This international and illustrated work challenges current writings focussing on the problems of urban public space to present a more nuanced and dialectical conception of urban life. Detailed and extensive international urban case studies show how urban open spaces are used for play, which is defined and discussed using Caillois' four-part definition - competition, chance, simulation and vertigo. Stevens explores and analyzes these case studies according to locations where play has been observed: paths, intersections, thresholds, boundaries and props. Applicable to a wide-range of countries and city forms, The Ludic City is a fascinating and stimulating read for all who are involved or interested in the design of urban spaces.


Whether the European Union's Takeover Directive should have adopted a mandatory neutrality rule has been the subject of much debate. As the European Commission commences its review of the Directive this debate is being reignited. A view is crystallising that the success and failure of the Directive can, in large part, be measured by the number of Member States that have opted-in, or out of the neutrality principle, or have opted-in subject to the reciprocity option. The contestability of European corporations is viewed through this lens as a function of the extent to which EU Member States have adopted an unqualified neutrality rule. This article takes issue with this viewpoint. It argues that the pre-Directive debate and the post-Directive assessment have failed to consider the core lesson of takeover defences in the United States, namely that the construction of defences and their potency are a function of basic corporate law rules. If corporate law rules do not enable the construction of takeover defences, or undermine the extent to which they can be potently deployed, then the adoption or rejection of the neutrality principle in Member States is of trivial significance. This article explores the triviality hypothesis in three central EU jurisdictions: the United Kingdom, Germany, and Italy. It concludes that, although there is variable scope to construct and deploy takeover defences in these jurisdictions, the triviality thesis is well founded.


Background. In the Nigerian setting the curriculum of each medical school is the sole responsibility of the senate of the respective university. This arrangement results in variability in learning objectives and in students' acquisition of skills to manage clinical problems. Educational objectives can be used to both standardise and evaluate curricula. This study aimed to: (i) identify main objectives of paediatric surgery at the undergraduate level; (ii) establish students' knowledge with regard to these objectives; (iii) evaluate the input of both specialists and non-specialists to these objectives; and (iv) examine the status of undergraduate paediatric surgery instruction in our medical schools.

Materials and methods. This was a cross-sectional survey of students, teachers and undergraduate deans with regard to undergraduate paediatric surgery teaching. The cognitive and perceived level of knowledge about common paediatric surgical conditions of 4th- and 6th-year medical students in four randomly selected Nigerian universities was surveyed using educational objectives. The same objectives were used to survey 26 paediatric surgeons, 46 senior house officers and 46 general surgeons. Undergraduate paediatric surgery curricula, obtained from the offices of the deans of the four medical schools, were also reviewed. Data were analysed using descriptive methods and one-way analysis of variance (ANOVA).

Results. The 6th-year students'and house officers' perceived knowledge of the objectives was remarkably similar. Overall, students' familiarity scores increased from the 4th to the 6th year (p 2.0) and 8 items to be non-essential (mean score 2.0) and 11 to be non-essential (mean score <1.5).

Data from the deans' offices varied, but indicated limited exposure to paediatric surgery in the undergraduate curriculum in 2 (50%) of the 4 institutions.

Conclusion. The study clarified the relationship between the expected and perceived students' knowledge of these objectives, and identified areas requiring specific attention. These results, and perhaps similar ones in future, can be used towards establishing a unified, standardised undergraduate paediatric surgery curriculum.


Let $a,b,c,d$ be four vertices in a graph $G$. A \emph{$K_4$-minor rooted} at $a,b,c,d$ consists of four pairwise-disjoint pairwise-adjacent connected subgraphs of $G$, respectively containing $a,b,c,d$. We characterise precisely when $G$ contains a $K_4$-minor rooted at $a,b,c,d$ by describing six classes of obstructions, which are the edge-maximal graphs containing no $K_4$-minor rooted at $a,b,c,d$. The following two special cases illustrate the full characterisation: (1) A 4-connected non-planar graph contains a $K_4$-minor rooted at $a,b,c,d$ for every choice of $a,b,c,d$. (2) A 3-connected planar graph contains a $K_4$-minor rooted at $a,b,c,d$ if and only if $a,b,c,d$ are not on a single face.


We propose that a consumer's purchase behaviour emulates a cognitive framework such that an appropriately selected queueing model can be used to assess the credibility of a consumer's expression of purchase intention to proceed into purchase action. The modelling idea is to envision that the customer has a mental queue of needs, and the surfacing of a need represents a new arrival to this queue while a purchase satisfying a need represents a departure from the queue. Using queueing formulae (and/or readily available tables on queueing), several statistics known as "operating characteristics" can be computed to capture and describe the individual's current need status. Hence, a description of the customer's state of readiness or prospect of actually executing the expressed purchase intention for a product (good or service) whose future sales are of interest in a market survey may be obtained. In this paper, such a description is termed Individual Buyer Profile (IBP), and IBP is offered as a purchase intention qualifier.


Objective To assess the effectiveness of acupuncture combined with selective serotonin reuptake inhibitors (SSRIs) for patients with depression in hospital using a pragmatic randomised controlled trial. Methods 76 patients with depression were randomly divided into two groups (randomisation ratio 2:1 for treatment and control groups (CGs), respectively) and 71 patients completed the study. The 45 patients in the treatment group (TG) underwent acupuncture and received an SSRI and the 26 patients in the CG received an SSRI only. The 17-item Hamilton Depression Rating Scale (HDRS-17) was used to quantitatively assess patients after 1, 2, 4 and 6 weeks of treatment. Results The mean (SD) baseline total HDRS scores were 22.2 (0.60) and 22.1 (0.33) in the TG and CG, respectively. After the first week of treatment the HDRS score for the TG was reduced to 15.6 (0.81), significantly different from the score of 18.3 (0.55) for the CG, p<0.05. This significant difference was maintained to the end of the 6-week treatment period, when HDRS scores had fallen to 6.3 (0.49) and 8.2 (0.35) for the TG and CG, respectively. Conclusions Acupuncture combined with an SSRI showed a statistically significant benefit for patients with depression in hospital over the 6-week period compared with SSRIs alone. This reduction in symptoms started in the first week and continued throughout the 6 weeks of treatment.


The secondary organic aerosol (SOA) yield of β-caryophyllene photooxidation is enhanced by aerosol acidity. In the present study, the influence of aerosol acidity on the chemical composition of β-caryophyllene SOA is investigated using ultra performance liquid chromatography/electrospray ionization-time-of-flight mass spectrometry (UPLC/ESI-TOFMS). A number of first-, second- and higher-generation gas-phase products having carbonyl and carboxylic acid functional groups are detected in the particle phase. Particle-phase reaction products formed via hydration and organosulfate formation processes are also detected. Increased acidity leads to different effects on the abundance of individual products; significantly, abundances of organosulfates are correlated with aerosol acidity. To our knowledge, this is the first detection of organosulfates and nitrated organosulfates derived from a sesquiterpene. The increase of certain particle-phase reaction products with increased acidity provides chemical evidence to support the acid-enhanced SOA yields. Based on the agreement between the chromatographic retention times and accurate mass measurements of chamber and field samples, three β-caryophyllene products (i.e., β-nocaryophyllon aldehyde, β-hydroxynocaryophyllon aldehyde, and β-dihydroxynocaryophyllon aldehyde) are suggested as chemical tracers for β-caryophyllene SOA. These compounds are detected in both day and night ambient samples collected in downtown Atlanta, GA and rural Yorkville, GA during the 2008 August Mini-Intensive Gas and Aerosol Study (AMIGAS).


Between 2001 and 2015, 3.4 million traumatic brain injury (TBI) occurrences in the U.S. were accounted for by sport participation. It is estimated between 12% and 60% of athletes delay seeking care after sustaining a concussion. Differences in sport-related concussion (SRC) reporting have been attributed to several different factors. Whereas prior research related to SRC reporting behavior focus on normative and competitive pressures to continue play, less attention is given to the interpersonal context in which reporting takes place. Grounded in attachment theory, this study investigated relationships between coach-athlete attachment and help-seeking behavior. Findings suggest that as coach-athlete anxiousness increases, not reporting increases. and as coach-athlete secureness increases, not reporting decreases. Logistic regression analyses indicate that secure coach attachment significantly predicts greater likelihood of SRC reporting. These findings underscore the important role coach-athlete relationships may have on care-seeking behaviors of student-athletes and can inform individual and group interventions promoting SRC reporting.


Summary: As part of the Amlodipine Cardiovascular Community Trial (ACCT), which was a large multicenter study designed to assess the effects of the calcium channel blocker amlodipine besylate (Norvasc) as monotherapy for treatment of mild to moderate hypertension, we sought to determine the effects of amlodipine on regression of left ventricular (LV) hypertrophy (LVH). The study began with a 2-week placebo run-in period (baseline), before which antihypertensive drugs had been discontinued. Amlodipine was then administered at 5–10 mg/ day during a 4-week titration/efficacy period. Patients achieving a goal diastolic blood pressure (DBP) of ≤90 mm Hg or a decrease in DBP of ≥10 mm Hg entered a 12-week maintenance phase and had the option to continue long-term therapy thereafter. Echocardiograms were obtained in a subset of patients at the end of the baseline period. In patients with LVH at baseline, echocardiograms were repeated at the end of 16 weeks of therapy (week 18), and at 42 weeks in patients continuing long-term therapy. Thirty-seven percent of 124 hypertensive patients screened for LVH at baseline had LVH detected on echocardiograms. Blacks had a higher incidence of LVH (64%) as compared with whites (34%, p < 0.05). Patients with LVH were more likely to have a higher baseline systolic BP (SBP) and DBP. Their sitting SBP and DBP decreased significantly from a mean of 163/102 mm Hg at baseline to 139/86 mm Hg with amlodipine therapy at week 18 (p < 0.0001). Amlodipine treatment produced a mean decrease of 20-g/m2 in LV mass index (p < 0.05) after 16 weeks of treatment and a mean decrease of 43 g/m2 in LV mass at week 42 (p < 0.001) as compared with baseline. There were no differences in the degree of LV mass regression between men or women or between older or younger patients; there was a trend to-ward less regression in blacks (–7 × 15 g/m2) as compared with whites (– 22 × 9 g/m2) at week 18.


