Anarchic hand with abnormal agency following right inferior parietal lobe damage: a case report

Anarchic hand syndrome (AHS) is characterized by goal-directed movements performed without volitional control (agency). Different AHS subtypes have been identified; however, few studies have examined the posterior subtype. We report a case of AHS following right-hemisphere parietal damage, with left-sided somatosensory and proprioceptive impairment. Agency was examined for nonanarchic (volitional) movements performed using the anarchic hand. The patient experienced abnormal agency for movements whether motor intention and visual feedback were congruent or incongruent, but not when intention was absent (passive movement). Findings suggest a general disturbance of veridical motor awareness and agency in this case of parietal AHS

Untangling the ATR-CHEK1 network for prognostication, prediction and therapeutic target validation in breast cancer

Background: ATR-Chk1 signalling network is critical for genomic stability. ATR-Chk1 may be deregulated in breast cancer and have prognostic, predictive and therapeutic significance. Patients and methods: We investigated ATR and phosphorylated CHK1Ser345 protein (pChk1) expression in 1712 breast cancers (Nottingham Tenovus series). ATR and Chk1 mRNA were evaluated in 1950 breast cancers (METABRIC cohort). Pre-clinically, biological consequences of ATR gene knockdown or ATR inhibition by small molecule inhibitor (VE-821) were investigated in MCF-7 and MDA-MB-231 breast cancer cell lines and in non-tumorigenic breast epithelial cells (MCF10A). Results: High ATR and high cytoplasmic pChk1 expression was significantly associated with higher tumour stage, higher mitotic index, pleomorphism and lymphovascular invasion. In univariate analysis, high ATR and high cytoplasmic pChk1 protein expression was associated with shorter breast cancer specific survival (BCSS). In multivariate analysis, high ATR remains an independent predictor of adverse outcome. At the mRNA level, high Chk1 remains associated with aggressive phenotypes including lymph node positivity, high grade, Her-2 overexpression, triple-negative phenotype and molecular classes associated with aggressive behaviour and shorter survival.. Pre-clinically, Chk1 phosphorylation at serine 345 following replication stress (induced by gemcitabine or hydroxyurea treatment) was impaired in ATR knockdown and in VE-821 treated breast cancer cells. Doxycycline inducible knockdown of ATR suppressed growth, which was restored when ATR was re-expressed. Similarly, VE-821 treatment resulted in a dose dependent suppression of cancer cell growth and survival (MCF7 and MDA-MB-231) but had no effect on non-tumorigenic breast epithelial cells (MCF10A). Conclusions: We provides evidence that ATR and Chk1 are promising biomarkers and rational drug target for personalized therapy in breast cancer

Mass extinctions and supernova explosions

A nearby supernova (SN) explosion could have negatively influenced life on Earth, maybe even been responsible for mass extinctions. Mass extinction poses a significant extinction of numerous species on Earth, as recorded in the paleontologic, paleoclimatic, and geological record of our planet. Depending on the distance between the Sun and the SN, different types of threats have to be considered, such as ozone depletion on Earth, causing increased exposure to the Sun's ultraviolet radiation, or the direct exposure of lethal x-rays. Another indirect effect is cloud formation, induced by cosmic rays in the atmosphere which result in a drop in the Earth's temperature, causing major glaciations of the Earth. The discovery of highly intensive gamma ray bursts (GRBs), which could be connected to SNe, initiated further discussions on possible life-threatening events in Earth's history. The probability that GRBs hit the Earth is very low. Nevertheless, a past interaction of Earth with GRBs and/or SNe cannot be excluded and might even have been responsible for past extinction events.Comment: Chapter for forthcoming book: Handbook of Supernovae, P. Murdin and A. Alsabeti (eds.), Springer International Publishing (in press

Higgs boson enhancement effects on squark-pair production at the LHC

We study the Higgs boson effects on third-generation squark-pair production in proton-proton collision at the CERN Large Hadron Collider (LHC), including \Stop \Stop^*, \Stop\Sbot^*, and \Sbot \Sbot^*. We found that substantial enhancement can be obtained through s-channel exchanges of Higgs bosons at large $\tan\beta$, at which the enhancement mainly comes from $b\bar b$, $b\bar c$, and $c\bar b$ initial states. We compute the complete set of electroweak (EW) contributions to all production channels. This completes previous computations in the literature. We found that the EW contributions can be significant and can reach up to 25% in more general scenarios and at the resonance of the heavy Higgs boson. The size of Higgs enhancement is comparable or even higher than the PDF uncertainties and so must be included in any reliable analysis. A full analytical computation of all the EW contributions is presented.Comment: 23 pages, 7 figures, 1 tabl

Ricci Flow Gravity

A theory of gravitation is proposed, modeled after the notion of a Ricci flow. In addition to the metric an independent volume enters as a fundamental geometric structure. Einstein gravity is included as a limiting case. Despite being a scalar-tensor theory the coupling to matter is different from Jordan-Brans-Dicke gravity. In particular there is no adjustable coupling constant. For the solar system the effects of Ricci flow gravity cannot be distinguished from Einstein gravity and therefore it passes all classical tests. However for cosmology significant deviations from standard Einstein cosmology will appear.Comment: 15 pages. V2: improved presentation, in particular Jordan vs. Brans-Dicke and on viability. Added section on physical interpretation. V3: more references. Reworked to agree with published versio

The future of enterprise groupware applications

This paper provides a review of groupware technology and products. The purpose of this review is to investigate the appropriateness of current groupware technology as the basis for future enterprise systems and evaluate its role in realising, the currently emerging, Virtual Enterprise model for business organisation. It also identifies in which way current technological phenomena will transform groupware technology and will drive the development of the enterprise systems of the future

