Cocrystal formation by Ionic liquid-assisted grinding: Case study with cocrystals of caffeine

iquid assisted grinding using imidazolium-based ionic liquids (IL-AG) was found to be effective in isolation of cocrystals and cocrystal polymorphs. Isolation of specific polymorphs of caffeine–citric acid (CAF–CA) and caffeine–glutaric acid (CAF–GLU) cocrystals highlights the tunability of ILs in polymorphic control

Hybridization of Common Reed in North America? The Answer is Blowing in the Wind

Background and aims: We review evidence for hybridization of Phragmites australis in North America and the implications for the persistence of native P. australis ssp. americanus populations in North America. We also highlight the need for an updated classification system, which takes P. australis intraspecific variation and hybridization into account. Methodology: We reviewed available published, in press, and in preparation literature to assess the likelihood of hybridization and interbreeding in genotypes of Phragmites australis present in North America. Principal results: Experimental results demonstrate that hybridization among introduced and native haplotypes is possible within the genus Phragmites, yet evidence that hybridization has naturally occurred is only starting to emerge. The lag in identifying hybridization in Phragmites in North America may be related to undersampling in some parts of North America and to a lack of molecular tools that provide the capability to recognize hybrids. Conclusions: Our understanding of the gene flow within and between species in the genus Phragmites is moving at a fast pace, especially on the east and Gulf coasts of North America. More attention should also be focused on the Great Lakes region, the southwestern and the west coast of the U.S. where sympatry has created opportunities for hybridization. Where hybridizations have been detected, there is currently no published data on how hybridization affects plant vigor, morphology, invasiveness, or conservation of the genetic integrity of the North American native subspecies. We conclude that detection of more hybridization is highly likely and that there is a need to develop new markers for the different Phragmites species and lineages to fill current knowledge gaps. Finally, we suggest that the classification system for P. australis should be updated and published to help clarify the nomenclature

A 700 year record of Southern Hemisphere extratropical climate variability

Annually dated ice cores from West and East Antarctica provide proxies for past changes in atmospheric circulation over Antarctica and portions of the Southern Ocean, temperature in coastal West and East Antarctica, and the frequency of South Polar penetration of El Niño events. During the period AD 1700–1850, atmospheric circulation over the Antarctic and at least portions of the Southern Hemisphere underwent a mode switch departing from the out-of-phase alternation of multi-decadal long phases of EOF1 and EOF2 modes of the 850 hPa field over the Southern Hemisphere (as defined in the recent record by Thompson and Wallace, 2000; Thompson and Solomon, 2002) that characterizes the remainder of the 700 year long record. From AD 1700 to 1850, lower-tropospheric circulation was replaced by in-phase behavior of the Amundsen Sea Low component of EOF2 and the East Antarctic High component of EOF1. During the first phase of the mode switch, both West and East Antarctic temperatures declined, potentially in response to the increased extent of sea ice surrounding both regions. At the end of the mode switch, West Antarctic coastal temperatures rose and East Antarctic coastal temperatures fell, respectively, to their second highest and lowest of the record. Polar penetration of El Niño events increased during the mode switch. The onset of the AD 1700–1850 mode switch coincides with the extreme state of the Maunder Minimum in solar variability. Late 20th-century West Antarctic coastal temperatures are the highest in the record period, and East Antarctic coastal temperatures close to the lowest. Since AD 1700, extratropical regions of the Southern Hemisphere have experienced significant climate variability coincident with changes in both solar variability and greenhouse gase

