Corporate Philanthropy, Research Networks, and Collaborative Innovation

Using a unique dataset of corporate philanthropy, we find that direct giving activities are positively associated with higher levels and more influential, collaborative, and original innovation. In contrast, our results do not hold for corporate foundations’ contributions. Our results suggest that much of what is ostensibly promoted as philanthropy actually reflects research-related networking activities. The effect of direct giving on innovation is more pronounced in more opaque firms and more innovative and competitive industries. These findings provide evidence of the distinct motives by which firms choose between direct giving and foundation giving. Our study suggests that firms can use direct philanthropy to expand firm-boundaries by developing innovation with research partners.postprin

CLEC5A-mediated enhancement of the inflammatory response in myeloid cells contributes to influenza virus pathogenicity in vivo

Human infections with influenza viruses exhibit mild to severe clinical outcomes as a result of complex virus-host interactions. Induction of inflammatory mediators via pattern recognition receptors may dictate subsequent host responses for pathogen clearance and tissue damage. We identified that human C-type lectin domain family 5 member A (CLEC5A) interacts with the hemagglutinin protein of influenza viruses expressed on lentiviral pseudoparticles through lectin screening. Silencing CLEC5A gene expression, blocking influenza-CLEC5A interactions with anti-CLEC5A antibodies, or dampening CLEC5A-mediated signaling using a spleen tyrosine kinase inhibitor consistently reduced the levels of proinflammatory cytokines produced by human macrophages without affecting the replication of influenza A viruses of different subtypes. Infection of bone marrow-derived macrophages from CLEC5A-deficient mice showed reduced levels of tumor necrosis factor alpha (TNF-α) and IP-10 but elevated alpha interferon (IFN-α) compared to those of wild-type mice. The heightened type I IFN response in the macrophages of CLEC5A-deficient mice was associated with upregulated TLR3 mRNA after treatment with double-stranded RNA. Upon lethal challenges with a recombinant H5N1 virus, CLEC5A-deficient mice showed reduced levels of proinflammatory cytokines, decreased immune cell infiltration in the lungs, and improved survival compared to the wild-type mice, despite comparable viral loads noted throughout the course of infection. The survival difference was more prominent at a lower dose of inoculum. Our results suggest that CLEC5A-mediated enhancement of the inflammatory response in myeloid cells contributes to influenza pathogenicity in vivo and may be considered a therapeutic target in combination with effective antivirals. Well-orchestrated host responses together with effective viral clearance are critical for optimal clinical outcome after influenza infections.published_or_final_versio

Prediction of Face-Lift Outcomes Using the Preoperative Supine Test

Patients considering a facelift (facial rhytidectomy) need some means of predicting their surgical outcomes. This will help them decide whether to proceed with the operation. A total of 50 consecutive patients were asked to examine themselves with a hand-held mirror while lying supine on an examining table to give them a reasonable approximation of their postoperative result. The tissues of the face redrape in a very aesthetic manner when lying completely supine. The appearance that the patient sees of himself or herself during the “supine test” correlated very well with the actual postop result after rhytidectomy consisting of subcutaneous undermining, SMAS plication, and platysmaplasty. This supine test may be useful in helping patients preoperatively predict their facelift outcomes and may serve as a good adjunct to imaging

Mycolactone-dependent depletion of endothelial cell thrombomodulin is strongly associated with fibrin deposition in Buruli ulcer lesions

A well-known histopathological feature of diseased skin in Buruli ulcer (BU) is coagulative necrosis caused by the Mycobacterium ulcerans macrolide exotoxin mycolactone. Since the underlying mechanism is not known, we have investigated the effect of mycolactone on endothelial cells, focussing on the expression of surface anticoagulant molecules involved in the protein C anticoagulant pathway. Congenital deficiencies in this natural anticoagulant pathway are known to induce thrombotic complications such as purpura fulimans and spontaneous necrosis. Mycolactone profoundly decreased thrombomodulin (TM) expression on the surface of human dermal microvascular endothelial cells (HDMVEC) at doses as low as 2ng/ml and as early as 8hrs after exposure. TM activates protein C by altering thrombin's substrate specificity, and exposure of HDMVEC to mycolactone for 24 hours resulted in an almost complete loss of the cells' ability to produce activated protein C. Loss of TM was shown to be due to a previously described mechanism involving mycolactone-dependent blockade of Sec61 translocation that results in proteasome-dependent degradation of newly synthesised ER-transiting proteins. Indeed, depletion from cells determined by live-cell imaging of cells stably expressing a recombinant TM-GFP fusion protein occurred at the known turnover rate. In order to determine the relevance of these findings to BU disease, immunohistochemistry of punch biopsies from 40 BU lesions (31 ulcers, nine plaques) was performed. TM abundance was profoundly reduced in the subcutis of 78% of biopsies. Furthermore, it was confirmed that fibrin deposition is a common feature of BU lesions, particularly in the necrotic areas. These findings indicate that there is decreased ability to control thrombin generation in BU skin. Mycolactone's effects on normal endothelial cell function, including its ability to activate the protein C anticoagulant pathway are strongly associated with this. Fibrin-driven tisischemia could contribute to the development of the tissue necrosis seen in BU lesions

