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Rapid response and strong mechanical properties are desired for smart materials used in soft actuators. A bioinspired hybrid hydrogel actuator was designed and prepared by series combination of three trunks of tough polymer-clay hydrogels to accomplish the comprehensive actuation of "extension-grasp-retraction" like a fishing rod. The hydrogels with thermo-creep and thermo-shrinking features were successively irradiated by near-infrared (NIR) to execute extension and retraction, respectively. The GO in the hydrogels absorbed the NIR energy and transformed it into thermo-energy rapidly and effectively. The hydrogel with adhesion or magnetic force was adopted as the "hook" of the hybrid hydrogel actuator for grasping object. The hook of the hybrid hydrogel actuator was replaceable according to applications, even with functional materials other than hydrogels. This study provides an innovative concept to explore new soft actuators through combining response hydrogels and programming the same stimulus.

Machining vibrations are harmful to workpiece surface quality and tool life, especially for thin-walled parts. A lightweight damping device is proposed by utilizing eddy current damping, and it can be easily attached onto the workpiece surface by glue. The cylindrical device is mainly composed of a magnet, an aluminum cylindrical conductor, and two springs. An induced repulsive force due to the machining vibration is generated and transmitted to the workpiece and then contributed to the vibration attenuation. Dynamic response evaluation on a cantilever beam by hammer tests demonstrates that the device is able to damp vibration mode and the effect of additive mass on the beam dynamics is investigated by roving the attaching point. Moreover, the device is applied to damp multiple modes and attenuate machining vibration of a thin-walled frame. Machining tests under different configurations of cutting parameters are carried out, and its effectiveness of wide band and adaptability to the varying machining processes are validated.

Objective— Adhesive ligand–receptor interactions play key roles in blood vessel angiogenesis but remain poorly characterized during lymphatic vessel growth. In this study, we use genetic approaches in both fish and mice to address the roles of cell surface integrin ligand vascular cell adhesion molecule (VCAM) and its 2 receptors, integrins α9 and α4, during lymphatic vascular development. Approach and Results— Conditional deletion of the Vcam gene was used to test VCAM function in lymphatic growth in midgestation mice. Morpholino knockdown and cRNA rescue of the 2 zebrafish vcam alleles, as well as integrins α9 and 4, were used to test the role of these ligands and receptors during lymphatic growth in the developing fish. We show that VCAM is essential for lymphatic development in the zebrafish embryo and that integrin α9 (Itgα9) rather than Itgα4 is the required VCAM receptor in the developing fish. VCAM is expressed along lines of lymphatic migration in the mouse intestine, but its loss only retards lymphatic growth. Conclusions— These studies reveal an unexpected role for cell–cell adhesion mediated by Itgα9–VCAM interactions during lymphatic development in the fish but not in the mouse. We propose that the relative importance of cellular adhesive ligands is magnified under conditions of rapid tissue growth when the cell number increases faster than cell matrix, such as in the early zebrafish embryo.

This study explores the influence of psychological resilience on the onset of activities of daily living (ADL) disability among Chinese older adults and examines whether this association varies by age.Using a sample of 11,112 older adults from 2 waves of the Chinese Longitudinal Healthy Longevity Survey, collected in 2002 and 2005, this study examines whether higher levels of psychological resilience (measured by a 5-item scale) predict lower risk of ADL incidence during a 3-year follow-up and whether this effect varies by age.Higher levels of resilience at the baseline are significantly associated with reduced risk of becoming ADL disabled during the 3-year follow-up period, independent of baseline sociodemographic characteristics, family support, and health. Moreover, resilience by age interaction is detected. Higher levels of resilience are more protective against the onset of disability for the younger old (aged 65-84) than the oldest old (aged 85 and older).Among older adults in China, psychological resilience is a protective factor against ADL disability, and the benefits are particularly significant for older adults younger than 85 years.

The tuned mass damper (TMD) has been applied to the machining vibration control widely, and it is categorized into several groups depending on the available degrees of freedom (DOF). Previous works have been mostly focused on the application of single-DOF TMD, but it is revealed that the damping performance could be further promoted by multiple-DOFs TMD. A two-DOF TMD for the milling vibration mitigation is investigated. The TMD possessing translation and rotation motion is designed with tunable stiffness and damping, and the design parameters are optimized numerically based on the H∞ criterion. The TMD is implemented on a workpiece fixture with single dominant mode, and the experimentally tuned frequency response function (FRF) has 80.8 percent reduction on the amplitude of the flexible mode. Spindle speeds corresponding to the resonance and chatter vibrations are selected for the machining tests. The measured vibrations and surface quality validate the improvement of the machining stability by the TMD, and the critical depth of cut is increased at least two folds.

