1,772 research outputs found
Energetics of jets from X-ray binaries
I discuss the energetics of synchrotron-emitting outflows, increasingly found
to be present in many different classes of X-ray binary systems. It is shown
that the outflow is likely to be comparable in power to the integrated X-ray
luminosity, traditionally taken to be an indicator of the global mass-transfer
rate. This is especially found to be the case in the (low/)hard states of black
hole candidate systems. I conclude that jets are extremely important,
energetically and dynamically, for the accretion process in the majority of
known X-ray binary systems.Comment: To be published in `Proceedings of the Third Microquasar Workshop:
Granada Workshop on galactic relativistic jet sources', Eds A. J.
Castro-Tirado, J. Greiner and J. M. Paredes, Astrophysics and Space Science,
in pres
Holographic duals of SQCD models in low dimensions
We obtain gravity duals to supersymmetric gauge theories in two and three
spacetime dimensions with unquenched flavor. The supergravity solutions are
generated by a set of color branes wrapping a compact cycle in a Calabi-Yau
threefold, together with another set of flavor branes extended along the
directions orthogonal to the cycle wrapped by the color branes. We construct
supergravity backgrounds which include the backreaction induced by a smeared
set of flavor branes, which act as delocalized dynamical sources of the
different supergravity fields.Comment: 42 pages, 5 figures;v2: typos correcte
Holographic Approach to Regge Trajectory and Rotating D5 brane
We study the Regge trajectories of holographic mesons and baryons by
considering rotating strings and D5 brane, which is introduced as the baryon
vertex. Our model is based on the type IIB superstring theory with the
background of asymptotic . This background is dual to a
confining supersymmetric Yang-Mills theory (SYM) with gauge condensate,
, which determines the tension of the linear potential between the quark
and anti-quark. Then the slope of the meson trajectory () is given
by this condensate as at large spin . This
relation is compatible with the other theoretical results and experiments. For
the baryon, we show the importance of spinning baryon vertex to obtain a Regge
slope compatible with the one of and series. In both cases, mesons
and baryons, the trajectories are shifted to large mass side with the same
slope for increasing current quark mass.Comment: 28 pages, 7 figure
Lower prevalence of drug resistance mutations at first-line virological failure to first-line therapy with atripla vs. tenofovirRemtricitabine/lamivudineRefavirenz administered on a multiple tablet therapy
Fixed-dose combination antiretroviral therapy administered as a single-tablet regimen (STR) may improve virologic suppression rates. The effect of STRs on development of resistance when virologic failure occurs on STRs is not known
Activity of the DNA minor groove cross-linking agent SG2000 (SJG-136) against canine tumours
BACKGROUND: Cancer is the leading cause of death in older dogs and its prevalence is increasing. There is clearly a need to develop more effective anti-cancer drugs in dogs. SG2000 (SJG-136) is a sequence selective DNA minor groove cross-linking agent. Based on its in vitro potency, the spectrum of in vivo and clinical activity against human tumours, and its tolerability in human patients, SG2000 has potential as a novel therapeutic against spontaneously occurring canine malignancies. RESULTS: In vitro cytotoxicity was assessed using SRB and MTT assays, and in vivo activity was assessed using canine tumour xenografts. DNA interstrand cross-linking (ICL) was determined using a modification of the single cell gel electrophoresis (comet) assay. Effects on cell cycle distribution were assessed by flow cytometry and measurement of γ-H2AX by immunofluorescence and immunohistochemistry. SG2000 had a multi-log differential cytotoxic profile against a panel of 12 canine tumour cell lines representing a range of common tumour types in dogs. In the CMeC-1 melanoma cell line, DNA ICLs increased linearly with dose following a 1 h treatment. Peak ICL was achieved within 1 h and no removal was observed over 48 h. A relationship between DNA ICL formation and cytotoxicity was observed across cell lines. The formation of γ-H2AX foci was slow, becoming evident after 4 h and reaching a peak at 24 h. SG2000 exhibited significant anti-tumour activity against two canine melanoma tumour models in vivo. Anti-tumour activity was observed at 0.15 and 0.3 mg/kg given i.v. either once, or weekly x 3. Dose-dependent DNA ICL was observed in tumours (and to a lower level in peripheral blood mononuclear cells) at 2 h and persisted at 24 h. ICL increased following the second and third doses in a repeated dose schedule. At 24 h, dose dependent γ-H2AX foci were more numerous than at 2 h, and greater in tumours than in peripheral blood mononuclear cells. SG2000-induced H2AX phosphorylation measured by immunohistochemistry showed good correspondence, but less sensitivity, than measurement of foci. CONCLUSIONS: SG2000 displayed potent activity in vitro against canine cancer cell lines as a result of the formation and persistence of DNA ICLs. SG2000 also had significant in vivo antitumour activity against canine melanoma xenografts, and the comet and γ-H2AX foci methods were relevant pharmacodynamic assays. The clinical testing of SG2000 against spontaneous canine cancer is warranted. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-015-0534-2) contains supplementary material, which is available to authorized users
