The Impact of Equity Engagement Evaluating the Impact of Shareholder Engagement in Public Equity Investing

Over the last decade, growing numbers of investors have become increasingly concerned with the environmental and social impact of their investments across asset classes. This trend has recently been driven by new waves of "impact investors" proactively seeking measurable social and environmental impact in addition to financial returns, and by "responsible investors" making commitments to engage on environmental, social, and governance (ESG) issues through initiatives such as the United Nations-backed Principles for Responsible Investment (PRI). At the same time, engaged shareholders have had long-standing experience using "the power of the proxy" and their voices as investors to hold companies accountable for the impacts they have on employees, stakeholders, communities, and ecosystems.While investor interest in shareholder engagement has grown, our understanding of the impacts associated with engagement activities remains largely anecdotal.In 2012, an important study on Total Portfolio Activation provided a new conceptual and analytical framework for investors to pursue environmental and social impact across all asset classes commonly found in a diversified investment portfolio. Building upon the insights of Total Portfolio Activation, the Impact of Equity Engagement (IE2) initiative seeks to deepen our understanding of the nature of impact in one specific asset class—public equities— where investors' engagement activities have generated meaningful social and environmental impacts.Given the large social and environmental footprints of publicly traded corporations and the persistently high allocation to public equities in most investor portfolios, public equity investing presents a major opportunity for impact investing. Yet impact investing, as currently practiced, has concentrated primarily on smallscale direct investments in private equity and debt, where many investors perceive that social and environmental impact can be more readily observed than in publicly traded companies where ownership is intermediated, diluted, and diffused through secondary capital markets.Indeed, the nature of impact within public equity investing remains poorly understood and insufficiently documented. Because of this, many investors may be overlooking readily available opportunities for generating impact within their existing investment portfolios.To address these misperceptions and missed opportunities, the IE2 initiative is developing a more rigorous framework for documenting the impact of engagement within the public equity asset class.

Gene expression analysis using single molecule detection

Recent developments of single molecule detection techniques and in particular the introduction of fluorescence correlation spectroscopy (FCS) led to a number of important applications in biological research. We present a unique approach for the gene expression analysis using dual‐color cross‐correlation. The expression assay is based on gene‐specific hybridization of two dye‐labeled DNA probes to a selected target gene. The counting of the dual‐labeled molecules within the solution allows the quantification of the expressed gene copies in absolute numbers. As detection and analysis by FCS can be performed at the level of single molecules, there is no need for any type of amplification. We describe the gene expression assay and present data demonstrating the capacity of this novel technology. In order to prove the gene specificity, we performed experiments with gene‐depleted total cDNA. The biological application was demonstrated by quantifying selected high, medium and low abundant genes in cDNA prepared from HL‐60 cell

Nature-based solutions to climate change mitigation and adaptation in urban areas: Perspectives on indicators, knowledge gaps, barriers, and opportunities for action

Nature-based solutions promoting green and blue urban areas have significant potential to decrease the vulnerability and enhance the resilience of cities in light of climatic change. They can thereby help to mitigate climate change-induced impacts and serve as proactive adaptation options for municipalities. We explore the various contexts in which nature-based solutions are relevant for climate mitigation and adaptation in urban areas, identify indicators for assessing the effectiveness of nature-based solutions and related knowledge gaps. In addition, we explore existing barriers and potential opportunities for increasing the scale and effectiveness of nature-based solution implementation. The results were derived from an inter- and transdisciplinary workshop with experts from research, municipalities, policy, and society. As an outcome of the workshop discussions and building on existing evidence, we highlight three main needs for future science and policy agendas when dealing with nature-based solutions: (i) produce stronger evidence on nature-based solutions for climate change adaptation and mitigation and raise awareness by increasing implementation; (ii) adapt for governance challenges in implementing nature-based solutions by using reflexive approaches, which implies bringing together new networks of society, nature-based solution ambassadors, and practitioners; (iii) consider socio-environmental justice and social cohesion when implementing nature-based solutions by using integrated governance approaches that take into account an integrative and transdisciplinary participation of diverse actors. Taking these needs into account, nature-based solutions can serve as climate mitigation and adaptation tools that produce additional cobenefits for societal well-being, thereby serving as strong investment options for sustainable urban planning

Future perspectives in melanoma research: meeting report from the "Melanoma Bridge";: Napoli, December 3rd-6th 2014.

