An e-Service delivery platform for building indoor environment and energy performance assessment

The volume of data relating to the built environment is expected to markedly increase as low cost, wireless monitoring devices proliferate. It is anticipated that the technology will provide facilities managers with new tools for cost-effective energy use reduction. To address this opportunity, several projects worldwide are developing data platforms possessing integrated analytics corresponding to distinct energy-related services (hereinafter referred to as ‘e-services’). This paper summarises the first year activity of a Korean project addressing the delivery of new information services relating to the energy and environmental performance of buildings. An e-service delivery platform based on pervasive sensors and the Hadoop ‘big data’ platform has been developed. The hardware and software components are designed to meet technical requirements for a range of energy and environment services for which the essential features are low cost devices and open communication protocols. The form of the hardware and software systems is herein described and results from deployments in Korea and the UK reported

Sphingosine-1-phosphate–induced smooth muscle cell migration involves the mammalian target of rapamycin

BackgroundVascular smooth muscle cell (SMC) migration is an important component of the development of intimal hyperplasia. Sphingosine-1-phosphate (S-1-P) is a lipid released from activated platelets with numerous cellular effects including the stimulation of SMC migration in vitro. We examined the role of the mammalian target of rapamycin and ribosomal p70S6 kinase (p70S6K) in S-1-P–induced SMC migration.MethodsRat arterial SMCs were cultured in vitro. Linear wound and Boyden microchemotaxis assays of migration were performed in the presence of S-1-P (0.01 to 100 μmol/L) with and without rapamycin (10 nmol/L). Western blotting was performed for phosphorylated and total p70S6K, ERK1/2, and p38MAPK after stimulation with S-1-P (0.1 μmol/L), with and without rapamycin pretreatment. Phosphorylation of p70S6K was also assayed after S-1-P treatment in the presence and absence of inhibitors of PI3 kinase (wortmannin, WN, and LY294002, LY), Akt (AktI), p38MAPK (SB203580), and MEK1 (PD98059).ResultsS-1-P stimulated migration of SMCs in both linear wound and Boyden chamber assays compared to control (P < .05); these responses were inhibited by rapamycin to below the level of control (P < .05 vs S-1-P alone for both assays) in a dose-dependent manner (inhibitory concentration of 50%, 10 nmol/L). S-1-P stimulated phosphorylation of ERK1/2, p38MAPK, and p70S6K, which peaked at 5 minutes for ERK1/2 and p38MAPK and10 minutes for p70S6K (2-fold increase over control for each, P < .05). Rapamycin prevented the phosphorylation of p70S6K at the Thr 389 site (which correlates with enzyme activity), reduced ERK1/2 phosphorylation, but had no effect on the Thr 421/Ser 424 site or on p38MAPK phosphorylation. Wortmannin and LY294002 inhibited phosphorylation of the Thr 389 site of p70S6K. AktI and SB203580 had no effect on p70S6K, whereas PD98059 had a marginal effect.ConclusionsS-1-P–induced SMC migration was completely inhibited by rapamycin, indicating that the p70S6K pathway is involved. This mechanism likely involves modulation of the ERK1/2 pathway. S-1-P stimulates phosphorylation of p70S6K in a MEK1-dependent, PI3 kinase–dependent, but Akt-independent manner.Clinical relevanceS-1-P is released from activated platelets at sites of vessel injury and contributes to the development of intimal hyperplasia after bypass grafting, angioplasty, and stenting. S-1-P is a potent pro-migratory molecule for SMCs. Rapamycin is a commonly used immunosuppressive agent that has most recently been incorporated as the biologic agent in drug eluting stents with good success in the coronary circulation. Rapamycin inhibits the mammalian target of rapamycin, which, in turn, controls the translational mechanisms of the cell. The role of translational control during S-1-P–induced SMC migration is poorly understood. This study identifies a link between the mammalian target of rapamycin translational pathway and S-1-P and demonstrates how rapamycin might interfere with another facet of a vessel's response to injury after a vascular intervention, namely by interfering with the cell signaling of factors released from platelets deposited at the injury site

Sestrins are evolutionarily conserved mediators of exercise benefits.

Exercise is among the most effective interventions for age-associated mobility decline and metabolic dysregulation. Although long-term endurance exercise promotes insulin sensitivity and expands respiratory capacity, genetic components and pathways mediating the metabolic benefits of exercise have remained elusive. Here, we show that Sestrins, a family of evolutionarily conserved exercise-inducible proteins, are critical mediators of exercise benefits. In both fly and mouse models, genetic ablation of Sestrins prevents organisms from acquiring metabolic benefits of exercise and improving their endurance through training. Conversely, Sestrin upregulation mimics both molecular and physiological effects of exercise, suggesting that it could be a major effector of exercise metabolism. Among the various targets modulated by Sestrin in response to exercise, AKT and PGC1α are critical for the Sestrin effects in extending endurance. These results indicate that Sestrin is a key integrating factor that drives the benefits of chronic exercise to metabolism and physical endurance

Diagnosis, monitoring and treatment of systemic lupus erythematosus: a systematic review of clinical practice guidelines.

