466 INSIGHTS | The Journal of Experimental Medicine <ID>JEM_2134insight1_Fig1.jpeg</ID>Unraveling the cellular changes elicited by pathogenic mutations is central to the development of novel targeted therapeutics. In this issue, <addart type="rel" doi="10.1084/jem.20150951">Patzke et al.</addart> use advanced stem cell technologies to underscore the role of human L1CAM for neuronal development and function. Mutations in the cell adhesion molecule L1CAM cause neurological alterations, including severe intellectual disabilities summarized as L1 syndrome. The requirements of L1CAM for neuronal development have been characterized extensively using in vitro, cell culture, and mouse model systems, which have implicated L1CAM in numerous signaling pathways with essential roles for neurite outgrowth, axon guidance, and synaptic transmission. However, distinct differences remain between the phenotypic strength of mouse models and clinical presentations in human patients. <ID>JEM_2134insight1_Fig2.eps</ID>Patzke et al. address the requirements of human L1CAM using embryonic stem (ES) cell–derived neurons and demonstrate that L1CAM is cell-autonomously required for the control of neuronal morphology and excitability, features likely contributing to impaired neurological performances in human patients. The novel approach of generating induced conditional knockout neurons with perfectly matched controls enables precise qualitative and quantitative analyses of disease-associated alterations. Loss of L1CAM not only resulted in reduced axonal outgrowth but also uncovered a requirement for dendritic development. In the absence of L1CAM, there is a reduction in the levels of ankyrinG and ankyrinB, two adaptor proteins that are essential organizers of axonal domains. Consequently, mutant neurons exhibited decreased excitability, resulting in impaired action potential generation. Pathogenic mutations in the ankyrin-binding site of L1CAM failed to restore ankyrin distribution, suggesting that L1CAM and ankyrins form interdependent stabilizing complexes controlling the subcellular protein composition of axonal domains. From a therapeutic point of view, this strategy of matched control and mutant human ES-derived neurons not only enables the identification of humanspecific gene functions but also facilitates the testing of potential gene-based or pharmacological interventions to ameliorate disease-associated deficits. However, in the case of adhesion molecules like L1CAM, it is also important to consider that transcellular interactions may alter intrinsic signaling properties and contribute to the establishment of functional neuronal circuits. In combination with in vivo animal models, the ES-based conditional knockout strategy provides an exciting and complementary route to human disease diagnostics and therapeutic development.


We establish the coccolith stratigraphy of the Maastrichtian through lower Eocene section recovered from the Dababiya Core taken ~200 m from the GSSP for the Paleocene/Eocene boundary, and correlate coccolith biozones with lithostratigraphic units in the core. The section extends from Maestrichtian Subzone CC25a to lowermost Eocene Subzone NP9c. The composite Paleocene-lower Eocene Dababiya section recovered in the core and accessible in outcrop in the Dababiya Quarry exhibits an unexpected contrast in thick- ness between the Lower Eocene succession (~Esna Shales) and the Paleocene one (~Dakhla Shales and Tarawan Chalk).


The majority of people in African countries, especially in South Africa, live subsistence livelihoods below the poverty line. Poverty is a condition characterised by a lack of basic needs such as water, health care, foods, suffi cient access to social and economic services, and few opportunities for formal income generation. This paper assesses the issues impacting on higher levels of poverty and hunger, and suggests an alternative policy framework for improving the wellbeing of the region's poor. In view of the causes of poverty and its predominance, poverty alleviation addresses constraints at the root of poverty. The premise of the paper is that including the poor is an important and progressive step in any attempt to sustain growth, development and socio-economic transformation in Africa, with South Africa as a case study.


Due to its sensitivity to isostatic and eustatic sea-level change the west coast of Scotland has been an important area for studying sea-level change. Recently, data from north west Scotland have been used to refine GIA models because of the presence of the ice sheets of the last glacial maximum (LGM) and its long record of sea-level change exceeding 10 000 yr. The Holocene highstand record of the area studied in Scotland is preserved within the many isolation basins, tidal marsh sediments and raised beaches which collectively preserve a diachronous record of marginal marine sedimentation over the course of the Holocene. The Arisaig area preserves one of the longest records of relative sea-level change in Great Britain, in excess of 16 ka (e.g. Shennan eta/., 1993, 1994, 1995a and 1995b). The microfossil sediment sequence from Mointeach Mhor North, is an important bio-stratigraphical sequence from the north west coast because it records both the rise and fall of sea level throughout the mid Holocene more precisely than many other sites. Where until recently the data used to reconstruct RSL were sea level index points taken from regressive and/or transgressive contacts, verified by the microfossil data, this investigation aims to for the first time reconstruct sealevel change through the sediment sequence using diatom, pollen and multiproxy microfossil-based transfer functions.This thesis also highlights some of the problems encountered associated with the transfer function technique and microfossil choice that may limit or constrain the applicability of transfer functions in sea-level studies, including spatial autocorrelation, over- and under-estimation of optima, multiple analogues, no analogues and the problem of allochthonous and autochthonous species.This research project has determined that regional and local multi-proxy transfer functions have the potential to reconstruct reference water levels (RWLs) more precisely than diatom and pollen training sets (Table 4.16). When the regional transfer functions were ran again using only the samples within the multi-proxy training set to allow direct comparison, the multi-proxy training set still produced the best performance statistics. When the training sets were used to calibrate the fossil cores/monoliths to produce estimates of RWL (Chapter 6) the original samples containing all available samples gave more sensible and reliable estimates of RWL than the training sets that only contained the 75 assemblages in the multi-proxy training set. In Chapter 6 the original regional diatom training set produced the most reliable and sensible estimates of RWL. The excellent statistical parameters produced during regression in Chapter 4 that indicated multi-proxy training sets performed better than diatom and pollen training sets are not reflected in the RWL reconstruction when the multi-proxy training sets are used to calibrate the fossil assemblages. This indicates that diatom-inferred RWL reconstructions are the most reliable but when diatoms are not present there is the potential to use a multi-proxy approach. When considering whether local or regional training sets are the most precise, the local diatom, pollen and multi-proxy training sets from Saideal nan Ceapaich in Morar continually provided the most precise estimates of RWL. However, regional training sets provided the most reliable estimates of RWL.


As the first facility of its kind anywhere in the world, EMEC provides wave and tidal developers with opensea grid-connected testing facilities for single devices and small arrays. In addition to its technical and operational services, EMEC also provides in-depth assistance with all matters relating to the consenting of devices, which includes regular close liaison with regulators and stakeholders. For devices being tested for the first time in the open sea, interactions with wildlife and other sea users need to be well understood. Primarily an operational test facility, there is also a key role for EMEC to play in establishing and facilitating monitoring of devices regarding their potential impacts on the receiving environment and other sea users. This paper presents an update on the environmental monitoring work underway at EMEC, together with work being undertaken by EMEC in the development of a Monitoring Strategy, which may be used as a basis for consistent monitoring by developers of individual units and small arrays of devices on test at the wave and tidal sites. The paper also presents EMEC's work to streamline the consents process for the marine renewables industry in Scotland (under contract from Marine Scotland).


Studies of political culture have long emphasized the importance of generalized trust for effective democratic governance. Individual-level models continue to treat generalized trust as a crucial predictor of more democratic political cultures, leading some scholars to suggest that building generalized trust is an important means of developing democratic prerequisites, like the appreciation of democratic values, in the nondemocratic world. In this paper we refute this conventional wisdom, arguing that the democratic utility of trust varies cross-nationally depending on existing levels of democracy within a country. Seldom have existing studies looked at the ways in which levels of generalized trust relate to microlevel indicators of support for democracy while controlling for overall institutional contexts. We argue existing government institutions play an important role in promoting levels of generalized trust because, in democracies and nondemocracies alike, political confidence in existing political in...


Bright small-scale magnetic elements found mainly in intergranular lanes at the solar surface are named bright points (BPs). They show high contrasts in Fraunhofer G-band observations and are described by nearly vertical slender flux tubes or sheets. A recent comparison between BP observations in the ultraviolet (UV) and visible spectral range recorded with the balloon-borne observatory SUNRISE and state-of-the-art magnetohydrodynamical (MHD) simulations revealed a kiloGauss magnetic field for 98% of the synthetic BPs. Here we address the opposite question, namely which fraction of pixels hosting kiloGauss fields coincides with an enhanced G-band brightness. We carried out 3D radiation MHD simulations for three magnetic activity levels (corresponding to the quiet Sun, weak and strong plage) and performed a full spectral line synthesis in the G-band. Only 7% of the kiloGauss pixels in our quiet-Sun simulation coincide with a brightness lower than the mean quiet-Sun intensity, while 23% of the pixels in the weak-plage simulation and even 49% in the strong-plage simulation are associated with a local darkening. Dark strong-field regions are preferentially found in the cores of larger flux patches that are rare in the quiet Sun, but more common in plage regions, often in the vertices of granulation cells. The significant brightness shortfall in the core of larger flux patches coincide with a slight magnetic field weakening. KiloGauss elements in the quiet Sun are on average brighter than similar features in plage regions. Almost all strong-field pixels display a more or less vertical magnetic field orientation. Hence in the quiet Sun, G-band BPs correspond almost one-to-one with kiloGauss elements. In weak plage the correspondence is still very good, but not perfect.


