Bali's rice production is organised in units called subak with compulsory membership for farmers who grow rice. The future of this highly productive system generating some of the highest yields across Indonesia is under threat. Urbanisation, rural diversification and tourism are encroaching on the immaculately groomed rice terraces, undermining a centuries-old sociocultural institution which, interwoven with kinship, neighbourhood and congregation groups, shapes Balinese society. Nonetheless, rice farming remains a vital source of income for many and rice the most important staple food. This predicament raises questions about the future of farmers' livelihoods, the subak, its cultural heritage and rice production in Bali. The author contemplates possible trajectories by developing three scenarios: (1) disintegration; (2) formalisation; and (3) reinvention. The resulting structured narratives are not forecasts but may encourage discussion of the place and value of the subak and local rice supply in the Balinese economy and society.


A group of verbal reasoning questions, of the type often used in intelligence tests, were included in the English paper of the Kenya secondary school selection examination (C.P.E. Certificate of Primary Education) from 1971, and from 1974 scientific reasoning questions were included in the general paper. In early 1974 a full-scale item analysis of the 1973 selection paper was made. This paper presents some results from the analysis carried out for the years 1973 to 1976 of the English paper and the science section of the general paper. The scores of pupils from Nairobi high-cost primary schools and from rural low-cost schools are compared. Three interesting results of this analysis are presented and some possible explanations offered. For one thing, pupils from the Nairobi high-cost schools perform up to 70 per cent better on English items testing knowledge of specialised words , expressions and idioms, whereas in the science paper, descriptive items testing knowledge of specialised and technical terms produce a mean difference of less than 12 per cent. Secondly, the verbal reasoning items in the English paper give the Nairobi high-cost pupils a smaller advantage than the achievement items; whereas in science, the reasoning items give a bigger advantage than the descriptive and explanatory items. Finally, the observation items in the science paper produce an especially large performance gap between the two types of schools. These and other results suggest that the huge performance advantage enjoyed by Nairobi high-cost pupils in the English paper can be ascribed entirely to two sources: first, their greater familiarity with the language, and second, the superior quality of the teaching they receive. In both papers, questions which test higher-level intellectual skills, such as the ability to reason, are particularly sensitive to the effects of teacher quality, rather than reflecting the innate capacity of the pupils.


The thesis shifts the explanatory framework of depression from the currently
predominant clinical model which explains depression as a problem located in the
individual, to a social psychological approach which explains depression in terms of its
meaning to the individual, as an experience of self, evolved through relationships with
others. Theoretically, the thesis draws on Mead's (1934) theory of social hehaviourism,
and symbolic interactionism (Blumer 1969).
An innovative and interpretative qualitative methodology, "Thematic Analysis", is
developed for the analysis of interview accounts acknowledging the perspectives of
participants. Analyses are presented as the subjective interpretations of the researcher but
accounts are approached as partial representations of real experiences. The methodology
of thematic analysis is developed through the research, drawing on grounded theory
(Glaser and Strauss, 1967) and discourse analytic techniques (Potter and Wetherell,
1987).
The thesis comprises four separate studies to investigate subjective experiences of
depression and the meaning of the term "depression", based on in-depth, semi-structured
interviews. Study I, an exploratory study with a university population (not necessarily
depressed), identifies themes and discourses in accounts of depression. Study II
investigates subjective experiences of depression from patients' perspectives, based on
accounts of psychiatric out-patients and patients of general practitioners who had been
diagnosed as depressed, and identifies the power of the medical discourse in legitimating
problems as depression. Study III discusses medical discourses of depression, as used
by psychiatrists, general practitioners and clinical psychologists in interview accounts
which emphasised the importance of organisational context. Study IV investigates
women's experiences of motherhood and depression from participants' perspectives and
based on their subjective accounts, and discusses gender identity and the social
construction of motherhood as part of their experiences of depression.
The analysis indicated that for most respondents depression is both a subjective and a
socially constructed experience. The powerful construction of depression as a clinical
problem located in the individual may legitimate problematic experiences, hut it is
insufficient to explain subjective experiences of depression, which are better understood
in terms of the construction of subjectivity through social interaction. The research has
implications for more helpful professional and personal approaches to understanding the
experience of depression.


For the problem of maximizing a monotone, submodular function with respect to a cardinality constraint $k$ on a ground set of size $n$, we provide an algorithm that achieves the state-of-the-art in both its empirical performance and its theoretical properties, in terms of adaptive complexity, query complexity, and approximation ratio; that is, it obtains, with high probability, query complexity of $O(n)$ in expectation, adaptivity of $O(\log(n))$, and approximation ratio of nearly $1-1/e$. The main algorithm is assembled from two components which may be of independent interest. The first component of our algorithm, LINEARSEQ, is useful as a preprocessing algorithm to improve the query complexity of many algorithms. Moreover, a variant of LINEARSEQ is shown to have adaptive complexity of $O( \log (n / k) )$ which is smaller than that of any previous algorithm in the literature. The second component is a parallelizable thresholding procedure THRESHOLDSEQ for adding elements with gain above a constant threshold. Finally, we demonstrate that our main algorithm empirically outperforms, in terms of runtime, adaptive rounds, total queries, and objective values, the previous state-of-the-art algorithm FAST in a comprehensive evaluation with six submodular objective functions.


The development of a simple model of the seawater inherent optical properties (IOPs) associated with bubbles and sediments would represent a great advance in surf zone optics. We present one solution for this problem using a combination of geometrical optics and Fraunhofer diffraction. An analytic model of the IOPs of bubbles and sediments (the extinction and absorption coefficients, and phase function) is developed in terms of the moments of the particle size distribution and the complex refractive index of particles.


History is made by those who write it, and preservationists write history through
the medium of historic buildings. The historic, built environment is irreplaceable, and the
work of historic preservation is indispensable in maintaining our sense of identity and
place. Historic preservation is a field that aims to maintain the character of a place by
renovating and retaining historic structures, and with them the memory of the people who
built and used them. Historic preservation was begun and is traditionally led by the upper
classes in American society. Early preservation in Wilmington, from the last decades of
the nineteenth to the mid-twentieth century, illustrates the fact that the powerful create
and preserve their own history, and that the upper classes are motivated to memorialize
their own heritage through the built environment. This work argues that the success of
early preservation in Wilmington was directly proportional to the degree of investment by
the upper classes in a specific property. Early successes and failures of preservation as
exemplified through the case studies of the Burgwin-Wright House, City Hall-Thalian
Hall, the main branch of the United States Post Office, and others support this argument.
These examples, as well as the historiography and evolution of historic preservation over
time, highlight upper class motivations for preservation such as memorializing, retaining
their sense of place and solidifying their position as leaders of society. An examination
of early efforts at preservation within the state of North Carolina and across the United
States indicates that events in Wilmington reflected larger trends.


William Hogarth is a house-hold name across the country, his prints hang in our pubs and leap out from our history-books. He painted the great and good but also the common people. His art is comically exuberant, 'carried away by a passion for the ridiculous', as Hazlitt said. Jenny Uglow, acclaimed author of Elizabeth Gaskell, Nature's Engraver and In These Times, uncovers the man, but also the world he sprang from and the lives he pictured. He moved in the worlds of theatre, literature, journalism and politics, and found subjects for his work over the whole gamut of eighteenth century London, from street scenes to drawing rooms, and from churches to gambling halls and prisons. After striving years as an engraver and painter, Hogarth leapt into lasting fame with A Harlot's Progress and A Rake's Progress, but remained highly critical of the growing gulf between the luxurious lives of the ruling elite and the wretched poverty of the massess. William Hogarth was an artist of flamboyant, overflowing imagination, he was a satirist with an unerring eye; a painter of vibrant colour and tenderness; an ambitious professional who broke all the art-world taboos. Never content, he wanted to excel at everything - from engraving to history painting - and a note of risk runs through his life. Shortlisted for the Whitbread Prize, Hogarth: A Life and a World brings art history to life in the voices of Hogarth's own age. The result is an unforgettable portrait of a great artist and a proud, stubborn, comic, vulnerable man.


A challenge with advertising communications is to better understand beliefs driving people's attitude toward advertising. Successful use of sport communication requires a better understanding of the beliefs composing attitudes toward advertising through sport. A 4-phase study was conducted to develop a scale measuring 7 belief dimensions as indicants of attitude toward advertising through sport. Phase 1 (N = 125) provided an initial test of the proposed instrument. Phase 2 (N = 215) included an assessment of the revised scale based on internal-consistency tests and exploratory factor analysis. In Phase 3 (N = 424) the scale's reliability and validity were verified using confirmatory factor analysis. In Phase 4 (N = 263) the internal consistency and factor structure of the scale were reexamined. The combined results provide support for the conceptualization and measurement of the belief dimensions for future investigation of the relationships between beliefs about and attitude toward advertising through sport.


The methods for estimating rotifer resting egg densities from lake sediment, and the use of emergence for determining community composition from lakes, were investigated in Lakes Tikitapu and Okaro, New Zealand. Significantly lower (P<0.01) estimates of resting egg densities were obtained by monitoring emergence from incubated sediments than from egg counts. However, incubation of sediments did not require the ability to recognise species on the basis of egg morphology as did egg counts. Significantly higher (P<0.01) densities of resting eggs were found in sediments from eutrophic Lake Okaro than from oligo-mesotrophic Lake Tikitapu. Incubation of sediments did not result in the emergence of all species found in the plankton during an earlier thirteen-month seasonal survey, including some common species. This currently limits the use of this method as a tool for rapid assessment of community composition. However, the method is likely to provide advantages over some traditional methods, such as vertical net hauls, by providing more complete species lists if only a single visit to a site is possible.