A Novel Putative miRNA Target Enhancer Signal

It is known that miRNA target sites are very short and the effect of miRNA-target site interaction alone appears as being unspecific. Recent experiments suggest further context signals involved in miRNA target site recognition and regulation. Here, we present a novel GC-rich RNA motif downstream of experimentally supported miRNA target sites in human mRNAs with no similarity to previously reported functional motifs. We demonstrate that the novel motif can be found in at least one third of all transcripts regulated by miRNAs. Furthermore, we show that motif occurrence and the frequency of miRNA target sites as well as the stability of their duplex structures correlate. The finding, that the novel motif is significantly associated with miRNA target sites, suggests a functional role of the motif in miRNA target site biology. Beyond, the novel motif has the impact to improve prediction of miRNA target sites significantly

Hybrid method for selection of the optimal process of leachate treatment in waste treatment and valorization plants or landfills

“The final publication is available at Springer via http://dx.doi.org/10.1007/s10098-014-0834-4”Leachate from waste landfill or treatment plants is a very complex and highly contaminated liquid effluent. In its composition, it is found dissolved organic matter, inorganic salts, heavy metals, and other xenobiotic organic compounds, so it can be toxic, carcinogenic, and capable of inducing a potential risk to biota and humans. European law does not allow such leachate to leave the premises without being depolluted. There are many procedures that enable debugging, always combining different techniques. Choosing the best method to use in each case is a complex decision, as it depends on many tangible and intangible factors that must be weighed to achieve a balance between technical, cost, and environmental sustainability. It is presenting a hybrid method for choosing the optimal combination of techniques to apply in each case, by combining a multicriteria hierarchical analysis based on expert data obtained by the Delphi method with an analysis by the method of VIKOR to reach a consensus solution.Martín Utrillas, MG.; Reyes Medina, M.; Curiel Esparza, J.; Cantó Perelló, J. (2015). Hybrid method for selection of the optimal process of leachate treatment in waste treatment and valorization plants or landfills. Clean Technologies and Environmental Policy. 17(4):873-885. doi:10.1007/s10098-014-0834-4S873885174Abbas AA, Guo J, Ping LZ, Ya PY, Al-Rekabi WS (2009) Review on landfill leachate treatments. AJAS 6(4):672–684Abood AR, Bao J, Abudi Z, Zheng D, Gao C (2013) Pretreatment of nonbiodegradable landfill leachate by air stripping coupled with agitation as ammonia stripping and coagulation–flocculation processes. Clean Technol Environ Policy 15(6):1069–1076Ahn WY, Kang MS, Yim SK, Choi KH (2002) Advanced landfill leachate treatment using an integrated membrane process. Desalination 149(1–3):109–114Al-Subhi Al-Harbi KM (2001) Application of the AHP in project management. Int J Proj Manag 19:19–27Bernasconi M, Choirat C, Seri R (2014) Empirical properties of group preference aggregation methods employed in AHP: theory and evidence. Eur J Oper Res 232(3):584–592Boopathy R, Karthikeyan S, Mandal AB, Sekaran G (2013) Characterization and recovery of sodium chloride from salt-laden solid waste generated from leather industry. Clean Technol Environ Policy 15(1):117–124Brechet T, Tulkens H (2009) Beyond BAT: selecting optimal combinations of available techniques, with an example from the limestone industry. J Environ Manag 90:1790–1801Canto-Perello J, Curiel-Esparza J, Calvo V (2013) Criticality and threat analysis on utility tunnels for planning security policies of utilities in urban underground space. Expert Syst Appl 40(11):4707–4714Chen Y, Liu C, Nie J, Wu S, Wang D (2014) Removal of COD and decolorizing from landfill leachate by Fenton’s reagent advanced oxidation. Clean Technol Environ Policy 16(1):189–193Chiochetta CG, Goetten LC, Almeida SM, Quaranta G, Cotelle S, Radetski CM (2014) Leachates from solid wastes: chemical and eco(geno)toxicological differences between leachates obtained from fresh and stabilized industrial organic sludge. Environ Sci Pollut R 21:1090–1098Chiumenti A, da Borso F, Chiumenti R, Teri F, Segantin P (2013) Treatment of digestate from a co-digestion biogas plant by means of vacuum evaporation: tests for process optimization and environmental sustainability. Waste Manag 33(6):1339–1344Council Directive 1999/31/EC (1999) April 26th 1999, on the landfill of waste. European Union Council, Official Journal L 182, 16/07/1999 P. 0001–0019Curiel-Esparza J, Canto-Perello J (2012) Understanding the major drivers for implementation of municipal sustainable policies in underground space. Int J Sust Dev World 19(6):506–514Curiel-Esparza J, Canto-Perello J (2013) Selecting utilities placement techniques in urban underground engineering. Arch Civ Mech Eng 13(2):276–285Curiel-Esparza J, Canto-Perello J, Calvo MA (2004) Establishing sustainable strategies in urban underground engineering. Sci Eng