Quantum critical states and phase transitions in the presence of non equilibrium noise

Quantum critical points are characterized by scale invariant correlations and correspondingly long ranged entanglement. As such, they present fascinating examples of quantum states of matter, the study of which has been an important theme in modern physics. Nevertheless very little is known about the fate of quantum criticality under non equilibrium conditions. In this paper we investigate the effect of external noise sources on quantum critical points. It is natural to expect that noise will have a similar effect to finite temperature, destroying the subtle correlations underlying the quantum critical behavior. Surprisingly we find that in many interesting situations the ubiquitous 1/f noise preserves the critical correlations. The emergent states show intriguing interplay of intrinsic quantum critical and external noise driven fluctuations. We demonstrate this general phenomenon with specific examples in solid state and ultracold atomic systems. Moreover our approach shows that genuine quantum phase transitions can exist even under non equilibrium conditions.Comment: 9 pages, 2 figure

Spina bifida-predisposing heterozygous mutations in Planar Cell Polarity genes and Zic2 reduce bone mass in young mice

Fractures are a common comorbidity in children with the neural tube defect (NTD) spina bifida. Mutations in the Wnt/planar cell polarity (PCP) pathway contribute to NTDs in humans and mice, but whether this pathway independently determines bone mass is poorly understood. Here, we first confirmed that core Wnt/PCP components are expressed in osteoblasts and osteoclasts in vitro. In vivo, we performed detailed µCT comparisons of bone structure in tibiae from young male mice heterozygous for NTD-associated mutations versus WT littermates. PCP signalling disruption caused by Vangl2 (Vangl2Lp/+) or Celsr1 (Celsr1Crsh/+) mutations significantly reduced trabecular bone mass and distal tibial cortical thickness. NTD-associated mutations in non-PCP transcription factors were also investigated. Pax3 mutation (Pax3Sp2H/+) had minimal effects on bone mass. Zic2 mutation (Zic2Ku/+) significantly altered the position of the tibia/fibula junction and diminished cortical bone in the proximal tibia. Beyond these genes, we bioinformatically documented the known extent of shared genetic networks between NTDs and bone properties. 46 genes involved in neural tube closure are annotated with bone-related ontologies. These findings document shared genetic networks between spina bifida risk and bone structure, including PCP components and Zic2. Genetic variants which predispose to spina bifida may therefore independently diminish bone mass

The effect of dutasteride on MRI-defined prostate cancer lesions: MAPPED (Magnetic resonance imaging in Primary Prostate Cancer after Exposure to Dutasteride) - a randomized placebo-controlled, double-blind clinical trial

PURPOSE: Dutasteride is licensed for symptomatic benign prostatic hyperplasia, and has been associated with a lower progression rate in low-risk prostate cancer. We have evaluated the effect of dutasteride on prostate cancer volume as assessed by T2-weighted Magnetic Resonance Imaging (MRI). MATERIALS AND METHODS: In this randomized, double-blind, placebo-controlled trial, men with biopsy-proven low-intermediate risk prostate cancer (up to Gleason 3+4 and PSA up to 15 ng/ml) who had an MR visible lesion of >/= 0.2ml on T2-weighted sequences were randomized to daily dutasteride 0.5mg or placebo for 6 months. Lesion volume was assessed at baseline, 3 and 6 months, with an image-guided biopsy to the lesion at study exit. The primary endpoint was percentage reduction in lesion volume over 6 months. This trial was registered with the European Clinical Trials register (EudraCT 2009-102405-18). RESULTS: Forty-two men were recruited between June 2010 and January 2012. In the dutasteride group, the average volumes at baseline and 6 months were 0.55ml and 0.38ml respectively, and the average percentage reduction was 36%. In the placebo group, the average volumes at baseline and 6 months were 0.65ml and 0.76ml respectively, and the average percentage reduction was -12%. The difference in percentage reductions between groups was 48% (95% CI 27.4-68.3%. p< 0.0001). The most common adverse event was deterioration in erectile function (25% in men randomized to dutasteride, 16% in men randomized to placebo). CONCLUSIONS: Dutasteride was associated with a significant reduction in prostate cancer volume on T2 weighted MRI images compared to placebo

Retrospective analysis of Schlafen11 (SLFN11) to predict the outcomes to therapies affecting the DNA damage response

BACKGROUND: The absence of the putative DNA/RNA helicase Schlafen11 (SLFN11) is thought to cause resistance to DNAdamaging agents (DDAs) and PARP inhibitors. METHODS: We developed and validated a clinically applicable SLFN11 immunohistochemistry assay and retrospectively correlated SLFN11 tumour levels to patient outcome to the standard of care therapies and olaparib maintenance. RESULTS: High SLFN11 associated with improved prognosis to the first-line treatment with DDAs platinum-plus-etoposide in SCLC patients, but was not strongly linked to paclitaxel–platinum response in ovarian cancer patients. Multivariate analysis of patients with relapsed platinum-sensitive ovarian cancer from the randomised, placebo-controlled Phase II olaparib maintenance Study19 showed SLFN11 tumour levels associated with sensitivity to olaparib. Study19 patients with high SLFN11 had a lower progression-free survival (PFS) hazard ratio compared to patients with low SLFN11, although both groups had the benefit of olaparib over placebo. Whilst caveated by small sample size, this trend was maintained for PFS, but not overall survival, when adjusting for BRCA status across the olaparib and placebo treatment groups, a key driver of PARP inhibitor sensitivity. CONCLUSION: We provide clinical evidence supporting the role of SLFN11 as a DDA therapy selection biomarker in SCLC and highlight the need for further clinical investigation into SLFN11 as a PARP inhibitor predictive biomarker

