Anti-de Sitter curvature radius constrained by quasars in brane-world scenarios

This paper is intended to investigate the luminosity due to accretion of gas in supermassive black holes (SMBHs) in the center of quasars, using a brane-world scenario naturally endowed with extra dimensions, whereon theories formulated introduce corrections in the field equations at high energies. SMBHs possess the necessary highly energetic environment for the introduction of these corrections, which are shown to produce small deviations in all SMBH properties and, consequentely, corrections in the accretion theory that supports quasars radiative processes. The radiative flux observed from quasars indicates these deviations, from which the magnitude of the AdS$_5$ bulk curvature radius, and consequently the extra dimension compactification radius is estimated.Comment: 11 pages, RevTeX, Eq.(2) and (3) expanded, and comments thereon update

Antioxidant activity of aminodiarylamines in the thieno[3,2-b]pyridine series: radical scavenging activity, lipid peroxidation inhibition and redox profile

The antioxidant activity of the aminodi(hetero)arylamines, prepared by C-N coupling of the methyl 3-aminothieno[3,2-b]pyridine-2-carboxylate with bromonitrobenzenes and further reduction of the obtained nitro compounds, was evaluated by chemical, biochemical and electrochemical assays. The aminodi(hetero)arylamine with the amino group ortho to the NH and a methoxy group in para, was the most efficient in radical scavenging activity (RSA, 63 µM) and reducing power (RP, 33 µM), while the aminodiarylamine with the amino group in para to the NH, gave the best results in β-carotene-linoleate system (41 µM) and inhibition of formation of thiobarbituric acid reactive substances in porcine brain cells homogenates (7 µM), with EC50 values even lower than those obtained for the standard trolox. This diarylamine also presented the lowest oxidation potential, lower than the one of trolox, and the highest antioxidant power in the electrochemical assays. The para substitution with an amino group enables higher antioxidant potential.The authors are grateful to FCT and FEDER (European Fund for Regional Development)-COMPETE/QREN/EU for financial support through the research unities PEst-C/QUI/UI686/2011 and PEst-OE/AGR/UI0690/2011, the research project PTDC/QUI-QUI/111060/2009 and the post-Doctoral grant attributed to R.C.C. (SFRH/BPD/68344/2010)

Cross-species genomic and functional analyses identify a combination therapy using a CHK1 inhibitor and a ribonucleotide reductase inhibitor to treat triple-negative breast cancer

INTRODUCTION: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that is diagnosed in approximately 15% of all human breast cancer (BrCa) patients. Currently, no targeted therapies exist for this subtype of BrCa and prognosis remains poor. Our laboratory has previously identified a proliferation/DNA repair/cell cycle gene signature (Tag signature) that is characteristic of human TNBC. We hypothesize that targeting the dysregulated biological networks in the Tag gene signature will lead to the identification of improved combination therapies for TNBC. METHODS: Cross-species genomic analysis was used to identify human breast cancer cell lines that express the Tag signature. Knock-down of the up-regulated genes in the Tag signature by siRNA identified several genes that are critical for TNBC cell growth. Small molecule inhibitors to two of these genes were analyzed, alone and in combination, for their effects on cell proliferation, cell cycle, and apoptosis in vitro and tumor growth in vivo. Synergy between the two drugs was analyzed by the Chou-Talalay method. RESULTS: A custom siRNA screen was used to identify targets within the Tag signature that are critical for growth of TNBC cells. Ribonucleotide reductase 1 and 2 (RRM1 and 2) and checkpoint kinase 1 (CHK1) were found to be critical targets for TNBC cell survival. Combination therapy, to simultaneously attenuate cell cycle checkpoint control through inhibition of CHK1 while inducing DNA damage with gemcitabine, improved therapeutic efficacy in vitro and in xenograft models of TNBC. CONCLUSIONS: This combination therapy may have translational value for patients with TNBC and improve therapeutic response for this aggressive form of breast cancer

Nanoinformatics: developing new computing applications for nanomedicine

Nanoinformatics has recently emerged to address the need of computing applications at the nano level. In this regard, the authors have participated in various initiatives to identify its concepts, foundations and challenges. While nanomaterials open up the possibility for developing new devices in many industrial and scientific areas, they also offer breakthrough perspectives for the prevention, diagnosis and treatment of diseases. In this paper, we analyze the different aspects of nanoinformatics and suggest five research topics to help catalyze new research and development in the area, particularly focused on nanomedicine. We also encompass the use of informatics to further the biological and clinical applications of basic research in nanoscience and nanotechnology, and the related concept of an extended ?nanotype? to coalesce information related to nanoparticles. We suggest how nanoinformatics could accelerate developments in nanomedicine, similarly to what happened with the Human Genome and other -omics projects, on issues like exchanging modeling and simulation methods and tools, linking toxicity information to clinical and personal databases or developing new approaches for scientific ontologies, among many others

