Literature in non-canonical Englishes is infused with distinct culture, history, and politics. Should the creative writer adhere strictly to traditional English literary norms, language use would seem artificial and unconvincing, and social nuances would be lost. This paper tests this hypothesis with African-American English (AAE) literature. One passage was scanned for AAE features, and examined for social nuances these features convey. European-American and African-American respondents received passages as written and with AAE features deleted, with follow-up questionnaires. Results indicate connections made between language used in the text and identification of character background and desire to read more by this author. The function of non-traditional linguistic elements is demonstrated, supporting their inclusion in pedagogical texts.


This intervention study collected data on Chinese, Filipino, and Vietnamese high-risk adults to ascertain similarities and differences in drug use patterns. Study participants (N = 126) participated in a 5-week intervention study to mitigate substance abuse and the prevalence of hepatitis C and HIV among high-risk adults in San Francisco, San Mateo, and Santa Clara Counties of California. Data reported were collected at baseline. The National Outcome Measures questionnaire was used to document individual substance use in the past 30 days. Filipinos reported higher use rates for alcohol, cigarettes, marijuana, and crack cocaine in the past 30 days compared with their Chinese and Vietnamese counterparts; these differences proved to be statistically significant (p ≤ .03). Data analysis also showed that the alcohol use of Filipino and Vietnamese homosexual men was significantly greater than their Chinese counterparts (p = .04). A statistically significant inverse association was found for alcohol use for those in the criminal justice system during the past 30 days (odds ratio [OR] = 0.37, p = .03). In addition, a positive association for other tobacco use (OR = 11.98, p = .00) was reported for those in the criminal justice system. Age group analyses indicated a positive association for those between 18-25 years old for alcohol use (OR = 5.40, p = .00). These data confirm the importance of disaggregation of data. If collapsed into a general Asian or Asian and Pacific Islander ethnic group category, as is often the case, the unique behaviors of the individual groups would be lost.


Samuel Pepys's affair with his wife's companion Deborah Willet is one of the most celebrated episodes in his journal of the 1660s. When Pepys ended his journal in May 1669, he also believed that he had ended contact with Deb. Unable to trace her in the historical record, scholars have been forced to accept this conclusion. However, new evidence shows that Deb Willet did not disappear from Pepys's life. Rather, she married soon after the end of the diary and her husband, the clergyman Jeremiah Wells, quickly became a client of Pepys. This article explores the evidence on the connections between the three in the 1670s, offering a case study of one individual's role in Pepys's patronage network, and reflecting back upon events in the journal.


The use of Neuromuscular Electrical Stimulation (NMES) to improve swallowing function in the Early Intervention home-based population with pharyngeal phase dysphagia is described using a case series design. Five children had Modified Barium Swallow studies (MBSS) completed followed by a course of swallowing therapy. The children had NMES administered home-based for 60-minute sessions. The number of treatment sessions ranged from 11 to 63, and the MBSS was repeated at the end of therapy. All five children improved functional swallowing as documented by the attending radiologist This case series design provides data that may support the use of NMES in the Early Intervention population as a treatment modality for pharyngeal phase dysphagia.


Rotavirus initiates, but blocks completion of, autophagy to replicate and assemble new viral particles. Viruses commonly use a cell's machinery for their own propagation and subvert antiviral defenses, such as autophagy, a cellular degradation process that can degrade intracellular viral particles. Crawford et al. found that rotavirus, which causes severe gastroenteritis and vomiting predominantly in children, depended on the autophagy machinery for its replication, because chemically inhibiting autophagosome formation or deleting critical autophagy genes drastically reduced the intracellular viral load. The rotavirus viroporin NSP4 (nonstructural protein 4), a protein that creates aqueous transmembrane pores, induced calcium release from the endoplasmic reticulum (ER) into the cytoplasm, initiating the early stages of autophagy through the calcium/calmodulin-dependent kinase kinase β (CaMKK-β) pathway. Initiation of autophagy was abrogated in cells treated with a calcium chelator or a CAMKK-β inhibitor. In cells infected with an NSP4 mutant that could not induce a cytosolic calcium increase, the increase in cytosolic calcium was restored when mutant-infected cells were cotreated with the ER calcium pump inhibitor thapsigargin, indicating that rotavirus-induced autophagy was mediated specifically through the viroporin-induced release of calcium that activated CaMKK-β rather than through an ER-mediated unfolded protein response induced by the accumulation of NSP4 in the cell. In a time-course analysis, the processed form of LC3, a component of the autophagosome, was lipidated soon after the NSP4-induced calcium release, followed by formation of autophagosomal puncta containing LC3 and NSP4 that surrounded viroplasms, sites of viral replication. However, autophagy was prevented from progressing to the later stage of lysosomal fusion, in which the virus would be degraded. Using a tandem-tagged red fluorescent protein and green fluorescent protein (RFP-GFP) LC3 probe in which the low pH within lysosomes quenches only the GFP fluorescence, the authors showed that GFP signal was only lost in NSP4-mutant virus-infected cells, whereas cells infected with wild-type rotavirus retained both signals. Furthermore, NSP4 and the rotavirus outer capsid protein VP7 were detected surrounding autophagosome-engulfed viroplasms, indicating completion of particle assembly into new, mature viruses. By inducing autophagosomal formation but inhibiting lysosomal fusion, rotavirus uses the autophagosome as a transient envelope for its own replication and assembly. Their findings demonstrate how the rotavirus requires, but ultimately escapes, the antiviral function of autophagy and suggests that this infectious mechanism may be targeted in treating rotavirus infection and possibly other viral infections in which the virus induces autophagy and increases cytosolic calcium. S. E. Crawford, J. M. Hyser, B. Utama, M. K. Estes, Autophagy hijacked through viroporin-activated calcium/calmodulin-dependent kinase kinase-β signaling is required for rotavirus replication. Proc. Natl. Acad. Sci. U.S.A.109, E3405–E3413 (2012). [Abstract] [Full Text]


In the past seven years, Genome-Wide Association Studies (GWAS) have identified hundreds of variants associated with cardiometabolic quantitative traits and diseases. Many genetic loci appear to harbour variants associated with multiple phenotypes (cross-phenotype associations, CP). CP associations highlight that phenotypes may share common underlying genetic mechanisms that might, or might not, be consistent with epidemiological expectations and, therefore, add complexity to the relationships between human phenotypes.
Pleiotropy occurs when the same genetic causal element affects more than one phenotype "in parallel" and can explain the presence of CP associations. It can appear at a single variant level, where a single causal variant is related to multiple phenotypes, or at a locus level, that is when multiple variants in the same gene or locus are associated with different phenotypes by affecting the same functional element. However, other potential genetic mechanisms, that can explain CP associations, exist. Among them, mediation occurs when a genetic variant is directly associated with a phenotype and that phenotype is itself causal for a second phenotype or more phenotypes; multi-phenotype allelic heterogeneity is a phenomenon which involves independent uncorrelated variants within the same locus which cause changes in multiple phenotypes, by affecting them through independent pathways related to distinct functional elements.
The identification and characterisation of CP associations across the genome may help uncovering the mechanistic basis of physiological processes that underlie variability of cardiometabolic quantitative traits, and of pathogenetic processes leading to metabolic disorders. The definition of specific patterns of effect combinations on cardiometabolic phenotypes will highlight novel biological pathways, targets for translational research, for therapeutic intervention, and for the understanding of the pathophysiology of human metabolism.

Based on this hypothesis, and in collaboration with the Cross-Consortia pleiotropy group and with the European Network for Genetic and Genomic Epidemiology (ENGAGE) consortium, my PhD project focused on dissection of CP effects, pleiotropy in particular, at common variants across the genome in association with cardiometabolic phenotypes. The objective was to improve our understanding of the extent of shared genetics between cardiometabolic phenotypes and of the influences of DNA sequence variation on risk of metabolic diseases, considering phenotypes as a range of inter-related manifestations of biological mechanisms rather than as isolated events.

My research has been divided into three sub-projects:
Project 1: Clustering and pathway analysis of univariate GWAS results for the detection of pleiotropic effects. We explored multi-phenotype effects at hundreds of established cardiometabolic genetic variants from published univariate GWAS meta-analyses on more than 20 respective phenotypes, by defining clusters of loci with similar multiple effects, comparing them to known epidemiological expectations, and identifying enriched biological networks within the most interesting groups of loci. Our results highlighted that many variants at cardiometabolic loci have multiple associations that characterise different aspects of metabolism. Cardiometabolic loci can be grouped according to their shared multi-phenotype effects and metabolic syndrome represents just one possible combination; in fact, several other unexpected combinations might be observed, for example healthy obesity/unhealthy leanness. We also highlighted that genetic loci with similar cardiometabolic effects are involved in shared biological pathways. Some of these may be expected, for instance, regulation of lipids metabolism or cholesterol transport for groups of loci with strong effects on lipids, and circulatory system processes for genes near blood pressure-association signals. Sometimes groups of loci affected fundamental cell functions, such as regulation of cellular processes, for the loci with effects on obesity and anthropometric traits. The enriched connectivity within pathway networks revealed new potential candidate genes and tissues of action that are more likely to have causal effect on phenotypes.

Project 2: Validating pleiotropy and analysis of locus architecture in potential pleiotropic regions. We aimed to dissect the architecture of established cardiometabolic loci showing multiple associations for a better definition of the underlying mechanisms of multi-phenotype effects and for the discernment of potential pleiotropy from allelic heterogeneity. To this aim, we applied an approximate conditional analysis, based on observed linkage disequilibrium patterns, which led us to the discovery of multiple associations at adjacent variants that underlie the same genetic cause for variability of different phenotypes. Our results also highlighted that a substantial proportion of metabolic loci incorporate complex patterns of multi-phenotype allelic heterogeneity, thus suggesting an important contribution of this mechanism into cross-phenotype effects.