This paper presents the ways in which Muslims and Arabs are represented in mainstream European and American digital games. It analyzes how games — particularly of the action genre — construct the Arab or Muslim 'Other.' Within these games, one finds the diverse ethnic and religious identities of the Islamic world reconstructed into a series of flat social typologies, often presented within the framework of hostility and terrorism. The second part of the paper deals with selected digital games created in the Middle East, whose authors are knowingly working with the topic of self-representation. Recent digital games originating in the Middle East can be perceived as examples of an ongoing digital emancipation taking place through the distribution of media images and their corresponding meanings. A key part of this ongoing digital emancipation involves the construction of Arab and Islamic heroes, a process accomplished by exploiting distinctive narrative structures and references to Islamic cultural heritage.


Culturegraphy visualizes cultural information exchange over time. Treating cultural works as nodes and influences as directed edges, the visualization of these cultural networks can provide new insights into the rich interconnections of cultural development. The graphics represent complex relationships of movie references by combining macro views summarizing 100 years of movie influences with micro views providing a close-up look at the embedding of individual movies. The macro view shows the rise of the self-referential character of postmodern cinema, while the micro level illustrates differences between individual movies, when they were referenced and by whom. The visualizations provide views that are closer to the real complexity of the relationships than aggregated views or rankings could do.


Clinical interventions for extensive tissue injury to the larger airways remain limited. Recently, respiratory tissue engineering strategies have emerged with a variety of biomimetic materials and tissue constructs to address these limitations, though rapid epithelialization of the construct with mucociliary function is still largely unresolved. The overall objective of this study was to manufacture an all-trans retinoic acid (atRA)-loaded bilayered collagen-hyaluronate (atRA-B) scaffold as a platform technology for tracheal tissue regeneration. atRA-loaded scaffolds were fabricated using a customized lyophilization process and characterized for drug loading and release properties using HPLC, followed by validation of their bioactivity using human primary tracheobronchial epithelial cells. atRA-loaded materials were reproducibly manufactured and exhibited the release of atRA following their hydration over 8-28 h that was significantly affected by collagen cross-linking. An optimal formulation consisting of 10 μg/mL atRA in a collagen-hyaluronate suspension to manufacture the scaffold film layer was identified and used to develop the atRA-B scaffold. Immunofluorescence studies and RT-PCR revealed that the atRA-loaded biomaterials increased the expression of two epithelial markers of mucociliary differentiation, MUC5AC and β-tubulin IV, via upregulation of MUC5AC and FOXJ1 genes, both in epithelial monoculture and in a 3D scaffold coculture system with lung fibroblasts. Overall, this study has demonstrated that the atRA-B scaffold can enhance functional epithelialization in primary tracheobronchial cells and can potentially pioneer the development of a novel and biocompatible device to address a currently unmet clinical need in tracheal replacement.


This paper re-examines Lilien's sectoral shifts hypothesis for U.S. unemployment. We employ a monthly panel that spans from 1990:01 to 2011:12 for 48 U.S. states. Panel unit root tests that allow for cross-sectional dependence reveal the stationarity of unemployment. Within a framework that takes into account dynamics, parameter heterogeneity and cross-sectional dependence in the panel, we show that sectoral reallocation is significant not only at the aggregate level but also at the state level. The magnitude and the statistical significance of the latter as measured by Lilien's index increases when both heterogeneity and cross-sectional dependence are taken into account.


The C domains of coagulation factors V (FV) and VIII (FVIII) are structurally conserved domains and share a common and essential function in membrane binding. In vivo regulation of thrombin formation strongly depends on the expression and regulation of the cofactor activities of FVIII and FV. With this study, we explored the possibility of inhibition of thrombin formation in full blood with small druglike molecules. Such compounds may serve as lead molecules for the development of a new type of orally available coagulation inhibitors that act by blocking the interaction between the C domains of FVIII and the membrane surface. We identified 9 novel molecules that are able to inhibit binding of the FVIII C2 domain to a model membrane by application of a combined ligand-based and target structure-based virtual screening approach that took into account the knowledge of a set of previously identified low-molecular-weight FVIII binders that were, however, not active in full blood. The half-maximal inhibitory concentration values of our newly identified compounds varied from 2.1 to 19.9 µM, of which 7 of 9 molecules did not appreciably inhibit FV membrane binding and were thus specific for FVIII. The most active bioactive compound showed activity in both plasma and in full blood.


This article is about entrepreneurial teacher continuing training, important aspects and tendencies of entrepreneurship education, entrepreneurship strategy and good practice examples of entrepreneurial teacher continuing training. The aim of this article is to present an actual aspect for entrepreneurial teacher continuing training, good practice, discuss entrepreneurship education tendencies in Europe, entrepreneurship education challenges. The research problem-there is no systematic analysis of the actual aspects of the development of entrepreneurship teachers' continuing training. The research methods that were applied: review of literature and strategic documents, legislation analysis, content analysis. This paper deals with two main themes: entrepreneurship education tendencies in Europe, actual aspects for entrepreneurial teacher continuing training and good practices in entrepreneurial teacher continuing training. The article shows that entrepreneurship education is now a part of the national strategy in most countries, but the experience of European countries in the field of entrepreneurship is different. In many European countries (Denmark, Estonia, Lithuania, Netherlands, Sweden, Norway, United Kingdom, Austria, Bulgaria, Czech Republic, Finland, Greece, Hungary, Iceland, Liechtenstein, Poland, Slovenia, Spain and Turkey) entrepreneurship education is included in their national programs, but it is not included in most initial teacher education and continuing professional development. The main problems in entrepreneurship education are embedding entrepreneurship into education and training, Curriculum development, entrepreneurial teacher continuing training, provision of methodological tools and professional development, partnership with the private sector. The best practices of entrepreneurial teacher continuing training are in the experiences of the United Kingdom, Norway, Austria, Belgium. These countries are examples of the best practices, because entrepreneurial teachers need systematic improvement of their qualifications, various study methods, forms and course levels for entrepreneurial teacher continuing training. It is emphasized that entrepreneurship teacher continuing training should be targeted, planned, and enabling teachers to develop their skills systematically in various continuing training courses, with innovative methods and with different duration and levels of courses. Targeted training centres for entrepreneurship in educating teachers can be universities, where entrepreneurship education and cooperation with business organizations is a priority. These are recommendations for the improvement of entrepreneurial teacher continuing training in Lithuania.


Critical to the goal of achieving sustainable development is governments' ability to maintain public information, including maps, charts, statistics, and narrative text, about a wide variety of environmental factors, indicators, resources, and threats in easily understandable formats that are readily accessible to the public. While federal and state freedom of information laws help to ensure a relatively high rate of public access to traditional information, such as environmental impact statements, studies and reports,significant environmental events and resources, and census data, the growing use and reliance on geographic information systems ("GIS") has the potential to move the public discourse to a more sophisticated plane. The availability of this data, however, was seriously curtailed in the aftermath of September 11, 2001, despite a Rand report concluding that most of this information would either be of no value to terrorists, or was not uniquely available through government sponsored portals. Withholding important environmental and public health related GIS data compromises important values of our democracy, including government accountability to the people and an open and honest communication between the government and the people. While many may have understood the immediate post-September 11 reaction that produced such an unprecedented shut-down of many information pipelines, these quick reactions should have been temporary in nature, a brief moratorium of sorts. Now that four years have passed, it is time to re-open the flow of facts and figures. Achieving a sustainable environment is dependent upon the ability of the community to access relevant, accurate and timely information from its federal,state, and local governments.


The overall nutritional quality of the American diet has not improved much over the past two decades. The Healthy Eating Index (HEI), USDA's tool for monitoring the diet quality of the U.S. population, measures how well a person's diet conforms to dietary recommendations. Out of a maximum score of 100, the index remained unchanged at 58 between 199496 and 2003-04. Likewise, using an older version of the index, the HEI improved only slightly from 62 in 1989 to 64 in 1996. A score above 80 is considered "good"; a score between 51 and 80 constitutes a diet that "needs improvement." Dietary indicators, such as self-rated diet quality and awareness of Federal nutrition information programs, are crucial for monitoring Americans' eating habits and devising solutions to mounting obesity rates. Through a partnership with the National Center for Health Statistics, ERS sponsored questions in the National Health and Nutrition Examination Survey (NH A NES). Responses reveal that although diet quality has remained low and shown no improvement, consumers' dietary awareness has changed: Americans have become more realistic in assessing their diet quality. In 1989-91, 44 percent of adults rated their diet quality as excellent or very good—an overly optimistic assessment given the low HEI score. By 2005-06, however, 33 percent rated their diets as excellent or very good, while the share of those regarding their diet quality as fair or poor increased from 18 to 27 percent. No amount of nutritional guidance or education can improve diets and reduce obesity unless it enables consumers to realistically assess the quality of their diets. In this respect, the Federal Government's efforts to provide nutritional recommendations to the public may be reaping some success. Presumably, people are more realistic today about their diet quality because they have greater knowledge of what constitutes a healthy diet. More Americans are aware of the Dietary Guidelines for Americans and the accompanying nutrition education tool, the Food Guide Pyramid (now MyPyramid). In 2005-06, 79 percent of U.S. adults had heard of the Food Guide Pyramid, up from 33 percent in 1994, and 51 percent knew about the Dietary Guidelines for Americans, compared with 30 percent in 1994.


Major depressive disorder (MDD) is one of the most common psychiatric disorders characterized by major depressive episodes. Although great efforts have been made to develop antidepressant drugs that target the monoaminergic system, these drugs are effective in only approximately 50% of MDD patients. In this study, we established a model of depression in PC12 cells using corticosterone to investigate the effect of ketamine and nuclear factor-κB (NF-κB) on the cell viability, apoptosis, levels of pro-inflammatory cytokines, apoptosis-related molecules, and enzymes of the Krebs cycle. PC12 cells were divided into control (no treatment, NC), ketamine treatment (KT), ketamine treatment with the inhibition of NF-κB (KI), and ketamine treatment with the overexpression of NF-κB (KO) group. Blood serum samples were collected from patients with MDD (n = 10) and healthy controls (n = 10) between 2015 and 2017. Ketamine significantly increased the viability and decreased the apoptosis of PC12 cells in KT and KI vs. NC group, but not in KO group. The levels of anti-apoptotic molecules and Krebs cycle enzymes were significantly increased in KI vs. KT group, while the levels of pro-apoptotic molecules and pro-inflammatory cytokines were decreased in KI vs. KT group. In addition, the levels of pro-inflammatory cytokines in the serum of MDD patients were significantly increased. The antidepressant effect of ketamine was enhanced in KI and reduced in KO group. Our results indicate that ketamine exerts its antidepressant effect via the inhibition of apoptosis and inflammation and the activation of the Krebs cycle in PC12 cells. NF-κB might be a potential therapeutic target in MDD.