In the early days of Community law the ECJ, still sheltered from political constraints, was able to develop its jurisprudence on the EC fundamental freedoms with a view to enhancing the development of Community law and to advancing the Internal Market. More recently, however, the case law in the field of direct taxation has more and more come into the political limelight as fundamental tax policy questions and billions of tax revenue are at stake. As the Court's decisions also take account of the dynamic evolution of the Community's legal system and are much influenced by considerations of policy and economics, recent case law seems to put more emphasis on a cautious re-balancing of taxpayer rights under the fundamental freedoms and possibilities for Member States to justify restrictive tax measures on the basis of overriding public interest reasons. However, the Court's recent attempts have also warranted criticism from the perspective of legal certainty, due to the potential disregard of legal precedent and the concern that the Court might deviate from general Internal Market principles in this particular area. Against this background, the present contribution aims at systematizing the recent developments and dogmatic approaches underlying the body of case law in the field of direct taxation with respect to (acceptable and unacceptable) justifications of infringements on taxpayer rights to free movement and non discrimination.


Coproduction of knowledge is believed to be an effective way to produce usable climate science knowledge through a process of collaboration between scientists and decision makers. While the general principles of coproduction—establishing long-term relationships between scientists and stakeholders, ensuring two-way communication between both groups, and keeping the focus on the production of usable science—are well understood, the mechanisms for achieving those goals have been discussed less. It is proposed here that a more deliberate approach to building the relationships and communication channels between scientists and stakeholders will yield better outcomes. The authors present five approaches to collaborative research that can be used to structure a coproduction process that each suit different types of research or management questions, decision-making contexts, and resources and skills available to contribute to the process of engagement. By using established collaborative research approaches scientists can be more effective in learning from stakeholders, can be more confident when engaging with stakeholders because there are guideposts to follow, and can assess both the process and outcomes of collaborative projects, which will help the whole community of stakeholder-engaged climate-scientists learn about coproduction of knowledge.


Highly enantioenriched chiral products may be obtained by using a combination of two moderately selective catalysts. Sequential enantioselective transformations comprising an asymmetric reaction followed by a kinetic resolution of the scalemic product mixture obtained in the first step are well known. In such processes, the minor, undesired enantiomer is transformed to a compound that can be more easily separated from the major enantiomer. Although chiral compounds may be obtained with high enantiopurity by such coupled processes, the yield of the desired product necessarily suffers. Recycling processes, whereby the minor enantiomer is transformed to prochiral starting material, avoid this limitation. In this Minireview, different types of sequential catalytic processes using two reinforcing catalysts are surveyed and their advantages and limitations discussed in relation to recycling processes.


The main aim of this thesis is to investigate whether residence near hazardous waste
landfill sites is associated with an increased risk of congenital anomaly. The thesis
reports results of a multi-centre case-control study carried out in 10 regions in 6
European countries. Cases were live births, stillbirths, and induced abortions with major
congenital anomalies resident at birth within a 7 km area around hazardous waste
landfill sites. Controls, two per case, were non-malformed births resident in the same
area. A total of 1089 cases of non-chromosomal anomaly, 270 cases of chromosomal
anomaly, and 2508 controls were selected around 26 landfill sites. A 3 km zone around
sites was defined as the zone of most likely exposure. An expert panel of four landfill
specialists scored each landfill site according to their potential to cause exposure of
nearby residents. A statistically significant 33% excess in risk of non-chromosomal
anomalies was found for living within 3 km of a hazardous waste landfill site. The risk of
non-chromosomal anomaly declined steadily with increasing distance from a site.
Confounding factors or biases do not readily explain these findings. Risk of
chromosomal anomalies was raised near sites but did not reach statistical significance.
There was little evidence for relative risk of congenital anomaly (non-chromosomal or
chromosomal) close to landfill sites to be associated with hazard potential of landfill
sites, adding little support to a possible causal relationship. However, in the absence of
a 'gold-standard' for the classification of hazard potential, misclassification of sites may
have occurred. Lack of information on exposure of residents near the study sites or near
landfill sites in general, limits interpretation of the results. Socio-economic status is a
potential confounding factor in the current study but little is known in the literature about
socio-economic status as a risk factor for congenital anomaly. This study finds a higher
risk of non-chromosomal congenital anomaly and certain specific malformation groups
in more deprived populations. These findings require follow-up in studies with larger
geographical coverage.


The EU protects EU growers of 15 kinds of fresh fruits and vegetables against international competition not only by the means of ad valorem tariffs of up to 20%, but also by the EU entry-price system (EPS), which is designed to restrict imports below the product-specific, politically designated entry price level. This study investigates the influence of the EPS on import prices of fruits and vegetables per product and country of origin. We utilise a unique data set comprising about 60,000 observations of daily synthetic import prices. We develop two indicators for the effectiveness of the EPS, which serve as variables in a cluster analysis identifying four classes differing in the relevance of the EPS. Results suggest that the relevance of the EPS is heterogeneous among products as well as countries of origin for most fruits and vegetables. Thus, an adequate assessment of the importance of the EPS requires not only a product-specific but also a country-specific analysis. Overall, our results indicate that the effectiveness of the EPS is highest for the import of artichokes, courgettes, cucumbers, lemons, plums and tomatoes. The influence of the EPS on apples, clementines and pears is significantly lower, and of least relevance for EU imports of apricots, mandarins, oranges, peaches and nectarines and table grapes. The EPS has the greatest effect on countries which neighbour the EU, whereas it is of minor importance for exports from far-away countries with the exception of China and South Africa.


In Northeast Thailand, about 80% of the 20 million inhabitants are engaged in rainfed agriculture. Climate vagaries combined with coarse-textured sandy and unevenly distributed saline soils explain low agriculture yields and the endemic relative poverty of the population. We conducted an in-depth analysis of change in the rainfall pattern using daily records (1953-2010) from 18 gauging stations scattered across Northeast Thailand. Based on an intimate knowledge of the local farming systems, particularly their strategies to deal with climate variability and their evolution during the past decades, we analyse and discuss how the cropping systems can adapt to the detected rainfall changes. We used the Mann–Kendall trend detection test, modified to account for serial correlation at each individual station, and the regional average Kendall's statistic designed for the detection of regional trends across the entire studied area. On-farm surveys carried out during the past two decades in both the upper and lower parts of Northeast Thailand provide a detailed understanding of the functioning of the agricultural production systems and their diversity. The analysis reveals very limited changes in rainfall frequency, intensity and extremes during the humid monsoon and therefore little change in the existing climatic constraints to agricultural production (early dry spells in the wet season and risk of floods at its peak in September). But we found a significant regional trend toward a wetter dry season that could offer new limited opportunities for agricultural production. The paper will discuss the implications of these findings and compare them with recently published research results. Differences in statistical significance between local and regional rainfall trends are also interpreted. If these trends extend, households would not face many difficulties because of their renowned adaptive capacity built over centuries of facing highly variable rainfall patterns, and due to the diversity of their resilient farming systems. (Texte integral)


Electroporation, is widely used method that can be directly applied to the field of gene therapy. However, very little is known about the basic mechanisms of DNA transfer and cell response to the electric pulse. As a more convenient and effective tool for the investigation on the mechanisms of electroporation and the enhancement of the functional efficiency, we developed a micro-electroporation chip with polydimethylsiloxane (PDMS). Owing to the transparency of PDMS, we could observe the process of Propidium Iodide (PI) uptake in real-time, which shows promise in visualization of gene activity in living cells. Furthermore, the design of the electroporation chip as a microchannel offers advantages in terms of efficiency in permeabilization of PI into SK-OV-3 cells. We also noticed the geometric effect on the degree of electroporation in microchannels with diverse channel width, which shows that the geometry can be another parameter to be considered for the electroporation when it is performed in microchannels.


The capacity of arrayed waveguide gratings (AWGs) has increased dramatically, to the point that as many as 400 channels can now be incorporated into a single wafer. A capacity of 1080 channels with 25-GHz channel spacing has been reported in tandem AWGs with a multichip configuration. Although the total capacity of the transport can be increased to the terabit level by use of wavelength-division multiplexing, signal processing in the electrical layer remains a serious problem because of the limits in electrical signal processing speed. The optical signal processing devices that can play an important role in solving this issue include dispersion slope equalizers, polarization-mode dispersion (PMD), equalizers, temporal pulse shapers, and optical label recognition circuits.


Identification of Cancer-Specific Essential Genes in Glioblastoma Multiforme Christopher G. Hubert Chair of the Supervisory Committee: Professor James M. Olson Pediatrics, Division of Hematology/Oncology, FHCRC Glioblastoma multiforme (GBM) is the most common and aggressive type of brain cancer and is notoriously drug and radiation resistant. Current therapies and trials have repeatedly failed to substantially increase the survival of patients over the last two decades. Although new therapeutic approaches are urgently needed, sophisticated strategies to identify novel GBM therapies have been precluded by several biological and technical barriers. First, established GBM cell lines poorly represent human glioblastoma. Second, powerful gene discovery and manipulation tools were not yet developed or applied to GBM. To overcome these historic challenges, we have applied both focused and genome-wide functional genetic screening techniques to multiple primary glioma stem cell (GSC) cultures that accurately model essential elements of this disease, as well as normal neural stem cells (NSCs). From these unbiased screens, we show that GSCs have an added requirement for the mitotic spindle checkpoint BUB1B to suppress lethal consequences of altered kinetochore function. Specifically, the activity of the Gle2-binding-sequence (GLEBS) domain within BUB1B is required to suppress lethal kinetochore-microtubule attachment defects in GBM isolates and genetically transformed cells. We also identified the pre-mRNA splicing protein PHF5A as a key GSC-specific essential gene. PHF5A knockdown or pharmacologic inhibition of its complex triggers a G2/M arrest in GSCs but not in NSCs or other untransformed cells. We show that PHF5A facilitates recognition of exons with unusual C-rich 3' splice sites and its suppression results in the cancer-specific mis-splicing of thousands of genes. PHF5A suppression compromises GBM tumor formation and maintenance in vivo and results in the regression of established GBM tumors. Rather than being isolated to GSCs, this sensitivity to splicing inhibition is conferred by Ras-mediated transformation of multiple normal cell types, suggesting that a therapy targeting PHF5A may be applicable to a wide range of cancer types.


