1,557 research outputs found
Genetic test to stop smoking (GeTSS) trial protocol: randomised controlled trial of a genetic test (Respiragene) and Auckland formula to assess lung cancer risk
In vitro and ex vivo testing of tenofovir shows it is effective as an HIV-1 microbicide
Background: Tenofovir gel has entered into clinical trials for use as a topical microbicide to prevent HIV-1 infection but has no published data regarding pre-clinical testing using in vitro and ex vivo models. To validate our findings with on-going clinical trial results, we evaluated topical tenofovir gel for safety and efficacy. We also modeled systemic application of tenofovir for efficacy. Methods and Findings: Formulation assessment of tenofovir gel included osmolality, viscosity, in vitro release, and permeability testing. Safety was evaluated by measuring the effect on the viability of vaginal flora, PBMCs, epithelial cells, and ectocervical and colorectal explant tissues. For efficacy testing, PBMCs were cultured with tenofovir or vehicle control gels and HIV-1 representing subtypes A, B, and C. Additionally, polarized ectocervical and colorectal explant cultures were treated apically with either gel. Tenofovir was added basolaterally to simulate systemic application. All tissues were challenged with HIV-1 applied apically. Infection was assessed by measuring p24 by ELISA on collected supernatants and immunohisto-chemistry for ectocervical explants. Formulation testing showed the tenofovir and vehicle control gels were >10 times isosmolar. Permeability through ectocervical tissue was variable but in all cases the receptor compartment drug concentration reached levels that inhibit HIV-1 infection in vitro. The gels were non-toxic toward vaginal flora, PBMCs, or epithelial cells. A transient reduction in epithelial monolayer integrity and epithelial fracture for ectocervical and colorectal explants was noted and likely due to the hyperosmolar nature of the formulation. Tenofovir gel prevented HIV-1 infection of PBMCs regardless of HIV-1 subtype. Topical and systemic tenofovir were effective at preventing HIV-1 infection of explant cultures. Conclusions: These studies provide a mechanism for pre-clinical prediction of safety and efficacy of formulated microbicides. Tenofovir was effective against HIV-1 infection in our algorithm. These data support the use of tenofovir for pre-exposure prophylaxis. Š 2010 Rohan et al
Extragalactic Radio Continuum Surveys and the Transformation of Radio Astronomy
Next-generation radio surveys are about to transform radio astronomy by
discovering and studying tens of millions of previously unknown radio sources.
These surveys will provide new insights to understand the evolution of
galaxies, measuring the evolution of the cosmic star formation rate, and
rivalling traditional techniques in the measurement of fundamental cosmological
parameters. By observing a new volume of observational parameter space, they
are also likely to discover unexpected new phenomena. This review traces the
evolution of extragalactic radio continuum surveys from the earliest days of
radio astronomy to the present, and identifies the challenges that must be
overcome to achieve this transformational change.Comment: To be published in Nature Astronomy 18 Sept 201
Fourientations and the Tutte polynomial
A fourientation of a graph is a choice for each edge of the graph whether to orient that edge in either direction, leave it unoriented, or biorient it. Fixing a total order on the edges and a reference orientation of the graph, we investigate properties of cuts and cycles in fourientations which give trivariate generating functions that are generalized Tutte polynomial evaluations of the form (k + m)[superscript nâ1](k + l)[superscript gT](Îąk + βl + m/k + m , Îł k + l + δm/ k + l) for Îą, Îł â {0, 1, 2} and β, δ â {0, 1}. We introduce an intersection lattice of 64 cutâcycle fourientation classes enumerated by generalized Tutte polynomial evaluations of this form. We prove these enumerations using a single deletionâcontraction argument and
classify axiomatically the set of fourientation classes to which our deletionâcontraction argument applies. This work unifies and extends earlier results for fourientations due to Gessel and Sagan (Electron J Combin 3(2):Research Paper 9, 1996), results for partial orientations due to Backman (Adv Appl Math, forthcoming, 2014. arXiv:1408.3962), and