Several new generation transfer- and working-standard illuminance meters and tristimulus colorimeters have been developed at the National Institute of Standards and Technology (NIST) [1] to measure all kinds of light sources with low uncertainty. The spectral and broad-band (illuminance) responsivities of the photometer (Y) channels of two tristimulus meters were determined at both the Spectral Irradiance and Radiance Responsivity Calibrations using Uniform Sources (SIRCUS) facility and the Spectral Comparator Facility (SCF) [2]. The two illuminance responsivities agreed within 0.1% with an overall uncertainty of 0.2% (k = 2), which is a factor of two improvement over the present NIST photometric scale. The first detector-based tristimulus color scale [3] was realized. All channels of the reference tristimulus colorimeter were calibrated at the SIRCUS. The other tristimulus meters were calibrated at the SCF and also against the reference meter on the photometry bench in broad-band measurement mode. The agreement between detector- and source-based calibrations was within 3 K when a tungsten lamp-standard was measured at 2856 K and 3100 K [4]. The color–temperature uncertainty of tungsten lamp measurements was 4 K (k = 2) between 2300 K and 3200 K, which is a factor of two improvement over the presently used NIST source-based color temperature scale. One colorimeter was extended with an additional (fifth) channel to apply software implemented matrix corrections. With this correction, the spectral mismatch caused color difference errors were decreased by a factor of 20 for single-color LEDs.


PaleontologyOn page [206][1] of this week's issue of Science , a team working in Argentina reports the discovery of a very early dinosaur—possibly a distant ancestor of Tyrannosaurus rex —that lived about 230 million years ago, during what paleontologists call the dawn of the dinosaurs. The researchers say the new finds—two specimens that together make up a nearly complete skeleton of a diminutive, 1-meter-long dinosaur—and neighboring fossils show that dinosaurs didn't outcompete other reptiles, but rather gradually replaced them as their predecessors died out for other reasons. More controversially, the team says the fossils show that one of the most well-known early dinosaurs, Eoraptor , long considered an ancestor of meat eaters like T. rex , was actually an ancestor of gigantic plant-eating dinosaurs like Apatosaurus .

 [1]: http://www.sciencemag.org/content/331/6014/206.short


This study presents a review of the recent advances in performing inference in probabilistic classifier chains for multilabel classification. The interest of performing such inference arises in an attempt of improving the performance of the approach based on greedy search (the well‐known CC method) and simultaneously reducing the computational cost of an exhaustive search (the well‐known PCC method). Unlike PCC and as CC, inference techniques do not explore all the possible solutions, but they increase the performance of CC, sometimes reaching the optimal solution in terms of subset 0/1 loss, as PCC does. The ε‐approximate algorithm, the method based on a beam search and Monte Carlo sampling are those techniques. An exhaustive set of experiments over a wide range of datasets are performed to analyze not only to which extent these techniques tend to produce optimal solutions, otherwise also to study their computational cost, both in terms of solutions explored and execution time. Only ε‐approximate algorithm with ε=.0 theoretically guarantees reaching an optimal solution in terms of subset 0/1 loss. However, the other algorithms provide solutions close to an optimal solution, despite the fact they do not guarantee to reach an optimal solution. The ε‐approximate algorithm is the most promising to balance the performance in terms of subset 0/1 loss against the number of solutions explored and execution time. The value of ε determines a degree to which one prefers to guarantee to reach an optimal solution at the expense of increasing the computational cost. WIREs Data Mining Knowl Discov 2016, 6:215–230. doi: 10.1002/widm.1185


The evolution that current advertising is experiencing, with new resources, omni-channel strategies and a better measurement capability, can also be appreciated in the creation of new methods to effect engagement. The companies have understood the need to earn credibility and to accept the new role of communication defined in the Cluetrain Manifesto, and have banked on non-conventional methods, including both the consumer and the streets in their strategies and generating a dialogue with them, so as to achieve such engagement. The integration of new marketing areas, the new communication tools, as well as those of innovation and strategic planning, are trends in the new and necessary connection with the consumer.


ABSTRACT The murine Igh locus has a 3′ regulatory region (3′ RR) containing four enhancers (hs3A, hs1,2, hs3B, and hs4) at DNase I-hypersensitive sites. The 3′ RR exerts long-range effects on class switch recombination (CSR) to several isotypes through its control of germ line transcription. By measuring levels of acetylated histones H3 and H4 and of dimethylated H3 (K4) with chromatin immunoprecipitation assays, we found that early in B-cell development, chromatin encompassing the enhancers of the 3′ RR began to attain stepwise modifications typical of an open conformation. The hs4 enhancer was associated with active chromatin initially in pro- and pre-B cells and then together with hs3A, hs1,2, and hs3B in B and plasma cells. Histone modifications were similar in resting splenic B cells and in splenic B cells induced by lipopolysaccharide to undergo CSR. From the pro-B-cell stage onward, the ∼11-kb region immediately downstream of hs4 displayed H3 and H4 modifications indicative of open chromatin. This region contained newly identified DNase I-hypersensitive sites and several CTCF target sites, some of which were occupied in vivo in a developmentally regulated manner. The open chromatin environment of the extended 3′ RR in mature B cells was flanked by regions associated with dimethylated K9 of histone H3. Together, these data suggest that 3′ RR elements are located within a specific chromatin subdomain that contains CTCF binding sites and developmentally regulated modules.


Coordination in socially intelligent agents is imperative because actions produced by the agents, without any deliberation on its consequences, may have non-local effects. These non-local effects will lead to a possibility of inefficient performance of the individual and the system. Socially intelligent agents can be best described as autonomous problem solvers that have to achieve their objectives by interacting with other similarly autonomous entities. The reason that such agents are inherently social makes the agents must produce decisions that are not only rational from the perspective of the individual agent but also rational from the perspective of the society. To solve the above problems we propose Akhlak coordination model stems from Akhlak concept to help and guide the agents to coordinate their tasks with other members. The model will be design as a social component of an agent-based architecture called Multi-agent Linkage Social Intelligent (MALSI) architecture. MALSI architecture that associated with Akhlak model is realized in an exemplar computational setting: a case study and a series of experiments are made of the relative performance of the model functions in a two different environment: homogeneous and heterogeneous environments. The case study measures performance of the system aided MALSI agent (embedded with Akhlak model) in perspective of users and designers of the system. The experiments measure coherency of multi-agent, which mean, how well the agents behaves as a unit, along some dimension of evaluation. The case study and the experiments are conducted in real-life industry in government agencies: Malaysian Administrative Modernization and Management Planning Unit (MAMPU) and Ministry of Education (MOE).


We discuss whether sulphur traces on Jupiter's moon Europa could be of biogenic origin. The compounds detected by the Galileo mission have been conjectured to be endogenic, most likely of cryovolcanic origin, due to their non-uniform distribution in patches. The Galileo space probe first detected the sulphur compounds, as well as revealing that this moon almost certainly has a volcanically heated and potentially habitable ocean hiding beneath a surface layer of ice. In planning future exploration of Europa there are options for sorting out the source of the surficial sulphur. For instance, one possibility is searching for the sulphur source in the context of the study of the Europa Microprobe In Situ Explorer (EMPIE), which has been framed within the Jovian Minisat Explorer Technology Reference Study (ESA). It is conceivable that sulphur may have come from the nearby moon Io, where sulphur and other volcanic elements are abundant. Secondly, volcanic eruptions in Europa's seafloor may have brought sulphur to the surface. Can waste products rising from bacterial colonies beneath the icy surface be a third alternative significant factor in the sulphur patches on the Europan surface ? Provided that microorganisms on Europa have the same biochemical pathways as those on Earth, over geologic time it is possible that autochthonous microbes can add substantially to the sulphur deposits on the surface of Europa. We discuss possible interpretations of the non-water-ice elements (especially the sulphur compound mercaptan) in the context of the studies for future missions. To achieve reliable biosignatures it seems essential to go back to Europa. Our work highlights the type of biogenic signatures that can be searched for when probing Europa's icy and patchy surface.


The diffraction by one or an arbitrary number of cascaded anisotropic planar gratings with slanted fringes is analyzed by using rigorous three-dimensional vector coupled-wave theory. Arbitrary angle of incidence and polarization are treated. The existence of uniaxial external regions and the treatment of both phase and amplitude anisotropic slanted gratings are included in the analysis. The anisotropy and the three-dimensionality of the problem cause coupling between orthogonally polarized waves. The Bragg conditions for various combinations of ordinary (O) and extraordinary (E) polarized waves are quantified. Sample calculations are presented for single anisotropic gratings (a lithium niobate hologram in air and an interdigitated-electrode-induced electro-optic grating in an optical waveguide), for two cascaded anisotropic gratings (a pair of interdigitated-electrode-induced gratings satisfying the OOO forward Bragg condition, the EEE forward Bragg condition, and the OOO backward Bragg condition), and for multiple cascaded gratings (a lithium niobate hologram with depth modulation). The same analysis applies in the limiting cases of isotropic materials, a grating vector lying in the plane of incidence, etc. Applications for this analysis include optical storage, switching, modulation, deflection, and data processing.


I have just been to Keir's funeral. There is little sadder than a child's funeral and I seldom go but I have looked after Keir for 9 years and it was the right thing to do this time. Keir had metachromatic leukodystrophy, initially diagnosed as Charcot Marie Tooth disease, until he lost his speech and mobility over a few months when he was five. Please see 'For our boy' by Michelle Tonge below.