This special section considers the interconnections of print culture and mobility across the Pacific in the early twentieth century. Th e contributors explore how print culture was part of the practices, experiences, mediations, and representations of travel and mobility, and understand mobility in a number of ways: from the movement of people and texts across space and the mobility of ideas to the opportunities of social mobility through travel. Th e special section moves beyond studies of travel writing and the literary analysis of travel narratives by discussing a range of genres, by paying attention to readers and reception, and by focusing on actual mobility and its representation as well as the mediation between the two.


Our chapter identifies key dimensions on which organizations make employee compensation decisions and examines the emerging research evidence on the consequences of such decisions for attitudes, behaviors, and organization performance. We provide some general suggestions that may prove helpful in future research. First, there is increased recognition that pay decisions take place in the context of implicit or explicit contracts between employees and specific organizations. As a result, we encourage researchers to continue to give greater attention to the role of organization differences in compensation. Second, because pay is multidimensional, attention should not be restricted to organization differences in pay level. Organization differences in benefits, structure, and means of recognizing individual employees contributions also warrant attention. As an example of how the focus can be expanded, we provide new empirical evidence on organization differences in the market sensitivity of pay structures. Third, we note that the success of pay programs depends not only on decisions about pay per se, but also the process used in making communicating, and administering such decisions. More broadly, the influence of contextual factors, such as the nature of other employee relations practices (e.g., staffmg, development, employment security), needs to be considered to a greater extent in compensation research. In addition to these broad suggestions, we provide specific ideas on future research directions throughout the chapter.


The aim of this research is to develop an information agent framework for knowledge discovery in enterprise architecture (EA). This framework is based on specific purpose ontology and knowledge discovery techniques. Such framework would facilitate strategic decision making for EA stakeholders by enabling them to analyze and monitor the portfolio of processes, data, applications, and organizational units in terms of their correlation and impact in the overall organization. This framework is very useful for affording key stakeholders with the appropriate view that is reliant on an accurate and concise picture of systems, applications, technologies and other infrastructure elements in the business and how these integrate to serve the enterprise. The paper discusses the concepts and components of this framework. Potential benefits of this framework over existing approaches are also discussed.


Purpose: To compare patient's perception of consent quality, clinical and quality-of-life outcomes after laser vision correction (LVC) and refractive lens exchange (RLE) between patients who met their treating surgeon prior to the day of surgery (PDOS) or on the day of surgery (DOS). Design: Retrospective, comparative case series. Setting: Optical Express, Glasgow, UK. Methods: Patients treated between October 2015 and June 2016 (3972 LVC and 979 RLE patients) who attended 1-day and 1-month postoperative aftercare and answered a questionnaire were included in this study. All patients had a thorough preoperative discussion with an optometrist, watched a video consent, and were provided with written information. Patients then had a verbal discussion with their treating surgeon either PDOS or on the DOS, according to patient preference. Preoperative and 1-month postoperative visual acuity, refraction, preoperative, 1-day and 1-month postoperative questionnaire were compared between DOS and PDOS patients. Multivariate regression model was developed to find factors associated with patient's perception of consent quality. Results: Preoperatively, 8.0% of LVC and 17.1% of RLE patients elected to meet their surgeon ahead of the surgery day. In the LVC group, 97.5% of DOS and 97.2% of PDOS patients indicated they were properly consented for surgery ( P = 0.77). In the RLE group, 97.0% of DOS and 97.0% of PDOS patients stated their consent process for surgery was adequate ( P = 0.98). There was no statistically significant difference between DOS and PDOS patients in most of the postoperative clinical or questionnaire outcomes. Factors predictive of patient's satisfaction with consent quality were postoperative satisfaction with vision (46.7% of explained variance), difficulties with night driving, close-up vision or outdoor/sports activities (25.4%), visual phenomena (12.2%), dry eyes (7.5%), and patient's satisfaction with surgeon's care (8.2%). Conclusion: Perception of quality of consent was comparable between patients that elected to meet the surgeon PDOS, and those who did not.


Low‐dimensional carbon materials occupy a relevant role in the field of nanotechnology. Herein, the authors report a study conducted by atomic force microscopy and Raman spectroscopy on the deposition of carbon dots onto graphene surfaces. The study aims at understanding if and how the morphology and the microstructure of chemical vapor deposited graphene on Si/SiO2 may change due to the interaction with the carbon dots. Potential alteration in the graphene's electrical properties might be detrimental for optoelectronic applications. The deposition of carbon dots dispersed in water and ethanol solvents are explored to investigate the effect of solvents with different fluidic properties. The obtained results indicate that the carbon dots do not alter the quality of graphene.


We performed a clinical pathological study of conventionally resected superficial esophageal carcinomas since this type of lesion has been increasing, in order to develop criteria of determination for therapeutic strategies. Pathological studies were performed on specimens obtained by radical surgical resection in 133 cases of superficial esophageal cancer. Evaluation was performed in terms of the gross classification of the lesion type, depth of invasion, lymph node metastasis, vascular invasion, size of the lesion, outcome, etc. In 0-I, 0-IIc+0-IIa, and 0-III type submucosal cancer lesions the rate of metastasis to lymph nodes was more than 40%, but in 0-IIa and 0-IIb mucosal cancer cases no lymph node metastasis was observed. 0-IIc type lesions showed a wide range of invasiveness, ranging from m1 to sm3. In cases with m1 or m2 invasion, no lymph node or lymph-vessel invasion was recognized, but in m3, sm1, sm2, and sm3 cases lymph node metastasis was recognized in 12.5%, 22.2%, 44.0% and 47.4%, respectively. In 47% of lesions with a greatest dimension of less than 30 mm invasion was limited to the mucosa. Seventy-two percent of m1 and m2 cases were 30 mm in size or less. Lymph node metastasis was recognized in only 16.7% of cases less than 30 mm in size, but in cases of lesions 30 mm or more the rate of lymph node metastasis was 35.8%. 0-IIb and 0-IIa type lesions are indications for endoscopic esophageal mucosal resection (EEMR), while 0-I, 0-IIc+0-IIa, and 0-III lesions should be candidates for radical surgical resection. In the 0-IIc category, lesions in which the depression is relatively flat and with a finely granular surface are indications for EEMR, but those cases in which the surface of depression shows granules of varying sizes should be treated with radical surgical resection. Cases of 0-IIa type 30 mm or larger in greatest dimension which have a gently sloping protruding margin shoulder or reddening should be treated with caution, but EEMR can be performed first and subsequent therapeutic strategy decided on, based on the pathological findings of the specimen.


The purpose of this study was to assess the perceptions of tourists and government officials on the development of sports tourism in selected regions of Kenya. A Survey research design was adopted for the study. The independent variables that were assessed included, sports as a pull factor that interest tourist to the Kenyan market, the extend of sports facilities, hosting of international sports event, cultural sporting activities, beach sports, high and low attitudes training centers, sports for sports icons. The study also _ looked at effectiveness of marketing, the level of security and political stability. A validated self administered questionnaire was used to collect the data. The sample size of 776 respondents that were raridomly selected for the study included 46 government officials from the Ministry in-charge of Sports and Ministry in-charge of Tourism in the headquarters Nairobi, and 730 both local and international tourists who resided in starred hotels and high altitude training centre within the eight tourism circuit were also visited for data collection. The eight tourism circuits included central Kenya region, Nairobi, coastline, southern region, eastern region, north rift, south rift and western Kenya. Chisquare was used 'to analyze the data. The findings indicated that sport is a pull factor for the tourists who visit the Kenyan market 564(77.3%) tourists and 37(80.45%) government officials agreed that sports was a significant activity in attracting tourists in the Kenyan market. On average 190(26%) of the tourists were of the view that facilities and infrastructure were not adequate while30( 65%) of the government official were of the same view. 252(34.4%) tourists were of the view that security and political stability was not fully explored for the development of sports tourism in Kenya. 24(52.2%) of the government officials were of the view that Kenya is capable of hosting major international sports events while 221(30.4%) disagreed on the same.14( 30.4%) of the government officials did not agree on the promotion of cultural activities while 290(39.7%) of the tourist were of the view that cultural event was a viable product for the development of sports tourism. 363(46.77%) of both tourists and government officials were of the view that high altitude training centers were fully explored for sports tourism development but when it come to low altitude 396(51.03%) of both had no opinion. 117(16%) of the tourists were of the view that organization of sports for Kenya's sports icons was not fully explored while 16(34.73%) of the government officials were of the view that it was fully explored. Ministries in-charge of Sports and Tourism needs to encourage sports tourism as a package in the Kenyan market. Recreational sporting facilities should be a requirement for starred hotels in Kenya. The Ministry of Youth Affairs Sports and Tourism should market sports tourism as a tourism package. Ministries in-charge of Sports and Tourism should beef up security; create more high and low altitude centers, and stadia to host cultural sporting events. Ministries in-charge of Sports and Tourism through the Ministry in-charge of Sports and Ministry in-charge of Tourism need to expand sports tourism as a package and encourage its growth in Kenya.


