Prostate cancer (PCa) is the most frequently diagnosed malignancy and the second leading cause of cancer-related deaths in American males. For these reasons, it is necessary to intensify our efforts for better understanding and development of novel treatment and chemopreventive approaches for this disease. In recent years, green tea has gained considerable attention as an agent that could reduce the risk of several cancer types. The cancer-chemopreventive effects of green tea appear to be mediated by the polyphenolic constituents present therein. Based on geographical observations that suggest that the incidence of PCa is lower in Japanese and Chinese populations that consume green tea on a regular basis, we hypothesized that green tea and/or its constituents could be effective for chemoprevention of PCa. To investigate this hypothesis, we initiated a program for the chemoprevention of PCa by green tea. In cell-culture systems that employ human PCa cells DU145 (androgen insensitive) and LNCaP (androgen sensitive), we found that the major polyphenolic constituent (-)-epigallocatechin-3-gallate (EGCG) of green tea induces 1) apoptosis, 2) cell-growth inhibition, and 3) cyclin kinase inhibitor WAF-1/p21-mediated cell-cycle dysregulation. More recently, using a cDNA microarray, we found that EGCG treatment of LNCaP cells results in 1) induction of genes that functionally exhibit growth-inhibitory effects, and 2) repression of genes that belong to the G-protein signaling network. In animal studies that employ a transgenic adenocarcinoma of the mouse prostate (TRAMP), which is a model that mimics progressive forms of human prostatic disease, we observed that oral infusion of a polyphenolic fraction isolated from green tea (GTP) at a human achievable dose (equivalent to 6 cups of green tea/d) significantly inhibits PCa development and metastasis. We extended these studies and more recently observed increased expression of genes related to angiogenesis such as vascular endothelial growth factor (VEGF) and those related to metastasis such as matrix metalloproteinases (MMP)-2 and MMP-9 in prostate cancer of TRAMP mice. Oral feeding of GTP as the sole source of drinking fluid to TRAMP mice results in significant inhibition of VEGF, MMP-2 and MMP-9. These data suggest that there are multiple targets for PCa chemoprevention by green tea and highlight the need for further studies to identify novel pathways that may be modulated by green tea or its polyphenolic constituents that could be further exploited for prevention and/or treatment of PCa.


Abstract During the last few years personas has become an established design technique within the IT-design field. Using personas has proven itself as a valuable approach for designers to switch between a developer's perspective and a user's perspectivein the design process. The technique is claimed to help designers in keeping a clear focus and shaping a consistent user-interface by making 'the user' present in the design work. In this paper we report on a number of projects where we have elaborated on the persona approach for collaborative design. With the goalof creating 'user presence' in the design process, we have developed an approach building on a combination of ethnographic exploration, participatory inquiry, and collaborative design. This paper carries two interrelated points: the grounding of personasin existing practice; and the notion that 'the user' is created as an ongoing process throughout the design work.


What makes high schools successful in a high-stakes accountability environment? This case study used documents, interviews, and site visits to create profiles of 11 diverse North Carolina high schools with records of high performance on state assessments. Profiles were analyzed by themes or patterns of success recurring in the data. The analysis indicated five patterns of success: relationships and connections; safety nets andfamily fteling; data-directed dialogue and collaborative instruction; departments as drivers; and collaborative leadership. Implications for educational practice are provided.


Field-effect mobility as high as 5 cm2/(V s) is achieved in solution-processed organic thin-film transistors with the development of a method for growing highly-oriented crystalline films of [1]benzothieno[3,2-b]benzothiophene derivatives. A droplet of the solution is sustained at an edge of a structure on an inclined substrate, so that the crystalline domain grows in the direction of inclination. The oriented growth realizes excellent molecular ordering that manifests itself in micrometer-scale molecular terraces on the surface as a result of the self-organizing function of the material. The unprecedented performance achieved using an easy fabrication process has increased attractiveness of organic thin-film transistors for industrial applications.


Despite the call for pluralism in IS research there is a lack of multi-method research published in information systems journals. While many researchers might find the idea of using multiple methods attractive, there are barriers that prevent them from employing this approach in practice. In this paper we try to address key philosophical concerns that often deter more extensive use of multiple methods, encourage openness to innovative methodological choices, and deepen practical understanding about how critical realism can be used as the foundation of IS research designs. We begin by exploring the value of critical realism as a theoretical foundation for mixed-method information systems research. After discussing the debate surrounding quantitative methods (especially economics) among critical realists, we propose making the identification of demi-regularities pivotal to the design of qualitative fieldwork. To provide support for this approach we present evidence from a study of IS innovation adoption in financial services which we believe highlights the value of multiple methods to inspire and inform the research process as it unfolds.


Paruresis, characterized by the difficulty or inability to urinate in a variety of social contexts, is a scientifically under-studied phenomenon. One reason for this state of affairs is the paucity of reliable and valid measures for assessing this problem. The present article attempted to address this limitation by investigating the psychometric properties and validity of a new measure of paruresis: the Shy Bladder Scale (SBS). In two undergraduate samples, the SBS demonstrated excellent internal consistency and a stable factor structure assessing difficulty urinating in public, impairment and distress, and paruresis-related fear of negative evaluation. Undergraduate students evidenced very low levels of paruresis-related concerns. In contrast, SBS scores were markedly elevated among individuals recruited from an online support network who appeared to meet diagnostic criteria for paruresis-specific social phobia. Our findings highlight the SBS's potential utility as a measure of paruresis in clinical and research contexts.


Purpose: Proof‐of‐concept of a three‐dimensional (3D) pelvic phantom for evaluation of deformable image registration algorithms. Methods: The phantom represents a cylindrical section of the human pelvic anatomy, modeled after human CT scan data, and is intended for use as an insert in a Modus QUASAR phantom. Polyurethane plastic was used to represent both fat and muscle sections with additives used to achieve appropriate Hounsfield units (HU) for the fat regions. The phantom consists of two halves, manufactured using silicon molds, which are placed together when the phantom is deformed. Keying on the inner surfaces was used to ensure proper alignment of the two halves. A grid of non‐radiopaque markers was printed on the surface of each half‐cylinder. We created two identical phantom sets, then deformed one. Optical imaging was used to characterize marker position pre‐and post‐deformation to calculate the 2D deformation. These can then be superimposed on laser scan profiles of the surface to measure the deformation in the third dimension. Identical markers were printed on both phantom halves to evaluate the effectiveness of the keys. Results: We achieved deformations up to 1.6 mm. The keys remained intact through the deformation process. The mean distance to agreement between the markers on the two halves of the phantoms was 0.28 mm. The deformation field centered around the keys suggests that the keys were effective in keeping the phantom together. Conclusion: We have demonstrated feasibility of a three‐dimensional deformable phantom for evaluation of DIR algorithms. Future tests will be performed to further characterize and optimize performance of the keys. Development of this 3D phantom will enable improved assessment of DIR algorithm accuracy, providing quality assurance and optimization of DIR algorithm usage in the clinical setting. This work was supported in part by a UC Proof of Concept Program Commercialization Gap Grant.


The effect of plant cultures, Brachiaria ruziziensis, Cajanus cajan, of the phosphate fertilizers and of the liming on amilolytic, cellulolytic, proteolytic and ureolytic bacteria and fungi were investigated. The proportion of bacteria with enzymatic activity in relation to the total varied from 25 to 87% and fungi from 2 to 36%. The groups of bacteria increased its population in plots added with superphosphate and lime in relation to the other treatments (except the ureolytic that increased in plots not fertilized) and the fungi enhanced in the unfertilized (except the ureolytics that increased with superphosphate) and limed plots. The highest counts of ureolytic bacteria and proteolytic fungi were found in the soil cultivated with B. ruziziensis. The CM-cellulolytic (CM, cellulose microcrystalline) and ureolytic fungi enhanced in the uncultivated plots and the amilolytic and CMC-cellulolytic (CMC, carboxymethylcellulose) in the plots cultivated with C. cajan. The other groups of bacteria were not influenced by the cultivation system. The population and the enzymatic ability of the fungi groups were smaller than the bacteria, suggesting a smaller participation in the nutrients cycling in the soil. The bacteria presented multiple enzymatic activities, showing larger versatility than the fungi.


Leachates from municipal solid waste (MSW) contain a large number of compounds many of which are not hazardous to health and nature as they represent degradation products ranging from small volatile acids to refractory fulvic and humic-like compounds and some of which are hazardous compounds including aromatic compounds, halogenated compounds, phenolic compounds, pesticides, heavy metals, and ammonium. Phenolic compounds released into the environment are of high concern because of their potential toxicity. These compounds found in the leachate include phenol, cresols and substituted and chlorinated phenols that have been designated as priority pollutants by the U.S. Environmental Protection Agency. Phenolic compounds degrade under anaerobic conditions in landfill sites. In this study, the degradation of phenolic compounds in leachate has been investigated by using leachate recirculated anaerobic reactors representing bioreactor landfills. Wastes representing Istanbul municipal solid wastes were disposed in the reactors. Phenolic compounds of leachate are analyzed by using Gas Chromatograph. Before injection of leachate to the Chromatograph, contaminants in the leachate are extracted by using solid phase micro extraction (SPME) method. A first-order kinetic model was adopted to represent the microbial degradation of phenolic compounds under anaerobic conditions.


China has in recent decades expanded its wind power generation capacity and become the world leader. Still, despite robust government support, wind power in China is obstructed by various barriers (e.g. quality deficiencies, inability to export, missing grid connections, and permit delays from central government for grid construction etc.). This paper synthesises the literature that has discovered weaknesses in the Chinese wind power development and suggests improvements. One energy policy relevant observation is that when the Chinese government sets command-and-control construction targets over new installed capacity, actors delivered to target – but with several power plants without grid connectivity and severe quality problems. The article contributes to the academic debate over the role of policy making in renewable energy development and argues that China should improve their incentive structure and coordination of regulations.


