121 research outputs found

    Total domination stable graphs upon edge addition

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    AbstractA set S of vertices in a graph G is a total dominating set if every vertex of G is adjacent to some vertex in S. The minimum cardinality of a total dominating set of G is the total domination number of G. A graph is total domination edge addition stable if the addition of an arbitrary edge has no effect on the total domination number. In this paper, we characterize total domination edge addition stable graphs. We determine a sharp upper bound on the total domination number of total domination edge addition stable graphs, and we determine which combinations of order and total domination number are attainable. We finish this work with an investigation of claw-free total domination edge addition stable graphs

    Publisher Correction: Hydro-climatic changes of wetlandscapes across the world (Scientific Reports, (2021), 11, 1, (2754), 10.1038/s41598-021-81137-3)

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    In the original version of this Article, V. H. Rivera-Monroy was incorrectly affiliated with ‘Alexander von Humboldt Biological Resources Research Institute, Calle 28 A No. 15-09, Bogotá, DC, 70803, Colombia’. The correct affiliation is listed below. Department of Oceanography and Coastal Sciences, College of the Coast and Environment, Louisiana State University, Baton Rouge, LA 70803, USA As a result, Affiliations 22–27 were incorrectly listed as Affiliations 21–26 respectively. The original Article has been corrected

    Hydro-climatic changes of wetlandscapes across the world

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    Assessments of ecosystem service and function losses of wetlandscapes (i.e., wetlands and their hydrological catchments) suffer from knowledge gaps regarding impacts of ongoing hydro-climatic change. This study investigates hydro-climatic changes during 1976–2015 in 25 wetlandscapes distributed across the world’s tropical, arid, temperate and cold climate zones. Results show that the wetlandscapes were subject to precipitation (P) and temperature (T) changes consistent with mean changes over the world’s land area. However, arid and cold wetlandscapes experienced higher T increases than their respective climate zone. Also, average P decreased in arid and cold wetlandscapes, contrarily to P of arid and cold climate zones, suggesting that these wetlandscapes are located in regions of elevated climate pressures. For most wetlandscapes with available runoff (R) data, the decreases were larger in R than in P, which was attributed to aggravation of climate change impacts by enhanced evapotranspiration losses, e.g. caused by land-use changes

    GDF15 promotes weight loss by enhancing energy expenditure in muscle

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    Funding Information: We thank R. Seeley for sharing GFRAL-null mice; B. Lowell for sharing β-less mice; and J. Wu for shipping β-less mice to us. G.R.S. was supported by a Diabetes Canada Investigator Award (DI-5-17-5302-GS), a Canadian Institutes of Health Research Foundation Grant (201709FDN-CEBA-116200), a Tier 1 Canada Research Chair in Metabolic Diseases and a J. Bruce Duncan Endowed Chair in Metabolic Diseases; D.W. by Fellowship Grants from the McMaster Institute for Research on Aging (MIRA) at McMaster University; S.R. by a postdoctoral fellowship supported by MITACS and Novo Nordisk; L.K.T. by a CIHR Post-Doctoral Fellowship Award and Michael DeGroote Fellowship Award in Basic Biomedical Science; E.M.D. by a Vanier Canada Graduate Scholarship; G.P.H. by the Natural Sciences and Engineering Research Council of Canada (NSERC: 400362); G.J.D. and S.M.F. by NSERC-CGSM scholarships; L.D. by the Fonds de Recherche du Québec-Santé doctoral training award; D.P.B. by the GSK Chair in Diabetes of Université de Sherbrooke and a FRQS J1 salary award. The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health, and by the NCI, NHGRI, NHLBI, NIDA, NIMH and NINDS. Funding Information: S.B.J. and R.E.K. are employees of Novo Nordisk, a pharmaceutical company producing and selling medicine for the treatment of diabetes and obesity. G.R.S. is a co-founder and shareholder of Espervita Therapeutics. McMaster University has received funding from Espervita Therapeutics, Esperion Therapeutics, Poxel Pharmaceuticals and Nestle for research conducted in the laboratory of G.R.S. S.R. is supported by a MITACS postdoctoral fellowship sponsored by Novo Nordisk. H.C.G. holds the McMaster-Sanofi Population Health Institute Chair in Diabetes Research and Care. G.R.S., G.P. and H.C.G. are inventors listed on a patent for identifying GDF15 as a biomarker for metformin. G.R.S. has received consulting/speaking fees from Astra Zeneca, Eli Lilly, Esperion Therapeutics, Merck, Poxel Pharmaceuticals and Cambrian Biosciences. The other authors declare no competing interests. Publisher Copyright: © 2023, The Author(s).Peer reviewedPublisher PD

