1,105 research outputs found
Thermophysical and Tribological Properties of Highly Viscous Biolubricants
Two new highly viscous biodegradable oils are investigated for use in wind turbine gearboxes (BIO-G00) and in mechanical transmissions of agricultural tractors (BIO-G02). Studies on their thermophysical and tribological properties were performed. High-pressure–viscosity measurements were obtained up to 250 MPa and 363.15 K using a falling-body apparatus. The viscosity of BIO-G00 and BIO-G02 reaches maximum values of 14720 and 7072 mPa·s, respectively. The film thickness and the tribological performance, from boundary to full-fluid lubrication regimes, under a slide-to-roll ratio of 5% obtained in an EHD2 ball-on-disk test rig are reported. Film thickness has also been computed through the Hamrock and Dowson equation, considering the inlet shear heating (thermal correction factor) due to the high viscosity of both biolubricants. Differences between the experimental and theoretical film thicknesses are around 4% at 353.15 K and 14% at 303.15 K for both oils. The universal pressure–viscosity coefficients, αfilm, for both oils are lower than those of other mineral and synthetic oils. Higher friction coefficients are obtained for BIO-G00 in all of the studied lubrication regimes for the different rough disks and in the entire temperature range. A suitable wetting behavior on steel surfaces is observed for both selected oils.Spanish Ministry of Economy and Competitiveness and the Xunta de Galicia have supported this work through GRC ED431C 2020/10 and ENE2017-86425-C2-2-R projects. The authors are grateful to the BIOVESIN (PSE-420000-2008-4) partners for the advice and for providing them the samples of the vegetable formulated oils and the reference lubricants. Dr. M.J.G.G. acknowledges a postdoctoral fellowship (ED481B-2019-015) from the Xunta de Galicia (Spain), and Dr. L.d.R. acknowledges the financial support through the Margarita Salas program (Ministry of Universities, Spain). The authors express their gratitude to Dr. K.R. Harris (University of New South Wales, Australia) for his high-pressure–viscosity study of DiPEiC9 and also to M.A. Marcos from the University of Vigo for his help with rheology tests.S
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
Extracellular cleavage and shedding of P-cadherin: a mechanism underlying the invasive behaviour of breast cancer cells
Cell-cell adhesion is an elementary process in normal epithelial cellular architecture. Several studies have shown the role mediated by cadherins in this process, besides their role in the maintenance of cell polarity, differentiation and cell growth. However, during tumour progression, these molecules are frequently altered. In breast cancer, tumours that overexpress P-cadherin usually present a high histological grade, show decreased cell polarity and are associated with worse patient survival. However, little is known about how this protein dictates the very aggressive behaviour of these tumours. To achieve this goal, we set up two breast cancer cell models, where P-cadherin expression was differently modulated and analysed in terms of cell invasion, motility and migration. We show that P-cadherin overexpression, in breast cancer cells with wild-type E-cadherin, promotes cell invasion, motility and migration. Moreover, we found that the overexpression of P-cadherin induces the secretion of matrix metalloproteases, specifically MMP-1 and MMP-2, which then lead to P-cadherin ectodomain cleavage. Further, we showed that soluble P-cadherin fragment is able to induce in vitro invasion of breast cancer cells. Overall, our results contribute to elucidate the mechanism underlying the invasive behaviour of P-cadherin expressing breast tumours.scientific project (POCI/BIA-BCM/59252/2004) financed by the Portuguese Science and Technology Foundation (FCT). FCT also provided research grants as follows: Programa Ciência 2007 (FCT) for Joana Paredes, and PhD research grants for Ana Sofia Ribeiro (SFRH/BD/36096/2007) and André Albergaria (SFRH/BD/15316/2005)
Multifrequency Strategies for the Identification of Gamma-Ray Sources
More than half the sources in the Third EGRET (3EG) catalog have no firmly
established counterparts at other wavelengths and are unidentified. Some of
these unidentified sources have remained a mystery since the first surveys of
the gamma-ray sky with the COS-B satellite. The unidentified sources generally
have large error circles, and finding counterparts has often been a challenging
job. A multiwavelength approach, using X-ray, optical, and radio data, is often
needed to understand the nature of these sources. This chapter reviews the
technique of identification of EGRET sources using multiwavelength studies of