Shape-resonant superconductivity in nanofilms: from weak to strong coupling
Ultrathin superconductors of different materials are becoming a powerful
platform to find mechanisms for enhancement of superconductivity, exploiting
shape resonances in different superconducting properties. Here we evaluate the
superconducting gap and its spatial profile, the multiple gap components, and
the chemical potential, of generic superconducting nanofilms, considering the
pairing attraction and its energy scale as tunable parameters, from weak to
strong coupling, at fixed electron density. Superconducting properties are
evaluated at mean field level as a function of the thickness of the nanofilm,
in order to characterize the shape resonances in the superconducting gap. We
find that the most pronounced shape resonances are generated for weakly coupled
superconductors, while approaching the strong coupling regime the shape
resonances are rounded by a mixing of the subbands due to the large energy gaps
extending over large energy scales. Finally, we find that the spatial profile,
transverse to the nanofilm, of the superconducting gap acquires a flat behavior
in the shape resonance region, indicating that a robust and uniform multigap
superconducting state can arise at resonance.Comment: 7 pages, 4 figures. Submitted to the Proceedings of the Superstripes
2016 conferenc
Turbulence and galactic structure
Interstellar turbulence is driven over a wide range of scales by processes
including spiral arm instabilities and supernovae, and it affects the rate and
morphology of star formation, energy dissipation, and angular momentum transfer
in galaxy disks. Star formation is initiated on large scales by gravitational
instabilities which control the overall rate through the long dynamical time
corresponding to the average ISM density. Stars form at much higher densities
than average, however, and at much faster rates locally, so the slow average
rate arises because the fraction of the gas mass that forms stars at any one
time is low, ~10^{-4}. This low fraction is determined by turbulence
compression, and is apparently independent of specific cloud formation
processes which all operate at lower densities. Turbulence compression also
accounts for the formation of most stars in clusters, along with the cluster
mass spectrum, and it gives a hierarchical distribution to the positions of
these clusters and to star-forming regions in general. Turbulent motions appear
to be very fast in irregular galaxies at high redshift, possibly having speeds
equal to several tenths of the rotation speed in view of the morphology of
chain galaxies and their face-on counterparts. The origin of this turbulence is
not evident, but some of it could come from accretion onto the disk. Such high
turbulence could help drive an early epoch of gas inflow through viscous
torques in galaxies where spiral arms and bars are weak. Such evolution may
lead to bulge or bar formation, or to bar re-formation if a previous bar
dissolved. We show evidence that the bar fraction is about constant with
redshift out to z~1, and model the formation and destruction rates of bars
required to achieve this constancy.Comment: in: Penetrating Bars through Masks of Cosmic Dust: The Hubble Tuning
Fork strikes a New Note, Eds., K. Freeman, D. Block, I. Puerari, R. Groess,
Dordrecht: Kluwer, in press (presented at a conference in South Africa, June
7-12, 2004). 19 pgs, 5 figure
The Gluonic Field of a Heavy Quark in Conformal Field Theories at Strong Coupling
We determine the gluonic field configuration sourced by a heavy quark
undergoing arbitrary motion in N=4 super-Yang-Mills at strong coupling and
large number of colors. More specifically, we compute the expectation value of
the operator tr[F^2+...] in the presence of such a quark, by means of the
AdS/CFT correspondence. Our results for this observable show that signals
propagate without temporal broadening, just as was found for the expectation
value of the energy density in recent work by Hatta et al. We attempt to shed
some additional light on the origin of this feature, and propose a different
interpretation for its physical significance. As an application of our general
results, we examine when the quark undergoes oscillatory motion,
uniform circular motion, and uniform acceleration. Via the AdS/CFT
correspondence, all of our results are pertinent to any conformal field theory
in 3+1 dimensions with a dual gravity formulation.Comment: 1+38 pages, 16 eps figures; v2: completed affiliation; v3: corrected
typo, version to appear in JHE
The basal epithelial marker P-cadherin associates with breast cancer cell populations harboring a glycolytic and acid-resistant phenotype
"BMC Cancer 2014 14:734"BACKGROUND:
Cancer stem cells are hypoxia-resistant and present a preponderant glycolytic metabolism. These characteristics are also found in basal-like breast carcinomas (BLBC), which show increased expression of cancer stem cell markers.Recently, we demonstrated that P-cadherin, a biomarker of BLBC and a poor prognostic factor in this disease, mediates stem-like properties and resistance to radiation therapy. Thus, the aim of the present study was to evaluate if P-cadherin expression was associated to breast cancer cell populations with an adapted phenotype to hypoxia.
