This research study focuses on parametric design as a leading global trend in many fields, including simulation, locomotion, industrial design and, most importantly, architecture and urbanism. Parametric design allows for seamless and simultaneous interaction and configuration in architecture. Based on established mathematical principles and rules that can be controlled and managed to produce what is known as 'free architecture', parametric design makes it possible to adjust design architectural components at the interior, exterior or urban levels. Flexible design technology, or modular design technique, (the term that most accurately defines how it functions), can be applied to the most minute design details and to all benchmarks. This technology has transformed architectural and urban design thinking and done away with many of the conditions that restrict creativity in architectural design. It has created a design methodology that emphasizes and is inspired by nature. However, in spite of the technology's capacity for interaction, simulation and creativity, it has to date not been to promote local architectural and urban heritage in the Arab World. This, despite the fact that computational designs date back to the golden ages of the Pharaohs and Islam when design regulations and codes were first developed, producing delicate ornamentation and intricate shapes, assembled together to produce and interact with an entire architectural unit, as in the case of Islamic architecture.


In recent years, focus of business world has been moved towards the Internet. Web applications provide a generous interface non-stop thus offering to malicious users a wide spectrum of possible attacks. Consequently, the security of web applications has become a crucial issue. The state-of-the-art tools for bug discovery in languages used for web-application development, such as PHP, suffer from a relatively high false-positive rate and low coverage of real errors; this is caused mainly by unprecise modeling of dynamic features of such languages and path-insensivity of the tools. In this paper, we will demonstrate weak points of the tools and describe our novel approach to these issues. We will show how our technique handles some of the situations where other tools fail and illustrate it on examples.


Maintenance of professional competence remains an exercise of permament learning and an essential requirement for evidence –based medical practice. Physicians attend continuing professional development (CPD) programs to acquire new knowledge. Often CPD programs remain the main source for updates of information. CPD organizers have a considerable responsibility in determining appropriate curriculum for their conferences. Organizing an effective CPD activity often requires understanding of the principles of adult education. Prior to deciding on the curriculum for a CPD, course organizers should conduct needs assessment of physicians. CPD planners should create activities that would consistently improve physician competence. CPD sessions that are interactive, using multiple methods of instructions for small groups of physicians from a single specialty are more likely to change physician knowledge and behavior. The effectiveness of a CPD program should be evaluated at a level beyond measuring physician satisfaction. CPD planners should incorporate methods to determine the course attendees' improvement of knowledge, skills and attitudes during the CPD activities. Pre and post conference evaluations of physicians using multiple choice questions may form a useful method of assessment.


JAGuaR is an alignment protocol for RNA-seq reads that uses an extended reference to increase alignment sensitivity. It uses BWA to align reads to the genome and reference transcript models (including annotated exon-exon junctions) specifically allowing for the possibility of a single read spanning multiple exons. Reads aligned to the transcript models are then re-mapped on to genomic coordinates, transforming alignments that span multiple exons into large-gapped alignments on the genome. While JAGuaR does not detect novel junctions, we demonstrate how JAGuaR generates fast and accurate transcriptome alignments, which allows for both sensitive and specific SNV calling.


This definitive guide, revised and updated with over 25% new material, empowers cancer patients and their loved ones to move beyond their disease. Greg Anderson, a cancer survivor, has designed this book for the recently diagnosed, those with recurring symptoms, and those who are well but have a lingering fear that the disease may strike again. Informative and inspiring, Cancer: 50 Essential Things to Do goes hand-in-hand with the patient's medical treatment and is an invaluable roadmap to recovery. Filled with practical, healing "action steps" that have been used by thousands of cancer survivors, the revised edition also contains important new information--including recently approved medical treatment options, updated cancer research, and Internet resources--geared toward making sense of the fast-changing world of cancer treatment and recovery.


Recently, the acquisition of three-dimensional maps has become more and more popular. This is motivated by the fact that robots act in the three-dimensional world and several tasks such as path planning or localizing objects can be carried out more reliable using three-dimensional representations. In this paper we consider the problem of extracting planes from three-dimensional range data. In contrast to previous approaches our algorithm uses a hierarchical variant of the popular Expectation Maximization (EM) algorithm [1] to simultaneously learn the main directions of the planar structures. These main directions are then used to correct the position and orientation of planes. In practical experiments carried out with real data and in simulations we demonstrate that our algorithm can accurately extract planes and their orientation from range data.


The crime of genocide was defined in the 1948 Convention on the Prevention and Punishment of the Crime of Genocide in reaction to the concept of crimes against humanity developed at Nuremberg, which insisted upon a connection with aggressive war in prosecutions for atrocity crimes. The convention stated genocide could be committed in time of peace, but it also narrowed the scope of the crime itself to the intentional destruction of a national, ethnic, racial, or religious group. Cultural genocide was intentionally excluded. Although the text of the definition remains unchanged, judicial interpretation has broadened it significantly. Recent decisions have held that there is no requirement of a state plan or policy. They have also set out a subjective approach to identification of the protected group. Although cultural genocide in an extensive sense is still not recognized within the definition, there is a definite tendency to extend the concept to what is colloquially called "ethnic cleansing." These broadening definitions influence determinations about genocides, even those committed many years ago.


BACKGROUND
We used the Nordic Arthroplasty Register Association database to evaluate whether age, sex, preoperative diagnosis, fixation, and implant design influence the risk of revision arthroplasty due to periprosthetic fracture within two years from operation of a primary total hip replacement.

METHODS
Included in the study were 325,730 cemented femoral stems and 111,899 uncemented femoral stems inserted from 1995 to 2009. Seven frequently used stems (two cemented stems [Exeter and Lubinus SP II] and five uncemented stems [Bi-Metric, Corail, CLS Spotorno, ABG I, and ABG II]) were specifically studied.

RESULTS
The incidence of revision at two years was low: 0.47% for uncemented stems and 0.07% for cemented stems. Uncemented stems were much more likely to have this complication (relative risk, 8.72 [95% confidence interval, 7.37 to 10.32]; p < 0.0005). Age had no consistent influence on the risk for revision of cemented stems, but revision in the uncemented group increased with increasing age. A cemented stem was associated with a higher risk in male patients compared with female patients (hazard ratio, 1.95 [95% confidence interval, 1.51 to 2.53]; p < 0.0005), whereas an uncemented stem was associated with a reduced risk in male patients compared with female patients (hazard ratio, 0.74 [95% confidence interval, 0.62 to 0.89]; p = 0.001). The risk for revision due to early periprosthetic fracture increased during the 2003 to 2009 period compared with the 1995 to 2002 period both before and after adjustment for demographic factors and fixation (relative risk, 1.44 [95% confidence interval, 1.18 to 1.69]; p < 0.0005). The hazard ratio for the Exeter stem was about five times higher than that for the Lubinus SP II stem (hazard ratio, 5.03 [95% confidence interval, 3.29 to 7.70]; p < 0.0005). Of the five uncemented stems, the ABG II stem showed an increased hazard ratio of 1.63 (95% confidence interval, 1.16 to 2.28) (p = 0.005), whereas the Corail stem showed a decreased hazard ratio of 0.47 (95% confidence interval, 0.34 to 0.65) (p < 0.0005) compared with the reference Bi-Metric design.

CONCLUSIONS
The shape and surface finish of the femoral stem and its fixation could be related to the increased risk of some prosthetic designs. Even if the incidence of early periprosthetic fracture in general is low and other reasons for revision must be considered, specific attention should be given to the choice of fixation and stem design in risk groups.

LEVEL OF EVIDENCE
Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.


The American Heart Association (AHA) recognizes diabetes as a risk factor for developing cardiovascular disease. Type 1 diabetes (T1D) is characterized by absolute insulin deficiency due to the destruction of the insulin-producing pancreatic beta cells. A common model for studying T1D is the streptozotocin (STZ) induced rat. STZ targets and destroys beta cells of the pancreas and therefore causes the rats to develop T1D. PURPOSE: The purpose of this project was to describe the procedure for inducing T1D in a in vivo rat model, to study the cardiovascular responses to exercise. METHODS: Male and female Sprague Dawley rats were fasted overnight (12 hours) and brought in to the lab the following day for injection. Rats were anesthetized with 5% isoflurane in 100% oxygen for about four minutes. Once rats were unresponsive to mechanical stimulation, they were weighed and placed on a nosecone and ventilated through a nose cone with 3% isoflurane in 100% oxygen. The tail was pricked, and venous blood sampled for measurement of baseline blood glucose (Nova Biomedical) level. While the rat was on the nose cone, STZ (Sigma Aldrich) dosage (50mg/kg) was calculated, based on recorded body weight, and dissolved in 200 μl of citrate buffer. The drug solution was vortexed for 30 sec before being injected intraperitoneally followed by lactated Ringers (5 ml), which was injected subcutaneously to prevent dehydration. The rat was then taken off isoflurane and returned to its cage in a supine position with its head slightly elevated to prevent choking. RESULTS: Rats typically developed T1D within 24 to 48 hrs following STZ injection. The rats were considered diabetic when non-fasted blood glucose level was >300 mg/dl. STZ induced T1D rats had an exaggerated blood pressure response to both static contraction and passive stretch compared to healthy controls. CONCLUSION: We have shown that inducing rats with T1D by injecting them with STZ resulted in a T1D rat model whose blood pressure response to exercise was exaggerated compared to healthy rats. This model allows for investigations addressing neurovascular control mechanisms during exercise in T1D.


Using pre-existing software components (COTS) to develop software sys- tems requires the composition and adaptation of the component interfaces to solve mismatch problems. These mismatches may appear at different interoperability levels (signature, behavioural, quality of service and semantic). In this article, we define an approach which supports composition and adaptation of software components based on model transformation by taking into account the four levels. Signature and behavioural levels are addressed by means of transition systems. Context-awareness and semantic- based techniques are used to tackle quality of service and semantic, respectively, but also both consider the signature level. We have implemented and validated our proposal for the design and application of realistic and complex systems. Here, we illustrate the need to support the variability of the adaptation process in a context-aware pervasive system through a real-world case study, where software components are implemented using Windows Workflow Foundation (WF). We apply our model transformation pro- cess to extract transition systems (CA-STS specifications) from WF components. These CA-STSs are used to tackle the composition and adaptation. Then, we generate a CA- STS adaptor specification, which is transformed into its corresponding WF adaptor component with the purpose of interacting with all the WF components of the system, thereby avoiding mismatch problems.


