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System-level simulation is significant in assisting microelectromechanical system (MEMS) optimization design due to time-saving and high efficiency. An accurate and efficient macromodel is greatly necessary for system-level simulation. Therefore, we present an energy analysis method based on decoupling and coupling energy fields to develop a parameterized macromodel, and a strongly thermal-electric coupling diode-based micro-Pirani vacuum sensor is used for demonstration and illustration. From the physics standpoint, the vacuum sensor is controlled by three energy fields (fluid field, thermal field, and electromagnetic field). As a self-heating device, the degree of electrothermal coupling in the vacuum sensor is greatly deep, and thus, diodes should first be modeled to facilitate the conversion from the electromagnetic field to the thermal field, which will simplify the order reduction process of the thermal field. Then, the state-space (ss) model of the thermal field, the parameterized behavioral model of the electromagnetic field, and the parameterized behavioral model of the fluid field are constructed. Subsequently, all models are described by Verilog-A and assembled to the macromodel based on the transfer information flow among three energy fields. To verify the accuracy of the macromodel, probe testing under forward current bias conditions, actual measurement of the vacuum sensor with the external interface circuit, and finite element analysis (FEA) are performed. The comparison results show that the steady-state results obtained by system-level simulation are in good agreement with the experimental results, and the maximum error is less than 0.63% under much the same parameters as the tested vacuum sensor.

Understanding the structure of the plastic deformation region is important for improving the mechanical property of amorphous alloys. What kind of structure is conducive to the formation of deformation zone is however still unclear yet. The uniaxial compression of amorphous Cu64.5Zr35.5has been conducted by a large-scale molecular dynamics simulation. The structure characteristics of the system, especially the deformation regions are systematically investigated based on the newly developed topologically close-packed cluster (TCP) method and the shear transformation zone theory. Results indicate that the deformation process is divided into three stages that can be reasonably explicated by the population and heredity of the 30 top largest standard clusters (LaSCs). It is also found that the response of topologically close-packed (TCP) atoms to strain is closely related with the bond number connected to icosahedra atoms, and the densely packed TCP atoms are more prone to non-affine displacement than the loosely packed ones, which act as the carrier of accommodating plastic deformation. In addition, the plastic deformation units are composed of various types of LaSCs, and the region with local translational symmetry is observed. These findings greatly improve the understanding of the relationship of microstructure and deformation of metallic glasses.

MicroRNAs (miRNAs) are abundant in neurons and play key roles in the function and development of the nervous system. This study focuses on the function of miR‐379‐5pin neurological function recovery during ischemic stroke. The expression of miR‐379‐5pin the serum of patients with ischemic stroke was determined. Human cerebral cortical neuron cells (HCN‐2) were subjected to oxygen/glucose deprivation (OGD) to mimic an ischemic stroke in vitro, whereas mice subjected to middle cerebral artery occlusion (MCAO) were used as an animal model. The serum of patients with ischemic stroke and OGD‐treated HCN‐2 cells displayed a poor expression of miR‐379‐5p. Upregulation of miR‐379‐5preduced the OGD‐induced cell damage and decreased the expression of the autophagy marker protein Beclin1 in cells. Rapamycin, an autophagy activator, blocked the protective functions of miR‐379‐5p. Further, miR‐379‐5pdirectly bound to MAP3K2. MAP3K2activated the JNK/c‐Jun signaling pathway and suppressed the neuroprotective events mediated by miR‐379‐5p. The in vitro results were reproduced in vivo, where upregulation of miR‐379‐5preduced neurological impairment and infarct size in MCAO‐induced mice. This study suggested that miR‐379‐5pshowed a neuroprotective effect on ischemic stroke and reduced autophagy of neurons through the suppression of MAP3K2and the JNK/c‐Jun axis.

The influence of trace Y on the microstructure evolution and mechanical properties of Mg100−xYx(x=0.25, 0.75, 1.5, 3, 4, 5, at.%) alloys during solidification process was investigated via molecular dynamics (MD) simulations. The results show that the Mg100−xYxalloys are mainly characterized by a face-centered cubic (FCC) crystal structure; this is different from pure metal Mg, which exhibits a hexagonal close packed (HCP) structure at room temperature. Among these alloys, Mg99.25Y0.75has a larger proportion of FCC cluster structures, with the highest fraction reaching 56.65%. As the content of the Y increases up to 5 at.% (Mg95Y5alloy), the amount of amorphous structures increases. The mechanical properties of the Mg100−xYxalloys are closely related to their microstructures. The Mg99.25Y0.75and Mg97Y3alloys exhibit the highest yield strengths of 1.86 and 1.90 GPa, respectively. The deformation mechanism of the Mg−Y alloys is described at the atomic level, and it is found that a difference in the FCC proportion caused by different Y contents leads to distinct deformation mechanisms.