Craft specialization is a major component in the organization of prehistoric complex societies. In the Moche society, which occupied the Peruvian coastal desert between the first and eighth centuries AD, craft specialist worked mostly ceramics, metals, textiles, and stones to create a great variety of practical or prestigious objects intended to the general population or made exclusively for the elites. This thesis focuses on craft specialization at Huacas de Moche, a site considered a major urban center in the political organization of the Moche society during its apogee phase. The research first aims at determining the organization of specialized craft production at Huacas de Moche. The second objective consists in identifying the roles of craft specialists in the functioning of the urban center. Archaeological data used in the research was first collected in various specialised workshops. Additional data comes from consumption contexts such as domestic compounds, monumental structures, and funerary contexts representing various levels of the social hierarchy at Huacas de Moche. The data collected for this research indicates that some goods produced at Huacas de Moche, especially those endowed with symbolic meaning, were crafted by specialists attached to elites, while other goods with a more utilitarian value were most likely produced by independent artisans. It also appears that attached craft production at Huacas de Moche was controlled directly by urban leaders at the head of small corporate groups or lineages, themselves submitted to the authority of the ruling elite. Craft specialists were disengaged from food production and worked in small and middle-scale workshops dispersed in urban domestic structures. Craft specialization at Huacas de Moche responded both to the needs of the general population and to the demands of the elite. The presence of artisans was necessary to the economic functioning of the city and to the adaptation of its occupants to the and environment. Craft specialization was above all highly significant in the sociopolitic and religious systems at Huacas de Moche and had a great importance in the development of Moche political complexity.


The authors have developed a method to measure intracellular calcium ion concentration ([Ca2+]i) during shear-induced platelet aggregation. A cone and plate viscometer was adapted for continuous recording of both light transmission and fluorescence intensity. Citrated platelet rich plasma was incubated with Indo-1AM at a concentration of 10 microns for 30 min at 37 degrees C, then applied to the albumin density gradient to prepare washed platelets. To Indo-1AM loaded washed platelets, fibrinogen, and von Willebrand factor (vWf) were added, with 1 mM CaCl2. Platelets were then exposed to changing shear stress (6-108 dynes/cm2) for simultaneous measurement of aggregation and [Ca2+]i. [Ca2+]i in resting platelets was estimated as approximately 100 nM. At low shear stress (10-20 dynes/cm2), [Ca2+]i did not change. In contrast, a marked increase in [Ca2+]i was observed concurrent with aggregation at high shear stress (100-108 dynes/cm2). However, no increase was seen in the presence of 1 mM EGTA. The increase was prevented by monoclonal antibodies against GPIb or vWf, which inhibited vWf binding to GPIb. A monoclonal anti-vWf antibody, which inhibited vWf binding to the GPIIb/IIIa complex, did not affect [Ca2+]i increase during high shear induced platelet aggregation. These results suggest that binding of vWf to GPIb may trigger Ca2+ influx.


This paper reflects upon the issue of population growth and reproductive health in the Philippines in the context of the ongoing Congressional deliberation of House Bill 5043. Specific attention is paid to the influence of the Roman Catholic Church upon this process, through the institutional pronouncements and edicts of the Catholic Bishops Conference of the Philippines (CBCP).As of late 2009, it still remains to be seen whether HB5043 shall be passed into law. What can be observed even at this stage, however, is that there may well be a discordance between Church proclamations regarding faith-based sexual morality on the one hand, and popular opinion and practices under difficult economic and social vicissitudes on the other. It is important to recognize that divergent voices within the Church hierarchy express opinions that do offer alternatives to the hard line stance of official CBCP proclamations, which are to a great extent reliant upon the promulgation of wider Roman Church theology. In light of the CBCPs historical role in Philippine politics, however, such alternative voices may have become subsumed by the conservative agenda, even though the former may correspond more closely to popular opinion.


New specimens of the oldest gorgonopsian taxon Eriphostoma microdon from the Pristerognathus Assemblage Zone (AZ) of South Africa significantly improve our understanding of the anatomy of this taxon. The new specimens consist of nearly complete skulls and lower jaws and allow for a more complete diagnosis of Eriphostoma than was possible based on the poorly preserved holotype. In addition to the characteristic palatal dentition and delta‐shaped palatine bosses previously recognized for Eriphostoma, this taxon can be diagnosed by the presence of three close‐packed upper postcanines occupying an indented margin of the maxilla, a large, tetragonal‐to‐rounded preparietal bone, and large, paired interorbital depressions expanding outwards in front of the pineal boss. The revised diagnosis permits Eoarctops vanderbyli, Galesuchus gracilis, and Scylacognathus parvus to be synonymized with Eriphostoma microdon, as previously suspected. Among gorgonopsians, Eriphostoma is most similar to Aelurosaurus and Gorgonops, although these similarities are likely plesiomorphic for Gorgonopsia. Eriphostoma ranges from the Tapinocephalus AZ (where it is the only valid gorgonopsian known from the Karoo Basin) through the Pristerognathus AZ (where it co‐occurs with Gorgonops).


• The fig tree-fig wasp obligate pollination mutualism has strong ancestral affinities with tropical communities, but is present in much drier contemporary biomes, especially at higher latitudes at the edge of their range. The extent to which adaptation to environmental variables is evolutionarily conserved and whether environmental differences function in ecological speciation of the mutualism are unknown. • Here we use climate models and phylogenetic reconstructions to test whether the Ficus-fig wasp mutualism has adapted and radiated into drier climates and led to ecological speciation in both plant and insect. • The results showed phylogenetic correspondence between closely related Ficus species with either savanna, forest, or riparian habitat categories, were most strongly explained by both climate and environmental variables. Rare episodes of adaptation to dry apotypic conditions have resulted in substantial radiations into savanna. • Inferences were consistent with predictions of niche conservatism and support the postulate that ecological speciation of the mutualism occurs, but under contrasting and intertwined circumstances among plant-pollinator adaptation and tolerance to the environment.


This paper analyzes the symbolism of the fictional space of Cube (1997) in the wider context of postmodern science fiction literature and film criticism. Its main point is that the movie's imaginary setting is a complex symbolic and metaphoric element whose ambiguous nature and connotative meaning enhances interpretation. The cube is a multiple metaphor that allows for the fictional exploration of the territory of the unconscious, of the contemporary social and political coordinates and of the general framework of reality. As a fictional space that reproduces the postmodern vision of reality through an artistic elaboration, the film can be read as a 'consensual hallucination', i.e. a virtual reality where real elements are transformed and reinterpreted and which is experienced by viewers simultaneously in order to achieve a deeper awareness of the 'real' world. In this sense, the movie epitomizes the role of science fiction film in postmodern culture, for it creates a virtual (fictional) reality that reveals the complex meanings and hidden structures of contemporary reality in Western technological societies.


The present research aimed at comparing the effectiveness of promethazine and diazepam in patients suffering from acute peripheral vertigo. This is a double blind clinical trial with a sample of 154 patients visiting the emergency section of Shahid Mohammadi Hospital in Bandar Abbas in 2017-18. The participants were randomly divided into two groups of 77, one treated with intravenous promethazine (50 mg) and the other with intravenous Diazepam (10 mg). The severity of vertigo was measured qualitatively and quantitatively 20 minutes later in both groups. Participants were 46 (29.9%) male and 108 (70.1%) female visiting the emergency section of hospital. The mean score of vertigo severity in Promethazine group was 44.44±17.94 and that of Diazepam group was 2.49±+3.87. The severity scores before and after the treatment in promethazine group were respectively 7.75±1.59 and 2.72±1.93. The mean scores of vertigo severity before and after the treatment in promethazine group was -5.04+2.10 and in the diazepam group it was -3.83+3.09. The intergroup difference was statistically significant (p=.013). The results revealed that intravenous promethazine and diazepam applied 20 minutes after prescription are both effective in controlling the severity of vertigo. Considering the probability of occurrence of extrapyramidal side-effects it can be suggested that the infusion of this medication can be done slowly as it takes longer time. Meanwhile, vital signs should be precisely controlled.


This is the second in a loose 'trilogy' of three papers that I presented at successive Obligations conferences: Obligations V (at the University of Oxford, in 2010, on the theme of 'Rights and Private Law'), Obligations VI (at the University of Western Ontario, in 2012, on the theme of 'Challenging Orthodoxy'), and Obligations VII (at Hong Kong University, in 2014, on the theme of 'Divergence and Convergence in Private Law').In this paper, I argue that giving effect to the 'balanced approach' to determining what rights we have that I set out in my paper on 'Rights and the basis of tort law' requires one to draw on a vision of what human flourishing entails, so that we can determine whether the benefit to A from finding that he has a particular right against B outweighs the burden that B will incur if we find that A has such a right against B. I go on to argue that the vision of human flourishing that underlies the law's practice in determining what rights we have against each other is a very familiar one – one that is widely prevalent in the West and best set out in the writings of John Finnis. I go on to criticise this account of human flourishing as radically defective, and explain what difference adopting a sounder view of what human flourishing entails would have on what rights we are recognised as having against other people.I hope that this paper and the other two papers in the trilogy will eventually form the basis of a book, to be called The Humanity of Private Law.