Thiazolidinediones (TZDs) are used as antidiabetic agents in the treatment of type II diabetes. These compounds are ligands for the nuclear hormone receptor PPARγ, which is highly expressed in adipose tissue. PPARγ acts as a molecular switch in the process of fat cell development. The quest for the ideal antidiabetic agent is challenged by the need to develop PPARγ ligands that improve insulin sensitivity, but do not promote fat cell formation. A newly described PPARγ ligand may represent an initial step in this direction and could lead to improved agents for treating insulin resistance in type II diabetes.


The book presents the international laws on the use of force whilst demonstrating the unique insight a feminist analysis offers this central area of international law. The book highlights key conceptual barriers to the enhanced application of the law of the use of force, and develops international feminist method through rigorous engagement with the key writers in the field

The book looks at the key aspects of the UN Charter relevant to the use of force – Article 2(4), Article 51 and Chapter VII powers – as well as engaging with contemporary debates on the possibility of justified force to meet self-determination or humanitarian goals. The text also discusses the arguments in favour of the use of pre-emptive force and reflects on the role feminist legal theories can play in exposing the inconsistencies of contemporary arguments for justified force under the banner of the war on terror. Throughout the text state practice and institutional documentation are analysed, alongside key instances of the use of force.

The book makes a genuine, urgently needed contribution to a central area of international law, demonstrating the capacity of feminist legal theories to enlarge our understanding of key international legal dilemmas


Renomedullary interstitial cells cultured from the Dahl salt-resistant rat have higher levels of basal cytosolic calcium and prostaglandin E2 and are more responsive to vasopressin than interstitial cells from the Dahl salt-sensitive rat We examined the potential role of inositol phospholipid hydrolysis in mediating these differences. Vasopressin-induced increases in labeled inositol phosphates were enhanced in renomedullary interstitial cells from Dahl salt-resistant compared with those from salt-sensitive rats. Addition of neomycin reduced basal production of labeled inositol phosphates and abolished the increase in inositol phosphates induced by vasopressin. Neomycin also prevented the peak decline pattern in cytosolic Ca2+ seen with vasopressin but did not influence basal cytosolic Ca2+. In the presence of neomycin, vasopressin induced a modest but prolonged increase in cytosolic calcium. In contrast to its marked effects on inositol phosphate production, neomycin was without effect on basal or vasopressin-responsive prostaglandin E2 production. Moreover, basal and vasopressin-induced increases in cytosolic Ca2+ remained higher in renomedullary interstitial cells from Dahl salt-resistant versus those from salt-sensitive rats exposed to neomycin. The results do not support a requirement for phospholipase C-induced inositol phospholipid hydrolysis in the mediation of vasopressin actions on prostaglandin E2 production by renomedullary interstitial cells and imply that the differences in cytosolic Ca2+ and prostaglandin E2 seen in these two cell lines are not related to differences in inositol phospholipid metabolism.


The Foreign Emoluments Clause is a constitutional backwater. So much so, that there is no substantial discussion of this clause in any federal adjudication (although the Office of Legal Counsel has regularly opined on it). Backwaters, however, have an unappreciated and significant virtue. They allow us to discuss our precommitments, assumptions, and methodological positions free from the distractions of the great political issues of the day – issues which naturally tend to divide us in ways which may be unconnected to the merits. Simply put, backwaters allow us to freely debate the merits of contestable worldviews. That is what I propose to do here. Both Professors Zephyr Rain Teachout and Akhil Reed Amar have discussed the Foreign Emoluments Clause in their recent publications. Amar is an originalist, perhaps the most influential American originalist of the late twentieth century; Teachout, although, perhaps, not an originalist per se, regularly writes in an originalist mode – parsing drafting history, text, structure, precedent, and history – in search of a public (or, perhaps, an intended) meaning contemporaneous with ratification. Both Teachout and Amar might be fairly characterized as left-of-center, but both are also clearly in the academic mainstream. Both Teachout and Amar's publications are actively cited, if not widely acclaimed, and my own view is that citations and public acclaim vastly underestimate the influence of these two scholars. (However, as do all mere humans, both Teachout and Amar stray into some truly puzzling errors from time to time.) Indeed, there are now several publications that cite both Teachout and Amar. Interestingly, each takes a position in regard to the Foreign Emoluments Clause which is in clear conflict with the position taken by the other. The stakes here involve more than the contours, scope, purpose, and original public meaning of the Foreign Emoluments Clause (which, in itself, is not an entirely minor thing). If Amar is correct, then Teachout must be wrong, and it follows that Teachout's views in regard to congressional power to limit election-related speech and spending are (if not flatly wrong) something that must be carefully reconsidered in light of Amar's contrary position. On the other hand, if Teachout is correct, then Amar must be wrong, and it follows that Amar's views in regard to constitutional structure, intratextualism, and the meaning of coordinate language in other constitutional clauses are (if not plainly wrong) something that must be closely reexamined in light of Teachout's contrary teachings. This paper will explore that conflict, and, then, I will attempt to reconcile the two positions.


Introduction: We aimed to investigate the vascular and neural anatomy of the hand in adult cadavers and to determine the normal anatomical structure and variations of these structures. Material and Methods: Twenty hands of adult cadavers were examined by the dissection method. After the superficial palmar arch (SPA), the ulnar nerve (UN), median nerve (MN), and deep palmar arch (DPA) were identified, their anatomical structures and variations were evaluated. Then, they were classified according to the number of branches they give off and the course of these branches. Results: When the number of the common palmar digital arteries emerging from the SPA was examined, four branches were observed to emerge from the arch in 80%, and five branches in 20%. When the innervation of the MN and UN was evaluated, 3.5 + 1.5 fingers innervation was observed in 90%, 3 + 1.5 fingers innervation and 3 + 2 fingers innervation were observed in 5% of the samples. When the DPA samples were examined, four metacarpal palmar arteries were observed to emerge from the arch in all of the samples. According to the number of branches they gave off and the course of these branches, the SPA was gathered under seven groups, the nerves were gathered under four groups, and the DPA was gathered under three groups. Discussion and Conclusion: We believe that the data obtained in our study will be used, especially in anatomy education and will guide neurologists, surgeons, orthopedists, radiologists, and anatomists in their studies, diagnosis, and treatments.


This paper explores policy and legal debates over same-sex marriage in the United States, focusing on the indirect effects of the struggle over same-sex marriage and how these implicate the interests of women, including women in heterosexual relationships. The paper highlights the effects of the institutional structures of American politics, which have shaped the same-sex marriage debate in particular ways, privileging an incremental path of policy evolution across the states. This has forced US state courts to engage repeatedly with the legal arguments over same-sex relationship recognition and marriage and, in doing so, courts have increasingly cast the heterosexual nuclear family as a fragile edifice in need of state protection. The paper argues that we must move beyond thinking of same-sex marriage and relationship recognition as struggles that pit allegedly normalized or assimilated same-sex couples against queer politics and sensibilities and, rather, recognize the increasingly complex gender politics of same-sex marriage and relationship recognition, a politics that implicates groups beyond the LGBT community. In doing so, the paper argues that struggles over same-sex marriage are much more than simply struggles for recognition by LGBT communities but, rather, that they are the canary in the mineshaft of broad and profound shifts in gender relations.


There is a global demand for constant increase in the production of textile fibres. Currently, the market for cellulosic fibres is dominated by cotton and viscose fibres. However, new alternative cellulosic fibres are being sought to meet the growing demand. The dyeing properties of novel fibres aiming at the marketplace are among the properties that determine their applicability to textiles. Recently, a novel process for producing cellulosic fibres, the Biocelsol process, has been scaled up so that the spinning of yarn from Biocelsol fibres is now possible. In this study, the reactive dye Levafix CA Blue was applied to cellulosic fabrics made from viscose, cotton, and Biocelsol yarns. The crystalline structure and morphology of the fibres were studied by Fourier transform infrared spectroscopy and field-emission scanning electron microscopy. The crystalline structure and morphology of the Biocelsol fibres resembled those of viscose fibres, but, owing to higher water absorption, the Biocelsol fabric had a higher dye exhaustion. The colour yield of the Biocelsol fabric was 62% and 41% higher than that of cotton and viscose fabrics respectively, suggesting that less dye is needed to gain a shade in Biocelsol fabric than in viscose and cotton fabrics.


Background During the last decades, several risk assessment models have been applied to predict the risk of mortality after cardiac surgery; however, none of them have been developed  in Latin American populations. These models have inferior performance when applied to patient groups other than the ones on whom they were developed. Objectives To perform external and temporal validation of a local risk score for cardiac surgery [Argentinean System for Cardiac Operative Risk Evaluation (ArgenSCORE)] and compare it to the EuroSCORE. Material and Methods A total of 5268 consecutive adult patients undergoing cardiac surgery were included from June 1994 to December 2009. The risk model was developed through logistic regression on the data of 2903 patients who underwent cardiac surgery between June 1994 and December 1999 at a center. Prospective internal validation was performed on 708 patients between January 2000 and June 2001. External and temporal validation of the recalibrated model were performed between February 2000 and December 2009, evaluating model discrimination and calibration in patients operated on at four centers different from the one where the score had been originally developed. The method was also compared to the EuroSCORE. Results The external validation was performed on 1657 patients, mean age was 62.8±13.3 years and global mortality was 4.58%. The ArgenSCORE showed both good discriminatory power with an area under the ROC curve of 0.80 and predictive capacity for risk assessment in all patients (observed mortality 4.58% vs. expected mortality 4.54%; p=0.842). The EuroSCORE showed good discriminatory power (area under the ROC curve of 0.79) but overestimated the risk (observed mortality 4.58% vs. expected mortality 5.23%; p <0.0001). Conclusions The ArgenSCORE showed an adequate capacity to predict in-hospital mortality in cardiac surgery 10 years after being developed. The score can be applied to populations with similar geographic characteristics, showing a better performance compared to an established international risk stratification model.


