Objectives To evaluate the effectiveness of a single intra-articular injection of hylan G-F 20 (Synvisc) for symptomatic first metatarsophalangeal joint (MTPJ) osteoarthritis (OA). Methods Participants (n = 151) with symptomatic first MTPJ OA were randomly allocated to receive up to 1 ml intra-articular injection of either hylan G-F 20 or placebo (saline). Participants and assessors were blinded. Outcomes were evaluated at 1, 3 and 6 months after injection. The primary outcome measurement was the foot pain domain of the Foot Health Status Questionnaire (FHSQ) at 3 months. Secondary outcome measurements were foot function assessed via the FHSQ, first MTPJ pain and stiffness, magnitude of symptom change, global satisfaction, health-related quality of life (assessed using the Short-Form-36 version two), first MTPJ dorsiflexion range of motion, hallux plantar flexion strength, use of pain-relieving medication or co-interventions and changes in plantar pressures. Results No statistically significant differences in foot pain were found between the groups at 3 months. There were few statistically significant differences in the secondary outcome measures. Overall, the incidence of adverse effects was not significantly different between groups. Conclusions An intra-articular injection of hylan G-F 20 is no more effective than a placebo in reducing symptoms in people with symptomatic first MTPJ OA.Australian New Zealand Clinical Trials Registry: number ACTRN12607000654459.


Accurate genomic evaluation depend on large reference population with reliable performance information such as predicted breeding value (PBVs). The aim of this study was to identify the most appropriate reference population to predict the genomic breeding value for Iran Holstein dairy breeding programs. Phenotypes and genotypes were simulated based on the dairy cattle Iran population program (open breeding nucleus with gene flows between the nucleus and the commercial population). Medium (0.3) and low (0.05) heritability levels were considered independently. All simulations were performed with 10 replications and the results were evaluated. In the first study, female cows were selected for genotyping in four scenarios: random selection, individuals with upper and lower extremities of phenotypic value, highest phenotypic value and highest breeding value with maximum accuracy; and these females are added to the reference population. Single Step BLUP (SSBLUP) was used to predict the genomic breeding value for individuals in the population. The accuracy and unbiased coefficient of predicted breeding value were investigated. The results showed that when female animals with the highest and lowest phenotypic values were selected (the second scenario of determining females), the highest accuracy of prediction of breeding value was observed compared to other scenarios. Determination of substances with high phenotypic value (third scenario of female selection) showed the least bias. The use of imported males with genotype and their use alone as a reference population showed the least accuracy and the most bias. The combination of males and females showed an increase in accuracy and a decrease in bias compared to the scenarios for males or females alone. However, in relation to the size of the population similar to females, no improvement in the prediction of the breeding value was observed. Therefore, in terms of economic conditions (genotyping costs), the use of only female cows in the reference population (2000 females genotyped), according to the second scenario of female selection, is the best strategy to form a reference population and genomic evaluation at the lowest cost, in Iran.


: The hygienic training of pediatricians is very important in terms of introducing research achievements into practical public health service. Knowledge must be permanently replenished in the system of postgraduate training by giving up the job for 4 months every 5 years, including an obligatory monthly training in ecological and hygienic problems. The licensing system of the specialists' right to professional activity requires to be introduced. The qualification grade of a pediatrician and the payment of his/her work should be determined by a set of specific licences.


Patients with obstructive sleep apnea demonstrate both acute and chronic hemodynamic changes attributable to their disease. Acutely, these patients experience repetitive nocturnal hemodynamic oscillations. Sudden increases in heart rate and arterial pressure occur in association with decreases in left ventricular stroke volume immediately following apnea termination. These hemodynamic changes are likely attributable primarily to the effects of oxygen desaturation and arousal, an abrupt change in state. These acute changes occur against a background of altered cardiovascular control. Patients with sleep apnea, even when sleeping without obstructions, fail to display the normal nocturnal decline in arterial pressure of 10-15% from the waking value. The absence of a nocturnal decline may have chronic consequences, such as development of left ventricular hypertrophy. Another chronic hemodynamic consequence of sleep apnea may be sustained diurnal hypertension. Epidemiologic studies suggest individuals with sleep disordered breathing are at greater risk of daytime hypertension, even after controlling for other risk factors. Although sleep apnea may contribute to pulmonary, as well as systemic hypertension, sleep apnea alone does not appear to be a cause of decompensated right heart failure. Although knowledge of the hemodynamic consequences of sleep apnea has grown in recent years, much remains to be learned.


Cloud computing technology has the potential to transform medical practices and improve patient engagement and quality of care. However, issues such as privacy and security and "fit" can make incorporation of the cloud an intimidating decision for many physicians. This article summarizes the four most common types of clouds and discusses their ideal uses, how they engage patients, and how they improve the quality of care offered. This technology also can be used to meet Meaningful Use requirements 1 and 2; and, if speculation is correct, the cloud will provide the necessary support needed for Meaningful Use 3 as well.


Wireless sensor networks require shared medium access management to prevent collisions, message corruption and other unhelpful effects. Cellular sensornets require minimal energy consumption to maximise network lifetime, and management of interaction with base stations and other cells. We present a protocol which dynamically generates a near-optimal duty schedule within a cell such that communication duty is shared evenly between participating nodes with exactly one node on-duty at any given time.


In high power operations, the ageing of power semiconductor modules has been often observed by several failures due to high temperature cycling. The main failures may be metallization reconstruction, solder delaminations, bond wire lift-offs or bond wire heel crackings, conchoidal breaking of ceramics. The paper focuses on the non-contact monitoring of the ageing of the aluminum metallization top layer and of the solder bottom layer of a power die, using the eddy current method. The ageing is assumed to induce a decrease of these layers conductivity. The evaluation of both layers conductivity changes are estimated using artificial neural networks starting from eddy current data provided by finite element computations carried out in the case of several aged die configurations. The error of estimation is less than a few percent in the considered cases and it demonstrates the relevance of the eddy current method to monitor the ageing state of power modules. The proposed approach provides relevant results which will be validated on experimental data in future works.


This LibGuide has been developed to assist anyone interested in the enjoyment and study of children's and young adult literature. Keep in mind that often the line between the two is blurred (as is the line between "young adult" and "adult").


At the present, base isolation system has been recognized by general earthquake resistant technique since the Great Hanshin Earthquake 1995. The seismic isolation will be aggressively applied to not only architectural and civil structures but also various structures, because the effectiveness on seismic safety had been demonstrated again in the Great East Japan Earthquake. In generally, although the base isolation system is divided into laminated rubber bearing type and friction sliding bearing type. In the case of former type, shape factor, maximum or minimum outer shapes and so on are restricted by the material characteristics in visco-elastic material.In previous study, the research and development of laminated type base isolation device using urethane elastomer was carried out to upgrade a seismic safety for various structures. The fundamental characteristics was investigated from several loading test by using various experimental devices, and the design formula for the stiffness and equivalent damping coefficient is formulated as an approximate expression of mechanical characteristics until now. The mechanical characteristics based on the loading test up to 500% shear strain using experimental specimen with 100 × 100 mm cross-sectional shape. It was confirmed that urethane elastomer is not hardening up to 500% shear strain. Moreover, the experimental examination for aged deterioration in the urethane material has been continuously carried out. As the results, it was confirmed that the laminated type seismic isolation device using urethane elastomer is possible to develop as a practicable device from the stable mechanical properties as considering in design step.In this study, the small-scale laminated type base isolation device using urethane elastomer is advanced to the direction of further technical upgrading and of scale down for light-weight structure as a sever rack. The first stage, basic properties of the urethane elastomer has been investigated by loading test. The second stage, the compression creep test with laminated type base isolation device has been investigated to confirm an effect on light-weight mechanical devices.Copyright © 2016 by ASME


Abstract In numerous UN policy documents, a sustainable future through education is set in a key position; the UNESCO Global Action Programme on Education for Sustainable Development (UNESCO, 2018) is no exception. Therefore, it is of great importance to examine and report how different UN member countries work towards the implementation of sustainability at all levels of education. This article is a review of recently published research in Finland, with a focus on sustainability in the educational system. Specifically, the article deals with teacher education, combined with theoretical research around sustainability and systems thinking, to find a pathway forward. The main finding is that higher education in Finland cannot guarantee that student teachers are prepared enough to teach about sustainability. This issue is discussed and addressed in the last part of the article.


The Hadoop file system is a large scale distributed file system used to manage and quickly process extremely large data sets. We want to utilize Hadoop to assist with data-intensive workloads in a distributed campus grid environment. Unfortunately, the Hadoop file system is not designed to work in such an environment easily or securely. We present a solution that bridges the Chirp distributed file system to Hadoop for simple access to large data sets. Chirp layers on top of Hadoop many grid computing desirables including simple deployment without special privileges, easy access via Parrot, and strong and flexible security Access Control Lists (ACL). We discuss the challenges involved in using Hadoop on a campus grid and evaluate the performance of the combined systems.


We study the effect of the intellectual property rights (IPR) regime of a host country (South) on a multinational's decision between serving a market via greenfield foreign direct investment to avoid the exposure of its technology or entering a joint venture (JV) with a local firm, which allows R&D spillovers under imperfect IPRs. JV is the equilibrium market structure when R&D intensity is moderate and IPRs strong. The South can gain from increased IPR protection by encouraging a JV, whereas policies to limit foreign ownership in a JV gain importance in technology intensive industries as complementary policies to strong IPRs.