Zebrafish hoxd4a Acts Upstream of meis1.1 to Direct Vasculogenesis, Angiogenesis and Hematopoiesis

10.1371/journal.pone.0058857PLoS ONE83

Adaptogenic and nootropic activities of aqueous extract of Vitis vinifera (grape seed): an experimental study in rat model

BACKGROUND: The aerial parts of Vitis vinifera (common grape or European grape) have been widely used in Ayurveda to treat a variety of common and stress related disorders. In the present investigation, the seed extract of V. vinifera was evaluated for antistress activity in normal and stress induced rats. Furthermore, the extract was studied for nootropic activity in rats and in-vitro antioxidant potential to correlate its antistress activity. METHODS: For the evaluation of antistress activity, groups of rats (n = 6) were subjected to forced swim stress one hour after daily treatment of V. vinifera extract. Urinary vanillylmandelic acid (VMA) and ascorbic acid were selected as non-invasive biomarkers to assess the antistress activity. The 24 h urinary excretion of vanillylmandelic acid (VMA) and ascorbic acid were determined by spectrophotometric methods in all groups under normal and stressed conditions. The nootropic activity of the extract as determined from acquisition, retention and retrieval in rats was studied by conditioned avoidance response using Cook's pole climbing apparatus. The in vitro antioxidant activity was determined based on the ability of V. vinifera to scavenge hydroxyl radicals. RESULTS: Daily administration of V. vinifera at doses of 100, 200 and 300 mg/kg body weight one hour prior to induction of stress inhibited the stress induced urinary biochemical changes in a dose dependent manner. However, no change in the urinary excretion of VMA and ascorbic acid was observed in normal animals at all the doses studied. The cognition, as determined by the acquisition, retention and recovery in rats was observed to be dose dependent. The extract also produced significant inhibition of hydroxyl radicals in comparison to ascorbic acid in a dose dependent manner. CONCLUSION: The present study provides scientific support for the antistress (adaptogenic), antioxidant and nootropic activities of V. vinifera seed extract and substantiate the traditional claims for the usage of grape fruits and seeds in stress induced disorders

Adaptive remodeling of the bacterial proteome by specific ribosomal modification regulates Pseudomonas infection and niche colonisation

Post-transcriptional control of protein abundance is a highly important, underexplored regulatory process by which organisms respond to their environments. Here we describe an important and previously unidentified regulatory pathway involving the ribosomal modification protein RimK, its regulator proteins RimA and RimB, and the widespread bacterial second messenger cyclic-di-GMP (cdG). Disruption of rimK affects motility and surface attachment in pathogenic and commensal Pseudomonas species, with rimK deletion significantly compromising rhizosphere colonisation by the commensal soil bacterium P. fluorescens, and plant infection by the pathogens P. syringae and P. aeruginosa. RimK functions as an ATP-dependent glutamyl ligase, adding glutamate residues to the C-terminus of ribosomal protein RpsF and inducing specific effects on both ribosome protein complement and function. Deletion of rimK in P. fluorescens leads to markedly reduced levels of multiple ribosomal proteins, and also of the key translational regulator Hfq. In turn, reduced Hfq levels induce specific downstream proteomic changes, with significant increases in multiple ABC transporters, stress response proteins and non-ribosomal peptide synthetases seen for both ΔrimK and Δhfq mutants. The activity of RimK is itself controlled by interactions with RimA, RimB and cdG. We propose that control of RimK activity represents a novel regulatory mechanism that dynamically influences interactions between bacteria and their hosts; translating environmental pressures into dynamic ribosomal changes, and consequently to an adaptive remodeling of the bacterial proteome

Boerhaave syndrome as a complication of colonoscopy preparation: a case report

<p>Abstract</p> <p>Introduction</p> <p>Colonoscopy is one of the most frequently performed elective and invasive diagnostic interventions. For every colonoscopy, complete colon preparation is mandatory to provide the best possible endoluminal visibility; for example, the patient has to drink a great volume of a non-resorbable solution to flush out all feces. Despite the known possible nauseating side effects of colonoscopy preparation and despite the knowledge that excessive vomiting can cause rupture of the distal esophagus (Boerhaave syndrome), which is a rare but severe complication with high morbidity and mortality, it is not yet a standard procedure to provide a patient with an anti-emetic medication during a colon preparation process. This is the first report of Boerhaave syndrome induced by colonoscopy preparation, and this case strongly suggests that the prospect of being at risk of a severe complication connected with an elective colonoscopy justifies a non-invasive, inexpensive yet effective precaution such as an anti-emetic co-medication during the colonoscopy preparation process.</p> <p>Case presentation</p> <p>A 73-year-old Caucasian woman was scheduled to undergo elective colonoscopy. For the colonoscopy preparation at home she received commercially available bags containing soluble polyethylene glycol powder. No anti-emetic medication was prescribed. After drinking the prepared solution she had to vomit excessively and experienced a sudden and intense pain in her back. An immediate computed tomography (CT) scan revealed a rupture of the distal esophagus (Boerhaave syndrome). After initial conservative treatment by endoluminal sponge vacuum therapy, she was taken to the operating theatre and the longitudinal esophageal rupture was closed by direct suture and gastric fundoplication (Nissen procedure). She recovered completely and was discharged three weeks after the initial event.</p> <p>Conclusions</p> <p>To the best of our knowledge, this is the first report of a case of Boerhaave syndrome as a complication of excessive vomiting caused by colonoscopy preparation. The case suggests that patients who are prepared for a colonoscopy by drinking large volumes of fluid should routinely receive an anti-emetic medication during the preparation process, especially when they have a tendency to nausea and vomiting.</p