Ethics 10(3):523–530Dong Y, Zhang G, Hong WC, Xu Y (2010) Consensus models for AHP group decision making under row geometric mean prioritization method. Decis Support Syst 49:281–289Duckstein L, Opricovic S (1980) Multiobjective Optimization in River Basin Development. Water Resour Res 16(1):14–20Ersahin ME, Ozgun H, van Lier JB (2013) Effect of support material properties on dynamic membrane filtration performance. Separ Sci Technol 48(15):2263–2269Gracht HA (2012) Consensus measurement in Delphi studies, review and implications for future quality assurance. Forecast Soc Chang 79(8):1525–1536Grisey E, Laffray X, Contoz O, Cavalli E, Mudry J, Aleya L (2012) The bioaccumulation performance of reeds and cattails in a constructed treatment wetland for removal of heavy metals in landfill leachate treatment (Etueffont, France). Water Air Soil Pollut 223:1723–1741Guoliang Z, Lei Q, Qin M, Zheng F, Dexin W (2013) Aerobic SMBR/reverse osmosis system enhanced by Fenton oxidation for advanced treatment of old municipal landfill leachate. Bioresour Technol 142:261–268Gupta SK, Singh G (2007) Assessment of the Efficiency and Economic Viability of Various Methods of Treatment of Sanitary Landfill Leachate. Environ Monit Assess 135:107–117Heyer KU, Stegmann R (2005) Landfill systems, sanitary landfilling of solid wastes, and long-term problems with leachate. In: Jördening HJ, Winter J (eds) Environmental Biotechnology. Wiley-VCH, Weinheim, p 375Hsu CC, Sandord BA (2007) The Delphi technique: making sense of consensus. PARE 12(10):1–7Kjeldsen P, Barlaz MA, Rooker AP, Baun A, Ledin A, Christensen TH (2002) Present and long-term composition of MSW landfill leachate: a review. Crit Rev Environ Sci Technol 32(4):297–336Lee WS (2013) Merger and acquisition evaluation and decision making model. Serv Ind J 33(15–16):1473–1494Lee GKL, Chan EHW (2008) The analytic hierarchy process (AHP) approach for assessment of urban renewal proposals. Soc Indic Res 89(1):155–168Li G, Wang W, Du Q (2010) Applicability of nanofiltration for the advanced treatment of landfill leachate. J Appl Polym Sci 116(4):2343–2347Mela K, Tiainen T, Heinisuo M (2012) Comparative study of multiple criteria decision making methods for building design. Adv Eng Inform 26:716–726Ozdemir MS, Saaty TL (2006) The unknown in decision making, what to do about it. Eur J Oper Res 174(1):349–359Renou S, Givaudan JG, Poulain S, Dirassouyan F, Moulin P (2008) Landfill leachate treatment: review and opportunity. J Hazard Mater 150(3):468–493Ritzkowski M, Stegmann R (2012) Landfill aeration worldwide: concepts, indications and findings. Waste Manag 32(7):1411–1419Romero C, Ramos P, Costa C, Marquez MC (2013) Raw and digested municipal waste compost leachate as potential fertilizer: comparison with a commercial fertilizer. J Clean Prod 59:73–78Roubelat F (2011) The Delphi method as a ritual: inquiring the Delphi Oracle. Forecast Soc Chang 78(9):1491–1499Saaty TL (1980) The analytic hierarchy process. Mc Graw-Hill, New YorkSaaty TL (2001) Decision making with dependence and feedback: the analytic network process, 2nd edn. RWS Publications, PittsburghSaaty TL (2008) Decision making with the analytic hierarchy process. Int J Serv Sci 1(1):83–98Saaty TL (2012) Decision making for leaders. The analytic hierarchy process for decisions in a complex world, 3rd edn. RWS Publications, PittsburghSan Cristobal J (2012) Contractor selection using multicriteria decision-making methods. J Constr Eng M 138(6):751–758Sayadi MK, Heydari M, Shahanaghi K (2009) Extension of VIKOR method for decision making problem with interval numbers. Appl Math Model 33:2257–2262Statnikova RB, Bordetskya A, Statnikov A (2005) Multi-criteria analysis of real-life engineering optimization problems: statement and solution. Nonlinear Anal 63:685–696Syamsuddin J (2010) The use of AHP in security policy decision making: an open office calc application. JSW 5(10):1162–1169Thapa RB, Murayama Y (2010) Drivers of urban growth in the Kathmandu valley, Nepal: examining the efficacy of the analytic hierarchy process. App Geogr 30(1):70–83van Praagh M, Heerenklage J, Smidt E, Modin H, Stegmann R, Persson KM (2009) Potential emissions from two mechanically–biologically pretreated (MBT) wastes. Waste Manag 29(2):859–868Vedaraman N, Shamshath BS, Srinivasan SV (2013) Response surface methodology for decolourisation of leather dye using ozonation in a packed bed reactor. Clean Technol Environ Policy 15(4):607–616Wang Q, Matsufuji Y, Dong L, Huang Q, Hirano F, Tanaka A (2006) Research on leachate recirculation from different types of landfills. Waste Manag 26:815–824Xing W, Lu W, Zhao Y (2013) Environmental impact assessment of leachate recirculation in landfill of municipal solid waste by comparing with evaporation and discharge (EASEWASTE). Waste Manag 33(2):382–389Yang W, Zhang KN, Chen YG, Zhou XZ, Jin FX (2013) Prediction on contaminant migration in aquifer of fractured granite substrata of landfill. J Cent South Univ 20(11):3193–3201Zavadskas EK, Turskis Z, Tamosaitiene J (2011) Selection of construction enterprises management strategy based on SWOT and multi-criteria analysis. ACME 11(4):1063–108