Project 3: Application of a multivariate statistical approach for the study of pleiotropy within cardiometabolic phenotypes. We developed and applied a statistical strategy for joint multivariate analysis of multiple correlated phenotypes using individual genetic data from the ENGAGE consortium to discover new uncovered multiple associations and to follow-up GWAS meta-analysis at two loci, FTO and FADS1. Using this approach we were able to take into account correlation between phenotypes, and we achieved a boost in power; moreover, we improved precision of parameter estimates and of the identification of novel candidate genes. Our results allowed us to identify several variants jointly associated with multiple lipid traits and body mass index. Our approach was useful for the identification of mediation: we, in fact, confirmed mediation underlying causal relationship between adiposity and other cardiometabolic phenotypes at the FTO locus. Additionally, we demonstrated that multiple effects on cardiometabolic phenotypes attributable to the FADS1 locus are mediated by its independent, thus pleiotropic, effect on total cholesterol and triglycerides.

In conclusion, we applied several statistical approaches which allowed dissecting suggestive CP effects and their mechanisms, including pleiotropy, mediation and allelic heterogeneity. Our analyses have demonstrated the complexity of the relationships between cardiometabolic phenotypes related to the variability of both, underlying genetic mechanisms and genetic loci architecture.


Illegal drug use by a large portion of students is an unfortunate feature of most American high schools. (1) Parents and school boards across the nation are debating the merits of fighting and reducing3drug use through drug testing. (2) In Board of Education v. Earls, the Supreme Court upheld a high school policy that required all students who participated in any extracurricular activity to submit to drug testing. This ruling extended the Court's decision in Vernonia School District 47J v. Acton, (4) in which the Court upheld a high school policy requiring student athletes to submit to suspicionless drug tests. The Earls Court's reasoning centered on the broad mandate of schools' "custodial and tutelary responsibility for children" (5) and thus arguably opened the way for drug testing of all students. (6) However, Justice Breyer's concurrence, which provided the crucial fifth vote for the majority, is a harmful obstacle to school boards wishing to implement student drug testing if proper public forums for discussion are not provided, or if substantial public opposition to the proposed drug testing arises from those public debates. In the fall of 1998, the School District of Tecumsech, Oklahoma, in an effort to fight the use of illegal drugs by students, adopted the Student Activities Drug Testing Policy ("Drug Testing Policy"), which requires all students who participate in any extracurricular activity, including the Academic Team and the Future Farmers of America, to submit to drug testing. (7) The Drug Testing Policy requires students to take drug tests (through urine samples) before starting ah extracurricular activity, submit to random testing during participation in that activity and submit to tests at any time upon reasonable suspicion. (8) Respondent Earls, a student at Tecumseh High School, participated in several extracurricular activities that the Drug Testing Policy covered, including the marching band and the National Honor Society. (9) Earls brought a 42 U.S.C. [section] 1983 suit that challenged the District's Drug Testing Policy as violating the Fourth Amendment's protection against unreasonable searches. (10) The District Court, applying Vernonia, rejected the respondent's claim that the Drug Testing Policy violated the Fourth Amendment and granted summary judgment for the school district. (11) The court found that there were "special needs" in the public school context, including maintaining discipline and order (12) and addressing the drug problem facing the school, (13) which exempted the school from showing probable cause. The court found that such unique needs also lowered the privacy interests of students (14) and justified the school district's implementation of the Drug Testing Policy as a reasonable action under the Fourth Amendment. (15) The Court of Appeals reversed and held that the Drug Testing Policy violated the Fourth Amendment. (16) While the Court of Appeals agreed that the issue had to be considered in the context of the unique environment of a public school, (17) the court held that the School District failed to identify a drug abuse problem reaching "epidemic" proportions, as was the case in Vernonia. (18) Without such a burden of proof, the Court of Appeals warned that schools would be able to test all students "simply as a condition of attending school." (19) The Supreme Court reversed. Justice Thomas, writing for the five-justice majority of Chief Justice Rehnquist and Justices Kennedy, Scalia, and Breyer, held that the Drug Testing Policy did not violate the Fourth Amendment. The Court said meeting the probable cause standard, necessary for criminal searches, which is unnecessary in the public school context, because such a requirement would "unduly interfere with the maintenance of the swift and informal disciplinary procedures [that are] needed" in schools. (20) Considering the safety and administrative concerns of the school, the Majority acknowledged that a search without probable cause that includes drug testing of students may be reasonable when there are "special needs. …


World population was about 2.5 billion in 1950; by 1988 it had doubled. Despite this unprecedented population explosion, global food supply kept pace with the additional demand for food. A technological revolution after World War II in the agriculture of the industrialized countries initially made this achievement possible. In the developing countries, where growth of food production had relied heavily on plowing up new land and on irrigation development, technology was increasingly responsible for production growth after 1965. Technology research in the following areas should receive high priority: (1) Improved application of technology to natural resource management; (2) Protection of crops from biotic stresses without heavy reliance on pesticides. (3) Genetic improvement of key crops. (4) Global action to advance scientific knowledge and its application.


Last years, European roller Coracias garrulus has undergone a moderately rapid decline across its global range and if this negative trend persists, the status of this species is likely to become Vulnerable in the IUCN Red List. Understanding the strong link between breeding success and bird conservation, this study aims to evaluate possible correlations between nest-site and landscape characteristics and habitat selection and breeding success in this species. This study has been conduct within the natural reserve "Els Aiguamolls de l'Emporda" (PNAE) where the last years European roller population has been stable up to now. Thirtyfive nest-boxes and three Green Woodpecker Picus viridis holes were analysed with field data collection on several nest-site and landscape characteristics. In addition, the establishment of breeding pairs and those with breeding success were quantified. A comparison to 2014 field database shows evidences of a worrying decreasing trend of European roller breeding pairs within the natural reserve indicating the deterioration and loss of suitable nest-boxes as the main factor. As a consequence, inter and intraspecific competition has been registered and also extremely rare data was collected, a nest-box has probably been parasitized by the European cuckoo Cuculus canorus. When compared to unoccupied nest-boxes, occupied nest-boxes were at a lower height (6,89 1,12 m), mostly oriented east, south and southeast therefore were in warmer nest-box microclimates and mostly had circular entrance holes. Although the foraging habitat selection data has been scarce, interesting data such as flight average distance and frequency during the foraging period for chicks has been collected. In this period flights were normally about 200-300 m long but quite fast (mostly about 3-5 min). The present study has also provided a detailed behavioural description during the nest foraging provisioning that highlight the importance of the hedgerows and riparian forest In the surroundings of the nest to allow the birds to perch and detect their prey. Finally, the results have led to the suggestion of a viable framework of conservation measures for the European roller in the natural reserve (PNAE)


Genetic risk assessment for potential hazard from environmental tritium to man becomes important with increasing nuclear-power industry. The purpose of this short review is to discuss the possible genetic effects of tritium from a view of genetic risk estimation.The discussion is based mainly on our experimental results on the chromosome aberrations induced in human lymphocytes by tritium at the very low-level. The types of chromosome aberrations induced by radiation from tritium incorporated into the cells are mostly chromatid types. The most interesting finding is that the dose-response relationship observed in both tritiated-water and tritiated-thymidine is composed of two phases. The examination on the nature of two-phase dose-response relationship is very important not only for the mechanisms of chromosome aberrations, but also for the evaluation of genetic risk from low-level radiation.


We develop a flexible business cycle indicator that accounts for potential time variation in macroeconomic variables. The coincident economic indicator is based on a multivariate trend cycle decomposition model and is constructed from a moderate set of US macroeconomic time series. In particular, we consider an unobserved components time series model with a common cycle that is shared across different time series but adjusted for phase shift and amplitude. The extracted cycle can be interpreted as a model-based bandpass filter and is designed to emphasize the business cycle frequencies that are of interest to applied researchers and policymakers. Stochastic volatility processes and mixture distributions for the irregular components and the common cycle disturbances enable us to account for the heteroskedasticity present in the data. Forecasting results are presented for a set of different specifications. Point forecasts from the preferred model indicate a future recession with the uncertainty over the business cycle growing quickly as the forecast horizon increases. Copyright © 2010 John Wiley & Sons, Ltd.


The introduction of the collaborative partnership model in initial teacher education at the Norwegian University for Science and Technology has paved the way for activities and components in its professional training that closely relate to the field of practice and meets the need to attain the more 'here‐and‐now'‐oriented objectives of the teacher education programme. The evaluation of the model reveals, however, that considerable work remains to be done before one can say that the education programme has achieved the national objectives set for a suitable training for the profession. This concerns the students' acquisition of educational theory, which is considered to be a prerequisite to the development of autonomy in the teaching profession. While a solid foundation of educational theory will be of importance for the students' future professional growth, teacher education must also include elements associated with control, thus ensuring the school system's implicit function as the bearer of society's values and culture.


Mouse tumor cells transfected with syngeneic MHC class II and costimulatory molecule genes are therapeutic vaccines in mice, provided they do not coexpress the class II-associated invariant chain (Ii). We demonstrated previously that the vaccine cells present tumor peptides via the endogenous antigen presentation pathway to activate CD4+ and CD8+ T cells. Because of their efficacy in mice, we are translating this vaccine strategy for clinical use. To obtain MHC class II+CD80+Ii− human tumor cells, we developed retroviruses encoding HLA-DR and CD80. The HLA-DR virus encodes the DRα and DRβ0101 chains using an internal ribosomal entry site to coordinate expression. SUM159PT mammary carcinoma and Mel 202 ocular melanoma cells transduced with the retroviruses DRB1/CD80 express high levels of DRB0101 and CD80 on the cell surface in the absence of Ii. Irradiated SUM159PT/DR1/CD80 vaccines stimulate proliferation of non-HLA-DRB0101 peripheral blood mononuclear cells and present an exogenous DR1-restricted tetanus toxoid (TT) peptide, indicating that the transduced DRB0101 is functional. SUM159PT/DR1/CD80 vaccines were further transduced with a retrovirus encoding the TT fragment C gene, as a model tumor antigen. These cells stimulate IFN-γ release from TT-primed human DRB0101 peripheral blood mononuclear cells, demonstrating their ability to present "endogenous" tumor antigen. Depletion and antibody blocking experiments confirm that MHC class II-restricted, endogenously synthesized epitopes are presented to CD4+ T cells. Therefore, the MHC class II vaccines are efficient antigen-presenting cells that activate tumor-specific MHC class II-restricted, CD4+ T lymphocytes, and they are a novel and potential immunotherapeutic for metastatic cancers.