In the European Union insider trading has been regulated much more recently than in the United States, and it can be argued that, at least traditionally, it has been more aggressively and successfully enforced in the United States than in the European Union. Several different explanations have been offered for this difference in enforcement attitudes, focusing in particular on resources of regulators devoted to contrasting this practice, but also diverging cultural attitudes toward insiders. This situation has evolved, however, and the prohibition of insider trading has gained traction also in Europe. Few studies have focused on the substantive differences in the regulation of the phenomenon on the two sides of the Atlantic. This work contributes to the debate by contrasting and comparing insider trading regulation in the U.S. and in Europe, putting them in an historical perspective (essential in particular to understand the U.S. approach), but also considering some recent developments in this area of both sides of the Atlantic: the 2009 Dorozhko decision in the U.S., which seems to expand the notion of misappropriation; the reform of the Market Abuse Directive in Europe; and the very recent case Grande Stevens v. Italy decided by the European Court of Human Rights in March 2014, which deeply affects the European approach to insider trading. One of the contributions of the piece is to underline how the U.S. has both the advantages and disadvantages of the "first comer" in this area. Since when the Supreme Court abandoned the "equal access to information" theory in favor of a theory of insider trading based on fiduciary duties, an overly complex web of rules developed through an intricate web of case law and SEC regulations. Comparatively speaking, the European approach, based on the "equal access to information" theory is more clear, easy to apply and broad, even if some authors have questioned the effectiveness of actual enforcement of these rules in some European countries.


The transpeptidase Ltd Mt2 catalyzes the formation of the (3–3) cross-links characteristic of the peptidoglycan layer in the Mycobacterium tuberculosis cell wall. Bioinformatics analysis suggests that the extramembrane part of the enzyme consists of three domains: two smaller domains (denoted as A and B domains) and a transpeptidase domain (the C domain) at the C-terminus. The crystal structures of two fragments comprising the AB domains and the BC domains have been determined. The structure of the BC module, which was determined to 1.86 A ˚ resolution using Se-SAD phasing, consists of the B domain with an immunoglobulin-related fold and the catalytic domain belonging to the ErfK/YbiS/ YbnG fold family. The structure of the AB-domain fragment, which was solved by molecular replacement to 1.45 A ˚ resolution, reveals that despite a lack of overall sequence identity the A domain is structurally very similar to the B domain. Combining the structures of the two fragments provides a view of the complete three-domain extramembrane part of Ldt Mt2 and shows that the protein extends at least 80– 100 A ˚ from the plasma membrane into the peptidoglycan layer and thus defines the maximal distance at which cross-links are formed by this enzyme. The Ldt Mt-related transpep-tidases contain one or two immunoglobulin domains, which suggests that these might serve as extender units to position the catalytic domain at an appropriate distance from the membrane in the peptidoglycan layer.


The "TRX, Inc.: Initial Public Offering" case provides comprehensive coverage of a firm's decision to undertake an initial public offering (IPO) and the process of going public. The case follows the sequence of events from the company's incorporation in 1999 through the completion of an IPO in September 2005. In addition to raising capital, the TRX IPO case also includes consideration of another motivation for going public. At the time of its incorporation in November 1999, TRX attempted to go public but in the ensuing dot-com collapse, the IPO was never completed. In response to the failed IPO, TRX president and CEO, Trip Davis, turned to strategic investors to raise $20 million in a note convertible into equity at $11 per share. Although Davis had hoped the strategic investors would provide guidance and business opportunities for TRX, they never materialized. By 2004, he had come to believe that the largest strategic investor, Sabre, Inc. was not working in TRX's best interest. Thus, the IPO is motivated by a twofold purpose: to raise money and to provide for a strategic reorganization of the firm's ownership structure.


The purpose of this research was to broaden our knowledge of the dietary changes and timing of the Mesolithic-Neolithic transition in Scotland. Despite the rich number of archaeological sites around mainland Scotland and the Orkney Isles that date to the transition period (c.4000 to 3600 BC), bones of humans and especially of fauna are rarely recovered. This lack of skeletal material necessary to investigate individual human diet has resulted in a gap in our understanding about dietary changes that occurred during the transition from a hunter-gatherer lifestyle to farming. One of the most widely used and reliable scientific tools available to investigate ancient diet is δ13C and δ15N isotope analysis; however, this technique requires samples of human bone and also a representative sample of bones from animals from the same spatial and chronological context as the humans to form an isotopic baseline. Studies of dietary change during the Scottish Mesolithic-Neolithic transition so far have largely relied on poor quality baselines to interpret the diets of the relatively small number of humans recovered from this period. A solution was therefore required in order to ensure that interpretations of dietary change during this time that employed stable isotope analysis of bone collagen were better defined and more secure.
In addition to the problems of interpreting changes in the diet, there are questions surrounding the timing of the Scottish Mesolithic-Neolithic transition as well. The dietary changes were characterised by replacing marine protein with terrestrial animal protein, however we are uncertain as to how fast and complete this shift in diet was. There is long-standing debate regarding how important marine protein was in the early Neolithic diet. If marine protein was only a minor component of the diet, this would be undetected by traditional interpretations of stable isotope data. However, the radiocarbon ages of the bone collagen of these humans may be affected by oceanic 14C. Ancient marine derived carbon in human bone collagen is on average c.400 years older than terrestrial carbon, resulting in the need to correct the ages of mixed marine/terrestrial samples for this Marine Reservoir Effect. Undetected marine protein in the Neolithic diet would result in human bones being assigned radiocarbon dates that are older than the true age of the sample. An improved method of interpreting stable isotope data from bone collagen was therefore sought to address these questions of timing in the Scottish Mesolithic-Neolithic transition.
δ13C, δ15N and δ34S isotope analysis was employed on human and faunal bones from Mesolithic and Neolithic sites predominantly in Orkney and the west coast of Scotland. Isotope faunal baselines were supplemented, where appropriate, with modern faunal samples. The abundance of marine and terrestrial resources in the human diet was modelled using the Bayesian mixing model, FRUITS (food reconstruction using isotopic transferred signals). Where marine protein was detected in the human diet, the radiocarbon dates of these samples were calibrated using the mixed marine/terrestrial radiocarbon calibration curve and compared against previously calculated dates, where these were available.
It was possible to supplement marine faunal isotope baselines with modern marine samples; however, modern terrestrial samples were unsuitable analogues. δ34S was also found to be an unsuitable proxy for diet in this research. Small amounts of dietary marine protein were detected in the majority of Neolithic humans; however, marine consumption did not have a significant effect on the radiocarbon dates of these individuals. The key finding of this research was, therefore, that the transition from the Mesolithic lifestyle to the Neolithic in Scotland was a lengthy and gradual process, contributing to the debate regarding the nature of the transition. The chronology of the transition that has been previously established by radiocarbon dating is secure: while modelling the isotope data in FRUITS resulted, in most cases, in a greater age range in calibrated radiocarbon dates, they were not erroneously old, as initially predicted.


Introduction
Many archaeologists believe that our early ancestors used poison to kill or incapacitate their prey using commonly found plants. It is believed that the hunting tools were dipped into a paste of the plant material containing alkaloids or cardenolides which in turn was used to aid in the process of hunting. Until now, very little scientific evidence has been available to support this claim.
Aims
The aim of this project is to analyse arrow heads and other hunting tools from international museum collections, for the presence of plant poisons by mass spectrometry and hyphenated techniques. It is also to initially establish if it is possible to detect the plant alkaloids after thousands of years and to consider the implications of the findings in relation to sample preparation/interpretation of results.

Methods
Plant standards were provided by Alnwick Gardens, Northumberland. A sample of curare was provided by the Pitt Rivers Museum (Oxford). Swabs of archaeological hunting tools have been provided by the Museum of Archaeology & Anthropology (Cambridge), the Pitt Rivers Museum (Oxford), and the Museo Etnografico Pigorini of Roma (Italy). LC-MS or MS analysis was carried out on the extracts from the swabs in comparison to the plant standards.
Results
Results have shown that it is possible to detect aconite in a pot 125 years old as well as alkaloids of the Strychnos species on arrow heads and darts swabbed in the museums. Current work includes the analysis of an arrow dating from 4000 BC, provided by the Phoebe A Hearst Museum of Berkeley (USA). Even though items were from the same collection, plant poisons were not found on all items when the same preparation and analysis technique were used. No information was provided with regards to where the samples were originally found or with respect to storage/cleaning therefore it is possible that the items may have come into contact with other poisoned items in the museum.
Conclusion
It is possible to detect plant poisons on hunting tools using MS and hyphenated chromatographic techniques. This work continues in the analysis of other archaeological artefacts from international museums.