High dimensional decision dilemmas in climate models

An important source of uncertainty in climate models is linked to the calibration of model parameters. Interest in systematic and automated parameter optimization procedures stems from the desire to improve the model climatology and to quantify the average sensitivity associated with potential changes in the climate system. Building upon on the smoothness of the response of an atmospheric circulation model (AGCM) to changes of four adjustable parameters, Neelin et al. (2010) used a quadratic metamodel to objectively calibrate the AGCM. The metamodel accurately estimates global spatial averages of common fields of climatic interest, from precipitation, to low and high level winds, from temperature at various levels to sea level pressure and geopotential height, while providing a computationally cheap strategy to explore the influence of parameter settings. Here, guided by the metamodel, the ambiguities or dilemmas related to the decision making process in relation to model sensitivity and optimization are examined. Simulations of current climate are subject to considerable regional-scale biases. Those biases may vary substantially depending on the climate variable considered, and/or on the performance metric adopted. Common dilemmas are associated with model revisions yielding improvement in one field or regional pattern or season, but degradation in another, or improvement in the model climatology but degradation in the interannual variability representation. Challenges are posed to the modeler by the high dimensionality of the model output fields and by the large number of adjustable parameters. The use of the metamodel in the optimization strategy helps visualize trade-offs at a regional level, e.g., how mismatches between sensitivity and error spatial fields yield regional errors under minimization of global objective functions

Oncogenic RIT1 mutations in lung adenocarcinoma

Lung adenocarcinoma is comprised of distinct mutational subtypes characterized by mutually exclusive oncogenic mutations in RTK/RAS pathway members KRAS, EGFR, BRAF and ERBB2, and translocations involving ALK, RET and ROS1. Identification of these oncogenic events has transformed the treatment of lung adenocarcinoma via application of therapies targeted toward specific genetic lesions in stratified patient populations. However, such mutations have been reported in only ∼55% of lung adenocarcinoma cases in the United States, suggesting other mechanisms of malignancy are involved in the remaining cases. Here we report somatic mutations in the small GTPase gene RIT1 in ∼2% of lung adenocarcinoma cases that cluster in a hotspot near the switch II domain of the protein. RIT1 switch II domain mutations are mutually exclusive with all other known lung adenocarcinoma driver mutations. Ectopic expression of mutated RIT1 induces cellular transformation in vitro and in vivo, which can be reversed by combined PI3K and MEK inhibition. These data identify RIT1 as a driver oncogene in a specific subset of lung adenocarcinomas and suggest PI3K and MEK inhibition as a potential therapeutic strategy in RIT1-mutated tumors

Options for National Parks and Reserves for Adapting to Climate Change

Past and present climate has shaped the valued ecosystems currently protected in parks and reserves, but future climate change will redefine these conditions. Continued conservation as climate changes will require thinking differently about resource management than we have in the past; we present some logical steps and tools for doing so. Three critical tenets underpin future management plans and activities: (1) climate patterns of the past will not be the climate patterns of the future; (2) climate defines the environment and influences future trajectories of the distributions of species and their habitats; (3) specific management actions may help increase the resilience of some natural resources, but fundamental changes in species and their environment may be inevitable. Science-based management will be necessary because past experience may not serve as a guide for novel future conditions. Identifying resources and processes at risk, defining thresholds and reference conditions, and establishing monitoring and assessment programs are among the types of scientific practices needed to support a broadened portfolio of management activities. In addition to the control and hedging management strategies commonly in use today, we recommend adaptive management wherever possible. Adaptive management increases our ability to address the multiple scales at which species and processes function, and increases the speed of knowledge transfer among scientists and managers. Scenario planning provides a broad forward-thinking framework from which the most appropriate management tools can be chosen. The scope of climate change effects will require a shared vision among regional partners. Preparing for and adapting to climate change is as much a cultural and intellectual challenge as an ecological challenge

Increasing Efforts to Reduce Cervical Cancer through State-Level Comprehensive Cancer Control Planning

Reducing cervical cancer disparities in the U.S. requires intentional focus on structural barriers such as systems and policy which impact access to human papillomavirus (HPV) vaccination, cervical cancer screening and treatment. Such changes are difficult and often politicized. State comprehensive cancer control (CCC) plans are vehicles that, if designed well, can help build collective focus on structural changes. Study objectives were to identify the prioritization of cervical cancer in state CCC plans, the conceptualization of HPV within these plans, and the focus of plans on structural changes to reduce cervical cancer disparities. Data were gathered by systematic content analysis of CCC plans from 50 states and the District of Columbia from February-June 2014 for evidence of cervical cancer prioritization, conceptualization of HPV, and focus on structural barriers to cervical cancer vaccination, screening or treatment. Findings indicate that prioritization of cervical cancer within state CCC plans may not be a strong indicator of state efforts to reduce screening and treatment disparities. While a majority of plans reflected scientific evidence that HPV causes cervical and other cancers, they did not focus on structural elements impacting access to evidence-based interventions. Opportunities exist to improve state CCC plans by increasing their focus on structural interventions that impact cervical cancer prevention, detection, and treatmentparticularly for the 41% of plans ending in 2015 and the 31% ending between 2016-2020. Future studies should focus on the use of policy tools in state CCC plans and their application to cervical cancer prevention and treatment