This paper presents a 14-tap 8-bit finite impulse response (FIR) test-chip that has been designed using a novel charge-recovery logic family, called Enhanced Boost Logic (EBL), to achieve high-speed and low-power operation. Compared to previous charge-recovery circuitry, EBL achieves increased gate overdrive, resulting in low latency overhead over static CMOS design. The EBL-based FIR has been designed with only 1.5 cycles of additional latency over its static CMOS counterpart, while consuming 21% less energy per cycle, based on post-layout simulations of the two designs. The test-chip has been fabricated in a 0.13 μ m CMOS process with a fully-integrated 3 nH inductor. Correct function has been validated in the 365-600 MHz range. At its resonant frequency of 466 MHz, the test-chip dissipates 39.1 mW with a 93.6 nW/MHz/Tap/InBit/CoeffBit figure of merit, recovering 45% of the energy supplied to it every cycle.


The objectives of this study were to analyze the factors that affected the food demand by the farmer households in Riau Province and to analyze how social capital is influential toward this demand. The research was conducted in four districts with different characteristics including indragiri hilir and rokan hilir as the regional representation with high activities of food crops, while Kampar and rokan hulu as the regional representation to the medium activities of food crops. The study was conducted in the two-survey period. The first survey was carried out in Indragiri Hilir and Kampar Regencies with the number of households as many as 114 in 2013, and the second survey was conducted in rokan hilir and rokan hulu regencies with the number of households of 96 farm households in 2014 so that the total samples reached 210 farm households 4. The sampling was carried out randomly. The function of farmer household food demand was analyzed using the model of farm household and was estimated by ordinary least sguare (ols). The results showed that the variables of age of the household head, education level of farmers, number of household members, household income, and social capital had positive effects on the food demand for the farmer households while the variables of the prices of rice, potatoes, eggs, chicken meat, fish, and cooking oil had negative effects on the food demand for the farmer households in Riau Province. furthermore, the results showed that social capital in the society built on the four (4) aspects, namely, trust, social networks within the support structure, norms and values, and levels of participation in the organization has contributed positively to food security of the farmers in riau Province. Therefore, the community needs to build a high social capital, cooperation and mutual assistance, especially for the environment that has difficulties in finding food.


Summary.  In epidemiologic studies, there is often interest in assessing the association between exposure history and disease incidence. For many diseases, incidence may depend not only on cumulative exposure, but also on the ages at which exposure occurred. This article proposes a flexible Bayesian approach for modeling age‐varying and waning exposure effects. The Cox model is generalized to allow the hazard of disease to depend on an integral, across the exposed ages, of a piecewise polynomial function of age, multiplied by an exponential decay term. Linearity properties of the model facilitate posterior computation via a Gibbs sampler, which generalizes previous algorithms for Cox regression with time‐dependent covariates. The approach is illustrated by an application to the study of protective effects of breastfeeding on incidence of childhood asthma.


Semantic distance is a measure of how close or distant in meaning two units of language are. A large number of important natural language problems, including machine translation and word sense disambiguation, can be viewed as semantic distance problems. The two dominant approaches to estimating semantic distance are the WordNet-based semantic measures and the corpus-based distributional measures. In this thesis, I compare them, both qualitatively and quantitatively, and identify the limitations of each.
This thesis argues that estimating semantic distance is essentially a property of concepts (rather than words) and that two concepts are semantically close if they occur in similar contexts. Instead of identifying the co-occurrence (distributional) profiles of words (distributional hypothesis), I argue that distributional profiles of concepts (DPCs) can be used to infer the semantic properties of concepts and indeed to estimate semantic distance more accurately. I propose a new hybrid approach to calculating semantic distance that combines corpus statistics and a published thesaurus (Macquarie Thesaurus). The algorithm determines estimates of the DPCs using the categories in the thesaurus as very coarse concepts and, notably, without requiring any sense-annotated data. Even though the use of only about 1000 concepts to represent the vocabulary of a language seems drastic, I show that the method achieves results better than the state-of-the-art in a number of natural language tasks.
I show how cross-lingual DPCs can be created by combining text in one language with a thesaurus from another. Using these cross-lingual DPCs, we can solve problems in one, possibly resource-poor, language using a knowledge source from another, possibly resource-rich, language. I show that the approach is also useful in tasks that inherently involve two or more languages, such as machine translation and multilingual text summarization.
The proposed approach is computationally inexpensive, it can estimate both semantic relatedness and semantic similarity, and it can be applied to all parts of speech. Extensive experiments on ranking word pairs as per semantic distance, real-word spelling correction, solving Reader's Digest word choice problems, determining word sense dominance, word sense disambiguation, and word translation show that the new approach is markedly superior to previous ones.


OBJECTIVE
To describe the prevalence and characteristics of non-inflammatory joint pain (NIJP) in patients with chronic inflammatory bowel disease (IBD) and its impact on patients' health related quality of life (HRQOL).

METHODS
In a population based cohort, 521 patients (80%) were clinically investigated 6 years after onset of IBD. NIJP was defined as a history of joint pain during the last 3 months prior to examination and the absence of concomitant signs or symptoms of inflammatory or degenerative joint disease or chronic pain syndromes. HRQOL was registered by the generic Medical Outcome Study Short Form 36 (SF-36) and by the disease specific IBDQ.

RESULTS
NIJP was reported by 85 (16%) patients and significantly more often in conjunction with Crohn's disease (CD, 22%) compared to ulcerative colitis (UC, 14%). The prevalence of NIJP was similar in men and women. No correlation with extension of intestinal disease, use of systemic medication, or frequency of surgery was found. NIJP exerted significant impact on HRQOL measured by SF-36 and IBDQ.

CONCLUSIONS
NIJP occurs frequently in IBD and more often in CD than in UC. NIJP significantly alters HRQOL and should be taken into account in trials estimating outcome in IBD and in clinical practice by attending clinicians.


This paper suggests that PA practitioners' professional identity is in transition with the practice now exhibiting multiple identities and cultural hybridity. It is argued that this has parallels to the work of Abbot et al. (2014) whose research reveals similar identity complexity in those working in global settings. This is one of the key findings from a wider study investigating the knowledge, skills and attributes for effective public affairs practice. It synthesizes scholarship from the field of career and professionalism studies with the theory and practice of public affairs (PA). It argues the narrow definition of PA practitioners as pure lobbyists providing the interface between the organization and government is outdated. The role has evolved to become one of a skilled influencer inside and outside the organization managing a complex set of relationships focusing on alliance and partnership building in a changing public policy environment.

The study leads on a qualitative investigation allowing rich data mirroring the complexity of work and policy construction and involves 31 in-depth interviews with practitioners and policy makers. It is supported by an additional quantitative survey that helps to elucidate identity and competency constructs in more detail. The limitations relate to its scope – a UK study. Further studies in different cultural and political settings need to be encouraged and perhaps longitudinal studies developed to look at how professional identity evolves and the influences on it.

Many PA scholars (Schuler, 2002; Hillman, 2002; Toth, 2006 and Fleisher, 2007) have all tried to define the practice but common to all is the understanding that PA is about building relationships with those who shape public policy. More recently Fleisher (2012) has reflected on the current state of public affairs practice suggesting that the full impact of globalization, multiple communication channels and the need for more collaborative approaches is set to transform the practice.

How does this evolution affect the identity of practitioners? According to Ibarra (1999: 764-765) professional identity is defined as "the relatively stable and enduring constellation of attributes, beliefs, values, motives and experiences in terms of which people define themselves in a professional role". Whilst traditional career scholars (Levinson et al., 1978; Super et al. 1996) view this as something passive as individuals travel through different career stages. More recent scholars such as Hall (2002) suggest that people actively develop their identities by improving their self-awareness and as suggested by Kegan (1994) by interacting with the complexity of their environments. Integral to both is an improved understanding of the competencies and strengths that are necessary in the role in order to provide greater recognition for the practice, the skill sets required and to establish career choices.

Early analysis suggests that PA practitioners recognize that their role has changed substantially in the last ten years in part due to the impact of globalization, technology including enabling easy access to information that was once seen as privileged and the changing policy landscape. PA appears to be fragmenting across a spectrum of interactions from narrow, regulatory one-to-one conversations between technical experts to campaigns that go to the heart of organizational reputation and survival involving multi-channel communication strategies across a range of stakeholder groups. Sector influences and organizational culture also impacts on the style and tone of PA. At the same time, there is an appetite to understand the practice better and improve self-efficacy.

The concept of multiple identities and cultural hybridity is just one aspect of this study that aims to have conceptual and practical value by creating a framework underpinned by a body of knowledge and competencies that captures the professional identity of this new breed of PA practitioner. In so doing it aims to improve understanding of the role of PA at the micro (individual self-aware), meso (organizational) and macro (societal) levels.

In terms of originality, the study aims to fill the research gap between PA and competency and professional identity scholarship. At the same time, most research into PA is North American focused. This paper adds value by looking at a UK and more broadly European perspective allowing for comparisons and shared learning.


We study discrete isospectral symmetries for the classical
acoustic spectral problem in spatial dimensions one and two by
developing a Darboux (Moutard) transformation formalism for this
problem. The procedure follows steps similar to those for the
Schrodinger operator. However, there is no one-to-one
correspondence between the two problems. The technique developed
enables one to construct new families of integrable potentials for
the acoustic problem, in addition to those already known. The
acoustic problem produces a nonlinear Harry Dym PDE. Using the
technique, we reproduce a pair of simple soliton solutions of this
equation. These solutions are further used to construct a new
positon solution for this PDE. Furthermore, using the
dressing-chain approach, we build a modified Harry Dym equation
together with its LA pair. As an application, we construct some
singular and nonsingular integrable potentials (dielectric
permitivity) for the Maxwell equations in a 2D inhomogeneous
medium.


Relation classification aims at detecting a particular relation type between two entities in text, whose methods mostly requires annotated data. Data annotation is either a manual process for supervised learning, or automated, using knowledge bases for distant learning. Unfortunately, both annotation methodologies are costly and time-consuming since they depend on intensive human labour for annotation or for knowledge base creation. With recent evidence that language models capture some sort of relational facts as knowledge bases, one-shot relation classification using language models has been proposed via matching a given instance against examples. The only requirement is that each relation type is associated with an exemplar. However, the matching approach often yields incorrect predictions. In this work, we propose NoelA, an auto-encoder using a noisy channel, to improve the accuracy by learning from the matching predictions. NoelA outperforms BERT matching and a bootstrapping baseline on TACRED and reWiki80.


