How Do Tourists React to Political Violence? An Empirical Analysis of Tourism in Egypt

This paper uses a detailed database of political violence in Egypt to study European and US tourists' attitudes towards a conflict region. We study the heterogeneous impacts of different dimensions of political violence and counter-violence on tourist flows to Egypt in the 1990s. Both US and EU tourists respond negatively to attacks on tourists, but are not influenced by casualties arising in confrontations between domestic groups. However, European tourists are sensitive to the counter-violence measures implemented by the Egyptian government. There is also evidence of arrivals of tourists into Egypt rising when fatalities in the Israeli/Palestinian conflict increase.</p

Mitochondrial function in heart failure: The impact of ischemic and non-ischemic etiology

Background Although cardiac mitochondrial dysfunction is associated with heart failure (HF), this is a complex syndrome with two predominant etiologies, ischemic HF (iHF) and non-ischemic HF (niHF), and the exact impact of mitochondrial dysfunction in these two distinct forms of HF is unknown. Methods and results To determine the impact of HF etiology on mitochondrial function, respiration was measured in permeabilized cardiac muscle fibers from patients with iHF (n = 17), niHF (n = 18), and healthy donor hearts (HdH). Oxidative phosphorylation capacity (OXPHOS), assessed as state 3 respiration, fell progressively from HdH to niHF, to iHF (Complex I + II: 54 ± 1; 34 ± 4; 27 ± 3 pmol·s− 1·mg− 1) as did citrate synthase activity (CSA: 206 ± 18; 129 ± 6; 82 ± 6 nmol·mg− 1·min− 1). Although still significantly lower than HdH, normalization of OXPHOS by CSA negated the difference in mass specific OXPHOS between iHF and niHF. Interestingly, Complex I state 2 respiration increased progressively from HdH, to niHF, to iHF, whether or not normalized for CSA (0.6 ± 0.2; 1.1 ± 0.3; 2.3 ± 0.3; pmol·mg− 1·CSA), such that the respiratory control ratio (RCR), fell in the same manner across groups. Finally, both the total free radical levels (60 ± 6; 46 ± 4 AU) and level of mitochondrial derived superoxide (1.0 ± 0.2; 0.7 ± 0.1 AU) were greater in iHF compared to niHF, respectively. Conclusions Thus, the HF-related attenuation in OXPHOS actually appears to be independent of etiology when the lower mitochondrial content of iHF is taken into account. However, these findings provide evidence of deleterious intrinsic mitochondrial changes in iHF, compared to niHF, including greater proton leak, attenuated OXPHOS efficiency, and augmented free radical levels

Enterprise social network success: Evidences from a multinational corporation

In a globalized world, where companies operate across different locations and work becomes increasingly complex, collaboration in a diversity of ways is required among employees to perform tasks more effectively. Following a case study methodology that involved six interviews across three different country locations, this research addresses the phenomenon of Enterprise Social Networks (ESN) in a multinational corporation with a focus on the assessment of ESN success. The findings show that the company, while trying to assess the success of Yammer, the freemium social networking service at use, has mainly relied on analytics tools to measure usage through indicators such as the total number of users. However, the extent to which ESN is used does not provide a complete picture of ESN success. Business value from that ESN usage is another dimension to be considered to assess success. Therefore, the study of specific ESN usage scenarios that are perceived to have a trackable impact on business results can be used to assess ESN business value on top of ESN usage to fully understand ESN success.COMPETE: POCI-01-0145-FEDER-007043 and FCT – Fundação para a Ciência e Tecnologia within the Project Scope: UID/CEC/00319/2013info:eu-repo/semantics/publishedVersio

A p53-independent role for the MDM2 antagonist Nutlin-3 in DNA damage response initiation.