Model transformations play a cornerstone role in Model-Driven Engineering (MDE), as they provide the essential mechanisms for manipulating and transforming models. The correctness of software built using MDE techniques greatly relies on the correctness of model transformations. However, it is challenging and error prone to debug them, and the situation gets more critical as the size and complexity of model transformations grow, where manual debugging is no longer possible. Spectrum-Based Fault Localization (SBFL) uses the results of test cases and their corresponding code coverage information to estimate the likelihood of each program component (e.g., statements) of being faulty. In this article we present an approach to apply SBFL for locating the faulty rules in model transformations. We evaluate the feasibility and accuracy of the approach by comparing the effectiveness of 18 different state-of-the-art SBFL techniques at locating faults in model transformations. Evaluation results revealed that the best techniques, namely Kulcynski2, Mountford, Ochiai, and Zoltar, lead the debugger to inspect a maximum of three rules to locate the bug in around 74% of the cases. Furthermore, we compare our approach with a static approach for fault localization in model transformations, observing a clear superiority of the proposed SBFL-based method.


A micro-electro-mechanical system (MEMS) silicon-based non-silicon mirror for a 2D optical switch is designed, fabricated and measured. The result shows that the mirror has good reflective performance. And driven by static electricity, it can rotate more than 10°at voltage less than 15 V. This kind of novel mirror will have good potential applications for MEMS optical switches.


Purpose of review To highlight the advances and the data published in the field of gynaecological oncology surgery in the last few years. The review includes not only newly introduced surgical techniques but also data that consolidate recent developments. Recent findings Ultimate data on the use of laparoscopy in the treatment of gynaecologic malignancies have proven similar survival outcomes to the traditional surgical route and confirmed the benefits in terms of faster recovery and lower morbidity. Thanks to a faster learning curve, the use of robotic surgery has contributed to the increase in the number of surgeons who moved away from open surgery. A few pioneers are expanding the indications of laparoscopy to exenterative surgery and treatment of ovarian cancer. Summary Laparoscopic surgery has become the gold standard treatment for patients with primary endometrial or cervical cancer. The advent of robotic surgery has reinforced the domain of endoscopic surgery.


This paper determines the materials cited in Ph.D. theses of Sociology, submitted to the Panjab University, Chandigarh during the years 2002-2012 to improve the existing collection development policy of University library. The study reveals that Books are the most preferred sources of information used by the researchers in the field of Sociology, accounting for 57.65% of the total citations, although citations from journals, proceedings, internet resources and reports are also found. It is also observed those researchers are not taking much advantage of internet resources. Bradford's law of scattering was applied. More cited materials were contributed by single authors and degree of collaboration of books was calculated as 0.28 and the degree of collaboration of authors in cited journal articles were calculated as 0.35.


Outcrops of the Cipero Formation that are currently exposed near San Fernando, Trinidad, are described. These contain exceptionally well-preserved planktonic foraminifer assemblages of latest Oligocene and earliest Miocene age. The full range of included species is documented, including some rarely reported forms. Details of foraminifer test construction and wall ultrastructures are examined using scanning electron microscopy of whole and dissected tests. Observations include (i) the presence of micrometer-scale spikes – confirmed by examination of comparable material from the Oligocene of Puerto Rico – on the interior test surface of Cassigerinella chipolensis , (ii) detailed investigation of the calcite crust on tests of Catapsydrax dissimilis and Turborotalita quinqueloba , (iii) well-preserved wall microstructure on tests of " Paragloborotalia " pseudokugleri , and (iv) confirmation of a radially crystalline wall in Tenuitella and Globigerinita that compares closely with Miocene Globigerinatella from ODP Site 871 (western Pacific Ocean). Multi-species oxygen and carbon stable isotope measurements divide the assemblage into various ecological groups, including mixed layer, thermocline, and sub-thermocline dwellers. The fossil assemblage and isotope data indicate an oligotrophic open-ocean setting with a well-defined and seasonally stable thermocline with sea surface temperatures of about 27°C (similar to modern) and sub-thermocline waters of about 13°C. The mixed layer was dominated by species of Globigerina , " Paragloborotalia " pseudokugleri , Cassigerinella , and Globigerinita . The base of the mixed layer and upper thermocline was inhabited by Turborotalita , Paragloborotalia , Dentoglobigerina larmeui , and Tenuitella . The deep thermocline was inhabited by the large species " Dentoglobigerina " venezuelana and " D ." rohri . Sub-thermocline intermediate water was occupied by Catapsydrax dissimilis .


With low government interest rates and increased correlation across sovereign markets in Europe and the United States, investors and money managers have been searching for new ways to increase the return of fixed-income portfolios. At the same time, bond markets outside the United States have seen significant growth in non-sovereign sectors like corporates and mortgages. In Europe this development is mainly a consequence of the introduction of a common currency. Global sovereign bond investors can now access credit sectors across markets to expand their investment universe. Single-currency investors, on the other hand, especially those domiciled in small and illiquid markets, profit from the wider global investment-grade markets through multimarket and multisector (global aggregate) portfolios, while hedging currency exposures. Money managers can thus add value to portfolios through a much wider investment opportunity set. Analysis of the advantages of global aggregate portfolios with respect to other types of fixed-income portfolios, especially on a currency-hedged basis, confirms the intuitive assessment that global aggregate portfolios offer a better risk-return trade-off than local or global sovereign portfolios. Money managers, while profiting from a wider opportunity set, have to balance this advantage against the increased complexity and number of strategy dimensions.


The organisational forms of networked business constellations in general are often interpreted as the new organisational forms of the 21st century. As far as such forms consist of multiple collaborating businesses, partner selection during the formation phase of a networked business constellation is a crucial task for successful operation in the future. We propose to choose the appropriate business partners by applying concepts from coordination theory. In particular, we decompose an identified business opportunity, usually an innovative product or service, into its embracing tasks and resources. These represent the competencies needed for meeting the business opportunity. The methodological approach for partner selection is discussed from a task-resource dependency perspective and the benefits for the networked business context are highlighted. The research in this paper is accompanied by an argumentation-based validation, as well as by an evaluation of sustainability.


Cognitive Radio built on top of spectrum sensing is promised to provide more capacity for users wherever and whenever needed and improve radio spectrum utilization in clever and fair manner. However, practical spectrum sensors have to be implemented and they should provide sufficient protection to legacy users of radio spectrum. This leads to trade-offs between primary user protection ratio, device form factor, cost and power consumption. In this research we have derived requirements for antenna efficiency, sensitivity and linearity of practical spectrum sensors. These are verified by field measurements using spectrum sensor embedded to a mobile phone.


Purpose: To test the viability of implanting the Artisan®/VerisyseTM lens in a low-income monocular aphakic African population with insufficient capsular support where contact lens wear is expensive and spectacle correction is not possible, by assessing the postoperative visual functions. To further assess whether adverse effects (e.g.: pigment dispersion with secondary glaucoma, prolonged uveitis) in patients with highly pigmented irises would be as low as with patients in European and American trials. Methods: A prospective, randomised, controlled clinical trial comparing outcomes in two groups of unilateral aphakic patients. The patients in the first group received an Artisan intra-ocular iris-claw lens as a secondary procedure while the second group remained aphakic (the current treatment status quo for public patients in KwaZulu-Natal province in South Africa). Follow-up was done for 1 year. Results: The study was terminated early due to ethical and statistical reasons. Nine treated and five control patients were included. Monocular uncorrected vision was significantly higher in the treatment group (P=0,012) and patient satisfaction was higher (p=0,002). Changes in other variables (intraocular pressure, angle pigmentation, change in cup-to-disc ratio, iris pigment changes and best spectacle corrected vision) were not significantly different between the two groups. Conclusion: The Artisan®/VerisyseTM lens is a feasible option for aphakic African patients with regard to visual outcome, safety and patient satisfaction. This form of refractive correction should be the standard for patients with no capsular support and where other options are too expensive or carry greater risk. ii


The Alternative Dispute Resolution (ADR) system provides an opportunity whereby the deficiencies, and costs, of court and arbitration proceedings may be avoided. In this work, the authors: * discuss the requirements of an effective ADR system for settling disputes * compare the merits and weakness of court proceedings and arbitral proceedings in achieving agreed settlements * provide a useful guide for students and practitioners to the legal roles within ADR, and the stages to expect during a mediation process. National and international mediation systems are examined, including those of the Centre for Effective Dispute Resolution, the World Intellectual Property Organization (WIPO) and the International Centre for Settlement of Investment Disputes (ICSID). The WIPO Mediation Rules and the ICSID Convention, Regulations and Rules are reproduced and discussed. A chapter focuses on the role of ADR and arbitration in national and international sport. This title will be of use to both students and practitioners with an interest in ADR systems for settling disputes, be they domestic or international in nature.