Wireless Sensor Networks (WSNs) make possible many new applications in a wide range of application domains. Many of these applications are based on a many-to-many communication paradigm in which multiple sensor nodes send their sensed data to multiple sinks. To support these many-to-many applications, this paper proposes an energy-efficient transport protocol in which each source sensor evaluates the multicast costs of various potential multicast trees between it and the destination sinks and then selects the tree with the minimum communication overhead. The simulation results demonstrate that the proposed multicast routing algorithm yields a significant reduction in the total energy consumption, and therefore enables a notable improvement in the network


INTRODUCTION
We undertook a study on a series of laryngeal sarcoidosis (LS), a very rare and often threatening localization to better specify laryngeal manifestations, sarcoidosis clinical expression and long-term follow-up.

METHODS
This was a retrospective case-control study. All LS patients from two French centers were included and compared to sarcoidosis patients without laryngeal localization with two controls for one patient.

RESULTS
Twelve consecutive LS patients were recruited between 1993 and 2011. LS revealed sarcoidosis in eight cases (67%). The most common symptoms were hoarseness (77%), inspiratory dyspnea (38%) and dysphagia (38%). Epidemiological characterisics were not different. Extrapulmonary localizations were significantly more common in LS patients than in controls (92% vs. 54%, p=0.02), particularly lupus pernio (25% vs. 0%, p=0.03) and nasosinusal involvement (83% vs. 4%, p<0.01) while thoracic involvement was less frequent (58% vs 100%, p < 0.01). Treatment rates were higher in the LS group (92% vs. 58%, p=0.04), and treatment duration was longer (median: 81 vs. 13 months, p=0.04), with frequent long-term treatment (67%, N=8/12). Two patients underwent surgery. One patient needed temporary tracheostomy during the course of the disease; Remission rates were lower in LS patients (9% vs. 58% at 2 years p<0.01). Eventually, there was no death nor definitive tracheotomy.

CONCLUSIONS
LS is a rare condition that is often associated to other loco-regional localizations. LS are often difficult to manage. Survival is good but may require a medico-surgical approach.


Pre-Salt development projects continue to expand offshore Brazil into ever deeper waters year after year. Consequently, the required Discharge Pressures for Re-Injection Compressors aboard FPSO's are likely to exceed current 550 bar levels, and requirements for design of higher pressure compressors becomes more severe. This paper presents development of super high pressure compressor and the results of verification tests. Super high pressure compressor can be used as re-injection compressor or injection compressor such as in the CCS plant and FPSO. Rotor stability is the most considerable requirement for super high pressure operation because of the high density flow destabilization force in the compressor. From the point of view of rotor dynamics, the short bearing span and high shaft diameter are desirable for the stability of the rotor. On the other hand, from the point of view of aerodynamics performance, that rotor arrangement may decrease the performance. Some parametric study was conducted to optimize the boss ratio of compressor stage to get both high rotor dynamic stability and high aerodynamic performance. Rotating stall can be the cause of sub-synchronous vibrations in super high pressure operation condition and it induces narrow operation range. To prevent such situation, vaned diffuser was applied for developed compressor stage and it can also help to reduce the diffuser radius space. Seal leakage flow have large effects on the rotor stability and aerodynamic performance. For this item, the hybrid construction of hole pattern seal and step labyrinth seal was proposed. Hole pattern seal is well known as damping seal for high pressure compressor. CFD dynamic analysis and dynamic characteristics test for this hybrid hole pattern seal are introduced under the condition of high density by using hydraulic shaker device. The extensive verification test of developed super high pressure compressor were conducted with impeller of optimized boss ratio, vaned diffuser and hybrid honeycomb seal, and has demonstrated the robustness for all field operation


In 1964, Carl Oglesby, a young copywriter for a Michigan-based defense contractor, was asked by a local Democratic congressman to draft a campaign paper on the Vietnam War. Oglesby's report argued that the conflict was misplaced and unwinnable. He had little idea that its subsequent publication would put him on a fast track to becoming the president of the now-legendary protest movement Students for a Democratic Society (SDS). In this book, Oglesby shares the triumphs and tribulations of an organization that burgeoned across America, only to collapse in the face of surveillance by the U.S. government and infighting.As an SDS leader, Oglesby spoke on the same platform as Coretta Scott King and Benjamin Spock at the storied 1965 antiwar demonstration in Washington, D.C. He traveled to war-ravaged Vietnam and to the international war crimes tribunal in Scandinavia, where he met with Jean-Paul Sartre and Simone de Beauvoir. He helped initiate the Venceremos Brigade, which dispatched thousands of American students to bring in the Cuban sugar harvest. He reluctantly participated in the protest outside the 1968 Democratic National Convention and was a witness for the defense at the trial of the Chicago Seven the following year. Eventually, after extensive battles with those in SDS who saw its future more as a vanguard guerrilla group than as an open mass movement, Oglesby was drummed out of the organization. Shortly after, it collapsed when key members of its leadership quit to set up the Weather Underground.This beautifully written and elegiac memoir is rich in contemporary echoes as America once again must come to terms with an ill-conceived military adventure abroad. Carl Oglesby warns of the destructive frustrations of a peace campaign unable to achieve its goals. But above all, he captures the joyful liberation of joining together to take a stand for what is right and just -- the soaring and swooping of a protest movement in full flight, like ravens in a storm.


This paper presents a literature review of research into interventions with people with medically unexplained symptoms (MUS). The review forms the basis for the research questions, provides a rationale for an innovative approach (The BodyMind Approach/BMA) to intervention for patients with anxiety/depression with MUS and justification for the most suitable methodology for the pilot study. An overview of the problem is provided as backdrop to the rationale. Patients with MUS make up a substantial percentage of all primary care (PC) consultations, are notoriously difficult to treat and make huge demands on resources. A pilot study took place in the National Health Service (NHS) in the UK between 2004 and 2007 receiving full NHS ethical approval for delivery in PC. Following on from the systematic search of the literature the argument for, and description of, the BMA (based on the discipline Authentic Movement from within the field of Dance Movement Psychotherapy) to group psychotherapy is presented. The intervention emphasises learning in a verbal and non-verbal-integrated approach, encouraging an awareness of the inter-relationship between body, self and mind. It uses meditative, mindful movement deriving from natural body gestures and posture, relaxation, massage promoting movement metaphor to change beliefs and to understand the meaning of the symptoms within a self-managing framework. The symptom is seen as a metaphor for connections between body, self and mind. It is founded on the principle that bodily experience can be an avenue for meaning-making in personal development leading to increased well-being; better coping strategies; changes in perception of the body-felt sense and improved lifestyle choices and behaviours. The research sought to answer a number of questions concerning the intervention such as benefits, process and outcomes from the perspective of participants and the facilitator. The methodology selected was mixed, using both qualitative (analysis of pre, post and follow-up interviews with participants and facilitator's process recordings); and quantitative whereby standardised outcome measures were completed by patients pre/during/post intervention and at follow-up. Medication, secondary referral and GP visits were also quantified pre/post-intervention and at follow-up. Findings supported the hypothesis, and went beyond it, revealing a reduction in, and disappearance of, symptoms to a significant effect.


With this present study, the improvements-carried out in the science education in Turkeywere investigated for the first time considering the science education policies of the European Union (EU)The participant views were taken into consideration on the science improvements carried out according to the EU education policies. With this purpose, science teachers, the personnel of the national education in a medium province in the Region of Eastern Anatolia, and administrative personnel were chosen to constitute the universe of the research. Mixed method was applied during the research. A Likert type questionnaire including 10 questions was conducted to the participants to learn their thoughts about the EU science education policies as the quantitative method. In the qualitative method, open-ended questions including 8 items for each were asked to the participants. According to the result of the study, when the collected data were evaluated, it was found out that most of the participants were ignorant of the EU policies, few numbers of the individuals constituting the sampling were informed about these policies; but, they thought that it would be more appropriate to take and implement policies in accordance with our national values. When the qualitative data were evaluated, it was expressed that some improvements were conducted in the science education lessons compared with the previous programs; but, that was insufficient.


This paper presents a low power, cost-effective, And Zigbee protocol based wireless sensor network that provides an intelligent surveillance and safety system for underground coal mines. The system consists of wireless connection of several nodes. Sensor node mainly consists of Zigbee protocol based low power CC2530 transceiver integrated with a high performance, low power microcontroller on single chip. This integrated chip connected through RF connector on smartRF05 Battery Board. This small size, low power device is easily interfaced with desired miniature size sensors. Wireless sensor nodes join to other sensor node in specific multihop mesh network topology, that creates a Zig8ee based wireless sensor network. This network can be easily placed in underground mines and it provides an effectively surveillance and safety system for underground coal miners. Especially, it provides the real-time data communication between miners and surface control room through highly secure, reliable wireless sensor nodes. The proposed system improves the existing miner's safety and early warning surveillance in underground coal mines


A constant research of more ecological and efficient structures has enabled bridges to be more innovative through the years. Nowadays, as the need is greater than ever, a new kind of bridge is expanding in the entire world: the network arch bridges. The concept was developed by professor and engineer Per Tveit in 1955 and has been improved since then. But it is only for 10 years that many bridges of this sort have been built. The aim of the thesis is to investigate the structural behavior of these bridges and their efficiency comparing to traditional bridges. It is also proving the efficiency of the network arches used for rail traffic. To do so, a single-track railway network arch has been designed according to the Eurocodes. A 2D model has been designed to be optimal and tested under Abaqus for the loads defined in the Eurocodes. Guidelines from the literature and Per Tveit's work have been used to determine the optimal geometry of the bridge. The steel weight needed for the 75 meters long bridge is assessed from the final design and is the main parameter to compare and evaluate the network arch structural efficiency. These results are compared with Tveit's statements and with other structures.


