Blue luminous stars in nearby galaxies - UIT005: a possible link to the luminous blue variable stage

(abridged) A detailed study of the blue supergiant UIT005 (B2-2.5Ia+) in M33 is presented. The results of our quantitative spectral analysis indicate that the star is a very luminous, log(L/Lsun)~5.9 dex, and massive, M~50 Msun, object, showing a very high nitrogen-to-oxygen ratio in its surface (N/O~8, by mass). Based on the derived Mg and Si abundances, we argue that this high N/O ratio cannot be the result of an initial low O content due to its location on the disk of M33, known to present a steep metallicity gradient. In combination with the He abundance, the most plausible interpretation is that UIT005 is in an advanced stage of evolution, showing in its surface N enrichment and O depletion resulting from mixing with CNO processed material from the stellar interior. A comparison with the predictions of current stellar evolutionary models indicates that there are significant discrepancies, in particular with regard to the degree of chemical processing, with the models predicting a much lower degree of O depletion than observed. At the same time, the mass-loss rate derived in our analysis is an order of magnitude lower than the values considered in the evolutionary calculations. Based on a study of the surrounding stellar population and the nearby cluster NGC588, using WFPC2 photometry, we suggest that UIT005 could be in fact a runaway star from this cluster.Comment: Accepted for publication by ApJ, 11 figures, 45 page

AdS4 flux vacua in type II superstrings and their domain-wall solutions

We investigate the emergence of supersymmetric negative-vacuum-energy ground states in four dimensions. First, we rely on the analysis of the effective superpotential, which depends on the background fluxes of the internal manifold, or equivalently has its origin in the underlying gauged supergravity. Four-dimensional, supersymmetric anti-de Sitter vacua with all moduli stabilized appear when appropriate Ramond and Neveu--Schwarz fluxes are introduced in IIA. Geometric fluxes are not necessary. Then the whole setup is analyzed from the perspective of the sources, namely D/NS-branes or Kaluza--Klein monopoles. Orientifold planes are also required for tadpole cancellation. The solutions found in four dimensions correspond to domain walls interpolating between AdS4 and flat spacetime. The various consistency conditions (equations of motion, Bianchi identities and tadpole cancellation conditions) are always satisfied, albeit with source terms. We also speculate on the possibility of assigning (formal) entropies to AdS4 flux vacua via the corresponding dual brane systems.Comment: Acknowledgment replace

Assessment of Serum Cytokines and Oxidative Stress Markers in Elite Athletes Reveals Unique Profiles Associated With Different Sport Disciplines

© Copyright © 2020 Sohail, Al-Mansoori, Al-Jaber, Georgakopoulos, Donati, Botrè, Sellami and Elrayess. Objectives: Circulating cytokines and oxidative stress markers vary in response to different exercise regimens. This study aims to compare the immune-inflammatory and oxidative stress profiles of elite athletes from different sport disciplines as potential biomarkers of muscle damage, and cardiovascular demand. Methods: Serum samples from 88 consented elite male athletes from different sports disciplines (aquatics, n = 11, athletics, n = 22, cycling, n = 19, football, n = 28 and weightlifting, n = 8) collected at the anti-doping lab in Italy were screened for 38 cytokines and oxidative stress markers. Comparisons were made between different level of power, cardiovascular demand (CD) and endurance, as well as among the sport types. Results: The anti-inflammatory interleukin (IL)-10 was higher (p = 0.04) in moderate power compared with the high power group. Conversely, superoxide dismutase (SOD; p = 0.001) and malondialdehyde (MDA; p = 0.007) levels were greater in the higher power groups compared with the lower power counterpart. Among athletes who belong to different CD ranks, IL-1β and monocyte chemoattractant protein-1(MCP1) levels were higher (p = 0.03) in the low CD-rank group compared with high CD counterpart, whereas, SOD levels were higher (p = 0.001) in high and moderate CD-rank groups compared to low counterpart. For endurance groups, IL-10 and macrophage inflammatory protein (MIP)-1beta were increased (p = 0.03) in low/moderate endurance compared with the high endurance group. Finally, MIP1-beta, SOD and catalase varied significantly among the sports groups. Conclusion: Specific markers of inflammation and oxidative stress are associated with different sports disciplines and could be utilized as potential biomarkers of athletes’ health, performance, and recovery from injury.We would like to thank Qatar National Research Fund (QNRF) for funding this project

The Composition Gradient in M101 Revisited. II. Electron Temperatures and Implications for the Nebular Abundance Scale