    Activation of Latent HIV Using Drug-Loaded Nanoparticles

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    Antiretroviral therapy is currently only capable of controlling HIV replication rather than completely eradicating virus from patients. This is due in part to the establishment of a latent virus reservoir in resting CD4+ T cells, which persists even in the presence of HAART. It is thought that forced activation of latently infected cells could induce virus production, allowing targeting of the cell by the immune response. A variety of molecules are able to stimulate HIV from latency. However no tested purging strategy has proven capable of eliminating the infection completely or preventing viral rebound if therapy is stopped. Hence novel latency activation approaches are required. Nanoparticles can offer several advantages over more traditional drug delivery methods, including improved drug solubility, stability, and the ability to simultaneously target multiple different molecules to particular cell or tissue types. Here we describe the development of a novel lipid nanoparticle with the protein kinase C activator bryostatin-2 incorporated (LNP-Bry). These particles can target and activate primary human CD4+ T-cells and stimulate latent virus production from human T-cell lines in vitro and from latently infected cells in a humanized mouse model ex vivo. This activation was synergistically enhanced by the HDAC inhibitor sodium butyrate. Furthermore, LNP-Bry can also be loaded with the protease inhibitor nelfinavir (LNP-Bry-Nel), producing a particle capable of both activating latent virus and inhibiting viral spread. Taken together these data demonstrate the ability of nanotechnological approaches to provide improved methods for activating latent HIV and provide key proof-of-principle experiments showing how novel delivery systems may enhance future HIV therapy

    Ultrathin Silicon Membranes for Wearable Dialysis

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    The development of wearable or implantable technologies that replace center-based hemodialysis (HD) hold promise to improve outcomes and quality of life for patients with ESRD. A prerequisite for these technologies is the development of highly efficient membranes that can achieve high toxin clearance in small-device formats. Here we examine the application of the porous nanocrystalline silicon (pnc-Si) to HD. pnc-Si is a molecularly thin nanoporous membrane material that is orders of magnitude more permeable than conventional HD membranes. Material developments have allowed us to dramatically increase the amount of active membrane available for dialysis on pnc-Si chips. By controlling pore sizes during manufacturing, pnc-Si membranes can be engineered to pass middle-molecular-weight protein toxins while retaining albumin, mimicking the healthy kidney. A microfluidic dialysis device developed with pnc-Si achieves urea clearance rates that confirm that the membrane offers no resistance to urea passage. Finally, surface modifications with thin hydrophilic coatings are shown to block cell and protein adhesion

    Data for wetlandscapes and their changes around the world

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    Geography and associated hydrological, hydroclimate and land-use conditions and their changes determine the states and dynamics of wetlands and their ecosystem services. The influences of these controls are not limited to just the local scale of each individual wetland but extend over larger landscape areas that integrate multiple wetlands and their total hydrological catchment – the wetlandscape. However, the data and knowledge of conditions and changes over entire wetlandscapes are still scarce, limiting the capacity to accurately understand and manage critical wetland ecosystems and their services under global change. We present a new Wetlandscape Change Information Database (WetCID), consisting of geographic, hydrological, hydroclimate and land-use information and data for 27 wetlandscapes around the world. This combines survey-based local information with geographic shapefiles and gridded datasets of large-scale hydroclimate and land-use conditions and their changes over whole wetlandscapes. Temporally, WetCID contains 30-year time series of data for mean monthly precipitation and temperature and annual land-use conditions. The survey-based site information includes local knowledge on the wetlands, hydrology, hydroclimate and land uses within each wetlandscape and on the availability and accessibility of associated local data. This novel database (available through PANGAEA https://doi.org/10.1594/PANGAEA.907398; Ghajarnia et al., 2019) can support site assessments; cross-regional comparisons; and scenario analyses of the roles and impacts of land use, hydroclimatic and wetland conditions, and changes in whole-wetlandscape functions and ecosystem services

    Basis for treatment of tuberculosis among HIV-infected patients in Tanzania: the role of chest x-ray and sputum culture

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    BACKGROUND: Active tuberculosis (TB) is common among HIV-infected persons living in tuberculosis endemic countries, and screening for tuberculosis (TB) is recommended routinely. We sought to determine the role of chest x-ray and sputum culture in the decision to treat for presumptive TB using active case finding in a large cohort of HIV-infected patients. METHODS: Ambulatory HIV-positive subjects with CD4 counts ≥ 200/mm3 entering a Phase III TB vaccine study in Tanzania were screened for TB with a physical examination, standard interview, CD4 count, chest x-ray (CXR), blood culture for TB, and three sputum samples for acid fast bacillus (AFB) smear and culture. RESULTS: Among 1176 subjects 136 (12%) were treated for presumptive TB. These patients were more frequently male than those without treatment (34% vs. 25%, respectively; p = 0.049) and had lower median CD4 counts (319/μL vs. 425/μL, respectively; p < .0001). Among the 136 patients treated for TB, 38 (28%) had microbiologic confirmation, including 13 (10%) who had a normal CXR and no symptoms. There were 58 (43%) treated patients in whom the only positive finding was an abnormal CXR. Blood cultures were negative in all patients. CONCLUSION: Many ambulatory HIV-infected patients with CD4 counts ≥ 200/mm3 are treated for presumptive TB. Our data suggest that optimal detection requires comprehensive evaluation, including CXR and sputum culture on both symptomatic and asymptomatic subjects.National Institutes of Health (A1 45407); Fogarty International Center (D43-TW006807
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