Derived from a more ambitious international youth justice research project, this article aims to critically interrogate the direction of contemporary youth justice policy in England and Wales and the political priorities that underpin it. By rethinking youth justice on the basis of comparative analysis, international human rights and research evidence, we challenge the current policy trajectory and offer an alternative formulation: a youth justice with integrity.


Identifying driver mutations and their functional consequences is critical to our understanding of cancer. Towards this goal, and because domains are the functional units of a protein, we explored the protein domain-level landscape of cancer-type-specific somatic mutations. Specifically, we systematically examined tumor genomes from 21 cancer types to identify domains with high mutational density in specific tissues, the positions of mutational hotspots within these domains, and the functional and structural context where possible. While hotspots corresponding to specific gain-of-function mutations are expected for oncoproteins, we found that tumor suppressor proteins also exhibit strong biases toward being mutated in particular domains. Within domains, however, we observed the expected patterns of mutation, with recurrently mutated positions for oncogenes and evenly distributed mutations for tumor suppressors. For example, we identified both known and new endometrial cancer hotspots in the tyrosine kinase domain of the FGFR2 protein, one of which is also a hotspot in breast cancer, and found new two hotspots in the Immunoglobulin I-set domain in colon cancer. Thus, to prioritize cancer mutations for further functional studies aimed at more precise cancer treatments, we have systematically correlated mutations and cancer types at the protein domain level.


Eigen-decomposition remains one of the most invaluable tools for signal processing algorithms. Although traditional algorithms based on QR decomposition, Jacobi rotations and block Lanczos tridiagonalization have been proposed to decompose a matrix into its eigenspace, associated computational expense typically hinders their implementation in a real-time framework. In this paper, we study recursive eigen perturbation (EP) of the symmetric eigenvalue problem of higher order (greater than one). Through a higher order perturbation approach, we improve the recently established first-order eigen perturbation (FOP) technique by creating a stabilization process for adapting to ill-conditioned matrices with close eigenvalues. Six algorithms were investigated in this regard: first-order, second-order, third-order, and their stabilized versions. The developed methods were validated and assessed on multiple structural health monitoring (SHM) problems. These were first tested on a five degrees-of-freedom (DOF) linear building model for accurate estimation of mode shapes in an automated framework. The separation of closely spaced modes was then demonstrated on a 3DOF + tuned mass damper (TMD) problem. Practical utility of the methods was probed on the Phase-I ASCE-SHM benchmark problem. The results obtained for real-time mode identification establishes the robustness of the proposed methods for a range of engineering applications.


Over the past number of months, the proposed new law school at Trinity Western University (TWU) has come under signifi cant attack, including by many whom I count as academic colleagues within the Canadian Association of Law Teachers and by many within the Canadian law school community more generally. Th ese attacks have had the unique eff ect of subjecting TWU's law school to a diff erent approval process than has been used for any other Canadian law school, with a dual-committee structure to apply additional scrutiny to it.2 Some have put their attacks explicitly in longer forms,3 and many others have signed petitions against TWU.


This paper describes VIRMANEL, a new, open source (LGPL) tool that we developed to run experiments and evaluate protocols and algorithms on mobile multihop networks using real software and real operating systems. VIRMANEL comprises an integrated domain-specific language to define new mobility models, a Graphical User Interface to study the behavior of mobiles nodes and a controller engine that emulates a multihop mobile network by setting firewall rules between virtual machines to define network connectivity. Designed to work with OpenVZ, an efficient operating system-level virtualization tool, VIRMANEL combines ease of use and efficiency by enabling the study of large networks distributed over multiple physical machines.


BACKGROUND
This double-blind, placebo-controlled, flexible-dose study was conducted to investigate the efficacy and tolerability of the controlled-release (CR) formulation of paroxetine in adults with social anxiety disorder.

METHOD
Outpatients with a primary diagnosis of social anxiety disorder according to DSM-IV criteria entered a 1-week, single-blind, placebo run-in period. Eligible patients were randomly assigned to receive paroxetine CR (flexible dose of 12.5-37.5 mg/day) or placebo for 12 weeks of treatment. The primary efficacy measures were the change from baseline in Liebowitz Social Anxiety Scale (LSAS) score and the proportion of responders based on Clinical Global Impressions (CGI)-Global Improvement scale score. Data were gathered from September 2001 to July 2002.

RESULTS
The intent-to-treat population consisted of 186 patients randomly assigned to paroxetine CR and 184 patients randomly assigned to placebo. Statistically significant differences in favor of paroxetine CR compared with placebo were observed in the change from baseline to week 12 last-observation-carried-forward (LOCF) dataset in LSAS total score (difference = -13.33, 95% confidence interval [CI] = -18.25 to -8.41, p <.001). In the CGI-Global Improvement responder analysis, 57.0% of patients treated with paroxetine CR achieved response (very much improved or much improved), compared with 30.4% of patients treated with placebo at week 12 LOCF (odds ratio = 3.12, 95% CI = 2.01 to 4.83, p <.001). Dropout rates due to adverse events were low and comparable in both treatment groups.

CONCLUSION
Paroxetine CR effectively treated the symptoms associated with social anxiety disorder and was well tolerated, with few patients stopping treatment due to adverse events. This favorable tolerability profile may enable more patients to experience the benefits of effective therapy.


This study examines the effects of gender, ethnicity, and work experience on college students' credit card debt and reveals that ethnicity, gender, and work experience are important factors affecting the amount of college students' credit card debt. Male students tend to have more credit card debt than female students, whereas students without work experience tend to accrue more credit card debt than students with work experience. Hispanic and African-American students tend to accumulate more credit card debt than Caucasian, Asian, Pacific-Islander, and other students. More important, the three-way interaction effect shows that African-American male students with work experience and Hispanic female students without work experience tend to amass the highest levels of credit card debt. Financial educators and wealth advisors should encourage responsible behavior, such as reducing existing debt, among these vulnerable groups of college students. They should also ensure that effective educational programs on using credit cards are available to college students and that the educational programs enhance their financial learning and experience of using credit cards.


The deployment of multi-antenna systems with software defined reconfigurable beam patterns can potentially benefit vehicle-to-vehicle (V2V) communications by increasing the channel coherence time. This in turn necessitates an accurate characterization and modeling of the angular statistics of vehicular radio propagation environments. This work proposes an improved three-dimensional (3-D) spatial description of vehicular propagation environments and derives the closed-form analytical expressions for the joint and marginal statistics of the 3-D angle-of-arrival (AoA) and angle-of-departure (AoD). Then, based on the proposed geometric channel model, the AoA and AoD angular spreads are quantified in terms of the joint angular spread, elevational constriction, and the azimuthal constriction. These considered quantifiers are shown to be of high significance in quantification of angular spread in V2V radio propagation environments. The impact of various physical parameters on the angular spread is also investigated. These parameters include the link-distance, scattering volume, and the number of scatterers along the azimuth and elevation axes. The derived analytical expressions are also validated by simulations.


The lack of association between wealth and fertility in contemporary industrialized populations has often been used to question the value of an evolutionary perspective on human behaviour. Here, we first present the history of this debate, and the evolutionary explanations for why wealth and fertility (the number of children) are decoupled in modern industrial settings. We suggest that the nature of the relationship between wealth and fertility remains an open question because of the multi-faceted nature of wealth, and because existing cross-sectional studies are ambiguous with respect to how material wealth and fertility are linked. A literature review of longitudinal studies on wealth and fertility shows that the majority of these report positive effects of wealth, although levels of fertility seem to fall below those that would maximize fitness. We emphasize that reproductive decision-making reflects a complex interplay between individual and societal factors that resists simple evolutionary interpretation, and highlight the role of economic insecurity in fertility decisions. We conclude by discussing whether the wealth–fertility relationship can inform us about the adaptiveness of modern fertility behaviour, and argue against simplistic claims regarding maladaptive behaviour in humans.


Procedural representations provide powerful means for generating complex geometric structures. They are also notoriously difficult to control. In this article, we present an algorithm for controlling grammar-based procedural models. Given a grammar and a high-level specification of the desired production, the algorithm computes a production from the grammar that conforms to the specification. This production is generated by optimizing over the space of possible productions from the grammar. The algorithm supports specifications of many forms, including geometric shapes and analytical objectives. We demonstrate the algorithm on procedural models of trees, cities, buildings, and Mondrian paintings.


This paper attempts to present a comprehensive and coherent picture of the role performed by science under the Sanitary and Phytosanitary Measures (SPS) Agreement and SPS case law. It argues that the approach adopted by the Appellate Body is predominantly based on a technical paradigm, supplemented, however, with some considerations arising from other paradigms. The paper argues that the approach adopted in the case law is generally compatible with the text of the SPS Agreement and provides a coherent SPS system. However, it also identifies certain areas which lack coherence, as certain standards seem to violate the right of the member states to establish an appropriate level of protection. These are: ascertainability of the risk as a precondition for valid risk assessment; strict specificity of the risk assessment in low-risk situations; the proportionality between the risk identified and the SPS measure; the notion of negligible risks; and the concept of likelihood in the quarantine risk assessments. The paper claims that these standards cannot be generally applied in SPS disputes as, in certain situations, they will result in the violation of the right of member states to establish an appropriate level of SPS protection. Finally, a number of specific issues are highlighted which require further clarification in case law, such as the issue of the quality of minority scientific opinions and the relationship between the insufficiency of scientific evidence and scientific uncertainty. The paper suggests that the ultimate role ascribed to science under the SPS Agreement can be assessed only after an interpretation of those issues is provided by future case law.