While the defensive function of glucosinolates is well established, their possible role as a nutrient reservoir is poorly understood and glucosinolate turnover pathways have not been elucidated. Previous research showed that glucosinolate content in germinating seeds of Arabidopsis thaliana Columbia-0 (Col-0) increases within the first two to four days on culture medium and then decreases below the level at day 0. In this study we used previously characterized T-DNA mutants to investigate if enzymes known to be involved in glucosinolate breakdown upon tissue damage affect the time course of glucosinolate content in germinating seeds. Besides dormant seeds, we analyzed seeds subjected to stratification in water for up to 72 h or germination on plates for up to ten days. Although seeds of tgg1 tgg2 (deficient in above-ground classical myrosinases) had higher glucosinolate levels than Col-0, the changes during germination were not different to those in seeds of Col-0. This demonstrates that TGG1/TGG2 are not responsible for the decline in glucosinolate content upon germination and suggests the involvement of other enzymes. Expression data extracted from publically available databases show a number of β-glucosidases of the BGLU18–BGLU33 clade to be expressed at specific time points of seed maturation and germination identifying them as good candidates for a role in glucosinolate turnover. Although nitrile-specifier proteins (NSPs) act downstream of myrosinases upon glucosinolate breakdown in tissue homogenates, mutants deficient in either seed-expressed NSP2 or seedling-expressed NSP1 were affected in glucosinolate content in seeds and during stratification or germination when compared to Col-0 indicating a direct role in turnover. The mutant lines nsp1-1, nsp2-1 and nsp2-2 had significantly higher glucosinolate levels in dry seeds than Col-0. After 24 h of stratification in water, nsp2-2 seeds contained 2.3 fold higher levels of glucosinolate than Col-0 seeds. This might indicate downregulation of hydrolytic enzymes when nitrile formation following glucosinolate hydrolysis is impaired. The time course of total glucosinolate content during ten days of germination depended on functional NSP1. Based on the present data, we propose a number of experiments that might aid in establishing the pathway(s) of glucosinolate turnover in germinating A. thaliana seeds.


Placement migration is a critical step to address a variety of post-placement design closure issues, such as timing, routing congestion, signal integrity, and heat distribution. To fix a design problem, one would like to perturb the design as little as possible while preserving the integrity of the original placement. This work presents a novel computational geometry based placement migration method, and a new stability metric to more accurately measure the "similarity" between two placements. It has two stages, a bin-based spreading at coarse scale and a Delaunay triangulation based spreading at finer grain. It has clear advantage over conventional legalization algorithms such that the neighborhood characteristics of the original placement are preserved. Thus, the placement migration is much more stable, which is important to maintain. Applying this technique to placement legalization demonstrates significant improvements in wire length and stability compared to other popular legalization algorithms.


Ecogeochemistry—the application of geochemical techniques to fundamental questions in population and community ecology—has been used in animal migration studies in terrestrial environments for several decades; however, the approach has received far less attention in marine systems. This review includes comprehensive meta‐analyses of organic zooplankton δ13C and δ15N values at the base of the food web, dissolved inorganic carbon δ13C values, and seawater δ18O values to create, for the first time, robust isoscapes for the Atlantic Ocean. These isoscapes present far greater geographic variability in multiple geochemical tracers than was previously thought, thus forming the foundation for reconstructions of habitat use and migration patterns of marine organisms. We review several additional tracers, including trace‐element‐to‐calcium ratios and heavy element stable isotopes, to examine anadromous migrations. We highlight the value of the ecogeochemistry approach by examining case studies on three components of connectivity: dispersal and natal homing, functional connectivity, and migratory connectivity. We also discuss recent advances in compound‐specific stable carbon and nitrogen isotope analyses for tracking animal movement. A better understanding of isotopic routing and fractionation factors, particularly of individual compound classes, is necessary to realize the full potential of ecogeochemistry.


Nonmelanoma skin cancer, including both squamous cell carcinoma and basal cell carcinoma, is a significant and increasing health problem in the United States. The precursor lesion of cutaneous squamous cell carcinoma, actinic keratosis (AK), is a major risk factor for nonmelanoma skin cancer, and it is also a marker of long-term sun exposure. AKs themselves can serve as biomarkers in chemopreventive studies, but in addition, they may contain phenotypic and genetic alterations that are related to the process of UV-induced skin carcinogenesis. One of these alterations, the tumor suppressor gene p53, is altered early in UV-induced skin carcinogenesis in humans. p53 protein expression was measured by immunohistochemistry in biopsies from AKs, tissue immediately adjacent to AKs (AK-adjacent), normal-appearing upper medial arm skin, and non-sun-exposed skin from 19 subjects. There was a significant difference and a progressively increasing mean p53 labeling index in total epidermis (basal and suprabasal layers) between upper medial arm skin (0.9 +/- 1.8%) and AK-adjacent (12.1 +/- 14.4%; P = 0.0004) and between AK (27.7 +/- 21.3%) and AK-adjacent skin (P = 0.04), whereas upper medial arm skin was marginally different from non-sun-exposed skin (0.1 +/- 0.2; P = 0.05). This pattern of p53 expression was also seen when epidermis was separated into basal and suprabasal layers. We conclude that epidermal p53 protein expression is associated with histological evidence of chronic sun damage.


Abstract In this study, the activation cross sections were, first, measured for the 144Sm(n,α)141mNd reaction at six different neutron energies from 13.57 to 14.83 MeV. The fast neutrons were produced by using a neutron generator, through the 3H(2H,n)4He reaction. The cyclic activation technique was used as the irradiation and counting method. Induced gamma activities were measured using a high-resolution gamma-ray spectrometer equipped with a high-purity germanium detector. In the cross-section measurements, corrections were made regarding the effects of gamma-ray attenuation, dead time, fluctuation of neutron flux, and low-energy neutrons. The measured cross sections were compared with the results of model calculations (TALYS code).


Amphioxus, or cephalochordates, are often used as the living invertebrate proxy of vertebrate ancestors and are widely used as evolutionary biology models of chordates. However, their phylogeny, divergence history, and speciation characteristics remain poorly understood, and phylogenomic studies to explore these problems lacking entirely from the literature. Here, we determined a new transcriptome of Branchiostoma japonicum. Combined with mass sequences of all other 18 species, a 19-way phylogeny was constructed via multiple methods (ML, BI, PhyloBayes, and ASTRAL), consistently supporting a phylogeny of [(B. belcheri + B. japonicum) + (B. lanceolatum + B. floridae) + Asymmetron lucayanum] in amphioxus. Congruent phylogenetic signals were found across mitochondrial genes, 12S RNA, and complete mitochondrial genomes according to previous reports, indicating that 12S RNA may have potential as a molecular marker for phylogenetic analysis in amphioxus. Molecular dating analysis indicated a radiation of the cephalochordates during the Cretaceous (∼104-61 million years ago), supporting an association between the diversification and speciation of cephalochordates with continental drift and associated changes in their respective habitats during this time. The identified functional enrichment analysis for species-specific domains indicated that their function mainly involves immune response, apoptosis, and lipid metabolism and utilization, signaling that pathogens and changes of energy requirements are an important driving force for amphioxus speciation. This study represents the first large-scale phylogenomic analysis of most major amphioxus genera based on phylogenomic data, providing a new perspective on both phylogeny and divergence speciation of cephalochordates.


Creatine kinase (CK) is considered the main phosphotransfer system in the heart, important for overcoming diffusion restrictions and regulating mitochondrial respiration. It is substrate limited in creatine-deficient mice lacking L-arginine:glycine amidinotransferase (AGAT) or guanidinoacetate methyltranferase (GAMT). Our aim was to determine the expression, activity and mitochondrial coupling of hexokinase (HK) and adenylate kinase (AK), as these represent alternative energy transfer systems. In permeabilized cardiomyocytes, we assessed how much endogenous ADP generated by HK, AK or CK stimulated mitochondrial respiration and how much was channeled to mitochondria. In whole heart homogenates, and cytosolic and mitochondrial fractions, we measured the activities of AK, CK and HK. Lastly, we assessed the expression of the major HK, AK and CK isoforms. Overall, respiration stimulated by HK, AK and CK was ~25, 90 and 80%, respectively, of the maximal respiration rate, and ~20, 0 and 25%, respectively, was channeled to the mitochondria. The activity, distribution and expression of HK, AK and CK did not change in GAMT KO mice. In AGAT KO mice, we found no changes in AK, but we found a higher HK activity in the mitochondrial fraction, greater expression of HK I, but a lower stimulation of respiration by HK. Our findings suggest that mouse hearts depend less on phosphotransfer systems to facilitate ADP flux across the mitochondrial membrane. In AGAT KO mice, which are a model of pure creatine-deficiency, the changes in HK may reflect changes in metabolism as well as influence mitochondrial regulation and reactive oxygen species production.


Observations have shown that the spatial distribution of satellite galaxies is not random, but aligned with the major axes of central galaxies. This alignment is dependent on galaxy properties, such that red satellites are more strongly aligned than blue satellites. Theoretical work conducted to interpret this phenomenon has found that it is due to the non-spherical nature of dark matter halos. However, most studies overpredict the alignment signal under the assumption that the central galaxy shape follows the shape of the host halo. It is also not clear whether the color dependence of alignment is due to an assembly bias or an evolution effect. In this paper we study these problems using a cosmological N-body simulation. Subhalos are used to trace the positions of satellite galaxies. It is found that the shapes of dark matter halos are mis-aligned at different radii. If the central galaxy shares the same shape as the inner host halo, then the alignment effect is weaker and agrees with observational data. However, it predicts almost no dependence of alignment on the color of satellite galaxies, though the late accreted subhalos show stronger alignment with the outer layer of the host halo than their early accreted counterparts. We find that this is due to the limitation of pure N-body simulations where satellite galaxies without associated subhalos ("orphan galaxies") are not resolved. These orphan (mostly red) satellites often reside in the inner region of host halos and should follow the shape of the host halo in the inner region.


The paper presents an original integrated MAC and routing scheme for wireless sensor networks. Our design objective is to elect the next hop for data forwarding by jointly minimizing the amount of signaling to complete a contention and maximizing the probability of electing the best candidate node. Towards this aim, we represent the suitability of a node to be the relay by means of locally calculated and generic cost metrics. Based on these costs, we analytically model the access selection problem through dynamic programming techniques, which we use to find the optimal access policy. Hence, we propose a contention-based MAC and forwarding technique, called cost and collision minimizing routing (CCMR). This scheme is then thoroughly validated and characterized through analysis, simulation and experimental results.