This paper presents an overview of integrated optics routing and coupling devices based on multimode interference. The underlying self-imaging principle in multimode waveguides is described using a guided mode propagation analysis. Special issues concerning the design and operation of multimode interference devices are discussed, followed by a survey of reported applications. It is shown that multimode interference couplers offer superior performance, excellent tolerance to polarization and wavelength variations, and relaxed fabrication requirements when compared to alternatives such as directional couplers, adiabatic X- or Y-junctions, and diffractive star couplers. >


ABSTRACT Alternaria spp. were sampled from two rough lemon (RL) and two Minneola tangelo (MIN) groves in a limited geographic area in central Florida to test for host-specialized forms of the pathogen. Isolates of Alternaria spp. were scored for variation at 16 putative random amplified polymorphic DNA (RAPD) loci and for pathogenicity on both hosts. Subpopulations on each host were differentiated genetically and pathogenically, which was consistent with the hypothesis of host specialization. Highly significant genetic differentiation was detected among all four subpopulations (Nei's coefficient of gene differentiation [G(ST)] = 0.292, P = 0.000); most of the differentiation occurred between hosts (G(ST) = 0.278, P = 0.000). Phenograms of qualitative similarities among isolates within subpopulations revealed two or three distinct clusters of isolates within each subpopulation. The majority of isolates sampled from RL were pathogenic on RL and not on MIN, although a few RL isolates were able to induce disease on MIN, and 44% were nonpathogenic on either host. In contrast, isolates from MIN were pathogenic only on MIN, never on RL, and only 3% of the isolates were nonpathogenic. Overall, three genetically distinct clusters of isolates were detected on both hosts. One of the clusters (cluster A) sampled from RL was pathogenic on RL and not on MIN and consisted almost entirely of one RAPD genotype. This cluster also contained two isolates that were 93% similar to the majority genotype but were pathogenic on MIN and not RL. In isolates from MIN, two distinct clusters of isolates were found in one subpopulation (clusters B and C), and three distinct clusters were found in another subpopulation (clusters A, B, and C). Clusters A and B were found on both hosts, while cluster C was limited to MIN. Populations of Alternaria spp. sampled from RL and MIN showed a high degree of host specificity; however, the specificity obscured a high level of genetic variation within subpopulations.


We report on the progress of our ongoing photometric monitoring program of spotted late-type stars with automatic photoelectric telescopes (APTs) on Mt. Hopkins in Arizona and on Mt. Etna in Sicily. We present 9 250 differential UBV and/or V (RI)C observations for altogether 23 chromospherically active stars, singles and binaries, pre main sequence and post main sequence, taken between 1991 and 1996. The variability mechanism of our target stars is mostly rotational modulation by an asymmetrically spotted stellar surface. Therefore, precise rotational periods and their seasonal variations are determined using baselines between 3 years for HD 129333 to 34 years for V410 Tauri. We report the largest V light-curve amplitude of any spotted star observed to date: 0. 65 for V410 Tau in 1994–95. Long-term variations of the overall light levels of our target stars are sometimes of similar amplitude as the rotational modulation itself and are most likely caused by an analog of the solar 11-year spot cycle but mostly without a well-defined periodicity. For some of our target stars (HD 12545, HD 17433, EI Eri, V410 Tau, LQ Hya, and HD 106225) we estimate a probable cycle period. A complete light curve of the semi-regular S-type giant HR Pegasii is presented. All data are available via the WorldWideWeb.


Most computer science (CS) and software engineering (SE) curricula include some form of SE project with the aim of lowering the gap between CS and SE education and real-world demands in industry. In this paper we briefly discuss and explain our findings of software engineering projects taught at LiU in Sweden. These courses use what we call the "tail" approach, where student projects are performed at the end of a degree program. We then argue that there are several problems with this approach and sketch an idea where SE projects are an integrated part of a curriculum. Furthermore, pros and cons of this idea, which we call the SE project "backbone" approach, are discussed and analyzed.


Open Process Innovation provides a framework for studying how to systematically make use of knowledge that lies outside of an organization's boundaries for process innovation initiatives. Here, we seek to investigate into variables that impact on the qualities of Open Process Innovation taking the example of the public sector domain. This paper examines how a lack of resources impacts on BPM. Specifically in investigates how personnel resource scarcity exerts influence on the involvement of i) customers (here citizens and local companies) and ii) consultants (here management and software consultants) in public sector BPM. Our multi-method analysis shows that personnel resource scarcity has consequences for BPM-related collaboration schema as it restricts the involvement of customers. Based on our findings, implications for theory and practice are discussed, including implications for studies on BPM maturity or on business process design. We call for a governancetheory perspective on process innovation as a fundamental basis for understanding and designing the institutions that shape collaboration in open process innovation.


This study investigated a particular form of social Q&A – Yahoo! Answers – and the nature of the questions posed by teens on the topic of eating disorders. The goals of this study were to identify the information needs of questioners in Yahoo! Answers vis a vis the topic of eating disorders, to create a taxonomy of question types in Yahoo! Answers on the topic of eating disorders, and finally, to contribute to broader models of question-asking in social Q&A. We achieved these goals through a content analysis of 2230 questions posed in Yahoo! Answers between December 2005 and April 2011. This resulted in a classification scheme with five overarching themes - Seeking Information, Seeking Emotional Support, Seeking Communication, Seeking Self-Expression, and Seeking Help to Complete a Task, and the sub-categories of factual, diagnosis, treatment or intervention, validation, seeking comfort, conversation starters, deep talk, confession, reflection, homework help, and manuscript ideas. Through the investigation of the socio-emotional aspects of social Q&A, this study enriches our understanding of the affective dimension of health information behavior.


Data from the Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) and the Airborne Visible/IR Image Spectrometer (AVIRIS) were used to characterize hot spring deposits in the Lower, Midway, and Upper Geyser Basins of Yellowstone National Park from the visible/near infrared (VNIR) to thermal infrared (TIR) wavelengths. Field observations of these basins provided the critical ground truth for comparison to the remote sensing results. Fourteen study sites were selected based on diversity in size, deposit type, and thermal activity. Field work included detailed site surveys such as land cover analysis, photography, Global Positioning System (GPS) data collection, radiometric analysis, and VNIR spectroscopy. Samples of hot spring deposits, geyser deposits, and soil were also collected. Analysis of ASTER provided broad scale characteristics of the hot springs and their deposits, including the identification of thermal anomalies. AVIRIS high spectral resolution short-wave infrared (SWIR) spectroscopy provided the ability to detect hydrothermally altered minerals as well as a calibration for the multispectral SWIR ASTER data. From the image analysis, differences in these basins were identified including the extent of thermal alteration, the location and abundance of alteration minerals, and a comparison of active, near-extinct, and extinct geysers. The activity level of each region was determined using a combination of the VNIR-SWIR-TIR spectral differences as well as the presence of elevated temperatures, detected by the TIR subsystem of ASTER. The results of this study can be applied to the exploration of extinct mineralized hydrothermal deposits on both Earth and Mars.


Brassica napus (AACC, 2n = 38), an oil crop of world-wide importance, originated from interspecific hybridization of B. rapa (AA, 2n = 20) and B. oleracea (CC, 2n = 18), and has six FLOWERING LOCUS T (FT) paralogues. Two located on the homeologous chromosomes A2 and C2 arose from a lineage distinct from four located on A7 and C6. A set of three conserved blocks A, B and C, which were found to be essential for FT activation by CONSTANS (CO) in Arabidopsis, was identified within the FT upstream region in B. napus and its progenitor diploids. However, on chromosome C2, insertion of a DNA transposable element (TE) and a retro-element in FT upstream blocks A and B contributed to significant structural divergence between the A and C genome orthologues. Phylogenetic analysis of upstream block A indicated the conserved evolutionary relationships of distinct FT genes within Brassicaceae. We conclude that the ancient At-α whole genome duplication contributed to distinct ancestral lineages for this key adaptive gene, which co-exist within the same genus. FT-A2 was found to be transcribed in all leaf samples from different developmental stages in both B. rapa and B. napus, whereas FT-C2 was not transcribed in either B. napus or B. oleracea. Silencing of FT-C2 appeared to result from TE insertion and consequent high levels of cytosine methylation in TE sequences within upstream block A. Interestingly, FT-A7/C6 paralogues were specifically silenced in winter type B. napus but abundantly expressed in spring type cultivars under vernalization-free conditions. Motif prediction indicated the presence of two CO protein binding sites within all Brassica block A and additional sites for FT activation in block C. We propose that the ancestral whole genome duplications have contributed to more complex mechanisms of floral regulation and niche adaptation in Brassica compared to Arabidopsis.


An assessment is made of the role the various error sources play in limiting the accuracy of infrared differential absorption lidar measurements used for the remote sensing of atmospheric species. An overview is presented of the relative contribution of each error source including the inadequate knowledge of the absorption coefficient, differential spectral reflectance, and background interference as well as measurement errors arising from signal fluctuations.


In this paper we analyze the impact of the Integrated Household Extension Program (IHEP) in the Tigray region in northern Ethiopia. The government of Ethiopia – in contrast to the majority of countries in Sub-Saharan Africa – invests heavily in agricultural extension but very little empirical evidence is available on the impact of public extension services on farm performance and household welfare that could justify these investments. The IHEP program is a particularly interesting case as it is an example for how agricultural extension systems in developing countries changed during the past two decades, from centralized top-down technology-transfer-orientated approaches to decentralized, participatory and more integrated approaches. We empirically assess the impact of participation in the IHEP program on household income, investment and income diversification. We use household survey data from 730 farm-households in the Tigray region and propensity score matching methods to estimate the impact. We find that the extension program had a large positive impact on household welfare – increasing income with about 10 percent – and on investment and income diversification.


The total binding energy of compact stars is the sum of the gravitational binding energy $(BE)_g$ and the nuclear binding energy $(BE)_n$, the last being related to the microphysics of the interactions. While the first is positive (binding) both for hadronic stars and for strange quark stars, the second is large and negative for hadronic stars (anti-binding) and either small and negative (anti-binding) or positive (binding) for strange quark stars. A hadronic star can convert into a strange quark star with a larger radius because the consequent reduction of $(BE)_g$ is over-compensated by the large increase in $(BE)_n$. Thus, the total binding energy increases due to the conversion and the process is exothermic. Depending on the equations of state of hadronic matter and quark matter and on the baryonic mass of the star, the contrary is obviously also possible, namely the conversion of hadronic stars into strange quark stars having smaller radii, a situation more often discussed in the literature. We provide a condition that is sufficient and in most of the phenomenologically relevant cases also necessary in order to form strange quark stars with larger radii while satisfying the exothermicity request. Finally, we compare the two schemes in which quark stars are produced (one having large quark stars and the other having small quark stars) among themselves and with the third-family scenario and we discuss how present and future data can discriminate among them.