A facile method was explored to reinforce the poly(N-isopropylacrylamide) (PNIPAm)-hectorite nanocomposite hydrogel (NC gel) by heat treatment at temperature above the volume phase transition temperature (VPTT), which enhanced mechanical strength and reduced swelling capacity with denser microporous structure as compared with the non-treated NC gel. This reinforcement effect was increased by increasing treating temperature and/or treating time, which still remained even after swelling, indicating an irreversible structure change in the treated NC gels. Heat treatment became more effective when the NC gel contained higher clay content. The quartz crystal microbalance (QCM) data showed that the interaction between PNIPAm chains and clay platelets became stronger at temperatures higher than the VPTT, causing an increase in the crosslinking density of the treated NC gels. A strong hydrogel was obtained by heat treatment of the aqueous mixture of PNIPAm and hectorite clay for the first time. POLYM. COMPOS., 2014. © 2014 Society of Plastics Engineers

The emergence of smartwatches poses new challenges to information security. Although there are mature touch-based authentication methods for smartphones, the effectiveness of using these methods on smartwatches is still unclear. We conducted a user study (n=16) to evaluate how authentication methods (PIN and Pattern), UIs (Square and Circular), and display sizes (38mm and 42mm) affect authentication accuracy, speed, and security. Circular UIs are tailored to smartwatches with fewer UI elements. Results show that 1) PIN is more accurate and secure than Pattern; 2) Pattern is much faster than PIN; 3) Square UIs are more secure but less accurate than Circular UIs; 4) display size does not affect accuracy or speed, but security; 5) Square PIN is the most secure method of all. The study also reveals a security concern that participants' favorite method is not the best in any of the measures. We finally discuss implications for future touch-based smartwatch authentication design., ISWC '17, Proceedings of the 2017 ACM International Symposium on Wearable Computers, 122-125, ACM New York, NY, USA

Prolonged isolated thrombocytopenia (PT) is a severe complication in patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Whether the megakaryoctic potential of hematopoietic stem cells (HSCs) in bone marrow is intact and what factors drive the pathological process of PT remain elusive. A retrospective study in patients (n = 285) receiving HSCT revealed that the occurrence of PT was approximately 8% and the number of platelets and megakaryocytes in PT patients is much lower compared with control subjects. To test whether the deficiency of thrombopoiesis was caused by the activities of HSCs, the megakaryocytic differentiation potential of HSCs before or after transplantation was assessed. Interestingly, a substantial decrease of megakaryocytic differentiation was observed 2 weeks after transplantation of HSCs in all of the allo-HSCT recipients. However, 4 weeks after transplantation, the ability of HSCs to generate CD41+CD42b+ megakaryocytes in successful platelet engraftment patients recovered to the same level as those of HSCs before implantation. In contrast, HSCs derived from PT patients throughout the postimplantation period exhibited poor survival and failed to differentiate properly. A protein array analysis demonstrated that multiple inflammation-associated cytokines were elevated in allo-HSCT recipients with PT. Among them, insulin-like growth factor–binding protein 1 and regulated on activation, normal T cell expressed and secreted were found to significantly suppress the proliferation and megakaryocytic differentiation of HSCs in vitro. Our results suggested that the occurrence of PT may be attributed, at least partially, to the damage to HSC function caused by inflammation-associated cytokines after HSCT. These findings shed light on the mechanism underlying HSC megakaryocytic differentiation in PT patients and may provide potential new strategies for treating PT patients after HSCT.

GPR54 is highly expressed in the central nervous system and plays a crucial role in pubertal development. However, GRP54 is also expressed in the immune system, implying possible immunoregulatory functions. Here we investigated the role of GPR54 in T cell and immune tolerance. GPR54 deficiency led to an enlarged thymus, an increased number of thymocytes, and altered thymic micro-architecture starting around puberty, indicating GPR54 function in T-cell development through its regulatory effect on the gonadal system. However, flow cytometry revealed a significant reduction in the peripheral regulatory T cell population and a moderate decrease in CD4 single-positive thymocytes in prepubertal Gpr54-/- mice. These phenotypes were confirmed in chimeric mice with GPR54 deficient bone marrow-derived cells. In addition, we found elevated T cell activation in peripheral and thymic T cells in Gpr54-/- mice. When intact mice were immunized with myelin oligodendrocyte glycoprotein, a more severe experimental autoimmune encephalomyelitis (EAE) developed in the Gpr54-/- mice. Interestingly, aggravated EAE disease was also manifested in castrated and bone marrow chimeric Gpr54-/- mice compared to the respective wild-type control, suggesting a defect in self-tolerance resulting from GPR54 deletion through a mechanism that bypassed sex hormones. These findings demonstrate a novel role for GPR54 in regulating self-tolerant immunity in a sex hormone independent manner.

Cerebral cavernous malformations (CCMs) are a cause of stroke and seizure for which no effective medical therapies yet exist. CCMs arise from the loss of an adaptor complex that negatively regulates MEKK3-KLF2/4 signalling in brain endothelial cells, but upstream activators of this disease pathway have yet to be identified. Here we identify endothelial Toll-like receptor 4 (TLR4) and the gut microbiome as critical stimulants of CCM formation. Activation of TLR4 by Gram-negative bacteria or lipopolysaccharide accelerates CCM formation, and genetic or pharmacologic blockade of TLR4 signalling prevents CCM formation in mice. Polymorphisms that increase expression of the TLR4 gene or the gene encoding its co-receptor CD14 are associated with higher CCM lesion burden in humans. Germ-free mice are protected from CCM formation, and a single course of antibiotics permanently alters CCM susceptibility in mice. These studies identify unexpected roles for the microbiome and innate immune signalling in the pathogenesis of a cerebrovascular disease, as well as strategies for its treatment.