Hopkins and Perkinson (Trans Am Math Soc 368(1):709â725, 2016), as well as results for total orientations due to Stanley (Discrete Math 5:171â178, 1973; Higher combinatorics (Proceedings of NATO Advanced Study Institute, Berlin, 1976). NATO Advanced Study Institute series, series C: mathematical and physical sciences, vol 31, Reidel, Dordrecht, pp 51â62, 1977), Las Vergnas (Progress in graph theory (Proceedings, Waterloo silver
jubilee conference 1982), Academic Press, New York, pp 367â380, 1984), Greene and Zaslavsky (Trans Am Math Soc 280(1):97â126, 1983), and Gioan (Eur J Combin 28(4):1351â1366, 2007), which were previously unified by Gioan (2007), Bernardi (Electron J Combin 15(1):Research Paper 109, 2008), and Las Vergnas (Tutte polynomial of a morphism of matroids 6. A multi-faceted counting formula for hyperplane regions and acyclic orientations, 2012. arXiv:1205.5424). We conclude by describing how these
classes of fourientations relate to geometric, combinatorial, and algebraic objects including bigraphical arrangements, cycleâcocycle reversal systems, graphic Lawrence ideals, RiemannâRoch theory for graphs, zonotopal algebra, and the reliability polynomial. Keywords: Partial graph orientations, Tutte polynomial, Deletionâcontraction, Hyperplane arrangements, Cycleâcocycle reversal system, Chip-firing, G-parking functions, Abelian sandpile model, RiemannâRoch theory for graphs, Lawrence ideals, Zonotopal algebra, Reliability polynomialNational Science Foundation (U.S.) (Grant 1122374
Localization of hRad9 in breast cancer
<p>Abstract</p> <p>Background</p> <p><it>hRad9 </it>is a cell cycle checkpoint gene that is up-regulated in breast cancer. We have previously shown that the mRNA up-regulation correlated with tumor size and local recurrence. Immunohistochemical studies were made to better define the role of <it>hRad9 </it>in breast carcinogenesis.</p> <p>Methods</p> <p>Localisation of hRad9 protein were performed on paired tumor and normal breast tissues. Immunoblotting with and without dephosphorylation was used to define the protein isolated from breast cancer cells.</p> <p>Results</p> <p>Increased hRad9 protein was observed in breast cancer cells nucleus compared to non-tumor epithelium. This nuclear protein existed in hyperphosphorylated forms which may be those of the hRad9-hRad1-hHus1 complex.</p> <p>Conclusion</p> <p>Finding of hyperphosphorylated forms of hRad9 in the nucleus of cancer cells is in keeping with its function in ameliorating DNA instability, whereby it inadvertently assists tumor growth.</p
Adaptive plasticity of killifish (Fundulus heteroclitus) embryos: dehydration-stimulated development and differential aquaporin-3 expression
13 pages, 7 figures, 3 tablesEmbryos of the marine killifish Fundulus heteroclitus are adapted to survive aerially. However, it is unknown if they are able to control development under dehydration conditions. Here, we show that air-exposed blastula embryos under saturated relative humidity were able to stimulate development, and hence the time of hatching was advanced with respect to embryos continuously immersed in seawater. Embryos exposed to air at later developmental stages did not hatch until water was added, while development was not arrested. Air-exposed embryos avoided dehydration probably because of their thickened egg envelope, although it suffered significant evaporative water loss. The potential role of aquaporins as part of the embryo response to dehydration was investigated by cloning the aquaporin-0 (FhAqp0), -1a (FhAqp1a), and -3 (FhAqp3) cDNAs. Functional expression in Xenopus laevis oocytes showed that FhaAqp1a was a water-selective channel, whereas FhAqp3 was permeable to water, glycerol, and urea. Expression of fhaqp0 and fhaqp1a was prominent during organogenesis, and their mRNA levels were similar between water- and air-incubated embryos. However, fhaqp3 transcripts were highly and transiently accumulated during gastrulation, and the protein product was localized in the basolateral membrane of the enveloping epithelial cell layer and in the membrane of ingressing and migrating blastomers. Interestingly, both fhaqp3 transcripts and FhAqp3 polypeptides were downregulated in air-exposed embryos. These data demonstrate that killifish embryos respond adaptively to environmental desiccation by accelerating development and that embryos are able to transduce dehydration conditions into molecular responses. The reduced synthesis of FhAqp3 may be one of these mechanisms to regulate water and/or solute transport in the embryo.This study was supported by the European Commission New and Emerging
Science and Technologies (NEST) program (contract no. 012674-2 Sleeping
Beauty) and by a grant from the Spanish Ministry of Education and Science
(MEC; AGL2004-00316/ACU) to J. Cerda`. Participation of C. Zapater and F.