I remember the first time I saw him, a bright little boy hooked on The Incredibles, and the last time I saw him peaceful and calm, having died a quiet death at home with his devoted family around him. In the intervening years, I saw him at home every 2 months, sometimes more often if needed. I got to know his parents, sister, grandad and all the carers, nurses, therapists and hospice staff trooping in and out of the house in a quiet cul-de-sac in the north of Bolton.

I first arrived at the family home armed with my sketchy knowledge of this rare condition and my draft Personal Resuscitation Plan. I talked earnestly to Keir's parents and filled in the plan—it was a long time before we needed it! I look back and think I was too forward with discussing end of life when there were no signs of it and I should have given the family more space without having to face such issues. However, another part of me reflects that laying that honest foundation gave a focus and reality to all our discussions since.

To be truthful, my two monthly visits were usually spent just chatting, often about what I was up to. Usually I left with a joke and a laugh. Keir was very stable for ages. We would …


The world is facing increasing pressures to reduce the amount of energy and resources that are being used. The UK government has targets to reduce carbon emissions and energy usage. Within the UK buildings are a significant contributor towards both energy and material usage. One approach to reduce the energy and carbon emissions from construction is to use natural materials that require minimal processing and energy input such as straw, timber, unfired earth and hemp-lime. Hemp-lime is a composite solid wall insulating material made from hemp shiv and a lime based binder and water which can be cast between shutters or spray applied. Hemp-lime is typically used with a load bearing timber studwork frame. Current design practice assumes that hemp-lime is a nonstructural material and only provides the insulation to the wall construction. However, as it encapsulates the studs it has to potential to enhance their load capacity by preventing buckling and resisting in-plane forces. This study aimed to establish the contribution of the hemp-lime to the structural performance of composite hemp-lime and studwork frame walls under three loading conditions; vertical compression, in-plane racking and out-of-plane bending. Both theoretical analysis and experimental testing were undertaken in order to establish the contribution. Tradical HF hemp shiv and Tradical HB binder were used to mix hemplime with a density of 275kg/m3. The wall constructions were initially theoretically analysed using existing approaches and both the stiffness and strength of the wall panels were calculated. Experimental testing was undertaken on 24 full size wall panels. Fifteen were tested with compressive loads, five with in-plane racking loads and four with out-of-plane bending loads. Initially two walls were tested with a concentric compressive load applied to the top of the encapsulated timber studs. The studs were shown to be restrained by the hemp-lime preventing buckling and increasing the failure load by over 500%. Four walls were tested with eccentrically applied compressive loads to investigate bursting of the studs through the hemp-lime surface. On three walls the studs burst through the hemp-lime showing that bursting is dependent upon the hemp-lime cover over the studs. In addition unrestrained studs were tested and shown to buckle at much lower loads than the hemp-lime lime encapsulated studs. Under in-plane racking loads two walls were initially tested and found to have increased stiffness and strength over an unrestrained studwork frame. The leading stud joints were found to be a weak point. These joints were improved and two further walls were tested, one with a sheathing board attached to the studwork frame and one without. The strengthened joints were found to improve the stiffness and strength of the wall panels. The wall panel with sheathing was also found to have a higher stiffness than the unsheathed walls. Two walls were initially tested with applied out-of-plane loads. One wall was hemplime with rendered surfaces and the other included a studwork frame. The studwork frame was found to provide continued load capacity once the render and the hemp-lime had failed. Two further wall panels were tested with a sheathing board attached to the studwork frame and render on the other face of the hemp-lime. Again the studwork frames were found to provide post crack load capacity. The walls were also found to perform with differing stiffness according to the load direction. Following experimental testing the theoretical results were compared with the experimental results. Generally good correlation is seen between the results. Prior to the experimental testing it was not possible to predict the bursting of the hemp-lime when the studs were loaded in compression, however following testing a technique was developed to allow this prediction to be made. In conclusion this study has shown that hemp-lime does enhance the load capacity of studwork framing under both compressive and in-plane racking loads. Under out-ofplane bending loads the studwork frame allows continued load capacity after the hemplime and render have cracked. This study has shown that material savings can be made when using this type of construction as a sheathing board is not necessary as the hemplime can fulfil its structural function. This will contribute towards a more efficient construction system and reduced energy and resource use.


A Lotka analysis was conducted of 14,149 references to knowledge management publications retrieved from a search of the ABI/Inform database. Results indicate that the sample of knowledge management publications conforms to the negative power distribution typical of Lotka analyses. Calculated Lotka constants were within expected parameters. A Kolmogorov-Smirnov test revealed no significant differences between observed and expected distributions. It is concluded that the knowledge management literature conforms to the principles of Lotka's Law. Analysis of author affiliations revealed that academics were prevalent among the most productive authors but that the top five authors in terms of productivity were practitioners.


Abstract. Recent
observation-based results show that the seasonal amplitude of surface ocean
partial pressure of CO2 (pCO2) has been increasing
on average at a rate of 2–3 µatm per decade
(Landschützer et al., 2018). Future increases in pCO2 seasonality
are expected, as marine CO2 concentration ([CO2])
will increase in response to increasing anthropogenic carbon emissions
(McNeil and Sasse, 2016). Here we use seven different global coupled
atmosphere–ocean–carbon cycle–ecosystem model simulations conducted as
part of the Coupled Model Intercomparison Project Phase 5 (CMIP5) to study
future projections of the pCO2 annual cycle amplitude and to
elucidate the causes of its amplification. We find that for the RCP8.5
emission scenario the seasonal amplitude (climatological maximum minus
minimum) of upper ocean pCO2 will increase by a factor of
1.5 to 3 over the next 60–80 years. To understand the drivers and mechanisms
that control the pCO2 seasonal amplification we develop a
complete analytical Taylor expansion of pCO2 seasonality in
terms of its four drivers: dissolved inorganic carbon (DIC), total
alkalinity (TA), temperature (T), and salinity (S). Using this linear
approximation we show that the DIC and T terms are the dominant
contributors to the total change in pCO2 seasonality. To
first order, their future intensification can be traced back to a doubling of
the annual mean pCO2, which enhances DIC and alters the
ocean carbonate chemistry. Regional differences in the projected seasonal
cycle amplitude are generated by spatially varying sensitivity terms. The
subtropical and equatorial regions (40∘ S–40∘ N) will
experience a ≈30–80 µatm increase in seasonal cycle
amplitude almost exclusively due to a larger background CO2
concentration that amplifies the T seasonal effect on solubility. This
mechanism is further reinforced by an overall increase in the seasonal cycle
of T as a result of stronger ocean stratification and a projected shoaling
of mean mixed layer depths. The Southern Ocean will experience a seasonal
cycle amplification of ≈90–120 µatm in response to the
mean pCO2-driven change in the mean DIC contribution and to
a lesser extent to the T contribution. However, a decrease in the DIC
seasonal cycle amplitude somewhat counteracts this regional amplification
mechanism.


Extracted from text ... 2
ISMAIL A PATEL, MB BCh, FCORL (SA)
Consultant Specialist, ENT Department,
University of the Witwatersrand and
Chris Hani Baragwanath Hospital,
Johannesburg
SYLVESTER D MASEGE, MB BCh,
FCORL (SA), DCH
ENT Specialist: Anglogold Health
Service, Carletonville
Snoring is an undesirable sound originating
from the soft tissues of the
upper airway during sleep. It has
more often than not been part of a
social dogma that has plagued society
through the sands of time. However, it
is a manifestation of a large group of
sleep disorders loosely termed sleepdisordered
breathing (SDB). SDB is a
broad term encompassing obstructive
sleep apnoea ..


ABSTRACT Aim: Progress made in the treatment and better management of cancer pts has significantly improved overall survival. Early involvement of palliative care can translate into improvements in quality of care, QoL and survival. Methods: From March 2012 an oncologist specialized and dedicated full time in palliative care is working in the oncology team of our OU. For pts with metastatic disease receiving anticancer treatment she manages the decision making, the assessment and early best palliative care. Inpatients are evaluated systematically on a day-schedule while outpatients are followed in an ambulatory of palliative care 3 days/week. She collaborates with Palliative Cancer Units (PCUs) and general practitioners with a systematic and early approach. Results: From March 2012 to March 2014, early palliative care was provided systematically to 770 pts (570 inpatients and 200 outpatients) from the palliativist oncologist. 384 pts of them were followed in palliative care ambulatory while 386 pts were taken in charge by PCUs ( 2010-2012 PCUs took in charge of 193 pts). 12.9% of them received chemotherapy in simultaneous care with PCUs with a longer time of median recovery in PCUs (75 days in 2012-2014 vs 67 days in 2010-2012). Assessment of symptoms with validated instruments (NRS, distress, QoL, ESAS, PS) was performed systematically; an effective communication and a care's relationship with pts, giving correct and clear information during all steps of the disease was established. These results show an improvement in metastatic cancer pts both in terms of quality of care and in terms of number of pts appropriately charged to PCUs. Conclusions: The presence of an oncologist dedicated to early palliative care in an oncology unit, according to AIOM and ESMO's integration models, makes appropriate the use of medical services, optimizes patient QoL throughout the course of cancer disease, improves the "non-abandonment"culture and guarantees continuity of care to all cancer pts at every step of the disease through strictly relationships with territorial structures, hospice and emergency department. Disclosure: All authors have declared no conflicts of interest.


This essay aims to explore the relationship between neoliberal ideologies and sexuality, by considering questions of criticality and political agency in relation to pornography. The essay identifies a trend in contemporary porn studies work towards a 'constrained optimism' that also expresses a wider deadlock in cultural and media studies. This arises from a need to protect the concept of individual agency against reactionary movements, alongside a tendency to elide the implications of consumerism in neoliberal cultures. Much porn studies work is critical of tendencies in altporn, most significantly around questions of labour and commodification. Yet work in this area also tends to remain invested in the promise of agency, where this agency is a function of the expansion of the technological resources available in a networked culture, the proliferation of choice, and the blurred boundary between consumer and producer. This essay seeks to move beyond this deadlock by drawing on recent work on the concept of the enterprise society, elaborated by Foucault in The Birth of Biopolitics, and taken up by writers such as McNay, who have suggested that Foucault's insight fundamentally challenges the relationship between individual autonomy and political resistance, where that autonomy guarantees not liberty but responsible self-management. The essay considers the figure of the entrepreneurial voyeur, in the light of concepts of immaterial labour offered by Lazzarato and critiqued by McRobbie, and goes on to make a sustained reading of the film Made in Secret in order to map ways in which we might be able to imagine how the affective pleasures of pornography might not simply underwrite alienated and competitive modes of being but might help us to imagine more radical forms of sociality.