(Abridged) We use high S/N spectra of 20 HII regions in the giant spiral galaxy M101 to derive electron temperatures for the HII regions and robust metal abundances over radii R = 0.19-1.25 Ro (6-41 kpc). We compare the consistency of electron temperatures measured from the [O III]4363, [N II]5755, [S III]6312, and [O II]7325 auroral lines. Temperatures from [O III], [S III], and [N II] are correlated with relative offsets that are consistent with expectations from nebular photoionization models. However, the temperatures derived from the [O II]7325 line show a large scatter and are nearly uncorrelated with temperatures derived from other ions. Our derived oxygen abundances O/H are well fitted by an exponential distribution over six disk scale lengths, from approximately 1.3 solar in the center to 1/15 solar in the outermost region studied (for solar 12 + log (O/H)=8.7). We measure significant radial gradients in N/O and He/H abundance ratios, but relatively constant S/O and Ar/O. Our abundances are systematically lower by 0.2-0.5 dex than those derived from the most widely used strong-line "empirical" abundance indicators. We suspect that most of the disagreement with the strong-line abundances arises from uncertainties in the nebular models that are used to calibrate the "empirical" scale, and that strong-line abundances derived for HII regions and emission-line galaxies are as much as a factor of two higher than the actual oxygen abundances. However other explanations, such as the effects of temperature fluctuations on the auroral line based abundances cannot be completely ruled out. These results point to the need for direct abundance determinations of a larger sample of extragalactic HII regions, especially for objects more metal-rich than solar.Comment: 50 pages, 14 figures, 8 tables. Accepted by Ap

Estimating Star Formation Rates from Infrared and Radio Luminosities: The Origin of the Radio-Infrared Correlation

I have assembled a diverse sample of galaxies from the literature with far-ultraviolet (FUV), optical, infrared (IR) and radio luminosities to explore the calibration of radio-derived and IR-derived star formation (SF) rates, and the origin of the radio-IR correlation. By comparing the 8-1000 micron IR, which samples dust-reprocessed starlight, with direct stellar FUV emission, I show that the IR traces most of the SF in luminous L* galaxies but traces only a small fraction of the SF in faint ~0.01 L* galaxies. If radio emission were a perfect SF rate indicator, this effect would cause easily detectable curvature in the radio-IR correlation. Yet, the radio-IR correlation is nearly linear. This implies that the radio flux from low-luminosity galaxies is substantially suppressed, compared to brighter galaxies. This is naturally interpreted in terms of a decreasing efficiency of non-thermal radio emission in faint galaxies. Thus, the linearity of the radio-IR correlation is a conspiracy: both indicators underestimate the SF rate at low luminosities. SF rate calibrations which take into account this effect are presented, along with estimates of the random and systematic error associated with their use

Severe metabolic alterations in liver cancer lead to ERK pathway activation and drug resistance

Background: The extracellular signal-regulated kinase (ERK) pathway regulates cell growth, and is hyper-activated and associated with drug resistance in hepatocellular carcinoma (HCC). Metabolic pathways are profoundly dysregulated in HCC. Whether an altered metabolic state is linked to activated ERK pathway and drug response in HCC is unaddressed. Methods: We deprived HCC cells of glutamine to induce metabolic alterations and performed various assays, including metabolomics (with 13C-glucose isotope tracing), microarray analysis, and cell proliferation assays. Glutamine-deprived cells were also treated with kinase inhibitors (e.g. Sorafenib, Erlotinib, U0126 amongst other MEK inhibitors). We performed bioinformatics analysis and stratification of HCC tumour microarrays to determine upregulated ERK gene signatures in patients. Findings: In a subset of HCC cells, the withdrawal of glutamine triggers a severe metabolic alteration and ERK phosphorylation (pERK). This is accompanied by resistance to the anti-proliferative effect of kinase inhibitors, despite pERK inhibition. High intracellular serine is a consistent feature of an altered metabolic state and contributes to pERK induction and the kinase inhibitor resistance. Blocking the ERK pathway facilitates cell proliferation by reprogramming metabolism, notably enhancing aerobic glycolysis. We have identified 24 highly expressed ERK gene signatures that their combined expression strongly indicates a dysregulated metabolic gene network in human HCC tissues. Interpretation: A severely compromised metabolism lead to ERK pathway induction, and primes some HCC cells to pro-survival phenotypes upon ERK pathway blockade. Our findings offer novel insights for understanding, predicting and overcoming drug resistance in liver cancer patients

The Functional DRD3 Ser9Gly Polymorphism (rs6280) Is Pleiotropic, Affecting Reward as Well as Movement

