We examined the number of tropical cyclones and cyclone days as well as tropical cyclone intensity over the past 35 years, in an environment of increasing sea surface temperature. A large increase ...was seen in the number and proportion of hurricanes reaching categories 4 and 5. The largest increase occurred in the North Pacific, Indian, and Southwest Pacific Oceans, and the smallest percentage increase occurred in the North Atlantic Ocean. These increases have taken place while the number of cyclones and cyclone days has decreased in all basins except the North Atlantic during the past decade.
The PI3K/Akt/mTOR pathway has a central role in cancer metastasis and radiotherapy. To develop effective therapeutics to improve radiosensitivity, understanding the possible pathways of ...radioresistance involved and the effects of a combination of the PI3K/Akt/mTOR inhibitors with radiotherapy on prostate cancer (CaP) radioresistant cells is needed. We found that compared with parent CaP cells, CaP-radioresistant cells demonstrated G0/G1 and S phase arrest, activation of cell cycle check point, autophagy and DNA repair pathway proteins, and inactivation of apoptotic proteins. We also demonstrated that compared with combination of single PI3K or mTOR inhibitors (BKM120 or Rapamycin) and radiation, low-dose of dual PI3K/mTOR inhibitors (BEZ235 or PI103) combined with radiation greatly improved treatment efficacy by repressing colony formation, inducing more apoptosis, leading to the arrest of the G2/M phase, increased double-strand break levels and less inactivation of cell cycle check point, autophagy and non-homologous end joining (NHEJ)/homologous recombination (HR) repair pathway proteins in CaP-radioresistant cells. This study describes the possible pathways associated with CaP radioresistance and demonstrates the putative mechanisms of the radiosensitization effect in CaP-resistant cells in the combination treatment. The findings from this study suggest that the combination of dual PI3K/Akt/mTOR inhibitors (BEZ235 or PI103) with radiotherapy is a promising modality for the treatment of CaP to overcome radioresistance.
The move to implement metal oxide based gate dielectrics in a metal-oxide-semiconductor field effect transistor is considered one of the most dramatic advances in materials science since the ...invention of silicon based transistors. Metal oxides are superior to SiO
2 in terms of their higher dielectric constants that enable the required continuous down-scaling of the electrical thickness of the dielectric layer while providing a physically thicker layer to suppress the quantum mechanical tunneling through the dielectric layer. Over the last decade, hafnium based materials have emerged as the designated dielectrics for future generation of nano-electronics with a gate length less than 45
nm, though there exists no consensus on the exact composition of these materials, as evolving device architectures dictate different considerations when optimizing a gate dielectric material. In addition, the implementation of a non-silicon based gate dielectric means a paradigm shift from diffusion based thermal processes to atomic layer deposition processes. In this report, we review how HfO
2 emerges from all likely candidates to become the new gold standard in the microelectronics industry, its different phases, reported electrical properties, and materials processing techniques. Then we use specific examples to discuss the evolution in designing hafnium based materials, from binary to complex oxides and to non-oxide forms as gate dielectric, metal gates and diffusion barriers. To address the impact of these hafnium based materials, their interfaces with silicon as well as a variety of semiconductors are discussed. Finally, the integration issues are highlighted, including carrier scattering, interface state passivation, phonon engineering, and nano-scale patterning, which are essential to realize future generations of devices using hafnium-based high-
k materials.
Research on strategic human resource (HR) management and organizational ambidexterity has assumed that organizational ambidexterity originates from operational managers that pursue both exploratory ...and exploitative activities. Yet, multilevel insights are absent about how and through which mechanisms HR practices may actually facilitate operational manager ambidexterity and how their ambidexterity may result into organizational ambidexterity. Our multisource and multilevel data from 467 operational managers and 104 senior managers within 52 firms reveals that the top-down effects of ability- and motivation-enhancing HR practices on operational manager ambidexterity are partially mediated by their role breadth self-efficacy and intrinsic motivational orientation. Furthermore, we find that the bottom-up relationship between operational manager and organizational ambidexterity is contingent on firm opportunity-enhancing HR practices. With that, our study provides important new multilevel insights into the effectiveness of strategic HR systems in supporting individual and organizational ambidexterity.