Turkey is the first modern secular state in a predominantly Islamic Middle East. In this major textbook, Feroz Ahmad provides a thorough examination of the political, social and economic processes which led to the formation of a new Turkey. After a chapter on "the Ottoman Legacy", the book covers the period since the revolution of 1908 and the development of the new Turkey. Successive chapters chart the progress through the single-party regime set up by Ataturk (1923-1945), the multi-party period (1945-1960) and the three military interventions of 1960, 1971 and 1980. The book ends in 1989 with the election of Turgat Ozal as president. In contrast to most current analyses of modern Turkey, the author emphasises the socio-economic changes rather than continuities as the motor of politics.


Plato's Sophist provides a careful translation of the Sophist, one of Plato's most complex and difficult dialogues, and includes materials designed to facilitate its usefulness as a text in college courses. The translation employs a minimum of interpretative paraphrasing while being presented in clear, readable English. Special attention has been given to consistency in translating key Greek terms. The book presents a special list of these terms and discusses them in the endnotes. The result is a translation that enables the reader who lacks a knowledge of Greek to get much closer than usual to the original text. Cobb's introduction contains a detailed summary of the entire dialogue, clarifying the main themes and the general structure. He offers a fresh interpretation of the dialogue that shows how each theme contributes to the exploration of the nature of, and the relation between, philosophy and sophistry. The introduction is particularly useful to first readers of the Sophist.


The largest expense of an intensive ostrich production unit is feed cost (ca.75%). Protein makes up a great portion of feed for monogastric animals and this expense can be lowered by utilizing locally produced feedstuffs such as full-fat canola, although it is not clear whether ostriches will readily consume full-fat canola because of its anti-nutritional and other known factors. To evaluate the feeding preference of ostriches towards full-fat canola, 60 South African Black ostriches (82.2 +/- 1.06 kg in live weight) were placed in 10 camps of six birds per camp. Each camp had five identical feed troughs containing diets in which full-fat canola seed (FFCS) incrementally (0, 25, 50, 75 and 100% of protein source) replaced the soybean oilcake meal (9.8% of the total diet composition in control diet was soybean oilcake meal and full-fat canola was included up to 27.5% of the total diet) as protein source. Dry matter intake (DMI) was measured daily and feed colour characteristics were measured, based on L*, a* and b* colour attributes. Only the 25%FFCS showed a higher DMI (817.38 +/- 81.98 g/bird/day) and percentage DMI (similar to 29.53%) than the other diets, with an average DMI of 488.8 g/bird/day) and percentage DMI of 17.62%. Although the 0%FFCS, 50%FFCS and 75%FFCS had a lighter colour than the 25%FFCS and 100%FFCS and the b* colour parameter for 100%FFCS was lower than the rest, it is believed that these differences had no effect on DMI. Based on the results of this study, diets with up to 27.5% full-fat canola seeds had no detrimental effect on feed intake of finishing ostriches. Birds prefer diets with a combination of 6.9% full-fat canola seed and 7.4% soybean oilcake meal.


The learning of evaluation functions from game records has been widely studied in the field of computer game-playing. Conventional learning methods optimize the evaluation function parameters by using the game records of expert players in order to imitate their plays. Such conventional methods utilize objective functions to increase the agreement between the moves selected by game-playing programs and the moves in the records of actual games. The methods, however, have a problem in that increasing the agreement does not always improve the strength of a program. Indeed, it is not clear how this agreement relates to the strength of a trained program. To address this problem, this paper presents a learning method to optimize objective function parameters for strength in game-playing. The proposed method employs an evolutionary learning algorithm with the strengths (Elo ratings) of programs as their fitness scores. Experimental results show that the proposed method is effective since programs using the objective function produced by the proposed method are superior to those using conventional objective functions.


This camera provides clear images 24/7 – even at night or under low-light conditions. The exceptional starlight sensitivity enables this camera to work with a minimum of ambient light. The extended dynamic mode provides detailed images in scenes with challenging lighting. The camera is available in 1080p or 720p resolution versions and provides up to 60 images per second. There is a selection of high quality lenses separately available.


Recent UK government policy calls for a strong public health function within health and local authority services. The recent restructuring of the National Health Service has drastically changed the organizational structure of Public Health, and has resulted in concerns over the capacity and capabilities of the specialist public health workforce. This paper presents findings from the first phase of a study assessing the capacity and development needs of specialists in public health. Face-to-face semi-structured interviews were conducted with a purposive sample of key public health informants. Four key themes were identified. First, interviewees noted the lack of clarity encompassing the term 'specialist in public health' and the consequent confusion regarding the role of a specialist and the public health function. Second, concern was expressed over the recent fragmentation of the workforce, the loss of critical mass and the potential for professional isolation. This was seen as particularly worrisome in light of a growing public heath agenda. Third, respondents identified key skills gaps within the workforce such as health protection, partnership working and leadership. Last, inadequacies and regional inequities in training and continuing professional development were identified, with interviewees calling for these issues to be addressed immediately. Capacity and skills gaps in the specialist public health workforce are evident and exacerbated by the confusion surrounding the definition of a specialist and, hence, individual roles and responsibilities. The ability of the public health workforce to meet the growing public heath agenda will be dependent on the success of various new mechanisms for joint working, capacity building, and skill enhancement.


We present Epiclomal, a probabilistic clustering method arising from a hierarchical mixture model to simultaneously cluster sparse single-cell DNA methylation data and infer their corresponding hidden methylation profiles. Using synthetic and published single-cell CpG datasets we show that Epiclomal outperforms non-probabilistic methods and is able to handle the inherent missing data feature which dominates single-cell CpG genome sequences. Using a recently published single-cell 5mCpG sequencing method (PBAL), we show that Epiclomal discovers sub-clonal patterns of methylation in aneuploid tumour genomes, thus defining epiclones. We show that epiclones may transcend copy number determined clonal lineages, thus opening this important form of clonal analysis in cancer.


This paper describes the development of an Advanced Speech Communication System for Deaf People and its field evaluation in a real application domain: the renewal of Driver's License. The system is composed of two modules. The first one is a Spanish into Spanish Sign Language (LSE: Lengua de Signos Española) translation module made up of a speech recognizer, a natural language translator (for converting a word sequence into a sequence of signs), and a 3D avatar animation module (for playing back the signs). The second module is a Spoken Spanish generator from sign-writing composed of a visual interface (for specifying a sequence of signs), a language translator (for generating the sequence of words in Spanish), and finally, a text to speech converter. For language translation, the system integrates three technologies: an example-based strategy, a rule-based translation method and a statistical translator. This paper also includes a detailed description of the evaluation carried out in the Local Traffic Office in the city of Toledo (Spain) involving real government employees and deaf people. This evaluation includes objective measurements from the system and subjective information from questionnaires. Finally, the paper reports an analysis of the main problems and a discussion about possible solutions.


From the stony streets of Boston to the rail lines of California, from General Relativity to Google, one of the surest truths of our history is the fact that America has been built by immigrants. The phrase itself has become a steadfast campaign line, a motto of optimism and good will, and indeed it is the rallying cry for progressives today who fight against tightening our borders. This is all well and good, Philip Cafaro thinks, for the America of the past—teeming with resources, opportunities, and wide open spaces—but America isn't as young as it used to be, and the fact of the matter is we can't afford to take in millions of people anymore. We've all heard this argument before, and one might think Cafaro is toeing the conservative line, but here's the thing: he's not conservative, not by a long shot. He's as progressive as they come, and it's progressives at whom he aims with this book's startling message: massive immigration simply isn't consistent with progressive ideals. Cafaro roots his argument in human rights, equality, economic security, and environmental sustainability—hallmark progressive values. He shows us the undeniable realities of mass migration to which we have turned a blind eye: how flooded labor markets in sectors such as meatpacking and construction have driven down workers' wages and driven up inequality; how excessive immigration has fostered unsafe working conditions and political disempowerment; how it has stalled our economic maturity by keeping us ever-focused on increasing consumption and growth; and how it has caused our cities and suburbs to sprawl far and wide, destroying natural habitats, driving other species from the landscape, and cutting us off from nature. In response to these hard-hitting truths, Cafaro lays out a comprehensive plan for immigration reform that is squarely in line with progressive political goals. He suggests that we shift enforcement efforts away from border control and toward the employers who knowingly hire illegal workers. He proposes aid and foreign policies that will help people create better lives where they are. And indeed he supports amnesty for those who have, at tremendous risk, already built their lives here. Above all, Cafaro attacks our obsession with endless material growth, offering in its place a mature vision of America, not brimming but balanced, where all the different people who constitute this great nation of immigrants can live sustainably and well, sheltered by a prudence currently in short supply in American politics.


It is observed recently in Sendai City that the motor traffic from suburban residential areas to the city center is rapidly increasing and incoming cars are often delayed in the morning peak hours. To improve this condition, we have installed a subway system extending 15 kilometers from north to south, and are now investigating another new transit system of medium size from east to west. We are now studying a plan to construct multiplex underground space (Underground Transit Mall) consisted of a new transit system and urban facilities by introducing a new transit system into underground of the Aoba-dori Street in the downtown area.