Abnormalities of motivation and behavior in the context of reward are a fundamental component of addiction and mood disorders. Here we test the effect of a functional missense mutation in the dopamine 3 receptor (DRD3) gene (ser9gly, rs6280) on reward-associated dopamine (DA) release in the striatum. Twenty-six healthy controls (HCs) and 10 unmedicated subjects with major depressive disorder (MDD) completed two positron emission tomography (PET) scans with [11C]raclopride using the bolus plus constant infusion method. On one occasion subjects completed a sensorimotor task (control condition) and on another occasion subjects completed a gambling task (reward condition). A linear regression analysis controlling for age, sex, diagnosis, and self-reported anhedonia indicated that during receipt of unpredictable monetary reward the glycine allele was associated with a greater reduction in D2/3 receptor binding (i.e., increased reward-related DA release) in the middle (anterior) caudate (p<0.01) and the ventral striatum (p<0.05). The possible functional effect of the ser9gly polymorphism on DA release is consistent with previous work demonstrating that the glycine allele yields D3 autoreceptors that have a higher affinity for DA and display more robust intracellular signaling. Preclinical evidence indicates that chronic stress and aversive stimulation induce activation of the DA system, raising the possibility that the glycine allele, by virtue of its facilitatory effect on striatal DA release, increases susceptibility to hyperdopaminergic responses that have previously been associated with stress, addiction, and psychosis

A systematic evaluation of expression of HERV-W elements; influence of genomic context, viral structure and orientation

<p>Abstract</p> <p>Background</p> <p>One member of the W family of human endogenous retroviruses (HERV) appears to have been functionally adopted by the human host. Nevertheless, a highly diversified and regulated transcription from a range of HERV-W elements has been observed in human tissues and cells. Aberrant expression of members of this family has also been associated with human disease such as multiple sclerosis (MS) and schizophrenia. It is not known whether this broad expression of HERV-W elements represents transcriptional leakage or specific transcription initiated from the retroviral promoter in the long terminal repeat (LTR) region. Therefore, potential influences of genomic context, structure and orientation on the expression levels of individual HERV-W elements in normal human tissues were systematically investigated.</p> <p>Results</p> <p>Whereas intronic HERV-W elements with a pseudogene structure exhibited a strong anti-sense orientation bias, intronic elements with a proviral structure and solo LTRs did not. Although a highly variable expression across tissues and elements was observed, systematic effects of context, structure and orientation were also observed. Elements located in intronic regions appeared to be expressed at higher levels than elements located in intergenic regions. Intronic elements with proviral structures were expressed at higher levels than those elements bearing hallmarks of processed pseudogenes or solo LTRs. Relative to their corresponding genes, intronic elements integrated on the sense strand appeared to be transcribed at higher levels than those integrated on the anti-sense strand. Moreover, the expression of proviral elements appeared to be independent from that of their corresponding genes.</p> <p>Conclusions</p> <p>Intronic HERV-W provirus integrations on the sense strand appear to have elicited a weaker negative selection than pseudogene integrations of transcripts from such elements. Our current findings suggest that the previously observed diversified and tissue-specific expression of elements in the HERV-W family is the result of both directed transcription (involving both the LTR and internal sequence) and leaky transcription of HERV-W elements in normal human tissues.</p

OptCircuit: An optimization based method for computational design of genetic circuits

<p>Abstract</p> <p>Background</p> <p>Recent years has witnessed an increasing number of studies on constructing simple synthetic genetic circuits that exhibit desired properties such as oscillatory behavior, inducer specific activation/repression, etc. It has been widely acknowledged that that task of building circuits to meet multiple inducer-specific requirements is a challenging one. This is because of the incomplete description of component interactions compounded by the fact that the number of ways in which one can chose and interconnect components, increases exponentially with the number of components.</p> <p>Results</p> <p>In this paper we introduce OptCircuit, an optimization based framework that automatically identifies the circuit components from a list and connectivity that brings about the desired functionality. Multiple literature sources are used to compile a comprehensive compilation of kinetic descriptions of promoter-protein pairs. The dynamics that govern the interactions between the elements of the genetic circuit are currently modeled using deterministic ordinary differential equations but the framework is general enough to accommodate stochastic simulations. The desired circuit response is abstracted as the maximization/minimization of an appropriately constructed objective function. Computational results for a toggle switch example demonstrate the ability of the framework to generate the complete list of circuit designs of varying complexity that exhibit the desired response. Designs identified for a genetic decoder highlight the ability of OptCircuit to suggest circuit configurations that go beyond the ones compatible with digital logic-based design principles. Finally, the results obtained from the concentration band detector example demonstrate the ability of OptCircuit to design circuits whose responses are contingent on the level of external inducer as well as pinpoint parameters for modification to rectify an existing (non-functional) biological circuit and restore functionality.</p> <p>Conclusion</p> <p>Our results demonstrate that OptCircuit framework can serve as a design platform to aid in the construction and finetuning of integrated biological circuits.</p