Microassembly promises to extend MEMS beyond the confines of silicon micromachining. This paper surveys research in both serial and parallel microassembly. The former extends conventional 'pick and place' assembly into the micro-domain, where surface forces play a dominant role. Parallel assembly involves the simultaneous precise organization of an ensemble of micro components. This can be achieved by microstructure transfer between aligned wafers or arrays of binding sites that trap an initially random collection of parts. Binding sites can be micromachined cavities or electrostatic traps; short-range attractive forces and random agitation of the parts serve to fill the sites. Microassembly strategies should furnish reliable mechanical bonds and electrical interconnection between the micropart and the target substrate or subassembly.


Background As the search for an immune privileged allogeneic donor mesenchymal stem cell (MSC) line continues in equine medicine, the characterization of the cells between different sources becomes important. Our research seeks to more clearly define the MSC marker expression of different equine MSC donors. Methods The bone marrow-derived MSCs from two equine breeds and different blood donor-types were compared over successive culture passages to determine the differential expression of important antigens. Eighteen Thoroughbreds and 18 Standardbreds, including 8 blood donor (erythrocyte Aa, Ca, and Qa antigen negative) horses, were evaluated. Bone marrow was taken from each horse for isolation and culture of MSCs. Samples from passages 2, 4, 6, and 8 were labelled and evaluated by flow cytometry. The cell surface expression of CD11a/18, CD44, CD90 and MHC class II antigens were assessed. Trilineage assays for differentiation into adipogenic, chondrogenic and osteogenic lines were performed to verify characterization of the cells as MSCs. Findings There were significant differences in mesenchymal stem cell marker expression between breeds and blood antigen-type groups over time. Standardbred horses showed a significantly lower expression of MHC class II than did Thoroughbred horses at passages 2, 4 and 6. CD90 was significantly higher in universal blood donor Standardbreds as compared to non-blood donor Standardbreds over all time points. All MSC samples showed high expression of CD44 and low expression of CD11a/18. Conclusions Universal blood donor- type Standardbred MSCs from passages 2–4 show the most ideal antigen expression pattern of the horses and passages that we characterized for use as a single treatment of donor bone marrow-derived MSCs. Further work is needed to determine the significance of this differential expression along with the effect of the expression of MHC I on equine bone marrow-derived MSCs.


The paper presents the Veredas Novas (New Paths) initiative of RNP, the Brazilian National Research and Education Network, to provide access to RNP's national backbone network at 100 Mb/s and 1 Gb/s from university and research institutions campi in smaller cities throughout the country. The initiative is supported by the Ministries of Science, Technology and Innovation (MCTI), of Education (MEC) and of Communications (MC), and involves partnerships with public and private companies, taking advantage of the current deployment of the National Broadband Plan of the Brazilian government. RNP has already interconnected nationally all the universities, university hospitals and research centres, but, in general, it is only in the 27 capital cities (26 state capitals and the national capital, Brasília) and in a handful of major non-capital cities that this is done with high-capacity connections – at 1 or 10 Gb/s. Veredas Novas, which began in February, 2012, aims to extend high-capacity connections – at 100 Mb/s or 1 Gb/s – to hundreds of campi in smaller non-capital cities. This will extend to these campi the use of advanced applications, databases, digital libraries, remote instruments and, most importantly, the opportunity for their researchers to participate in research groups and collaborative research with other institutions across the country and abroad, contributing to creating the same conditions of communication and collaboration that already exist in major centres.


Male guppy mating behavior has many displays. Some of these displays include sigmoid behavior, Gonopodial swings, fin fanning, and biting. In this study, the amount of times that each courtship behavior was displayed was calculated to determine one factor that a male uses to attract a mate. The goal of this experiment was to test if male guppies prefer female guppies that reflect longer wavelengths of light as sexual partners. To test this, two 3D printed female models, one red and one blue, were used to entice male guppies. The time spent with each model, as well as the mating behaviors displayed with each model was measured. The results from this study showed that the red female model received more displays of courtship, as well as more time with the male guppy. This supported the hypothesis that the male guppies would prefer the color with longer wavelengths.


We examine theoretically and experimentally the implications of trust arising under sequential and simultaneous designs, where one player makes an investment choice, and another player decides whether to share the investment gains. We show analytically that in some cases the sequential design may be outperformed by the simultaneous design. In an experiment we find that the investment levels and sharing rates are higher in the sequential design, but there are no corresponding differences in beliefs. We conjecture that this happens because in the sequential design substantially more trust is necessary to induce cooperation. Our data strongly support this conjecture.


— This research analyses the non-linear and complex effects of drivers of system imbalance prices in the GB electricity market. Unlike day-ahead prices, the balancing settlement prices are comparatively under-researched, yet their importance is growing with greater market risks. The fundamental drivers of these prices are analysed over 2016-2019. The result of a non-linear modelling approach reveals that system imbalance price exhibits a regime-switching behaviour, driven by weather and demand forecast errors, as well as other system effects. Surprisingly, balancing prices are predictable out of sample and a regime switching specification is more accurate than a linear model for prediction.


Nurses and marines epitomize accepted definitions of femininity and masculinity. Using ethnographic research and provocative in-depth interviews, Christine Williams argues that our popular stereotypes of individuals in nontraditional occupations - male nurses and female marines for example - are entirely unfounded. This new perspective helps to account for the stubborn resilience of occupational stratification in the face of affirmative action and other anti-discrimination policies.


A key signaling protein in the brain known to play a critical role in the development of addiction-related behaviors acts as a positive modulator of oxycodone reward in both pain-free and chronic pain states, according to a study conducted at the Icahn School of Medicine at Mount Sinai and published online January 17 in the journal Neuropsychopharmacology. The mechanisms of oxycodone action uncovered through this study will help scientists and physicians develop strategies and tools to dissociate the analgesic (pain relief) actions of opioids from the addiction-related effects. Using mouse models of acute and chronic pain, Mount Sinai researchers found that RGS9-2, the intracellular protein that controls the function of opioid receptors in the brain reward center, promotes addiction to oxycodone in pain-free, acute, and chronic pain states. Mice that lacked the gene responsible for encoding RGS9-2 (RGS9KO mice) showed less propensity to develop addiction-related behaviors. Furthermore, the loss of RGS9-2 function does not affect the acute analgesic effects of oxycodone. The research team also found that RSG9-2 plays a protective role towards the development of oxycodone tolerance, as RGS9KO mice became tolerant to the analgesic effects of the drug earlier than those that had the gene. Researchers found that the same mechanisms control sensitivity to oxycodone addiction in pain-free as well as chronic pain states. Although there has been extensive investigation into the mechanisms underlying the analgesia, dependence, and addiction potential of morphine, the mechanism by which oxycodone exerts its actions remained unknown. "Although oxycodone produces similar analgesic and behavioral effects to those observed with morphine, our study demonstrates that the intracellular actions of morphine and oxycodone are distinct," says Venetia Zachariou, PhD, associate professor in the Fishberg Department of Neuroscience and The Friedman Brain Institute, Icahn School of Medicine at Mount Sinai. "Our work reveals that intracellular factors that prevent the actions of morphine may actually promote the actions of oxycodone. This information is particularly important for pain management strategies, as a common course is to have patients oscillate between oxycodone and morphine to achieve pain relief." The Mount Sinai study provides new information on pathways involved in behavioral responses to oxycodone in pain-free and neuropathic pain states, which will help researchers and clinicians to determine the risks and benefits of oxycodone prescription for the treatment of pain. This knowledge may lead to the development of more efficacious and less addictive compounds for pain management. This research was supported by the National Institute of Neurological Disorders and Stroke (NS086444).


This presentation will look at the LERU Roadmap for Research Data, which was issued by the League of European Research Universities in January 2014. In a series of seven chapters, the Roadmap discusses a series of issues related to research data management and open data: Policy and Leadership; Advocacy; Selection and Collection, Curation, Description, Citation, Legal Issues; Research Data Infrastructure; Costs; Roles, Responsibilities and Skills; Recommendations. The Roadmap is the first analysis of its kind explicitly to the needs of universities and their researchers. Following a description of the main Recommendations in the Roadmap, the presentation will look at levels of takeup of the Roadmap and its Recommendations based on a recent survey of LERU members. Comparisons with the level of takeup for the LERU Roadmap Towards Open Access will provide instructive insights into how European research-led universities are tackling issues around research data management. Finally, the presentation will draw a number of conclusions about research data management in European research-led universities.


Drying of soil may increase the hydrophobicity of soil and affect the mobilization of colloids after re-wetting. Results of previous research suggest that colloid hydrophobicity is an important parameter in controlling the retention of colloids and colloid-associated substances in soils. We tested the hypothesis that air-drying of soil samples increases the hydrophobicity of water-dispersible colloids and whether air-drying affects the mobilization of colloid-associated heavy metals. We performed batch experiments with field-moist and air-dried (25 degrees C) soils from a former sewage farm (sandy loam), a municipal park (loamy sand), and a shooting range site (loamy sand with 25% C(org)). The filtered suspensions (<1.2 microm) were analyzed for concentrations of dissolved and colloidal organic C and heavy metals (Cu, Cd, Pb, Zn), average colloid size, zeta potential, and turbidity. The hydrophobicity of colloids was determined by their partitioning between a hydrophobic solid and a hydrophilic aqueous phase. Drying increased hydrophobicity of the solid phase but did not affect the hydrophobicity of the dispersed colloids. Drying decreased the amount of mobilized mineral and (organo-)mineral colloids in the sewage farm soils but increased the mobilization of organic colloids in the C-rich shooting range soil. Dried samples released less colloid-bound Cd and Zn than field-moist samples. Drying-induced mobilization of dissolved organic C caused a redistribution of Cu from the colloidal to the dissolved phase. We conclude that drying-induced colloid mobilization is not caused by a change in the physicochemical properties of the colloids. Therefore, it is likely that the mobilization of colloids in the field is caused by increasing shear forces or the disintegration of aggregates.