In seismic data processing, attenuation of random noise is the basic step to improve quality of data for further application of seismic data in exploration and development in different gas and oil industries. The signal-to-noise ratio of the data also highly determines quality of seismic data. This factor affects the reliability as well as the accuracy of seismic signal during interpretation for different purposes in different companies. To use seismic data for further application and interpretation, we need to improve the signal-to-noise ration while attenuating random noise effectively. To improve the signal-to-noise ration and attenuating seismic random noise by preserving important features and information about seismic signals, we introduce the concept of anisotropic total fractional order denoising algorithm. The anisotropic total fractional order variation model defined in fractional order bounded variation is proposed as a regularization in seismic denoising. The split Bregman algorithm is employed to solve the minimization problem of the anisotropic total fractional order variation model and the corresponding denoising algorithm for the proposed method is derived. We test the effectiveness of theproposed method for synthetic and real seismic data sets and the denoised result is compared with F-X deconvolution and non-local means denoising algorithm. Keywords—Anisotropic total fractional order variation, fractional order bounded variation, seismic random noise attenuation, Split Bregman Algorithm.


Background The huge proportion of child marriage contributes to high rates of pregnancies among adolescent girls in Bangladesh. Despite substantial progress in reducing maternal mortality in the last two decades, the rate of adolescent pregnancy remains high. The use of skilled maternal health services is still low in Bangladesh. Several quantitative studies described the use of skilled maternal health services among adolescent girls. So far, very little qualitative evidence exists about attitudes and practices related to maternal health. To fill this gap, we aimed at exploring maternal health care-seeking behavior of adolescent girls and their experiences related to pregnancy and delivery in Bangladesh. Methods and Findings A prospective qualitative study was conducted among thirty married adolescent girls from three Upazilas (sub-districts) of Rangpur district. They were interviewed in two subsequent phases (2014 and 2015). To triangulate and validate the data collected from these married adolescent girls, key informant interviews (KIIs) and focus group discussions (FGDs) were conducted with different stakeholders. Data analysis was guided by the Social-Ecological Model (SEM) including four levels of factors (individual, interpersonal and family, community and social, and organizational and health systems level) which influenced the maternal health care-seeking behavior of adolescent girls. While adolescent girls showed little decision making-autonomy, interpersonal and family level factors played an important role in their use of skilled maternal health services. In addition, community and social factors and as well as organizational and health systems factors shaped adolescent girls' maternal health care-seeking behavior. Conclusions In order to improve the maternal health of adolescent girls, all four levels of factors of SEM should be taken into account while developing health interventions targeting adolescent girls.


A correlated inhomogeneous mean-field approach is proposed in order to study a tight-binding model of the manganite heterostructures (LaMnO3)2n/(SrMnO3)n with average hole doping x = 1/3. Phase diagrams, spectral and optical properties of large heterostructures (up to 48 sites along the growth direction) with a single interface are discussed analyzing the effects of electron-lattice anti-adiabatic fluctuations and strain. The formation of a metallic ferromagnetic interface is quite robust with varying the strength of electron-lattice coupling and strain, though the size of the interface region is strongly dependent on these interactions. The density of states never vanishes at the chemical potential due to the formation of the interface, but it shows a rapid suppression with increasing the electron-lattice coupling. The in-plane and out-of-plane optical conductivities show sharp differences since the in-plane response has metallic features, while the out-of-plane one is characterized by a transfer of spectral weight to high frequency. The in-plane response mainly comes from the region between the two insulating blocks, so that it provides a clear signature of the formation of the metallic ferromagnetic interface.


In this paper, we present the design of a novel waveguide structure capable of multifrequency transmission bands with strongly enhanced electric field states. The concept of the structure is based on aperiodic and quasi-periodic fractal ordering of scattering subunits combined within a traditional channel-waveguide scheme. The resulting 3-D fractal waveguides are characterized by complex transmission spectra and sustain quasi-localized field modes with strong enhancement effects due to the lack of translational symmetry. In this paper, we will describe how it is possible to accurately model these complex waveguide structures within a simple 1-D model. We will explore the formation of photonic band gaps and the character of the quasi-localized states in fractal waveguide structures generated according to different deterministic rules, such as Fibonacci, Thue-Morse, and Rudin-Shapiro sequences. Furthermore, we will qualitatively compare the characteristics of the optical gaps and field states in periodic, fractal, and aperiodic waveguides. The results of our comparative study will show that fractal waveguides based on aperiodic order exhibit the richest transmission spectra with field-enhancement effects occurring at multiple frequencies. The proposed fractal waveguide design can provide an attractive route toward the fabrication of optically active devices for multiwavelength operation.


Abstract A critical review of published studies investigating the dielectric barrier discharge (DBD) treatment of four polymers widely employed in the packaging sector, namely: polyethylene (PE), polypropylene (PP), poly(ethylene terephthalate) (PET) and polystyrene (PS) is presented. The DBD treatment process operates at atmospheric pressure in air, and thereby offers a low cost method of enhancing the surface properties of polymers. The method is suitable for high volume in-line applications such as packaging. It has been reported that treatment doses as low as 0.01 J/cm2 result in significant increases in surface energy and wettability, leading to enhanced adhesive bonding and printing performance. Two critical issues limit the improvements obtained via the DBD processing of polymers. Firstly, DBD processing can produce a poorly adhered surface layer of low molecular weight material, which can then interfere with bonding and printing processes. Secondly, the properties of DBD treated polymers tend to revert towards that of the untreated state during storage.


—Recent advances in media-related technologies, in- cluding capturing and processing, have facilitated novel forms of 3D media content, increasing the degree of user immersion. In order to ensure these technologies can readily support the rising demand for more captivating entertainment, both the production and delivery mechanisms should be transformed to support the application of media or network-related optimiza- tions and refinements on-the-fly. Network peculiarities deriving from geographic and other factors make it difficult for a greedy or a supervised machine learning algorithm to successfully foresee the need for reconfiguration of the content production or delivery procedures. For these reasons, Reinforcement Learning (RL) approaches have lately gained popularity as partial information on the environment is enough for an algorithm to begin its training and converge to an optimal policy. The contribution of this work is a Cognitive Network Optimizer (CNO) in the form of an RL agent, designed to perform corrective actions on both the production and consumption ends of an immersive 3D media platform, depending on a collection of real-time monitoring parameters, including infrastructure, application-level and quality of experience (QoE) metrics. Our work demonstrates CNO approaches with different foci, i.e., a greedy maximization of the users' QoE, a QoE-focused RL approach and a combined QoE-and-Cost RL approach.


The name of John Calvin is frequently associated with the doctrine of predestination. Published in 1552 to counteract the criticisms and contrary views being taught by others, this work shows Calvin rigorously defending his controversial position. Readers will witness Calvin masterfully arguing his points, wrestling with scriptures, and fully engaged in the rough-and-tumble polemical world of sixteenth-century theological debate.


This paper investigates the association between executive compensation and performance. It uniquely utilises a comprehensive set of corporate governance mechanisms within a three‐stage least squares (3SLS) simultaneous equation framework. Results based on estimating a conventional single equation model indicate that the executive pay and performance sensitivity is relatively weak, whereas those based on estimating a 3SLS model generally suggest improved executive pay and performance sensitivity. Our findings highlight the need for future research to control for possible simultaneous interdependencies when estimating the executive pay and performance link. The findings are generally robust across a raft of econometric models that control for different types of endogeneities, executive pay and performance proxies. Copyright © 2013 John Wiley & Sons, Ltd.


Digital Linguistics (DL) is an interdisciplinary study that identifies human language as a digital evolution of mammal analog vocal sign communications, founded on the vertebrate spinal sign reflex mechanism [Tokumaru 2017 a/b, 2018 a/b/c/d]. Analog signs are unique with their physical sound waveforms but limited in number, whilst human digital word signs are infinite by permutation of their logical property, phonemes. The first digital evolution took place 66,000 years ago with South African Neolithic industries, Howiesons Poort, when linguistic humans acquired a hypertrophied mandibular bone to house a descended larynx for vowel accented syllables containing logical properties of phonemes and morae. Morae made each syllable distinctive in the time axis and enabled grammatical modulation by alternately transmitting conceptual and grammatical syllables. The sign reflex mechanism is an unconscious self-protection and life-support mechanism, operated by immune cell networks inside the ventricle system. DL identified cellular and molecular structures for the sign (=concept) device as a B lymphocyte (or, in other words, Mobile Ad-Hoc Networking Neuron), connects to sensory, conceptual and networking memories, which consist of its meanings [Table 1]. Its antibodies can network with antigens of CSF-Contacting Neurons at the brainstem reticular formation and of Microglia cells at the neocortex [Figure 1]. It is plausible that the 3D structure of the antigen molecule takes the shape of word sound waveform multiplexing intensity and pitch, and that specifically pairing the antibody molecule consists of three CDRs (Complementality Defining Regions) in the Antibody Variable Region network with the logic of dichotomy and dualism. As sign reflex deals with survival issues such as food, safety and reproduction, it is stubborn, passive and inflexible: It does not spontaneously look for something new, and it is not designed to revise itself. These characteristics are not desirable for the development of human intelligence, and thus are to be overcome. All the word, sensory and network memories in the brain must be acquired postnatally through individual learning and thought. The reason and intelligence of humans depend on how correctly and efficiently humans learn new words and acquire appropriate meanings for them.


