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Cloud manufacturing (CMfg), as a new service-oriented technology, is aiming towards delivering on-demand manufacturing services over the internet by facilitating collaboration among different producers with distributed manufacturing resources and capabilities. To this end, addressing service composition and optimal selection (SCOS) problem has been the pivotal challenge. This NP-hard combinatorial problem deals with selecting and combining the available resources into a composite service to meet the user’s requirements while keeping up the optimal quality of service. This study proposes a new hybrid approach based on the recently developed grey wolf optimizer (GWO) algorithm and evolutionary operators of the genetic algorithm. The embedded crossover and mutation operators carry out a twofold functionality: (1) they make it possible to adapt the continuous structure of GWO to a combinatorial problem such as SCOS, and (2) they help to avoid the local optimal stagnation at the hunting process by providing more exploration strength. A series of experiments were designed and conducted to prove the effectiveness of the proposed algorithm, and the experimental results demonstrated that the proposed algorithm delivers superior performance compared with that of both existing discrete variations of GWO and genetic algorithm, especially in large-scale SCOS problems.

With the rapid development of cloud manufacturing (CMfg) as a new service-oriented manufacturing paradigm, a considerable progress has been made in research of different aspects of it. One of the most challenging topics of interest has been service composition and optimal selection (SCOS) problem. Since CMfg is aiming towards sharing and collaborating among distributed manufacturing resources and capabilities, selecting and combining these services into a composite service to meet the user’s requirements while keeping up the optimal service performances is gaining higher emphasis. As a result, a comprehensive survey of research to date on this NP-hard problem becomes highly desirable. In this paper, first we summarize the recent advancements in CMfg and categorize them into six main areas in a brief but concise way. Then, after a short explanation of the SCOS problem, existing research work around it has been investigated and discussed in detail from the viewpoint of selection criteria, algorithms, optimization functions, correlation consideration, mapping approaches between subtasks and services, and dynamic composition. The goal of this article is to provide a comprehensive highlight for researchers who are inspired to explore work in the related areas and acquaint them with related research work done to date.

Acetylation of the RelA subunit of NF- κ B at lysine-310 regulates the transcriptional activation of NF- κ B target genes and contributes to maintaining constitutively active NF- κ B in tumors. Bromodomain-containing factor Brd4 has been shown to bind to acetylated lysine-310 (AcLys310) and to regulate the transcriptional activity of NF- κ B, but the role of this binding in maintaining constitutively active NF- κ B in tumors remains elusive. In this study, we demonstrate the structural basis for the binding of bromodomains (BDs) of bromodomain-containing protein 4 (Brd4) to AcLys310 and identify the BD inhibitor JQ1 as an effective small molecule to block this interaction. JQ1 suppresses TNF- α -mediated NF- κ B activation and NF- κ B-dependent target gene expression. In addition, JQ1 inhibits the proliferation and transformation potential of A549 lung cancer cells and suppresses the tumorigenicity of A549 cells in severe combined immunodeficiency mice. Furthermore, we demonstrate that depletion of Brd4 or treatment of cells with JQ1 induces the ubiquitination and degradation of the constitutively active nuclear form of RelA. Our results identify a novel function of Brd4 in maintaining the persistently active form of NF- κ B found in tumors, and they suggest that interference with the interaction between acetylated RelA and Brd4 could be a potential therapeutic approach for the treatment of NF- κ B-driven cancer.

Glaucoma is the most prevalent neurodegenerative disease and a leading cause of blindness worldwide. The mechanisms causing glaucomatous neurodegeneration are not fully understood. Here we show, using mice deficient in T and/or B cells and adoptive cell transfer, that transient elevation of intraocular pressure (IOP) is sufficient to induce T-cell infiltration into the retina. This T-cell infiltration leads to a prolonged phase of retinal ganglion cell degeneration that persists after IOP returns to a normal level. Heat shock proteins (HSP) are identified as target antigens of T-cell responses in glaucomatous mice and human glaucoma patients. Furthermore, retina-infiltrating T cells cross-react with human and bacterial HSPs; mice raised in the absence of commensal microflora do not develop glaucomatous T-cell responses or the associated neurodegeneration. These results provide compelling evidence that glaucomatous neurodegeneration is mediated in part by T cells that are pre-sensitized by exposure to commensal microflora. Glaucoma is a neurodegenerative disease of which the etiology is still unclear. Here the authors show that elevation of intraocular pressure induces T cell infiltration in the eyes. Furthermore, they show that T cell cross-reactivity between endogenous and commensal antigens contributes to disease onset in mice.