Drug-resistant malarial strains have been continuously emerging recently, which posts a great challenge for the global health. Therefore, new antimalarial drugs with novel targeting mechanisms are urgently needed for fighting drug-resistant malaria. NADH-ubiquinone oxidoreductase of Plasmodium falciparum (PfNDH2) represents a viable target for antimalarial drug development. However, the absence of structural information on PfNDH2 limited rational drug design and further development. Herein, we report high resolution crystal structures of the PfNDH2 protein for the first time in Apo-, NADH-, and RYL-552 (a new inhibitor)-bound states. The PfNDH2 inhibitor exhibits excellent potency against both drug-resistant strains in vitro and parasite-infected mice in vivo via a potential allosteric mechanism. Furthermore, it was found that the inhibitor can be used in combination with dihydroartemisinin (DHA) synergistically. These findings not only are important for malarial PfNDH2 protein-based drug development but could also have broad implications for other NDH2-containing pathogenic microorganisms such as Mycobacterium tuberculosis.

An unprecedented double C-S bond formation method has been developed to prepare both symmetric and unsymmetric diarylsulfones with simple arenes in a single step. This represents the first example that K2S2O8 can be employed as a highly effective sulfonating agent to synthesize diarylsulfones. The reaction demonstrates excellent reactivity, good functional group tolerance and high yields.

Host-defense peptides (HDPs) are produced by eukaryotes to defend against bacterial infection, and diverse synthetic polymers have recently been explored as mimics of these natural peptides. HDPs are rich in both hydrophobic and cationic amino acid residues, and most HDP-mimetic polymers have therefore contained binary combinations of hydrophobic and cationic subunits. However, HDP-mimetic polymers rarely duplicate the hydrophobic surface and cationic charge density found among HDPs ( Hu , K. ; et al. Macromolecules 2013 , 46 , 1908 ); the charge and hydrophobicity are generally higher among the polymers. Statistical analysis of HDP sequences ( Wang , G. ; et al. Nucleic Acids Res. 2009 , 37 , D933 ) has revealed that serine (polar but uncharged) is a very common HDP constituent and that glycine is more prevalent among HDPs than among proteins in general. These observations prompted us to prepare and evaluate ternary nylon-3 copolymers that contain a modestly polar but uncharged subunit, either serine-like or glycine-like, along with a hydrophobic subunit and a cationic subunit. Starting from binary hydrophobic-cationic copolymers that were previously shown to be highly active against bacteria but also highly hemolytic, we found that replacing a small proportion of the hydrophobic subunit with either of the polar, uncharged subunits can diminish the hemolytic activity with minimal impact on the antibacterial activity. These results indicate that the incorporation of polar, uncharged subunits may be generally useful for optimizing the biological activity profiles of antimicrobial polymers. In the context of HDP evolution, our findings suggest that there is a selective advantage to retaining polar, uncharged residues in natural antimicrobial peptides.

Thin-walled workpieces are largely manufactured in the aerospace industry. The manufacturing process has been a problem due to its flexibility, and chatter vibrations are apt to occur, which restricts the machining efficiency and quality. A vibration suppression device for thin-walled workpieces is presented based on the electromagnetic induction principle, which utilizes machining vibrations to generate resistant force on the workpiece. The formulated force varies with the workpiece vibration velocity, but in an opposite direction. Excitation tests using the electromagnetic shaker illustrate that the device is effective in vibration attenuation. Finally, machining tests are carried out with applications to two thin-walled structures for further verification. The machining vibrations and surface quality demonstrate the damping promotion of the workpiece assembly, and milling stability limit is increased by more than twofold.

The present paper reports an interesting and versatile thermo-moldable property of poly(N,N-dimethylacrylamide)-clay nanocomposite hydrogels (NC gel). The NC gel can be thermo-pressed and molded to a desired shape at 80 °C, and the shape can be fixed by cooling to 20 °C. Mechanical test and small-angle X-ray scattering demonstrate that the molded NC gel still exhibits high strength with an elastic network structure. Viscoelastic measurements show that with increasing the temperature, the equilibrium shear modulus Ge decreases, and the creep and permanent deformation increases obviously, suggesting a decrease in the cross-linking density. Ge recovers when the gel is cooled down to room temperature, reflecting the recovery of the cross-linking density. This thermo-moldable property is attributed to reversible cross-linking in such NC gels by changing the temperature. This work provides a facile method to deform or pattern the tough NC gels after synthesis.

Based on the modeling of circular corner milling process, the implicit three-step four-order ADAMS numerical analysis method is presented in this article to solve the differential equation of milling dynamics, which considers non-uniform variation of the radial depth of cut and nonlinear feature of tool–workpiece system. The dynamic cutting forces are predicted in time domain and experimentally verified. On this basis, with comprehensive application of time-domain stability criteria for predicted data, the chatter stability of the milling process is simulated. The predicted stability lobe diagrams are compared against experimental results to confirm the validity of the simulation algorithm, which provides an effective way to optimize cutting parameters for circular corner milling.