This research is concerned with utilizing new technologies to harvest existing narrative, symbolic and emotive value for use in a digital environment enabling "emotional durability" (Chapman, 2005) in future design.
The projects discussed in this paper have been conducted as part of PhD research by Rosemary Wallin into 'Technology for Sustainable Luxury' at University of the Arts London, and visual effects technology research undertaken by Florian Stephens at University of West London.
Jonathan Chapman describes vast consumer waste being "symptomatic of failed relationships" between consumers and the goods they buy, and suggests approaches for designing love, dependency, and even cherishability into products to give them a longer lifespan. 'Failed relationships' might also be observed in the transference of physical objects to their virtual cousins. Consider the throwaway nature of digital photography when compared to the carefully preserved prints in a family album.
Apple often use a skeuomorphic (Hobbs, 2012) approach to user interface design, to digitally replicate the patina and 'value' of real objects. However, true transference of physical form and texture presumably occurs when an object is scanned and a virtual 3D model is created.
This paper presents three practice-based approaches to storing and transferring patina from an original object, utilizing high resolution scanning, photogrammetry, mobile applications and 3D print technologies. The objective is not merely accuracy, but evocation of the emotive data connecting the digital and physical realm.
As the human face holds experience in the lines and wrinkles of the skin, so the surface of an object holds its narrative. From the signs of the craftsman to the bumps and scratches that accumulate over the life of an item over time and generations, marks gather like evidence to be read by a familiar or a trained eye. According to the time and the culture these marks are read within, they will either add to or detract from its value. These marks can be captured via complex 3D modelling and scanning technologies, which allow detailed forms to be recreated as dense 3D wireframe, but the result is often unsatisfying. 3D greyscale surfaces can never fully capture the richness of patina. Authentic surfaces require other qualities such as colour, texture and depth, but there is something else - more difficult to define.
Donald A. Norman expands on the idea of emotion and objects by describing three 'levels' of design "visceral, behavioural and reflective". Visceral is based on "look, feel and sound", behavioural is focused on an object's use, and reflective is concerned with its message. New technology is commonly seen in terms of its ability to increase efficiency, but this research has longer-term objectives: to repair or even rebuild Chapman's 'broken relationships' and enable 'emotionally durable' design.
The PhD that has formed the context for this paper examines the concept of luxury value, and how and why the value of patina has been replaced by fashion. Luxury goods are aspirational items often emulated in the bulk of mass production. If we are to alter behaviour around consumption, one approach might be to use technology to harvest patina as a way to retain emotional, symbolic and poetic value with a view to maintaining a relationship with the things we buy.


Fratricide in the Holy Land: A Psychoanalytic View of the Arab-Israeli Conflict, by Avner Falk. Madison: University of Wisconsin Press Terrace Books, 2004. 271 pp. $35.00. In his book Fratricide in the Holy Land, Avner Falk attempts to analyze the Arab Israeli conflict, as well as key leaders and issues, from a psychoanalytic point of view. This is an important perspective often missing from historical accounts. As with any situation, understanding is deepened if one looks for the psychoanalytic interpretations. Falk's attempt to explain an age-old conflict, nuanced with political, religious, racist, territorial, and fundamentalist aspects, as a psychoanalytic conflict is commendable and risky. It is not clear which audience this book is written for. As a psychoanalyst, I find it worrisome that Falk would represent psychoanalytic thinking and attitudes to the lay person. His armchair analysis of characters whom he has not had as patients (Sharon, Arafat, Bush) trivializes the practice of psychoanalysis. His sweeping generalizations are the very stereotypes that have plagued the reputation of psychoanalysis. There is nothing new in the recognition that many in power have narcissistic characters and are "working out" personal issues. He is more relevant when he looks at the psychology of large groups to understand how one leader can hold such power over masses. For the historian or student of conflict resolution, he certainly offers an important aspect that cannot be overlooked if one is to understand the conflict in its totality. Hopefully, for all readers, his approach will broaden understanding of both sides. For any person interested in the topic, the book offers a tremendous bibliography and a taste of all that has been written on the debates of the history of this conflict. The book opens the reader's eyes to the potential power of applied psychoanalytic thinking. Fratricide in the Holy Land is set up in an orderly fashion, although many of the chapters repeat the same few important points. It is very readable; however, there are cliches that are a bit contrived and as a result diminish the power of important psychoanalytic concepts. For example, "Denial is Not a River in Egypt" and "Reality is in the Eye of the Beholder" are titles of two of the chapters. The introduction and the literature review in the first chapter give the reader most of the information that will come later. Falk does not feel there has been much written from an analytic perspective about the conflict. However, there is a literature in conflict resolution, psychoanalysis, holocaust studies, and social psychology which he does not mention. Perhaps Falk means that not much thought has been given to psychological processes specifically by historians. There are several chapters devoted to psychobiography of Sharon, Arafat, and Bush, which are the weaker parts of the book. His chapters on reality, psychogeography, and the inability to mourn are the strength and heart of his thesis-that great losses on both sides, not collectively mourned, force each side to deny their losses, and make each unable to recognize the pain and existence of the other. His other central point, generating the title of the book, is that the Jews and Arabs are brothers, engaged in sibling rivalry for the love and possession of the mother, the land. The strengths of the book are Falk's discussions of group psychology. He refers to the important work done by Vamik Volkan, who has looked at ethnic conflict groups psychoanalytically. Volkan addresses the importance of the group identity and was the first to coin the term "chosen trauma"-the trauma in its history which a group holds onto and around which forms an identity. This is a key concept to understand if one is to work in any productive way with the two sides. Volkan has also recognized the importance of working with individuals out of their group context, who can bridge the two worlds and introduce a new possibility to the group of origin. …


OBJECTIVE
To investigate the effectiveness and reliability of posterior sub-Tenon triamcinolone acetonide (PSTA) application in branch retinal vein occlusion (BRVO)-related macular edema.

METHODS
Patients with confirmed BRVO-related macular edema were enrolled in the study. Patients were injected with a single, therapeutic dose of 40 mg PSTA. Detailed ophthalmic examination was performed at baseline and at 1, 3 and 6 months after the treatment. Best corrected visual acuity (BCVA), intraocular pressure (IOP), cataractogenic change (CC) and macular optical coherence tomography (OCT) analysis results were evaluated. The results were compared statistically.

RESULTS
Forty-one eyes of 41 patients with a mean age of 63.49 ± 10.99 (55-86) years, 15 (36.6%) females, were included in the study. BCVA in LogMAR values at 1 and 3 months were significantly better than at baseline, while no significant difference from baseline was observed in sixth month values (p < 0.001, p < 0.001 and p = 0.846, respectively). Central macular thickness values obtained using OCT were significantly lower at the first, third and sixth months compared to baseline (p < 0.001 for all). IOP elevation was determined in only two eyes (4.8%) at the end of the study period, and no CC was detected in any case.

CONCLUSION
PSTA application is an effective and safe option in BRVO-related macular edema.


This chapter describes the efforts of the LARICS team in the 2019 European Robotics League (ERL) Emergency Robots and the 2020 Mohamed Bin Zayed International Robotics Challenge (MBZIRC) robotics competitions. We focus on the implementation of hardware and software modules that enable the deployment of aerial-ground robotic teams in unstructured environments for joint missions. In addition to the overall system specification, we outline the main algorithms for operation in such conditions: autonomous exploration of unknown environments and detection of objects of interest. Analysis of the results shows the success of the developed system in the competition arena of two of the largest outdoor robotics challenges. Throughout the chapter, we highlight the evolution of the robotic system based on the experience gained in the ERL competition. We conclude the chapter with key findings and additional improvement ideas to advance the state of the art in search and rescue applications of heterogeneous robotic teams.


ABSTRACT APOBEC3G (A3G) is a cytidine deaminase that restricts human immunodeficiency virus type 1 (HIV-1) and other lentiviruses. Most of these viruses encode a Vif protein that directly binds A3G and leads to its proteasomal degradation. Both Vif proteins of HIV-1 and African green monkey simian immunodeficiency virus (SIVagm) bind residue 128 of A3G. However, this position does not control the A3G degradation by Vif variants derived from HIV-2 and SIVmac, which both originated from SIV of sooty mangabey monkeys (SIVsmm), suggesting that the A3G binding site for Vif proteins of the SIVsmm/HIV-2 lineage differs from that of HIV-1. To map the SIVsmm Vif binding site of A3G, we performed immunoprecipitations of individual A3G domains, Vif/A3G degradation assays and a detailed mutational analysis of human A3G. We show that A3G residue 129, but not the adjacent position 128, confers susceptibility to degradation by SIVsmm Vif. An artificial A3G mutant, the P129D mutant, was resistant to degradation by diverse Vifs from HIV-1, HIV-2, SIVagm, and chimpanzee SIV (SIVcpz), suggesting a conserved lentiviral Vif binding site. Gorilla A3G naturally contains a glutamine (Q) at position 129, which makes its A3G resistant to Vifs from diverse lineages. We speculate that gorilla A3G serves as a barrier against SIVcpz strains. In summary, we show that Vif proteins from distinct lineages bind to the same A3G loop, which includes positions 128 and 129. The multiple adaptations within this loop among diverse primates underscore the importance of counteracting A3G in lentiviral evolution.


Knowledge represents things as they are. But how are things? Traditionally, epistemology has based knowledge on experience. To accept a proposition means to find it consistent with one's experience. But can we trust experience to give us the 'facts' in an unadulterated way? There are scholars who claim just that, for instance Roy Harris in his new book After Epistemology, and Martin Heidegger in his Being and Time, now almost a century old. While I agree with both of them that Cartesian rationality is not a sound basis for making epistemological claims, I take issue with their argument that knowledge can be generated by a prelinguistic interpretation of authentic experience. I argue that there is no interpretable experience without participation in discourse, and that therefore the discursive construction of the category 'cat' is prior to any cat experience. Instead of viewing ourselves as solitary knowing minds, we should assign intentionality ('aboutness') to discourse as a collective mind. Knowledge that can be represented in the form of arbitrary signs only exists in discourse, of which we, the selves, are a part.