Abstract The EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP) was requested by the European Commission to re‐evaluate the safety of styrene (FCM No 193) for use in plastic food contact materials (FCM) following the classification by the International Agency for Research on Cancer (IARC) as 'probably carcinogenic to humans'. The IARC Monograph pertains to hazard identification, based on studies on high‐dose occupational exposures by inhalation and animal studies, also mainly by inhalation. The Panel considered that the IARC conclusions cannot be directly applied to the evaluation of risks for consumers from the oral exposure to styrene, but also concluded that, based on the data provided in the IARC Monograph and by the industry, a concern for genotoxicity associated with oral exposure to styrene cannot be excluded. The migration of styrene into foods packed in styrenic plastics is below 10 μg/kg for the majority of the foods, but up to 230 μg/kg was reported. Migration tends to be high for contact with fatty foods, and/or with high surface to volume ratios of the FCM. Dietary exposure of the consumers to styrene migrating from styrenic plastics was estimated in the order of 0.1 μg/kg body weight (bw) per day. It is in the same range as exposure from styrene present in foods as such. The dietary exposure (food component plus migration from styrenic plastics) is similar or lower than that by inhalation in the general population. Taking the human exposure data into account, the Panel concluded that a systematic review of genotoxicity and mechanistic data, comparative toxicokinetics and analysis of species differences is required for assessing the safety of styrene for its use in FCM.


Proteins bearing a nuclear localization signal (NLS) are targeted to the nucleus by the heterodimeric transporter importin. Importin alpha binds to the NLS and to importin beta, which carries it through the nuclear pore complex (NPC). Importin disassembles in the nucleus, evidently by binding of RanGTP to importin beta. The importin subunits are exported separately. We investigated the role of Cse1p, the Saccharomyces cerevisiae homologue of human CAS, in nuclear export of Srp1p (yeast importin alpha). Cse1p is located predominantly in the nucleus but also is present in the cytoplasm and at the NPC. We analyzed the in vivo localization of the importin subunits fused to the green fluorescent protein in wild-type and cse1-1 mutant cells. Srp1p but not importin beta accumulated in nuclei of cse1-1 mutants, which are defective in NLS import but not defective in NLS-independent import pathways. Purified Cse1p binds with high affinity to Srp1p only in the presence of RanGTP. The complex is dissociated by the cytoplasmic RanGTP-binding protein Yrb1p. Combined with the in vivo results, this suggests that a complex containing Srp1p, Cse1p, and RanGTP is exported from the nucleus and is subsequently disassembled in the cytoplasm by Yrb1p. The formation of the trimeric Srp1p-Cse1p-RanGTP complex is inhibited by NLS peptides, indicating that only NLS-free Srp1p will be exported to the cytoplasm.


Electron and photon triggers are essential for signal selection in a wide variety of ATLAS physics analyses to study Standard Model processes and to search for new phenomena. Final states including leptons and photons had, for example, an essential role in the discovery and measurement of the Higgs particle. Dedicated triggers are also used for the collection of J=y! ee, W! en, and QCD background samples for calibration, efficiency, and fake rate measurements. The ATLAS trigger system is divided in a hardware-based (Level 1) and a software-based high level trigger, both of which were upgraded during the long shutdown of the LHC in preparation for data taking in 2015. The increasing luminosity and more challenging pile-up conditions as well as the planned higher center-of-mass energy demanded the optimization of the trigger selections at each level to control the rates and keep efficiencies high. The evolution of the ATLAS electron and photon triggers and their performance will be presented, including initial results from the early days of the LHC Run 2 operation.


Table of Contents I. Introduction II. The Civil Damages Origins of Market Loss at Sentencing A. Securities Fraud in Private 10b-5 Actions B. Victim Loss C. Calculation Method D. Causation 1. Transaction Causation 2. Loss Causation E. Pre-Guidelines Market Loss in Sentencing III. The Federal Sentencing Guidelines and Evolution in Criminal Cases A. The Guidelines B. Federal Courts' Calculations of Loss IV. Current Problems with Securities Price Reduction as Loss A. Civil Causation Should Be the Bare Minimum for Criminal Sentencing 1. Basic's Fraud-on-the-Market Should Not Apply at Criminal Sentencing 2. Civil Doctrine Should Apply to Criminal Market Loss Calculations B. Market Loss Is Not Reasonably Foreseeable as Required by the Guidelines C. United States v. Booker V. A Workable Solution VI. Conclusion I. Introduction On December 16, 2008, the United States District Court for the District of Connecticut sentenced Ronald E. Ferguson, CEO of Gen Re Corporation, on charges of conspiracy, securities fraud, and mail fraud for his role in orchestrating an illegal scheme that resulted in almost $600 million in market decline of AIG Corporation's stock price. (1) Despite the Federal Sentencing Guidelines (Guidelines) recommending life in prison (2) for these crimes, the court sentenced Ferguson for two years. (3) At sentencing, the court emphasized that Ferguson did not gain directly from this loss amount. (4) Instead, this amount resulted from later marketplace transactions. (5) Ferguson's direct responsibility involves the issue of market loss, a unique type of victim loss that a court calculates for sentencing purposes, which consists of losses third-party shareholders suffer, normally after revelation of the fraud. (6) This Article will discuss how the victim loss amount influences the Guidelines for fraud under section 2B1.1 and how these Guidelines provide harsh imprisonment terms when loss amounts reach the hundreds of millions of dollars. such dollar amounts are common when employing market loss. When the fraud becomes public knowledge, the price of a security listed on an efficient market quickly will incorporate the new information, causing a sharp decrease in the security's price. (7) Because defendant responsibility is unclear with market loss, judges often are hesitant to apply severe Guideline sentences to such defendants, (8) as was the case with Ferguson. such hesitance creates disparities between judges who apply the Guidelines, and those judges who do not. This Article will examine these problems and how they result from a failure to differentiate market loss from direct loss. Part II analyzes the history of market loss, a calculation of loss that arose as a damage calculation in private plaintiff civil securities fraud actions. This Part describes the evolving theory of loss causation in order to understand the foundation for market loss at criminal sentencing. This Part also explains how market loss might have been used in sentencing before the Guidelines. After the codification of the Guidelines, victim loss became the official driving factor in fraud sentencing. Thus, Part III examines the loss table and how a large loss finding leads to a long prison term recommendation. Because the court must calculate victim loss to adhere to the Guidelines, courts determine market loss in a manner similar to previous civil securities fraud cases. Part III also analyzes the subsequent developments in federal court. Part IV argues that market loss is inappropriate for criminal sentencing in its current form, because it differs from direct victim loss due to weaker causation. A defendant might be civilly liable for market loss, but he is not responsible for that loss in the way that criminal sentencing should require. Loss causation, even if sufficient in civil cases, should be afforded special treatment for sentencing purposes. …


The recent financial crisis and associated real estate bubble demonstrated the damage that can be caused by imperfect financial market pricing. On the basis of these imperfections, strong financial returns earned by financial institutions in the run-up to 2008 were, in fact, illusory. Executive Compensation in Imperfect Financial Markets explores the relationship between bank lending, real estate markets and stock market prices. Offering a heterodox view of financial market pricing and its relationship with executive pay, this book offers a competing interpretation of the recent crisis, which emphasises the role of bank leverage and investor expectations in generating instability - particularly through the interaction of financial institutions with the real estate market. In the process, it reveals that equity-based compensation incentivized increased bank leverage, which was a cardinal cause of the crisis. This timely book will be an essential read for all legal scholars and policy analysts operating in the field of banking and finance, as well as all those seeking a more rounded understanding of the financial crisis.


Zika virus (ZIKV) is an emergent arbovirus that has attracted attention in the last year as a possible causative agent of congenital malformation; it shows a remarkably increased microcephaly risk during otherwise healthy pregnancies. We present here an analysis of all ZIKV sequences available in Genbank up to April 2016, studying the mutations in the whole polyprotein and their possible structural implications for the proteins E, NS1, NS3 and NS5. This study suggests that microcephaly is not a consequence of any particular amino acid substitution but, conceivably, is a feature of ZIKV itself. Moreover, the structural analysis of ZIKV proteins, together with the mutational landscape of ZIKV and a structure-sequence comparison with other flaviviruses, allows the suggestion of regions that could be exploited as anti-ZIKV targets, including some allosteric sites found in the NS3 and NS5 proteins of DENV.


In this study, sausage from spiny dog fish (Squalus acanthias) was produced. The purpose of study was to determine sausage made from shark meat was consumable or not. In order to find out quality characters of shark meat, paste and products, physical and chemical analysis were carried out. No significant differences for pH were observed among the meat, paste and product (P>0.05). Due to similar studies; the quantity of seperated gel and seperated fat, water holding capacity and loss of weight caused by cooking method were found low in paste of sausage while process efficiency was found high. In addition, chemical analysis of water (moisture), protein and fat amounts were not higher than the required values. In conclusion, the quality evaluation results indicated that shark (by-catch fish species) meat can be used for sausage processing.


Abstract Seemannia Regel belongs to the Gesnereacieae family. It is an herbaceous perennial plant with colorful and brilliant flowers that produces fleshy scaly rhizomes with axillary dormant buds. The objective of this study was to evaluate the effect of the volume of the container in the production and the quality of the rhizomes. Plants of a select hybrid of Seemnania were used. Three volume of container were tested: v1 of 1 L, v2 of 1,5 L and v3 of 2 L. Plants were cultivated in the containers following a conventional management. Dry matter, production (number and weight of rhizomes) and quality of the rhizomes were recorded. The rhizomes were classified into four qualities (A, B, C, D) according to the length and width, and the number of the scales. All data was subject to statistical analysis. Dry matter, weight and number of rhizomes increased as the volume of container increased. The v3 container recorded the highest values for these three parameters. Major volume of container, major was the development of vegetative mass and consequently the number and the weight of rhizomes were higher. In regard to the qualities of the rhizomes, v1 and v3 treatments had a better proportion of A rhizomes (the bigger size) compared to v2 treatment. The knowledge of the rhizome quality can be useful to the growers in order to select the best rhizome size for a good production. The v3 treatment recorded the highest number of A rhizomes, that we consider a good quality, because it has the bigger size with more scales and consequently more propagules.


The aim of the work described here is to use the optical absorption characteristics of phytoplankton to identify the taxonomic groups present in seawater. The spectral absorption of phytoplankton is determined by the pigment assemblage within each cell and taxonomic groups can have specific pigment combinations. Each individual pigment has distinct absorption characteristics, therfore phytoplankton communities containing different pigment assemblages should have absorption spectra that have distinctive characteristics.

