Paramagnetic Meissner effect in ZrB12 single crystal with non-monotonic vortex-vortex interactions

The magnetic response related to paramagnetic Meissner effect (PME) is studied in a high quality single crystal ZrB12 with non-monotonic vortex-vortex interactions. We observe the expulsion and penetration of magnetic flux in the form of vortex clusters with increasing temperature. A vortex phase diagram is constructed which shows that the PME can be explained by considering the interplay among the flux compression, the different temperature dependencies of the vortex-vortex and the vortex-pin interactions, and thermal fluctuations. Such a scenario is in good agreement with the results of the magnetic relaxation measurements.Comment: accepted by New Journal of Physic

Observational entropy with general quantum priors

Observational entropy captures both the intrinsic uncertainty of a thermodynamic state and the lack of knowledge due to coarse-graining. We demonstrate two interpretations of observational entropy, one as the statistical deficiency resulted from a measurement, the other one as the difficulty to infer the input state from the measurement statistics by quantum Bayesian retrodiction. These interpretations reveal that the observational entropy implicitly includes a uniform reference prior, from which we propose fully quantum generalizations by replacing the uniform prior by arbitrary quantum states. We propose three candidates for this generalization, discuss their properties, and show one of them gives a unified expression relating both interpretations.Comment: 11 pages, no figure, 1 tabl

Missense-depleted regions in population exomes implicate ras superfamily nucleotide-binding protein alteration in patients with brain malformation.

Genomic sequence interpretation can miss clinically relevant missense variants for several reasons. Rare missense variants are numerous in the exome and difficult to prioritise. Affected genes may also not have existing disease association. To improve variant prioritisation, we leverage population exome data to identify intragenic missense-depleted regions (MDRs) genome-wide that may be important in disease. We then use missense depletion analyses to help prioritise undiagnosed disease exome variants. We demonstrate application of this strategy to identify a novel gene association for human brain malformation. We identified de novo missense variants that affect the GDP/GTP-binding site of ARF1 in three unrelated patients. Corresponding functional analysis suggests ARF1 GDP/GTP-activation is affected by the specific missense mutations associated with heterotopia. These findings expand the genetic pathway underpinning neurologic disease that classically includes FLNA. ARF1 along with ARFGEF2 add further evidence implicating ARF/GEFs in the brain. Using functional ontology, top MDR-containing genes were highly enriched for nucleotide-binding function, suggesting these may be candidates for human disease. Routine consideration of MDR in the interpretation of exome data for rare diseases may help identify strong genetic factors for many severe conditions, infertility/reduction in reproductive capability, and embryonic conditions contributing to preterm loss

The benefits of neighborhood racial diversity: Neighborhood factors and its association with increased physical activity in ACS patients

Regular physical activity reduces the risk of adverse events after an acute coronary syndrome (ACS) [1]. Physical activity level is influenced by neighborhood factors such as racial diversity in the general population [2] and [3], but the impact of neighborhood factors on physical activity after an ACS is unknown. We therefore prospectively evaluated the relationship of post-ACS physical activity assessed by continuous activity monitors with neighborhood characteristics, including ethnic density, income, female headed households, and racial diversity, in patients enrolled in the Prescription Use, Lifestyle, and Stress Evaluation (PULSE) Study. We included 107 patients enrolled in the PULSE study from February 1, 2009 to June 30, who were monitored with an Actical® (Philips Respironics, Inc., Bend, Oregon) accelerometer device during the first 45 days following discharge from their ACS. For this analysis, physical activity level was operationalized as the mean maximum 6 min of activity during the day (M6m), which has previously been employed in studies of patients with chronic heart failure to summarize the patients' peak activity level [4] and [5]. Because the trajectory of physical activity is expected to change after hospital discharge, we calculated the M6m measure at 7, 14, 21, and 28 days post-discharge

Engineering linear, branched-chain triterpene metabolism in monocots

Triterpenes are thirty-carbon compounds derived from the universal five-carbon prenyl precursors isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). Normally, triterpenes are synthesized via the mevalonate (MVA) pathway operating in the cytoplasm of eukaryotes where DMAPP is condensed with two IPPs to yield farnesyl diphosphate (FPP), catalyzed by FPP synthase (FPS). Squalene synthase (SQS) condenses two molecules of FPP to generate the symmetrical product squalene, the first committed precursor to sterols and most other triterpenes. In the green algae Botryococcus braunii, two FPP molecules can also be condensed in an asymmetric manner yielding the more highly branched triterpene, botryococcene. Botryococcene is an attractive molecule because of its potential as a biofuel and petrochemical feedstock. Because B. braunii, the only native host for botryococcene biosynthesis, is difficult to grow, there have been efforts to move botryococcene biosynthesis into organisms more amenable to large-scale production. Here, we report the genetic engineering of the model monocot, Brachypodium distachyon, for botryococcene biosynthesis and accumulation. A subcellular targeting strategy was used, directing the enzymes (botryococcene synthase [BS] and FPS) to either the cytosol or the plastid. High titres of botryococcene (\u3e1 mg/g FW in T0 mature plants) were obtained using the cytosolic-targeting strategy. Plastid-targeted BS + FPS lines accumulated botryococcene (albeit in lesser amounts than the cytosolic BS + FPS lines), but they showed a detrimental phenotype dependent on plastid-targeted FPS, and could not proliferate and survive to set seed under phototrophic conditions. These results highlight intriguing differences in isoprenoid metabolism between dicots and monocots

Attenuation of osteoarthritis via blockade of the SDF-1/CXCR4 signaling pathway

This study was performed to evaluate the attenuation of osteoarthritic (OA) pathogenesis via disruption of the stromal cell-derived factor-1 (SDF-1)/C-X-C chemokine receptor type 4 (CXCR4) signaling with AMD3100 in a guinea pig OA model. OA chondrocytes and cartilage explants were incubated with SDF-1, siRNA CXCR4, or anti-CXCR4 antibody before treatment with SDF-1. Matrix metalloproteases (MMPs) mRNA and protein levels were measured with real-time polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. The 35 9-month-old male Hartley guinea pigs (0.88 kg ± 0.21 kg) were divided into three groups: AMD-treated group (n = 13); OA group (n = 11); and sham group (n = 11). At 3 months after treatment, knee joints, synovial fluid, and serum were collected for histologic and biochemical analysis. The severity of cartilage damage was assessed by using the modified Mankin score. The levels of SDF-1, glycosaminoglycans (GAGs), MMP-1, MMP-13, and interleukin-1 (IL-1β) were quantified with ELISA. SDF-1 infiltrated cartilage and decreased proteoglycan staining. Increased glycosaminoglycans and MMP-13 activity were found in the culture media in response to SDF-1 treatment. Disrupting the interaction between SDF-1 and CXCR4 with siRNA CXCR4 or CXCR4 antibody attenuated the effect of SDF-1. Safranin-O staining revealed less cartilage damage in the AMD3100-treated animals with the lowest Mankin score compared with the control animals. The levels of SDF-1, GAG, MMP1, MMP-13, and IL-1β were much lower in the synovial fluid of the AMD3100 group than in that of control group. The binding of SDF-1 to CXCR4 induces OA cartilage degeneration. The catabolic processes can be disrupted by pharmacologic blockade of SDF-1/CXCR4 signaling. Together, these findings raise the possibility that disruption of the SDF-1/CXCR4 signaling can be used as a therapeutic approach to attenuate cartilage degeneration