Multiattribute auction mechanisms generally either remain agnostic about traders' preferences, or presume highly restrictive forms, such as full additivity. Real preferences often exhibit dependencies among attributes, yet may possess some structure that can be usefully exploited to streamline communication and simplify operation of a multiattribute auction. We develop such a structure using the theory of measurable value functions, a cardinal utility representation based on an underlying order over preference differences. A set of local conditional independence relations over such differences supports a generalized additive preference representation, which decomposes utility across overlapping clusters of related attributes. We introduce an iterative auction mechanism that maintains prices on local clusters of attributes rather than the full space of joint configurations. When traders' preferencesare consistent with the auction's generalized additive structure, the mechanism produces approximately optimal allocations, atapproximate VCG prices.


The study presented here provides support for Rokeach's (1973) contention that followers of different political viewpoints may be differentiated by their relative endorsements of the values of Freedom and Equality. A previous test of the hypothesis in New Zealand (in 1975) proved inconclusive and this was argued as reflecting the homogeneous two-party political environment of the time. Since 1996, however, New Zealand has implemented a proportional representation electoral system that allows a degree of political heterogeneity absent from earlier tests of the hypothesis. The present paper describes a content analysis of parliamentary speeches by representatives of five ideologically distinct political parties. Contrary to previous local findings (but consistent with overseas research) the parties were classifiable in their differential endorsement of the target values. The classification related systematically to the parties' positions in the current political climate, with left-wing parties endorsing Equality over Freedom, while the reverse was increasingly true of parties of the right. ********** The most frequently cited definition of what constitutes a human value (psychologically defined) is offered by Rokeach (1973) as an "enduring belief that a specific mode of conduct or end-state of existence is personally or socially preferable to an opposite or converse mode of conduct or end-state of existence" (p.5). Rokeach argued that, considered together, values form values systems where a value system is "an enduring organisation of beliefs concerning preferable modes of conduct or end-states of existence along a continuum of importance" (1973, p.5). Thus the importance of different values should co-vary with the importance of others in the value system. Human values are strongly prescriptive in nature and form the core around which other less enduring beliefs are organised. As such they are important in a range of other processes. For example, the formation of specific attitudes is theoretically predicated upon more general values. Rokeach's conceptualisation of values, and the conceptualisation of a finite set of values as the foundation for an infinite set of attitudes continues to be a focus of research (e.g., Allen, Ng & Wilson, 2002; Allen, Wilson, Ng & Dunne, 2000; Barnea & Schwartz, 1998; Braithwaite, 1997, 1998; Schwartz, 1992; Thannhauser & Caird, 1990). If attitudes are predicated upon value systems then by extension political attitudes are also predicated upon values. Indeed, Rokeach (1973) contended that the traditional left-right (liberal-conservative) continuum was not sufficient to differentiate (or make comparisons) between all the varieties of political ideologies active in the political environment. In its place, Rokeach proposed that the minimum number of independent (theoretically uncorrelated) dimensions necessary to describe different ideologies was two, and outlined a programme of research intended to show that proponents of different political philosophies differ in their relative support for the two values of Freedom and Equality. For example, adherents of liberal democratic or socialist doctrine should endorse both values equally highly while the reverse is true of Nazist or fascist sympathisers who should endorse neither. Differential endorsement of the two values is illustrated by Republican or right-wing supporters valuing Freedom over Equality and communists favouring Equality over Freedom. In this respect, Rokeach's (1973) emphasis on Freedom and Equality has proven durable. These two values continue to be implicated in a range of social and political issues, and have been shown to reflect basic attitudinal dimensions. For example, based on his cross-cultural values analysis, Hofstede (1980) suggested that power-distance (Equality versus hierarchy) and individualism-collectivism (Freedom versus interdependence) represent two primary psychological dimensions. …


The pathogenic bacterium Mycobacterium tuberculosis (Mt) is the causative agent of tuberculosis, a widespread and fatal infectious disease. Today, treatment against tuberculosis involves a combination of drugs, which need to be taken for at least six months and which often causes severe side effects. Therefore, new drugs that are more effective and that give fewer side effects are needed. A characteristic feature of the Mt bacterium is its very complex and thick cell wall, which prevents many potential drug molecules from penetrating it. Inhibiting any one of the enzymes that are involved in its biosynthesis would therefore seem to be a good strategy for eliminating the Mt bacteria. The aim of this study was to characterize four enzymes involved in Mt cell wall biosynthesis. In order to do that, they were produced recombinantly in E. coli and purified. Crystallization experiments were set up in order to produce diffracting crystals, with the aim of structure determination and drug design.


The paradigm of differentiable programming has significantly enhanced the scope of machine learning via the judicious use of gradient-based optimization. However, standard differentiable programming methods (such as autodiff) typically require that the machine learning models be differentiable, limiting their applicability. Our goal in this paper is to use a new, principled approach to extend gradient-based optimization to functions well modeled by splines, which encompass a large family of piecewise polynomial models. We derive the form of the (weak) Jacobian of such functions and show that it exhibits a block-sparse structure that can be computed implicitly and efficiently. Overall, we show that leveraging this redesigned Jacobian in the form of a differentiable"layer"in predictive models leads to improved performance in diverse applications such as image segmentation, 3D point cloud reconstruction, and finite element analysis.


Background There are many empirical studies that demonstrate the associations between problematic internet use, psychopathological symptoms, and personality traits. However, complex models are scarce. Objective The aim of this study was to build and test a mediation model based on problematic internet use, psychopathological symptoms, and personality traits. Methods Data were collected from a medical addiction center (43 internet addicts) and internet cafés (222 customers) in Beijing (mean age 22.45, SD 4.96 years; 239/265, 90.2% males). Path analysis was applied to test the mediation models using structural equation modeling. Results Based on the preliminary analyses (correlations and linear regression), two different models were built. In the first model, low conscientiousness and depression had a direct significant influence on problematic internet use. The indirect effect of conscientiousness—via depression—was nonsignificant. Emotional stability only affected problematic internet use indirectly, via depressive symptoms. In the second model, low conscientiousness also had a direct influence on problematic internet use, whereas the indirect path via the Global Severity Index was again nonsignificant. Emotional stability impacted problematic internet use indirectly via the Global Severity Index, whereas it had no direct effect on it, as in the first model. Conclusions Personality traits (ie, conscientiousness as a protective factor and neuroticism as a risk factor) play a significant role in problematic internet use, both directly and indirectly (via distress level).


This paper examines MC enabling technologies and their impact on the success of MC systems in Cosay Company by using System Dynamics analyzing. It also demonstrated the effect of technology on the level of customization and production volume. This paper shows how technology contributes in the handling of the customers, the realization of the product or service, and the coordination between those two sides, which is a vital element to the success of an MC system. It has been found from the system dynamics model that the company's information system plays a major role in linking and coordinating the different sides of the MC cycle and also has a valuable input in market research and development.


Trust is a critically important ingredient in the recipes for a successful economy and a well-functioning securities market. Due to scandals, ranging in nature from massive incompetence to massive irresponsibility to massive fraud, investor trust is in shorter supply today than in years past. This is troubling, and commentators, policy makers, and industry leaders have all recognized the need for trust's restoration. As in times ofsimilar crises, many have turned to law and regulation for the answers to our problems. The imposition of additional regulatory oversight, safeguards, and remedies, some advocate, can help resuscitate investor trust. These advocates have it half right. For trust is complicated, and exists in a variety offorms. Some forms, predicated primarily upon reasoned calculation, respond well to law and regulation. But other forms, predicated primarily upon relationship and emotion, respond poorly to law and regulation. In fact, these latterforms of trust can be seriously harmed by legal intervention. Wise policymakers would carefully assess the nature of whatever particular trust relationship they wish to strengthen before taking action to ostensibly strengthen the trust in that relationship. Unfortunately, such an assessment has not been part ofthe significant securities law reforms recently proposed. As such, some of these reforms threaten to undermine, rather than enhance, the remaining supply of trust.


Whenever a program runs within the operating system, there will be data or artefacts created on the system. This condition applies to the malicious software (malware). Although they intend to obscure their presence on the system with anti-forensic techniques, still they have to run on the victim's system to acquire their objective. Modern malware creates a significant challenge to the digital forensic community since they are being designed to leave limited traces and misdirect the examiner. Therefore, every examiner should consider performing all the forensics approaches such as memory forensic, live-response and Windows file analysis in the related malware incidents to acquire all the potential evidence on a victim's system. There is a challenge when an examiner only has an option to perform post-mortem forensic approach. It leads to a question: what is a forensic examination and analysis that available to obtain evidence in such incidents? The paper shows how the Prefetching process works on a system, common characteristics and the differences in the Prefetching process related to the various versions of Windows. Thus, the paper shows how the Prefetch files contain the evidentiary value which could answer what, how, where and when the banking Trojan malware infects the system. Finally, the paper shows that forensic examination and analysis of the Prefetch files can find the data remnants of banking Trojan malware incidents.


This volume explores the relationship between law and economics principles and the promotion of social justice. By social justice, we mean a vision of society that embraces more than traditional economic efficiency. Such a vision might include, for example, a reduction of subordination and discrimination based on race, religion, gender, sexual orientation, age, disability or class; increased wealth dispersion throughout all sectors of society; a safe and healthy environment; worker rights; and, a flourishing political democracy. The volume chapters here fall into four main categories, Assumptions of Law & Economics; Law & Economics: Implications of Behavioralism; Economics and Corporate Governance: Finding the Holes; and, Gender, Class and Race: Implications of and Alternatives to the Dominant Economic Paradigm. In addition, most of the chapters invoke the lens of corporate law theory or the corporate context as part of their analysis of the intersection of economics and social justice.