Objectives: Management of SLE is complex and variability in practices exists. Guidelines have been developed to help improve the management of SLE patients but there has been no formal evaluation of these guidelines. This study aims to compare the scope, quality and consistency of clinical practice guidelines on the diagnosis, monitoring and treatment of patients with systemic lupus erythematosus (SLE). Methods: Electronic databases were searched up to April 2014. The Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument and textual synthesis was used to appraise and compare recommendations. Results: Nine clinical practice guidelines and five consensus statements were identified, which covered seven topics: diagnosis, monitoring, treatment, neuropsychiatric SLE, lupus nephritis, anti-phospholipid syndrome and other manifestations of lupus. The methodological quality of the guidelines was variable, with the overall mean AGREE II scores ranging from 31% to 75% out of a maximum 100%. Scores were consistently low for applicability, with only one guideline scoring above 50%. There was substantial variability in the treatments recommended for class II and V lupus nephritis, the recommended duration of maintenance therapy for class III/IV lupus nephritis (from 1 to 4 years), and timing of ophthalmological examination for patients on corticosteroids. Conclusion: Published guidelines on SLE cover a complex area of clinical care but the methodological quality, scope and recommendations varied substantially. Collaborative and multidisciplinary efforts to develop comprehensive, high-quality evidence-based guidelines are needed to promote best treatment and health outcomes for patients with SLE.DT is funded by a postgraduate scholarship from the Sydney Medical School, The University of Sydney

Hydrodynamic attraction of swimming microorganisms by surfaces

Cells swimming in confined environments are attracted by surfaces. We measure the steady-state distribution of smooth-swimming bacteria (Escherichia coli) between two glass plates. In agreement with earlier studies, we find a strong increase of the cell concentration at the boundaries. We demonstrate theoretically that hydrodynamic interactions of the swimming cells with solid surfaces lead to their re-orientation in the direction parallel to the surfaces, as well as their attraction by the closest wall. A model is derived for the steady-state distribution of swimming cells, which compares favorably with our measurements. We exploit our data to estimate the flagellar propulsive force in swimming E. coli

Next Steps: Improving the Medicaid Buy-in for Workers with Disabilities

The Bipartisan Policy Center's Health Program is building on its previous report, Improving Opportunities for Working People with Disabilities (January 2021), to address barriers to employment for Medicaid beneficiaries with disabilities who often rely on Medicaid's unique services, such as home and community-based services (HCBS), to live independently in the community and work.The Medicaid Buy-In (MBI) for Workers with Disabilities refers to three eligibility groups within Medicaid that allow states to cover working individuals with disabilities who, excluding earned income, generally meet Social Security's definition of disability. The MBI for Workers with Disabilities therefore allows individuals with disabilities to work and retain their Medicaid coverage, or to use their Medicaid coverage to access wraparound services that are not covered under employer-sponsored insurance or Medicare. Enrollment in the MBI for Workers with Disabilities eligibility groups is associated with increased employment and earnings, while also having a positive impact on the economy, state Medicaid agencies, employers, and state and federal governments.In this report, BPC identifies federal policy reforms that will encourage more states to cover or optimize their coverage of the MBI for Workers with Disabilities eligibility groups. These reforms will improve access to the MBI for Workers with Disabilities programs and, thus, allow more Medicaid beneficiaries with disabilities to work and achieve their employment potential. More specifically, BPC has identified a set of federal policy recommendations that Congress and the administration should advance. These federal policy reforms will clarify existing flexibilities that states can adopt when designing their MBI for Workers with Disabilities programs while also strengthening outreach, data, and interagency coordination.

Approximate Treatment of Lepton Distortion in Charged-Current Neutrino Scattering from Nuclei

The partial-wave expansion used to treat the distortion of scattered electrons by the nuclear Coulomb field is simpler and considerably less time-consuming when applied to the production of muons and electrons by low and intermediate-energy neutrinos. For angle-integrated cross sections, however, a modification of the "effective-momentum-transfer" approximation seems to work so well that for muons the full distorted-wave treatment is usually unnecessary, even at kinetic energies as low as an MeV and in nuclei as heavy as lead. The method does not work as well for electron production at low energies, but there a Fermi function usually proves adequate. Scattering of electron-neutrinos from muon decay on iodine and of atmospheric neutrinos on iron are discussed in light of these results.Comment: 11 pages, LaTeX, submitted to Phys. Rev.

Protein-Polymer Conjugates Synthesized Using Water-Soluble Azlactone-Functionalized Polymers Enable Receptor-Specific Cellular Uptake Toward Targeted Drug Delivery

Conjugation of proteins to drug-loaded polymeric structures is an attractive strategy for facilitating target-specific drug delivery for a variety of clinical needs. Polymers currently available for conjugation to proteins generally have limited chemical versatility for subsequent drug loading. Many polymers that do have chemical functionality useful for drug loading are often insoluble in water, making it difficult to synthesize functional protein–polymer conjugates for targeted drug delivery. In this work, we demonstrate that reactive, azlactone-functionalized polymers can be grafted to proteins, conjugated to a small-molecule fluorophore, and subsequently internalized into cells in a receptor-specific manner. Poly(2-vinyl-4,4-dimethylazlactone), synthesized using reversible addition–fragmentation chain transfer polymerization, was modified post-polymerization with substoichiometric equivalents of triethylene glycol monomethyl ether to yield reactive water-soluble, azlactone-functionalized copolymers. These reactive polymers were then conjugated to proteins holo-transferrin and ovotransferrin. Protein gel analysis verified successful conjugation of proteins to polymer, and protein–polymer conjugates were subsequently purified from unreacted proteins and polymers using size exclusion chromatography. Internalization experiments using a breast cancer cell line that overexpresses the transferrin receptor on its surface showed that the holo-transferrin–polymer conjugate was successfully internalized by cells in a mechanism consistent with receptor-mediated endocytosis. Internalization of protein–polymer conjugate demonstrated that the protein ligand maintained its overall structure and function following conjugation to polymer. Our approach to protein–polymer conjugate synthesis offers a simple, tailorable strategy for preparing bioconjugates of interest for a broad range of biomedical applications