Stability lobes are widely used to avoid chatter which restricts the machining quality and productivity. A lot of work has been done to predict the stability lobes fast and accurately. However, most of them are based on the linear force model, and the chatter stability limit is formulated as independent on the feed rate, which is inconsistent with the machining practice. By referencing with the zero-order solution, this paper investigates the chatter stability prediction based on the exponential force model. Focusing on the cutters with a lead angle (i.e., inserted face mill, the ball-end mill, and bull-nose end mill) where chatter is likely to be brought up in Z direction, the stability model is extended to three-dimensional. Taylor equation is utilized to linearize the exponential expressions when computing the directional coefficients in order to solve the stability limit analytically as the linear force model. Simulation results show that the exponential force model agrees with the measurements as well as the linear force model in the cutting force prediction, and it is able to demonstrate the feed rate effect on the stability limit. The stability limit is found to be increased as the feed rate increases, which is evidenced by the time domain simulation. Cutting tests are performed in the end to verify the stability model. The proposed model could be reduced to either X/Y dimensional or linear force model-based stability model by further simplifications.

Mammals must inflate their lungs and breathe within minutes of birth to survive. A key regulator of neonatal lung inflation is pulmonary surfactant, a lipoprotein complex which increases lung compliance by reducing alveolar surface tension (Morgan, 1971). Whether other developmental processes also alter lung mechanics in preparation for birth is unknown. We identify prenatal lymphatic function as an unexpected requirement for neonatal lung inflation and respiration. Mice lacking lymphatic vessels, due either to loss of the lymphangiogenic factor CCBE1 or VEGFR3 function, appear cyanotic and die shortly after birth due to failure of lung inflation. Failure of lung inflation is not due to reduced surfactant levels or altered development of the lung but is associated with an elevated wet/dry ratio consistent with edema. Embryonic studies reveal active lymphatic function in the late gestation lung, and significantly reduced total lung compliance in late gestation embryos that lack lymphatics. These findings reveal that lymphatic vascular function plays a previously unrecognized mechanical role in the developing lung that prepares it for inflation at birth. They explain respiratory failure in infants with congenital pulmonary lymphangiectasia, and suggest that inadequate late gestation lymphatic function may also contribute to respiratory failure in premature infants.

The secreted protein CCBE1 is required for lymphatic vessel growth in fish and mice, and mutations in the CCBE1 gene cause Hennekam syndrome, a primary human lymphedema. Here we show that loss of CCBE1 also confers severe anemia in midgestation mouse embryos due to defective definitive erythropoiesis. Fetal liver erythroid precursors of Ccbe1 null mice exhibit reduced proliferation and increased apoptosis. Colony-forming assays and hematopoietic reconstitution studies suggest that CCBE1 promotes fetal liver erythropoiesis cell nonautonomously. Consistent with these findings, Ccbe1(lacZ) reporter expression is not detected in hematopoietic cells and conditional deletion of Ccbe1 in hematopoietic cells does not confer anemia. The expression of the erythropoietic factors erythropoietin and stem cell factor is preserved in CCBE1 null embryos, but erythroblastic island (EBI) formation is reduced due to abnormal macrophage function. In contrast to the profound effects on fetal liver erythropoiesis, postnatal deletion of Ccbe1 does not confer anemia, even under conditions of erythropoietic stress, and EBI formation is normal in the bone marrow of adult CCBE1 knockout mice. Our findings reveal that CCBE1 plays an essential role in regulating the fetal liver erythropoietic environment and suggest that EBI formation is regulated differently in the fetal liver and bone marrow.

The productivity of many industrial cutting processes is limited by high amplitude chatter vibrations. An optimization technique based on the use of the stability lobes helps to increase the productivity of these processes, improving the life of machine elements and reducing the tool wear as well. The best-known lobes correspond to Hopf bifurcations. However, in case of interrupted cutting, additional lobes appear due to period doubling or flip bifurcation. When the system has more than one dominant vibration mode, important variations can appear in stability due to interaction between modes. The basic mathematics for the appearance of these new lobes are shown in this article. The frequency domain study shows that lobes related to flip bifurcation are a special case of the interaction between modes. The results of these interactions are verified by comparison with semi-discretization method and time domain simulations, respectively.

Melanocortin-3 and 4 receptors (MC3R and MC4R) can regulate energy homeostasis, but their respective roles especially the functions of MC3R need more exploration. Here Mc3r and Mc4r single and double knockout (DKO) rats were generated using CRISPR-Cas9 system. Metabolic phenotypes were examined and data were compared systematically. Mc3r KO rats displayed hypophagia and decreased body weight, while Mc4r KO and DKO exhibited hyperphagia and increased body weight. All three mutants showed increased white adipose tissue mass and adipocyte size. Interestingly, although Mc3r KO did not show a significant elevation in lipids as seen in Mc4r KO, DKO displayed even higher lipid levels than Mc4r KO. DKO also showed more severe glucose intolerance and hyperglycaemia than Mc4r KO. These data demonstrated MC3R deficiency caused a reduction of food intake and body weight, whereas at the same time exhibited additive effects on top of MC4R deficiency on lipid and glucose metabolism. This is the first phenotypic analysis and systematic comparison of Mc3r KO, Mc4r KO and DKO rats on a homogenous genetic background. These mutant rats will be important in defining the complicated signalling pathways of MC3R and MC4R. Both Mc4r KO and DKO are good models for obesity and diabetes research.