The Fourth Amendment protects against unreasonable "searches and seizures," but in the digital age of stingray devices and IP tracking, what constitutes a search or seizure? The Supreme Court has held that the threshold question is supposed to depend on and reflect the "reasonable expectations" of ordinary members of the public concerning their own privacy. For example, the police now exploit the "third party" doctrine to access data held by email and cell phone providers, without securing a warrant, on the Supreme Court's intuition that the public has no expectation of privacy in that information. Is that assumption correct? If judges' intuitions about privacy do not reflect actual public expectations, it may undermine the legitimacy of the criminal justice system and exacerbate social unrest.

Although prior research has shown that the police disproportionately target younger people and minority communities, judges tend to be male, white, educated, affluent, and older than the general population. Their intuitions may thus be systematically different. Even worse, cognitive science suggests that judges may have difficulty putting themselves into the shoes of the searched person or considering the reasonableness of the police tactics from an ex ante perspective, without knowledge about the fruits of the search.

With 1200 respondents, we conducted a large-scale survey experiment to test whether, and if so, why, contemporary Fourth Amendment jurisprudence diverges from the societal norms it purports to protect and reflect. We identify a range of privacy expectations for 18 different police practices. We use oversampling, reweighting, and randomization to investigate particular causes of this disparity between judicial and public expectations. We conclude by suggesting better ways forward, so that social science evidence can replace judicial speculation.


Bringing together experts from historical linguistics and psychology, this volume addresses core factors and processes in language change, exploring the potential (and limitations) of such an interdisciplinary approach. Easily accessible chapters by psycholinguists present cuttingedge research on frequency, salience, chunking, priming, analogy, ambiguity and acquisition, and develop models of how these may be involved in language change. Each chapter is complemented with one or more case studies in the history of English in which the psycholinguistic factor in question may be argued to have played a decisive role. Thus, for the first time, a single volume provides a platform for an integrated exchange between psycholinguistics and historical linguistics on the question of how language changes over time.


Merkel cell carcinoma is a rare neuroendocrine tumour. Predisposing factors for its development are age, immunosuppression, ultraviolet light exposure, and exposure to the polyoma virus. It is usually localized in the head region, neck, and extremities. Primary neuroendocrine tumours of the vulva are extremely rare and so far there have been only 20 cases reported in the English language literature. Tumors at this location have a more aggressive clinical course than neuroendocrine tumours at other sites. The majority of patients present with metastases in regional lymph nodes at the time of diagnosis. Due to the low incidence there is no algorithm for diagnostic and therapeutic procedures. We present a case of a 79-year-old patient with a primary vulvar neuroendocrine tumor with metastases in the regional lymph nodes. Diagnostic and therapeutic measures are described.


Titles in this highly international set consider every problem of socio-political importance that affected society in the years following the Second World War. This set includes important texts by key social and political theorists including Stanislaw Ossowski, as well as extensive comparative material from China, Palestine, the USA, South Africa and Great Britain. Drawing on important empirical material, titles included here consider in-depth questions of ethnicity, unemployment, immigration, colour prejudice, social mobility, new elites and class formation.


PmoD, a recently discovered protein from methane-oxidizing bacteria, forms a homodimer with a dicopper CuA center at the dimer interface. Although the optical and electron paramagnetic resonance (EPR) spectroscopic signatures of the PmoD CuA bear similarities to those of canonical CuA sites, there are also some puzzling differences. Here we have characterized the rapid formation (seconds) and slow decay (hours) of this homodimeric CuA site to two mononuclear Cu2+ sites, as well as its electronic and geometric structure, using stopped-flow optical and advanced paramagnetic resonance spectroscopies. PmoD CuA formation occurs rapidly and involves a short-lived intermediate with a λmax of 360 nm. Unlike other CuA sites, the PmoD CuA is unstable, decaying to two type 2 Cu2+ centers. Surprisingly, NMR data indicate that the PmoD CuA has a pure σu* ground state rather than the typical equilibrium between σu* and πu of all other CuA proteins. EPR, ENDOR, ESEEM, and HYSCORE data indicate the presence of two histidine and two cysteine ligands coordinating the CuA core in a highly symmetrical fashion. This report significantly expands the diversity and understanding of known CuA sites.


We report findings of a survey of 555 women 18-35 years of age living in Northern Manhattan in New York City. The survey was conducted by the Columbia Center for Children's Environmental Health (CCCEH) to learn what community women knew about environmental risks to health and what they did to protect themselves and their families, to validate the findings of focus groups held with community women, and to provide information for planning the Healthy Home, Healthy Child campaign sponsored by CCCEH. Survey findings showed that overall awareness of environmental risks to children's health was high, with more than 95% of respondents identifying lead, household pests, pesticides, environmental tobacco smoke, and drugs as harmful to health. Similarly, more than 95% of respondents reported taking one or more protective actions to reduce these risks, suggesting that these factors significantly concern women living in Northern Manhattan. The reported levels of specific protective actions to reduce these risks, however, varied greatly. In each area of risk the most frequently reported actions were effective ones, but many other important protective actions were rarely mentioned, suggesting that there was room for an educational campaign to teach women new ways to protect their families. Survey respondents and CCCEH scientists differed in the priorities they placed on the importance of key protective actions, confirming earlier focus group findings and suggesting the importance of incorporating community concerns into the planning of environmental campaigns.


Recently Nickle et al. introduced a new model of genetic diversity that summarizes a large input dataset into a short sequence containing overlapping subsequences from the dataset. This model has direct applications to rational vaccine design. In this paper we formally investigate the combinatorics of the vaccine optimization problem. Here the vaccine is constructed as a sequence S of amino-acids such that as many of the most frequently occurring epitopes found in mutated viruses are subsequences to S. We rigorously present the related design optimization problem, establish its complexity, and present a simple probabilistic algorithm to find an efficient solution. Our vaccine designs show improvement of over 20% in the coverage score over the previously best designs and produce over 15% shorter vaccines that achieve equivalent epitope coverage.


This article includes a previously unpublished document, an address to the military officials of the Priamurye Zemstvo Host and civil refugees. The address was written in April 1923 in the Girin camp for Russian internees formed as a result of the White Army's withdrawal from Primorye to Northeastern China at the end of the Civil War. The address was authored by Lieutenant General M. K. Diterikhs, former head of the last White government in Russia, supreme leader of the Provisional Priamurye Government and the governor of the Zemstvo Host. The original of the address is kept in the Archive of the Hoover Institution on War, Revolution, and Peace (Fund of General P. P. Petrov) at Stanford University. The document reflects Diterikhs' views on the nature of the Civil War and the prospects of continuing the anti-Bolshevik struggle following the defeat of the White movement. According to the general, the Civil War in Russia had a religious meaning, being a confrontation between the forces of Christ and the Antichrist. Members of the White movement, as well as Russian society as a whole, bore the stamp of the sin of regicide. They opposed the Antichrist power of Bolsheviks only by means of physical force and lost. Meanwhile, the victory over the Soviet regime and the future revival of Russia of Christ was only considered possible through the spiritual unification of all opponents of the Antichrist and the creation of an anti-Bolshevik Brotherhood in Christ.


Research shows the development of teachers' professional identity to be in a state of flux and that there is a strong correlation between a sense of teacher professional identity and their propensity to stay in teaching. Our study examines pre-service teachers' emerging sense of professional teacher identity at exit point of their pre-service programme. For the first part, data was collected from an open-ended questionnaire which asked participants about their perceptions of the profession. 22 statements were used for the second part to elicit participants' perceptions about teaching. The open- ended questionnaire showed a high percentage perceiving a sense of reality, followed by a smaller percentage experiencing mismatched expectations. For the second part, five factors were extracted with 'role of teaching and learning' emerging with the highest mean. The final part discusses the implications for the continual enhancement of teacher preparation programmes.


Since launching as a website for everyday video-sharing in 2005, YouTube has become one of the world's most powerful digital media platforms. Originally published in 2009 when YouTube was only four years old, this book was the first to systematically investigate its cultural impacts and politics, highlighting the productive tensions between its amateur community rhetoric and its commercial media logics.

Since then, YouTube has grown as a platform and matured as a company. Its business model is built on coordinating the interests of and extracting value from its content creators, audiences, advertisers and media partners, in a commercial setting where YouTube now competes with other powerful social media and streaming television platforms. Meanwhile, YouTube's diverse communities of content creators, who developed the platform's most distinctive cultural forms and genres, have strong ideas and interests of their own.

While preserving the original edition's forensic analysis of YouTube's early popular culture and uses, this fully revised and updated edition weaves fresh examples, updated theoretical perspectives and comparative historical insights throughout each of its six chapters. Burgess and Green show how, over its more than a decade of existence, YouTube's dual logics of commerciality and community have persisted, generating new genres of popular culture, new professional identities and business models for the media industries, and giving rise to ongoing platform governance challenges.

The book is essential reading for anyone interested in the contemporary and future implications of digital media platforms and will be particularly valuable for students and scholars in media, communication and cultural studies.


A combination of Lagrangian measurements and fixed current meter moorings were used during the summer of 1974 and the winter of 1974-75 to determine the circulation patterns of Saginaw Bay. Because the bay is shallow, the water responds rapidly to wind changes. Distinct circulation patterns were determined for southwest and northeast winds. These directions parallel the major axis of the bay and were the prevailing wind directions during the study. A typical exchange rate between the inner , _. and outer bay during moderate winds aligned with the bay axis is 3700 m s '~s If sustained, this flushing rate would completely exchange the water of the inner bay in about 26.5 days. However, winds perpendicular to the axis of the bay cause little water to be exchanged and the residence time of water in the bay is much longer. Comparison of measured currents with the results of an indpendently-developed numerical model for the bay indicates there is good agreement between the observations and the simulation of the circulation in the shallow inner bay. Agreement is poor in the deeper outer bay, where specification of proper boundary conditions at the open mouth of the bay is important for meaningful model simulations. Ice cover during winter shields the water surface from wind stress. Currents are sluggish and driven almost entirely from interactions with the lakescale circulation of Lake Huron.