Unlike the capillaries conventionally used for gas-based spectral broadening of ultrashort (<100 fs) multi-millijoule pulses, which produce only normal dispersion at usable pressure levels, ...hollow-core photonic crystal fibres provide pressure-adjustable normal or anomalous dispersion. They also permit low-loss guidance in a hollow channel that is about ten times narrower and has a 100-fold-higher effective nonlinearity than capillary-based systems. This has led to several dramatic results, including soliton compression to few-cycle pulses, widely tunable deep-ultraviolet light sources, novel soliton-plasma interactions and multi-octave Raman frequency combs. A new generation of versatile and efficient gas-based light sources, which are tunable from the vacuum ultraviolet to the near infrared, and of versatile and efficient pulse compression devices is emerging.
Myelin sheaths provide critical functional and trophic support for axons in white matter tracts of the brain. Oligodendrocyte precursor cells (OPCs) have extraordinary metabolic requirements during ...development as they differentiate to produce multiple myelin segments, implying that they must first secure adequate access to blood supply. However, mechanisms that coordinate myelination and angiogenesis are unclear. Here, we show that oxygen tension, mediated by OPC-encoded hypoxia-inducible factor (HIF) function, is an essential regulator of postnatal myelination. Constitutive HIF1/2α stabilization resulted in OPC maturation arrest through autocrine activation of canonical Wnt7a/7b. Surprisingly, such OPCs also show paracrine activity that induces excessive postnatal white matter angiogenesis in vivo and directly stimulates endothelial cell proliferation in vitro. Conversely, OPC-specific HIF1/2α loss of function leads to insufficient angiogenesis in corpus callosum and catastrophic axon loss. These findings indicate that OPC-intrinsic HIF signaling couples postnatal white matter angiogenesis, axon integrity, and the onset of myelination in mammalian forebrain.
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•Oxygen tension directly regulates oligodendrocyte maturation through HIF signaling•Oligodendrocyte-encoded HIF activates Wnt signaling and angiogenesis in the brain•Oligodendrocyte-driven angiogenesis is critical for axon/white matter integrity
Oxygen tension induces oligodendrocyte-driven angiogenesis through HIF signaling, which provides metabolic support for myelination and early developing axons in mammalian forebrain.
Hepatocellular carcinoma (HCC) is the fifth most common cancer with high mortality, due to late diagnosis and limited treatment options. Blood miRNAs, which circulate in a highly stable, cell-free ...form, show promise as novel potential biomarkers for early detection of HCC. Whole miRNome profiling was performed to identify deregulated miRNAs between HCC and normal healthy (NH) volunteers. These deregulated miRNAs were validated in an independent cohort of HCC, NH and chronic Hepatitis B (CHB) volunteers and finally in a 3
cohort comprising NH, CHB, cirrhotic and HCC volunteers to evaluate miRNA changes during disease progression. The associations between circulating miRNAs and liver-damage markers, clinicopathological characteristics and survival outcomes were analysed to identify prognostic markers. Twelve miRNAs are differentially expressed between HCC and NH individuals in all three cohorts. Five upregulated miRNAs (miR-122-5p, miR-125b-5p, miR-885-5p, miR-100-5p and miR-148a-3p) in CHB, cirrhosis and HCC patients are potential biomarkers for CHB infection, while miR-34a-5p can be a biomarker for cirrhosis. Notably, four miRNAs (miR-1972, miR-193a-5p, miR-214-3p and miR-365a-3p) can distinguish HCC from other non-HCC individuals. Six miRNAs are potential prognostic markers for overall survival.
Plasma wakefield accelerators are capable of sustaining gigavolt-per-centimeter accelerating fields, surpassing the electric breakdown threshold in state-of-the-art accelerator modules by 3-4 orders ...of magnitude. Beam-driven wakefields offer particularly attractive conditions for the generation and acceleration of high-quality beams. However, this scheme relies on kilometer-scale accelerators. Here, we report on the demonstration of a millimeter-scale plasma accelerator powered by laser-accelerated electron beams. We showcase the acceleration of electron beams to 128 MeV, consistent with simulations exhibiting accelerating gradients exceeding 100 GV m
. This miniaturized accelerator is further explored by employing a controlled pair of drive and witness electron bunches, where a fraction of the driver energy is transferred to the accelerated witness through the plasma. Such a hybrid approach allows fundamental studies of beam-driven plasma accelerator concepts at widely accessible high-power laser facilities. It is anticipated to provide compact sources of energetic high-brightness electron beams for quality-demanding applications such as free-electron lasers.
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