This study aims to identify correlates of satisfaction in late life parental role, using a sample of 432 older parents (not couples) aged 60 to 79 with 1,223 adult children living in one of the least devel-oped counties of northern China. Drawing upon the symbolic interactionism perspective and Chin-ese cultural emphasis on filial piety, we tested a parental satisfaction model including a set of vari-ables capturing parental perceptions of relationship quality with each of their grown children (hereafter offspring), expectations of various forms of support from offspring, and evaluations of offspring’s filial piety (being filial). Most parents in our sample were satisfied with their parental role. Logistic regression analysis indicated that getting along with offspring, offspring met parental expectations in terms of pro-viding emotional, practical, and financial support, and offspring being filial were significantly associated with parental satisfaction, respectively, net of parent and offspring characteristics. When simultaneously examined in the full model, however, only two correlates remained significant: getting along with offspring and offspring being filial. Offspring’s filial piety was associated with parental satisfaction in a dose-re-sponse manner, indicating the importance of considering multiple children in a family on parental well-being. Findings underscore the significance of parental perceptions of relationship quality with offspring and offspring’s filial piety for parental satisfaction. Findings suggest that filial piety, a multifaceted concept deeply rooted in Confucianism, continues to exert a strong influence today on Chinese family relationships despite the dramatic socioeconomic and cultural transformation China has been experiencing in the past three decades.

Lymphangiogenesis is supported by 2 homologous VEGFR3 ligands, VEGFC and VEGFD. VEGFC is required for lymphatic development, while VEGFD is not. VEGFC and VEGFD are proteolytically cleaved after cell secretion in vitro, and recent studies have implicated the protease a disintegrin and metalloproteinase with thrombospondin motifs 3 (ADAMTS3) and the secreted factor collagen and calcium binding EGF domains 1 (CCBE1) in this process. It is not well understood how ligand proteolysis is controlled at the molecular level or how this process regulates lymphangiogenesis, because these complex molecular interactions have been difficult to follow ex vivo and test in vivo. Here, we have developed and used biochemical and cellular tools to demonstrate that an ADAMTS3-CCBE1 complex can form independently of VEGFR3 and is required to convert VEGFC, but not VEGFD, into an active ligand. Consistent with these ex vivo findings, mouse genetic studies revealed that ADAMTS3 is required for lymphatic development in a manner that is identical to the requirement of VEGFC and CCBE1 for lymphatic development. Moreover, CCBE1 was required for in vivo lymphangiogenesis stimulated by VEGFC but not VEGFD. Together, these studies reveal that lymphangiogenesis is regulated by two distinct proteolytic mechanisms of ligand activation: one in which VEGFC activation by ADAMTS3 and CCBE1 spatially and temporally patterns developing lymphatics, and one in which VEGFD activation by a distinct proteolytic mechanism may be stimulated during inflammatory lymphatic growth.

Milling cutter with large length-diameter ratio is usually used in machining complex aerospace parts with deep pockets and thin ribs. Large overhang causes stiffness reduction of the cutting tool, which is a significant factor leading to machining chatter. Damped milling cutter can effectively suppress the vibration. Three structural designs of damped cutter are proposed, and modal analysis and harmonious analysis are performed by ANSYS. Simulation results show that the milling cutter embedded with two degree-of-freedom passive damper exhibits the best vibration suppression and the magnitude of frequency response is reduced by 63.7 %, which therefore enhances the machining stability.

SummaryNeural progenitor cell (NPC) therapy is considered a promising treatment modality for multiple sclerosis (MS), potentially acting through neural repair. Here, we showed that intravenous administration of NPCs ameliorated experimental autoimmune encephalomyelitis (EAE) by selectively inhibiting pathogenic T helper 17 (Th17) cell differentiation. Leukemia inhibitory factor (LIF) produced by NPCs was responsible for the observed EAE suppression. Through the inducible LIF receptor expression, LIF inhibited the differentiation of Th17 cells in EAE mice and that from MS subjects. At the molecular level, LIF exerted an opposing effect on interleukin 6 (IL-6)-induced signal transducer and activator of transcription 3 (STAT3) phosphorylation required for Th17 cell differentiation by triggering a signaling cascade that activated extracellular signal-regulated MAP kinase (ERK) and upregulated suppressor of cytokine signaling 3 (SOCS3) expression. This study reveals a critical role for LIF in regulating Th17 cell differentiation and provides insights into the mechanisms of action of NPC therapy in MS.

A new-type nonlinear tuned mass damper (TMD) containing an additional element of elastic support dry friction compared with the common linear TMD is proposed to suppress machining chatter. The design and tuning process of this nonlinear TMD have used a combination of analytical modeling with experimentally measured frequency response function (FRF) of the machining system. Theoretical studies and experimental results show that the proposed nonlinear TMD can remarkably improve the machining stability by effectively suppressing the magnitude of the real part of the FRF of the damped machining system.

The industrial robot has been employed in the field of machining processes due to its high flexibility, while its applications are restricted by the structural disadvantages (i.e., poor stiffness and low positional accuracy). The robotic high flexibility is evidenced by the ability of reaching a specified position through various postures. Therefore it is important to identify the dynamic behaviours of a specific point at different postures. The frequency responses of the cutter tip of a robot are measured by separating the working area into several layers. The result shows that dynamic characteristics are dependent on posture. The critical depth of cut is ranged from 0.35 mm to 0.93 mm by taking an example of spindle speed 2,000 rpm. And the critical depth of cut when feeding in Y direction is much larger than the X direction.