BACKGROUND: The mammalian DNA-damage response (DDR) has evolved to protect genome stability and maximize cell survival following DNA-damage. One of the key regulators of the DDR is p53, itself tightly regulated by MDM2. Following double-strand DNA breaks (DSBs), mediators including ATM are recruited to the site of DNA-damage. Subsequent phosphorylation of p53 by ATM and ATM-induced CHK2 results in p53 stabilization, ultimately intensifying transcription of p53-responsive genes involved in DNA repair, cell-cycle checkpoint control and apoptosis. METHODS: In the current study, we investigated the stabilization and activation of p53 and associated DDR proteins in response to treatment of human colorectal cancer cells (HCT116p53+/+) with the MDM2 antagonist, Nutlin-3. RESULTS: Using immunoblotting, Nutlin-3 was observed to stabilize p53, and activate p53 target proteins. Unexpectedly, Nutlin-3 also mediated phosphorylation of p53 at key DNA-damage-specific serine residues (Ser15, 20 and 37). Furthermore, Nutlin-3 induced activation of CHK2 and ATM - proteins required for DNA-damage-dependent phosphorylation and activation of p53, and the phosphorylation of BRCA1 and H2AX - proteins known to be activated specifically in response to DNA damage. Indeed, using immunofluorescent labeling, Nutlin-3 was seen to induce formation of γH2AX foci, an early hallmark of the DDR. Moreover, Nutlin-3 induced phosphorylation of key DDR proteins, initiated cell cycle arrest and led to formation of γH2AX foci in cells lacking p53, whilst γH2AX foci were also noted in MDM2-deficient cells. CONCLUSION: To our knowledge, this is the first solid evidence showing a secondary role for Nutlin-3 as a DDR triggering agent, independent of p53 status, and unrelated to its role as an MDM2 antagonist

COMPETENCES AND JOB OPPORTUNITIES OF ORGANIC MEDICINAL AND AROMATIC PLANTS DOMAIN DEVELOPED BY HERBAL.MEDNET PROJECT

Herbal.Mednet project aims to design an e-learning training program for advisors and trainers in the field of organic Medicinal and Aromatic Plants (MAPs) in order to equip them with knowledge, competences and skills necessary for providing a support and technical and managerial assistance to producers, processors and traders of organic medicinal and aromatic plants domain. The results showed that more than 65% of the participants are quite familiar with using competences to describe a job profile, hence the overall feedback is of high importance.Almost of all users respond that competences are very useful in the thematic area of organic MAPs.The most of survey participants (over 65%) already are familiar and use the competence to describe job opportunities, and believe that it is a useful tool. From the results, it can be seen that the competence list that is been identified and is being used by the Herbal.Mednet consortium, reflects the needs in the organic MAPs job profiles

Activation of the p53 pathway by the MDM2 inhibitor nutlin-3a overcomes BCL2 overexpression in a preclinical model of diffuse large B-cell lymphoma associated with t(14;18)(q32;q21)

p53 is frequently wild type (wt) in diffuse large B-cell lymphoma (DLBCL) associated with t(14;18)(q32;q21) that overexpresses BCL2. Nutlin-3a is a small molecule that activates the p53 pathway by disrupting p53–MDM2 interaction. We show that nutlin-3a activates p53 in DLBCL cells associated with t(14;18)(q32;q21), BCL2 overexpression and wt p53, resulting in cell cycle arrest and apoptosis. Nutlin-3a treatment had similar effects on DLBCL cells of activated B-cell phenotype with wt p53. Cell cycle arrest was associated with upregulation of p21. Nutlin-3a-induced apoptosis was accompanied by BAX and PUMA upregulation, BCL-XL downregulation, serine-70 dephosphorylation of BCL2, direct binding of BCL2 by p53, caspase-9 upregulation and caspase-3 cleavage. Cell death was reduced when p53-dependent transactivation activity was inhibited by pifithrin-α (PFT-α), or PFT-μ inhibited direct p53 targeting of mitochondria. Nutlin-3a sensitized activation of the intrinsic apoptotic pathway by BCL2 inhibitors in t(14;18)-positive DLBCL cells with wt p53, and enhanced doxorubicin cytotoxicity against t(14;18)-positive DLBCL cells with wt or mutant p53, the latter in part via p73 upregulation. Nutlin-3a treatment in a xenograft animal lymphoma model inhibited growth of t(14;18)-positive DLBCL tumors, associated with increased apoptosis and decreased proliferation. These data suggest that disruption of the p53–MDM2 interaction by nutlin-3a offers a novel therapeutic approach for DLBCL associated with t(14;18)(q32;q21)