: Experimental whole-culture oral polyvalent meningococcal vaccines against serogroups A, B and C consisting of three monovalent components in different proportions have been developed and evaluated. Kinetics of IgG response to meningococcal antigens (outer membrane proteins, polysaccharide, lypooligosaccharide of these serogroups) in sera of rabbits immunized orally with these preparations was measured. Sharp rise of IgG levels (on 2 - 3 orders) compared to baseline has been detected as well as persistence of high titers during the observation period (322 days).


Background The Palliative Care Outcome Scale (POS) is a holistic, validated, Patient Reported Outcome Measure (PROM). PROMs can enable evaluation of patient care, helping to improve service quality. Aims To assess POS as a tool for patient assessment and clinical audit in a nurse-led hospital liaison palliative care team (HPCT). Methods We used POS and POS-S (symptoms) at initial, weekly and last consultations in 30 patients and evaluated the HPCT experience of this. We used the following Minimal Clinically Important Difference in scores to determine PCT effectiveness 80% percent achieving a one-point reduction in pain score Statistically significant reductions in grouped POS and POS-S scores (Wilcoxon signed rank test) Results The HPCT saw 57 patients to collect 30 patients' data. (23 clinically unsuitable, 4 missed). Follow-up questionnaires were available in 19 patients for POS, 15 for POS-S (7 patients seen once, 1 data set destroyed, remainder missed). A one-point reduction in pain score occurred in 74% patients (14 out of 19 with follow-up POS data). Both POS and POS-S median scores improved. POS median score: initial consultation 17, last consultation 6 (p=0.002) POS-S median score: initial consultation 17, last consultation 8.5 (p=0.04). ▸ The HPCT felt that POS was useful to: ▸ Establish the patient's agenda ▸ Enable early discussion of psychosocial concerns ▸ Reduce the risk of missing significant needs Concerns were: ▸ The staff time required to complete POS ▸ That patients found repeated questionnaires burdensome That POS data may underestimate HPCT effectiveness as sometimes advice was disregarded and patients were discharged before a final assessment Conclusions The HPCT significantly improved patient well-being. However, repeat use of POS was burdensome and low inclusion and follow-up rates suggest POS is not a suitable audit tool to measure our HPCT effectiveness at this time. Using POS and POS-S at the initial consultation usefully established the patients' baseline status and needs. The HPCT will continue to use it in this manner.


Modification of the tumor microenvironment (TME) to promote immune-mediated tumor cell destruction is considered to be an essential step for effective immunotherapy. We are evaluating recombinant live-attenuated, double deleted Listeria monocytogenes (LADD) as an immunotherapy platform for the treatment of cancer in several clinical trials in diverse indications. One LADD strain, known as CRS-207, has been engineered to express the tumor-associated antigen mesothelin and is being tested in pancreatic, ovarian and mesothelioma malignancies. Using multi-dimensional immunohistochemistry of paired biopsies from three patients with mesothelioma, we demonstrate the recruitment and expansion of effector tumor-infiltrating lymphocytes, including CD8+ T cells, mature DCs, CD163− macrophages and NK cells, following two prime infusions of CRS-207. In several different syngeneic mouse tumor models, we demonstrate that treatment with LADD engineered to express endogenous tumor antigens also induced significant changes in the TME that were consistent with changes observed in cancer patients, including enhanced CD8+ T cell effector function, recruitment of critical antigen presenting cells and reduction of regulatory T cells, and these changes correlated with significant therapeutic benefit in the mouse. LADD-induced changes to the TME were required for synergistic therapeutic antitumor efficacy combined with immune checkpoint blockade, including targeting MC38 tumor-specific neoantigens. Together, these findings demonstrate that intravenous administration of recombinant LADD therapy induces favorable changes in the tumor microenvironment in mice and humans with promise for effective outcomes in human clinical trials. Citation Format: Weiwen Deng, Takahiro Tsujikawa, Nitya Nair, Thomas Hudson, Weiqun Liu, Chris S. Rae, Edward E. Lemmens, Anthony W. Desbien, William Hanson, Peter Lauer, Lisa M. Coussens, Dirk G. Brockstedt, Thomas W. Dubensky, Jr., Meredith L. Leong. Favorable changes in tumor microenvironment following intravenous dosing with live attenuated Listeria monocytogenes-based immunotherapy [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr A013.


Early predictions of a potential drug candidate's time-course of effect and side-effects, based on models describing drug concentrations, drug effects and disease progression, would be valuable to make drug development more efficient. Pharmacodynamic modeling can incorporate and propagate prior knowledge and be used for simulations of different scenarios.In this thesis three population pharmacodynamic models were developed to describe the antipsychotic effects and the side-effects prolactin elevation and Extra Pyramidal Symptoms (EPS) following administration of D2-receptor antagonists, commonly used in the treatment of schizophrenia.Model parameter estimates of prolactin elevating potencies of six compounds correlated with in vitro values of receptor affinities, and parameters related to diurnal prolactin variation and tolerance were similar for the different compounds. The developed prolactin model can thereby be used to predict the time-course of prolactin elevation in patients for a drug candidate using information on in vitro affinity to the D2-receptor. Furthermore, the clinical antipsychotic effect and the prolactin elevation was found to correlate on the individual level for the three antipsychotic compounds investigated and a quantitative relation between D2-receptor occupancy in the brain and prolactin elevation was established. These results support the use of prolactin concentrations as a biomarker in drug development or for individual dose adjustments in clinical care.The developed model for spontaneously reported EPS adverse events, following treatment with one of five antipsychotics drugs, characterized both the duration and severity of EPS. The model successfully described both the proportions and number of transitions between severity grades and was shown to adequately simulate longitudinal categorical EPS data.Complex pharmacodynamic models are often associated with long estimation times and non-normal distributions of individual parameters. A method for shortening computation times by substituting differential equations for difference equations was evaluated and shown to be valuable for some models. In addition, transformation of distributions allowed for non-normal distributions of between-subject variability to be better characterized and thereby simulation properties were improved.In conclusion, population pharmacodynamic models for a range of D2-receptor antagonists were developed and together with the investigated methods the models can facilitate prediction of effects and side-effects in drug development.


4H-SiC p-i-n diodes were fabricated on epitaxial layers grown by Sublimation Epitaxy in Vacuum (SEV) and were evaluated for microwave power switching applications. Full electrical characterization (C-V, DC I-Vs, reverse recovery characteristics, low and high power microwave testing) has been performed. The results showed that SEV-grown SiC material is suitable for bipolar device fabrication. A doping higher than 1019 cm-3 for the p-type contact layer and lower than 1016 cm-3 for the n-type base layer is necessary to demonstrate microwave p-i-n diodes with similar performance as the ones fabricated on commercially available CVD-grown material.


The role of a plasma inhibitor of erythropoiesis is evaluated in rats with Walker‐256 carcinoma (W‐256). Plasma from tumor‐bearing rats was treated by gel filtration chromatography (Sephadex G‐150) and fractions were combined into four pools on the basis of mol. wt. Inhibitory activity was assayed by adding an aliquot of the plasma fractions to normal rat marrow cells which were cultured for 24 hr with and without erythropoietin. 59Fe‐heme synthesis, [3H]thymidine DNA synthesis, and 14C‐leucine protein synthesis were studied. The results indicated that cultures containing the high mol. wt. pool (>400,000 daltons) had significantly decreased heme, DNA and protein synthesis. This inhibitor also diminished the response to erythropoietin in polycythemic mice. The lower mol. wt. pool stimulated heme synthesis in vitro. To identify the inhibitor further, plasma lipo‐protein classes were isolated by density gradient ultracentrifugation. The very low density lipoprotein (VLDL) and chylomicron fractions markedly inhibited DNA, protein and heme synthesis. Low density and high density lipoprotein fractions were inactive. A lipoprotein inhibitor of erythropoiesis was also identified in cancerous ascitic fluid, and to a lesser degree, in normal rat plasma. We suggest that this VLDL inhibitor of marrow erythropoiesis is a contributing factor in the anaemia of cancer.