OBJECTIVES
To quantify influenza vaccination rates and determine perceived barriers to influenza vaccination among U.S. pharmacists from various practice settings.

DESIGN
Prospective study.

SETTING
United States in 2008.

PARTICIPANTS
1,028 respondents, including 895 pharmacists.

INTERVENTION
A survey request was distributed manually at the 2008 National Community Pharmacists Association annual meeting, and an initial e-mail was sent with two follow-up e-mails to all pharmacists who receive e-mails via Pharmacist e-link.

MAIN OUTCOME MEASURES
Vaccination rates and barriers to vaccination among pharmacists.

RESULTS
Pharmacists reported an influenza vaccination rate of 78%, with coverage varying across practice settings: hospital (88%), academia (86%), clinic (83%), and community (75%). Employers infrequently required the influenza vaccine as a condition of employment (7%), and slightly more than one-half (58%) compensated pharmacists for being vaccinated; both of these were significantly associated with higher influenza vaccination rates (P < 0.001 for both). One-quarter of pharmacists (26%) expressed at least one issue regarding the influenza vaccine. Pharmacists were significantly less likely to be vaccinated if they expressed a concern (91% vs. 43%, P < 0.0001). Community pharmacists were significantly less likely to be compensated for receiving the influenza vaccination and significantly more likely to express one or more concerns than pharmacists from any other practice setting.

CONCLUSION
Pharmacists reported high influenza vaccination rates overall, with slight variability among practice settings. Although employers infrequently required influenza vaccination, approximately one-half of employers compensated their pharmacists for being vaccinated. Employer incentives and pharmacist attitudes were highly correlated with influenza vaccination.


Supporting programmable stateful packet forwarding functions in hardware requires a tight balance between functionality and performance. Current state-of-the-art solutions are based on a very conservative model that assumes worst-case workloads. This finally limits the programmability of the system, even if actual deployment conditions may be very different from the worst-case scenario.
 We use trace-based simulations to highlight the benefits of accounting for specific workload characteristics. Furthermore, we show that relatively simple additions to a switching chip design can take advantage of such characteristics. In particular, we argue that introducing stalls in the switching chip pipeline enables stateful functions to be executed in a larger but bounded time without harming the overall forwarding performance. Our results show that, in some cases, the stateful processing of a packet could use 30x the time budget provided by state of the art solutions.


The achievement of FFA members' regional goals for their tuna fisheries depends heavily upon the effective implementation by national governments of a comprehensive range of MCS measures. In support of this, FFA members have established various regional MCS measures that provide a framework to enable effective management and control of the region's tuna fisheries. However, problematic implementation at the national level continues to undermine the ability of FFA members and the secretariat to fully implement these initiatives and effectively monitor and control the region's tuna fisheries, thereby threatening their returns. While some FFA members have developed strong MCS systems with high levels of implementation, much of the FFA membership continues to suffer from inconsistent implementation of MCS measures. Various studies have identified the need to improve MCS implementation, noting that weaknesses in MCS were critical obstacles to sustainable management and profitable development.. This is no simple task for any country – developed or developing; island or continent. In 2006, an international study assessed compliance by 53 countries (95% of global fish landings) with key provisions of the Code of Conduct for Responsible Fisheries. The study noted that approximately 57% of the countries 'failed' on compliance with MCS related measures. Of these, 30% had particularly poor 'fail' grades, including the regionally significant countries: France, Philippines, China, Indonesia, Taiwan, and Spain. Project Two reviews the implementation by FFA members of MCS measures and provides recommendations for improving performance and monitoring where necessary. This review focuses primarily on implementation of regional and global MCS measures that have been agreed to by the FFA membership.


This address was given as part of a podium discussion on Judaism in Norway today held at the Jewish Museum in Oslo on 4 March 2018. Other participants in the panel were Rabbi Lynn Feinberg (Jewish Renewal movement), Rabbi Joav Melchior (Orthodox movement, current rabbi of Det Mosaiske Trossamfund in Oslo), Rabbi Shaul Wilhelm (Chabad shaliach in Oslo) and Professor Catherine Hezser (SOAS, London, and University of Oslo) as chair. The comments argue that Judaism in Norway is diverse and relatively unknown, with a majority of Jews in Norway probably being uncounted in current population estimates. As such there is no single experience of Norwegian Jewish identity.


The production conditions and characteristics of mycelium-bound lipase (MBL) from
Rhizomucor miehei, its catalytic performance in fat transesterification (TE) and the
feasibility of using the enzyme to produce a transesterified fat suitable for use in ice
cream formulation were investigated. The production of MBL was studied over a 5-day
incubation period. Maximum dry mycelium weight and highest lipolytic activity were
obtained after 3 days incubation in a medium containing 0.1% (w/v) glucose and 1.0%
(w/v) palm olein. Production of MBL was demonstrated to be inducible where the
addition of 0.5-5.0% (w/v) of palm oil resulted in a significantly (p..0.05) higher
lipolytic activity than culture without any added oil. High levels (>0.5%) of glucose
concentrations were found to inhibit the synthesis of MBL and insufficient lipase was produced to catalyse the TE reaction of palm stearin (POs) and palm kernel olein
(PKOo) (1:1, w/w) mixture at 60°C.
MBL was found to achieve optimum TE activity after 24 h reaction time and its
catalytic stability was demonstrated following five repeated usage in TE reaction.
Results obtained also illustrated the capability of MBL in transesterifying different oil
substrates in a manner similar to that of Lipozyme 1M 60 (Novo Nordisk Industries,
Copenhagen, Denmark), which is a commercial preparation of immobilised R. miehei
lipase.
Mixtures of PKOo:anhydrous milk fat (AMF) at different ratios (100:0, 70:30,
60:40,50:50 and 0:100, w/w) were transesterified using MBL in a solvent-free system.
The triglyceride (TG) profile, slip melting point (SMP), solid fat content (SFC), melting
thermogram and the polymorphic forms of the unreacted and trans esterified mixtures
were evaluated. Results indicated that TE by MBL produced oil mixtures with new TG
profiles, relatively lower slip melting points and solid fat contents. The melting
thermo grams from differential scanning calorimetric analysis indicated an overall shift
to lower melting TG. This study also demonstrated that the transesterified PKO₀:AMF
mixture at 70:30 (w/w) ratio completely melted at 25°C which meets the melting criteria
for fat used in ice cream formulation.
AMF, unmodified PKO₀:AMF mixture (70:30, w/w) (control mixture) and
transesterified PKO₀:AMF (70:30, w/w) were used in the preparation of ice cream
emulsions. Results obtained show that emulsion prepared using TE-PKO₀:AMF (70:30,w/w) blend exhibited higher viscosity and greater strength than that of either AMF or
unmodified PKO₀:AMF (70:30, w/w), which are amongst the desired properties of ice
cream emulsion. This further support that TE of PKO₀:AMF (70:30, w/w) is capable of
producing fat that is suitable for use in the preparation of ice cream emulsion.


Transgenic mice have important implications in biomedicine, and are widely employed to understand gene functions and their regulation. The improvement of transgenic efficiency is relevant because of the low rate of success for this technology. CXCL2 is a chemokine secreted by macrophages and epithelial cells under proinflammatory stimulus of the innate immune response such as bacterial endotoxins. The main effect of CXCL2 is the recruitment of neutrophils to the site of production to fight infections. The objective of this study was to evaluate the effect of 2 DNA concentrations in the efficiency of the transgenesis process. To this aim we used a luciferase reporter under the control of CXCL2 promoter for the generation of a transgenic line to report activation of innate immune response. A total of 1727 1-cell embryos were divided into 2 experimental groups to be microinjected with 0.5 or 1.0 ng μL-1 of DNA in 25 sessions. Three-week-old B6SJL F1 females (n = 131) were superovulated with 5 IU of eCG i.p. (Novormon, Syntex, Buenos Aires, Argentina) and 5 IU of hCG i.p. (Ovusyn, Syntex) 46 h later, and mated with B6SJL F1 stud males. At the moment of hCG treatment, foster females were mated with vasectomized males to induce pseudogestation. Donor females were euthanized by cervical dislocation 20 h after hCG treatment, and embryos were recovered from the ampulla, denuded in 300 μg mL-1 hyaluronidase (Sigma, St. Louis, MO, USA) and incubated at 37°C with 5% CO2, in drops of M16 media (Sigma) under mineral oil, until microinjection. DNA construction consisted of the luciferase reporter gene under the control of the murine CXCL2 gene promoter. Embryos were microinjected into 1 pronucleus under an inverted microscope (Nikon, NY, USA) using glass microtools and mechanic micromanipulators (Eppendorf, Hamburg, Germany). Intact/injected embryos were assessed 30 min after microinjection. Fifteen to 20 embryos per foster female were transferred in both oviducts. Birth rate, survival of pups at Day 7 after birth, number of transgenic pups assessed by standard PCR, and overall transgenic efficiency was registered for each group. Data were analyzed by Yates-corrected chi-square test. No statistical differences were founded except for a higher number of pups alive/embryo transferred in the lower DNA concentration, suggesting the advantage of using 0.5 ng μL-1 v. 1.0 ng μL-1. Table 1.Effect of DNA concentration in the generation of CXCL2-luc transgenic mice


In this paper we present our implementation of a complete multiple machine precision interval package in FORTRAN 77. The operations are designed to perform optimally with up to about 100 significant digits. The implementation only requires IEEE 754 compliant floating point operations, and thus is highly portable to virtually any modern computer platform. Intervals are stored as unevaluated floating point sums. Elementary operations such as addition and multiplication are based on exact floating point operations, while higher level operations such as division and square root are implemented based on those elementary operations. While there are several other non-rigorous high precision libraries based on these concepts, to the best of our knowledge this implementation is the first fully rigorous interval package. Besides basic operations on high precision intervals, the library also provides a wide range of verified intrinsic functions such as sin, arctan, and ln. The library is integrated into the COSY INFINITY rigorous computation environment, providing fast and rigorous interval operations from within the COSY environment.