In order to support the future economic developments in the world, one of the most important objectives is the reduction of energy losses. Apart from this objective, hydropower dams which are considered a renewable energy source encounter this problem. Karun III Dam and Hydropower Plant is constructed on the Karun River in the province of Khuzestan, Iran, with a capacity of 2000 MW. The Dam is a double arch concrete type, 205m high from the foundation and 185m high from the river bed. In the present work by using the physical model of Karun III Dam and measuring pressures in all parts of conveyance members, energy losses for each part were calculated separately. Experiments were conducted in three different elevations and with maximum design discharge. By calculating the cavitation index along the related hydraulic structures, probability of cavitation was studied. Discharge coefficient was also estimated in the operation conditions. Experiments showed that when the reservoir elevation was increased in constant discharge; the discharge coefficient was increased respectively. Also it was observed that increasing the reservoir elevation causes head losses to increase in different parts of conveyance members except the antivortex structure which was installed at the top of the intake. Moreover, energy losses at the Y-Branch member were observed more than other parts.


How do you manage a conversation that you dread having? Many of us are confronted by scary conversations every day: standing up to a toxic boss who is verbally abusive, discussing a niggling problem with a close friend, talking to an interfering mother-in-law or confronting a controlling parent, to name but a few. And of course, everyone would rather avoid having them! Yet by putting off these conversations we often exacerbate the problem, or one day our emotions simply explode. In the process, we lose friends and jobs, damage our marriages and become estranged from family members. In this book, the author illustrates how to manage scary conversations so that you no longer need to fear them. Following tried-and-tested methods, she provides readers with real-life examples on which to model their own conversations, so that they will feel comfortable talking to anybody about almost anything.


Last decades observed a considerable increase of literature devoted to innovation-related studies. This area is characterized by fruitful interdisciplinary and there is not a single discipline that embraces all aspects of innovation. From the analysis of nearly 60.000 references, included in the 1442 articles published in the area' seed journal, we concluded that the Economics and Management of Innovation discipline presents a lower degree of autonomy as its dependency upon broader and core scientific areas such as Economics is rather high - about a third of the references were made to articles published in top (mainstream) journals of Economics. Nevertheless, the apparent large dependency on the mainstream, the most influential authors are associated with heterodox approaches, namely the evolutionary approach (e.g., Richard R. Nelson) and the European approach to innovation (e.g., Keith Pavitt and Chris Freeman).


Introduction: There are some reports suggesting a link between lead exposure and cardiovascular disease but understanding the contribution of lead to specific cardiovascular diseases has remained incompletely. Materials and Methods: In this case-control study, serum lead level in 30 patients with diagnosed coronary slow flow phenomenon (CSFP) documented by coronary angiography was evaluated and compared with the values of the control group containing 30 patients with normal coronary angiography. Results: Age, sex, major clinical risk factors for coronary artery disease, laboratory and echocardiographic parameters were similar in patients with and without CSFP (p > 0.05). Significant differences were found between the 2 study groups regarding serum lead level. Conclusion: Lead is a highly poisonous metal (whether inhaled or swallowed), affecting almost every organ and system in the body. Long-term exposure to lead can cause nephropathy and rise in blood pressure. We found it may also contribute to ischemic heart disease and CSFP. The suspected mechanism is oxidative stress and inflammation.


In studying orogenic processes, the mechanism of viscous Rayleigh-Taylor–type removal of gravitationally unstable lithosphere is often invoked to explain the behavior of the mantle lithosphere. Using numerical models, we consider this mechanism and explore alternate styles of deep lithospheric deformation during tectonic convergence. The numerical experiments incorporate a mix of viscous and plastic rheologies to model the mechanical evolution of the lithosphere-asthenosphere system. Our results suggest that there are a number of deformational modes of the model mantle lithosphere: (1) a dripping or Rayleigh-Taylor–type instability; (2) an asymmetric underthrusting or subduction; (3) symmetric, ablative plate consumption; (4) slab breakoff, the failure and detachment of the strong lithosphere; and (5) mixed modes with combinations of these processes. The development of the modes is controlled by the rate of convergence associated with the background tectonic regime, the density field, and the rheology of the mantle lithosphere. It is important to determine whether these modes occur in the Earth beneath collisional orogens.


Abstract Throughout his ten years of teaching writing and literature at the college level, the author observed with great interest the paralyzing effect that the lack of preparation in grammar has on students when they are given writing assignments. When students are challenged to express their thoughts in a more appropriate academic style, they generally show various responses to that challenge. Some students simply freeze and do not write at all; others express anger and frustration when their writing is "rejected" by the writing instructor. This essay emphasizes the importance of reconciling the teaching of grammar and genre to help students bring together two fundamental aspects of discourse: style and genre. By doing so, teachers of language and writing will help students go beyond a grammar of sentences and reach a grammar of discourse, which is traditionally referred to as discourse analysis. On Grammar and Writing In The Nuptials of Philology and Mercury, Martianus Capella, a rhetorician from Carthage, draws a nice allegorical picture of the seven liberal arts, which made his work highly attractive to the Middle Ages. According to Capella, at the nuptials of Philology and Mercury, the bride receives as a wedding gift the seven liberal arts personified as women. The first part of this gift is Grammar, represented as a severe old woman, carrying a knife and file with which to remove children's grammatical errors. The second item is Rhetoric, represented as a tall, beautiful woman, wearing a rich dress decorated with the figures of speech and carrying weapons with which to wound her adversaries (pp. 268-270). We encounter the same image in the work of Theodulphus of Orleans, who portrayed Grammar with a whip and shears to spur the lazy and to prune faults. When I first met my Traditional and Modern Grammars class at the University of Northern Colorado in 1997, the anxiety on the faces of the students made me almost feel that I was back in the times of Martianus Capella and Theodulphus of Orleans. The course that I was about to deliver was "a gift" from the academy, but it was certainly not a gift that the students looked forward to. This was a 200-level course, and yet most of the students who signed up for the class were juniors and seniors who stalled this course until the last semester in their career as college students. Grammar was definitely not a friendly course to take since it was associated with the idea of discipline and punishment. Many of them most likely learned some grammar at high school. It was almost equally certain that they were bored by it. The irony is that these students, most of whom were English majors with a liberal arts emphasis or an elementary and secondary school teaching emphasis, clearly constituted the new task force of teachers who would eventually spare school children the trouble of learning any grammar, because grammar was dropped from the curriculum and their students might well never know the difference between an adjective and a verb in their lives. Those very few students with keen interest in the study of grammar and discourse would have to go to departments of linguistics to learn about the structure of the English language. The word "grammar" derives from grammatike or grammatike techne, which in classical Greek meant "the art of writing." Grammaticus was considered a connoisseur of the word, the expression, and the form of discourse. From these definitions and from the story of Martianus Capella, we can draw a number of consequences, some of which have been thoroughly examined by linguists from different schools. Firstly, in a widely literate society such as ours, we are presented with the challenge of the primacy of writing over speech. Current spoken language, particularly in the academy, is subjected to the rules of traditional grammar. Secondly, written language is the language of education and power. Today, though all humans are virtually endowed with the faculty of speech, they still willingly or unwillingly acknowledge the power of writing. …


This study aimed to test a model that hypothesized that the compassionate coach, as perceived by the athletes, has an impact on athlete-related social safeness and psychological health, through shame and self-criticism. The sample comprised 270 Portuguese adult athletes, who practiced different competitive sports. The path analysis results confirmed the adequacy of the proposed model, which explained 45% of the psychological health's variance. Results demonstrated that athletes who perceive their coaches as more compassionate tend to present higher levels of social safeness (feelings of belonging to the team) and of psychological health, through lower levels of shame and self-criticism. These novel findings suggest the importance of the adoption of supportive, warm, safe, and compassionate attitudes from coaches in athletes' mental health. This study also offers important insights by suggesting that feelings of acceptance and connectedness in team relationships may be at the root of athletes' emotional processes and well-being.


The FibreMap project aims at the development of an automatic quality control and feedback mechanism to improve draping of carbon fibres on complex parts. There is a strong need in the automotive industry for automatic systems that perform quality control and improve draping processes in order to allow high production volumes. As illustrated in Fig. 1, the technology that is being developed in the project will include a new sensor system for robust detection of fibre orientation combined with a robotic system to scan complex parts. This is based on a new technology that uses reflection models of carbon fibre to solve the problems encountered with earlier vision-based approaches. The data coming from the inspection system will be fed into draping simulation to improve the accuracy of the processes. Draping is the process of placing woven carbon material on typically complex 3D parts (preforms) with the goal of having the fibres oriented along specific directions predicted by finite element calculations. This is done to maximize the strength-to-weight ratio of the part. There is a strong trend in the automotive industry towards lightweight parts to increase fuel efficiency, also considering the needs of electrical vehicles. Setting up the draping process for a complex part takes up to 50 preforms for trial-anderror improvements. Current production processes are thus not yet adequate to cover the expected volumes of several 100.000 parts per year. The project aims at shortening process development times by 90% and allowing automatic 100% quality control of fibre orientation. The industry-led consortium consists of European key partners in draping simulation, manufacturing of carbon parts for the automotive industry, sensor developers and robotic experts. It is complemented by a group of European car manufacturers that are linked to the project as associated partners. The FibreMap project started in September 2013 and it will last for three years.


We evaluated the effects of long-term daily cows' milk (CM) administration on insulin resistance induced by a high-sucrose diet. F344 rats, aged 3 weeks, were divided into two groups according to diet (dextrin-fed v. sucrose-fed). These groups were further divided into two groups receiving either CM or artificial milk (AM; isoenergetic emulsion of egg white protein, maltose, lard and minerals). Rats were fed a sucrose- or dextrin-based diet for 7 weeks and orally administered CM or AM at 25 ml/kg following an 8 h fast on a daily basis. Insulin sensitivity was evaluated via postprandial changes in serum glucose and insulin, oral glucose tolerance tests, and fasting serum insulin and fructosamine concentrations. The sucrose-fed rats showed an overall decrease in insulin sensitivity, but postprandial insulin levels were lower in the CM-treated subgroup than in the AM-treated subgroup. Peak serum glucose and insulin concentrations were highest in the sucrose-fed rats, but CM administration reduced peak glucose and insulin values in comparison with AM administration. By area under the curve analysis, insulin levels after feeding and glucose loads were significantly lower in the CM-treated groups than in the AM-treated groups. The CM-treated groups also demonstrated lower fasting insulin and fructosamine levels than the AM-treated groups. Improved insulin sensitivity due to CM administration seemed to be associated with reduced duodenal GLUT2 mRNA levels and increased propionate production within the caecum.