the gamma-ray fields.Comment: 35 pages, 22 figures. Chapter prepared for the book "Cosmic Gamma-ray
Sources", edited by K.S. Cheng and G.E. Romero, to be published by Kluwer
Academic Press, 2004. For complete article and higher resolution figures, go
to: http://www.astro.columbia.edu/~muk/mukherjee_multiwave.pd
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
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
Thyrotropin-releasing hormone (TRH) promotes wound re-epithelialisation in frog and human skin
There remains a critical need for new therapeutics that promote wound healing in patients suffering from chronic skin wounds. This is, in part, due to a shortage of simple, physiologically and clinically relevant test systems for investigating candidate agents. The skin of amphibians possesses a remarkable regenerative capacity, which remains insufficiently explored for clinical purposes. Combining comparative biology with a translational medicine approach, we report the development and application of a simple ex vivo frog (Xenopus tropicalis) skin organ culture system that permits exploration of the effects of amphibian skin-derived agents on re-epithelialisation in both frog and human skin. Using this amphibian model, we identify thyrotropin-releasing hormone (TRH) as a novel stimulant of epidermal regeneration. Moving to a complementary human ex vivo wounded skin assay, we demonstrate that the effects of TRH are conserved across the amphibian-mammalian divide: TRH stimulates wound closure and formation of neo-epidermis in organ-cultured human skin, accompanied by increased keratinocyte proliferation and wound healing-associated differentiation (cytokeratin 6 expression). Thus, TRH represents a novel, clinically relevant neuroendocrine wound repair promoter that deserves further exploration. These complementary frog and human skin ex vivo assays encourage a comparative biology approach in future wound healing research so as to facilitate the rapid identification and preclinical testing of novel, evolutionarily conserved, and clinically relevant wound healing promoters
High energy emission from microquasars
The microquasar phenomenon is associated with the production of jets by X-ray
binaries and, as such, may be associated with the majority of such systems. In
this chapter we briefly outline the associations, definite, probable, possible,
and speculative, between such jets and X-ray, gamma-ray and particle emission.Comment: Contributing chapter to the book Cosmic Gamma-Ray Sources, K.S. Cheng
and G.E. Romero (eds.), to be published by Kluwer Academic Publishers,
Dordrecht, 2004. (19 pages
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Modifiable predictors of depression following childhood maltreatment: a systematic review and meta-analysis
Although maltreatment experiences in childhood increase the risk for depression, not all maltreated children become depressed. This review aims to systematically examine the existing literature to identify modifiable factors that increase vulnerability to, or act as a buffer against, depression, and could therefore inform the development of targeted interventions. Thirteen databases (including Medline, PsychINFO, SCOPUS) were searched (between 1984 and 2014) for prospective, longitudinal studies published in English that included at least 300 participants and assessed associations between childhood maltreatment and later depression. The study quality was assessed using an adapted Newcastle-Ottawa Scale checklist. Meta-analyses (random effects models) were performed on combined data to estimate the effect size of the association between maltreatment and depression. Meta-regressions were used to explore effects of study size and quality. We identified 22 eligible articles (N=12 210 participants), of which 6 examined potential modifiable predictors of depression following maltreatment. No more than two studies examined the same modifiable predictor; therefore, it was not possible to examine combined effects of modifiable predictors with meta-regression. It is thus difficult to draw firm conclusions from this study, but initial findings indicate that interpersonal relationships, cognitive vulnerabilities and behavioral difficulties may be modifiable predictors of depression following maltreatment. There is a lack of well-designed, prospective studies on modifiable predictors of depression following maltreatment. A small amount of initial research suggests that modifiable predictors of depression may be specific to maltreatment subtypes and gender. Corroboration and further investigation of causal mechanisms is required to identify novel targets for intervention, and to inform guidelines for the effective treatment of maltreated children
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