Background: Autophagy is a programmed cell survival mechanism that has a key role in both physiologic and pathologic conditions. The relationship between autophagy and cancer is complex because autophagy can act as either a tumour suppressor or as a tumour promoter. The role of autophagy in oral squamous cell carcinoma (OSCC) is controversial. Several studies have claimed that either a high or low expression of autophagy-related proteins was associated with poor prognosis of OSCCs. The aims of the study were to compare autophagy in OSCCs, verrucous hyperplasias, and normal oral mucosas, and to inspect the prognostic role of autophagy in OSCCs. Methods: We used the autophagosome marker, LC3B, and autophagy flux marker, p62/SQSTM1 (p62), by using immunohistochemistry, and examined p62 mRNA by RNA in situ hybridization, to evaluate autophagy in 195 OSCCs, 47 verrucous hyperplasias, and 37 normal oral mucosas. The prognostic roles of LC3B and p62 protein expressions in OSCCs were investigated. Results: We discovered that the normal oral mucosa exhibited limited LC3B punctae and weak cytoplasmic p62 staining, whereas the OSCCs exhibited a marked increase in LC3B punctae and cytoplasmic p62 expression. The expression pattern of LC3B and cytoplasmic p62 of the verrucous hyperplasias were between normal oral mucosas and OSCCs. The normal oral mucosas, verrucous hyperplasias, and OSCCs presented no differences in nuclear p62 expression and the p62 mRNA level. p62 mRNA expression was elevated in a minority of cases. High p62 mRNA expression was associated with high p62 protein expression in the cytoplasm. Increased LC3B punctae, high cytoplasmic p62, and low nuclear p62 expressions in OSCCs were associated with aggressive clinicopathologic features and unfavourable prognosis. In addition, low nuclear p62 expression was an independent prognostic factor for overall and disease-specific survival rates. Furthermore, we disclosed that high cytoplasmic p62 expression accompanied with either a low or high LC3B expression, which indicated autophagy impairment under basal or activated autophagic activity, was associated with aggressive behaviour in advanced OSCCs. Conclusions: We suggested that autophagy was altered during cancer initiation and progression. Autophagy impairment contributed to cancer progression in advanced OSCCs.

Topological Dirac and Weyl semimetals not only host quasiparticles analogous to the elementary fermionic particles in high-energy physics, but also have a non-trivial band topology manifested by gapless surface states, which induce exotic surface Fermi arcs1,2. Recent advances suggest new types of topological semimetal, in which spatial symmetries protect gapless electronic excitations without high-energy analogues3–11. Here, using angle-resolved photoemission spectroscopy, we observe triply degenerate nodal points near the Fermi level of tungsten carbide with space group \\[P\\bar{6}m2\\] (no. 187), in which the low-energy quasiparticles are described as three-component fermions distinct from Dirac and Weyl fermions. We further observe topological surface states, whose constant-energy contours constitute pairs of ‘Fermi arcs’ connecting to the surface projections of the triply degenerate nodal points, proving the non-trivial topology of the newly identified semimetal state.

The analysis aimed to identify the treatment gaps in current fracture liaison services (FLS) and to provide recommendations for best practice establishment of future FLS across the Asia-Pacific region. The findings emphasize the unmet need for the implementation of new programs and provide recommendations for the refinement of existing ones. The study’s objectives were to evaluate fracture liaison service (FLS) programs in the Asia-Pacific region and provide recommendations for establishment of future FLS programs. A systematic literature review (SLR) of Medline, PubMed, EMBASE, and Cochrane Library (2000–2017 inclusive) was performed using the following keywords: osteoporosis, fractures, liaison, and service. Inclusion criteria included the following: patients ≥ 50 years with osteoporosis-related fractures; randomized controlled trials or observational studies with control groups (prospective or retrospective), pre–post, cross-sectional and economic evaluation studies. Success of direct or indirect interventions was assessed based on patients’ understanding of risk, bone mineral density assessment, calcium intake, osteoporosis treatment, re-fracture rates, adherence, and mortality, in addition to cost-effectiveness. Overall, 5663 unique citations were identified and the SLR identified 159 publications, reporting 37 studies in Asia-Pacific. These studies revealed the unmet need for public health education, adequate funding, and staff resourcing, along with greater cooperation between departments and physicians. These actions can help to overcome therapeutic inertia with sufficient follow-up to ensure adherence to recommendations and compliance with treatment. The findings also emphasize the importance of primary care physicians continuing to prescribe treatment and ensure service remains convenient. These findings highlight the limited evidence supporting FLS across the Asia-Pacific region, emphasizing the unmet need for new programs and/or refinement of existing ones to improve outcomes. With the continued increase in burden of fractures in Asia-Pacific, establishment of new FLS and assessment of existing services are warranted to determine the impact of FLS for healthcare professionals, patients, family/caregivers, and society.

SmB 6 , a well-known Kondo insulator, exhibits a transport anomaly at low temperature. This anomaly is usually attributed to states within the hybridization gap. Recent theoretical work and transport measurements suggest that these in-gap states could be ascribed to topological surface states, which would make SmB 6 the first realization of topological Kondo insulator. Here by performing angle-resolved photoemission spectroscopy experiments, we directly observe several dispersive states within the hybridization gap of SmB 6 . These states show negligible k z dependence, which indicates their surface origin. Furthermore, we perform photoemission circular dichroism experiments, which suggest that the in-gap states possess chirality of the orbital angular momentum. These states vanish simultaneously with the hybridization gap at around 150 K. Together, these observations suggest the possible topological origin of the in-gap states. The Kondo insulator samarium hexaboride exhibits low-temperature transport anomalies, which might be due to topological surface states. Here Jiang et al. perform angle-resolved photoemission and its circular dichroism measurements, which suggest that the anomalies might be of topological origin.

This paper presents a hysteretic water retention curve (WRC) and unsaturated hydraulic conductivity model for deformable soils based on the change in pore-size distribution (PSD). The PSD plays a decisive role in the water retention behaviour of soils. Although its evolution during deformation is rather complicated, experimental data showed that the overall shapes and distribution characteristics of the PSD function are not significantly altered. Based on these findings, the PSD function at a deformed state is obtained by horizontal shifting and vertical scaling of the corresponding PSD function at a reference state. On this basis, a hysteretic WRC model is formulated to account for the influences of deformation and hysteresis on the variation of saturation, using seven model parameters with clear physical meanings. The proposed model is then incorporated in the Mualem model to predict the unsaturated hydraulic conductivity for deformable soils, using only one additional parameter. A large number of published laboratory tests are used to validate the proposed model, showing that it can reasonably capture important features of retention and permeability properties for deformable soils in most cases under consideration.