For nearly 40 years, engineers, researchers and scientists from the nuclear industry across the World have been trying to understand the behaviors of deposition, bounce and re-suspension of heavy, radioactive particles suspended as a dilute secondary phase in the cooling circuits of primary reactor systems. The aim is to understand the mechanism of transport and deposition of such particles through large, complex geometry systems, so that the risk of dispersal of radioactive particles may be assessed, and confirmed to be acceptably small both in closed containers and in the atmosphere in the case of an accident scenario. The first part of the present work addresses the challenge of robustly and efficiently predicting the behaviors of rigid and spherical particles (referred to as heavy particles) within turbulent boundary layers, the underlying physics of which is the controlling factor on particle deposition in smooth pipes and ducts. In the second component of work we study the deposition and bounce of heavy particles suspended in turbulent flows across heat exchanger tube banks, using Large Eddy Simulation (LES). It was originally proposed to extend the boundary layer work to this application, but it was quickly identified that the deposition mechanisms here are governed by the high core flow turbulence, rather than boundary layer phenomena, so that LES provides the only realistic modelling approach. In both cases the dispersed heavy particles are expressed in a Lagrangian framework solved in an independently developed large-scale parallel code; whilst the fluid phase is described in an Eulerian framework, either based on correlations from published Direct Numerical Simulation (DNS) for the boundary layer models, or from Computational Fluid Dynamics (CFD) simulations for both the boundary layer and tube-bank models, making use of the unstructured-grid based Navier-Stokes solver ANSYS FLUENT. Underpinning this work we implement a complete stochastic Lagrangian particle tracking module, based on a robust and efficient particle localization algorithm which can determine and update the cell containing each particle as the particles move through an unstructured finite volume grid overlying the flow domain. The module can handle correctly the interactions of particles with complex boundaries, and uses a novel numerical scheme for interpolating the carrier-phase velocity field seen by the particles from cell-centred values obtained from CFD computation. It implements a Gear three-level implicit scheme to compute the particle velocity, which is more robust, accurate and efficient than the conventional explicit and implicit schemes. The module has been fully parallelized using MPI (Message Passing Interface) settings on a Linux cluster consisting of 20 single CPU node, and further been successfully integrated with both the steady and unsteady ANSYS FLUENT solvers, complete replacing the built-in Lagrangian particle tracking model provided by ANSYS FLUENT. The algorithm and numerical schemes have been validated against analytical solutions of particle transport in a two-dimensional straining shear flow and other cases. For turbulent boundary layer flows, a simpler but more promising stochastic quadrant model, inspired by the discrete random walk model of Kallio and Reeks and the quadrant analysis of Wu and Willmarth, is developed in order to account for the effects of near wall large-scale coherent structures, e.g. sweeps and ejections, on particle transport. The input parameters for the stochastic quadrant model are educed from the corresponding statistics obtained from a Large Eddy Simulation (LES) of a fully developed channel flow. The model is applied to the prediction of deposition of heavy particles in a turbulent boundary layer; both using a Kallio and Reeks correlation based model of the flow, and also a Reynolds-Averaged Navier-Stokes (RANS) flow solution of using ANSYS FLUENT, the latter flow model having the potential to be extended to complex duct geometries. These solutions are compared to those of by solving an alternative Langevin equation of Dehbi, or continuous random walk model, which satisfies the fully mixed condition and describes the fluid velocity fluctuations seen by heavy particles. Prior to the current work no systematic investigation of the potential errors in particle deposition in turbulent boundary layers due to the modified hydrodynamic forces experienced by particles when very close to the wall has been carried out, possibly because of the complexity of the correlations involved. The effect is explored with the present stochastic quadrant model, using recently published composite correlations of Zeng and Balachandar for the particle drag coefficient CD and lift coefficient CL for near wall particles. This work provides an important first confirmation that for practical cases hydrodynamic effects can reasonably be neglected for particle deposition in turbulent boundary layers. The boundary layer methods developed in the first part of this thesis are applicable to the prediction of heavy particle deposition in fairly complex duct geometries, but are shown to be inappropriate for flow over tube-banks, where the boundary layers are no longer the rate limiting feature. Consequently the parallel Lagrangian stochastic particle tracking model is extended to study the particle impaction efficiency on tube banks in a turbulent flow in the framework of Large Eddy Simulation (LES). The flow field, obtained from Large Eddy Simulation with the dynamic Smagorinsky sub-grid scale model within ANSYS FLUENT, is fully validated against existing experimental data. As far as the dispersed particle phase is concerned, the energy losses when particles impact on and generally, but not always, rebound from cylinders within the tube-bank is taken into account using an empirical critical-impact velocity model. The efficiency of particle impaction is measured for particles of three Stokes number, and the results are compared with existing experimental data.


Integrated design of urban drainage systems aims on the abatement of water pollution in the receiving water. This paper outlines the basic approaches in order to formulate and assess appropriate water quality criteria. The analysis of a hypothetical system is performed by means of a deterministic model of the total system. It is shown that the discharges of both the sewer system and the treatment plant into the receiving water have to be taken into account for the assessment of water pollution.


The last decade has witnessed very significant developments in the field of bone marrow transplantation (BMT), resulting in the improved safety and availability of this procedure. The expansion of international registries of voluntary, unrelated donors, the establishment of banks of fetal cord blood stem cells, as well as improved technology for transplantation of stem cells derived from partially matched family members, offer this treatment to patients hitherto not eligible for BMT. In addition to better donor availability, there has been a change in the concept regarding the role of BMT in the treatment of cancer: the understanding that the transplanted donor cells are capable of mounting an immunological assault against the host malignant cells. This goal can be achieved without fully destroying the patient's bone marrow stem cells and thus prepare the patient for transplantation with a reduced dose intensity of the myelotoxic drugs. Such nonmyeloablative conditioning increases the safety of the procedure. These developments have resulted in a vast expansion of the patient population eligible for BMT, including patients older than those who could have benefited from conventional allogeneic BMT with its associated high mortality in the older age groups, and those lacking fully matched family donors. This article surveys these developments and reviews the clinical indications for BMT in selected malignancies that are evidence-based. The role of BMT and its timing, in the light of new alternative solutions already in the market, is also discussed. Such critical evaluation is particularly warranted in view of the vastly higher rate of BMT per capita in Israel, as compared to other western countries, and given the late side effects inherent in the procedure.


INTRODUCTION
Respiratory muscle training is the most commonly used method to revert respiratory muscle weakness; however, the effect of protocols based on non-respiratory maneuvers has not been adequately studied in the pediatric population. The objective of this study was to establish the effect of abdominal muscle training on respiratory muscle strength and forced expiratory flows in healthy adolescents.

METHODS
This was a quasi-experiment. The sample was made up of healthy adolescents divided into two groups: an experimental group who completed eight weeks of active abdominal muscle training, and an equivalent control group. The following indicators were measured: abdominal muscle strength, maximal inspiratory pressure, maximal expiratory pressure (MEP), peak expiratory flow, and peak cough flow, before and after protocol completion. A value of p < 0.05 was considered significant.

RESULTS
All studied outcome measures increased significantly in the experimental group but only MEP increased in the control group. In addition, a higher MEP was observed in the experimental group compared to the control group at the end of the protocol, together with a greater increase in MEP and peak expiratory flow. Finally, the increase in MEP was associated with an increase in cough peak flow in the experimental group but not in the control group.

CONCLUSION
After eight weeks of abdominal muscle training, MEP and peak expiratory flow increased in healthy (sedentary) adolescents. Such effects were associated with intervention-induced increases in cough peak flow.


We assume that the state of a number of nodes in a network could be investigated if necessary, and study what configuration of those nodes could facilitate a better solution for the diffusion-source-localization (DSL) problem. In particular, we formulate a candidate set which contains the diffusion source for sure, and propose the method, Percolation-based Evolutionary Framework (PrEF), to minimize such set. Hence one could further conduct more intensive investigation on only a few nodes to target the source. To achieve that, we first demonstrate that there are some similarities between the DSL problem and the network immunization problem. We find that the minimization of the candidate set is equivalent to the minimization of the order parameter if we view the observer set as the removal node set. Hence, PrEF is developed based on the network percolation and evolutionary algorithm. The effectiveness of the proposed method is validated on both model and empirical networks in regard to varied circumstances. Our results show that the developed approach could achieve a much smaller candidate set compared to the state of the art in almost all cases. Meanwhile, our approach is also more stable, i.e., it has similar performance irrespective of varied infection probabilities, diffusion models, and outbreak ranges. More importantly, our approach might provide a new framework to tackle the DSL problem in extreme large networks.


1 Abstract The choice of corrosion protection system depends on the environment and needed lifetime for the product. The right corrosion protection should be selected in a sustainable point of view, since a well-selected coating system can reduce the environmental and economical impact, by using less and better material. The systems used for classifying corrosion protection often give a passed/not passed result for the number of years it is expected to last in a specific corrosive environment. In the last decades, Electrochemical Impedance Spectroscopy (EIS) has become a popular method for evaluating corrosion protection for organic coatings. EIS can collect quantitative data by monitoring the coatings electrochemical behavior over time, which can be used for optimizing the coating system. The purpose of this thesis was to try to predict how different combinations of coating layers and substrates will perform as a corrosion protection, which could provide information that can optimize the coating process. In this thesis, EIS has been used as a test method to evaluate organic coating systems for corrosion protection, by looking at barrier properties and adhesion for powder coatings on aluminum substrates. The main part of the coatings were applied in the coating plant at Fagerhult AB, but an external supplier has been used as a reference. The powders used in the coating process were based on polyester resins and the substrates were different aluminum alloys. The EIS measurements were performed in the chemistry lab at the School of Engineering at Jönköping University and depending on the sample setup was each sample evaluated for two or four weeks of testing. Two groups of samples had intact coatings and a third group had samples with an applied defect in the coating. The analysis of sample setups with intact coatings showed that the topcoat absorbed water faster than the primer. The samples showed no significant degradation in corrosion protection for the evaluated period and could thereby not provide enough information to be able to conclude which setup give the best corrosion protection over time. The samples with a defect in the coating indicated that two of the substrates provided similar adhesion in the coating-substrate interface. The coating from the external supplier was also included in the test and it showed the best adhesion of the tested samples. The main conclusion is that the coating system used at Fagerhult AB provides a very good corrosion protection. Longer testing time with EIS measurements on intact coatings is needed to be able to rank the different sample setups by failure of corrosion protection.


Novel microwave absorbers combining Co0.33Ni0.67 alloy and reduced graphene oxide (RGO) are fabricated and their excellent microwave absorption properties demonstrated. Co0.33Ni0.67 alloy particles are prepared by a one-pot solvent-thermal method from CoCl2$6H2O and NiCl2$6H2O. The prepared Co0.33Ni0.67 alloy particles are confirmed from SEM observation, EDS analysis and XRD measurements. RGO/Co0.33Ni0.67 composites are then fabricated by adding the Co0.33Ni0.67 alloy particles into a colloidal dispersion of GO and thermally reducing at 210 C. The composition of RGO/Co0.33Ni0.67 is characterized by Raman, XPS, VSM, XRD and FTIR measurements. An SEM micrograph indicates the sandwich-like structure of RGO/ Co0.33Ni0.67 with Co0.33Ni0.67 alloy particles intercalated into the RGO sheets. By suitably adjusting the dielectric loss and magnetic loss derived from different contents of the RGO and Co0.33Ni0.67, an RGO/ Co0.33Ni0.67 composite with excellent microwave absorption properties is obtained. The maximum reflection loss is up to 50 dB at a thickness of only 1.8 mm. In addition, the absorption bandwidth exceeding 10 dB reaches up to 14.0 GHz with matching thicknesses of 5.0–1.4 mm and covers the whole Ku band at a thickness of only 2.0 mm.