This chapter examines what the pragmatic skills of autistic individuals suggest about the claim by Sadock (1970, 1972) and others that questions like "Can you pass the salt" are conventionalized for use as indirect requests. A review of the autism literature indicates that the primary pragmatic deficit in autism is in reading speakers' minds. Autistic individuals should thus only fail at inferences involving speakers' beliefs and intents, for example conversational implicatures. Anecdotal and empirical evidence bears this out. Autistic individuals correctly interpret non-literal uses of language so long as such uses are conventionalized, and so long as the conventions in question have entered their lexicons. In particular, they readily process "Can you" utterances as indirect requests, confirming Sadock's thesis.


The global burden of cancer is growing rapidly with an estimated 15 million new cases per year worldwide in 2015, growing to 19 million by 2025 and 24 million by 2035. The largest component of this growth will occur in low-to-middle income countries (LMICs). About half of these cases will require radiation treatment. The gap for available cancer
treatment, including radiation therapy, between high-income countries (HICs) and LMICs is enormous. Accurate data and quantitative models to project the needs and the benefits of cancer
treatment are a critical first step in closing the large cancer divide between LMICs and HICs. In this context, the Union for International Cancer
Control (UICC) has developed a Global Task Force on Radiotherapy for Cancer
Control (GTFRCC) with a charge to answer the question as to what it will take to close the gap between what exists today and reasonable access to radiation therapy globally by 2035 and what the potential clinical and economic benefits are for doing this. The Task Force has determined the projections of cancer incidence and the infrastructure required to provide access to radiation therapy globally. Furthermore it has shown that appropriate investment not only yields improved clinical outcomes for millions of patients but that it also provides an overall economic gain throughout all the income settings where this investment is made. This symposium will summarize the facets associated with this global cancer challenge by reviewing the cancer burden, looking at the requirements for radiation therapy, reviewing the benefits of providing such therapy both from a clinical and economic perspective and finally by looking at what approaches can be used to aid in the alleviation of this global cancer challenge. The speakers are world renowned experts in global public health issues (R. Atun), medical physics (D. Jaffray) and radiation
oncology (N. Coleman).
Learning Objectives:
1.
To describe the global cancer challenge and the corresponding potential benefits of addressing this challenge.
2.
To describe what radiation therapy infrastructure, in terms of facilities, equipment and personnel, will be required to address this challenge.
3.
To describe models of addressing personnel and infrastructure mobilization and capacity building within regions where significant cancer
treatment disparities exist.


Soluble CD95L (s-CD95L) is a chemoattractant for certain lymphocyte subpopulations. We examined whether this ligand is a prognostic marker for high-grade serous ovarian cancer (HGSOC) and whether it is associated with accumulation of immune cells in the tumor. Serum s-CD95L levels in 51 patients with advanced ovarian cancer were tested by ELISA. IHC staining of CD3, CD4, CD8, CD20, CD163, CD31, FoxP3, CCR6, IL-17, Granzyme B, PD-L1, and membrane CD95L was used to assess tumor-infiltrating immune cells. Although the intensity of CD3, CD8, CD4, CD20, and CD163 in tumor tissues remained constant regardless of membrane CD95L expression, tumors in patients with HGSOC with s-CD95L levels ≥516 pg/mL showed increased infiltration by CD3+ T cells (P = 0.001), comprising both cytotoxic CD8+ (P = 0.01) and CD4+ (P = 0.0062) cells including FoxP3+ regulatory T cells (P = 0.0044). Also, the number of tumor-infiltrating CD20+ B cells (P = 0.0094) increased in these patients. Multivariate analyses revealed that low s-CD95L concentrations [<516 pg/mL, HR, 3.54; 95% confidence interval (CI), 1.13–11.11), and <1,200 activated CD8+ (Granzyme B+) cells (HR, 2.63; 95% CI, 1.16–5.95) were independent poor prognostic factors for recurrence, whereas >6,000 CD3+ cells (HR, 0.34; 95% CI, 0.15–0.79) was a good prognostic factor. Thus, low levels of s-CD95L (<516 pg/mL) are correlated with lower numbers of tumor-infiltrating lymphocytes (CD3+ and CD8+, and also CD4 and FoxP3 T cells) in advanced HGSOC and are a poor prognostic marker. Implications: Serum s-CD95L is correlated with a number of tumor-infiltrating immune cells in HGSOC and could be used as a noninvasive marker of tumor immune infiltration to select patients referred for immunotherapy trials that evaluate checkpoint inhibitor treatment.


This article employs an actor–network (ANT) and materialist approach to examine the changing relations among nature, society, and technology in dynamic groundwater-irrigated landscapes. Drawing on a case study from Rajasthan, India, it merges these frameworks to advance our understanding of the role that tubewell irrigation technologies play, through their associations with other objects, in altering existing social power relationships, environmental practices, and socioecologies, paying attention to the directedness of these relationships. This article demonstrates, first, that tubewell adoption is made possible through the creation of tubewell partnerships, a new social institution. Second, although tubewell adoption initially enhances production, significant groundwater withdrawal negatively alters groundwater and soil chemistry. This undermines farmers' abilities to grow high-yielding seed varieties, prompting a return to traditional crops, and exacerbates existing social inequalities both within and between partnerships. Third, irrigation practices and daily production activities follow from the demands and constraints of the tubewell, enabling and constraining human and nonhuman action. The adoption of the technology, therefore, sets in motion a recursive process of technological adaptation, social institution formation, and ecological change. Although this is presently leading to socioecological differentiation, the results suggest that these social institutions formed around the tubewell are very durable. The conclusion offers suggestions for encouraging them toward more equitable outcomes.


Background In drug trials, adverse events (AEs) burden can induce treatment non-adherence or discontinuation. The non-adherence and discontinuation induce selection bias, affecting drug safety interpretation. Nested case-control (NCC) study can efficiently quantify the impact of the AEs, although choice of sampling approach is challenging. We investigated whether NCC study with incidence density sampling is more efficient than NCC with path sampling under conditional logistic or weighted Cox models in assessing the effect of AEs on treatment non-adherence and participation in preventive antimalarial drug during pregnancy trial. Methods Using data from a trial of medication to prevent malaria in pregnancy that randomized 600 women to receive chloroquine or sulfadoxine-pyrimethamine during pregnancy, we conducted a NCC study assessing the role of prospectively collected AEs, as exposure of interest, on treatment non-adherence and study non-completion. We compared estimates from NCC study with incidence density against those from NCC with path sampling under conditional logistic and weighted Cox models. Results Out of 599 women with the outcomes of interest, 474 (79%) experienced at least one AE before delivery. For conditional logistic model, the hazard ratio for the effect of AE occurrence on treatment non-adherence was 0.70 (95% CI: 0.42, 1.17; p = 0.175) under incidence density sampling and 0.68 (95% CI: 0.41, 1.13; p = 0.137) for path sampling. For study non-completion, the hazard ratio was 1.02 (95% CI: 0.56, 1.83; p = 0.955) under incidence density sampling and 0.85 (95% CI: 0.45, 1.60; p = 0.619) under path sampling. We obtained similar hazard ratios and standard errors under incidence density sampling and path sampling whether weighted Cox or conditional logistic models were used. Conclusion NCC with incidence density sampling and NCC with path sampling are practically similar in efficiency whether conditional logistic or weighted Cox analytical methods although path sampling uses more unique controls to achieve the similar estimates. Trial registration ClinicalTrials.gov: NCT01443130.


Rotavirus has been recognized as a leading cause of the diarrhoeal illness in children under 5 years of age in the developing world. Latex agglutination test was used to detect group A rotavirus from 157 in-patients from different hospitals in Malaysia during 2000 to 2001. Diarrhoea was detected in 31 (19.7%) children and majority were under two years of age.
When viewed under electron microscope by negative staining, rotavirus was seen as both double-shelled and single-shelled particles. Thirty one rotavirus antigen positive samples with typical group A electropherotype were further characterized
into their G or P types by polymerase chain reaction (PCR) assay. The two common electropherotypes were IIC (51.6%) and IIG (35.5%). The most prevalent VP4 genotype was 25 (80.6%) P[8] and 1 (3.2 %) P[6]. Genotype P[4] and P[9] were not isolated and 5 (16.1 %) were P untypable (PUT). Regarding the VP7 genotype, G4 was the most prevalent (64.5 %), followed by G1 (6.45%), G2 (6.45%) and G3 (3.2 %). Neither G8 nor G9 was found and 6 (19.4 %) were G untypable (GUT). Studies in many countries found that G1P[8], G4P[8], G2P[4] and G3P[8] are the group A rotavirus strains more commonly seen in children. However from this present study, the common strains in Malaysia were G4P[8], G1P[8] and G3P[8]. One GUTP[6] strain (designated as 7W) was identified for the first time in Kuala Lumpur. Restriction endonuclease HaeIII and Sau96I were also used to characterize the VP7 gene of the local 7W strain. However a restriction profile could not be assigned. The P[8] and P[6] local strains (represented by 67F and 7W, respectively) were also characterized by nucleotide sequence analysis. Phylogenetic analysis revealed that the VP4 genes of the 67F and 7W formed a distinct lineage.
The P[8] and P[6] are encoded by distinct VP4 gene alleles. The main diagnostic problem is the genetic diversity of these alleles among different rotavirus strains. To overcome this problem, a method that employs non-radioactive dot
hybridization was successfully developed for P[8] and P[6]. VP4 cDNA rotavirus-specific probes were prepared and labelled with digoxigenin (DIG). Anti-DIG-alkaline phosphatase and the substrate NBT/BCIP were used to detect the binding of the probe to target sequence.
A simple, practical, sensitive and specific assay based on polymerase chain reaction (PCR) and a colorimetric detection method (ELISA) for the typing of rotavirus in infected faeces has been developed succesfully. A set of oligonucleotides was employed for a single-tube reverse-transcription nested PCR (RT-nPCR). Upon synthesis of the first strand cDNA, a first stage of 10 cycles of PCR amplification was run to generate an 876-bp dsDNA from the 5' terminal third of gene 4. The process was completed in the same tube by performing another 35 cycles of second stage amplification incorporating a biotinylated and digoxigenin 5'-end labelled primers. The RT-nPCR produced a 180-bp amplicon representing the VP4 P[8] type. The sensitivity of the RT-nPCR method was compared to non-nested PCR method and nested PCR was found to be 100 times more sensitive. To further increase the sensitivity, the enzyme-linked immunoassay (ELISA) was incorporated into the system. Streptavidin-coated microtitre plate was used to capture the biotinylated PCR-amplified products. This RT-nPCR ELISA was able to detect RNA as low as 4 pg nucleic acid. It was designed to type the single most
epidemiologically important human rotavirus VP4 P[8] type which is often associated with rotavirus G1, G3 and G4 types. Monoclonal antibodies (Mabs) were used for G serotyping, but no Mabs were availabe for P serotyping. Therefore, the RT-nPCR ELISA method is a very useful technique to detect rotavirus.