Discrete choice models are defined conditional to the analyst's knowledge of the actual choice set. The common practice for many years has been to assume that individual-based choice sets can be deterministically generated on the basis of the choice context and characteristics of the decision maker. This assumption is not valid or not applicable in many situations, and probabilistic choice set formation procedures must be considered. The constrained multinomial logit model (CMNL) has recently been proposed as a convenient way to deal with this issue, as it is also appropriate for models with a large choice set. In this paper, how well the implicit choice set generation of the CMNL approximates the explicit choice set generation is analyzed as described in earlier research. The results based on synthetic data show that the implicit choice set generation model may be a poor approximation of the explicit model.


Recommender Systems are software tools and techniques providing suggestions for items to be of use to a user. Context is providing information that can influence the perception of the usefulness of an item for a user. For this reason Recommender Systems must take into account this information to deliver more useful (perceived) recommendations. There are several examples motivating the importance of context for Recommender Systems. For instance, to suggest a meaningful travel to a user a Recommender System must know if the travel is scheduled in summer or winter, and if the user is traveling alone or with kids. Moreover, only considering the context of an evaluation -- the user rating for an item -- one can assign a proper meaning to that. For instance while one can judge a Ferrari a 5 star car; this does not mean that it is a proper recommendation if the user is looking for a new car to buy. Context modeling and context-dependent reasoning is a complex subject and still there are major technical and practical difficulties to solve: obtain sufficient and reliable data describing the user preferences in context; selecting the right context information, i.e., relevant in a particular personalization task; understanding the impact of the contextual dimensions on the personalization process; embedding the contextual dimensions in a recommendation computational model. Besides, Recommender Systems research should consider the wider scope of contextual computing, defined as the enhancement of the user's interactions by understanding the user, the context, and the applications and information being used, typically across a wide set of user goals. Actively adapting the computational environment -- for each user -- at each point of computation should be the ultimate goal. So, contextual computing for Recommender Systems must also focus on understanding the information consumption patterns of each user, and on the process not only on the output of the recommendation process.


In order to quantify the risk of pancreatic cancer associated with history of any allergy and specific allergies, to investigate differences in the association with risk according to age, gender, smoking status, or body mass index, and to study the influence of age at onset, we pooled data from 10 case-control studies. In total, there were 3,567 cases and 9,145 controls. Study-specific odds ratios and 95% confidence intervals were calculated by using unconditional logistic regression adjusted for age, gender, smoking status, and body mass index. Between-study heterogeneity was assessed by using the Cochran Q statistic. Study-specific odds ratios were pooled by using a random-effects model. The odds ratio for any allergy was 0.79 (95% confidence interval (CI): 0.62, 1.00) with heterogeneity among studies (P < 0.001). Heterogeneity was attributable to one study; with that study excluded, the pooled odds ratio was 0.73 (95% CI: 0.64, 0.84) (Pheterogeneity = 0.23). Hay fever (odds ratio = 0.74, 95% CI: 0.56, 0.96) and allergy to animals (odds ratio = 0.62, 95% CI: 0.41, 0.94) were related to lower risk, while there was no statistically significant association with other allergies or asthma. There were no major differences among subgroups defined by age, gender, smoking status, or body mass index. Older age at onset of allergies was slightly more protective than earlier age.


A polyuric syndrome with nephrogenic diabetes insipidus (NDI) is a frequent consequence of prolonged administration of lithium (Li) salts. Studies in the past, mainly the acute and in vitro experiments, indicated that Li ions can inhibit hydroosmotic effect of [8-arginine]vasopressin (AVP) at the step of cAMP generation in vitro. However, the pathogenesis of the NDI due to chronic oral administration of low therapeutic doses of Li salts is not yet clarified. We conducted a comprehensive study to clarify the mechanism by which Li administered orally for several weeks induces polyuria and NDI in rats. Albino rats consuming a diet which contained Li (60 mmol/kg) for 4 wk developed marked polyuria and polydipsia; at the end of 4 wk the plasma Li was 0.7 +/- 0.09 mM (mean +/- SEM; n = 36). Li-treated rats had a significantly decreased (-33%) tissue osmolality in papilla and greatly reduced cortico-papillary gradient of urea (cortex--43%; medulla--64%; papilla--74%). Plasma urea was significantly (P less than 0.001) lower in Li-treated rats (5.4 +/- 0.2 mM) compared with controls (6.8 +/- 0.3 mM). Medullary collecting tubules (MCT) and papillary collecting ducts (PCD) microdissected from Li-treated animals had higher content of protein than MCT and PCD from the control rats. The cAMP accumulation in response to AVP added in vitro was significantly (delta = -60%) reduced. Also, the cAMP accumulation in MCT and PCD after incubation with forskolin was markedly lower in Li-treated rats. Addition of 0.5 mM 1-methyl,3-isobutyl-xanthine did not restore the cAMP accumulation in response to AVP and forskolin in MCT from Li-treated animals. In collecting tubule segments from polyuric rats with hypothalamic diabetes insipidus (Brattleboro homozygotes) the AVP-dependent cAMP accumulation was not diminished. The activity of adenylate cyclase (AdC) in MCT of Li-treated rats, both the basal and the activity stimulated by AVP, forskolin, or fluoride, was significantly (delta approximately equal to -30%) reduced, while the activity of cAMP phosphodiesterase (cAMP-PDIE) in the same segment showed no significant difference from the controls. Also, the content of ATP in MCT microdissected from Li-treated rats and incubated in vitro did not differ from controls. The rate of [14C]succinate oxidation to 14CO2 in MAL was inhibited (-77%) by 1 mM furosemide, which indicates that this metabolic process is coupled with NaCl cotransport in MAL. The rate of (14)CO(2) production from [14C]succinate in MAL was not significantly different between control and Li-treated rats. In MCT of control rats, the rate of [14C]succinate oxidation was approximately 3 times lower than in MAL. The rate of (14)CO(2) production from [(14)C]succinate in MCT of Li-treated rats was significantly (delta +33%) higher than in MCT dissected from control rats. Based on these results, we conclude that at least two factors play an important role in the pathogenesis of NDI consequent to chronic oral administration of Li: (a) decreased ability of MCT and PCD to generate and accumulate cAMP in response to stimulation by AVP; this defect is primarily due to diminished activity of AdC in these tubular segments caused by prolonged exposure to Li; and (b) lower osmolality of renal papillary tissue, due to primarily to depletion of urea, which decreases osmotic driving force for water reabsorption in collecting tubules. On the other hand, NaCI reabsorption in MAL is apparently not affected by chronic Li treatment.


We have studied the void growth problem by employing the Taylor-based strain gradient plasticity theories, from which we have chosen the following three, namely, the mechanism-based strain gradient (MSG) plasticity (Gao et al 1999 J. Mech. Phys. Solids 47 1239, Huang et al 2000 J. Mech. Phys. Solids 48 99–128), the Taylor-based nonlocal theory (TNT; 2001 Gao and Huang 2001 Int. J. Solids Struct. 38 2615) and the conventional theory of MSG (CMSG; Huang et al 2004 Int. J. Plast. 20 753). We have addressed the following three issues which occur when plastic deformation at the void surface is unconstrained. (1) Effects of elastic deformation. Elasticity is essential for cavitation instability. It is therefore important to guarantee that the gradient term entering the Taylor model is the effective plastic strain gradient instead of the total strain gradient. We propose a simple elastic–plastic decomposition method. When the void size approaches the minimum allowable initial void size related to the maximum allowable geometrically necessary dislocation density, overestimation of the flow stress due to the negligence of the elastic strain gradient is on the order of near the void surface, where l, εY and R0 are, respectively, the intrinsic material length scale, the yield strain and the initial void radius. (2) MSG intrinsic inconsistency, which was initially mentioned in Gao et al (1999 J. Mech. Phys. Solids 47 1239) but has not been the topic of follow-up studies. We realize that MSG higher-order stress arises due to the linear-strain-field approximation within the mesoscale cell with a nonzero size, lε. Simple analysis shows that within an MSG mesoscale cell near the void surface, the difference between microscale and mesoscale strains is on the order of , indicating that when , the higher-order stress effect can make the MSG result considerably different from the TNT or CMSG results. (3) Critical condition for cavitation instability. When Taylor plasticity replaces classical plasticity as the flow rule, the critical cavitation condition, appearing when the derivative of the externally imposed mean stress with respect to the current void radius becomes zero, is rewritten analytically according to the Leibniz relation and found to be very different from the classical counterpart.


A wide range of studies find that democracies experience more terrorism than non-democracies. However, surprisingly little terrorism research takes into account the variation among democracies in terms of their electoral institutions. Furthermore, despite much discussion of the differences in terrorist groups' goals in the literature, little quantitative work distinguishes among groups with different goals, and none explores whether and how the influence of electoral institutions varies among groups with different goals. The argument in this article posits that electoral institutions influence the emergence of within-system groups, which seek policy changes, but do not influence the emergence of anti-system groups, which seek a complete overthrow of the existing regime and government. The study finds that within-system groups are significantly less likely to emerge in democracies that have a proportional representation system and higher levels of district magnitude, while neither of these factors affects the emergence of anti-system groups.


Petrol consumption has become one of the most important sustainability issues for Australia. The central contention in this article is whether Australia's current Fringe Benefits Tax (FBT) regime is promoting unnecessary mileage (and use of petrol) in salary packaged vehicles to obtain tax concessions under the FBT "statutory formula method" for cars. This article draws together the results of FBT survey data collected via a questionnaire and from respondents' websites, which has been analysed by the authors. The evidence assembled generally supports the central contention. We have also reviewed and included commentary on similar studies that support our key claim. The findings are important because the questionnaire responses represent a significant sample. The outcomes of our research provide further support for a call to amend the current FBT legislation and therefore foster more environmentally sustainable car salary packaging polices for Australian business.


