Tropical cyclone genesis across palaeoclimates

Tropical cyclone genesis is investigated for the Pliocene, Last Glacial Maximum (LGM) and the mid-Holocene through analysis of five climate models. The genesis potential index is used to estimate this from large scale atmospheric properties. The mid-Pliocene and LGM characterise periods where carbon dioxide levels were higher and lower than pre-industrial respectively, while the mid-Holocene differed primarily in its orbital configuration. The number of tropical cyclones formed each year is found to be fairly consistent across the various palaeoclimates. Although there is some model uncertainty in the change of global annual tropical cyclone frequency, there are coherent changes in the spatial patterns of tropical cyclogenesis. During the Pliocene and LGM, changes in carbon dioxide led to sea surface temperature changes throughout the tropics, yet the potential intensity of tropical cyclones appears relatively insensitive to these variations. Changes in tropical cyclone genesis during the mid-Holocene are observed to be asymmetric about the Equator: genesis is reduced in the Northern Hemisphere, but enhanced in the Southern Hemisphere. This is clearly driven by the altered seasonal insolation. Nonetheless, the enhanced seasonality may have driven localised effects on tropical cyclone genesis, through changes to the strength of monsoons and shifting of the inter-tropical convergence zone. Trends in future tropical cyclone genesis are neither consistent between the five models studied, nor with the palaeoclimate results. It is not clear why this should be the case

Cug2 is essential for normal mitotic control and CNS development in zebrafish.

Background: We recently identified a novel oncogene, Cancer-upregulated gene 2 (CUG2), which is essential for kinetochore formation and promotes tumorigenesis in mammalian cells. However, the in vivo function of CUG2 has not been studied in animal models. Results: To study the function of CUG2 in vivo, we isolated a zebrafish homologue that is expressed specifically in the proliferating cells of the central nervous system (CNS). Morpholino-mediated knockdown of cug2 resulted in apoptosis throughout the CNS and the development of neurodegenerative phenotypes. In addition, cug2-deficient embryos contained mitotically arrested cells displaying abnormal spindle formation and chromosome misalignment in the neural plate. Conclusions: Therefore, our findings suggest that Cug2 is required for normal mitosis during early neurogenesis and has functions in neuronal cell maintenance, thus demonstrating that the cug2 deficient embryos may provide a model system for human neurodegenerative disorders

Agonistic aptamer to the insulin receptor leads to biased signaling and functional selectivity through allosteric modulation

Due to their high affinity and specificity, aptamers have been widely used as effective inhibitors in clinical applications. However, the ability to activate protein function through aptamer-protein interaction has not been well-elucidated. To investigate their potential as target-specific agonists, we used SELEX to generate aptamers to the insulin receptor (IR) and identified an agonistic aptamer named IR-A48 that specifically binds to IR, but not to IGF-1 receptor. Despite its capacity to stimulate IR autophosphorylation, similar to insulin, we found that IR-A48 not only binds to an allosteric site distinct from the insulin binding site, but also preferentially induces Y1150 phosphorylation in the IR kinase domain. Moreover, Y1150-biased phosphorylation induced by IR-A48 selectively activates specific signaling pathways downstream of IR. In contrast to insulin-mediated activation of IR, IR-A48 binding has little effect on the MAPK pathway and proliferation of cancer cells. Instead, AKT S473 phosphorylation is highly stimulated by IR-A48, resulting in increased glucose uptake both in vitro and in vivo. Here, we present IR-A48 as a biased agonist able to selectively induce the metabolic activity of IR through allosteric binding. Furthermore, our study also suggests that aptamers can be a promising tool for developing artificial biased agonists to targeted receptors.111615Ysciescopu

Photoconductivity of biased graphene

Graphene is a promising candidate for optoelectronic applications such as photodetectors, terahertz imagers, and plasmonic devices. The origin of photoresponse in graphene junctions has been studied extensively and is attributed to either thermoelectric or photovoltaic effects. In addition, hot carrier transport and carrier multiplication are thought to play an important role. Here we report the intrinsic photoresponse in biased but otherwise homogeneous graphene. In this classic photoconductivity experiment, the thermoelectric effects are insignificant. Instead, the photovoltaic and a photo-induced bolometric effect dominate the photoresponse due to hot photocarrier generation and subsequent lattice heating through electron-phonon cooling channels respectively. The measured photocurrent displays polarity reversal as it alternates between these two mechanisms in a backgate voltage sweep. Our analysis yields elevated electron and phonon temperatures, with the former an order higher than the latter, confirming that hot electrons drive the photovoltaic response of homogeneous graphene near the Dirac point

Splenectomy for solitary splenic metastasis of ovarian cancer

BACKGROUND: Splenic metastases occur in rare cases with a few case reports of patients in the literature. Generally, splenic metastases mean late dissemination of a disease. Solitary splenic metastases from solid tumors are extremely unusual. CASE PRESENTATION: We report a case of a patient with ovarian mucinous cystadenocarcinoma who underwent splenectomy for isolated parenchymal metastasis. CONCLUSION: Ovarian epithelial tumors comprised most of isolated splenic metastases from gynecologic tumor. When isolated splenic recurrence is suspected on image studies and serum tumor markers, intraabdominal gross findings should be examined to exclude peritoneal carcinomatosis. If only spleen was under suspicion of recurrence of ovarian cancer, splenectomy may play a therapeutic role

Parameter Estimation Error Dependency on the Acquisition Protocol in Diffusion Kurtosis Imaging