ABSTRACTIschemic stroke is a common cerebrovascular disease with the main cause considered to be cerebral ischemia and reperfusion (I/R), which exerts irreparable injury on nerve cells. Thus, the development of neuroprotective drugs is an urgent concern. Curcumin, a known antioxidant, has been found to have neuroprotective effects. To determine the protective mechanism of curcumin in ischemic stroke, oxygen and glucose deprivation/reoxygenation (OGD/R) was used to treat PC12 cells to mimic the cerebral I/R cell model. Curcumin (20 μM) was applied to OGD/R PC12 cells, followed by Ca2+concentration, transepithelial electrical resistance (TEER), and cell permeability measurements. The results showed that OGD/R injury induced a decrease in TEER and increases in Ca2+concentration and cell permeability. In contrast, curcumin alleviated these effects. The protein kinase C θ (PKC-θ) was associated with the protective function of curcumin in the OGD/R cell model. Moreover, the middle cerebral artery occlusion and reperfusion model (MCAO/R) was applied to simulate the I/R rat model. Our results demonstrated that curcumin could reverse the MCAO/R-induced increase in Ca2+concentration and blood–brain barrier (BBB) disruption. Our study demonstrates the mechanisms by which curcumin exhibited a protective function against cerebral I/R through PKC-θ signaling by reducing BBB dysfunction.

ABSTRACTBruton’s tyrosine kinase (BTK) is involved in the diabetogenic process and cerebral ischemic injury. However, it remained unclear whether BTK inhibition has remedial effects on ischemia/reperfusion (I/R) injury complicated with diabetes. We aim to investigate the regulatory role and potential mechanism of ibrutinib, a selective inhibitor of BTK, in cerebral I/R injured diabetic mice. The cytotoxicity and cell vitality tests were performed to evaluate the toxic and protective effects of ibrutinib at different incubating concentrations on normal PC12 cells or which were exposed to high glucose for 24 h, followed by hypoxia and reoxygenation (H/R), respectively. Streptozotocin (STZ) stimulation-induced diabetic mice were subjected to 1 h ischemia and then reperfusion. Then the diabetic mice received different dosages of ibrutinib or vehicle immediately and 24 h after the middle cerebral artery occlusion (MCAO). The behavioral, histopathological, and molecular biological tests were then performed to demonstrate the neuroprotective effects and mechanism in I/R injured diabetic mice. Consequently, Ibrutinib improved the decreased cell viability and attenuated oxidative stress in the high glucose incubated PC12 cells which subjected to H/R injury. In the I/R injured diabetic mice, ibrutinib reduced the cerebral infarct volume, improved neurological deficits, ameliorated pathological changes, and improved autophagy in a slightly dose-dependent manner. Furthermore, the expression of PI3K/AKT/mTOR pathway-related proteins were significantly upregulated by ibrutinib treatment. In summary, our finding collectively demonstrated that Ibrutinib could effectively ameliorate cerebral ischemia/reperfusion injury via ameliorating inflammatory response, oxidative stress, and improving autophagy through PI3K/Akt/mTOR signaling pathway in diabetic mice.

The phase transition of tungsten (W) under high pressures was investigated with molecular dynamics simulation. The structure was characterized in terms of the pair distribution function and the largest standard cluster analysis (LSCA). It is found that under 40−100 GPa at a cooling rate of 0.1 K/ps a pure W melt first crystallizes into the body-centred cubic (BCC) crystal, and then transfers into the hexagonal close-packed (HCP) crystal through a series of BCC−HCP coexisting states. The dynamic factors may induce intermediate stages during the liquid−solid transition and the criss-cross grain boundaries cause lots of indistinguishable intermediate states, making the first-order BCC−HCP transition appear to be continuous. Furthermore, LSCA is shown to be a parameter-free method that can effectively analyze both ordered and disordered structures. Therefore, LSCA can detect more details about the evolution of the structure in such structure transition processes with rich intermediate structures.