This paper explores the complexity of engaging undergraduate student designers with sustainability in the master and apprentice model of the design studio. There is a growing call for design practice to reorientate towards a more sustainable form and it is suggested that design educators have a responsibility in driving this shift. A four-year action research project enquired as to why undergraduate industrial design students could not Design for Sustainability (DfS). Interventions were identified and implemented to address this concern. These were: (1.) increasing students' understanding of unsustainability and its relational complexity, and (2.) improving student engagement by focusing on the pedagogy of deep learning. Deep learning almost mirrors the problem based learning model of the design studio. However in practice, realising deep learning as the desired pedagogy required critical reflection from the educator to introduce a student centred approach to teaching. The paper then locates these findings amongst broader educational and industrial design education for sustainability literature. This exposes the juxtaposition of the studio as a place where the teacher-as-researcher can actively integrate progressive DfS concepts, however, leaves the studio susceptible to the troubling question of what happens when the master does not know?


ABSTRACT Previously, we defined a novel class of ligands for the human progesterone receptor (PR) which function as mixed agonists. These compounds induce a conformational change upon binding the receptor that is different from those induced by agonists and antagonists. This establishes a correlation between the structure of a ligand-receptor complex and its transcriptional activity. In an attempt to define the cellular components which distinguish between different ligand-induced PR conformations, we have determined, by using a mammalian two-hybrid assay, that the nuclear receptor corepressor (NCoR) and the silencing mediator for retinoid and thyroid hormone receptor (SMRT) differentially associate with PR depending upon the class of ligand bound to the receptor. Specifically, we observed that the corepressors preferentially associate with antagonist-occupied PR and that overexpression of these corepressors suppresses the partial agonist activity of antagonist-occupied PR. Binding studies performed in vitro, however, reveal that recombinant SMRT can interact with PR in a manner which is not influenced by the nature of the bound ligand. Thus, the inability of SMRT or NCoR to interact with agonist-activated PR when assayed in vivo may relate more to the increased affinity of PR for coactivators, with a subsequent displacement of corepressors, than to an inherent low affinity for the corepressor proteins. Previous work from other groups has shown that 8-bromo-cyclic AMP (8-bromo-cAMP) can convert the PR antagonist RU486 into an agonist and, additionally, can potentiate the transcriptional activity of agonist-bound PR. In this study, we show that exogenous expression of NCoR or SMRT suppresses all 8-bromo-cAMP-mediated potentiation of PR transcriptional activity. Further analysis revealed that 8-bromo-cAMP addition decreases the association of NCoR and SMRT with PR. Thus, we propose that 8-bromo-cAMP-mediated potentiation of PR transcriptional activity is due, at least in part, to a disruption of the interaction between PR and the corepressors NCoR and SMRT. Cumulatively, these results suggest that NCoR and SMRT expression may play a pivotal role in PR pharmacology.


The distribution of anaphoric pronouns in prepositional phrases has garnered much attention in the literature on antecedent binding since, contrary to fundamental binding principles, this syntactic environment appears to allow either reflexive or coreferential nonreflexive pronouns (c.f. Safir 2004; Reinhart a Reuland 1993; Pollard and Sag 1992). This paper takes a closer look at two prepositional phrase contexts in English and Norwegian, which seem to allow the reflexive pronoun when the PP superficially denotes directionality. With careful examination of the semantics of these constructions, it is shown that a vague notion of directionality evoked in the formal syntax notion of the functional projection PATH is insuffi cient to capture the data's distribution pattern. The grammar must make reference to more detailed spatial configurations in order to model the real-world examples.


Although scholarly interest in available "alternatives" to early modern London theater has recently grown, a focused examination of their relation to Shakespeare has been somewhat absent. Beginning with the position that London's "entertainment industry" invites a perspective on Shakespeare's theater which is not dismissive of these entertainments but sees them as integral to and indices of pleasure-production of the time, this seminar aims to redress the existing scholarly gap. Seminar papers may examine single entertainments (such as bear-baiting, gambling, sports, hearing sermons, drinking, fairs, or other activities), or elements of them in representations or allusions, or they may address the complex theoretical relationship between this culture and Shakespeare's work. Central questions may include these: what similar or different aesthetics were available in London's wider entertainment offerings? In what ways was Shakespeare's work informed by or even in competition with these entertainments? What entertainments did Shakespeare depict, how were they inserted, and to what ends? What was the audience reception of these, either as original recreations or in their secondary representations by Shakespeare? What is gained or lost in Shakespeare's "translation" of them? What sorts of pleasures did they embody for Shakespeare, whether disorderly and "low," or licit and "higher"?


Purpose: The aim of the current study was to assess the accuracy of the Polar M430 fitness watch for the measurement of heart rate (HR) and energy expenditure (EE) during low, moderate, and high intensity treadmill exercise. Methods: Twenty subjects (males, n = 12; Age: 24.2 ± 2.41 yrs., Height: 175.7 ± 6.85 cm, Weight: 88.1 ± 13.02 kg; BMI: 28.44 ± 2.90 kg/m) (females, n = 8; Age: 22.5 ± 2.98 yrs., Height: 171.9 ± 4.48 cm, Weight: 73.3 ± 9.10 kg; BMI: 24.81 ± 3.00 kg/m) completed a single bout of exercise on a treadmill at three incremental intensities using self-selected ratings of perceived exertion (RPE) derived workloads at RPE 11 (low intensity), RPE 13 (moderate intensity), and RPE 15 (high intensity), respectively. Each workload was 5-minutes in duration and subjects wore a PolarM430 watch throughout the entire protocol. An electrocardiogram (ECG) and indirect calorimetry were used as criterion measures of HR and EE, respectively. Two-way ANOVA with repeated measures was used to examine differences in HR and EE between the PolarM430 and criterion measures. Pairwise comparisons were made using Tukey's post-hoc tests. Intraclass correlation coefficients were used to examine the relationship between HR and EE. Data are presented as mean ± 95% confidence intervals. Results: The PolarM430 significantly underestimated HR at RPE 15 -3.20 (-5.00, -1.40) bpm. ICC analysis indicated an excellent level of agreement between the PolarM430 and criterion measures for HR (ICC =.96-.99). The PolarM430 significantly underestimated EE by -19.25 (-14.77, -3.37) kcals (14.9%) at RPE 15 and -10.5 (-20.09, -0.91) kcals (-8.78%) throughout the entire testing protocol. ICC analysis indicated a moderate to good level of agreement (ICC = .66-.89) for EE. Conclusions: Based on these results, it appears the Polar M430 fitness watch is an accurate tool to measure HR at low to moderate exercise intensities, but may underestimate HR at higher exercise intensities. The PolarM430 watch appears to be an accurate tool to measure EE during low and moderate intensity exercise, but may underestimate EE at higher exercise intensities, as well as over the course of an entire bout of exercise.


In the post-digital, heterotopic society, human activities have transcended the limiting confines of physical space. The prevailing urban/architectural philosophies that defined programmed spaces by material enclosures and boundaries are less relevant when information, programs and activities transpire independent of such physical fields. Thus, architecture needs to address this emerging paradigm by conceiving new types of traversable spaces. This design thesis develops the use of electroacoustic techniques to generate immaterial sonic enclosures that allow unhindered penetration of light and matter, while blocking out sound within a strepitous environment. Sound is explored as a material for constructing interconnected spaces without physical boundaries. Through the use of the proposed Virtual Sonic Enclosures (VSE), this thesis aims to provide a weak infrastructure rather than an 'object' such as a building to facilitate the seamless networking of spaces and programs to generate new architectural possibilities that reflect contemporary conditions.


Korean teachers are generally considered well trained to integrate ICT into their teaching since the inception of the first IT Master Plan of Korea in 1996. However, the emergence and adoption of cutting-edge technologies create demands for evolving roles and competencies of teachers in the new knowledge society. Given this changing landscape of teacher education, the purpose of this paper is to explore new educational approaches to enhance teachers' ICT capabilities in the 21st century learning environment in Korea. The literature indicates that the new roles of teachers include new media literacy skills and adaptive expertise with efficiency and innovation. From this perspective, we examined three cases: (1) learning Scratch for computational and creative thinking, (2) learning robotics as emerging technology for convergent and divergent thinking, and (3) learning by design with ICT for systems thinking. The new approaches, such as focusing on thinking skills rather than technical skills, and providing various contexts different from ordinary classroom lessons, help teachers to develop adaptive expertise. On the other hand, participants in all three cases indicated difficulties in integrating new ideas, dealing with various course activities, and understanding unfamiliar design contexts in their comprehensive projects. For further studies, it is necessary to investigate learning processes and outcomes of teachers' learning with more depth and a larger number of cases and multiple sources of data to verify the potentials and challenges of these approaches more rigorously.


Tractive-force distribution in open channels are derived with the aid of simplifying assumptions that reduce the turbulent flow problem to the computer solution of laminar flow equations. Boundary drag and other effects, caused by restraint of the turbulent fluctuations at the wall and the free surface, are considered to originate two superimposed laminar velocity distributions on the same flow. Two laminar flow cases are solved; (1) The usual laminar open channel case, and (2) a closed channel, or pipe, having the same cross-sectional shape as the open channel. The two solutions are superimposed to obtain the final velocity distribution from which the tractive-force distribution is derived. The relative influence of the two solutions on the final velocity distribution is determined experimentally based on channel geometry and roughness. It is assumed that the relative tractive force distributions for these laminar-type flows are similar.