Evidence of Glycolysis Up-Regulation and Pyruvate Mitochondrial Oxidation Mismatch During Mechanical Unloading of the Failing Human Heart: Implications for Cardiac Reloading and Conditioning

This study sought to investigate the effects of mechanical unloading on myocardial energetics and the metabolic perturbation of heart failure (HF) in an effort to identify potential new therapeutic targets that could enhance the unloading-induced cardiac recovery. The authors prospectively examined paired human myocardial tissue procured from 31 advanced HF patients at left ventricular assist device (LVAD) implant and at heart transplant plus tissue from 11 normal donors. They identified increased post-LVAD glycolytic metabolites without a coordinate increase in early, tricarboxylic acid (TCA) cycle intermediates. The increased pyruvate was not directed toward the mitochondria and the TCA cycle for complete oxidation, but instead, was mainly converted to cytosolic lactate. Increased nucleotide concentrations were present, potentially indicating increased flux through the pentose phosphate pathway. Evaluation of mitochondrial function and structure revealed a lack of post-LVAD improvement in mitochondrial oxidative functional capacity, mitochondrial volume density, and deoxyribonucleic acid content. Finally, post-LVAD unloading, amino acid levels were found to be increased and could represent a compensatory mechanism and an alternative energy source that could fuel the TCA cycle by anaplerosis. In summary, the authors report evidence that LVAD unloading induces glycolysis in concert with pyruvate mitochondrial oxidation mismatch, most likely as a result of persistent mitochondrial dysfunction. These findings suggest that interventions known to improve mitochondrial biogenesis, structure, and function, such as controlled cardiac reloading and conditioning, warrant further investigation to enhance unloading-induced reverse remodeling and cardiac recovery

The COSMOS-Web ring: in-depth characterization of an Einstein ring lensing system at z~2

Aims. We provide an in-depth analysis of the COSMOS-Web ring, an Einstein ring at z=2 that we serendipitously discovered in the COSMOS-Web survey and possibly the most distant lens discovered to date. Methods. We extract the visible and NIR photometry from more than 25 bands and we derive the photometric redshifts and physical properties of both the lens and the source with three different SED fitting codes. Using JWST/NIRCam images, we also produce two lens models to (i) recover the total mass of the lens, (ii) derive the magnification of the system, (iii) reconstruct the morphology of the lensed source, and (iv) measure the slope of the total mass density profile of the lens. Results. The lens is a very massive and quiescent (sSFR < 10^(-13) yr-1) elliptical galaxy at z = 2.02 \pm 0.02 with a total mass Mtot(<thetaE) = (3.66 \pm 0.36) x 10^11 Msun and a stellar mass M* = (1.37 \pm 0.14) x 10^11 Msun. Compared to SHMRs from the literature, we find that the total mass is consistent with the presence of a DM halo of mass Mh = 1.09^(+1.46)_(-0.57) x 10^13 Msun. In addition, the background source is a M* = (1.26 \pm 0.17) x 10^10 Msun star-forming galaxy (SFR=(78 \pm 15) Msun/yr) at z = 5.48 \pm 0.06. Its reconstructed morphology shows two components with different colors. Dust attenuation values from SED fitting and nearby detections in the FIR also suggest it could be partially dust-obscured. Conclusions. We find the lens at z=2. Its total, stellar, and DM halo masses are consistent within the Einstein ring, so we do not need any unexpected changes in our description of the lens (e.g. change its IMF or include a non-negligible gas contribution). The most likely solution for the lensed source is at z = 5.5. Its reconstructed morphology is complex and highly wavelength dependent, possibly because it is a merger or a main sequence galaxy with a heterogeneous dust distribution.Comment: 16 pages, submitted to A&