Genome-scale analysis identifies paralog lethality as a vulnerability of chromosome 1p loss in cancer.

Functional redundancy shared by paralog genes may afford protection against genetic perturbations, but it can also result in genetic vulnerabilities due to mutual interdependency1-5. Here, we surveyed genome-scale short hairpin RNA and CRISPR screening data on hundreds of cancer cell lines and identified MAGOH and MAGOHB, core members of the splicing-dependent exon junction complex, as top-ranked paralog dependencies6-8. MAGOHB is the top gene dependency in cells with hemizygous MAGOH deletion, a pervasive genetic event that frequently occurs due to chromosome 1p loss. Inhibition of MAGOHB in a MAGOH-deleted context compromises viability by globally perturbing alternative splicing and RNA surveillance. Dependency on IPO13, an importin-β receptor that mediates nuclear import of the MAGOH/B-Y14 heterodimer9, is highly correlated with dependency on both MAGOH and MAGOHB. Both MAGOHB and IPO13 represent dependencies in murine xenografts with hemizygous MAGOH deletion. Our results identify MAGOH and MAGOHB as reciprocal paralog dependencies across cancer types and suggest a rationale for targeting the MAGOHB-IPO13 axis in cancers with chromosome 1p deletion

Liminal Roles as a Source of Creative Agency in Management: The Case of Knowledge-Sharing Communities

Studies suggest that the experience of liminality – of being in an ambiguous, ‘betwixt and between’ position – has creative potential for organizations. We contribute to theory on the link between liminality and creative agency through a study of the coordinators of ‘knowledge-sharing communities’; one of the latest examples of a ‘neo-bureaucratic’ practice that seeks to elicit innovative responses from employees while intensifying control by the organization. Through a role-centred perspective, our study found that both the structural and interpretive aspects of coordinators’ role enactments promoted a degree of creative agency. ‘Front-stage’ and ‘back-stage’ activities were developed to meet the divergent expectations posed by senior management and community members, and the ambiguity of their roles prompted an array of different role interpretations. Our findings contribute to theory by showing how the link between liminality and creative agency is not confined to roles and spaces (consultancy work, professional expertise) that are positioned across organizational boundaries, or free from norms and expectations, but may also apply to roles that are ambiguously situated within organizational contexts and which are subject to divergent expectations. This shows how neo-bureaucratic forms may be both reproduced and renewed through the creative responses of individual managers

Solar Forcing of the Polar Atmosphere

We present highly resolved, annually dated, calibrated proxies for atmospheric circulation from several Antarctic ice cores (ITASE (International Trans-Antarctic Scientific Expedition), Siple Dome, Law Dome) that reveal decadal-scale associations with a South Pole ice-core Be-10 proxy for solar variability over the last 600 years and annual-scale associations with solar variability since AD 1720. We show that increased (decreased) solar irradiance is associated with increased (decreased) zonal wind strength near the edge of the Antarctic polar vortex. The association is particularly strong in the Indian and Pacific Oceans and as such may contribute to understanding climate forcing that controls drought in Australia and other Southern Hemisphere climate events. We also include evidence suggestive of solar forcing of atmospheric circulation near the edge of the Arctic polar vortex based on ice-core records from Mount Logan, Yukon Territory, Canada, and both central and south Greenland as enticement for future investigations. Our identification of solar forcing of the polar atmosphere and its impact on lower latitudes offers a mechanism for better understanding modern climate variability and potentially the initiation of abrupt climate-change events that operate on decadal and faster scales