In Reply. — The appetite disturbance noted by the Weissmans was not included in our table because, as stated in our "Methods" section (p 133), To be included in a particular diagnostic syndrome, a symptom had to be a temporally related part of the symptom cluster. For example, the weight loss experienced by Mark Vonnegut during his manic episode was not included in the diagnosis of a possible depression, which occurred temporally before the manic episode. For similar reasons, the suicidal behavior was not included in the depression table. It is possible that the admixture of suicidal ideation with the manic episode (if not literary license) represented a mixed affective condition, since the author does report marked mood swings (eg, "My happiness and sadness was all out of proportion to anything that was happending." 1(p108) ).


This article focuses in particular on the recent economic dynamism of the state of Coahuila, situated directly along the US-Mexican border. Since the mid-1970s, the development strategy of Coahuila's administrative elites has become increasingly centred on creating favourable conditions for foreign direct investment, which became widely considered a recipe for triggering higher levels of productivity and economic growth.
Besides generating employment and contributing to manufactured exports, foreign direct investment can theoretically generate positive spill-overs to domestic firms by transferring technology and upgrading worker skills. In particular after the effectuation of the North American Free Trade Agreement (NAFTA) in 1994, Coahuila has become a major receptor of foreign direct investments, making it one of Mexico's most important export-oriented manufacturing states, backed above all by sizeable investments in the automobile and garment industries. However, detailed analysis of these investments shows that the total number and volume of new investments since NAFTA, as well as the employment it has generated, has been unevenly divided across Coahuila's sub-regions.
Moreover, qualitative analysis of the different industrial sectors demonstrates that Coahuila's export-oriented growth in the second half of the 1990s relied predominantly on foreign capital instead of building upon existing local industrial traditions. Consequently, there is only little evidence of local learning, innovation and upgrading. These outcomes argue for an institutional approach, where supportive public policies are needed to promote endogenous productive capacities and create more sustainable, long-term economic development.


Background: The old-age home industry is mostly unregulated and there is a need for putting in place certain minimum standards. Many times poor and destitute persons who may need institution-based care cannot afford them. Long-term care has a price, and there is also a need for debate on its policy and best practice.  Objectives: 1) To find out the various factors for availing the residential services of old age homes. 2) To assess the facilities available in old age homes. 3) To study the quality of life of elderly people in old age homes. Methods: It was a descriptive cross-sectional study. Study population was elderly (age ≥60 years) enrolled in free and paid old age homes (OAHs) of Lucknow city. All the elderly living in OAHs for ≥ 6 months and had given the consent for interview were included in the study. Results: The most important reason for elderly people living in Free OAHs was no care giver (77.1%) followed by poverty (20.0%).  In case of Paid OAHs it was no care giver (36.4%) followed by self-satisfaction (34.8%). Services were significantly better (p <0.05) in paid type of OAHs. Statistically significant differences in the mean score of quality of life were found in case of type of OAH and financial dependency status of elderly people. Conclusions: No care giver, self-satisfaction and loneliness were important reasons in Paid OAHs whereas in Free OAHs no care giver, poverty and support from children were the main reasons. With the exception of food all other facilities were significantly better in paid OAHs. Quality of life and facilities of Paid OAHs were significantly better than Free OAHs. Financial status of elderly people was responsible for this significant difference.


Changes to landscape can be drastic or gradual, but where humans take up residence change is inevitable. Artistic depictions of landscape often reflect these changes.


This thesis investigates the reconstruction of \(Z\)(\(\to\) \({ee}\))\(\gamma\) events with the ATLAS detector at the LHC. The capabilities of the detector are explored for the initial run scenario with a proton-proton centre of mass collision energy of \(\sqrt{s}\) = 7TeV, and an integrated luminosity of \(\char{cmsy10}{0x4C}\) = 1 fb\(^{-2}\). Monte Carlo simulations are used to predict the expected precision of a differential cross-section measurement for initial state radiation \(Z\) + \(\gamma\) events, both with respect to the transverse momentum of the photon, \(p_T\) (\(\gamma\)), and the three body \({ee}\)\(\gamma\) invariant mass. A bin-by-bin correction is used to account for the signal selection efficiency and purity, and to correct the measured (simulated) distribution back to the theoretical prediction. The main backgrounds are found to be from the final state radiation \(Z\) + \(\gamma\) process, and from jets faking photons in \(Z\) \( \to\) \({ee}\) events. The possible QCD multijet background is studied using a fake-rate method, and found to be negligible for the particle identification cuts used in the analysis. The main systematic uncertainties on the differential cross-section measurements are explored with Monte Carlo simulations, and found to be of a similar scale to the statistical errors for the chosen distribution binning. The three body \({ee}\)\(\gamma\) invariant mass distribution was then used as the basis of an exclusion study on new particles decaying to the \(Z\)(\({ee}\))\(\gamma\) final state. Under the assumption that the measured data agrees with the Standard Model prediction, exclusion limits were placed at 95% confidence level on the cross-section times branching ratio for a new scalar (modelled by SM Higgs process), or vector (based on a low-scale technicolor process) particle hypothesis, for particles in the mass range 200 to 900GeV. Limits of the order \(\char{cmsy10}{0x4f}\)(0.01) - \(\char{cmsy10}{0x4f}\)(0.1) pb on the cross section times branching ratios are predicted, which would improve on the equivalent limits previously calculated by the DO experiment at the Tevatron collider, albeit in a different \(\sqrt{s}\) region, where cross-sections will generally be higher for new massive particles. In addition to the \(Z\)\(\gamma\) measurements, a digital timing calibration procedure was developed for the Cluster Processor (CP) subsystem of the level-1 calorimeter trigger. This work was essential to providing a repeatable and robust mechanism for timing in the digital processing in the CP system, a necessary ingredient for a robust and reliable trigger system; a pre-requisite of any physics analysis. This calibration procedure is described here.


The authors studied the content of beta 2-microglobulin (beta 2-MG) in the blood serum and its excretion with the urine in 85 patients with chronic and 35 with lupoid glomerulonephritis (CGN and LGN) depending on the activity of the disease and state of the renal function. In active CGN and LGN one could observe a distinct increase of the content of beta 2-MG in the blood serum and an increase of its excretion with the urine that may be related to presence of marked dystrophic changes of the canalicular apparatus of the kidneys leading to disorders of reabsorption and beta 2-MG catabolism as well as disorders of the immune homeostasis revealed in these diseases. Results indicate that the beta 2-MG levels in the blood serum and urine may be considered as criteria of CGN and LGN activity.


The High Temperature Engineering Test Reactor (HTTR) is the first high-temperature gas-cooled reactor (HTGR) in Japan. The HTTR is a graphite-moderated and helium gas-cooled reactor with thermal power of 30MW and the maximum reactor outlet coolant temperature of 950°C. Main objectives of the HTTR are to establish and develop HTGR technology and to demonstrate process heat application. The HTTR has conducted two test operations which are safety demonstration test and continuous operation. The safety demonstration tests focus on the verification of the inherent safety features of the HTGR that is the negative reactivity feedback effect of the core brings the reactor power safely to a safe and stable level without a reactor scram and the temperature transient of the reactor is slow in case of anticipated operational occurrences (AOOs). The safety demonstration tests include reactivity insertion test, coolant flow reduction test and loss of forced cooling (LOFC) test. Reactivity insertion test and coolant flow reduction test have been conducted since 2002. These tests demonstrated the inherent safety features of the HTGR in case of reactivity insertion and coolant flow reduction, and provided valuable data for code validation. LOFC test will start in the middle of 2010. LOFC is one of the important accident scenarios in the safety assessment of the HTGR. This test result will show extreme safety features of the HTGR and further improve the safety design approach of the HTGR. Obtained data can be useful to validate plant safety analysis codes. The continuous operation has been conducted to obtain plant data to establish HTGR technology and to demonstrate capability of the HTTR to supply stable heat to heat utilization system for long-term. Two operations of 30-day continuous operation in rated operation mode (in which designed reactor outlet coolant temperature of 850°C) and 50-days continuous operation in high temperature test operation mode (in which designed reactor outlet coolant temperature of 950°C) have been conducted so far. The 30-day continuous operation was achieved in 2007 and a good fuel performance to retain fission products within the coated fuel particle was clarified. The HTTR conducts 50-days continuous operation in 2010 to add useful operation data at high temperature to improve technical basis of HTGR and to realize high temperature heat application of HTGR.Copyright © 2010 by ASME


Reinforcement Learning (RL) is a popular machine learning paradigm where intelligent agents interact with the environment to fulfill a long-term goal. Driven by the resurgence of deep learning, Deep RL (DRL) has witnessed great success over a wide spectrum of complex control tasks. Despite the encouraging results achieved, the deep neural network-based backbone is widely deemed as a black box that impedes practitioners to trust and employ trained agents in realistic scenarios where high security and reliability are essential. To alleviate this issue, a large volume of literature devoted to shedding light on the inner workings of the intelligent agents has been proposed, by constructing intrinsic interpretability or post-hoc explainability. In this survey, we provide a comprehensive review of existing works on eXplainable RL (XRL) and introduce a new taxonomy where prior works are clearly categorized into model-explaining, reward-explaining, state-explaining, and task-explaining methods. We also review and highlight RL methods that conversely leverage human knowledge to promote learning efficiency and performance of agents while this kind of method is often ignored in XRL field. Some challenges and opportunities in XRL are discussed. This survey intends to provide a high-level summarization of XRL and to motivate future research on more effective XRL solutions. Corresponding open source codes are collected and categorized at https://github.com/Plankson/awesome-explainable-reinforcement-learning.