The purpose of this study was twofold: to determine the construct validities of comparable AD/HD instruments that were developed according to our current, DSM-IV classification system for AD/HD; and to identify potential +neurocognitive and socioemotional markers for AD/HD. The sample consisted of 145 children ages 8 to 11 years of age who were diagnosed with Attention Deficit Hyperactivity Disorder (AD/HD), or Central Auditory Processing Disorder (CAPD). Children were administered a battery of neurocognitive tests and completed a self-report measure of personality. Parents completed several, AD/HD instruments pertaining to their children. The AD/HD instruments used in this study were the Attention Deficit Disorder Evaluation Scale-Home Version (ADDES), Attention Deficit Hyperactivity Disorder Test (ADHDT), and the Attention Problems and Hyperactivity scales from the BASC-Monitor (BASC-M). Of interest was how each AD/HD instrument compared to the DSM-IV, particularly in terms of the cross-consistency of AD/HD subtype classifications. The findings showed that the AD/HD instruments classified participants differently from the initial, DSM-IV entry diagnosis. Rates of agreement were better for some of the AD/HD instruments than for others yet there was little overall consistency. The neurocognitive measures used in the study were the Cognitive Assessment System-Basic Battery scales. The socioemotional measures used in the study were two parent-report scales from the BASC-M (Internalizing Problems and Adaptive Skills), and the child report scales from the BASC-Self Report of Personality. Results showed that the neurocognitive measures were relatively insensitive to AD/HD symptomatology while a nearly opposite trend was observed on the socioemotional measures. For the most part, participants classified as the ADHD-Combined Type (ADHD-CT), (regardless of which AD/HD instrument was used) had the most significant impairment in areas of social functioning and emotional symptoms across parent and self-reports.


Purpose

The purpose of this paper is to examine what the term sustainable fashion means from the perspective of micro-organisations, experts, and consumers.

Design/methodology/approach

This research is qualitative in nature, utilising a multi-methods case study approach (semi-structured interviews, semiotics, questionnaires). Grounded analysis was applied to analyse the data.

Findings

Findings indicate that interpretation of sustainable fashion is context and person dependent. A matrix of key criteria provides the opportunity to find common elements.

Research limitations/implications

Due to the nature of this research the sample size is limited and may not be generalised. Data were collected in the UK and are limited to a geographical region.

Practical implications

An important implication is that defining sustainable fashion is vital in order to avoid challenges, such as greenwashing, which were faced in other industries that have a longer history in sustainable practices. Micro-organisations should take advantage of identifying key sustainable fashion criteria, which will enable them to promote their fashion collections more effectively.

Social implications

The criteria identified provide assurance for consumers that sustainable fashion is produced with social aspects in mind (fair wages, good working conditions).

Originality/value

The paper proposes a matrix that allows micro-organisations to clearly identify their collections as sustainable.


IMPORTANCE
Parkinson disease (PD) is a progressive neurodegenerative disease for which susceptibility is linked to genetic and environmental risk factors.

OBJECTIVE
To identify genetic variants contributing to disease risk in familial PD.

DESIGN, SETTING, AND PARTICIPANTS
A 2-stage study design that included a discovery cohort of families with PD and a replication cohort of familial probands was used. In the discovery cohort, rare exonic variants that segregated in multiple affected individuals in a family and were predicted to be conserved or damaging were retained. Genes with retained variants were prioritized if expressed in the brain and located within PD-relevant pathways. Genes in which prioritized variants were observed in at least 4 families were selected as candidate genes for replication in the replication cohort. The setting was among individuals with familial PD enrolled from academic movement disorder specialty clinics across the United States. All participants had a family history of PD.

MAIN OUTCOMES AND MEASURES
Identification of genes containing rare, likely deleterious, genetic variants in individuals with familial PD using a 2-stage exome sequencing study design.

RESULTS
The 93 individuals from 32 families in the discovery cohort (49.5% [46 of 93] female) had a mean (SD) age at onset of 61.8 (10.0) years. The 49 individuals with familial PD in the replication cohort (32.6% [16 of 49] female) had a mean (SD) age at onset of 50.1 (15.7) years. Discovery cohort recruitment dates were 1999 to 2009, and replication cohort recruitment dates were 2003 to 2014. Data analysis dates were 2011 to 2015. Three genes containing a total of 13 rare and potentially damaging variants were prioritized in the discovery cohort. Two of these genes (TNK2 and TNR) also had rare variants that were predicted to be damaging in the replication cohort. All 9 variants identified in the 2 replicated genes in 12 families across the discovery and replication cohorts were confirmed via Sanger sequencing.

CONCLUSIONS AND RELEVANCE
TNK2 and TNR harbored rare, likely deleterious, variants in individuals having familial PD, with similar findings in an independent cohort. To our knowledge, these genes have not been previously associated with PD, although they have been linked to critical neuronal functions. Further studies are required to confirm a potential role for these genes in the pathogenesis of PD.


Although concerns over the environmental impact of excess P in the excreta from pig production and governmental regulations have driven research toward reducing dietary supplementation of P to swine diets for over a decade, recent dramatic increases in feed costs have further motivated researchers to identify means to further reduce dietary P supplementation. We have demonstrated that genetic background impacts P utilization in young pigs and have identified genetic polymorphisms in several target genes related to mineral utilization. In this study, we examined the impact of a SNP in the calcitonin receptor gene (CALCR) on P utilization in growing pigs. In Exp. 1, 36 gilts representing the 3 genotypes identified by this CALCR SNP (11, 12, and 22) were fed a P-adequate (PA) or a marginally P-deficient (approximately 20% less available P; PD) diet for 14 wk. As expected, P deficiency reduced plasma P concentration, bone strength, and mineral content (P < 0.05). However, the dietary P deficiency was mild enough to not affect the growth performance of these pigs. A genotype x dietary P interaction (P < 0.05) was observed in measures of bone integrity and mineral content, with the greatest reduction in bone strength and mineral content due to dietary P deficiency being associated with the allele 1. In Exp. 2, 168 pigs from a control line and low residual feed intake (RFI) line were genotyped for the CALCR SNP and fed a PA diet. As expected, pigs from the low RFI line consumed less feed but also gained less BW when compared with the control line (P < 0.05). Although ADFI did not differ between genotypes, pigs having the 11 genotype gained less BW (P < 0.05) than pigs having the 12 or 22 genotypes. Pigs of the 11 and 12 genotypes had bones that tolerated greater load when compared with animals having the 22 genotype (P < 0.05). A similar trend was observed in bone modulus and ash % (P < 0.10). These data are supportive of the association of this CALCR SNP with bone integrity and its response to dietary P restriction. Although the allele 1 is associated with greater bone integrity and mineral content during adequate P nutrition, it is also associated with the greatest loss in bone integrity and mineral content in response to dietary P restriction. Understanding the underlying genetic mechanisms that regulate P utilization may lead to novel strategies to produce more environmentally friendly pigs.


The characterisation of cohesive powders for flowability is often required for reliable design and consistent operation of powder processes. This is commonly achieved by the unconfined compression test or shear test, but these techniques require a relatively large amount of powder and are limited to large pre-consolidation loads. There are a number of industrial cases where these tests are not applicable because small amounts of powders have to be handled and processed, such as filling and dosing of small quantities of powder in capsules and dispersion in dry powder inhalers. In other cases, the availability of testing powders could be a limiting issue. It has been shown by Hassanpour and Ghadiri (2007) that under certain circumstances, indentation on a cohesive powder bed by a blunt indenter can give a measure of the resistance to powder flow, which is related to flowability. However, the specification of the operation window in terms of sample size, penetration depth, indenter properties and strain rate has yet to be fully analysed. In the present work, the ball indentation process is analysed by numerical simulations using the Distinct Element Method (DEM). The flow resistance of the assembly, commonly termed hardness, is evaluated for a range of sample quantities and operation variables. It is shown that a minimum bed height of 20 particle diameters is required in order to achieve reliable measurements of hardness. A sensitivity analysis of indenter size reveals that small indenters with diameters less than 16 times the particle diameter exhibit fluctuations in powder flow stress measurements, which do not represent shear deformation. The penetration depth should be sufficiently large to cause notable bed shear deformation. It is found that this minimum penetration depth is approximately equal to 10% of the indenter radius. The hardness measurements are found to be independent of indenter stiffness within the wide range investigated.
The friction between the indenter and the particles slightly increases the hardness, although its influence on the internal stresses is negligible. Cubic and cylindrical indenters measure significantly larger hardness value compared to the spherical indenter. Increasing the inter-particle friction and cohesion results in higher hardness values and internal stresses, due to the increase in resistance to shear deformation. Simulations at a range of indenter velocities confirm that the ball indentation technique can be used to analyse powder flowability over a wide range of shear rates.