To determine the possible involvement of neutrophils in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), we examined their infiltration pattern during the course of MOG35-55-induced EAE in the C57BL/6 mice. Using immunohistochemistry and flow cytometry, we found that the number of neutrophils was significantly increased during onset of disease, remained high at the peak stage and dramatically declined thereafter. Moreover, dual labeling provided anatomical evidence of a prominent accumulation of neutrophils in the center and vicinity of lesion areas of demyelination, axonal loss or axonal degeneration at early stages of EAE. These observations provide evidence that neutrophils are one of the major sources of inflammatory cells to initiate EAE, which suggest that neutrophils may contribute to demyelination and axonal degeneration in the acute phase of EAE and play a greater role than previously thought in the pathogenesis of EAE.

The KCNQ1 channel is abundantly expressed in the gastric parietal cells. Although the functional coupling of KCNQ1 with the H(+)/K(+)-ATPase has already been confirmed on the basis of pharmacological kinetics, the effect of a KCNQ1 loss-of-function mutation on gastric acidification remains unclear. In this study, parietal cells and gastric glands from both C57BL/6 J mice (normal control) and J343 mice (mice with a KCNQ1 loss-of-function mutation) were isolated to study the effects of KCNQ1 on gastric acidification. We found that the mutation limited intracellular acidification of parietal cells and H(+) secretion of the stomach in response to histamine. Thus, a KCNQ1 loss-of-function mutation may impair gastric acid secretion.

Berbamine (BM) is an herbal compound derived from Berberis vulgaris L commonly used in traditional Chinese medicine. In this study, we show that BM has potent anti-inflammatory properties through novel regulatory mechanisms, leading to reduced encephalitogenic T cell responses and amelioration of experimental autoimmune encephalomyelitis (EAE). The treatment effect of BM was attributable to its selective inhibitory effect on the production and action of IFN-γ in CD4+ T cells, which was mediated through altered STAT4 expression in T cells. BM was found to up-regulate SLIM, a ubiquitin E3 ligase for STAT4, and promote STAT4 degradation, resulting in markedly decreased IFN-γ production in CD4+ T cells in EAE mice. Regulation of IFN-γ by BM had profound anti-inflammatory actions through its effect on both CD4+ T cells and APCs. BM-treated APCs exhibited reduced stimulatory function as a result of altered expression of PD-L1, CD80, and CD86 in treated mice. The treatment effect of BM in EAE was directly related to its action on IFN-γ, and was abolished in IFN-γ knockout mice. The study also confirmed that BM was able to inhibit NFAT translocation through effecting calcium mobilization in lymphocytes. However, this effect was not directly responsible for the treatment efficacy of BM in EAE. The study has important implications in our approaches to evaluating the utility of natural compounds in drug discovery and to probing the role of cytokine network in the development of autoimmune conditions.

The incidence of cardiac arrhythmia and heart failure continues to rapidly increase, leading to a growing epidemic which constitutes a serious financial burden for society (Chugh et al., 2014; Melman et al., 2014). Despite the standard therapeutic strategies to treat adverse cardiac remodeling that precedes the development of arrhythmia and overt heart failure, their prevalence is still increasing and their morbidity and mortality have not been largely improved (Melman et al., 2014; Sardar et al., 2014). Continued and deeper understanding of the molecular mechanisms responsible for arrhythmia and heart failure will help identify novel effective therapies. In the past few years, research has implicated the contribution of genetic and epigenetic factors to arrhythmia and heart failure. This research hot topic entitled “Genetic and epigenetic basis of arrhythmia and heart failure” provides a snapshot in this area. The 10 selected papers in this special research topic will enhance current understanding of the genetic and epigenetic basis of arrhythmia and heart failure, and also will expand our knowledge on novel interventions. In this issue, genetic aspects of arrhythmia were described by 3 different groups. Crump and Abbott (2014) provided an update about arrhythmogenic KCNE gene variants and their roles, Nielsen et al., (2013) showed that the Ito regulatory subunit Klf15 was not associated with early-onset long atrial fibrillation in their cohort. Besides familial atrial fibrillation, genome wide association studies (GWAS) have identified common variants in the general population for atrial fibrillation. Yao et al. (2014) gave an overview on the paired-like homeodomain 2, which was identified as a common variant to be involved in atrial fibrillation, highlighting the potential of paired-like homeodomain 2 as a new therapeutic target. Duygu et al. (2013) provided an outstanding overview about the genetics and epigenetics of arrhythmia and heart failure. Besides highlighting specific genetic mutations associated with heart failure, they also summarized epigenetic mechanisms including DNA methylation, ATP-dependent chromatin remodeling, histone modification and RNA-based mechanisms, highlighting the relationship among epigenetics, heart failure and arrhythmiaogenesis. Finally, they also introduced a discussion on the role of non-coding RNAs especially microRNAs (miRNAs, miRs) in heart failure and arrhythmia. miRNAs are endogenous non-coding RNAs which post-transcriptionally regulate gene expressions (Condorelli et al., 2014). A single miRNA can target several target genes while an individual gene can be regulated by many miRNAs (Viereck et al., 2014). Therefore, miRNAs have been considered as central regulators of gene expression, which participate in many essential biological processes including cellular proliferation, differentiation, apoptosis, and cardiac metabolism (Condorelli et al., 2014; Viereck et al., 2014). Dysregulations of miRNAs have been connected to many cardiovascular diseases, including arrhythmia and heart failure (Kwekkeboom et al., 2014; Melman et al., 2014). In this special research topic, 4 opinion articles have been provided about miRNAs in arrhythmia and heart failure. Fu et al. (2014) presented the current understanding about miRNAs as novel players in atrial fibrillation, a most common form of arrhythmia that affects at least 1% persons in the general population. Changes in cardiac structure and function (termed diabetic cardiomyopathy) may play a role in the increased incidence of sudden death and heart failure in the diabetic patients. Zhou et al. (2014) summarized dysregulations of miRNAs in diabetic cardiomyopathy. Interestingly, changes of circulating miRNAs in diabetic patients have also been noted, although their associations with diabetic cardiomyopathy are unclear. Better understanding of circulating miRNAs in diabetic cardiomyopathy would help the development of biomarkers and novel therapies. Ageing is correlated with an increase in the incidence of both heart failure (particularly heart failure with preserved ejection fraction) and atrial fibrillation. Considering the rapid increase in the geriatric population, it is urgent to understand the role of miRNAs in aging. Zhuo et al. (2014) provided some insights into the dysregulation of miRNAs in aging-related heart failure. New therapeutics via targeting microRNAs are being developed based on the detailed understanding of the role of miRNAs in heart failure and arrhythmia using either antagomirs or mimics (Kwekkeboom et al., 2014). In contrast to the previous articles on the role of miRNAs in pathological heart diseases, Fu et al. (2013) dissected the role of miRNAs in physiological hypertrophy. Physiological hypertrophy, which is associated with exercise and pregnancy, is not associated with pathological processes like apoptosis and fibrosis, and unlike its counterpart (pathological hypertrophy), is not the harbinger of sudden death or heart failure. Given the known beneficial effects of exercise on cardiovascular outcomes, a better understanding of miRNAs in physiological hypertrophy may lead to novel miRNA-based therapies for heart failure. Finally Stagnaro and Caramel (2013) proposed a “Quantum Biophysics Semeiotics” (QBS) microcirculatory theory of atherosclerosis, which could be used for diagnosis or therapies. In addition, Tao et al. (2013) provided their prospects of using Qiliqiangxin, a traditional Chinese medicine, in the treatment of heart failure potentially through epigenetic regulation of regeneration. In conclusion, this research topic offers a detailed and updated summary about genetic and epigenetic basis of arrhythmia and heart failure, and provides a forum for discussion on ways to translate these genetic and epigenetic findings into novel therapies for arrhythmia and heart failure.

