breast cancer progression in the isogenic MCF10 model

© 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. The initiation and progression of breast cancer from the transformation of the normal epithelium to ductal carcinoma in situ (DCIS) and invasive disease is a complex process involving the acquisition of genetic alterations and changes in gene expression, alongside microenvironmental and recognized histological alterations. Here, we sought to comprehensively characterise the genomic and transcriptomic features of the MCF10 isogenic model of breast cancer progression, and to functionally validate potential driver alterations in three-dimensional (3D) spheroids that may provide insights into breast cancer progression, and identify targetable alterations in conditions more similar to those encountered in vivo. We performed whole genome, exome and RNA sequencing of the MCF10 progression series to catalogue the copy number and mutational and transcriptomic landscapes associated with progression. We identified a number of predicted driver mutations (including PIK3CA and TP53) that were acquired during transformation of non-malignant MCF10A cells to their malignant counterparts that are also present in analysed primary breast cancers from The Cancer Genome Atlas (TCGA). Acquisition of genomic alterations identified MYC amplification and previously undescribed RAB3GAP1–HRAS and UBA2–PDCD2L expressed in-frame fusion genes in malignant cells. Comparison of pathway aberrations associated with progression showed that, when cells are grown as 3D spheroids, they show perturbations of cancer-relevant pathways. Functional interrogation of the dependency on predicted driver events identified alterations in HRAS, PIK3CA and TP53 that selectively decreased cell growth and were associated with progression from preinvasive to invasive disease only when cells were grown as spheroids. Our results have identified changes in the genomic repertoire in cell lines representative of the stages of breast cancer progression, and demonstrate that genetic dependencies can be uncovered when cells are grown in conditions more like those in vivo. The MCF10 progression series therefore represents a good model with which to dissect potential biomarkers and to evaluate therapeutic targets involved in the progression of breast cancer. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland

Genetic and transcriptomic analysis of transcription factor genes in the model halophilic Archaeon: coordinate action of TbpD and TfbA

<p>Abstract</p> <p>Background</p> <p>Archaea are prokaryotic organisms with simplified versions of eukaryotic transcription systems. Genes coding for the general transcription factors TBP and TFB are present in multiple copies in several Archaea, including <it>Halobacterium </it>sp. NRC-1. Multiple TBP and TFBs have been proposed to participate in transcription of genes via recognition and recruitment of RNA polymerase to different classes of promoters.</p> <p>Results</p> <p>We attempted to knock out all six TBP and seven TFB genes in <it>Halobacterium </it>sp. NRC-1 using the <it>ura</it>3-based gene deletion system. Knockouts were obtained for six out of thirteen genes, <it>tbp</it>CDF and <it>tfb</it>ACG, indicating that they are not essential for cell viability under standard conditions. Screening of a population of 1,000 candidate mutants showed that genes which did not yield mutants contained less that 0.1% knockouts, strongly suggesting that they are essential. The transcriptomes of two mutants, Δ<it>tbp</it>D and Δ<it>tfb</it>A, were compared to the parental strain and showed coordinate down regulation of many genes. Over 500 out of 2,677 total genes were regulated in the Δ<it>tbp</it>D and Δ<it>tfb</it>A mutants with 363 regulated in both, indicating that over 10% of genes in both strains require the action of both TbpD and TfbA for normal transcription. Culturing studies on the Δ<it>tbp</it>D and Δ<it>tfb</it>A mutant strains showed them to grow more slowly than the wild-type at an elevated temperature, 49°C, and they showed reduced viability at 56°C, suggesting TbpD and TfbA are involved in the heat shock response. Alignment of TBP and TFB protein sequences suggested the expansion of the TBP gene family, especially in <it>Halobacterium </it>sp. NRC-1, and TFB gene family in representatives of five different genera of haloarchaea in which genome sequences are available.</p> <p>Conclusion</p> <p>Six of thirteen TBP and TFB genes of <it>Halobacterium </it>sp. NRC-1 are non-essential under standard growth conditions. TbpD and TfbA coordinate the expression of over 10% of the genes in the NRC-1 genome. The Δ<it>tbp</it>D and Δ<it>tfb</it>A mutant strains are temperature sensitive, possibly as a result of down regulation of heat shock genes. Sequence alignments suggest the existence of several families of TBP and TFB transcription factors in <it>Halobacterium </it>which may function in transcription of different classes of genes.</p

Modeling Transmission Dynamics and Control of Vector-Borne Neglected Tropical Diseases

Neglected tropical diseases affect more than one billion people worldwide. The populations most impacted by such diseases are typically the most resource-limited. Mathematical modeling of disease transmission and cost-effectiveness analyses can play a central role in maximizing the utility of limited resources for neglected tropical diseases. We review the contributions that mathematical modeling has made to optimizing intervention strategies of vector-borne neglected diseases. We propose directions forward in the modeling of these diseases, including integrating new knowledge of vector and pathogen ecology, incorporating evolutionary responses to interventions, and expanding the scope of sensitivity analysis in order to achieve robust results

The infuence of skin colour on the experience of ownership in the rubber hand illusion

Racial prejudice is associated with a fundamental distinction between "us" and "them"-a distinction linked to the perceived overlap between representations of the self and others. Implicit prejudice has been shown to reduce the intensity of White individuals' hand ownership sensation as induced by the Rubber Hand Illusion (RHI) with dark rubber hands. However, evidence for this link to implicit prejudice comes from self-report questionnaire data regarding the RHI. As an alternative, we assessed the onset time of the RHI. We hypothesized that onset time of the RHI would be higher for the black compared to the white RH, acting as the mediator between implicit prejudice and magnitude of the RH illusion and proprioceptive drift. As expected, participants took longer to incorporate the black RH and presented lower RH illusion magnitude and a smaller proprioceptive drift for the black RH. Mediation analysis revealed a significant indirect effect of implicit racial bias on proprioceptive drift and magnitude of illusion through onset time to illusion only for the black RH. These findings further illuminate the connection between implicit prejudice and embodied perception, suggesting new perspectives on how implicit biases operate.This work was supported by Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq; grant numbers: 466922/2014-0 and 401143/2014-7).info:eu-repo/semantics/publishedVersio