Why are some psychoactive substances regarded as a ~dangerous drugsa (TM), to be controlled by the criminal law within a global prohibition regime, whilst others a "from alcohol and tobacco, through to those we call a ~medicinesa (TM) a "are seen and regulated very differently? A History of Drugs traces a genealogy of the construction and governance of the a ~drug problema (TM) over the past 200 years: calling into question some of the most fundamental ideas in this field: from a ~addictiona (TM) to the very concept of a ~drugsa (TM).

At the heart of the book is the claim that it was with the emergence in the late eighteenth century of modern liberal capitalism, with its distinctive emphasis on freedom, that our concerns about the consumption of some of these substances began to grow. And, indeed, notions of freedom, free will and responsibility remain central to the drug question today. Pursuing an innovative inter-disciplinary approach, A History of Drugs provides an informed and insightful account of the origins of contemporary drug policy. It will be essential reading for students and academics working in law, criminology, sociology, social policy, history and political science.


Mastl kinase promotes mitotic progression and cell cycle reentry after DNA damage. We report here that Mastl is frequently upregulated in various types of cancer. This upregulation was correlated with cancer progression in breast and oral cancer, poor patient survival in breast cancer, and tumor recurrence in head and neck squamous cell carcinoma. We further investigated the role of Mastl in tumor resistance using cell lines derived from the initial and recurrent tumors of the same head and neck squamous cell carcinoma patients. Ectopic expression of Mastl in the initial tumor cells strongly promoted cell proliferation in the presence of cisplatin by attenuating DNA damage signaling and cell death. Mastl knockdown in recurrent tumor cells re-sensitized their response to cancer therapy in vitro and in vivo. Finally, Mastl targeting specifically potentiated cancer cells to cell death in chemotherapy while sparing normal cells. Thus, this study revealed that Mastl upregulation is involved in cancer progression and tumor recurrence after initial cancer therapy, and validated Mastl as a promising target to increase the therapeutic window.


Communities of Practice (CoPs) in organisation science are often described as 'the shop floor of human capital' where learning and knowledge creation which underpins innovation evolves. Adopting the Bristol area geocaching community as a case study, this paper draws on the 'practice turn' in contemporary social theory to study the everyday interaction of the community members in their situated practice. Taking the geocaching community and their practice as a collective unit of analysis, the study employed the qualitative methods of ethnographic interviewing, participant observation and content analysis of archival internet forum logs of members to extend our understanding of the performative processes of social learning and knowledge creations in CoPs. A conceptual framework showing how the interactions among actors and their artefacts and reflexivity in practice could lead to learning and knowledge creation that stimulates innovation in a CoP is presented as a modest attempt to improve our understanding of the dynamics of a CoP renewal and sustainability.


We present an implementation of the F-statistic to carry out the first search in data from the Virgo laser interferometric gravitational wave detector for periodic gravitational waves from a priori unknown, isolated rotating neutron stars. We searched a frequency f0 range from 100 Hz to 1 kHz and the frequency dependent spindown f1 range from −1.6 (f0/100 Hz) × 10 Hz/s to zero. A large part of this frequency spindown space was unexplored by any of the all-sky searches published so far. Our method consisted of a coherent search over twoday periods using the F-statistic, followed by a search for coincidences among the candidates from the two-day segments. We have introduced a number of novel techniques and algorithms that allow the use of the Fast Fourier Transform (FFT) algorithm in the coherent part of the search resulting in a fifty-fold speed-up in computation of the F-statistic with respect to the algorithm used in the other pipelines. No significant gravitational wave signal was found. The sensitivity of the search was estimated by injecting signals into the data. In the most sensitive parts of the detector band more than 90% of signals would have been detected with dimensionless gravitational-wave amplitude greater than 5 × 10. PACS numbers: 04.80.Nn, 95.55.Ym, 97.60.Gb, 07.05.Kf


Plant pathogens secrete an arsenal of small secreted proteins (SSPs) acting as effectors that modulate host immunity to facilitate infection. SSP-encoding genes are often located in particular genomic environments and show waves of concerted expression at diverse stages of plant infection. To date, little is known about the regulation of their expression. The genome of the Ascomycete Leptosphaeria maculans comprises alternating gene-rich GC-isochores and gene-poor AT-isochores. The AT-isochores harbor mosaics of transposable elements, encompassing one-third of the genome, and are enriched in putative effector genes that present similar expression patterns, namely no expression or low-level expression during axenic cultures compared to strong induction of expression during primary infection of oilseed rape (Brassica napus). Here, we investigated the involvement of one specific histone modification, histone H3 lysine 9 methylation (H3K9me3), in epigenetic regulation of concerted effector gene expression in L. maculans. For this purpose, we silenced the expression of two key players in heterochromatin assembly and maintenance, HP1 and DIM-5 by RNAi. By using HP1-GFP as a heterochromatin marker, we observed that almost no chromatin condensation is visible in strains in which LmDIM5 was silenced by RNAi. By whole genome oligoarrays we observed overexpression of 369 or 390 genes, respectively, in the silenced-LmHP1 and -LmDIM5 transformants during growth in axenic culture, clearly favouring expression of SSP-encoding genes within AT-isochores. The ectopic integration of four effector genes in GC-isochores led to their overexpression during growth in axenic culture. These data strongly suggest that epigenetic control, mediated by HP1 and DIM-5, represses the expression of at least part of the effector genes located in AT-isochores during growth in axenic culture. Our hypothesis is that changes of lifestyle and a switch toward pathogenesis lift chromatin-mediated repression, allowing a rapid response to new environmental conditions.


This article argues in support of state corporate law either prohibiting CEOs from serving as chairman of the board or from serving as directors of public companies. By limiting the ability of CEOs to dominate the governance process and giving directors increased separation and independence from the CEOs' influence, boards will be better equipped to ask the tough questions of management and hopefully discover problems before they occur. Moreover, by limiting the role of executive management on public company boards, state law can delineate the roles of CEO and director. Separating the CEO's work as an executive from that of a director benefits the courts as it continues to develop the fiduciary duties of both roles. This article examines the social science data on leadership and group decision-making and argues that such data can improve corporate governance by eliminating the structural reasons for CEO dominance and board groupthink, which exists under corporate laws. Part II examines CEO dominance and firm performance. Part II explores the factors that contribute to CEO dominance, including how the personality traits of CEOs influence decision-making, the environment in which directors fail to critically examine the decisions or information provided to them by CEOs, and the social science data on board groupthink behavior. Part IV examines the pros and cons of CEOs as board members. Part V looks at how separating the role of CEO from chairman of the board can minimize CEO dominance of the board and why removing the CEO as a director offers even more assurance that the CEO likely will not control the board through sheer force of personality. Finally, Part VI proposes solutions to minimize the effect of CEO dominance on board decision-making.


Abstract. Arctic soils store large amounts of organic carbon and
other elements, such as amorphous silicon, silicon, calcium, iron, aluminum,
and phosphorous. Global warming is projected to be most pronounced in the
Arctic, leading to thawing permafrost which, in turn, changes the soil
element availability. To project how biogeochemical cycling in Arctic
ecosystems will be affected by climate change, there is a need for data on
element availability. Here, we analyzed the amorphous silicon (ASi) content
as a solid fraction of the soils as well as Mehlich III extractions for the
bioavailability of silicon (Si), calcium (Ca), iron (Fe), phosphorus (P),
and aluminum (Al) from 574 soil samples from the circumpolar Arctic region.
We show large differences in the ASi fraction and in Si, Ca, Fe, Al, and P
availability among different lithologies and Arctic regions. We summarize
these data in pan-Arctic maps of the ASi fraction and available Si, Ca, Fe, P,
and Al concentrations, focusing on the top 100 cm of Arctic soil.
Furthermore, we provide element availability values for the organic and
mineral layers of the seasonally thawing active layer as well as for the
uppermost permafrost layer. Our spatially explicit data on differences in
the availability of elements between the different lithological classes and
regions now and in the future will improve Arctic Earth system models for
estimating current and future carbon and nutrient feedbacks under climate
change (https://doi.org/10.17617/3.8KGQUN, Schaller and Goeckede, 2022).


Research and clinical activities are often portrayed as arising from different motivations and having different goals. This study sought to determine lay and professional understandings of research and clinical care within the translational subspecialty of cancer genetics. Fifty-nine lay research participants and 20 professional stakeholders were interviewed. Research and clinical care were described in similar ways by both groups of interviewees, who distinguished these activities according to their temporal orientation and focus. Stakeholders' accounts tended to focus upon the epistemological motivations underlying research activities, whereas research participants emphasized concrete goals, for example, finding a cure for cancer. We discuss the implications of these findings for informed consent. We argue that informed consent for research and clinical interventions should be redefined so that establishing potential research participants'/patients' understanding of the purpose of an intervention, why it is taking place, should be seen as secondary to confirming their understanding of its nature, namely, what will happen and the associated risks.