Ghrelin has been found to be associated with anti-inflammatory effects, inhibition of atherosclerotic plaque formation, and plaque stability in the cardiovascular system. We investigated whether ghrelin affected atherosclerotic plaque and inflammation found in atherosclerosis. We crossed ghrelin receptor knock out mice (growth hormone secretagogue receptor (GHSR)-/-) and low-density lipoprotein receptor-null (low-density lipoprotein receptor (LDLR)-/-) mice. In this model, atherosclerotic lesions were promoted by administering a high-fat, high-cholesterol, Western-type diet for 18 weeks. Serum lipid levels, atherosclerotic plaque on the aortic arches, and expression of intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), T cells, macrophages, and smooth muscle cells of atherosclerotic plaque were observed. Although serum lipid levels and atherosclerotic plaque in aortic arches were not significantly different between GHSR+/+/LDLR-/- and GHSR -/-LDLR-/- mice, ICAM-1 and VCAM-1 protein expression in atherosclerotic plaques were increased in GHSR -/-LDLR-/- mice compared with GHSR+/+/LDLR-/- mice. T cells and macrophages were increased, while smooth muscle cells of atherosclerotic plaques were less in GHSR -/-LDLR-/- mice than that in GHSR+/+/LDLR-/- mice. In conclusion, ghrelin receptor deficiency aggravates atherosclerotic plaque instability and vascular inflammation but not the surface area of atherosclerotic plaque. This information will provide novel avenues for the treatment of patients with atherosclerosis.

Objective To identify factors associated with mother-to-child-transmission and late access to prevention of maternal to child transmission (PMTCT) services among HIV-infected women; and risk factors for infant mortality among HIV-exposed infants in order to assess the feasibility of virtual elimination of vertical transmission and pediatric HIV in this setting. Design Observational study evaluating the impact of a provincial PMTCT program. Methods The intervention was implemented in 26 counties of Yunnan Province, China at municipal and tertiary health care settings. Log linear regression models with generalized estimating equations were used to identify unadjusted and adjusted correlates for late ARV intervention and MTCT. Cox proportional hazard models with robust sandwich estimation were applied to examine correlates of infant mortality. Results Mother-to-child- transmission rate of HIV was controlled to 2%, with late initiation of maternal ARV showing a strong association with vertical transmission and infant mortality. Risk factors for late initiation of maternal ARV were age, ethnicity, education, and having a husband not tested for HIV. Mortality rate among HIV-exposed infants was 2.9/100 person-years. In addition to late initiation of maternal ARV, ethnicity, low birth weight and preterm birth were associated with infant mortality. Conclusions This PMTCT program in Yunnan achieved low rates of MTCT. However the infant mortality rate in this cohort of HIV-exposed children was almost three times the provincial rate. Virtual elimination of MTCT of HIV is an achievable goal in China, but more attention needs to be paid to HIV-free survival.