An initial investigation into pigment distribution within the taxonomic classes reveals that the pigments fucoxanthin and 19'hexanoloxyfucoxanthin which are used as speficic biomarkers for diatoms and coccolithophores respectively are present in other taxonomic groups and so can not be considered to be indicative of diatoms of coccolithophores alone The chlorophyll a to accessory pigment ratios within taxonomic groups were also investigated and found to be inconsistent, varying due to light and nutrigent conditions. This is important as the pigment assemblage and relative concentration will have an effect on the ability to distinguish between the absorption spectro of phytoplankton.

The absorption spectra of pure culturers of six different phytoplankton taxonomic groups were measured using the filter pad technique. Investigation of the extent to which the pigment assemblage needs to differ for the absorption sepctra to be statistically different, revealed that phytoplankton containing pigment assemblages that differ only in the chlorophyll a to major accessory pigment ratio have absorption spectra that can be distinguished. Fourth derivative analysis was used to locate the in vivo absorption peaks on the absorption spectra, multiple regression analysis was then used to identify the pigments responsible. Only one absorption peak located at 650nm provides a phytoplankton taxonomic identification, of CHLb containing chlorophytes. A spectral library was constructed using the absorption spectra of each of the six different taxonomic groups. Multiple regression analysis performed between the spectral library and the absorption spectra of mixed phytoplankton samples, was successful in identifying the pigments present in samples providing fucoxanthin was not present.

These analysis techniques were applied to natural samples collected from the Atlantic Meridional Transect (AMT) cruise 10 in May 2000. This transect encompasses several different oceanographic provinces, Tropical gyres, Upwelling and Shelf waters which were experiencing a spring bloom. The absorption of the phytoplankton communities in each of these zones showed varied characteristics. The fourth derivative method identified high chlorophyll b containing areas. Comparison of the spectral library with the absorption spectra of eachprovince correctly predicted the pigment assemblage. From this the taxonomy was estimated, this concurred the microscopy analysis, with exception to the pigment HEX which was misleading predicting a dominance of coccolithophores, when other taxonomic groups were responsible for the presence of this pigment.

Conclusions drawn from this investigation are that pigments FUCO and HEX can not any longer be considered to be biomarker pogments for diatoms and coccolithophores. It is possible to identify the presence of chlorophyll a, b, c and total carotenoids from fourth derivative analysis. Of these pigments, only thepresence of chlorophyll b is useful in identifying the presence of a phytoplankton taxonomic group. It is possible with limitations to identify the taxonomic groups in a sample by regression of the absorption shape with a library of pure phytoplankton absorption spectra, although this is only an indication of the dominant pigments not phytoplankton biomass.


Studies on surrogate motherhood have mostly explored paid arrangements through the lens of a contract model, as clinical work or as a maternal identity-building project. Turning to the under-examined case of unpaid, so-called altruistic surrogate motherhood and based on an analysis of interviews with women who had been unpaid surrogate mothers in a full gestational surrogacy with a friend or relative in Canada, the United States or Australia, this article explores altruistic surrogate motherhood as relational work. It argues that this form of surrogate motherhood within close interpersonal relations can be conceptualised through the relational work involved in hosting a child for the intended parents. The article explores how relational work in this context implies an embodied, asymmetrical and far-reaching sense of responsibility that surrogate mothers describe as characteristic of their surrogacy experience. In this way, the article sheds light on feminist concerns about surrogacy as an embodied and objectifying work of women while at the same time illuminating how surrogate mothers respond to the intended parents in light of their pre-surrogacy relationship, how meanings are negotiated by them and how relationships are managed during the pregnancy.


We discover a new capacity scaling law in ultradense networks (UDNs) under practical system assumptions, such as a general multi-piece path loss model, a non-zero base station (BS) to user equipment (UE) antenna height difference, and a finite UE density. The intuition and implication of this new capacity scaling law are completely different from that found in year 2011. That law indicated that the increase of the interference power caused by a denser network would be exactly compensated by the increase of the signal power due to the reduced distance between transmitters and receivers, and thus network capacity should grow linearly with network densification. However, we find that both the signal and interference powers become bounded in practical UDNs, which leads to a constant capacity scaling law. As a result, network densification should be stopped at a certain level for a given UE density, because the network capacity will reach its limit due to (i) the bounded signal and interference powers, and (ii) a finite frequency reuse factor because of a finite UE density. Our new discovery on the constant capacity scaling law also resolves the recent concerns about network capacity collapsing in UDNs, e.g., the capacity crash due to a non-zero BS-to-UE antenna height difference, or a bounded path loss model of the near-field (NF) effect, etc.


This chapter is the first in a book that proposes a new theoretical approach to religious liberty that both transcends and transforms current approaches to law and religion. The text's broad interdisciplinary analysis overcomes longstanding challenges to existing religious rights regimes and identifies a new analytical paradigm that specifically addresses the types of tensions that arise in religiously pluralist societies. The goal is to create a system that both religious and non-religious people can support and thereby increase civic peace between individuals and groups. The discussion includes both analytical and practical elements. On the one hand, the book relies heavily on the work of renowned legal and political philosophers ranging from John Rawls to John Finnis to generate a new jurisprudential framework for religious liberty. On the other hand, the text tests the validity of the new proposals against actual "hard cases" generated through historical, comparative and international inquiry. Existing approaches to religious freedom are subject to the same inquiries, thereby allowing an accurate comparison of the old and the new. Although the book takes various principles of national and international law into account, it is not set within any particular legal system. As a result, the proposals reflected herein are suitable for adoption in a variety of national and international legal systems. Chapter one introduces the book's research goals and methodology so as to lay the foundation for subsequent analysis. The discussion includes basic background information on various international instruments concerning freedom of religion and outlines the religio-legal structures of the three countries (the United States, the United Kingdom and the Republic of Ireland) that serve as primary exemplars of domestic approaches to religious liberty. These three nations have been chosen to reflect the three standard means of addressing the intersection between law and religion, namely secular disestablishment, religious establishment and religiously intermediate. Although all three countries come from the common law tradition, the same range of religio-legal structures exist in civil law nations (for example, France is secular, Greece is established and Germany is intermediary) and Islamic nations (for example, Turkey is secular, Iran is established and Indonesia is intermediary). The analysis cites common law, civil law and Islamic law examples throughout the book in addition to cases generated by the European Court of Human Rights. In so doing, the text ensures that its proposals are suitable for adoption not only as a matter of international law but also in a wide range of national systems.


Nature is a weekly journal of multidisciplinary sciences with a huge range of followers in the scientific community. The purpose of the study is to analyse the citations of the full research articles published in Nature journal from 2006 to 2015. During this period Nature has published 8335 research articles. In the study the weightage of the research articles published in Nature were measured through immediacy index comparison of the research articles to the overall journal. The authorship pattern of the articles were measured and a cited references study was also conducted for measuring the self citations generated by Nature each year,the references per articles present and identifying core cited journals by Nature and their respective subject areas, which libraries in turn may use for collection development policies. Ranking of contributing countries and contributing organizations were also made by % share of article contribution. To check if any kind of biasness is present in Nature publications, a comparative evaluation of top contributing countries has also been made based on Nature Index. Web of Science core collection was used as the data source and Bibexcel bibliometric tool was used for data analysis purpose.


The proteasome (MCP) is a high relative molecular mass multicatalytic proteinase complex composed of nonidentical protein subunits. We have investigated the cellular distribution of the enzyme complex during Drosophila embryogenesis using the proteasome specific antibodies N19- 35 and N19-28 for immunocytology. Antibody staining of whole-mount embryos shows that during embryogenesis proteasomes are present in proliferating cells and that their accumulation and turnover is differentially regulated. Our data suggest that the proteasome may serve different proteolytic processes and that the enzyme may be involved in cell-specific proteolytic events required for cell proliferation and morphogenesis during early Drosophila development.


Background: Assessment of parenting behaviors in parents of children with autism is crucial in the assessment and treatment processes. Efficient tools and instruments with known psychometric properties are needed to assess parenting behaviors in parents of children with autism. Given the lack of such tools in the Indian context, there is a need to develop and/or adapt tools/scale to assess the parenting behaviors in regional languages. Aim of the Study: To adapt, translate and validate the Parental behavioral scale for Autism spectrum disorder (PBS-A) to Kannada. Materials and Methods: The original version of PBS-A was given to three healthcare professionals to examine the sociocultural suitability of items. The linguistic adaptation was performed through a forward-backward translation scheme. It was then administered on 50 parents of children with autism. Further, the psychometric properties of PBS-A Kannada version were examined, viz. acceptability, test-retest reliability and internal consistency. Results: Kannada version of PBS-A showed an excellent test-retest reliability (ICC = 0.993) and an overall high level of internal consistency (α = 0.93). The acceptability was found to be good among the Speech-language pathologists (SLP) ratings (k = 0.485). Conclusions: Kannada version of PBS-A is a valid and reliable scale that can be useful for assessing the parenting behavior.


"Web scraping" is a ubiquitous technique for extracting data from the World Wide Web, done through a computer script that will send tailored queries to websites to retrieve specific pieces of content. The technique has proliferated under the ever-expanding shadow of the Computer Fraud and Abuse Act (CFAA), which, among other things, prohibits obtaining information from a computer by accessing the computer without authorization or exceeding one's authorized access.

Unsurprisingly, many litigants have now turned to the CFAA in attempt to police against unwanted web scraping. Yet despite the rise in both web scraping and lawsuits about web scraping, practical advice about the legality of web scraping is hard to come by, and rarely extends beyond a rough combination of "try not to get caught" and "talk to a lawyer." Most often the legal status of scraping is characterized as something just shy of unknowable, or a matter entirely left to the whims of courts, plaintiffs, or prosecutors.