Use of herbs as combinations is a common practice with many herbal practitioners. The main idea behind this usually is the synergistic action expected to take place by the traditional healer hence being able to give better results as compared to one herb and also treat more than one ailment, even those not mentioned by the patient. However, other interactions such as additive and antagonism too take place when herbs are used in combinations. In this study, anti-aspergillus and anti-candida efficacy of crude extracts of five plants used in combination to treat malaria were investigated. Toddalia asiatica (root), Rhamnus staddo (root) , Momordica foetida (shoot), Podocarpus falcatus (bark), Aloe sp (secculent leaves) used by traditional health practitioners in the Kalenjin community were extracted using water and dichloromethane/methanol (1:1) and the crude extracts tested for in vitro antifungal activity singly and in combinations against Aspergillus niger and Candida albicans. Dichloromethane/methanol extracts of P. falcatus showed the highest activity (77.77% inhibition) against A.niger while M. foetida showed the highest activity (77.78% inhibition) against C. albicans. Aloe sp. Showed no activity against A. niger when tested singly. A.niger was more sensitive to the plants extracts than C.albicans. Aqueous extracts did not show any activity. Antagonism, additive and synergism were observed when combinations of the herbal plants were assayed. Findings in this study are a preliminary verification of the usefulness of using herbal plants in combinations as a prevalent practice among the traditional healers.


In many respects, our understanding of innate immune responses to protozoan parasites still lags behind that for other infectious organisms. However, recent work has shown that an important part of the armory against African trypanosomes is serum apolipoprotein L-I (apoL1), which can kill the parasite by causing lysis—why, then, would the parasites take it in? Vanhollebeke et al. show that apoL1 is taken up by the parasite via a specific glycoprotein receptor, which the parasite normally uses to supply heme for its growth and resistance to oxidative stress within the host. In human serum, however, the receptor also inadvertently recognizes a component of certain high-density lipoprotein complexes, of which apoL1 is a part, explaining how the uptake of this detrimental host protein is triggered. B. Vanhollebeke, G. De Muylder, M. J. Nielsen, A. Pays, P. Tebabi, M. Dieu, M. Raes, S. K. Moestrup, E. Pays, A haptoglobin-hemoglobin receptor conveys innate immunity to Trypanosoma brucei in humans. Science 320, 677-681 (2008). [Abstract] [Full Text]


This chapter provides a counter-example to the usual story of legal secularization and modernization. It suggests that the enactment of a secular law code in a non-European setting can interact in unexpected ways with local religious traditions and customary law and can ultimately produce a widespread rejection of liberal legalism.Legal modernization in Thailand during the early Twentieth Century brought the semi-autonomous Lanna region under the control of the emergent Thai state (Then known as Siam). Thai leaders sought to suppress a vibrant Lanna legal tradition that linked village-level customary practices to the formal laws of the Lanna princes. In this tradition, legal concepts and practices were closely connected to a distinctive form of Buddhism that incorporated non-Buddhist elements associated with spirit worship. When the Thai state adopted a European-style civil code, it aimed to shatter these connections between law and religion and curb local traditions that might challenge state supremacy. Instead, customary legal beliefs and practices were driven underground and continued to shape the behavior of potential litigants, lawyers, and judges in ways that could not be openly acknowledged. Only in recent years, with the disruptions and dislocations caused by global influences, have Lanna legal and religious practices begun to fade. Yet this recent development has not brought a greater acceptance of secular legalism but rather a new form of Buddhism that views law and religion as inherently oppositional. Focusing on injury cases, this analysis shows how religious consciousness can be transformed and strengthened within a modern state, leading to a widespread perception that secular law is contrary to fundamental values and beliefs.


An inspiring look at the remarkable women who fought so tirelessly for equality. Using new material, this study moves away from the ardent activists in London and focuses on the campaign for the vote for women in Scotland. Non-militant 'suffragist' groups were found countrywide -- from Ayrshire to Orkney -- and involved thousands of Scottish women of all ages and from all backgrounds. Unlike their attention-grabbing counterparts the Suffragettes, these women laboured not only for the right to vote, but also for the right to higher education, to separate legal existence from their husbands, and to be actively involved in local government. This is the story of individual Scottish suffragists, resolute and passionate women whose lives have been 'hidden from history', but who now receive the recognition they deserve.


Overcrowding is one of the most crucial issues confronting emergency departments (EDs) throughout the world. Efficient management of patient flows for ED services has become an urgent issue for most hospital administrations. Handling and detection of abnormal situations is a key challenge in EDs. Thus, the early detection of abnormal patient arrivals at EDs plays an important role from the point of view of improving management of the inspected EDs. It allows the EDs mangers to prepare for high levels of care activities, to optimize the internal resources and to predict enough hospitalization capacity in downstream care services. This study reports the development of statistical method for enhancing detection of abnormal daily patient arrivals at the ED, which able to provide early alert mechanisms in the event of abnormal situations. The autoregressive moving average (ARMA)-based exponentially weighted moving average (EWMA) anomaly detection scheme proposed was successfully applied to the practical data collected from the database of the pediatric emergency department (PED) at Lille regional hospital center, France.


Abstract Purpose: The aim of this study was to examine what factors affect the acceptance behavior and use of new technologies for rehabilitation by therapists at a large rehabilitation hospital in Canada. Method: A self-administrated paper-based survey was created by adapting scales with high levels of internal consistency in prior research using the Unified Theory of Acceptance and Use of Technology (UTAUT). Items were scored on a 7-point Likert scale, ranging from "strongly disagree (1)" to "strongly agree (7)". The target population was all occupational therapists (OT) and physical therapists (PT) involved with the provision of therapeutic interventions at the hospital. Our research model was tested using partial least squares (PLS) technique. Results: Performance expectancy was the strongest salient construct for behavioral intention to use new technologies in rehabilitation, whereas neither effort expectancy nor social influence were salient constructs for behavioral intention to use new technologies; (4) facilitating condition and behavioral intention to use new technologies were salient constructs for current use of new technologies in rehabilitation, with facilitating condition the strongest salient for current use of new technologies in rehabilitation. Conclusion: In a large rehabilitation hospital where use of new technologies in rehabilitation is not mandatory, performance expectancy, or how the technology can help in therapists' work, was the most important factor in determining therapists' acceptance and use of technologies. However, effort expectancy and social influence constructs were not important, i.e. therapists were not influenced by the degree of difficulty or social pressures to use technologies. Behavioral intention and facilitating condition, or institutional support, are related to current use of new technologies in rehabilitation. Implications for Rehabilitation Rehabilitation professionals who are faced with using new technologies are less concerned about effort and social pressures, than they are about what the technologies can do for them or their clients. When it comes to new rehabilitation technologies, actual users express intention. Rehabilitation professionals' acceptance and adoption of technologies rely on conditions that facilitate their use. These conditions include scheduling, support and a conductive environment.


We ionize small mixed pinene-water clusters by electron impact or by using photons after sodium doping and analyze the products by mass spectrometry. Electron ionization results in the formation of pure pinene, mixed pinene-water and protonated water cluster cations. The "fragmentation free" photoionization after sodium doping results into the formation of only water-Na+ clusters with a mean cluster size below that observed after electron ionization. We show that protonated water clusters are formed both directly and indirectly via pinene ionziation. The latter pathway is detailed by ab intio calculations, demonstrating the feasibility of proton transfer from pinene for larger water clusters. In small clusters, the proton transfer reaction is controlled by proton solvation energy and we can thus estimate its value for finite size clusters. The observed stabilization mechanism of water clusters may contribute to the formation of cloud condensation nuclei in the atmosphere.


Evidence-based medicine (EBM) has been influencing medicine for almost 20 years. It is important because the volume of medical literature available means it is impossible to stay up to date. This article looks at the background and definitions of EBM together with an outline of the tools that can support EBM in practice. Methods of grading the reliability of published articles are discussed. The role of systematic reviews and the utility of forest plots, L'Abbe plots and numbers needed to treat are presented. Some see EBM as a rule book whereas its strengths are in the ability to give tools to assess evidence. While evidence is primarily used for individual patient care, it can also be used for professional interventions and changing systems. Clinical pharmacists are encouraged to develop these skills in their clinical practice.


A mid to late Tertiary lake, Palaeolake Etosha, was the single collective end point of three drainage systems feeding southwards off the central Angolan highlands, the Cubango and Kunene Megafans and the Cuvelai Drainage System. The lake beds consist of 50 m of saline, olive green clay, the Etosha Pan Clay Member, containing authigenic analcime, monoclinic K-feldspar and glauconite. Fossil suites in two local sandstones near or at the top of the clay, the Oshigambo and Ekuma Delta Sandstone Members, include various antelope, pig, zebra, quagga, rhinoceros, elephant, lion, spring hare, ostrich, flamingo, crocodile, hippopotamus, freshwater turtles, catfish, bivalves and trees, which have respective ages of 6 ± 1 Ma and 4 ± 1 Ma. An oolitic, pan-margin limestone of limited lateral extent, the Poacher's Point Carbonate Member, was the last unit deposited in the palaeolake. Flooding and complete desiccation were common occurrences in Palaeolake Etosha before it dried up completely at about 4 Ma under conditions of progressively increasing aridity. Over the ensuing 2 Ma, a huge groundwater calcrete, the Etosha Calcrete Formation, advanced northwards over the dry lake deposits and the surface Kalahari sands were reworked to produce the regional Kalahari dune fields.

Resumption of periodic flow in the Cuvelai system resulted in cycles of flooding and desiccation in an ephemeral Cuvelai endpoint lake atop the Etosha Calcrete Formation in the Etosha area. Fragmentation of the calcrete by salt enabled strong easterly winds to remove the calcrete fines from the Etosha depression. This initiated the 'excavation' of the present Etosha Pan by wind ablation. Lunette dunes on the western side of Etosha Pan contain an inverted pan stratigraphy. Flooding of the present pan occurs occasionally and has been as deep as 10 m in the past. White magadi-type chert nodules have formed locally on the pan floor in animal footprints.


Given the impact of YouTube on Internet services and social networks, a healthy quantity of research has been conducted over the past few years. The majority of studies on traffic capture and evaluation were carried out prior to Google's acquisition of YouTube in 2007. Since then, there have been some changes made to the user policy and service infrastructure, including limits placed on video duration, file size, and resolution. This article depicts the latest YouTube traffic profiles and delivers updated and valuable information for future researchers. To obtain a detailed understanding of YouTube video characteristics, a customized Web spider was employed to crawl over a million YouTube videos. The study demonstrates consistency with previous research for major video streams while revealing that new categories of features have emerged within the YouTube service provision. Compared with traditional video repositories, YouTube exhibits many unique characteristics that could introduce novel challenges and opportunities for optimizing the performance of short video-sharing services.