The inward rectifier potassium channel, Kir2.1, contributes to the I(K1) current in cardiac myocytes and is closely associated with atrial fibrillation. Strong evidences have shown that atrial dilatation or stretch may result in atrial fibrillation. However, the role of Kir2.1 channels in the stretch-mediated atrial fibrillation is not clear. In this study, we constructed the recombinant plasmid of KCNJ2 that encodes the Kir2.1 channel and expressed it in CHO-K1 cells. We recorded I(K1) currents using the whole-cell patch clamping technique. Our data showed that I(K1) currents were significantly larger under stretch in the hypotonic solution than under non-stretch in the iso-osmotic solution, and the activation kinetics of the Kir2.1 channel were changed markedly by stretch as well. Thus, atrial stretch in human heart might result in excessive I(K1) currents, which is likely to increase the resting membrane potential and decrease the effective refractory period, to initiate and/or maintain atrial fibrillation.

The inward rectifier K(+) channel Kir2.1 mediates the potassium I(K1) current in the heart. It is encoded by KCNJ2 gene that has been linked to Andersen's syndrome. Recently, strong evidences showed that Kir2.1 channels were associated with mouse atrial fibrillation (AF), therefore we hypothesized that KCNJ2 was associated with familial AF. Thirty Chinese AF kindreds were evaluated for mutations in KCNJ2 gene. A valine-to-isoleucine mutation at position 93 (V93I) of Kir2.1 was found in all affected members in one kindred. This valine and its flanking sequence is highly conserved in Kir2.1 proteins among different species. Functional analysis of the V93I mutant demonstrated a gain-of-function consequence on the Kir2.1 current. This effect is opposed to the loss-of-function effect of previously reported mutations in Andersen's syndrome. Kir2.1 V93I mutation may play a role in initiating and/or maintaining AF by increasing the activity of the inward rectifier K(+) channel.

Controlled degradation of misassembled and dispensable proteins is a crucial cellular process for maintaining the quality control of proteomes. While a majority of studies have focused on degradation of water soluble proteins, it is poorly understood how membrane proteins are degraded in cells. This discrepancy is largely due to the difficulties in reconstituting the degradation process in vitro, which is necessary for biochemical and biophysical analysis of the mechanism. In this study, we successfully reconstituted ATP-dependent proteolysis of membrane proteins mediated by the membrane-integrated AAA+ protease FtsH of E.

This paper proposes a novel image parsing framework to solve the semantic pixel labeling problem from only label strokes. Our framework is based on a network of voters, each of which aggregates both a self voting vector and a neighborhood context. The voters are parameterized using sparse convex coding. To efficiently learn the parameters, we propose a regularized energy function that propagates label information in the training data while taking into account of context interaction and a backward composition algorithm for efficient gradient computation. Our framework is capable of handling label strokes and is scalable to a code book of millions of bases. Our experiment results show the effectiveness of our framework on both synthetic examples and real world applications.

Ethyl benzoate (EB), bis(2-ethyl hexyl) sebacate (BEHS), di-n-butyl phthalate (DNBP), and bis(2-ethyl hexyl) phthalate (BEHP) were employed as internal electron donors of heterogeneous Ziegler-Natta catalysts and the obtained polypropylene (PP) samples were fractionated by temperature rising elution fractionation (TREF). The influence of different internal donors on the tacticity distributions of PPs was compared. PPs have narrower tacticity distributions with aromatic esters. Based on TREF results, different interactions of internal donor, which may depend on their structures, were proposed. The effects of internal donors on microstructure of the fractions, especially the first fractions, were examined.

In this paper, a commercial impact-resistant polypropylene alloy sample was fractionated with preparative temperature rising elution fractionation (t.r.e.f.) technique and a series of ethylene-propylene block copolymer fractions with different ethylene contents were obtained. Combined with fractionation results, the block structure of them was identified with 13 C nuclear magnetic resonance (n.m.r.) spectroscopy and differential scanning calorimetry (d.s.c.). There are some transition segments between polyethylene and polypropylene segment in the block copolymer. It was found that the number and kind of transition segments decreased with elution temperature, the length and melting temperature of polyethylene segment in block copolymer fractions showed a similar tendency.

Mammals transport blood through a high-pressure, closed vascular network and lymph through a low-pressure, open vascular network. These vascular networks connect at the lymphovenous (LV) junction, where lymph drains into blood and an LV valve (LVV) prevents backflow of blood into lymphatic vessels. Here we describe an essential role for platelets in preventing blood from entering the lymphatic system at the LV junction. Loss of CLEC2, a receptor that activates platelets in response to lymphatic endothelial cells, resulted in backfilling of the lymphatic network with blood from the thoracic duct (TD) in both neonatal and mature mice. Fibrin-containing platelet thrombi were observed at the LVV and in the terminal TD in wild-type mice, but not Clec2-deficient mice. Analysis of mice lacking LVVs or lymphatic valves revealed that platelet-mediated thrombus formation limits LV backflow under conditions of impaired valve function. Examination of mice lacking integrin-mediated platelet aggregation indicated that platelet aggregation stabilizes thrombi that form in the lymphatic vascular environment to prevent retrograde blood flow. Collectively, these studies unveil a newly recognized form of hemostasis that functions with the LVV to safeguard the lymphatic vascular network throughout life.