Mono-exponential kurtosis model is routinely fitted on diffusion weighted, magnetic resonance imaging data to describe non-Gaussian diffusion. Here, the purpose was to optimize acquisitions for this model to minimize the errors in estimating diffusion coefficient and kurtosis. Similar to a previous study, covariance matrix calculations were used, and coefficients of variation in estimating each parameter of this model were calculated. The acquisition parameter, b values, varied in discrete grids to find the optimum ones that minimize the coefficient of variation in estimating the two non-Gaussian parameters. Also, the effect of variation of the target values on the optimized values was investigated. Additionally, the results were benchmarked with Monte Carlo noise simulations. Simple correlations were found between the optimized b values and target values of diffusion and kurtosis. For small target values of the two parameters, there is higher chance of having significant errors; this is caused by maximum b value limits imposed by the scanner than the mathematical bounds. The results here, cover a wide range of parameters D and K so that they could be used in many directionally averaged diffusion weighted cases such as head and neck, prostate, etc

Mitochondrial DNA Copy Number Is Associated with Breast Cancer Risk

Mitochondrial DNA (mtDNA) copy number in peripheral blood is associated with increased risk of several cancers. However, data from prospective studies on mtDNA copy number and breast cancer risk are lacking. We evaluated the association between mtDNA copy number in peripheral blood and breast cancer risk in a nested case-control study of 183 breast cancer cases with pre-diagnostic blood samples and 529 individually matched controls among participants of the Singapore Chinese Health Study. The mtDNA copy number was measured using real time PCR. Conditional logistic regression analyses showed that there was an overall positive association between mtDNA copy number and breast cancer risk (Ptrend = 0.01). The elevated risk for higher mtDNA copy numbers was primarily seen for women with <3 years between blood draw and cancer diagnosis; ORs (95% CIs) for 2nd, 3rd, 4th, and 5th quintile of mtDNA copy number were 1.52 (0.61, 3.82), 2.52 (1.03, 6.12), 3.12 (1.31, 7.43), and 3.06 (1.25, 7.47), respectively, compared with the 1st quintile (Ptrend = 0.004). There was no association between mtDNA copy number and breast cancer risk among women who donated a blood sample ≥3 years before breast cancer diagnosis (Ptrend = 0.41). This study supports a prospective association between increased mtDNA copy number and breast cancer risk that is dependent on the time interval between blood collection and breast cancer diagnosis. Future studies are warranted to confirm these findings and to elucidate the biological role of mtDNA copy number in breast cancer risk. © 2013 Thyagarajan et al

Application of Graphene within Optoelectronic Devices and Transistors

Scientists are always yearning for new and exciting ways to unlock graphene's true potential. However, recent reports suggest this two-dimensional material may harbor some unique properties, making it a viable candidate for use in optoelectronic and semiconducting devices. Whereas on one hand, graphene is highly transparent due to its atomic thickness, the material does exhibit a strong interaction with photons. This has clear advantages over existing materials used in photonic devices such as Indium-based compounds. Moreover, the material can be used to 'trap' light and alter the incident wavelength, forming the basis of the plasmonic devices. We also highlight upon graphene's nonlinear optical response to an applied electric field, and the phenomenon of saturable absorption. Within the context of logical devices, graphene has no discernible band-gap. Therefore, generating one will be of utmost importance. Amongst many others, some existing methods to open this band-gap include chemical doping, deformation of the honeycomb structure, or the use of carbon nanotubes (CNTs). We shall also discuss various designs of transistors, including those which incorporate CNTs, and others which exploit the idea of quantum tunneling. A key advantage of the CNT transistor is that ballistic transport occurs throughout the CNT channel, with short channel effects being minimized. We shall also discuss recent developments of the graphene tunneling transistor, with emphasis being placed upon its operational mechanism. Finally, we provide perspective for incorporating graphene within high frequency devices, which do not require a pre-defined band-gap.Comment: Due to be published in "Current Topics in Applied Spectroscopy and the Science of Nanomaterials" - Springer (Fall 2014). (17 pages, 19 figures

Effects of a contoured articular prosthetic device on tibiofemoral peak contact pressure: a biomechanical study

Many middle-aged patients are affected by localized cartilage defects that are neither appropriate for primary, nor repeat biological repair methods, nor for conventional arthroplasty. This in vitro study aims to determine the peak contact pressure in the tibiofemoral joint with a partial femoral resurfacing device (HemiCAP®, Arthrosurface Inc., Franklin, MA, USA). Peak contact pressure was determined in eight fresh-frozen cadaveric specimens using a Tekscan sensor placed in the medial compartment above the menisci. A closed loop robotic knee simulator was used to test each knee in static stance positions (5°/15°/30°/45°) with body weight ground reaction force (GRF), 30° flexion with twice the body weight (2tBW) GRF and dynamic knee-bending cycles with body weight GRF. The ground reaction force was adjusted to the living body weight of the cadaver donor and maintained throughout all cycles. Each specimen was tested under four different conditions: Untreated, flush HemiCAP® implantation, 1-mm proud implantation and 20-mm defect. A paired sampled t test to compare means (significance, P ≤ 0.05) was used for statistical analysis. On average, no statistically significant differences were found in any testing condition comparing the normal knee with flush device implantation. With the 1-mm proud implant, statistically significant increase of peak contact pressures of 217% (5° stance), 99% (dynamic knee bending) and 90% (30° stance with 2tBW) compared to the untreated condition was seen. No significant increase of peak contact pressure was evaluated with the 20-mm defect. The data suggests that resurfacing with the HemiCAP® does not lead to increased peak contact pressure with flush implantation. However, elevated implantation results in increased peak contact pressure and might be biomechanically disadvantageous in an in vivo application