Two distinct phases of island-are evolution are recognized in late Mesozoic sedimentary rocks of the northern Antarctic Peninsula. During late Jurassic (Kimmeridgian-Tithonian) times, alternating radiolaria-rich mudstones and ash-fall tuffs were deposited under shallow marine euxinic conditions in association with restricted volcanic centres. The name Nordenskjöld Formation is proposed for this lithostratigraphic unit. Subsequently, during the early Cretaceous, a major episode of volcanism and uplift led to the construction of an emergent are-terrane. Simultaneous development of a retro-arc basin resulted in the accumulation of coarse volcaniclastic detritus along the eastern side of the arc. Retro-are sedimentation and intermittent volcanism continued into the late Cretaceous and early Tertiary. Although the pattern of sedimentation in the northern Antarctic Peninsula is broadly comparable to that of the southern Andes, an active marginal basin has not been recognized in the former area. Interbedded mudstones and tuffs, identical to those of the Nordenskjöld Formation, were deposited in the southern Andes and South Georgia during the late Jurassic - early Cretaceous.


Winkle protects any validator-based byzantine fault tolerant consensus mechanisms, such as those used in modern Proof-of-Stake blockchains, against long-range attacks where old validators' signature keys get compromised. Winkle is a decentralized secondary layer of client-based validation, where a client includes a single additional field into a transaction that they sign: a hash of the previously sequenced block. The block that gets a threshold of signatures (confirmations) weighted by clients' coins is called a "confirmed" checkpoint. We show that under plausible and flexible security assumptions about clients the confirmed checkpoints can not be equivocated. We discuss how client key rotation increases security, how to accommodate for coins' minting and how delegation allows for faster checkpoints. We evaluate checkpoint latency experimentally using Bitcoin and Ethereum transaction graphs, with and without delegation of stake.


BACKGROUND
Recent progress in understanding the genetic basis of breast cancer and widely publicized reports of celebrities undergoing risk-reducing mastectomy (RRM) have increased interest in RRM as a method of preventing breast cancer. This is an update of a Cochrane Review first published in 2004 and previously updated in 2006 and 2010.

OBJECTIVES
(i) To determine whether risk-reducing mastectomy reduces death rates from any cause in women who have never had breast cancer and in women who have a history of breast cancer in one breast, and (ii) to examine the effect of risk-reducing mastectomy on other endpoints, including breast cancer incidence, breast cancer mortality, disease-free survival, physical morbidity, and psychosocial outcomes.

SEARCH METHODS
For this Review update, we searched Cochrane Breast Cancer's Specialized Register, MEDLINE, Embase and the WHO International Clinical Trials Registry Platform (ICTRP) on 9 July 2016. We included studies in English.

SELECTION CRITERIA
Participants included women at risk for breast cancer in at least one breast. Interventions included all types of mastectomy performed for the purpose of preventing breast cancer.

DATA COLLECTION AND ANALYSIS
At least two review authors independently abstracted data from each report. We summarized data descriptively; quantitative meta-analysis was not feasible due to heterogeneity of study designs and insufficient reporting. We analyzed data separately for bilateral risk-reducing mastectomy (BRRM) and contralateral risk-reducing mastectomy (CRRM). Four review authors assessed the methodological quality to determine whether or not the methods used sufficiently minimized selection bias, performance bias, detection bias, and attrition bias.

MAIN RESULTS
All 61 included studies were observational studies with some methodological limitations; randomized trials were absent. The studies presented data on 15,077 women with a wide range of risk factors for breast cancer, who underwent RRM.Twenty-one BRRM studies looking at the incidence of breast cancer or disease-specific mortality, or both, reported reductions after BRRM, particularly for those women with BRCA1/2 mutations. Twenty-six CRRM studies consistently reported reductions in incidence of contralateral breast cancer but were inconsistent about improvements in disease-specific survival. Seven studies attempted to control for multiple differences between intervention groups and showed no overall survival advantage for CRRM. Another study showed significantly improved survival following CRRM, but after adjusting for bilateral risk-reducing salpingo-oophorectomy (BRRSO), the CRRM effect on all-cause mortality was no longer significant.Twenty studies assessed psychosocial measures; most reported high levels of satisfaction with the decision to have RRM but greater variation in satisfaction with cosmetic results. Worry over breast cancer was significantly reduced after BRRM when compared both to baseline worry levels and to the groups who opted for surveillance rather than BRRM, but there was diminished satisfaction with body image and sexual feelings.Seventeen case series reporting on adverse events from RRM with or without reconstruction reported rates of unanticipated reoperations from 4% in those without reconstruction to 64% in participants with reconstruction.In women who have had cancer in one breast, removing the other breast may reduce the incidence of cancer in that other breast, but there is insufficient evidence that this improves survival because of the continuing risk of recurrence or metastases from the original cancer. Additionally, thought should be given to other options to reduce breast cancer risk, such as BRRSO and chemoprevention, when considering RRM.

AUTHORS' CONCLUSIONS
While published observational studies demonstrated that BRRM was effective in reducing both the incidence of, and death from, breast cancer, more rigorous prospective studies are suggested. BRRM should be considered only among those at high risk of disease, for example, BRCA1/2 carriers. CRRM was shown to reduce the incidence of contralateral breast cancer, but there is insufficient evidence that CRRM improves survival, and studies that control for multiple confounding variables are recommended. It is possible that selection bias in terms of healthier, younger women being recommended for or choosing CRRM produces better overall survival numbers for CRRM. Given the number of women who may be over-treated with BRRM/CRRM, it is critical that women and clinicians understand the true risk for each individual woman before considering surgery. Additionally, thought should be given to other options to reduce breast cancer risk, such as BRRSO and chemoprevention when considering RRM.


Large scale molecular dynamics (MD) simulations are performed to study the oxidation of highly oriented pyrolytic graphite (HOPG) by hyperthermal atomic oxygen beam (5 eV). Simulations are performed using the ReaxFF classical reactive force field. We present here additional evidence that this method accurately reproduces ab initio derived energies relevant to HOPG oxidation. HOPG is modeled as multilayer graphene and etch-pit formation and evolution is directly simulated through a large number of sequential atomic oxygen collisions. The simulations predict that an oxygen coverage is first established that acts as a precursor to carbon-removal reactions, which ultimately etch wide but shallow pits, as observed in experiments. In quantitative agreement with experiment, the simulations predict the most abundant product species to be O2 (via recombination reactions), followed by CO2, with CO as the least abundant product species. Although recombination occurs all over the graphene sheet, the carbon-removal reactions occur only about the edges of the etch pit. Through isolated defect analysis on small graphene models as well as trajectory analysis performed directly on the predicted etch pit, the activation energies for the dominant reaction mechanisms leading to O2, CO2, and CO product species are determined to be 0.3, 0.52, and 0.67 eV, respectively. Overall, the qualitative and quantitative agreement between MD simulation and experiment is very promising. Thus, the MD simulation approach and C/H/O ReaxFF parametrization may be useful for simulating high-temperature gas interactions with graphitic materials where the microstructure is more complex than HOPG.


This is the third extended and improved edition of the dictionary. Previous editions having been confined mainly to English and German, this is, with the addition of French, the first trilingual edition. The number of terms has been expanded from 20 000 to 30 000. A partial thesaurus structure is provided in the form of broader terms, narrower terms, related terms, synonyms, antonyms and brief definitions, where appropriate. As before, there is a separate list of scientific names (of Latin origin), together with linguistic equivalents.


Single layer coatings of Al(2)O(3).H(2)O have been prepared on fused silica and BK-7 substrates from aqueous colloidal suspensions of hydrated alumina at room temperature. These coatings were porous and had a refractive index of ~1.44. Multilayer, high reflectivity, dielectric coatings were also prepared by laying down quarterwave-thick, alternating coats of this alumina with silica, also prepared from colloidal suspension, and having a refractive index of 1.22. To achieve 99% reflectivity, 30-35 layers were required. Single shot, laser damage threshold measurements at 1064 nm wavelength with a pulse length of 10 ns were carried out on both the single layer and multilayer system. The thresholds averaged 21 and 12 J/cm(2), respectively.


In this Idea, Professor Sedler, who litigated the Kentucky version of Roe v. Wade for the ACLU of Kentucky while on the faculty of the University of Kentucky, gives his opinion as to why the Supreme Court will not overrule Roe v. Wade. The Idea is based on an op-ed that Professor Sedler published in the Detroit Free Press in connection with the nomination of Chief Justice John Roberts to the Supreme Court. Professor Sedler maintains that the Court is not likely to overrule Roe v. Wade for two related reasons. The first reason goes to the operation of the Court itself. The Court operates as an institution, and, although the Court has the power to overrule its decisions, a longitudinal analysis indicates that over a period of time, comparatively few decisions have been overruled. More significantly, the Court has never overruled a decision recognizing a constitutional liberty interest, or for that matter, any other constitutionally-protected interest. Where the Court has overruled cases involving constitutional rights, it has been to overrule a case rejecting a claimed constitutional right and to hold that the claimed right is indeed protected by the Constitution. Second, for the Court to overrule Roe v. Wade would have a cataclysmic effect on American society. For large numbers of American women, abortion has become a fully acceptable way of ending an unwanted pregnancy. Professor Sedler reviews the latest available data, which shows that approximately 1.3 million American women have abortions every year, with almost 90% being performed during the first 12 weeks, and most during the first 9 weeks. Less than 1% of these abortions are performed after 24 weeks. On the other hand, the data shows that more than half of the women reporting unwanted pregnancies choose to continue with their pregnancies rather than have an abortion. The right of a woman to choose to continue with an unwanted pregnancy or to choose to terminate that pregnancy by a medical abortion is firmly established in American society today and is part of the value acceptances of that society. The Supreme Court will not take that choice away from American women.