An effective healing response is critical to healthy aging. In particular, energy homeostasis has become increasingly recognized as a factor in effective skin regeneration. ANT2 is a mediator of adenosine triphosphate import into mitochondria for energy homeostasis. Although energy homeostasis and mitochondrial integrity are critical for wound healing, the role played by ANT2 in the repair process had not been elucidated to date. In our study, we found that ANT2 expression decreased in aged skin and cellular senescence. Interestingly, overexpression of ANT2 in aged mouse skin accelerated the healing of full-thickness cutaneous wounds. In addition, upregulation of ANT2 in replicative senescent human diploid dermal fibroblasts induced their proliferation and migration, which are critical processes in wound healing. Regarding energy homeostasis, ANT2 overexpression increased the adenosine triphosphate production rate by activating glycolysis and induced mitophagy. Notably, ANT2-mediated upregulation of HSPA6 in aged human diploid dermal fibroblasts downregulated proinflammatory genes that mediate cellular senescence and mitochondrial damage. This study shows a previously uncharacterized physiological role of ANT2 in skin wound healing by regulating cell proliferation, energy homeostasis, and inflammation. Thus, our study links energy metabolism to skin homeostasis and reports, to the best of our knowledge, a previously unreported genetic factor that enhances wound healing in an aging model.

The polymorph selection during rapid solidification of zinc melt was investigated by molecular dynamics simulation. Several methods including g(r), energy, CNS, basic cluster and visualization were used to analyze the results. The results reveal that the cooling rate has no observable effect on the microstructure as T>Tc(Tcis the onset temperature of crystallization); and at the first stage of crystallization, although microstructures are different, the morphologies of nucleus are similar, which are composed of HCP and FCC layers; the polymorph selection of cooling rate finally takes place at the second stage of crystallization: at a high cooling rate, the rapid increase of FCC atoms leads to a FCC crystal mixed with less HCP structures; while at a low cooling rate, HCP atoms grow at the expense of FCC atoms, resulting in an almost perfect HCP phase. The results reveal that the cooling rate is one of the important factors for polymorph selection.

AbstractPrivacy is an important value which is internationally recognised as worthy of protection. However, it has been under constant challenge for a number of reasons including changes in technology which facilitate informational and other forms of surveillance and privacy-invasive media practices. Because of its multi-faceted nature, privacy is typically regulated by a variety of different means. Data protection laws seek to ensure the fair handling of personal information. Criminal sanctions are used to outlaw more serious invasions of privacy, including certain breaches of communications privacy and uses of surveillance devices. Assorted civil actions are relied on to protect broader interests in privacy. However, the piecemeal nature of privacy protection is often found to be inadequate and victims frequently lack appropriate remedies. Therefore, many common law countries either provide for or are actively considering the introduction of civil remedies to specifically address general privacy issues. There has also been active consideration of measures to regulate media organisations, especially in the light of the Murdoch scandal in the United Kingdom. The inadequacies in the law have prompted calls for law reform in Hong Kong, and recommendations have been made in the report on Civil Liability for Invasion of Privacy (2004). It examined the need of individuals to be able to seek civil remedies for unwarranted invasion of privacy. In it the Law Reform Commission of Hong Kong (HKLRC) proposed the introduction of specific statutory torts of privacy to cover acts and conduct frustrating the reasonable expectation of an individual’s privacy. It proposed that a person, who invaded another’s privacy by intruding upon their solitude or seclusion, or by intruding into their private affairs or concerns, should be liable in tort. It also recommended another tort for invasion of privacy arising out of public disclosure of private facts. This article focuses on the issue of civil liability and analyses the inadequacies of existing laws and regulatory regimes and attempts to come up with a model that is most suitable for Hong Kong. It takes the HKLRC’s recommendations as its starting point but refines and modifies them, drawing on the insights that have since become available from the work of other law reform bodies and further developments in overseas case law.

The glass-forming ability (GFA) of metallic glasses can be enhanced by adding trace elements, but it is difficult to explain the reasons from microcosmic viewpoint due to the limitation of experimental conditions. Therefore, in order to reveal the effects of trace elements on GFA, the rapid solidification process of Mg65Cu(35-x)Yx(x = 5,10,15,20,25) ternary alloys are simulated by molecular dynamics (MD) in this paper, then the short- and medium-range order, thermodynamics and dynamics are investigated. The average atomic potential energy shows that the GFA becomes stronger monotonically with the increase of Y element. S433 and S544 can evolve into S555 with higher fivefold symmetry and packing density during solidification, which the topologically close-packed (TCP) clusters are mainly composed of S555. And the higher TCP clusters system has stronger GFA, because TCP clusters are easy to connect with each other to form large-sized nanoclusters, and the larger size nanoclusters have the smaller average displacement, which hinders the crystallization. As TCP atoms with slower dynamic characteristics than other atoms, the dynamics with higher Y element becomes slower with the increase of TCP clusters, and thus adding Y element plays a promoting role for GFA.