The fourth "Melanoma Bridge Meeting" took place in Naples, December 3-6th, 2014. The four topics discussed at this meeting were: Molecular and Immunological Advances, Combination Therapies, News in Immunotherapy, and Tumor Microenvironment and Biomarkers. Until recently systemic therapy for metastatic melanoma patients was ineffective, but recent advances in tumor biology and immunology have led to the development of new targeted and immunotherapeutic agents that prolong progression-free survival (PFS) and overall survival (OS). New therapies, such as mitogen-activated protein kinase (MAPK) pathway inhibitors as well as other signaling pathway inhibitors, are being tested in patients with metastatic melanoma either as monotherapy or in combination, and all have yielded promising results. These include inhibitors of receptor tyrosine kinases (BRAF, MEK, and VEGFR), the phosphatidylinositol 3 kinase (PI3K) pathway [PI3K, AKT, mammalian target of rapamycin (mTOR)], activators of apoptotic pathway, and the cell cycle inhibitors (CDK4/6). Various locoregional interventions including radiotherapy and surgery are still valid approaches in treatment of advanced melanoma that can be integrated with novel therapies. Intrinsic, adaptive and acquired resistance occur with targeted therapy such as BRAF inhibitors, where most responses are short-lived. Given that the reactivation of the MAPK pathway through several distinct mechanisms is responsible for the majority of acquired resistance, it is logical to combine BRAF inhibitors with inhibitors of targets downstream in the MAPK pathway. For example, combination of BRAF/MEK inhibitors (e.g., dabrafenib/trametinib) have been demonstrated to improve survival compared to monotherapy. Application of novel technologies such sequencing have proven useful as a tool for identification of MAPK pathway-alternative resistance mechanism and designing other combinatorial therapies such as those between BRAF and AKT inhibitors. Improved survival rates have also been observed with immune-targeted therapy for patients with metastatic melanoma. Immune-modulating antibodies came to the forefront with anti-CTLA-4, programmed cell death-1 (PD-1) and PD-1 ligand 1 (PD-L1) pathway blocking antibodies that result in durable responses in a subset of melanoma patients. Agents targeting other immune inhibitory (e.g., Tim-3) or immune stimulating (e.g., CD137) receptors and other approaches such as adoptive cell transfer demonstrate clinical benefit in patients with melanoma as well. These agents are being studied in combination with targeted therapies in attempt to produce longer-term responses than those more typically seen with targeted therapy. Other combinations with cytotoxic chemotherapy and inhibitors of angiogenesis are changing the evolving landscape of therapeutic options and are being evaluated to prevent or delay resistance and to further improve survival rates for this patient population. This meeting's specific focus was on advances in combination of targeted therapy and immunotherapy. Both combination targeted therapy approaches and different immunotherapies were discussed. Similarly to the previous meetings, the importance of biomarkers for clinical application as markers for diagnosis, prognosis and prediction of treatment response was an integral part of the meeting. The overall emphasis on biomarkers supports novel concepts toward integrating biomarkers into contemporary clinical management of patients with melanoma across the entire spectrum of disease stage. Translation of the knowledge gained from the biology of tumor microenvironment across different tumors represents a bridge to impact on prognosis and response to therapy in melanoma

Minimum information about a protein affinity reagent (MIAPAR)

This is a proposal developed within the community as an important first step in formalizing standards in reporting the production and properties of protein binding reagents, such as antibodies, developed and sold for the identification and detection of specific proteins present in biological samples. It defines a checklist of required information, intended for use by producers of affinity reagents, qualitycontrol laboratories, users and databases. We envision that both commercial and freely available affinity reagents, as well as published studies using these reagents, could include a MIAPAR-compliant document describing the product’s properties with every available binding partner. This would enable the user or reader to make a fully informed evaluation of the validity of conclusions drawn using this reagent

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements