AGRICULTURAL VALUE ADDED: PROSPECTS FOR NORTH DAKOTA

Introduction: This report provides an overview of the important factors affecting investments in agricultural value-added ventures. The introductory section outlines current research on factors important in the location of economic activity. Research applied to specific agricultural value-added ventures, such as food manufacturing and livestock feeding and finishing operations, are discussed. A listing of resources available to entrepreneurs considering value-added investments concludes the introductory section. Following the introductory section are short overviews of industries that already have, or may have, potential for increasing economic activity in the state. All are based on the important foundation of agriculture in the state's economy or upon the natural resource base giving the state a comparative advantage in investments in alternative energy or resource-based recreation.Agribusiness,

Science and society: The Role of Long-term Studies in Environmental Stewardship

Long-term research should play a crucial role in addressing grand challenges in environmental stewardship. We examine the efforts of five Long Term Ecological Research Network sites to enhance policy, management, and conservation decisions for forest ecosystems. In these case studies, we explore the approaches used to inform policy on atmospheric deposition, public land management, land conservation, and urban forestry, including decisionmaker engagement and integration of local knowledge, application of models to analyze the potential consequences of policy and management decisions, and adaptive management to generate new knowledge and incorporate it into decisionmaking. Efforts to enhance the role of long-term research in informing major environmental challenges would benefit from the development of metrics to evaluate impact; stronger partnerships among research sites, professional societies, decisionmakers, and journalists; and greater investment in efforts to develop, test, and expand practice-based experiments at the interface of science and society

An Analysis of Costs and Health Co-Benefits for a U.S. Power Plant Carbon Standard

Reducing carbon dioxide (CO2) emissions from power plants can have important “co-benefits” for public health by reducing emissions of air pollutants. Here, we examine the costs and health co-benefits, in monetary terms, for a policy that resembles the U.S. Environmental Protection Agency’s Clean Power Plan. We then examine the spatial distribution of the co-benefits and costs, and the implications of a range of cost assumptions in the implementation year of 2020. Nationwide, the total health co-benefits were $29 billion 2010 USD (95$2.3 to $68 billion), and net co-benefits under our central cost case were$12 billion (95% CI: -$15 billion to$51 billion). Net co-benefits for this case in the implementation year were positive in 10 of the 14 regions studied. The results for our central case suggest that all but one region should experience positive net benefits within 5 years after implementation

Sources to Seafood: Mercury Pollution in the Marine Environment

In 2010, the Toxic Metals Superfund Research Program at Dartmouth College brought together a group of 50 scientists and policy stakeholders to form C-MERC, the Coastal and Marine Mercury Ecosystem Research Collaborative. The goal was to review current knowledge—and knowledge gaps—relating to a global environmental health problem, mercury contamination of the world’s marine fish. C-MERC participants attended two workshops over a two-year period, and in 2012 C-MERC authors published a series of peer-reviewed papers in the journals Environmental Health Perspectives and Environmental Research that elucidated key processes related to the inputs, cycling, and uptake of mercury in marine ecosystems, effects on human health, and policy implications. This report synthesizes the knowledge from these papers in an effort to summarize the science relevant to policies being considered at regional, national, and global levels. The Dartmouth Toxic Metals Superfund Research Program uses an interdisciplinary approach to investigate the ways that arsenic and mercury in the environment affect ecosystems and human health. Arsenic and mercury are commonly found in Superfund sites around the U.S. as well as other areas that result in exposures to certain communities. The Research Translation Core of the program communicates program science to government partners, non-governmental organizations, health care providers and associations, universities and the lay community, and facilitates the use of its research for the protection of public health. The Research Translation Core organized the C-MERC effort. The Superfund Research Program of the National Institute of Environmental Health Sciences supports a network of university programs that investigate the complex health and environmental issues associated with contaminants found at the nation’s hazardous waste sites. The Program coordinates with the Environmental Protection Agency and the Agency for Toxic Substances and Disease Registry of the Centers for Disease Control and Prevention, federal entities charged with management of environmental and human health hazards associated with toxic substances

Glanzmann thrombasthenia: Genetic basis and clinical correlates

Glanzmann thrombasthenia (GT) is an autosomal recessive disorder of platelet aggregation caused by quantitative or qualitative defects in integrins αIIb and β3. These integrins are encoded by th

Meeting Report: Methylmercury in Marine Ecosystems—From Sources to Seafood Consumers

Mercury and other contaminants in coastal and open-ocean ecosystems are an issue of great concern globally and in the United States, where consumption of marine fish and shellfish is a major route of human exposure to methylmercury (MeHg). A recent National Institute of Environmental Health Sciences–Superfund Basic Research Program workshop titled “Fate and Bioavailability of Mercury in Aquatic Ecosystems and Effects on Human Exposure,” convened by the Dartmouth Toxic Metals Research Program on 15–16 November 2006 in Durham, New Hampshire, brought together human health experts, marine scientists, and ecotoxicologists to encourage cross-disciplinary discussion between ecosystem and human health scientists and to articulate research and monitoring priorities to better understand how marine food webs have become contaminated with MeHg. Although human health effects of Hg contamination were a major theme, the workshop also explored effects on marine biota. The workgroup focused on three major topics: a) the biogeochemical cycling of Hg in marine ecosystems, b) the trophic transfer and bioaccumulation of MeHg in marine food webs, and c) human exposure to Hg from marine fish and shellfish consumption. The group concluded that current understanding of Hg in marine ecosystems across a range of habitats, chemical conditions, and ocean basins is severely data limited. An integrated research and monitoring program is needed to link the processes and mechanisms of MeHg production, bioaccumulation, and transfer with MeHg exposure in humans