XML has been widely used for information exchange and storage as the de facto data representation format nowadays. Several XML query languages such XPath, XQuery and XML-QL have been proposed. Many structural join algorithms have been proposed for processing XPath queries, Although holistic twig join algorithms has been proved to be I/O optimal in terms of input and output sizes for queries with only ancestor-descendant edges, it cannot control the size of intermediate results for queries with parent-child edges. We address the problem of efficient path queries with mixed of ancestor-descendant and parent-child edges on a simple but novel index, called BI (i.e. Binary Index) based on Dewey labeling scheme. And we propose a new holistic path join algorithm, namely PSBI, which has the same performance as PathStack for query path with only ancestor-descendant edges, but it is significantly more efficient than PathStack for queries with the presence of parent-child edges. Experimental results demonstrate that the PSBI and BI index has a substantial performance improvement compared to original PathStack algorithm.

Dark green islands (DGIs) are a common symptom of plants systemically infected with the mosaic virus. DGIs are clusters of green leaf cells that are free of virus but surrounded by yellow leaf tissue that is full of virus particles. In Cucumber mosaic virus (CMV)-infected Nicotiana tabacum leaves, the respiration and photosynthesis capabilities of DGIs and yellow leaf tissues were measured. The results showed that the cyanide-resistant respiration was enhanced in yellow leaf tissue and the photosynthesis was declined, while in DGIs they were less affected. The activities of the oxygen-scavenging enzymes catalase (CAT), peroxidase (POD), and superoxide dismutase (SOD) in infected leaves were signifi cantly higher than those in the healthy leaves, and the enzyme activities in DGIs were always lower than in the yellow leaf tissues. Reactive oxygen species (ROS) staining showed that the hydrogen peroxide content in yellow leaf tissues was apparently higher than that in DGIs, while the superoxide content was on the contrary. Formation of DGIs may be a strategy of the host plants resistance to the CMV infection.

The purpose of this study was to evaluate the extent and mechanism of uptake of wheat germ agglutinin-conjugated PLGA nanoparticles by A549 cells. PLGA nanoparticles of 150nm were prepared by a solvent diffusion method and covalently conjugated to FITC-WGA (fWGA) or FITC-bovine serum albumin (fBSA) by a two-step carbodiimide method. Uptake of fWGA-PLGA and fBSA-PLGA nanoparticles by confluent A549 cells was quantified by fluorometry. A549 cellular uptake of fWGA-PLGA nanoparticles at 2h, 37°C was 5.02-fold that of fBSA-PLGA nanoparticles at a loading concentration of 2.65mg/mL. The difference in uptake between the two types of nanoparticles was increased to 7.84-fold at a higher loading concentration of 5.3mg/mL, but was reduced to 2.07-fold by lowering the uptake temperature to 4°C. Coincubation with 5mg/mL of unlabeled WGA negated the differential uptake of fWGA-PLGA nanoparticles at 4°C, suggesting that the nanoparticles interacted with a specific WGA-binding receptor on the cell membrane. Internalization of the fWGA-PLGA nanoparticles by the A549 cells was confirmed by confocal microscopy. Filipin (1 μg/mL), a known inhibitor of caveolae, reduced the 1-h uptake of the nanoparticles by 75%. Surface modification of PLGA nanoparticles with WGA significantly enhanced its endocytosis by A549 cells by a receptor-mediated, caveola-dependent pathway. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:20–28, 2004

Objective The aim of this study was to determine the role of spinal adenosine A1 receptors (A1Rs) in the analgesic effects of electroacupuncture (EA) for neuropathic pain.Methods We performed EA for 30 minutes at the zusanli acupoint in the legs of rats with previously induced chronic constriction injuries and observed the mechanical and thermal pain thresholds 1 hour later. We also examined adenosine levels by high-performance liquid chromatography and A1R expression in the L4–6 spinal cord by western blot analysis. We then injected A1R short interfering RNA (AV-shA1RNA) into the L4–6 spinal cord to downregulate A1R expression and re-examined the mechanical and thermal pain thresholds.Results Adenosine levels and A1R expression in the L4–6 spinal cord were increased at 1 hour after EA. In addition, EA exhibited an analgesic effect that was reversed by AV-shA1RNA.Conclusions Our results suggest that EA at the zusanli acupoint elicits an analgesic effect against neuropathic pain, mediated by A1Rs in the spinal cord.

The article offers cooking tips and techniques from readers. A reader stores the flour in the freezer overnight before making pie dough, which helps keep the fat in the dough from melting so that it will roll out without sticking. A reader found out that saffron powder is easier to work with than saffron threads. Adding cool water could aid in easily removing or flipping fried eggs.