Developed more than a century ago, the potential of vacuum sewerage systems remains underexploited. At the same time, the rapid urbanization in Asia brings about major challenges for municipal utilities. In this context, the GIZ (Deutsche Gesellschaft fuer Internationale Zusammenarbeit) project 'Integrated Resource Management in Asian Cities: the Urban Nexus' gives technical advice to stakeholders in the partner cities. Fraunhofer IGB, having operated a vacuum sewer system for more than ten years in the context of a research project, carried out a survey regarding current experiences with vacuum sewer systems and the transferability to countries of the Global South. In an environment with existing infrastructure, it is often not economically reasonable to install an additional sewer system. Nevertheless, with aging infrastructure and an increasing importance of circular economy concepts including water reuse, nutrient recovery and biogas generation, vacuum sewers can pose a viable alternative for refurbishments or new developments in semi-decentralized sanitation approaches involving local treatment and resource recovery.


Endocannabinoids and some phytocannabinoids bind to CB1 and CB2 cannabinoid receptors, transient receptor potential vanilloid one (TRPV1) receptor and the orphan G protein receptor fifty-five (GPR55). Studies using C57BL/10 and C57BL/6 (Cnr2 tm1Zim) CB2 cannabinoid receptor knockout mice have demonstrated an immune-augmenting effect in experimental autoimmune encephalomyelitis (EAE) models of multiple sclerosis. However, other EAE studies in Biozzi ABH mice often failed to show any treatment effect of either CB2 receptor agonism or antagonism on inhibition of T cell autoimmunity. The influence of genetic background on the induction of EAE in endocannabinoid system-related gene knockout mice was examined. It was found that C57BL/6.GPR55 knockout mice developed less severe disease, notably in female mice, following active induction with myelin oligodendrocyte glycoprotein 35-55 peptide. In contrast C57BL/6.CB2 (Cnr2 Dgen) receptor knockout mice developed augmented severity of disease consistent with the genetically and pharmacologically-distinct, Cnr2 tm1Zim mice. However, when the knockout gene was bred into the ABH mouse background and EAE induced with spinal cord autoantigens the immune-enhancing effect of CB2 receptor deletion was lost. Likewise CB1 receptor and transient receptor potential vanilloid one knockout mice on the ABH background demonstrated no alteration in immune-susceptibility, in terms of disease incidence and severity of EAE, in contrast to that reported in some C57BL/6 mouse studies. Furthermore the immune-modulating influence of GPR55 was marginal on the ABH mouse background. Whilst sedative doses of tetrahydrocannabinol could induce immunosuppression, this was associated with a CB1 receptor rather than a CB2 receptor-mediated effect. These data support the fact that non-psychoactive doses of medicinal cannabis have a marginal influence on the immune response in MS. Importantly, it adds a note of caution for the translational value of some transgenic/gene knockout and other studies on low-EAE susceptibility backgrounds with inconsistent disease course and susceptibility.


Most existing models of Stackelberg security games ignore the underlying topology of the space in which targets and defence resources are located. As a result, allocation of resources is restricted to a discrete collection of exogenously defined targets. However, in many practical security settings, defense resources can be located on a continuous plane. Better defense solutions could therefore be potentially achieved by placing resources in a space outside of actual targets (e.g., between targets). To address this limitation, we propose a model called Security Game on a Plane (SGP) in which targets are distributed on a 2-dimensional plane, and security resources, to be allocated on the same plane, protect targets within a certain effective distance. We investigate the algorithmic aspects of SGP. We find that computing a strong Stackelberg equilibrium of an SGP is NP-hard even for zero-sum games, and these are inapproximable in general. On the positive side, we find an exact solution technique for general SGPs based on an existing approach, and develop a PTAS (polynomial-time approximation scheme) for zero-sum SGP to more fundamentally overcome the computational obstacle. Our experiments demonstrate the value of considering SGP and effectiveness of our algorithms.


Malonyl-thioesters are reactive at the thioester
carbonyl and the carboxylate moieties, as seen in acyl transfer or hydrolysis
and decarboxylation. Enzymes use these reactive centers to perform different
enzyme chemistry throughout metabolism. This enzyme chemistry coupled with the
inherent reactivity of malonyl-thioesters makes structure-function studies
difficult. When malonyl-thioesters are used for structure-function studies, it
usually results in a hydrolyzed or decarboxylated product. There are examples,
however, where this is overcome, many of which are discussed throughout this
thesis. To overcome the inherent reactivity of malonyl-thioesters and enzymes,
analogs have been synthesized to perform structure-function studies. Initial
studies focused on altering the thioester carbonyl to limit hydrolysis and
decarboxylation; however, these studies revealed the importance of retaining
the thioester carbonyl to be positioned in the oxyanion hole. My thesis work
focused on the synthesis, characterization, and use in structure-function
studies of malonyl-thioester analogs that either preserve the thioester
carbonyl or alter it to an ester or amide, and alter the carboxylate to a
sulfonate or nitro group. After synthesizing the methylmalonyl-CoA analogs, we
performed structure-function studies with methylmalonyl-CoA decarboxylase. This
case study revealed the potential of these analogs to both inhibit
decarboxylase activity and their use in structure-function studies to gain
mechanistic insights. This successful study prompted us to continue these
structure-function studies in enzymes with different chemistries such as an
epimerase or bi-functional acyltransferase/decarboxylase. The widespread use of
these methylmalonyl-CoA analogs also motivated us to add more malonyl-thioester
analogs to our toolbox. I have preliminary data that these malonyl-thioester
analogs inhibit β-keto-acyl-synthase III, an enzyme involved in fatty acid
production in E. coli. This
inhibition gives us confidence that these analogs will be useful in
structure-function studies that will reveal answers to long standing mechanism
and protein-protein interaction questions in the polyketide and fatty acid
synthase field.


Supercomputers have seen an exponential increase in their size in the last two decades. Such a high growth rate is expected to take us to exascale in the timeframe 2018-2022. But, to bring a productive exascale environment about, it is necessary to focus on several key challenges. One of those challenges is fault tolerance. Machines at extreme scale will experience frequent failures and will require the system to avoid or overcome those failures. Various techniques have recently been developed to tolerate failures. The impact of these techniques and their scalability can be substantially enhanced by a parallel programming model called migratable objects. In this paper, we demonstrate how the migratable-objects model facilitates and improves several fault tolerance approaches. Our experimental results on thousands of cores suggest fault tolerance schemes based on migratable objects have low performance overhead and high scalability. Additionally, we present a performance model that predicts a significant benefit of using migratable objects to provide fault tolerance at extreme scale.


In this paper, we explore the links between pension reform, early retirement, and the use of
unemployment as an alternative pathway to retirement. We use a dynamic rational expectations
model to analyze the search and retirement behaviour of employed and unemployed workers aged
50 or over. The model is calibrated to reproduce the main reemployment and retirement patterns
observed between 2002 and 2008 in Spain. It is subsequently used to analyze the effects of the
2011 pension reform in Spain, characterized by two-year delays in both the early and the normal
retirement ages. We find that this reform generates large increases in labour supply and sizable cuts
in pension costs, but these are achieved at the expense of very large welfare losses, especially among
unemployed workers. As an alternative, we propose leaving the early retirement age unchanged,
but penalizing the minimum pension (reducing its generosity in parallel to the cuts imposed on
individual pension benefits, and making it more actuarially fair with age). This alternative reform
strikes a better balance between individual welfare and labour supply stimulus.


The Akt family of protein kinases is involved in mediating cell survival signals, and cancers are often associated with mutations in genes encoding negative regulators of Akt activity, such as the lipid phosphatase PTEN. Activation of Akt involves recruitment to the plasma membrane, followed by phosphorylation by activating kinases. Cinar et al. report that the kinases Mst1 and Mst2 inhibit Akt activity in a mechanism that is independent of the kinase activity of Mst. Fractionation of lipid rafts (Triton X-100-insoluble membranes) showed that ~10% of Akt1 was present in this compartment in the prostate cancer cell line LNCaP (a PTEN-deficient cell line in which Akt1 is constitutively active), and coimmunoprecipitation followed by mass spectrometry analysis revealed that Mst1 (also known as STK4) was in a complex with Akt1 in this compartment. The interaction appeared to be direct in that purified proteins interacted. Mst1 is cleaved by caspase into a C-terminal domain containing the regulatory region (Mst1-C) and a N-terminal domain containing the kinase domain (Mst1-N). Full-length Mst1, Mst1-C, and Mst1-N interacted with a tagged form of Akt1 when overexpressed in HEK 293T cells. A kinase-inactive form of the Mst1-N also interacted with Akt1, suggesting that kinase activity was not required for the interaction. All three forms of Mst1 interacted with the C-terminal hydrophobic domain of Akt1 based on experiments with Akt1 mutants. Proteins expressed in transfected cells [Mst1, Mst1-N, and Mst1-C and GFP-Myr-Akt1 (myristoylated and tagged with green fluorescent protein)] and in LNCaP cells (endogenous phosphorylated Akt1 and transfected Mst1-N and Mst1-C) showed that although the full-length Mst1 and Mst1-C colocalized with Akt1 at the plasma membrane and cytoplasm, Mst1-N did not colocalize with Akt1 at the membrane; instead, in the LNCaP cells it colocalized with Akt1 in the nucleus. RNA interference experiments with LNCaP cells showed that depletion of either Mst1 or the related protein Mst2 enhanced Akt1 activity, whereas overexpression of the Mst proteins inhibited Akt1 activity. Expression of Mst1, Mst1-C, Mst1-N, or the kinase-inactive Mst1-N reverted a gastrulation defect induced by expression of constitutively active Akt (Myr-Akt1) in zebrafish embryos, further confirming the negatively regulatory role of Mst. Finally, immunohistochemical analysis of a human prostate cancer tissue array showed that tissues with the highest levels of activated Akt had the lowest levels of Mst1, suggesting that loss of this inhibitory input may be clinically relevant during cancer progression. B. Cinar, P.-K. Fang, M. Lutchman, D. Di Vizio, R. M. Adam, N. Pavlova, M. A. Rubin, P. C. Yelick, M. R. Freeman, The pro-apoptotic kinase Mst1 and its caspase cleavage products are direct inhibitors of Akt1. EMBO J. 26, 4523-4534 (2007). [PubMed]