Uncertainty does indeed exist in the caselaw, and may stem in part from how courts approach the act of web scraping on a technical level. In the way that courts describe the act of web scraping, they misstate some of the qualities of scraping to suggest that the technique is inherently more invasive or burdensome. The first goal of this piece is to clarify how web scrapers operate, and explain why one should not think of web scraping as being inherently more burdensome or invasive than humans browsing the web.

The second goal of this piece is to more fully articulate how courts approach the all-important question of whether a web scraper accesses a website without authorization under the CFAA. I aim to suggest here that there is a fair amount of madness in the caselaw, but not without some method. Specifically, this piece breaks down the twenty years of web scraping litigation (and the sixty-one opinions that this litigation has generated) into four rough phases of thinking around the critical access question.

The first runs through the first decade of scraping litigation, and is marked with cases that adopt an expansive interpretation of the CFAA, with the potential to extend to all scrapers so long as a website can point to some mechanism that signaled access was unauthorized. The second, starting in the late 2000s, was marked by a narrowing of the CFAA and a focus more on the code-based controls of scraping, a move that tended to benefit scrapers. In the third phase courts have receded back to a broad view of the CFAA, brought about by the development of a "revocation" theory of unauthorized access. And most recently, spurred in part by the same policy concerns that led courts to initially constrain the CFAA in the first place, courts have begun to rethink this result.

The conclusion of this piece identifies the broader questions about the CFAA and web scraping that courts must contend with in order to bring more harmony and comprehension to this area of law. They include how to deal with conflicting instructions on authorization coming different channels on the same website, how the analysis should interact with existing technical protocols that regulate web scraping, including the Robots Exclusion Standard, and what other factors beyond the wishes of the website host should govern application of the CFAA to unwanted web scraping.


This paper describes a mechatronics methodology that allows the design of systems that are simple and intuitive to analyze and control. The primary application of this methodology is the design of a leg mechanism for a running robot. The approach first divides the system behaviour into several phases, and then finds Simple to Control Mechanisms (SCMs) that can achieve the desired performance in each phase. The mechanical element of the system is designed to emulate these SCMs. It is shown that simple controllers designed for the SCMs of the running robot leg can provide the desired system behaviour.


Enforcing cooperation among substantial agents is one of the main objectives for multi-agent systems. However, due to the existence of inherent social dilemmas in many scenarios, the free-rider problem may arise during agents' long-run interactions and things become even severer when self-interested agents work in collusion with each other to get extra benefits. It is commonly accepted that in such social dilemmas, there exists no simple strategy for an agent whereby she can simultaneously manipulate on the utility of each of her opponents and further promote mutual cooperation among all agents. Here, we show that such strategies do exist. Under the conventional repeated public goods game, we novelly identify them and find that, when confronted with such strategies, a single opponent can maximize his utility only via global cooperation and any colluding alliance cannot get the upper hand. Since a full cooperation is individually optimal for any single opponent, a stable cooperation among all players can be achieved. Moreover, we experimentally show that these strategies can still promote cooperation even when the opponents are both self-learning and collusive.


This paper, originally written as an encyclopaedia survey, considers as globalisation all the consequences of the long-term cheapening of, and expansion of the technical possibilities of -transport and communication; a process more or less uninterrupted since the improvements of navigation in the fifteenth century, though recently much accelerated. It considers five main areas of contemporary discussion: 1. How integrated global markets really are. (Not as much as one might think.) 2. How far globalisation erodes the sovereignty of nation-states, reducing their autonomy in making economic policy. (More for some than for others.) 3. The consequences of globalisation for the distribution of income among the world''s population; both among nations (equalising for good learners, not for others) and within nations (generally unequalising). 4. The problematic growth of a transnational ''world society'' (slow, probably unstoppable, but still a long way from creating a ''world class system'') and international governance (hesitant and more likely to be hegemonic than conciliar). 5. The interaction of national economic, political, military and cultural power, and the possibility and desirability of retaining distinctive national institutions, embodying distinctive national value preferences and cultures. (in the end, as much a matter of neo-liberalism vs. social democracy as of the persistence of Germanness or Japaneseness).


Galicia (NW Spain) is an important fishing region with a high potential for cetacean–fishery interactions. Cetacean depredation on catch and damage to fishing gear can potentially lead to substantial economic loss for fishers, while cetacean bycatch raises conservation concerns. With the aim of gathering information on the types and scale of interactions and of suggesting possible management strategies, we conducted face-to-face interviews with fishers in local fishing harbours, in particular to identify specific problematic interactions and to quantify the level of economic loss and bycatch rates associated with these interactions. We found that cetacean–fishery interactions are frequent, although damage to catch and fishing gear by cetaceans was mostly reported as small. Nevertheless, substantial economic loss can result fromcommon bottlenose dolphins (Tursiops truncatus) damaging coastal gillnets and from short-beaked common dolphins (Delphinus delphis) scattering fish in purse-seine fisheries. Cetacean bycatch mortality was reported to be highest for trawls and set gillnets, and probably exceeds sustainable levels for local common and bottlenose dolphin populations. Although interviewdata may be biased due to the perceptions of interviewees, and therefore should be interpreted with care, the methodology allowed us to covermultiple sites and fisheries within a reasonable time frame. Minimizing cetacean–fishery interactions requires the implementation of case-specific management strategies with the active participation of fishers. For set gillnet and purse-seine fisheries, the use of acoustic deterrent devices (pingers) may prevent cetaceans from approaching and getting trapped in the nets. For trawl fisheries, where bycatch appears to be particularly high at night in water depths of 100–300 m, possible solutions include the implementation of time/area closures and the relocation of some fishing effort to deeper waters.


Objective To evaluate the management strategies following bile duct injuries. Design and duration This was a prospective analysis conducted from March 2015 to March 2017. Setting The study was conducted at the Department of Surgery, Zagazig University Hospitals. Patients and methods The study included all patients who were admitted with iatrogenic biliary injuries during this period. The patients were evaluated according to their clinical features and certain laboratory and imaging investigations. After appropriate preparations, they were managed based on Bismuth Classification. Results A total of 27 patients presented with iatrogenic biliary injuries over a period of 2 years among all 420 cases that underwent cholecystectomy during this period. There were 16 females and 11 males, with a median age of 40 years. A total of 18 patients had laparoscopic cholecystectomy, whereas nine had open cholecystectomy. Twelve cases belonged to our unit whereas 15 were referred from other institutes. Four patients were detected intraoperatively, 15 patients presented with obstructive jaundice, four patients presented with biliary fistula, and four patients presented with collection. Of which, one had ultrasound-guided aspiration and five had endoscopic retrograde cholangiopancreatography (ERCP) stenting done, whereas two underwent peritoneal lavage with drain placement, 16 patients had hepaticojejunostomy, and one patient had choledechodoudenostomy. We had one postoperative mortality owing to hepatorenal failure. Conclusion Strategies need to be developed for dealing with bile duct injuries, with a view to reduce morbidity and mortality, as early recognition and timely management improve the outcome of these patients.


YAN HUANG Exploring Structure, Function & Regulation of the Human Glucagon-like Peptide-1 Receptor Glucagon-like peptide-1 (GLP-1) enhances glucose-dependent insulin secretion and promotes β-cell function via its receptor (GLP-1R), which therefore is a validated target for the treatment of type 2 diabetes. Due to difficulties with peptide therapeutics, it is important to find small-molecule GLP-1R agonists. This leads to a need to understand the structure, function and regulation of the receptor, particularly, differences between agonisms mediated by GLP-1 (orthosteric agonist) and small molecules. The GLP-1R contains a putative N-terminal signal peptide sequence, which is assessed here by recombinantly expressing several epitope-tagged GLP-1R constructs in HEK293 cells. The findings demonstrate that the GLP-1R is expressed predominately at the plasma membrane and also slightly cytosolic. Only fully glycosylated, mature form of the receptor is able to traffic to the cell surface and performs the function. The signal peptide sequence of the GLP-1R is essential for synthesis. After fulfilling the function, this sequence is cleaved and thus not part of the mature protein. The cleavage of signal peptide is critical for processing and trafficking of the GLP-1R. Based on one of these constructs generated here, a cell line (HEK293: GLP-1R-EGFP) with stable expression of the visible GLP-1R is established, which allows observations and determinations for ligand-mediated receptor internalisation in real time. Compound 2 (6,7-dichloro-2-methylsulfonyl-3-N-tert-butylaminoquinoxaline) has been described as a GLP-1R allosteric modulator and agonist. Findings here that compound 2-mediated agonisms on both the wild-type (WT) GLP-1R and the mutant with removal of the N-terminal domain provide direct evidence for the allosteric agonism. Interestingly, compound 2-mediated cAMP response is enhanced by orthosteric antagonist exendin 9-39, but the latter inhibits receptor internalisation mediated by compound 2. Recently, it has been hypothesised that the binding of GLP-1 allows a sequence of NRTFD (Asn 63 -Asp 67 ) in the N-terminus of the GLP-1R to interact with another part of the receptor and cause agonism. This was examined here by generating receptor mutants and synthetic peptides. Findings here that Asp 67 plays a key role in stabilising the Nterminal structure of the GLP-1R and thus is critical for processing and trafficking of the receptor protein do not support such hypothesis although synthetic NRTFD mediates a weak and partial agonism on the WTGLP-1R.


Lesbian Sexuality has remained largely ignored in Japan despite increasing exposure of disadvantaged minority groups, including gay men. This book is the first comprehensive academic exploration of contemporary lesbian sexuality in Japanese society. The author employs an interdisciplinary approach and this book will be of great value to those working or interested in the areas of Japanese, lesbian and gender studies as well as Japanese history, anthropology and cultural studies.