METHODS:
Immunohistochemistry was performed to address the expression of P-cadherin, hypoxic, glycolytic and acid-resistance biomarkers in primary human breast carcinomas. In vitro studies were performed using basal-like breast cancer cell lines. qRT-PCR, FACS analysis, western blotting and confocal microscopy were used to assess the expression of P-cadherin after HIF-1a stabilization, achieved by CoCl2 treatment. siRNA-mediated knockdown was used to silence the expression of several targets and qRT-PCR was employed to evaluate the effects of P-cadherin on HIF-1a signaling. P-cadherin high and low breast cancer cell populations were sorted by FACS and levels of GLUT1 and CAIX were assessed by FACS and western blotting. Mammosphere forming efficiency was used to determine the stem cell activity after specific siRNA-mediated knockdown, further confirmed by western blotting.
RESULTS:
We demonstrated that P-cadherin overexpression was significantly associated with the expression of HIF-1a, GLUT1, CAIX, MCT1 and CD147 in human breast carcinomas. In vitro, we showed that HIF-1a stabilization was accompanied by increased membrane expression of P-cadherin and that P-cadherin silencing led to a decrease of the mRNA levels of GLUT1 and CAIX. We also found that the cell fractions harboring high levels of P-cadherin were the same exhibiting more GLUT1 and CAIX expression. Finally, we showed that P-cadherin silencing significantly decreases the mammosphere forming efficiency in the same range as the silencing of HIF-1a, CAIX or GLUT1, validating that all these markers are being expressed by the same breast cancer stem cell population.
CONCLUSIONS:
Our results establish a link between aberrant P-cadherin expression and hypoxic, glycolytic and acid-resistant breast cancer cells, suggesting a possible role for this marker in cancer cell metabolismo.This work was funded by FEDER funds through the COMPETE Program (Programa Operacional Factores de Competitividade) and by national funds through FCT (Portuguese Foundation for Science and Technology, Portugal), mainly in the context of the scientific project PTDC/SAU-GMG/120049/2010-FCOMP-01-0124-FEDER-021209, and partially by PTDC/SAU-FCF/104347/2008. FCT funded the research grants of BS (SFRH/BD/69353/2010), ASR (SFRH/BPD/75705/2011), ARN (grant from the project PTDC/SAU-GMG/120049/2010), CP (SFRH/BPD/69479/2010), AV (SFRH/BPD/90303/2012), as well as JP, with Programa Ciencia 2007 (Contratacao de Doutorados para o SCTN - financiamento pelo POPH - QREN - Tipologia 4.2 - Promocao do Emprego Cientifico, comparticipado pelo Fundo Social Europeu e por fundos nacionais do MCTES) and Programa IFCT (FCT Investigator). IPATIMUP is an Associate Laboratory of the Portuguese Ministry of Science, Technology and Higher Education and is partially supported by FCT
Long-term effectiveness of unboosted atazanavir plus abacavir/lamivudine in subjects with virological suppression: A prospective cohort study
Effectiveness data of an unboosted atazanavir (ATV) with abacavir/lamivudine (ABC/3TC) switch strategy in clinical routine are scant.We evaluated treatment outcomes of ATV + ABC/3TC in pretreated subjects in the EuroSIDA cohort when started with undetectable plasma HIV-1 viral load (pVL), performing a time to loss of virological response (TLOVR 50 copies/mL.We included 285 subjects, 67% male, with median baseline CD4 530 cells, and 44 months with pVL ≤50 copies/mL. The third drug in the previous regimen was ritonavir-boosted atazanavir (ATV/r) in 79 (28%), and another ritonavir-boosted protease inhibitor (PI/r) in 29 (10%). Ninety (32%) had previously failed with a PI. Proportions of people with virological success at 48/96/144 weeks were 90%/87%/88% (TLOVR) and 74%/67%/59% (snapshot analysis), respectively. The rates of VF were 8%/8%/6%. Rates of adverse events leading to study discontinuation were 0.4%/1%/2%. The multivariable adjusted analysis showed an association between VF and nadir CD4+ (hazard ratio [HR] 0.63 [95% confidence interval [CI]: 0.42-0.93] per 100 cells higher), time with pVL ≤50 copies/mL (HR 0.87 [95% CI: 0.79-0.96] per 6 months longer), and previous failure with a PI (HR 2.78 [95% CI: 1.28-6.04]). Resistance selection at failure was uncommon.A switch to ATV + ABC/3TC in selected subjects with suppressed viremia was associated with low rates of VF and discontinuation due to adverse events, even in subjects not receiving ATV/r. The strategy might be considered in those with long-term suppression and no prior PI failure
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