Migration and colonization are major forces affecting the frequency, spatial pattern and spread of genes in human populations. Here, Alan Fix reviews theories of migration developed by biologists and social scientists, and surveys patterns of migration in a diverse sample of human populations. Using these empirical studies, he evaluates models of migration developed by population geneticists and explores more realistic models using computer simulation. He then shows the relevance of studies of migration as a microevolutionary process to the understanding of longer term global patterns of human diversification, by examining the spread of anatomically modern Homo sapiens, the demic diffusion of agriculture in Europe, and the origins of human diversity in the Malayan Peninsula. By focusing on migration as a process rather than as its genetic consequences, the book provides a bridge between biological and social science studies of migration, genetic microevolutionary theory and longer term human evolution.


AIM AND OBJECTIVE
Vinca domain of tubulin protein is the potential target for different microtubule targeting drugs (MTD). However, its binding mechanism and structure-activityrelationship (SAR) is not well understood in terms of ligand-receptor interactions and structure functionality requirements. This limits the exploitation of vinca domain for developing novel clinical leads. Herein, as a progressive step towards the exploration of this target, we rendered the in-silico insight through the development of a robust pharmacophore model followed by the QSAR, Molecular Docking and Molecular Dynamics (MD) simulations. Furthermore, the study was undertaken to identify potent inhibitors that can inhibit vinca domain of tubulin.

MATERIALS AND METHODS
Utilizing the well-defined tubulin polymerization inhibition activities, common pharmacophore hypotheses were constructed and scored for their rankings. The hypotheses were validated by 3D-Atom based QSAR and tested for various statistically relevant metrices. Thereafter, virtual screening was performed with ZINC natural product database and the screened hits were evaluated for structure-based studies via molecular docking and molecular dynamics simulations.

RESULTS
The predictive 3D-QSAR based pharmacophore model consists of two hydrogen bond acceptors (A), two hydrogen bond donors (D) and one hydrophobic (H) group. Significance of the model was reflected from the statistical parameters viz. r2 = 0.98, q2 = 0.72, F = 562.9, RMSE = 0.11 and Pearson-R = 0.87. Further, the docking scores of the retrieved hits deciphered that the ligands were adequately bound in the pocket. Moreover, RMSD fluctuations of protein (1.0 to 1.75A) and ligand (0.3 to 2.3 Å) in molecular dynamics simulations insinuate towards the conformational and interactions stability of the complexes.

CONCLUSION
The quantitative pharmacophore model was developed from range of natural product scaffolds in order to incorporate all the complimentary features accountable for inhibition. The obtained hits were found to occupy similar binding region and superimpose well over the reference ligand. Therefore, it can be concluded that hierarchical combination of methods exploited in this study can steer the identification of novel scaffolds. Moreover, the rendered hit molecules could serve as potential inhibitory leads for the development of improved inhibitors targeting Vinca domain.


Lonely Planet: The world's leading travel guide publisher Lonely Planet Thailand's Islands & Beaches is your passport to all the most relevant and up-to-date advice on what to see, what to skip, and what hidden discoveries await you. Island-hop in a long-tail boat, explore the nooks and crannies underwater in Ko Tao, or scramble skywards on the rocks of Railay; all with your trusted travel companion. Get to the heart of Thailand's Islands and Beaches and begin your journey now! Inside Lonely Planet Thailand's Islands & Beaches Travel Guide: *Colour maps and images throughout *Highlights and itineraries show you the simplest way to tailor your trip to your own personal needs and interests *Insider tips save you time and money and help you get around like a local, avoiding crowds and trouble spots *Essential info at your fingertips - including hours of operation, phone numbers, websites, transit tips, and prices *Honest reviews for all budgets - including eating, sleeping, sight-seeing, going out, shopping, and hidden gems that most guidebooks miss *Cultural insights give you a richer and more rewarding travel experience - including customs, history, art, literature, cinema, music, dance, theatre, architecture, politics, wildlife, and cuisine *Free, convenient pull-out Bangkok map (included in print version), plus over 85 local maps *Useful features - including Walking Tours, Month-by-Month (annual festival calendar), and Travel with Children *Coverage of Bangkok, Ko Chang, the Eastern Seaboard, Hua Hin, the Southern Gulf, Phuket, the Andaman Coast, Ko Samui, the Lower Gulf, Ko Phi-Phi, Ko Pha-Ngan, Railay, and more The Perfect Choice: Lonely Planet Thailand's Islands & Beaches, our most comprehensive guide to Thailand's islands and beaches, is perfect for those planning to both explore the top sights and take the road less travelled. * Looking for more coverage? Check out Lonely Planet's Thailand guide for a comprehensive look at what the whole country has to offer, or Lonely Planet's Discover Thailand, a photo-rich guide to all the most popular attractions in that country. Authors: Written and researched by Lonely Planet, Brandon Presser, Celeste Brash, and Austin Bush. About Lonely Planet: Started in 1973, Lonely Planet has become the world's leading travel guide publisher with guidebooks to every destination on the planet, as well as an award-winning website, a suite of mobile and digital travel products, and a dedicated traveller community. Lonely Planet's mission is to enable curious travellers to experience the world and to truly get to the heart of the places they find themselves in. TripAdvisor Travelers' Choice Awards 2012 and 2013 winner in Favorite Travel Guide category 'Lonely Planet guides are, quite simply, like no other.' - New York Times 'Lonely Planet. It's on everyone's bookshelves; it's in every traveller's hands. It's on mobile phones. It's on the Internet. It's everywhere, and it's telling entire generations of people how to travel the world.' - Fairfax Media (Australia)


The damage caused by the soybean cyst nematode, Heterodera glycines, not only limits expansion of the soybean (Glycine Max) crop but also reduces the yield of soybeans in Brazil. Knowledge of  the spatial distribution of this pathogen is needed in order to establish management measures. This study was conducted in Florinea County, Sao Paulo, Brazil, in a commercial soybean field, cultivar BRS133, previously known to be infected with H. glycines. In order to see the pattern of the spectral response of plants attacked by the phytonematode, field spectroradiometry measurements in the visible and near infrared regions of the electromagnetic spectrum were obtained 112 days after sowing. At the same time, soil samples were taken to the "Laboratorio de Nematologia do Departamento de Fitossanidade da Universidade Estadual Paulista Julio de Mesquita Filho, Campus de Jaboticabal", where they were processed and where the population density of the nematode was determined. The spectroradiometric measurements were transformed to the normalized difference vegetation index (NDVI) that was related to population density of the nematode, to fresh biomass and to pods per plant. It was observed that different population densities are directly related to the spectral response of the plants expressed by NDVI values.


This book accompanies an international exhibition of paintings and drawings from the Oskar Reinhart Foundation in Winterthur, one of the finest collections of German, Austrian and Swiss art in Europe. Oskar Reinhart (1885 - 1965) presented his extraordinary collection of Northern Romantic and Realist art to the town of Winterthur, establishing a museum with over five hundred paintings and several thousand drawings. The collection opened to the public in 1951 but still remains little known outside Switzerland - paintings from the Foundation are lent only on rare occasions and the Reinhart collection has never been shown abroad. With introductory essays and detailed texts on each artist, this book surveys a rich pictorial tradition, ranging from the quiet introspection of the Romantic era and the gentle charm of Biedermeier to the robust art of Realist and Symbolist painters at the end of the century. Paintings by major artists (including Friedrich, Runge, Menzel, Bocklin, Liebermann and Hodler) are discussed alongside works by less familiar figures whose work deserves greater recognition.


ABSTRACT This study investigates the impact of Catholic schooling on academic achievement of native Belgian and Muslim immigrant pupils. The distinctive characteristics of Catholic schools in Belgium (Flanders) form an exceptionally suitable context to study this. Multilevel latent growth curve analyses are conducted with data from approximately 5,000 pupils across 200 primary schools. No support was found for the Catholic school advantage hypothesis as the overall achievement growth for math and reading was not significantly better in Catholic schools than in public schools. Likewise, no evidence was found for the so-called "common school effect" hypothesis: The learning growth of Muslim pupils was not significantly better in Catholic schools. In fact, the initial achievement gap was found to be higher in Catholic schools than in public schools. Implications of these findings are discussed.


ABSTRACT We show that every finite affine algebra A admits a full duality. In the process, we prove that A also allows a strong duality, and that the duality may be induced by a dualizing structure of finite type. We give an explicit bound on the arities of the partial and total operations appearing in . In addition, we show that the enriched partial hom-clone of A is finitely generated as a clone.