Summary Objective: To investigate the possibilities and limitations of planar bone scintigraphy and high resolution single photon emission computed tomography (HiSPECT) to diagnose flexor enthesopathy and to distinguish primary flexor enthesopathy from the concomitant form. Materials and methods: A prospective study of 46 dogs with primary flexor enthesopathy, concomitant flexor enthesopathy, medial coronoid disease, and normal elbows was performed. All dogs underwent planar bone scintigraphy and HiSPECT imaging. The obtained images were visually scored for increased radiopharmaceutical uptake in the medial humeral epicondylar and medial coronoid process region using a score from 1-3. Results: Planar bone scintigraphy demonstrated increased radiopharmaceutical uptake in all diseased elbow joints, except for one. HiSPECT demonstrated increased radiopharmaceutical uptake of the medial humeral epicondyle in nearly all clinically affected joints with primary and concomitant flexor enthesopathy. Additional uptake of the medial coronoid process was recorded in all clinically affected joints with concomitant flexor enthesopathy and in six out of 18 with primary flexor enthesopathy. No difference in intensity of the uptake was noticed. Clinical significance: Planar bone scintigraphy allows the attribution of lameness to the elbow joint in cases of primary flexor enthesopathy with minimal or even absent radiographic changes. The more detailed HiSPECT enables the localization of pathology within the elbow joint and is a sensitive technique to detect flexor enthesopathy. However HiSPECT is insufficient to distinguish primary from concomitant flexor enthesopathy.


In domains like automotive, safety-critical features are increasingly realized by software. Some features might even require fail-operational behavior, so that they must be provided even in the presence of random hardware failures. A new fault-tolerant SW/HW architecture for electric vehicles provides inherent safety capabilities that enable fail-operational features. In this paper we introduce a formal model of this architecture and an approach to calculate valid deployments of mixed-critical software-components to the execution nodes, while ensuring fail-operational behavior of certain components. Calculated redeployments cover the cases in which faulty execution nodes have to be isolated. This allows to formally analyze which set of features can be provided under decreasing available execution resources.


Despite the vast amount of research being devoted to the field of sexual abuse and trauma, literature surrounding a gender informed stance is still very much in its infancy. This article presents a systematic review aiming to provide an impartial critical examination of relevant existing literature with the main aim of exploring the role of gender in staffs' experience of working with survivors of sexual trauma. Electronic databases were searched online. Studies were eligible for inclusion if they investigated the experience and gender of staff working with adult survivors of sexual trauma. The exclusion criteria were studies that focussed on child and adolescent participants, and survivors with an intellectual disability. Eight studies were eligible for inclusion, and as such reviewed by authors; each highlighted the crucial role gender plays in the unique work between professionals and survivors of sexual trauma. Findings from the review highlighted gender as influencing interpersonal dynamics when focussing in on the client and/or the clinician. Clinician gender was felt to be particularly impactful and potentially detrimental should the gender of the professional be the same of that of the client's historic abuser. Further societal stereotypes and perceptions of what connotes an abuse survivor has implications for working with male and female survivors of sexual trauma. As a result, there is potential for males being discouraged from making disclosures due to a subconscious reduced openness to males as survivors, rather than abusers. Increased empathy was found more often to be afforded to female survivors, with harsher punishments attributed to their abusers. Evidence was also suggested for the global adverse impact of working with this client group on professionals with an increased risk of vicarious traumatisation and burnout highlighted amongst clinicians. Limitations are highlighted in relation to the review's ability to truly explore gender as the study only made reference to biological sex.


The presence of γH2AX foci on apparently intact mitotic chromosomes is controversial because they challenge the assumed relationship between γH2AX foci and DNA double-strand breaks (DSBs). In this work, we show that after irradiation during interphase, a variety of γH2AX foci are scored in mitotic cells. Surprisingly, approximately 80% of the γH2AX foci spread over apparently undamaged chromatin at Terminal or Interstitial positions and they can display variable sizes, thus being classified as Small, Medium and Big foci. Chromosome and chromatid breaks that reach mitosis are spotted with Big (60%) and Medium (30%) Terminal γH2AX foci, but very rarely are they signaled with Small γH2AX foci. To evaluate if Interstitial γH2AX foci might be signatures of misrejoining, an mFISH analysis was performed on the same slides. The results show that Interstitial γH2AX foci lying on apparently intact chromatin do not mark sites of misrejoining, and that misrejoined events were never signaled by a γH2AX foci during mitosis. Finally, when analyzing the presence of other DNA-damage response (DDR) factors we found that all γH2AX foci—regardless their coincidence with a visible break—always colocalized with MRE11, but not with 53BP1. This pattern suggests that these γH2AX foci may be hallmarks of both microscopically visible and invisible DNA damage, in which an active, although incomplete or halted DDR is taking place.


Research has consistently recognized that youth and adults share risk factors for crime, although whether certain factors are of increased importance during adolescence is debated. The present research evaluated the extent to which two risk assessment tools could predict criminal and breach reconviction in a matched sample of youth (aged 17-19) and adult (aged 20-60) community- supervised offenders: The Dynamic Risk Assessment for Offender Re-entry (DRAOR) and the static Risk of re-Conviction X Risk of re-Imprisonment (RoC*RoI). Cox regression and AUC analyses revealed initial DRAOR scores had mixed predictive validity for both groups, while proximal risk scores showed comparably moderate to high accuracy for youth and adults. Protective scores were consistently poor predictors for adults. The proximal assessment predicted reconviction better than the initial assessment, and decreases in risk scores between assessments were associated with a reduction in the likelihood of reconviction, showing the value in monitoring risk and updating assessment. The RoC*RoI predicted criminal reconviction for adults but did not predict either reconviction outcome for youth. These findings support the use of the DRAOR for identifying which youth and adults are likely to reoffend, and suggest that dynamic factors might be more useful predictors than static for assessing and monitoring youth offenders.


The majority of the population that is middle and lower income people cannot afford a lawyer's services that are more than simple, routine legal services. That is the "access to justice" problem (the A2J problem). Law societies make no attempt to regulate the legal profession so as to make legal services affordable for that majority. The problem is victimizing not only the majority of the population, but also the functioning of the justice system, particularly so the courts system, which is being overwhelmed by self-represented litigants, and the legal profession itself. Legal services are unaffordable because there are no economies-of-scale in the practice of law. As a result, the method by which the work is done to produce legal services is obsolete.

This article proposes that law societies sponsor a transition to a "support services method" of producing legal services with the aid of a national "civil service for law societies." That would allow their elected lawyer-managers ("benchers") to operate as do government Cabinet ministers and not also have to be a law society's civil service. All goods and services are now made by means of highly specialized, high volume support services. Manufacturers no longer make all parts of their goods and services themselves. Otherwise the A2J problem cannot be solved. That will leave the legal profession increasingly vulnerable to having its markets taken over by the large commercial producers of legal services, and by the great many small "start-ups" that have developed software programs to provide legal services direct to the retail market. The general practitioner will be the first to disappear. But law societies have no history of sponsoring such substantial innovations and governments do not hold them sufficiently accountable to the political-democratic process. As a result, in Canada now: law societies rule by law, but they themselves are not in fact subject to the rule of law; law society lawyer-managers ("benchers") operate in a 19th century management structure; as a result, law societies in the 21st century are inherently incompetent as is shown by their inability and unwillingness to deal adequately with the A2J problem; because the major problems of law societies now require more than the expertise of lawyers: (1) our law societies are managed by part-time amateurs (amateurs who work only part-time); and, (2) our law societies operate like an elected government without a civil service. Such a government cannot govern, and neither can Canada's law societies deal successfully with their major problems, such as the A2J problem; therefore, it is no longer possible to be both a good lawyer and a good bencher, but because benchers are not held accountable in fact (as distinguished from accountability in law), they do nothing to resolve that conflict of interest, which has led to incompetent management; while everything in the world around them is under constant and rapid change, law societies do not change, including doing only that which is consistent with what they have always done; law societies have successfully resisted any significant change since their creation, in particular: (1) they have not changed their management structure, nor (2) sponsored changes to the way the work is done by lawyers to produce legal services; as a result, it is impossible for Canada's law societies to solve the A2J problem, because without change to those two factors, it is impossible to produce the large economies-of-scale that the affordability of all goods and services, including legal services, require; and so, the A2J problem exists and will persist until the rapidly increasing sophistication of software and marketing of the commercial producers enables them to displace general practitioners, or law societies adequately respond to the A2J problem and the political-democratic process; therefore, our law societies are incapable of protecting: (1) the future of the legal profession from new sources of legal services such as the commercial producers of legal services such as, LegalZoom, LegalX, and RocketLawyer; they are now in Canada. (2) the general practitioner, and small unspecialized law firm from loss of their market to those commercial producers, and therefore the disappearance of those practitioners; and, from all of the many "AI Start-Ups" that automate many legal services.); and, (3) they are incapable of protecting themselves from being abolished or drastically shrinking along with the drastic shrinkage of the legal profession itself, i.e., the reduction in the per capita number of lawyers in private practice has been on-going for more than 20 years and will be speeded-up by those commercial producers.

And so, the severely economically depressed condition of the legal profession will remain as long as these present circumstances remain; and so, because of this institutional culture and mind-set of law societies, the A2J problem of unaffordable lawyers' services will be solved, if ever, only by some form of government-sponsored socialized law.