Hearing Loss![Figure][1]

Hair cells (green) and supporting cells (cyan) in a neonatal mouse cochlea

PHOTO: GUOQIANG WAN

"Supporting cells" in the inner ear have more to offer than their uninspiring name suggests. Studies of deafness often emphasize the role of hair cells, the sensory cells that transmit sound signals to the brain. Loss of hair cells causes permanent deafness, because these cells cannot regenerate. Loss of supporting cells also causes deafness, but a new study suggests that there may be hope. Mellado Lagarde et al. found that supporting cells can regenerate during a brief time period after birth. When they selectively eliminated supporting cells in newborn mice, nearby cells rapidly replaced them, thereby preserving hearing. The next step is to find a drug that induces regeneration.

Proc. Natl. Acad. Sci. U.S.A. 10.1073/pnas.1408064111 (2014).

 [1]: pending:yes


: Out of 21 male patients with osteoporosis who visited an outpatient clinic for endocrine diseases in two years (1994-1995), three had systemic mastocytosis as diagnosed histopathologically. Two of these had characteristic features of urticaria pigmentosa, consisting of multiple brown nodules on the skin of trunk and extremities, and a positive Darier sign. In all of them the excretion of the histamine metabolites methylhistamine and methylimidazoleacetic acid in a 24-hour urine specimen was increased. When osteoporosis is diagnosed in men or premenopausal women, underlying pathology could be considered. Cautious investigation of signs and symptoms of systemic mastocytosis in such patients might prove this disease be less rare than is often assumed.


ABSTRACT Injury and subsequent insufficiency of the medial patellofemoral ligament (MPFL) has been described as the "essential lesion" of recurrent lateral dislocation of the patella. As the biomechanical role of the MPFL has become better understood, techniques for surgical reconstruction are being popularized. Unfortunately, to date, there is no scientific evidence to support one technique over another. However, we do have sound information regarding the biomechanics of the MPFL. The primary purpose of the MPFL is to help guide the patella safely into the confines of the trochlea during the initial 20 to 30 degrees of knee flexion. Before undertaking surgical reconstruction of the MPFL, a thorough understanding of the anatomy of the retinacular layers of the medial side of the knee, as well the recognition of the biomechanics of the MPFL, is mandatory. The MPFL is under greatest tension with the knee in full extension and maintains this tension throughout the initial 30 to 40 degrees of flexion. To avoid overconstraint of the knee, the placement of fixation upon the femur is critical. The femoral attachment site should preferably be anatomic but never proximal to the native origin between the medial epicondyle and the adductor tubercle as this can lead to postoperative stiffness and/or ultimate graft failure.


For solving the problem of drill breakage and increasing productivity, a built-in adaptive drilling control scheme has been proposed. The torque of the spindle detected using a floating torque measuring mechanism has been regulated by controlling the feed rate of the spindle using PID control algorithm. The adaptive control algorithm has been integrated into a numerical controller. Motor control functions are performed in a timer interrupt subroutine to realize real-time parallel processing. An experimental system has been established. Experiments have demonstrated that the system is applicable in preventing drill breakage and increasing productivity.


The discrete spectral problem of Ablowitz{Ladik is considered in the case in which the potential has a nite support of length L. The spectral transform is explicitly computed and a recurrence relation on the length L for computing it in L algebraic step is given. This spectral transform can be used to generate via the scattering method a nite dimensional version of the dynamical systems associated to the Ablowitz{Ladik spectral problem. A special case in which the potential can be constraint to evolve in time on a semi-line is proposed. The truncated soliton, i.e. the potential obtained by putting to zero the one soliton outside an interval of length L is examined in detail. The suucient and necessary condition for having a soliton contained in the truncated soliton solution is derived. Finally, the continuous counterpart of these nite{dimensional systems is considered. The spectral transform is derived via a Riccati equation and the special case of the truncated soliton is studied.


Cardiovascular diseases (CVDs) are still the principal cause of death worldwide. Weakened endothelial function followed by inflammation of the vessel wall hints at atherosclerotic lesion formation that causes myocardial infarction and stroke. Heart failure can arise as consequence of large myocardial infarctions. In its more severe stages, heart failure patients have a life anticipation that is parallel to destructive cancers. Accordingly, the increase in risk factor load by metabolic diseases and age augments the incidence for vascular and cardiac diseases and provides a challenge for developing efficient treatments. There is widespread proof to show that drug treatment of conventional risk factors is effective in reducing cardiovascular events. More effective treatment of CVD with various classes of antihypertensive drugs has been associated with greater benefits, but some recent studies suggest we may be reaching the optimal level of treated blood pressure in some patient groups. Apart from the treatment of cardiovascular risk factors with pharmacological agents and the use of antithrombotic drugs, there is growing awareness of the role of dietary factors and herbal medicines in the prevention of CVD and the possibility of their use in treatment. Investigators from different places of the world like China, Taiwan, Bangladesh, Pakistan, and so forth contributed to this special issue by presenting tremendous papers. These papers deliver an analysis in this field and create innovative contributions concerning the mechanism of action of bioactives and traditional herbal medicine for the treatment of cardiovascular/cerebrovascular diseases.

Some interesting papers in this special issue address the cardioprotective effects of Chinese herbal medicine and natural compounds. For instance, a paper summarized the synergetic cardioprotective potential of herbal combination of four plants, namely, Terminalia arjuna, Cactus grandiflorous, Crataegus oxyacantha, and Piper nigrum through curative and preventive mode of treatment analysis and this paper reported preadministration and postadministration of herbal mixture restore the levels of biomarker of cardiotoxicity, which includes cardiac marker enzymes, lipids profile, and antioxidant enzymes. Similarly, another paper in this issue reports the cardioprotective effects of Sundarban honey on cardiac troponin I, cardiac marker enzymes, the lipid profile, lipid peroxidation products, and histoarchitecture of the myocardium against isoproterenol-induced myocardial infarction in Wistar rats. Pinggan Qianyang recipe (PQR), a Chinese medicine recipe, has long been used for calming the liver. It has also been used to treat essential hypertension with satisfactory results. Consistent with this concern, this special issue published a paper that reports PQR exerts its antihypertensive effect through deterioration of the vascular remodeling process. The mechanism might be associated with regulating differentially expressed miRNAs in aorta tissue.

Despite the fact that there are major developments in treating ischemic stroke over the last decade, stroke is still a serious concern for which effective drug therapy is not yet available. In the search for neuroprotective agents from natural sources, a number of plant extracts and several natural products were isolated and reported to provide neuroprotection against ischemic stroke. A few papers in this special issue report the neuroprotective effects of Chinese herbal medicine and natural compounds. For instance, Antrodia camphorata (A. camphorata), a fungus generally used in Chinese folk medicine for the treatment of viral hepatitis and cancer, has shown neuroprotective effects in embolic rats. This effect may correlate with the downregulation of the iNOS, HO-1, Bax, and activated caspase-3 and the inhibition of OH° signals. Another study shows alpha-lipoic acid attenuates middle cerebral artery occlusion-induced cerebral ischemia and reperfusion injury via insulin receptor-dependent and PI3K/Akt-dependent inhibition of NADPH oxidase. Moreover, an interesting study in this special issue established the effects of tetramethylpyrazine (TMP) on functional recovery and neuronal dendritic plasticity after experimental stroke. In this study, the authors have shown that enhanced dendritic plasticity contributes to TMP-elicited functional recovery after ischemic stroke.

Hinokitiol is a naturally occurring compound isolated from the wood of Chamaecyparis taiwanensis. It is involved in multiple biological activities, including antimicrobial and antitumorigenic activities. Although hinokitiol has been reported to inhibit inflammation, its immunological regulation in lymphocytes remains inadequate. With this context, a well-designed study reported that hinokitiol downregulated cyclin D3, E2F1, and Cdk4 expression and upregulated p21 expression in concanavalin A- (ConA-) stimulated T lymphocytes. It further demonstrated that hinokitiol upregulates p21 expression and attenuates IFN-γ secretion in T lymphocytes from the spleens of mice, thereby arresting the cell cycle in the G0/G1 phase. These authors concluded that hinokitiol provides benefits in treating patients with autoimmune diseases. We expect that this special issue grants inventive awareness to increase the therapeutic value of herbal and/or Chinese medicines for treatment or prevention of cardiovascular and ischemia-reperfusion injury-related disorders.

Joen-Rong Sheu

Pitchairaj Geraldine

Mao-Hsiung Yen


A study of 50 women undergoing first-time induced abortion and 50 women undergoing second-time induced abortion is reported. Although repeat aborters can not be characterised as a special group of women, it is important that initiatives be taken to reduce the incidence of repeat induced abortion. A suggestion for possible intervention is a thorough post-abortion contraceptive counselling and follow up of women who undergo initial induced abortion. Further general improvement in sex education and use of contraceptive methods is necessary. In this area, avoidance of risk-taking is very important as well as caution during periods of change from one contraceptive method to another. Generally, use of contraceptive methods with a very high effectiveness must be recommended, i.e. oral contraceptives, IUDs, and sterilisation.


We study a dynamical model of interconnected firms which allows for certain market imperfections and frictions, restricted here to be myopic price forecasts and slow adjustment of production. Whereas the standard rational equilibrium is still formally a stationary solution of the dynamics, we show that this equilibrium becomes linearly unstable in a whole region of parameter space. When agents attempt to reach the optimal production target too quickly, coordination breaks down and the dynamics becomes chaotic. In the unstable, 'turbulent' phase, the aggregate volatility of the total output remains substantial even when the amplitude of idiosyncratic shocks goes to zero or when the size of the economy becomes large. In other words, crises become endogenous. This suggests an interesting resolution of the 'small shocks, large business cycles' puzzle.