Every prospective home buyers has their own criteria in selecting home that suit their needs. But many of these criteria are followed by the availability of more than one choice of homes that meet those criteria. Therefore, we need a computerized system that can help them to obtain a good home selection decisions based on their needs. Method used in this research is K-nearest Neighbor (KNN). KNN is a method to classify the new objects based on the training data that were located closest to the object. This paper discusses about recommendation system to select house using 11 kinds of criteria, such as price, location, land area, building area, floor, bedroom, bathroom, maid's room, garage/carport, electric power and water resources. This system also used a geographical information system to display the results in the form of a map. The testing was conducted by 25 users, they tried out the system and filled the satisfaction questionnaire system. The level of satisfaction obtained from two main aspects : result satisfaction and user interface design satisfaction, which is including the usability and the attractivess system. The results of this tests indicate the level of user satisfaction by 38% very satisfied, 58% satisfied and 4% not satisfied. Keywords : Decision Support System, Geographic Information System, House Purchasing, K-Nearest Neighbor,


Q: On 20 November 2009, it was the 20th anniversary of the United Nations Convention on the Rights of the Child (CRC). Sri Lanka is often cited as a model for its work in reducing child and maternal mortality and in improving literacy. How has the CRC contributed to this? A: Sri Lanka has a good record of achievement with regard to children. In my country, we have had visionary policies on health and education, meaning that every child has had the right to go to school and the right to basic health and that has been reflected in very good social indicators for children even before the CRC. In a sense, politicians had put rights in place through these policies but they weren't written into the 1978 Constitution's Bill of Rights. Q: What changes followed the CRC in Sri Lanka? A: Before the convention, we did not consider "rights" were necessary for all children, and child abuse was addressed only from the point of view that they are "children in difficult situations". The convention linked the concept of good governance and state accountability. Giving access to health and education for all children, recognizing gaps in coverage and the need to prevent disparities in health delivery are now state obligations. Protecting children from abuse and exploitation must also receive high priority. The CRC is a powerful accountability measure for ensuring an effective public health system. Q: Is the CRC really necessary for a country with sound laws and policies? A: Implementing all the standards on child rights in the CRC is not an easy task. An ideal situation does not prevail in any country, not even developed countries. Some argue that if "the health policies are in place, why do we need to put them in the constitution and other laws?" The reason is clear. Political systems are very fragile. All it takes is a change in a health minister. If someone comes in with a different attitude, everything can change. If a right is not in place in a law or constitution, it's very easy to pull it back. Q: Is there cynicism about what human rights can achieve? A: There is a cynicism about rights and what they can do, especially in developing countries. This just encourages states not to implement the treaties they have signed. Human rights laws create a culture of support for implementing health policies by helping the community to monitor the state's actions and programmes. They can't get away with saying "we can't help this situation". Even in a country such as ours, which has some fairly sound laws and policies on health systems and a fairly good administrative system for health delivery, there are gaps and weaknesses. Examples are the regional variations in health and education services and child abuse. Q: You have completed an assessment of adolescents' rights of access to reproductive and sexual health information and services in Sri Lanka. What did you find? A: We found that Sri Lanka's focus on child protection has benefited children in the younger age group, but has largely neglected young people. The problem is that we group adolescents as either children or young people but their needs are quite specific. Adolescents' health problems are becoming more complex. Health providers need to acknowledge adolescents have a right to basic health services in some neglected areas such as reproductive health based on access to information and the right of choice. Over the years, problems have emerged including exploitation of children, particularly young girls who work in domestic service when they should be in school, sexual abuse of adolescents within the family and in the community. Teenage pregnancy is an emerging problem. Q: Sri Lanka has an exceptionally good record in the region for its attempts to eliminate child marriages. Why do they still occur? A: Our laws and policies on access to education helped in the implementation of minimum age laws. …


In releasing the songs Courtesy of the Red, White and Blue (The Angry American) and American Soldier in the aftermath of September 11, country artist Toby Keith enacts a tradition that has been established in the world of country music since the Civil War, that of producing wartime songs of patriotism. I conducted an organic analysis of both songs as rhetorical acts produced and consumed within a particular rhetorical context. Because country music is fundamentally a discourse that celebrates the attitudes, values and experiences of its audience, I first analyzed these two songs as instances of epideictic rhetoric. As an epideictic rhetor, Keith reinforces the traditional values of the country music audience, uniting them in celebration of the communal identity that renders them a rhetorical community. That shared identity enables Keith to advance a rhetorical vision of a post-September 11 reality, attributing meaning to the events of September 11 and the ensuing conflicts in Afghanistan and Iraq. I use pentadic analysis to illuminate the vision presented in each song, and I utilize both media coverage and the Billboard charts to determine how well this vision "chained out" amongst the country music audience. Lastly, I utilize media coverage to explore the rhetorical context in which these songs were written and consumed.


The process of respiration is a pattern of spontaneity and automatic motor control that originate in the brainstem. The mechanism by which the brainstem detects CO2 is termed central CO2 chemoreception (CCR). Since the early 1960's there have been tremendous efforts placed on identification of central CO2 chemoreceptors (molecules that detect CO2). Even with these efforts, what a central CO2 chemoreceptor looks like remain unknown. To test the hypothesis that inward rectifier K (Kir) channels are CO2 sensing molecules in CCR, a series of experiments were carried out. 1) The first question asked was whether the Kir4.1-Kir5.1 channel is expressed in brainstem chemosensitive nuclei. Immunocytochemistry was performed on transverse medullary and pontine sections using antibodies raised against Kir4.1 and Kir5.1. Positive immunoassays for both Kir4.1 and Kir5.1 subunits were found in CO2 chemosensitive neurons. In the LC the Kir4.1 and Kir5.1 were co-expressed with the neurokinin-1 receptor that is the natural receptor for substance P. 2) The second question asked was whether the Kir4.1-Kir5.1 channel is subject to modulation by neurotransmitters critical for respiratory control. My studies demonstrated that indeed the Kir4.1-Kir5.1 channel is subject to modulation by substance P, serotonin and thyrotropin releasing hormone. 3) I performed studies to demonstrate the intracellular signaling system underlying the Kir4.1-Kir5.1 channel modulation by these neurotransmitters. The modulation by all three neurotransmitters was dependent upon the activation of protein kinase C (PKC). The Kir4.1-Kir5.1 but not the Kir4.1 channel was modulated by PKC. Both the Kir4.1 and Kir5.1 subunits can be phosphorylated by PKC in vitro. However, systematic mutational analysis failed to reveal the phosphorylation site. 4) The fourth question asked was whether Kir channels share a common pH gating mechanism that can be identified. Experiments were performed to understand the gating of the Kir6.2+SUR1 channel as specific sites for ligand binding and gating have been demonstrated. I identified a functional gate that was shared by multiple ligands that is Phe168 in the Kir6.2. Other Kir channels appear to share a similar gating mechanism. Taken together, these studies demonstrate the modulation of Kir channels in central CO2 chemoreception. INDEX WORDS: Kir4.1-Kir5.1, Kir6.2+SUR1, Central CO2 Chemoreception, Neuromodulation, Phosphorylation, Channel Gating, Ligand Modulation, CO2/pH sensing KIR CHANNELS IN CO2 CENTRAL CHEMORECEPTION: ANALYSIS WITH A FUNCTIONAL GENOMICS APPROACH


Both the intrinsic and the acquired anticancer drug resistance presents until today a major drawback in the management of cancer. The handling with drug resistance is aggravated by the facts that drug resistance is a multifactorial and multifaceted phenomenon. The development of tumor-targeted pharmacological and genetic strategies to overcome intrinsic resistance and to prevent the resistance acquisition is thus still a pressing need. We put forward the two main objectives: 1) The reversal of the pre-existing drug resistance in p53-deficient cells by either the concomitant abrogation of DNA repair functions or by the concomitant blocking of cytoprotective signaling pathways. 2) The identification of members of the novel class of histone deacetylase (HDAC) inhibitors with anticancer activity that have (or do not have) the potential to cause resistance acquisition in tumor cells.
 Mutations in the p53 gene and dysregulation of p53-dependent cellular processes are often associated with cancer and resistance to radio- and chemotherapy. Many Advances have been taken to reconstitute the (wildtype) p53 tumor suppressor pathway in cancer cells. We showed that genetic abrogation of the expression of the DNA mismatch repair (MMR) gene Pms2 in cells depleted for the p53 tumor suppressor function hypersensitized these cells to the cytotoxic effect of some anticancer agents through an increase in the rate of apoptosis. Expanding on this, we also showed that genetic depletion of either ATM, BRCA1, or DNA-PK resulted in an increase in the chemosensitivity of p53-deficient cells against a variety of anticancer agents. These studies indicate that tumor-targeted functional inhibition of either one or the other of these DNA repair genes may reverse resistance in p53-mutated tumors and therefore provide a strategy for increasing chemotherapy efficacy for these tumors. Analogous as well as opposing results were reported for loss of the MMR protein MLH1 in p53-deficient cells with Cisplatin. However, neither Radicicol (HSP90 inhibitor) nor LY294002 and LY294005 (Akt inhibitors) were found to reverse Cisplatin resistance specifically in MMR-deficient tumor cells. These Akt inhibitors even further decreased the sensitivity against Cisplatin, suggesting - in addition to its acknowledged cytoprotective function - a cytodestructive function of Akt.
 On the other hand, we showed the potential of the HDAC inhibitor SAHA to induce stable and MDR-independent resistance in HCT116 colon tumor cells. As these results differ from those reported with FK-228, we propose a novel mechanism of resistance acquisition by the SAHA, the nature of which is still obscure. This is under investigation, as is novel and intriguing molecular approach to reverse drug resistance: the liposomal delivery of (exogenous) cytochrome c to tumor cells.


This chapter focuses on the classifier systems found around the world, with particular attention to Amerindian languages. It first proposes a typology of these systems that takes into account their different characteristics (morpho-syntactic, semantic, pragmatic. . .) and their dynamic dimensions (grammaticalization, age, productivity. . .). It then describes in more detail a sample of classifier systems (fromAmerica, Asia, Oceania. . .), shows some of their invariants and specificities, and relates them to other linguistic systems. The final part of the chapter presents a summary of the types of information that are conveyed by classifier systems and other nominal classification systems about spatial entities (e.g., spatial properties, perceptual modalities. . .) and examines, as well, the different encoding strategies that seem to be used across languages.