Chauvigne´ was financed by a predoctoral fellowship from MEC (Spain) and by
the European Commission [Marie Curie Research Training Network Aqua
(glycero)porins, MRTN-CT-2006-035995], respectively.Peer reviewe
РОСŃĐ°Ń ŃнОк ŃĐ° ĐżŃОокŃŃĐ˛Đ°Đ˝Đ˝Ń ĐžĐşŃоПОгО ŃŃндаПонŃŃ ĐąŃĐ´ŃĐ˛ĐťŃ Đ˝Đ° ĐżŃиŃОднŃĐš ŇŃŃĐ˝ŃОвŃĐš ĐžŃнОвŃ. ĐĐľŃОдиŃĐ˝Ń ŃокОПондаŃŃŃ Đ´Đž Đ˛Đ¸ĐşĐžĐ˝Đ°Đ˝Đ˝Ń ĐżŃĐ°ĐşŃиŃĐ˝Đ¸Ń ĐˇĐ°Đ˛Đ´Đ°Đ˝Ń ŃĐ° ĐşŃŃŃОвОгО ĐżŃОокŃŃ Đˇ диŃŃипНŃни ÂŤĐĐľŃ Đ°Đ˝Ńка ŇŃŃĐ˝ŃŃв, ĐžŃнОви Ń ŃŃндаПонŃи ŃŃŃ- донŃаПи напŃŃĐźŃв ĐżŃдгОŃОвки 6.060101 ĐŃĐ´ŃвниŃŃвО ŃĐ° 6.050301 ĐŃŃниŃŃвО
ĐОданО ПоŃОдиŃĐ˝Ń ŃокОПондаŃŃŃ Đ´Đž Đ˛Đ¸ĐşĐžĐ˝Đ°Đ˝Đ˝Ń ĐżŃĐ°ĐşŃиŃниŃ
ĐˇĐ°Đ˛Đ´Đ°Đ˝Ń ŃĐ° ĐşŃŃ-
ŃОвОгО ĐżŃОокŃŃ Đˇ диŃŃипНŃни ÂŤĐĐľŃ
Đ°Đ˝Ńка ŇŃŃĐ˝ŃŃв, ĐžŃнОви Ń ŃŃндаПонŃи Đ´ĐťŃ ŃŃŃ-
донŃŃв напŃŃĐźŃв ĐżŃдгОŃОвки 6.060101 ĐŃĐ´ŃвниŃŃвО ŃĐ° 6.050301 ĐŃŃниŃŃвО.
РОСгНŃĐ˝ŃŃĐž пОŃŃдОк ĐżŃОокŃŃĐ˛Đ°Đ˝Đ˝Ń ŃŃндаПонŃŃ ĐąŃĐ´ŃĐ˛ĐťŃ ĐźŃНкОгО СакНадан-
Đ˝Ń Đ˝Đ° ĐżŃиŃОднŃĐš ŇŃŃĐ˝ŃОвŃĐš ĐžŃнОвŃ.