The dissolved organic phosphorus (DOP) pool in marine waters contains a variety of different compounds. Knowledge of the distribution and utilization of DOP by phyto- and bacterioplankton is limited, but critical to our understanding of the marine phosphorus cycle. In the Baltic Sea, detailed information about the composition of DOP and its turnover is lacking. This study reports the concentrations and uptake rates of DOP compounds, namely, adenosine triphosphate (dATP), deoxyribonucleic acid (dDNA), and phospholipids (dPL), in the Baltic Proper and in Finnish coastal waters in the summers of 2011 and 2012. Both areas differed in their dissolved inorganic phosphorus (DIP) concentrations (0.16 and 0.02–0.04 μM), in the C:P (123–178) and N:P (18–27) ratios, and in abundances of filamentous cyanobacteria and of autotrophic and heterotrophic picoplankton. The mean concentrations of dATP-P, dDNA-P, and dPL-P were 4.3–6.4, 0.05–0.12, and 1.9–6.8 nM, respectively, together contributing between 2.4 and 5.2% of the total DOP concentration. The concentrations of the compounds varied between and within the investigated regions and the distribution patterns of the individual components are not linked to each other. DIP was taken up at rates of 10.1–380.8 nM d-1. dATP-P and dDNA-P were consumed simultaneously with DIP at rates of 6.9–24.1 and 0.09–0.19 nM d-1, respectively, with the main proportion taken up by the size fraction <3 μm and with DIP to be the dominant source. Groups of hydrographical and biological parameters were identified in the multiple regression analysis to impact the concentrations and uptake rates. It points to the complexity of the regulation. Our results indicate that the investigated DOP compounds, particularly dATP-P, can make significant contributions to the P nutrition of microorganisms and their use seems to be not intertwined. Therefore, more detailed knowledge of all DOP components including variation of concentrations and the utilization is required to understand the roles of DOP in marine ecosystems.


Various commentators have written on the conditions contributing to an increasing interest in professional doctorates, both in the UK and Australia, with many attributing this, at least in part, to the emergence of the knowledge economy and shifts from Mode 1 to Mode 2 knowledge production (Lester, 2004; Scott, Brown, Lunt, & Thorne, 2004; Usher, 2002). The emphasis in recent government policy in the UK on university-industry collaborations, both in research and teaching and learning (BIS, 2009; CBI, 2008), as well as an emerging literature on the co-production of knowledge for action (Antonacopoulou, 2009) suggest that professional doctorates will continue to be of interest as a way of organising doctoral education in the UK. However, as Usher (2002) has pointed out, the intertwining of governments, universities and workplaces in innovation processes is not always unproblematic.
Research is currently being undertaken at a UK HE institution exploring the question of 'what counts as learning, and for whom, in a professional doctorate'? This question links with a broader interest in the politics of work based learning and an exploration of power relations in the production, distribution and consumption of practice-based knowledges. We contend that the professional doctorate provides a rich research site for examining intersections between workplace discourses and discourses of Higher Education. The conceptual framework underpinning the study is Foucauldian poststructuralist theory, which draws attention to relationships between language, power, social institutions and subjectivity (Weedon, 1987). We are exploring alignments and contestations around what counts as knowledge and how it might be produced for different players in the field of Work Based Learning (WBL) including professional doctorate candidates, WBL academics and examiners of professional doctorates. The overall study includes the collection and analysis of various texts including: electronic copies of research projects undertaken as a major component of a Professional Doctorate Award; the Module Handbook provided to candidates which provides a guide to candidates completing the research component of their award; interviews with Module tutors and advisers working on the Professional Doctorate programme; and examiners reports of the doctoral level research.
The focus of this paper is on 'what counts' for WBL academics. Interviews exploring: what makes a 'good' professional doctorate? have been undertaken with advisers working on a Professional Doctorate programme in a UK university. The interviews were conducted with the aim of establishing a model of 'best practice' for the induction of new advisers working on WBL programmes. However, rather than reading the interview texts in order to develop normative themes as to how the DProf 'should' be, the interviews have been analysed with a focus on language, identity/ies, academic practices and values. We are interested in how the DProf is constituted by academic advisers and the implications in terms of how it might be assessed.
We found that in many of the interviews that WBL academics slipped into a binary ordering where the professional doctorate was constructed in opposition to the PhD. For example, advisers spoke of development versus research, practice versus theory, relevance versus rigour; with the former often privileged over the latter. There was also a great emphasis on the importance of self development. We suggest that the binary separation of practice and theory evident in the interview texts may not be helpful as it overlooks the complex processes whereby practice and theory are intertwined.
The analysis points to tensions and contradictions in the interview texts. We suggest that the 'in between' spaces of WBL, where the discourses of workplaces intersect with discourses of HE, provides a site for examining the ongoing renegotiation of academic identity/ies. It is in this sense that academics can be understood as workplace learners too. For example, at times the WBL academics drew on more traditional discourses associated with the academy, such as the value of academic literacy, while at other times organisational discourses seemed to be privileged.
The paper provides a more nuanced account of struggles around 'what gets to count as learning' in professional doctorates that foregrounds the tensions experienced by WBL academics rather than trying to smooth them over. For example, professional doctorates (as they are organised at this particular university) provide a challenge to the authority of academia and subject-based disciplines as WBL awards seek to recognise knowledges produced in workplaces and workplaces as sites of learning. However, in the process of certifying such knowledge WBL academics are also inserting their own norms, standards and values into this space. In drawing attention to values and what counts for WBL advisers the analysis contributes to ongoing discussions and questions around doctoral level learning within the academy and how it might be assessed.
In summary, there are different stakeholders associated with the production, circulation and consumption of workplace knowledges. The interests of these stakeholders are not necessarily aligned and the ways doctoral level learning in HE is organised and assessed both comes out of and contributes to the mobile and contingent force relations in play. It is important that academics involved in the organisation and assessment of professional doctorates have a good understanding of where they are positioned, and how they position others, in these intersecting discourses.


The working paper discusses the trends in farm employment over time in South Africa. This is followed by the presentation of six case studies of specific commodities and regions with the view to establishing the potential employment effects of various changes in the policy environment. The article ends with an assessment of selected aspects of the wider environment within which the sector operates, to ascertain the extent to which such policy shifts are feasible, i.e. whether the measured effects in employment generation are likely to happen.


Objectives: Accurate, economical identification of cognitive impairment would increase dementia detection and improve care of older patients. Design: Analysis of archival neuropsychological data combined 3-word recall, time orientation, list memory, and clock drawing into the Memory Orientation Screening Test (MOST ™). The MOST was compared with Folstein Mini Mental State Examination (MMSE) and Mini-Cog to detect dementia presence and severity, and convergence with standardized neuropsychological tests. Internal consistency, retest reliabilities, completion likelihood, and time costs were calculated. Results: The MOST was significantly more sensitive than MMSE or Mini-Cog, twice as accurate as MMSE for identifying mild dementia, better correlated with standardized memory tests, more reliable over time, and minimally related to depression. Conclusions: The MOST is routinely administered in less than 5 minutes by a medical assistant, more accurately identifies dementia and severity than current screening tests, and emulates longer memory testing, making it valuable for Annual Wellness Visits and many applied clinical settings.


Through-bond conjugated polymers have been widely studied and shown great potential in various applications due to their conductive or luminescence properties, while through-space conjugated polymers are less explored. In this work, a unique through-space conjugated monomer derived from folded tetraphenylethene (TPE) is utilized to build a series of new polymers by Pd-catalyzed Suzuki or Stille coupling reactions. The new polymers are well characterized, and their optical and thermal properties and potential application in explosive detection are investigated. All the polymers show good thermal stability with high decomposition temperatures (340–436 °C). They exhibit higher fluorescence quantum yields in aggregates and films than in solutions, namely they show aggregation-enhanced emission (AEE) properties. They perform well in explosive detection in aqueous media using picric acid as a model. The nanoaggregates of the polymers show high quenching constants of up to 552 000 M−1, which is much higher than those in THF solution (78 200 M−1), demonstrating the superamplification effect of the polymer nanoaggregates in aqueous media. These new through-space conjugated polymers could be new kinds of fluorescent materials and worth further exploration.


INTRODUCTION Reliable data on the decomposition of inhomogeneous reaction masses can be difficult to obtain. Sampling can be a particular problem when carrying out small scale work and can lead to a wide variation in results, such variation could have potentially hazardous implications for process operations. This paper highlights some of the advantages and disadvantages that can occur when using Differential Scanning Calorimetry and provides a comparison with an alternative experimental method using a RADEX.


Sound is all around. In movies. On TV. On the radio. Now the idea that sound can be an artistic medium in its own right is shaking the art world. Written by an authority in the field, The Fundamentals of Sonic Arts and Sound Design describes and begins the process of defining this entirely new subject. Topics covered include new and radical approaches to sound recording, performance, installation works and exhibitions, plus visits with sonic artists and sound designers. Designed for students, yet packed with exciting examples of the principles and practice of this new art form, this book is on the cutting edge where technology and art meet.