To survive, animals must adapt synaptic weights based on external stimuli and rewards. And they must do so using local, biologically plausible, learning rules – a highly nontrivial constraint. One possible approach is to perturb neural activity (or use intrinsic, ongoing noise to perturb it), determine whether performance increases or decreases, and use that information to adjust the weights. This algorithm – known as node perturbation – has been shown to work on simple problems, but little is known about either its stability or its scalability with respect to network size. We investigate these issues both analytically, in deep linear networks, and numerically, in deep nonlinear ones. We show analytically that in deep linear networks with one hidden layer, both learning time and performance depend very weakly on hidden layer size. However, unlike stochastic gradient descent, when there is model mismatch between the student and teacher networks, node perturbation is always unstable. The instability is triggered by weight diffusion, which eventually leads to very large weights. This instability can be suppressed by weight normalization, at the cost of bias in the learning rule. We confirm numerically that a similar instability, and to a lesser extent scalability, exist in deep nonlinear networks trained on both a motor control task and image classification tasks. Our study highlights the limitations and potential of node perturbation as a biologically plausible learning rule in the brain.


In contrast to accepted notions regarding the necessity of shared meanings for effective organizing, the basic premise of this paper is that organizational meanings are not shared as such but rather overlap to varying degrees, while they are used by organizational members as if shared. That is, following Weick (1979) it is argued that it is only necessary for organizational meanings to overlap among members to the degree that sense can be made and organization enacted. Secondly, it is argued in this paper that organizational activity is enacted despite, or more likely because of, the partially shared or overlapped nature of communication meanings. That is, because of the inherent ambiguity in symbolic language forms such as humour and metaphor, organizational members communicate as if they share meanings and thus exact their organization on the basis of the appearance of shared meanings. Finally, it is argued that the sense of community that results from shared activity and the appearance of shared meanings is more important to the process of group development than whether meanings are, in fact, shared. To test this argument, the ethnographic research presented in this dissertation focused on the communicative behaviours of the members of a temporary organization: a group of candidates--senior police executives--on a six week Executive Development Course at the Canadian Police College in Ottawa. Through observation of behaviour and conversation, survey questionnaires, sociometric analysis and semi-structured interviews, the meanings for organizational symbols (humour and metaphor) were identified. Then, individual members' interpretations of these symbols, and the implicit social rules influencing them, were identified and analyzed for comparison and contrast. The findings demonstrate that organizational activity was enacted under conditions of limited overlap of meanings. Furthermore, the data show that meanings themselves were not shared completely, but that a complex set of implicit rules regarding the meanings was shared. As well, importantly, a pattern of putdown humour was found, wherein subjects moved from putting themselves down, to putting down their shared occupation and other people, to finally putting each other down. Related to this pattern of putdown humour was a set of implicit social rules regarding putdown behaviour which appeared to be shared by the candidates. Finally, it is clear from the data that the sense of community that was created through the appearance of sharedness was of greater interest and import than whether the actual meanings were shared. This dissertation thus focused specifically on the meanings held by organizational members, and, unlike any previous work, uncovers a number of layers of meaning and sharedness.


The use of tri-n-butyltin hydride and an initiator to mediate free radical cyclisation as a
synthetic organic process is well documented throughout the chemical literature. By using
BU3SnH, and developing new 'catalytic' BU3SnH methods, many new heterocyclic
compounds have been synthesised successfully. The search for new 'tin-free' radical reagents
is important in order to provide a non-toxic alternative to tin. We have started initial studies
on the replacement oftriorganotin hydrides with germanium analogues. An interesting
number of reactions using BU3SnH do not give reduced products and have an oxidation step
in the mechanism. These BU3SnH mediated cyclisations provide a useful synthetic method.
Our studies were aimed at developing the synthetic protocol as well as determining the
mechanism.
'Shilajit' is an ancient tribal panacea, believed to have many advantageous biological
properties. The active constituents are based upon a benzochromenone skeleton. The key
component of the natural product Shilajit, 3-methoxy-6H-benzo[c]chromen-6-one, as well as
several analogues have been synthesised using this BU3SnH mediated 'oxidative' free radical
approach. The mechanism proposed for these reactions by Bowman et ai, the pseudo SRN I
mechanism, has also been studied in order to try to determine the presence of the radical
anion intermediates which are essential for the pseudo SRN 1 mechanism to be correct.
The BU3SnH mediated 'oxidative' cyclisation protocol was successfully applied to electron
deficient pyrroles, i.e. pyrroles with electron withdrawing substituents. Radicals generated
on N-substituted chains readily undergo cyclisation onto the pyrrole ring. The protocol was
also applied to cyclisation reactions of analogous imidazoles. The imidazole reactions were
used for an extensive examination of the mechanism of the 'oxidative' BU3SnH protocol. The
studies have disproved the pseudo SRN 1 mechanism (where BU3SnH is the oxidising agent)
and suggest possible alternative oxidising agents. The importance of the functionality on the
heterocyclic ring is also emphasised. Free radicals have been generated using photolytic
methods, and the results are contrasted with those from traditional BU3SnH reactions. The
synthesis of several substituted pyrazoles and radical cyclisation reactions were attempted on
various pyrazole systems with the aim of synthesising the natural product withasomnine.


We explore the quantified morphology of atomic hydrogen (H i) discs in the Virgo cluster. These galaxies display a wealth of phenomena in their H i morphology, e.g., tails, truncation and warps. These morphological disturbances are related to the ram pressure stripping and tidal interaction that galaxies undergo in this dense cluster environment. To quantify the morphological transformation of the H i discs, we compute the morphological parameters of Concentration, Asymmetry, Smoothness, Gini and M20 and our own GM for 51 galaxies in 48 H i column density maps from the VLA Imaging of Virgo spirals in Atomic gas (VIVA) project.

Some morphological phenomena can be identified in this space of relatively low-resolution H i data. Truncation of the H i disc can be cleanly identified via the Concentration parameter (C < 1), and Concentration can also be used to identify H i deficient discs (1 < C < 5). Tidal interaction is typically identified using combinations of these morphological parameters, applied to (optical) images of galaxies. We find that some selection criteria (Gini–M20, Asymmetry and a modified Concentration–M20) are still applicable for the coarse (∼15 arcsec  full  width  at  half - maximum) VIVA H i data. We note that Asymmetry is strongly affected by the choice for the centre of these galaxies. The phenomena of tidal tails can be reasonably well identified using the Gini–M20 criterion (60 per cent of galaxies with tails identified but with as many contaminants).

Ram pressure does move H i discs into and out of most of our interaction criteria: the ram pressure sequence identified by previous authors tracks into and out of some of these criteria (Asymmetry-based and the Gini–M20 selections, but not the Concentration–M20 or the GM-based ones). Therefore, future searches for interaction using H i morphologies should take ram pressure into account as a mechanism to disturb H i discs enough to make them appear as gravitationally interacting. One mechanism would be to remove all the H i deficient (C < 5) discs from the sample, as these have undergone more than one H i removal mechanism.


The Common Agricultural Policy (CAP) has evolved through various reforms since its outline in 1958 and formal inception in 1962. It has changed from a policy focused on farm production outputs to one focusing more on social, rural and environmental support. UK policy interest in the CAP is being shaped by the Referendum decision on whether or not to remain a part of the EU. To disentangle UK food and farm policy from that of European neighbours and then to re-establish workable trading links is not a small task. We argue that ideally the CAP would become a Common Sustainable Food Policy or Common Food Policy. This framework would help integrate farm and fisheries policies with diverse measures that are needed to reduce food's impact on health, environment and social inequalities.

Policy-makers at EU and national levels must help shift the food system to meet the needs of the 21st century. Some of CAP's founding aims – for food security, affordability, health – remain appropriate today, although what is meant by those goals has altered since the CAP was mooted in the late 1950s. Written before the UK's 2016 Referendum on EU membership, this paper argues that, whether the UK is in or out, the drive to more sustainable consumption and production needs to be an essential characteristic of the UK's diet and supply chain. The UK like all EU member states needs to review its entire food system. At the EU level, a Common Food Policy would translate existing commitments to Sustainable Consumption and Production and help meet the new Sustainable Development Goals. The paper signals out some elements where new broader thinking is already emerging or being debated: animal welfare, water, public health, waste reduction and the commitment to the 'circular economy'. Clearer political leadership and policy leverage is required to enable the structural shifts required. Civil society and academics can play an important role in creating the appropriate arguments, data and conditions for the transition that is sorely needed.

Specifically, the paper explains how:
• The CAP was first introduced over 50 years ago in response to post-war food insecurity and has been constantly changing over time. The latest reforms of 2013 began to take effect in 2015.
• The 2013 reforms introduced a new greening element into the CAP in an effort to encourage sustainable production. Following from the 2000 reforms, payments under so-called Pillar 1 are now made on a per hectare basis rather than per unit of output.
• Although considerably less than the 70% seen in the 1980s, the CAP now absorbs 40% of the EU budget.
• The Directorate-General for Agriculture and Rural Development in Brussels has only 1,000 civil servants, yet accounts for over a third of the total EU budget. Defra in the UK has 2,000 for England alone.
• In the UK, farmers receive only £10 billion of the £198 billion that UK consumers spend on food per year. Many farmers rely on the additional income from subsidies to keep them in farming.
• The CAP has social, economic, health and environmental impacts, not all of which are beneficial. Perhaps most success in the UK has come in terms of environmental improvements, but there is still much to be done in this area.
• Although the CAP has not impacted animal welfare directly, it does have indirect effects as the subsidies given to arable farming have allowed an increase in the intensive pig and poultry sectors.
• Many problems are noted with the current CAP, which means it will need to radically change in the future. Four broad options about CAP's purpose and preparations for the next phase of reform are explored in which CAP: (a) weakens significantly; (b) evolves pragmatically; (c) becomes a rural development policy; or (d) becomes a Common (Sustainable) Food Policy. The paper favours a Common Sustainable Food Policy that addresses current health crises and environmental costs.
• Problems in the food and farming sectors remain whether the public votes to Brexit or Bremain on 23rd June. A Common Sustainable Food Policy will be relevant whatever the outcome.