ĐĐľŃОдиŃĐ˝Ń ŃокОПондаŃŃŃ ĐżĐľŃодйаŃĐ°ŃŃŃ Đ˛Đ¸ĐşĐžĐ˝Đ°Đ˝Đ˝Ń ĐşŃŃŃОвОгО ĐżŃОокŃŃ
РОСŃĐ°Ń
ŃнОк ŃĐ° ĐżŃОокŃŃĐ˛Đ°Đ˝Đ˝Ń ĐžĐşŃоПОгО ŃŃндаПонŃŃ ĐąŃĐ´ŃĐ˛ĐťŃ Đ˝Đ° ĐżŃиŃОднŃĐš ŇŃŃĐ˝-
ŃОвŃĐš ĐžŃнОвŃÂť ŃĐş ŃС викНадаŃоП, ŃĐ°Đş Ń ĐżŃĐ´ ŃĐ°Ń ŃаПОŃŃŃĐšĐ˝ĐžŃ ŃОйОŃи.
ĐОМна викОŃиŃŃОвŃваŃи ŃакОМ Ń ĐżŃдгОŃОвŃŃ ĐşŃŃŃОвОгО ŃĐ° дипНОПнОгО ĐżŃĐž-
окŃŃваннŃ
Formation of Supermassive Black Holes
Evidence shows that massive black holes reside in most local galaxies.
Studies have also established a number of relations between the MBH mass and
properties of the host galaxy such as bulge mass and velocity dispersion. These
results suggest that central MBHs, while much less massive than the host (~
0.1%), are linked to the evolution of galactic structure. In hierarchical
cosmologies, a single big galaxy today can be traced back to the stage when it
was split up in hundreds of smaller components. Did MBH seeds form with the
same efficiency in small proto-galaxies, or did their formation had to await
the buildup of substantial galaxies with deeper potential wells? I briefly
review here some of the physical processes that are conducive to the evolution
of the massive black hole population. I will discuss black hole formation
processes for `seed' black holes that are likely to place at early cosmic
epochs, and possible observational tests of these scenarios.Comment: To appear in The Astronomy and Astrophysics Review. The final
publication is available at http://www.springerlink.co
The effectiveness of interventions to change six health behaviours: a review of reviews
Background: Several World Health Organisation reports over recent years have highlighted the high incidence of chronic diseases such as diabetes, coronary heart disease and cancer. Contributory factors include unhealthy diets, alcohol and tobacco use and sedentary lifestyles. This paper reports the findings of a review of reviews of behavioural change interventions to reduce unhealthy behaviours or promote healthy behaviours. We included six different health-related behaviours in the review: healthy eating, physical exercise, smoking, alcohol misuse, sexual risk taking (in young people) and illicit drug use. We excluded reviews which focussed on pharmacological treatments or those which required intensive treatments (e. g. for drug or alcohol dependency).
Methods: The Cochrane Library, Database of Abstracts of Reviews of Effectiveness (DARE) and several Ovid databases were searched for systematic reviews of interventions for the six behaviours (updated search 2008). Two reviewers applied the inclusion criteria, extracted data and assessed the quality of the reviews. The results were discussed in a narrative synthesis.
Results: We included 103 reviews published between 1995 and 2008. The focus of interventions varied, but those targeting specific individuals were generally designed to change an existing behaviour (e. g. cigarette smoking, alcohol misuse), whilst those aimed at the general population or groups such as school children were designed to promote positive behaviours (e. g. healthy eating). Almost 50% (n = 48) of the reviews focussed on smoking (either prevention or cessation). Interventions that were most effective across a range of health behaviours included physician advice or individual counselling, and workplace- and school-based activities. Mass media campaigns and legislative interventions also showed small to moderate effects in changing health behaviours. Generally, the evidence related to short-term effects rather than sustained/longer-term impact and there was a relative lack of evidence on how best to address inequalities.
Conclusions: Despite limitations of the review of reviews approach, it is encouraging that there are interventions that are effective in achieving behavioural change. Further emphasis in both primary studies and secondary analysis (e.g. systematic reviews) should be placed on assessing the differential effectiveness of interventions across different population subgroups to ensure that health inequalities are addressed.</p
- âŚ