The apoptotic response in HCT116BAX-/- cancer cells becomes rapidly saturated with increasing expression of a GFP-BAX fusion protein

Abstract Background Many chemotherapeutic agents promote tumor cell death by activating the intrinsic pathway of apoptosis. Intrinsic apoptosis involves permeabilization of the mitochondrial outer membrane and the release of cytochrome c, a process that is controlled by proteins of the BCL2 gene family. Chemoresistance is often associated with abnormalities in concentrations of BCL2 family proteins. Although stoichiometirc interactions between anti-apoptotic and BH3-only BCL2 family proteins have been well documented as affecting cell death, the association between changes in BAX concentration and intrinsic apoptosis are poorly understood. Methods Exogenous GFP-murine Bax fusion constructs were transfected into BAX-deficient HCT116 cells. To titrate the expression of the fusion protein, GFP-BAX was cloned into a tetracycline sensitive expression cassette and cotransfected with a plasmid expressing the rtTA transcription factor into HCT116 BAX-/- cells. Linear expression of the fusion gene was induced with doxycycline and monitored by quantitative PCR and immunoblotting. Cell death was assayed by DAPI staining cells after exposure to indomethacin, and scoring nuclei for condensed chromatin and fragmented nuclei. Results HCT116 BAX-/- cells were resistant to indomethacin, but susceptibility could be recovered in cells expressing a GFP-BAX fusion protein. Titration of GFP-BAX expression revealed that the concentration of BAX required to induce a saturating apoptosis response from baseline, was rapidly achieved. Increased levels of GFP-BAX were unable to stimulate higher levels of cell death. Examination of GFP-BAX distribution before and after indomethacin treatment indicated that BAX protein did not form aggregates when present at sub-lethal concentrations. Conclusion Within the limitations of this experimental system, BAX-dependent apoptosis in HCT116 cells exhibits an all-or-none response depending on the level of BAX protein present. The lack of BAX aggregation at sub-saturation levels suggests that the translocation step of BAX activation may be impaired

The effect of renal perfusion pressure on renal vascular resistance in the spontaneously hypertensive rat

Renal hemodynamics and renal vascular resistance (RVR) were measured in the spontaneously hypertensive rat (SHR) and in the normotensive Wistar-Kyoto rat (WKY). In addition, the autoregulatory response and segmental RVR in the SHR were studied after aortic constriction. Mean arterial pressure (MAP) and RVR were higher in the SHR than in the WKY, but renal blood flow (RBF) and glomerular filtration rate were similar in both groups. Measurement of mean afferent arteriolar diameter (AAD) by a microsphere method showed a significantly smaller AAD in SHR (17.7±0.35 μm) than in the WKY (19.5±0.20 μm). This decrease in AAD could account for a 47% increase in preglomerular resistance. Aortic constriction in the SHR, sufficient to reduce renal perfusion pressure from 152 to 115 mm Hg, did not alter the AAD. Since RBF and glomerular filtration were also well maintained following aortic constriction, these autoregulatory responses suggest that vessels proximal to the afferent arteriole rather than postglomerular vasculature are primarily involved in the changes on intrarenal vascular resistance in SHR.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47448/1/424_2004_Article_BF00581421.pd