A dominant gain-of-function mutation in universal tyrosine kinase <i>SRC </i>causes thrombocytopenia, myelofibrosis, bleeding, and bone pathologies

The Src family kinase (SFK)member SRC is amajor target in drug development because it is activated in many human cancers, yet deleterious SRC germline mutations have not been reported. We used genome sequencing and Human Phenotype Ontology patient coding to identify a gain-of-function mutation in SRC causing thrombocytopenia, myelofibrosis, bleeding, and bone pathologies in nine cases. Modeling of the E527K substitution predicts loss of SRC's self-inhibitory capacity, whichwe confirmedwith in vitro studies showing increased SRC kinase activity and enhanced Tyr419 phosphorylation in COS-7 cells overexpressing E527K SRC. The active form of SRC predominates in patients' platelets, resulting in enhanced overall tyrosine phosphorylation. Patientswith myelofibrosis have hypercellular bone marrow with trilineage dysplasia, and their stem cells grown in vitro form more myeloid and megakaryocyte (MK) colonies than control cells. These MKs generate platelets that are dysmorphic, low in number, highly variable in size, and have a paucity of a-granules. Overactive SRC in patient-derived MKs causes a reduction in proplatelet formation, which can be rescued by SRC kinase inhibition. Stem cells transduced with lentiviral E527K SRC formMKs with a similar defect and enhanced tyrosine phosphorylation levels. Patient-derived and E527K-transduced MKs show Y419 SRC- positive stained podosomes that induce altered actin organization. Expression of mutated src in zebrafish recapitulates patients' blood and bone phenotypes. Similar studies of platelets andMKs may reveal the mechanism underlying the severe bleeding frequently observed in cancer patients treated with next-generation SFK inhibitors. © 2016 by the American Association for the Advancement of Science; all rights reserved

A gain-of-function variant in <i>DIAPH1 </i>causes dominant macrothrombocytopenia and hearing loss

Macrothrombocytopenia (MTP) is a heterogeneous group of disorders characterized by enlarged and reduced numbers of circulating platelets, sometimes resulting in abnormal bleeding. In most MTP, this phenotype arises because of altered regulation of platelet formation from megakaryocytes (MK). We report the identification of DIAPH1, which encodes the Rho-effector diaphanous-related formin 1 (DIAPH1), as a candidate gene for MTP using exome sequencing, ontological phenotyping and similarity regression. We describe two unrelated pedigrees with MTP and sensorineural hearing loss that segregate with a DIAPH1 p.R1213* variant predicting partial truncation of the DIAPH1 diaphanous autoregulatory domain. The R1213* variant was associated with reduced proplatelet formation from cultured MKs, cell clustering and abnormal cortical filamentous actin. Similarly, in platelets there was increased filamentous actin and stable microtubules, indicating constitutive activation of DIAPH1. Over-expression of DIAPH1 R1213* in cells reproduced the cytoskeletal alterations found in platelets. Our description of a novel disorder of platelet formation and hearing loss extends the repertoire of DIAPH1-related disease and provides new insights into the autoregulation of DIAPH1 activity

Phase I study of IMGN901, a CD56-targeting antibody-drug conjugate, in patients with CD56-positive solid tumors.

Background IMGN901 is a CD56-targeting antibody-drug conjugate designed for tumor-selective delivery of the cytotoxic maytansinoid DM1. This phase 1 study investigated the safety, tolerability, pharmacokinetics, and preliminary activity of IMGN901 in patients with CD56-expressing solid tumors. Methods Patients were enrolled in cohorts of escalating IMGN901 doses, administered intravenously, on 3 consecutive days every 21 days. A dose-expansion phase accrued patients with small cell lung cancer (SCLC), Merkel cell carcinoma (MCC), or ovarian cancer. Results Fifty-two patients were treated at doses escalating from 4 to 94 mg/m(2)/day. The maximum tolerated dose (MTD) was determined to be 75 mg/m(2). Dose-limiting toxicities included fatigue, neuropathy, headache or meningitis-like symptoms, chest pain, dyspnea, and myalgias. In the dose-expansion phase (n = 45), seven patients received 75 mg/m(2) and 38 received 60 mg/m(2) for up to 21 cycles. The recommended phase 2 dose (RP2D) was established at 60 mg/m(2) during dose expansion. Overall, treatment-emergent adverse events (TEAEs) were experienced by 96.9 % of all patients, the majority of which were Grade 1 or 2. The most commonly reported Grade 3 or 4 TEAEs were hyponatremia and dyspnea (each 8.2 %). Responses included 1 complete response (CR), 1 clinical CR, and 1 unconfirmed partial response (PR) in MCC; and 1 unconfirmed PR in SCLC. Stable disease was seen for 25 % of all evaluable patients who received doses ≥60 mg/m(2). Conclusions The RP2D for IMGN901 of 60 mg/m(2) administered for 3 consecutive days every 3 weeks was associated with an acceptable tolerability profile. Objective responses were observed in patients with advanced CD56+ cancers