Processes controlling streamflow generation were determined using geochemical tracers for water years 2004–2007 at eight headwater catchments at the Kings River Experimental Watersheds in southern Sierra Nevada. Four catchments are snow‐dominated, and four receive a mix of rain and snow. Results of diagnostic tools of mixing models indicate that Ca2+, Mg2+, K+ and Cl− behaved conservatively in the streamflow at all catchments, reflecting mixing of three endmembers. Using endmember mixing analysis, the endmembers were determined to be snowmelt runoff (including rain on snow), subsurface flow and fall storm runoff. In seven of the eight catchments, streamflow was dominated by subsurface flow, with an average relative contribution (% of streamflow discharge) greater than 60%. Snowmelt runoff contributed less than 40%, and fall storm runoff less than 7% on average. Streamflow peaked 2–4 weeks earlier at mixed rain–snow than snow‐dominated catchments, but relative endmember contributions were not significantly different between the two groups of catchments. Both soil water in the unsaturated zone and regional groundwater were not significant contributors to streamflow. The contributions of snowmelt runoff and subsurface flow, when expressed as discharge, were linearly correlated with streamflow discharge (R2 of 0.85–0.99). These results suggest that subsurface flow is generated from the soil–bedrock interface through preferential pathways and is not very sensitive to snow–rain proportions. Thus, a declining of the snow–rain ratio under a warming climate should not systematically affect the processes controlling the streamflow generation at these catchments. Copyright © 2012 John Wiley & Sons, Ltd.


When 2-propanol is added to a chloroform solution containing a mixture of CdSe quantum dots (QDs) plus a polystyrene-block-poly(4-vinylpyridine) diblock copolymer (PS404-b-P4VP76, the subscripts refer to the degree of polymerization), the block copolymer assembles into uniform 40 nm diameter spherical micelles with a PS core and a thin P4VP corona to which the QDs are attached. As we reported in Macromolecules, 2010, 43, 5066–5074, vigorous magnetic stirring of this mixture over two days leads to a change in morphology to finite (1 to 2 μm) networks consisting of interconnected cylindrical PS struts surrounded by a P4VP corona in which the QDs are embedded. Here we find that these networks settle but do not lose their structure if allowed to age without stirring. Continued vigorous stirring over one month leads to a complete change in morphology, to form clusters of oval-shaped vesicles similar in size to the networks, in which individual vesicles are a few hundred nm long. Some of the vesicles appear to have popped open to form pairs of bowl-like structures. These bowls are single-walled structures, with walls similar in thickness (35 to 40 nm) to the core of the micelles formed in the initial step. We believe the walls consist of a PS core with P4VP chains protruding from the inner and out surfaces. The QDs are attached to both surfaces of both the vesicles and the bowls, presumably still embedded in the P4VP corona. These colloidal nanocomposites provide a striking example of kinetically controlled self-assembly in which the system evolves from small spheres of high curvature to cylinders of lower curvature, to larger vesicles, and each step takes place on its own characteristic time scale.


Introduction: Cervical nabothian cysts are common in women of reproductive age. Although cysts are generally small and asymptomatic, large ones are extremely rare and may be misdiagnosed as malignancy. Case Study: We report a case of large multiple complex nabothian cyst, which was suspected as malignant one on imaging and examination. Pelvic examination and ultrasonography revealed ballooned cervix with multiple large complex nabothian follicles. There was an associated large adnexal mass with ascites. The patient was treated with total hysterectomy and omentectomy after aspiration of the fluid from the cervical cysts for debulking and limiting complications. Pathology revealed granulosa cell ovarian tumor, omental panniculitis, and cervical nabothian follicles. Conclusion: Large nabothian cysts should be kept in mind for differential diagnosis of cervical tumors. Ultrasonography is of value for the diagnosis of giant nabothian cysts and can aid in exclusion of malignancy. Differentiation between a malignant cystic lesion, such as an adenoma malignum, and a benign cystic lesion is crucial but difficult. Cervical nabothian follicles can be multiple and attain a large size up to 4 cm each. It is commonly benign but we should keep in mind the rare adenoma malignum on imaging and histopathology.


Plasminogen (Plg) is the zymogen form of the serine protease plasmin (Plm), and it plays a crucial role in fibrinolysis as well as wound healing, immunity, tissue remodeling and inflammation. Binding to the targets via the lysine-binding sites allows for Plg activation by plasminogen activators (PAs) present on the same target. Cellular uptake of fibrin degradation products leads to apoptosis, which represents one of the pathways for cross-talk between fibrinolysis and tissue remodeling. Therapeutic manipulation of Plm activity plays a vital role in the treatments of a range of diseases, whereas Plm inhibitors are used in trauma and surgeries as antifibrinolytic agents. Plm inhibitors are also used in conditions such as angioedema, menorrhagia and melasma. Here, we review the rationale for the further development of new Plm inhibitors, with a particular focus on the structural studies of the active site inhibitors of Plm. We compare the binding mode of different classes of inhibitors and comment on how it relates to their efficacy, as well as possible future developments.


On-farm diversification towards multifunctional activities is perceived as central in the Common Agricultural Policy (CAP) reform and in the Horizon 2020 strategies, because it strengthens territorial and social cohesion of rural areas. While from a "macro" point of view relations between farm-household diversification and rural economies are central in the process of multi-functionality and in the provision of public goods through agricultural activities, from a "micro" point of view on-farm diversification activities can represent a relevant share of farm income. Agricultural Economics and Rural Sociology have developed models aiming to explain the determinants of on-farm diversification thus providing a set of variables potentially influencing on-farm diversification. The paper applies a count model to explain the number of on-farm diversification activities that are implemented by farms in Tuscany. Since the high number of agricultural holdings that do not apply any diversification activity, we propose a two-step model where, firstly a simulation of adoption of diversified strategy as binary variable is considered and secondly, a model analysing the determinants of diversification intensity among the farms that have decided to diversify is implemented. Results confirm that location near main touristic areas and vicinity to urban markets are important determinants of on-farm diversification intensity. Results highlight a positive contribution of the Pillar 2 agricultural policies both in determining the diffusion of on-farm diversification activities and in influencing the intensity of adoption, while high per hectare Single Farm Payments have a negative influence on diversification intensity.


Ardennite-(V), ideally Mn4[Al4(AlMg)][Si5V]O22(OH)6, is the analogue of ardennite, ideally Mn4[Al4(AlMg)][Si5As]O22(OH)6, with V dominant at the T4 site. The history of the discovery of ardennite is outlined, with special accent on its chemical composition; revision of the old literature evidenced that even if vanadium-containing specimens were considered since the first description, the analytical data contained in the first papers are very questionable, and ardennite has been so far considered an arsenate-silicate. A new occurrence of ardennite-(V) is described from Sparone, Locana Valley (TO), Piedmont, Italy. Here ardennite-(V) occurs within a piemontite-bearing micaschist. Crystals are elongated along [010] and very thin (up to 1 mm in length and a few microns in diameter), are yellow with a white streak, transparent with a vitreous lustre, and brittle. No cleavage or parting were observed. The calculated density is 3.55 g/cm3. Optically, ardennite-(V) is biaxial, with α > 1.765(5), β < 1.775(5), and γ = 1.775(5), and is weakly pleochroic, with X, Y = pale yellow; Z = yellowish. Electron microprobe analyses (P2O5 0.38 wt.%, As2O5 0.37, V2O5 4.60, SiO2 31.21, TiO2 0.21, Al2O3 22.60, Fe2O3 1.64, Cr2O3 0.34, MgO 4.44, MnO tot 23.28, CaO 4.24, Na2O 0.02, F 0.17, H2O calc 5.70), gave the following empirical formula: [Mn2+3.221Ca0.774Na0.006]∑ = 4.001 [Al4.456Mg1.127Fe3+0.210Mn3+0.137Cr0.046Ti0.027] ∑ = 6.003 [Si5.000] [V0.518Si0.315Al0.080P0.055As0.033] ∑ =1.001 O21.433 (OH)6.475 F0.092. The five strongest peaks in the X-ray powder diffraction pattern [ d (A)( I )( hkl )] are: 2.948(90)(115), 2.609(100)(310/116), 2.033(55)(225), 1.585(75)(425), 1.477(45)(2.2.10). Ardennite-(V) is orthorhombic, space group Pnmm , with a 8.760(3), b 5.838(2), c 18.56(2) A. Both the new mineral and its name were approved by the IMA CNMNC. Chemical analyses which point to the occurrence of ardennite-(V) were recorded also at Varenche mine, S. Barthelemy, Aosta Valley, Italy, but the crystal showed a marked zoning.


Based on intensive collecting from various sites in Sweden, the genus Dasyhelea Kieffer, 1911 was reviewed and the number of species now known from the country increased from five to twenty. Among the new species recorded there are two species described as new to science, D. dominiakae sp. nov. and D. gothlandica sp. nov., both in the subgenus Dicryptoscena Enderlein, 1936. The following subgenera are now documented from Sweden: Dasyhelea , Dicryptoscena , Pseudoculicoides Malloch, 1915, Prokempia Kieffer, 1913 and Sebessia Remm, 1979, the two latter subgenera being reported for the first time.