It is well recognized that the proliferation of vascular smooth muscle cells (VSMCs) is a key event in the pathogenesis of various vascular diseases, including atherosclerosis and hypertension. It is generally considered that the phosphorylation/dephosphorylation reactions of a variety of enzymes belonging to the family of mitogen-activated protein kinases (MAPKs) play an important role in the transduction of mitogenic signal. We have previously shown that among extracellular signal-regulated protein kinases (ERKs), the 42 and 44 kDa isoforms (ERK1/2) participate in the cellular mitogenic machinery triggered by several VSMCs activators, including thrombin. ERK1/2 activation by G-protein-coupled receptors (GPCRs) has been shown to be Ca2+-dependent and to require the transactivation of epidermal growth factor receptor (EGFR). In addition, it is generally admitted that variations of the intracellular Ca2+ concentration ([Ca2+] i) play an important role in the transduction of mitogenic signal. Recently, we have shown that in thrombin-stimulated VSMCs, EGFR-independent activation of ERK1/2 activation could occur when agonist-induced ([Ca2+] i) elevation was reduced. This review examines recent findings in ERK1/2 signaling pathway that have been identified as critically important mediator of VSMCs hypertrophy and vascular diseases. Future investigations should now focus on the mechanisms of MAPK activation which might therefore represent a new mechanism involved in the antiproliferative effect revealed in this review.


Coronaviruses are sharing several protein regions notable the spike protein (S) on their enveloped membrane surface, with the S1 subunit recognizing and binding to the cellular receptor, while the S2 subunit mediates viral and cellular membrane fusion. This similarity opens the question whether infection with one coronavirus will confer resistance to other coronaviruses? Investigating patient serum samples after SARS-CoV-2 infection in cross-reactivity studies of immunogenic peptides from Middle East respiratory syndrome coronavirus (MERS-CoV), we were able to detect the production of antibodies also recognizing MERS virus antigens. The cross-reactive peptide comes from the heptad repeat 2 (HR2) domain of the MERS virus spike protein. Indeed, the peptide of the HR2 domain of the MERS spike protein, previously proven to induce antibodies against MERS-CoV is sharing 74% homology with the corresponding sequence of SARS-CoV-19 virus. Sera samples of 47 convalescent SARS-CoV-2 patients, validated by RT-PCR-negative testes 30 days post-infection, and samples of 40 sera of control patients (not infected with SARS-CoV-2 previously) were used to establish eventual cross-bind reactivity with the MERS peptide antigen. Significantly stronger binding (p<0.0001) was observed for IgG antibodies in convalescent SARS-CoV-2 patients compared to the control group. If used as an antigen, the peptide of the HR2 domain of the MERS spike protein allows discrimination between post-Covid populations from non-infected ones by the presence of antibodies in blood samples. This suggests that polyclonal antibodies established during SARS-CoV-2 infection has the ability to recognize and probably decrease infectiveness of MERS-CoV infections as well as other coronaviruses. The high homology of the spike protein domain suggests in addition that the opposite effect can also be true: coronaviral infections producing cross-reactive antibodies affective against SARS-CoV-19. The collected data prove in addition that despite the core HR2 region being hidden in the native viral conformation, its exposure during cell entry makes it highly immunogenic. Since inhibitory peptides to this region were previously described, this opens new possibilities in fighting coronaviral infections.


Philosophers have postulated the existence of God to explain (I) why any contingent objects exist at all rather than nothing contingent, and (II) why the fundamental laws of nature and basic facts of the world are exactly what they are. Therefore, we ask: (a) Does (I) pose a well-conceived question which calls for an answer? and (b) Can God's presumed will (or intention) provide a cogent explanation of the basic laws and facts of the world, as claimed by (II)? We shall address both (a) and (b). To the extent that they yield an unfavourable verdict, the afore-stated reasons for postulating the existence of God are undermined. As for question (I), in 1714, G. W. Leibniz posed the Primordial Existential Question (hereafter 'PEQ'): 'Why is there something contingent at all, rather than just nothing contingent?' This question has two major presuppositions: (1) A state of affairs in which nothing contingent exists is indeed genuinely possible ('the Null Possibility'), the notion of nothingness being both intelligible and free from contradiction; and (2) De jure, there should be nothing contingent at all, and indeed there would be nothing contingent in the absence of an overriding external cause (or reason), because that state of affairs is 'most natural' or 'normal'. The putative world containing nothing contingent is the so-called 'Null World'. As for (1), the logical robustness of the Null Possibility of there being nothing contingent needs to be demonstrated. But even if the Null Possibility is demonstrably genuine, there is an issue: Does that possibility require us to explain why it is not actualized by the Null World, which contains nothing contingent? And, as for (2), it originated as a corollary of the distinctly Christian precept (going back to the second century) that the very existence of any and every contingent entity is utterly dependent on God at any and all times. Like (1), (2) calls for scrutiny. Clearly, if either of these presuppositions of Leibniz's PEQ is ill founded or demonstrably false, then PEQ is aborted as a non-starter, because in that case, it is posing an ill-conceived question. In earlier writings (Grünbaum [2000], p. 5), I have introduced the designation 'SoN' for the ontological 'spontaneity of nothingness' asserted in presupposition (2) of PEQ. Clearly, in response to PEQ, (2) can be challenged by asking the counter-question, 'But why should there be nothing contingent, rather than something contingent?' Leibniz offered an a priori argument for SoN. Yet it will emerge that a priori defences of it fail, and that it has no empirical legitimacy either. Indeed physical cosmology spells an important relevant moral: As against any a priori dictum on what is the 'natural' status of the universe, the verdict on that status depends crucially on empirical evidence. Thus PEQ turns out to be a non-starter, because its presupposed SoN is ill founded! Hence PEQ cannot serve as a springboard for creationist theism. Yet Leibniz and the English theist Richard Swinburne offered divine creation ex nihilo as their answer to the ill-conceived PEQ. But being predicated on SoN, their cosmological arguments for the existence of God are fundamentally unsuccessful. The axiomatically topmost laws of nature (the 'nomology') in a scientific theory are themselves unexplained explainors, and are thus thought to be true as a matter of brute fact. But theists have offered a theological explanation of the specifics of these laws as having been willed or intended by God in the mode of agent causation to be exactly what they are. A whole array of considerations are offered in Section 2 to show that the proposed theistic explanation of the nomology fails multiply to transform scientific brute facts into specifically explained regularities. Thus, I argue for The Poverty of Theistic Cosmology in two major respects. 1. Why is there something rather than nothing? 1.1 Refined statement of Leibniz's Primordial Existential Question (PEQ) 1.2 Is it imperative to explain why there isn't just nothing contingent? 1.3 Must we explain why any and every de facto unrealized logical possibility is not actualized? 1.4 Is a world not containing anything contingent logically possible? 1.5 Christian doctrine as an inspiration of PEQ 1.6 Henri Bergson 1.7 A priori justifications of PEQ by Leibniz, Parfit, Swinburne and Nozick 1.7.1 Leibniz 1.7.2 Derek Parfit 1.7.3 Richard Swinburne and Thomas Aquinas vis-à-vis SoN 1.7.4 The 'natural' status of the world as an empirical question 1.7.5 Robert Nozick 1.8 Hypothesized psychological sources of PEQ 1.9 PEQ as a failed springboard for creationist theism: the collapse of Leibniz's and Swinburne's theistic cosmological arguments2. Do the most fundamental laws of nature require a theistic explanation? 2.1 The ontological inseparability of the laws of nature from the furniture of the universe 2.2 The probative burden of the theological explanation of the world's nomology 2.3 The theistic explanation of the cosmic nomology 2.4 Further major defects of the theological explanation of the fundamental laws of nature3. Conclusion Why is there something rather than nothing? 1.1 Refined statement of Leibniz's Primordial Existential Question (PEQ) 1.2 Is it imperative to explain why there isn't just nothing contingent? 1.3 Must we explain why any and every de facto unrealized logical possibility is not actualized? 1.4 Is a world not containing anything contingent logically possible? 1.5 Christian doctrine as an inspiration of PEQ 1.6 Henri Bergson 1.7 A priori justifications of PEQ by Leibniz, Parfit, Swinburne and Nozick 1.7.1 Leibniz 1.7.2 Derek Parfit 1.7.3 Richard Swinburne and Thomas Aquinas vis-à-vis SoN 1.7.4 The 'natural' status of the world as an empirical question 1.7.5 Robert Nozick 1.8 Hypothesized psychological sources of PEQ 1.9 PEQ as a failed springboard for creationist theism: the collapse of Leibniz's and Swinburne's theistic cosmological arguments 1.1 Refined statement of Leibniz's Primordial Existential Question (PEQ) 1.2 Is it imperative to explain why there isn't just nothing contingent? 1.3 Must we explain why any and every de facto unrealized logical possibility is not actualized? 1.4 Is a world not containing anything contingent logically possible? 1.5 Christian doctrine as an inspiration of PEQ 1.6 Henri Bergson 1.7 A priori justifications of PEQ by Leibniz, Parfit, Swinburne and Nozick 1.7.1 Leibniz 1.7.2 Derek Parfit 1.7.3 Richard Swinburne and Thomas Aquinas vis-à-vis SoN 1.7.4 The 'natural' status of the world as an empirical question 1.7.5 Robert Nozick 1.7.1 Leibniz 1.7.2 Derek Parfit 1.7.3 Richard Swinburne and Thomas Aquinas vis-à-vis SoN 1.7.4 The 'natural' status of the world as an empirical question 1.7.5 Robert Nozick 1.8 Hypothesized psychological sources of PEQ 1.9 PEQ as a failed springboard for creationist theism: the collapse of Leibniz's and Swinburne's theistic cosmological arguments Do the most fundamental laws of nature require a theistic explanation? 2.1 The ontological inseparability of the laws of nature from the furniture of the universe 2.2 The probative burden of the theological explanation of the world's nomology 2.3 The theistic explanation of the cosmic nomology 2.4 Further major defects of the theological explanation of the fundamental laws of nature 2.1 The ontological inseparability of the laws of nature from the furniture of the universe 2.2 The probative burden of the theological explanation of the world's nomology 2.3 The theistic explanation of the cosmic nomology 2.4 Further major defects of the theological explanation of the fundamental laws of nature Conclusion