Our aims were to evaluate the primary and clinical evisceration indications and to analyse orbital implant related complications.We included in our retrospective review all eviscerations between 2006 and 2016 at the Department of Ophthalmology of Semmelweis University, Budapest, Hungary. Primary evisceration indications were classified into six groups: trauma, surgical diseases, infections or inflammations, systemic diseases, tumours and unclassifiable diseases. Clinical immediate evisceration indications were also classified into six groups: painful blind eye due to glaucoma, atrophia/phthisis bulbi, endophthalmitis, cosmetic reasons, acute trauma and expulsive bleeding.Evisceration was performed in 46 eyes of 46 patients (54.3% males, age 43.0 ± 18.6 years). The most common primary evisceration indications were trauma (37%), surgical diseases (34.8%), infection or inflammation (10.9%), systemic diseases (6.5%), tumours (8.7%) and unclassifiable diseases (2.2%). Painful blind eye due to glaucoma (34.8%) was the most common clinical indication for evisceration, followed by atrophia/phthisis bulbi (26.1%), endophthalmitis (17.4%), cosmetic reasons (13.0%), acute trauma (6.5%) and expulsive bleeding (2.2%). After evisceration, 91.3% of the patients received orbital implant and during 26.8±28.9 months follow-up implant related complications were found in 14.3% of the cases, including implant extrusion (4.8%), partial wound dehiscence (4.8%), implant exposure (2.4%) and orbital inflammation (2.4%).Painful blind eye and atrophia/phthisis bulbi due to ocular trauma and surgical diseases represent the most common indications for ocular evisceration. If malignant intraocular tumours can be excluded, evisceration surgery combined with a silicon-based orbital implant is a safe and effective procedure.


Evidence is steadily accumulating that prolonged exposure to violent TV programming during childhood is associated with subsequent aggression. In their Perspective,
 Anderson and Bushman
 discuss new work (
 Johnson
 et al .) that clearly demonstrates this association in adolescents and young adults, thus broadening the range of individuals affected by media violence.


Evidence indicates that longitudinal changes in dietary patterns may predict variations in blood pressure (BP) and risk of incident hypertension. We aimed to identify distinct trajectories in the levels of Mediterranean diet adherence (MDA) in China and explore their association with BP levels and hypertension risk using the China Health and Nutrition Survey 1997–2011 data. Three levels of MDA were constructed. The trajectories in these levels were constructed using group-based trajectory modeling. A Cox proportional hazards model was used to measure the association between MDA trajectory groups and the risk of incident hypertension after adjusting for covariates. Finally, 6586 individuals were included. Six distinct MDA trajectory groups were identified: persistently low and gradual decline; rapidly increasing and stabilized; persistently moderate; slightly increasing, steady, and acutely descending; slightly decreasing and acutely elevated; and persistently high. The systolic BP and diastolic BP were significantly lower in trajectory groups with rapidly increasing and stabilized MDA; slightly increasing, steady, and acutely descending MDA; and persistently high MDA. Cox regression analysis showed that the risks of developing hypertension were relatively lower in the group with slightly increasing, steady, and acutely descending MDA (hazard ratio (HR) = 0.17, 95% confidence interval (CI): 0.09–0.32) and the group with rapidly increasing and stabilized MDA (HR = 0.32, 95% CI: 0.23–0.42), but the risk was the highest in the trajectory with persistently moderate MDA (HR = 0.96, 95% CI: 0.84–1.08). In conclusion, MDA in China was categorized into six distinct trajectory groups. BP was relatively lower in trajectory groups with initially high or increasing MDA levels. Greater MDA was significantly associated with a lower risk of developing hypertension.


A field recording is any audio recording made outside of the studio. Such recordings have lately become important to contemporary musicians, sound artists and environmentalists. However, less attention has been given to the relation of sound, as manifested in the theory and practice of the field recording, to writing. The 11 essays collected here take the recent explosion of interest in field recording as the point of departure for an investigation of the sounded field in music and its relationship to literature and writing. Including seminal pieces on field thinking by John Berger and Lisa Robertson, Writing the Field Recording analyses contemporary text scores, histories, composer statements, critical literature, poetry and nature writing in the context of sound studies. Drawing on expertise from a range of backgrounds, including composers, musicians, poets and critics, the collection presents an inter-disciplinary exploration of the various registers in which the field recording is written, such as the essayistic, the creatively exploratory, the experimental and the philosophical alongside critical reflections on artistic practice.


Schooling for Aboriginal and Torres Strait Islander students in remote or 'Red Dirt' communities has been cast as 'problematic', and 'failing'. The solutions to deficit understandings of remote schooling are often presented as simple. But for those who work in Red Dirt schools, the solutions are not simple, and for education leaders positioned between the local Red Dirt school and upward accountability to departments of education, they are complex. Between 2011 and 2016, the Cooperative Research Centre for Remote Economic Participation's (CRC-REP) Remote Education Systems project explored how education could better meet the needs of those living in remote communities. More than 1000 people with interests in remote education contributed to the research. Education leaders were identified as one stakeholder group. These leaders included school-based leaders, bureaucrats, community-based leaders and teacher educators preparing university graduates for Red Dirt schools. This paper focusses on what Red Dirt education leaders think is important for schooling. The findings show school leaders as 'caught in the middle' (Gonzalez & Firestone, 2013) between expectations from communities, and of system stakeholders who drive policy, funding and accountability measures. The paper concludes with some implications for policy and practice that follow on from the findings.


In this paper we generalise the notion of extensional (functional) equivalence of programs to abstract equivalences induced by abstract interpretations. The standard notion of extensional equivalence is recovered as the special case, induced by the concrete interpretation. Some properties of the extensional equivalence, such as the one spelled out in Rice's theorem, lift to the abstract equivalences in suitably generalised forms. On the other hand, the generalised framework gives rise to interesting and important new properties, and allows refined, non-extensional analyses. In particular, since programs turn out to be extensionally equivalent if and only if they are equivalent just for the concrete interpretation, it follows that any non-trivial abstract interpretation uncovers some intensional aspect of programs. This striking result is also effective, in the sense that it allows constructing, for any non-trivial abstraction, a pair of programs that are extensionally equivalent, but have different abstract semantics. The construction is based on the fact that abstract interpretations are always sound, but that they can be made incomplete through suitable code transformations. To construct these transformations, we introduce a novel technique for building incompleteness cliques of extensionally equivalent yet abstractly distinguishable programs: They are built together with abstract interpretations that produce false alarms. While programs are forced into incompleteness cliques using both control-flow and data-flow transformations, the main result follows from limitations of data-flow transformations with respect to control-flow ones. A further consequence is that the class of incomplete programs for a non-trivial abstraction is Turing complete. The obtained results also shed a new light on the relation between the techniques of code obfuscation and the precision in program analysis.


Aims: The aim of this study was to report on the prevalence and correlates of pseudoexfoliation syndrome (PXF) in a rural Burmese population. Methods: The study was a cross-sectional, population-based survey of the inhabitants ⩾40 years in the Meiktila District. Ophthalmic examination included Snellen visual acuity, slit lamp examination, tonometry, gonioscopy, dilated fundus examination and frequency doubling perimetry. Results: In a population of 2076 subjects (4016 eyes) the prevalence of PXF was 3.4% (95% CI 2.14 to 4.67%; 78 eyes). Twelve eyes with PXF were blind. In the univariate analysis, PXF was associated with: increasing age, blindness (odds ratio (OR) 4, 95% CI 1.84 to 8.68; p<0.0004), increasing intraocular pressure (IOP) (OR 1.08, 95% CI 1.04 to 1.11; p<0.00001), nuclear cataract (OR 6.92, 95% CI 2.89 to 16.59; p<0.00001), cortical cataract (OR 4.78, 95% CI 2.37 to 9.65; p<0.00001) and the presence of an occludable angle (OR 3.05, 95% CI 1.52 to 6.13; p<0.002). In the multivariate analysis, only increasing age and IOP remained significantly associated with PXF. Conclusions: The prevalence of PXF in the Burmese population is greater than previously reported in other East Asian populations. Increasing age and IOP are the strongest predictors of PXF, and it is associated with cataract, occludable angles and blindness.


Minimum error rate training is a crucial component to many state-of-the-art NLP applications, such as machine translation and speech recognition. However, common evaluation functions such as BLEU or word error rate are generally highly non-convex and thus prone to search errors. In this paper, we present LP-MERT, an exact search algorithm for minimum error rate training that reaches the global optimum using a series of reductions to linear programming. Given a set of N-best lists produced from S input sentences, this algorithm finds a linear model that is globally optimal with respect to this set. We find that this algorithm is polynomial in N and in the size of the model, but exponential in S. We present extensions of this work that let us scale to reasonably large tuning sets (e.g., one thousand sentences), by either searching only promising regions of the parameter space, or by using a variant of LP-MERT that relies on a beam-search approximation. Experimental results show improvements over the standard Och algorithm.


Here we studied new fossil chondrichthyans from two localities, Rio de Las Minas, and Sierra Dorotea, both in the Magallanes Region, southernmost Chile. In Rio de Las Minas, the upper section of the Priabonian Loreto Formation have yielded material referable to the taxa Megascyliorhinus sp., Pristiophorus sp., Rhinoptera sp., and Callorhinchus sp. In Sierra Dorotea, middle-to-late Eocene levels of the Rio Turbio Formation have provided teeth referable to the taxa Striatolamia macrota (Agassiz), Palaeohypotodus rutoti (Winkler), Squalus aff. weltoni Long, Carcharias sp., Paraorthacodus sp., Rhinoptera sp., and indeterminate Myliobatids. These new records show the presence of common chondrichtyan diversity along most of the Magallanes Basin. The new record of Paraorthacodus sp. and P. rutoti, support the extension of their respective biochrons in the Magallanes Basin and likely in the southeastern Pacific.