Adjustable Robust Optimization (ARO) yields, in general, better worst-case solutions than static Robust Optimization (RO). However, ARO is computationally more difficult than RO. In this paper, we derive conditions under which the worst-case objective values of ARO and RO problems are equal. We prove that if the uncertainty is constraint-wise and the adjustable variables lie in a compact set, then under one of the following sets of conditions robust solutions are optimal for the corresponding (ARO) problem: (i) the problem is fixed recourse and the uncertainty set is compact, (ii) the problem is convex with respect to the adjustable variables and concave with respect to the parameters defining constraint-wise uncertainty. Furthermore, if we have both constraint-wise and nonconstraint-wise uncertainty, under similar sets of assumptions we prove that there is an optimal decision rule for the Adjustable Robust Optimization problem that does not depend on the parameters defining constraint-wise uncertainty. Also, we show that for a class of problems, using affine decision rules that depend on both types of uncertain parameters yields the same optimal value as ones depending solely on the nonconstraint-wise uncertain parameter. Additionally, we provide several examples not only to illustrate our results, but also to show that the assumptions are crucial and omitting one of them can make the optimal worst-case objective values different.


[Extract] As with many Western nations with high numbers of immigrant intake, the Australian public debates have placed doubt on:

• The levels and success of integration of newly arrived migrants and refugees

• The success or failure of multicultural policies

• The threat that migrants from different cultures and religions pose to national identity, national values and social cohesion

The cornerstone of the democratic nation state is the establishment of rights: political, social and civil. Membership in a nation state denotes both civic belonging in the political community and cultural belonging in the national community. In the political community all citizens are seen as equal. However, evidence points to the continued disadvantage, social exclusion and marginalisation which characterise Australian society. Current and past policies, programs and ideas on social exclusion have focused on exclusion from the labour market, economic exclusion (including poverty), exclusion based on social isolation, geographic or spatial exclusion, and exclusion based on institutional processes and systems. In the considerations of social exclusion/inclusion, very little attention has been paid to exclusion based on culture, ethnicity, racism and other diversity signifiers as causal factors of disadvantage. Recent social inclusion debates in Australia have not resulted in any meaningful consideration of cultural diversity as a force for inclusion or exclusion. Furthermore, the nation state has been actively engaged in the construction of Australian identity in particular ways that have denied the consideration of "ethnic identity" as a positive feature of nation building. Through the use of fear, law and order, and a neo-liberal approach, the Australian state has constructed an environment which has depleted a sense of belonging for minorities. In so doing, it has depleted social capital in communities and social cohesion across the nation. This chapter explores the concepts of identity and belonging for minority communities in the context of globalisation and the nation state in Australia.


This article contributes to the new governance literature by analyzing how private parties profit from standards. Scholars previously have focused on what I call first-order profits from the right to extract rent directly from the ownership or application of standards. But some parties also make second-order indirect profits by engaging in some new enterprise not directly related to the value of the relevant standard. For example, an accounting firm can offer consulting services based on its reputation as a standard bearer. Second-order profits are most substantial for strong-form standards, which arise when the government designates a private entity as standard setter and assigns it the task of enforcement and regulation. This article suggests that the question of whether such privatization is beneficial depends not only on first-order rents, but also on second-order costs and benefits. It considers two examples from the financial markets: over-the-counter derivatives and credit rating agencies.


From 2006 to 2014, the professional US company Ballet Austin hosted an ambitious biennial competition, New American Talent/Dance, as an experimental platform to support "emerging" choreographers. However, after five seasons of this competition and despite self-reported success in meeting project goals to provide new learning experiences for participating choreographers, dancers, and audiences, Ballet Austin suspended the event. The reasons behind this decision, along with the insights gained through the process of producing these shows, reveal dimensions of US contemporary ballet in practice. This chapter illuminates how ballet pedagogy often fails the needs of contemporary ballet artists in the education of both future choreographers and the dancers who work with them, impacting not only the lives and careers of these artists but also, more generally, field aesthetics and development. The research further describes how audiences judged emerging choreographers, an analysis that may inform future lines of inquiry with regard to contemporary ballet and the sustainability of the field in the United States.


When a physician fails to provide adequate, appropriate pain care and the patient, or the patient's survivors, complain to the state medical board, should the board take corrective or disciplinary action? We believe so. The phenomenon of undertreatment of pain is, and has been for some time, widespread, with many reports documenting that 50 percent of dying patients experience unrelieved pain. Medical boards have long been active in investigating perceived excessive prescribing as a form of "inappropriate prescribing" and the boards' willingness to investigate perceived excessive prescribing has contributed to an environment in which physicians are reluctant to prescribe controlled substances for treatment of pain. As a result, countless patients have suffered unnecessarily. The boards have an opportunity to correct this and bring some balance to a badly skewed situation by showing a willingness and commitment to investigate inappropriate prescribing when it occurs on the other end of the spectrum. Such a commitment would be an effective tool in motivating physicians to prescribe appropriately and an effective means of seeing that physicians who lack adequate knowledge of pain management get needed education in this area. Medical boards plainly have the power and authority to take on responsibility of correcting licensees who fail to treat pain adequately. Failure to prescribe adequate amounts of pain medication constitutes "inappropriate prescribing," and gives rise to board jurisdiction. There are often multiple bases upon which board jurisdiction in a case of failure to adequately treat pain could be grounded, including professional or medical incompetence, unprofessional conduct, failure to satisfy prevailing and accepted standards of care, abandonment of the patient, and failure to monitor controlled substance treatment efficacy.


Scientists have used a glowing protein from fireflies to observe the activity of a molecule that is an important target for new drugs to treat cancer, autoimmune diseases and several other disorders. The target molecule, known as IKK (for IKappa kinase), regulates processes that can trigger dramatic changes in cellular physiology. Scientists have linked these changes to many different disorders."Our new system allows researchers to monitor whether drugs for these conditions are hitting this exact molecular target in cell culture and laboratory animals," says senior investigator David Piwnica-Worms, M.D., Ph.D., professor of molecular biology and pharmacology and of radiology. Piwnica-Worms and lead author Shimon Gross, Ph.D., a postdoctoral fellow, measured light from the firefly protein, luciferase, to monitor IKK activity in tumor cells and inflamed liver cells in live mice. They also showed that the technique can greatly reduce the costs of tests that establish the best dosages for drugs that target IKK. Their results appear in the August 2005 issue of Nature Methods. IKK stands at a pivot point in the middle of an important set of linked chain reactions known as the NF-KappaB pathway. The pathway can start at many different receptors on cell surfaces; its finish changes the activity levels of varying genes. The result, according to Piwnica-Worms, is that the potential reaction patterns in the NF-KappaB pathway form an hourglass-like shape, fanning out among many options at the start, narrowing in the middle, and again fanning out among many options at the end."At the waist of that hourglass is IKK," he explains. "This appears to put it in a position to be the key regulator of the pathway, and that has made it a subject of great interest both from the perspective of understanding how this pathway works and from that of developing new drugs for conditions that involve this pathway. " Piwnica-Worms' laboratory has previously developed techniques that use luciferase to monitor protein-protein interactions. Researchers can employ an instrument known as an in-vivo bioluminescence camera to take real-time measurements of light from luciferase in cell cultures and in cells within live animals. To use the firefly protein to monitor IKK, Gross altered cell lines to genetically fuse the luciferase protein to IKB (IKappaB), the protein that comes immediately after IKK in the NF-KappaB pathway. When the pathway is enabled, IKK triggers reactions that lead to the degradation of IKB. In cells with genetically altered IKB, the attached luciferase is broken down too, meaning scientists can detect increased IKK activity via decreased light from the cells. "This is like doing in-vivo pharmacodynamics and pharmacokinetics," says Piwnica-Worms in reference to the sciences that study the effects, distribution and dissipation of drugs. "Traditionally the only ways we could do those kinds of studies were either to test for levels of the drug in the blood or to label the drug with a radioactive tracer. "In the case of NF-KappaB, there were also methods that monitored IKK activity via changes in the levels of gene activation at the end of the pathway," he notes. "But those took hours to days to deliver results, and our approach works continuously and in real time." In their study, Gross and Piwnica-Worms tested the technique in live mice by transplanting genetically altered tumor cells and by using a technique that inserted the fused IKB/luciferase protein into liver cells only. They are currently working to develop a line of mice with the IKB/luciferase fusion built into its genetic code. In addition, they showed that the system is not only helpful for learning if a drug is having the desired effect, it can also be used to fine-tune drug dosage for maximum benefit. "One of the reviewers of our paper suggested that we should use the system to produce a full dose-response curve, which helps establish how to best use a drug," Piwnica-Worms says. "Establishing that normally takes 6 months and 300 mice. With our monitoring technique, Shimon did it in a 5-day period using 30 mice. That's going to lead to tremendous cost savings." Because the luciferase-based monitoring system allows monitoring in live animals, Gross could perform multiple tests on the same mouse over time. He was also able to monitor the mice for individual variances that could inappropriately bias the results. Contact: Michael Purdy; 314.286.0122; email@example.com


Gazing into the future of women's health requires either extraordinary prescient capabilities or a very large crystal ball. Nevertheless, the dawn of 2015 is a tempting opportunity to take stock and steal a glimpse into the future. The eight Millennium Development Goals (MDGs) have shaped efforts to promote global women's health, with bold targets to empower women and improve sexual and reproductive health. Some targets have been reached and surpassed; others, notably those related to women's health, have not been fully achieved (Figure 1).


Paper-based electronics have been considered as one of the most exciting technologies in the near future due to sustainability, low cost, mechanical flexibility, etc. Even though there have been numerous studies regarding this technology, there is not any available quantitative study on how paper electronics would minimize the impact on the environment. This work aims to give the first detailed analysis regarding this important question. To this end, we for the first time designed and prototyped paper-based multilayer printed circuit boards (P-PCBs), which show comparable functions to the currently available organic printed circuit boards (O-PCBs); yet the P-PCBs adopt a "green" preparation process. A life cycle assessment study was performed to quantify the P-PCBs' environmental impacts, e.g. acidification potential, global warming potential, human toxic potential, ozone layer depletion potential, etc. Our current research reveals that the P-PCBs have about two magnitude lower impact on the environment than O-PCBs based on the results of the life cycle assessment, which suggests that the P-PCB technique is beneficial for the environment at the regional or global production level. The current study gives useful information and sheds light on the future technological directions for various paper based electronics studies.