Effective government oversight of law societies that makes them accountable to the political-democratic process must begin now, along with beginning to replace them with permanent institutions having the requisite expertise. Or, law societies in Canada should create the equivalent of a civil service, for which there is a method to finance it described.
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The present research was conducted with the purpose of examining the effect of the marketing mix elements on the performance of Pakat Restaurants Complex based on the surveys of the consumers and experts. The data were obtained from 171 questionnaires gathered from the consumers and the experts of the restaurant. Generally, all variables (including quality, price, information, packing, distribution and branding) were important according to the consumers and experts of this industry. The results showed that all variables were significant according to the consumers of this complex except the distribution. According to ANOVA table, the effect of all demographic variables on the level of quality showed a significant difference among the communities. The effect of the experience of the consumption on the price became also significant. According to the strategies predicted in Pakat Complex, it became clear that the performance of the complex was successful to derive customer's satisfaction and increase the number of loyal customers and is proved to promote a brand of healthy and high quality food for the consumers.


This study was designed to measure the porcelain margin angles of completed collarless metal ceramic restorations and determine if these angles correspond to the most frequently recommended porcelain margin angle of 90 degrees. A sample of 99 metal ceramic restorations with porcelain labial margins were evaluated. A 1.0 mm slice taken from the midfacial impression of each restoration was evaluated by tooth location with a stereomaster microscope and the angle of the labial porcelain margin was calculated. The comparison of margin angles by tooth location showed no statistical difference between the groups. Comparison of the average margin angle with the most suggested 90-degree angle was analyzed with a One-Sample t-test and found to be statistically significant (p = 0.000). Although the majority of dental schools teach the shoulder preparation for collarless metal ceramic restorations, only 43% of the restorations measured fell within 10 degrees of this standard.


Research efforts have intensified to foresee the prospects for marine biomes under climate change and anthropogenic drivers over varying temporal and spatial scales. Parallel with these efforts is the utilization of terminology, such as 'ocean acidification' (OA) and 'ocean deoxygenation' (OD), that can foster rapid comprehension of complex processes driving carbon dioxide (CO2) and oxygen (O2) concentrations in the global ocean and thus, are now widely used in discussions within and beyond academia. However, common usage of the terms 'acidification' and 'deoxygenation' alone are subjective and, without adequate contextualization, have the potential to mislead inferences over drivers that may ultimately shape the future state of marine ecosystems. Here we clarify the usage of the terms OA and OD as global, climate change‐driven processes and discuss the various attributes of elevated CO2 and reduced O2 syndromes common to coastal ecosystems. We support the use of the existing terms 'coastal acidification' and 'coastal deoxygenation' because they help differentiate the sometimes rapid and extreme nature of CO2 and O2 syndromes in coastal ecosystems from the global, climate change‐driven processes of OA and OD. Given the complexity and breadth of the processes involved in altering CO2 and O2 concentrations across marine ecosystems, we provide a workflow to enable contextualization and clarification of the usage of existing terms and highlight the close link between these two gases across spatial and temporal scales in the ocean. These distinctions are crucial to guide effective communication of research within the scientific community and guide policymakers responsible for intervening on the drivers to secure desirable future ocean states.


A detailed assessment of the respective roles of production, export, and subsequent preservation of organic carbon (Corg) in the eastern Mediterranean (EMED) sediments during the formation of sapropels remains elusive. Here we present new micropaleontological results for both surface samples taken at several locations in the EMED and last interglacial sapropel S5 from core LC21 in the southeastern Aegean Sea. A strong exponential anticorrelation between relative abundances of the lower photic zone coccolithophore Florisphaera profunda in the surface sediments and modern concentrations of chlorophyll a (Chl-a) at the sea surface suggests that F. profunda percentages can be used to track past productivity changes in the EMED. Prior to S5 deposition, an abrupt and large increase of F. profunda percentages in LC21 coincided (within the multidecadal resolution of the records) with the marked freshening of EMED surface waters. This suggests a strong coupling between freshwater-bound surface to intermediate water (density) stratification and enhanced upward advection of nutrients to the base of the photic zone, fuelling a productive deep chlorophyll maximum (DCM) underneath a nutrient-starved surface layer. Our findings imply that (at least) at the onset of sapropel formation physical and biogeochemical processes likely operated in tandem, enabling high Corg accumulation at the seafloor.


A jurisdiction such as the Scottish one, reputedly with solid Roman roots, is practically bereft of the fundamental concept of a deposit in the concluding passage of the missives. Conversely, the relevant 'ancestor' (Roman law) has been profoundly permeated, throughout the course of its history, by the notion of an arrha (the earnest) in the conclusion of a contract annexed to the transfer of heritable properties. Moreover, in contemporary times and outwith Scotland, a Continental jurisdiction (the Italian one) is resolutely lingering on the Roman caparra penitenziale while, ironically, the English system (comprehensively 'un-Roman' in its formation) has expressly adopted the 'deposit' as part of the closing particulars. These asymmetries, brim-full with inviting legal ingredients, seem, in the present work, to conjure up an intriguing and captivating plot worthy of an Indiana Jones' film, where the lost treasure can be deemed replaceable, for the distracted reader, by the ancient Roman notion of an arrha, so evidently not inherited by the contemporary Scottish jurisprudence. Ultimately, the contribution engenders the usual unsettling query: in the light of the phenomenology of the arrha so neglected in Scotland in contemporary times, is Scottish law still a mixed legal system or, conversely, a jurisdiction progressively getting closer to the English common law counterpart?


We examine the reputational impact of an audit office issuing adverse internal control opinions (adverse ICOs). While prior research has examined how clients that receive an adverse ICO respond, we focus on clients that did not receive an adverse ICO. We find that audit offices that issue more adverse ICOs experience lower growth and that this effect is stronger when the adverse ICO is associated with a more visible client or refers to an entity-level control weakness. Finally, we find that clients are less likely to select auditors with a history of issuing adverse ICOs and that auditors are able to recoup some of their lost growth when they issue fewer adverse ICOs. Our results indicate that the market for audit services penalizes auditors for disclosing information critical of management, which undermines the value of direct-to-investor auditor communications and provides insight into potential longer-term implications of the expanded auditor's report.


Dynamic probabilistic networks are a compact representation of complex stochastic processes. In this paper we examine how to learn the structure of a DPN from data. We extend structure scoring rules for standard probabilistic networks to the dynamic case, and show how to search for structure when some of the variables are hidden. Finally, we examine two applications where such a technology might be useful: predicting and classifying dynamic behaviors, and learning causal orderings in biological processes. We provide empirical results that demonstrate the applicability of our methods in both domains.


This study presents the economic system of the Federal Republic of Germany, the Social Market Economy. Its aim is to describe the elements of this system that ensure its openness, dynamism, efficiency, stability and social balance. Taking Germany as an example, the study thus seeks to identify what is specifically German about its market economy system rather than to explain how a market economy system works.


The controversy surrounding the recovery at common law of negligently caused pure economic loss is a source of great wonderment for a civilian. Indeed, there does not appear to be, within civil law jurisdictions, any analogous debate on the nature of the prejudice entitling an injured party to claim compensation. Civil law knows of no rule precluding the recovery of pure economic loss as a category. Therefore, the mass of scholarly discussions is bound to unsettle the civilian: are we missing something important?This paper presents an overview of the manner in which civil law responds to the concerns embodied in the concept of pure economic loss. From a civilian's point of view, the various problems discussed under this heading are heterogeneous. It is likely that common lawyers recognize the somewhat artificial nature of the category of pure economic loss. Yet, it is a catalyst for important debates about the foundation, function and domain of tort liability. This makes it an ideal concept for a comparative endeavor. In order to make this comparison more significant, however, it will be necessary to articulate my understanding of the various preoccupations underlying the judicial and doctrinal discussions of pure economic loss. I shall then turn to the civil law to look for signs of these preoccupations in its categories of reasoning.


After a decade of negotiations and additional preparatory work, the WTO Trade Facilitation Agreement (TFA) is poised to enter into force. It promises to streamline and substantially prune the red tape that all too often slows and impedes international commerce - thereby significantly reducing both cost and time needed to do business across borders. The paper chronicles the path from the conclusion of the talks at the 2013 Bali Ministerial Conference to the present day as we prepare for the Agreement to take effect. It reviews the state of the ratification process, analyses implementation schedules and outlines work still to be done. The study shows that the emerging application of the TFA, like its negotiation, has once again confounded the sceptics - who first doubted that a TF Agreement would see the light of day and then questioned if it would ever be put into practice. While plenty remains to be done to implement the TFA across the full WTO membership, its entry into force is set to happen - a valedictory moment.


Protein folding and unfolding have been the subject of active research for decades. Most of previous studies in protein unfolding were focused on temperature, chemical, and/or force (such as in atomic force microscopy (AFM)) induced denaturations. Recent studies on the functional roles of proteasomes (such as ClpXP) revealed a different unfolding process in cell, during which a target protein is mechanically unfolded and pulled into a confined, pore-like geometry for degradation. While the proteasome nanomachine has been extensively studied, the mechanism for unfolding proteins with the proteasome pore is still poorly understood. Here, we investigate the mechanical unfolding process of ubiquitin with (or really outside) a generic nanopore, and compare such process with that in the AFM pulling experiment. Unexpectedly, the required force for protein unfolding through a pore can be much smaller than that by the AFM. Simulation results also unveiled different nanomechanics, tearing fracture vs shearing friction, in these two distinct types of mechanical unfoldings.


In this work, we study the problem of measuring relational similarity between two word pairs (e.g., silverware:fork and clothing:shirt). Due to the large number of possible relations, we argue that it is important to combine multiple models based on heterogeneous information sources. Our overall system consists of two novel general-purpose relational similarity models and three specific word relation models. When evaluated in the setting of a recently proposed SemEval-2012 task, our approach outperforms the previous best system substantially, achieving a 54.1% relative increase in Spearman's rank correlation.