The design of eco-friendly electrocatalysts for ethanol valorization is an open challenge towards sustainable hydrogen production. Herein we present an original fabrication route to effective electrocatalysts for the ethanol oxidation reaction (EOR). In particular, hierarchical MnO2 nanostructures are grown on high-area nickel foam scaffolds by a plasma-assisted strategy and functionalized with low amounts of optimally dispersed Au nanoparticles. This strategy leads to catalysts with a unique morphology, designed to enhance reactant–surface contacts and maximize active site utilization. The developed nanoarchitectures show superior performances for ethanol oxidation in alkaline media. We reveal that Au decoration boosts MnO2 catalytic activity by inducing pre-dissociation and pre-oxidation of the adsorbed ethanol molecules. This evidence validates our strategy as an effective route for the development of green electrocatalysts for efficient electrical-to-chemical energy conversion.


The authors have been developing a large AC current source with a single-phase Bi2223 superconducting transformer. The authors aim to develop the source of supplying current with the maximum frequency of 1 kHz and the maximum amplitude of 1 kA. However, the conventional transformer has some leakage inductance resulting in large voltage drop, and therefore it was unable to transport the current with high frequency and large amplitude. In this paper, the authors propose a configuration of the transformer with less leakage inductance than inductance of the conventional one. Improved current source has output current with the maximum frequency of 1 kHz and the maximum amplitude of 900 A. In addition, a protection system for normal transition in the transformer is proposed. The authors have proposed the active power method to detect the normal transition. For high frequency and large current, however, the normal transition may be incorrectly detected by using the method due to large AC loss. The authors show a new method to avoid the incorrect detection by an empirical formula based on measurement results of the AC loss. From the experimental results of the normal transition, the authors show that the proposed method is more correct to detect the normal transition than the conventional method.


This paper describes an analysis of the performance overheads caused by the processing and space requirements of the IKEv2 protocol using Diameter and EAP-TLS authentication when protecting Mobile IPv6 signaling. IKEv2 negotiation between mobile nodes, the home agent, and the AAA server in a large-scale reference scenario is considered. The analysis is based on queuing theory and focuses on the overall utilization of the home agent and the AAA server by the IKEv2 reauthentication processes as well as the total mean response time for such a process in the network.


Recent studies have demonstrated the usefulness of dendritic cells (DCs) genetically modified by adenovirus vectors (Ad) to immunotherapy, while sufficient gene transduction into DCs is required for high doses of Ad. The RT-PCR analysis revealed that the relative resistance of DCs to Ad-mediated gene transfer is due to the absence of Coxsackie-adenovirus receptor expression, and that DCs expressed adequate alpha(v)-integrins. Therefore, we investigated whether fiber-mutant Ad containing the Arg-Gly-Asp (RGD) sequence in the fiber knob can efficiently transduce and express high levels of the LacZ gene into DCs. The gene delivery by fiber-mutant Ad was more efficient than that by conventional Ad in both murine DC lines and normal human DCs (NHDC). Furthermore, NHDC transduced with fiber-mutant Ad and conventional Ad at 8000-vector particles/cell resulted in a 70-fold difference in beta-galactosidase activity. We propose that alpha(v)-integrin-targeted Ad is a very powerful tool with which to implement DC-based vaccination strategies.


This study sought to investigate the relationship between parental psychopathology and health‐related quality of life in a group of Nigerian adolescents with epilepsy. The participants were 86 adolescents with epilepsy (50 males, 36 females; mean age 14y 5mo [SD 2y 1mo]; age range 12–18y). There were 54 (62.8%) adolescents with complex partial seizures, six (7.0%) with simple partial seizures, 14 (16.3%) with generalized tonic‐clonic seizures, four (4.7%) with absence seizures, and eight (9.2%) with other types of seizure. They completed the Quality of Life in Epilepsy Inventory for Adolescents (QOLIE‐AD‐48). Parents also completed the General Health Questionnaire, Zung's Self‐Rating Anxiety Scale, and Zung's Self‐Rating Depressive Scale as measures of their psychopathology. Factors correlating with poor overall quality of life in the adolescents include longer duration of illness, large number of antiepileptic drugs, more severe medication toxicity, and psychopathology in the parents. General psychopathology in parents is significantly associated with QOLIE‐AD‐48 subscales of Epilepsy Impact (r= 0.527, p < 0.001), Attitude (r= 0.214, p= 0.047), Physical Function (r= 0.417, p < 0.001), Stigma (r= 0.305, p= 0.004), Social Support (r= 0.365, p= 0.001), and School Behaviour (r= 0.220, p= 0.042). There is a possibility of a cross‐cultural difference on the effect of epilepsy on the quality of life of adolescents. Psychopathology in parents is significantly associated with poorer quality of life of these adolescents. Physicians should consider this, therefore, when planning intervention strategies in improving the quality of life in adolescents with epilepsy.


Recent advances in generative modeling, based on large scale deep neural networks, provide a novel approach for sharing individual-level datasets (micro-data) without privacy concerns. Unlike differential privacy, which enforces a specific query mechanism on data to ensure privacy, generative models can accurately learn the statistical patterns of such micro-data and then be used to generate "synthetic data" that accurately reflects these statistical patterns, yet contain none of the original data itself, and thus can be safely shared for analysis and modeling without compromising privacy. The successful application of these techniques to various industries including healthcare, finance, and autonomous vehicles is promising and results in continued investment in research and development of generative models in both academia and industry.


This report describes the use of 99mtechnetium pertechnetate (99mTcO4−) and 131[for imaging of a metastatic thyroid carcinoma in a dog. The 131] imaging showed metastatic lesions undetected by the 99mTcO4− imaging on 2 separate occasions. The possible mechanisms for the discrepancies between 131I and 99mTcO4− imaging of thyroid carcinomas are discussed. The use of 131I for the imaging of functional thyroid carcinomas in the dog is recommended.


The selectins: E-selectin, P-selectin, and L-selectin are adhesion molecules that are crucial for binding of circulating leukocytes to vascular endothelium during the inflammatory response to injury or infection. Accumulated evidence indicates that selectins regulate adhesion of circulating cancer cells to the walls of blood vessels. Selectin ligands are transmembrane glycoproteins expressed on leukocytes and cancer cells that promote bond formations with selectins to mediate inflammatory processes. Selectins and selectin ligands also participate in signal transduction to regulate diverse cellular functions. Sialyl Lewis X (sLe(x)) and sialyl Lewis A (sLe(a)) tetrasaccharides are carbohydrate motifs displayed on protein or lipid scaffolds that are critical components of functional selectin ligands. Selectin binding to sLe(x) and sLe(a) present on colon, gastric, bladder, pancreatic, breast, and prostate carcinomas enhances distant organ metastasis. High expression of sialyl Lewis ligands on these cancers is significantly correlated with a poor post-operative prognosis. This review will focus on the roles of E-selectin and P-selectin in cancer progression. Understanding the role of selectins in cancer supports the development of novel selectin-based therapies to control metastasis.


ABSTRACT A lower jaw was recently discovered in a limestone concretion in association with the Late Cretaceous (Turonian) ammonite Spathites puercoensis (Herrick and Johnson, 1900) from the Carlile Member of the Mancos Shale in Sandoval County, New Mexico. It is nearly complete and comprises the aptychus with a hinge along the midline. The better-preserved plate, the left (according to its position in life), is roughly triangular in shape with a broadly rounded lateral margin, a narrowly rounded posterior margin, and a weakly concave anterior margin. It is 26.2 mm wide and 33.0 mm long. Together, the left and right plates form an escutcheonlike shape that projects slightly forward at the apex. The ratio of jaw width to length (26.2 mm × 2 / 33.0 mm) equals 1.59. The aptychus consists of yellow-orange calcite and is covered with comarginal ribs that parallel the lateral and posterior margins and become more prominent toward the posterior end. It is likely that this jaw belongs to the associated ammonite and would have comfortably fit inside the body chamber, based on a comparison of the length of the jaw and the whorl height, suggesting that it functioned as a jaw, rather than as an operculum. It is the first report of an ammonite jaw in the genus Spathites and the first reported occurrence of an ammonite jaw from New Mexico.


Three simple protocols for the determination of the enantiomeric excess of chiral amines, hydroxylamines and diols have been developed utilising boronic acid templates. In Chapter 1 some of the existing methods for determining the enantiomeric excess of chiral substrates have been reviewed including the use of chiral solvating agents, chiral derivatization agents, chiral gas chromatography, chiral HPLC, circular dichroism, UV-visible spectroscopy and fluorescence spectroscopy. In Chapter 2 the previous work by the Bull-James group is discussed along with the cited uses of our three-component derivatization protocols for determining the enantiomeric excess of chiral amines and diols. The syntheses of a range of α-arylglycines are described and their optical purities determined by a simple 1H NMR derivatization protocol. In Chapter 3 the first reported chiral derivatization protocol for determining the enantiomeric excess of chiral hydroxylamines by 1H NMR spectroscopy has been developed by formation of nitrono-boronate ester complexes whose structures have been confirmed by X-ray crystallography. A range of chiral hydroxylamines have been prepared and the mechanism for the conversion of a chiral amine to its corresponding hydroxylamine has been proposed by analysis of the side product formed during the final reaction step converting an oxaziridine to the desired hydroxylamine. In Chapter 4 the Horeau Principle is discussed and its applications in the literature reviewed. A new derivatization protocol based on this principle has been developed employing an achiral boronic acid template to form diastereomeric dimeric boronate complexes by its reaction with two equivalents of a chiral diol. The scope and limitations of this protocol have been determined and molecular modelling has been used to explain the differences in diastereomeric resonances observed for the boronate complexes formed.