A computational framework to emulate the human perspective in flow cytometric data analysis

Background: In recent years, intense research efforts have focused on developing methods for automated flow cytometric data analysis. However, while designing such applications, little or no attention has been paid to the human perspective that is absolutely central to the manual gating process of identifying and characterizing cell populations. In particular, the assumption of many common techniques that cell populations could be modeled reliably with pre-specified distributions may not hold true in real-life samples, which can have populations of arbitrary shapes and considerable inter-sample variation. <p/>Results: To address this, we developed a new framework flowScape for emulating certain key aspects of the human perspective in analyzing flow data, which we implemented in multiple steps. First, flowScape begins with creating a mathematically rigorous map of the high-dimensional flow data landscape based on dense and sparse regions defined by relative concentrations of events around modes. In the second step, these modal clusters are connected with a global hierarchical structure. This representation allows flowScape to perform ridgeline analysis for both traversing the landscape and isolating cell populations at different levels of resolution. Finally, we extended manual gating with a new capacity for constructing templates that can identify target populations in terms of their relative parameters, as opposed to the more commonly used absolute or physical parameters. This allows flowScape to apply such templates in batch mode for detecting the corresponding populations in a flexible, sample-specific manner. We also demonstrated different applications of our framework to flow data analysis and show its superiority over other analytical methods. <p/>Conclusions: The human perspective, built on top of intuition and experience, is a very important component of flow cytometric data analysis. By emulating some of its approaches and extending these with automation and rigor, flowScape provides a flexible and robust framework for computational cytomics

Integrative analyses identify modulators of response to neoadjuvant aromatase inhibitors in patients with early breast cancer

Introduction Aromatase inhibitors (AIs) are a vital component of estrogen receptor positive (ER+) breast cancer treatment. De novo and acquired resistance, however, is common. The aims of this study were to relate patterns of copy number aberrations to molecular and proliferative response to AIs, to study differences in the patterns of copy number aberrations between breast cancer samples pre- and post-AI neoadjuvant therapy, and to identify putative biomarkers for resistance to neoadjuvant AI therapy using an integrative analysis approach. Methods Samples from 84 patients derived from two neoadjuvant AI therapy trials were subjected to copy number profiling by microarray-based comparative genomic hybridisation (aCGH, n = 84), gene expression profiling (n = 47), matched pre- and post-AI aCGH (n = 19 pairs) and Ki67-based AI-response analysis (n = 39). Results Integrative analysis of these datasets identified a set of nine genes that, when amplified, were associated with a poor response to AIs, and were significantly overexpressed when amplified, including CHKA, LRP5 and SAPS3. Functional validation in vitro, using cell lines with and without amplification of these genes (SUM44, MDA-MB134-VI, T47D and MCF7) and a model of acquired AI-resistance (MCF7-LTED) identified CHKA as a gene that when amplified modulates estrogen receptor (ER)-driven proliferation, ER/estrogen response element (ERE) transactivation, expression of ER-regulated genes and phosphorylation of V-AKT murine thymoma viral oncogene homolog 1 (AKT1). Conclusions These data provide a rationale for investigation of the role of CHKA in further models of de novo and acquired resistance to AIs, and provide proof of concept that integrative genomic analyses can identify biologically relevant modulators of AI response

Vector boson pair production at the LHC

We present phenomenological results for vector boson pair production at the LHC, obtained using the parton-level next-to-leading order program MCFM. We include the implementation of a new process in the code, pp -> \gamma\gamma, and important updates to existing processes. We incorporate fragmentation contributions in order to allow for the experimental isolation of photons in \gamma\gamma, W\gamma, and Z\gamma production and also account for gluon-gluon initial state contributions for all relevant processes. We present results for a variety of phenomenological scenarios, at the current operating energy of \sqrt{s} = 7 TeV and for the ultimate machine goal, \sqrt{s} = 14 TeV. We investigate the impact of our predictions on several important distributions that enter into searches for new physics at the LHC.Comment: 35 pages, 14 figure

Many faces of low mass neutralino dark matter in the unconstrained MSSM, LHC data and new signals

If all strongly interacting sparticles (the squarks and the gluinos) in an unconstrained minimal supersymmetric standard model (MSSM) are heavier than the corresponding mass lower limits in the minimal supergravity (mSUGRA) model, obtained by the current LHC experiments, then the existing data allow a variety of electroweak (EW) sectors with light sparticles yielding dark matter (DM) relic density allowed by the WMAP data. Some of the sparticles may lie just above the existing lower bounds from LEP and lead to many novel DM producing mechanisms not common in mSUGRA. This is illustrated by revisiting the above squark-gluino mass limits obtained by the ATLAS Collaboration, with an unconstrained EW sector with masses not correlated with the strong sector. Using their selection criteria and the corresponding cross section limits, we find at the generator level using Pythia, that the changes in the mass limits, if any, are by at most 10-12% in most scenarios. In some cases, however, the relaxation of the gluino mass limits are larger ($\approx 20$). If a subset of the strongly interacting sparticles in an unconstrained MSSM are within the reach of the LHC, then signals sensitive to the EW sector may be obtained. This is illustrated by simulating the $blj$\etslash, $l= e and \mu$, and $b\tau j$\etslash signals in i) the light stop scenario and ii) the light stop-gluino scenario with various light EW sectors allowed by the WMAP data. Some of the more general models may be realized with non-universal scalar and gaugino masses.Comment: 27 pages, 1 figure, references added, minor changes in text, to appear in JHE