Trends in Silicates in the β\beta Pictoris Disk

While beta Pic is known to host silicates in ring-like structures, whether the properties of these silicate dust vary with stellocentric distance remains an open question. We re-analyze the beta Pictoris debris disk spectrum from the Spitzer Infrared Spectrograph (IRS) and a new IRTF/SpeX spectrum to investigate trends in Fe/Mg ratio, shape, and crystallinity in grains as a function of wavelength, a proxy for stellocentric distance. By analyzing a re-calibrated and re-extracted spectrum, we identify a new 18 micron forsterite emission feature and recover a 23 micron forsterite emission feature with a substantially larger line-to-continuum ratio than previously reported. We find that these prominent spectral features are primarily produced by small submicron-sized grains, which are continuously generated and replenished from planetesimal collisions in the disk and can elucidate their parent bodies' composition. We discover three trends about these small grains: as stellocentric distance increases, (1) small silicate grains become more crystalline (less amorphous), (2) they become more irregular in shape, and (3) for crystalline silicate grains, the Fe/Mg ratio decreases. Applying these trends to beta Pic's planetary architecture, we find that the dust population exterior to the orbits of beta Pic b and c differs substantially in crystallinity and shape. We also find a tentative 3-5 micron dust excess due to spatially unresolved hot dust emission close to the star. From our findings, we infer that the surfaces of large planetesimals are more Fe-rich and collisionally-processed closer to the star but more Fe-poor and primordial farther from the star.Comment: 19 pages, 12 figures, Accepted for Publication in Ap

Validity and Reliability of the Robotic Objective Structured Assessment of Technical Skills

Objective structured assessments of technical skills (OSATS) have been developed to measure the skill of surgical trainees. Our aim was to develop an OSATS specifically for trainees learning robotic surgery

Acupuncture and rehabilitation of the painful shoulder: study protocol of an ongoing multicentre randomised controlled clinical trial [ISRCTN28687220]

BACKGROUND: Although the painful shoulder is one of the most common dysfunctions of the locomotor apparatus, and is frequently treated both at primary healthcare centres and by specialists, little evidence has been reported to support or refute the effectiveness of the treatments most commonly applied. According to the bibliography reviewed, physiotherapy, which is the most common action taken to alleviate this problem, has not yet been proven to be effective, because of the small size of sample groups and the lack of methodological rigor in the papers published on the subject. No reviews have been made to assess the effectiveness of acupuncture in treating this complaint, but in recent years controlled randomised studies have been made and these demonstrate an increasing use of acupuncture to treat pathologies of the soft tissues of the shoulder. In this study, we seek to evaluate the effectiveness of physiotherapy applied jointly with acupuncture, compared with physiotherapy applied with a TENS-placebo, in the treatment of painful shoulder caused by subacromial syndrome (rotator cuff tendinitis and subacromial bursitis). METHODS/DESIGN: Randomised controlled multicentre study with blind evaluation by an independent observer and blind, independent analysis. A study will be made of 465 patients referred to the rehabilitation services at participating healthcare centres, belonging to the regional public health systems of Andalusia and Murcia, these patients presenting symptoms of painful shoulder and a diagnosis of subacromial syndrome (rotator cuff tendinitis and subacromial bursitis). The patients will be randomised into two groups: 1) experimental (acupuncture + physiotherapy); 2) control (TENS-placebo + physiotherapy); the administration of rescue medication will also be allowed. The treatment period will have a duration of three weeks. The main result variable will be the change produced on Constant's Shoulder Function Assessment (SFA) Scale; as secondary variables, we will record the changes in diurnal pain intensity on a visual analogue scale (VAS), nocturnal pain intensity on the VAS, doses of non-steroid anti-inflammatory drugs (NSAIDs) taken during the study period, credibility scale for the treatment, degree of improvement perceived by the patient and degree of improvement perceived by the evaluator. A follow up examination will be made at 3, 6 and 12 months after the study period has ended. Two types of population will be considered for analysis: per protocol and per intention to treat. DISCUSSION: The discussion will take into account the limitations of the study, together with considerations such as the choice of a simple, safe method to treat this shoulder complaint, the choice of the control group, and the blinding of the patients, evaluators and those responsible for carrying out the final analysis

Attrition, physical integrity and insecticidal activity of long-lasting insecticidal nets in sub-Saharan Africa and modelling of their impact on vectorial capacity

Long-lasting insecticidal nets (LLINs) are the primary malaria prevention and control intervention in many parts of sub-Saharan Africa. While LLINs are expected to last at least 3 years under normal use conditions, they can lose effectiveness because they fall out of use, are discarded, repurposed, physically damaged, or lose insecticidal activity. The contributions of these different interrelated factors to durability of nets and their protection against malaria have been unclear.; Starting in 2009, LLIN durability studies were conducted in seven countries in Africa over 5 years. WHO-recommended measures of attrition, LLIN use, insecticidal activity, and physical integrity were recorded for eight different net brands. These data were combined with analyses of experimental hut data on feeding inhibition and killing effects of LLINs on both susceptible and pyrethroid resistant malaria vectors to estimate the protection against malaria transmission-in terms of vectorial capacity (VC)-provided by each net cohort over time. Impact on VC was then compared in hypothetical scenarios where one durability outcome measure was set at the best possible level while keeping the others at the observed levels.; There was more variability in decay of protection over time by country than by net brand for three measures of durability (ratios of variance components 4.6, 4.4, and 1.8 times for LLIN survival, use, and integrity, respectively). In some countries, LLIN attrition was slow, but use declined rapidly. Non-use of LLINs generally had more effect on LLIN impact on VC than did attrition, hole formation, or insecticide loss.; There is much more variation in LLIN durability among countries than among net brands. Low levels of use may have a larger impact on effectiveness than does variation in attrition or LLIN degradation. The estimated entomological effects of chemical decay are relatively small, with physical decay probably more important as a driver of attrition and non-use than as a direct cause of loss of effect. Efforts to maximize LLIN impact in operational settings should focus on increasing LLIN usage, including through improvements in LLIN physical integrity. Further research is needed to understand household decisions related to LLIN use, including the influence of net durability and the presence of other nets in the household