Variations in the genetic code, from single point mutations to large structural or copy number alterations, influence susceptibility, onset, and progression of genetic diseases and tumor transformation. Next-generation sequencing analyses are unable to reliably capture aberrations larger than the typical sequencing read length of several hundred bases. Long-read, single-molecule sequencing methods such as SMRT and nanopore sequencing can address larger variations, but require costly whole genome analysis. Here we describe a method for isolation and enrichment of a large genomic region of interest for targeted analysis based on Cas9 excision of two sites flanking the target region and isolation of the excised DNA segment by pulsed field gel electrophoresis. The isolated target remains intact and is ideally suited for optical genome mapping and long-read sequencing at high coverage. In addition, analysis is performed directly on native genomic DNA that retains genetic and epigenetic composition without amplification bias. This method enables detection of mutations and structural variants as well as detailed analysis by generation of hybrid scaffolds composed of optical maps and sequencing data at a fraction of the cost of whole genome sequencing.


The career of Professor Eric F. Wood has focused on the resolution of problems of scale in hydrologic systems. Within this context, we consider an evolving approach known as the thermodynamically constrained averaging theory (TCAT), which has broad applicability to hydrology. We consider the case of modeling of two-fluid-phase flow in porous media, and we focus on issues of scale as they relate to various measures of pressure, capillary pressure, and state equations needed to produce solvable models. We apply TCAT to perform physics-based data assimilation to understand how the internal behavior influ5 ences the macroscale state of two-fluid porous medium systems. A microfluidic experimental method and a lattice Boltzmann simulation method are used to examine a key deficiency associated with standard approaches. In a hydrologic process such as evaporation, the water content will ultimately be reduced below the so-called irreducible wetting phase saturation determined from experiments. This is problematic since the derived closure relationships cannot predict the associated capillary pressures for these states. We demonstrate that the irreducible wetting-phase saturation is an artifact of the experimental design, caused 10 by the fact that the boundary pressure difference does not approximate the true capillary pressure. Using averaging methods, we compute the true capillary pressure for fluid configurations at and below the irreducible wetting phase saturation. Results of our analysis include a state function for the capillary pressure expressed as a function of fluid saturation and interfacial area.


Atmospheric deposition of trace elements and isotopes (TEI) is an important source of trace metals to the open ocean, impacting TEI budgets and distributions, stimulating oceanic primary productivity, and influencing biological community structure and function. Thus, accurate sampling of aerosol TEIs is a vital component of ongoing GEOTRACES cruises, and standardized aerosol TEI sampling and analysis procedures allow the comparison of data from different sites and investigators. Here, we report the results of an aerosol analysis intercalibration study by seventeen laboratories for select GEOTRACES‐relevant aerosol species (Al, Fe, Ti, V, Zn, Pb, Hg, NO3−, and SO42−) for samples collected in September 2008. The collection equipment and filter substrates are appropriate for the GEOTRACES program, as evidenced by low blanks and detection limits relative to analyte concentrations. Analysis of bulk aerosol sample replicates were in better agreement when the processing protocol was constrained (± 9% RSD or better on replicate analyses by a single lab, n = 7) than when it was not (generally 20% RSD or worse among laboratories using different methodologies), suggesting that the observed variability was mainly due to methodological differences rather than sample heterogeneity. Much greater variability was observed for fractional solubility of aerosol trace elements and major anions, due to differing extraction methods. Accuracy is difficult to establish without an SRM representative of aerosols, and we are developing an SRM for this purpose. Based on these findings, we provide recommendations for the GEOTRACES program to establish consistent and reliable procedures for the collection and analysis of aerosol samples.


Eleven years after it was first mooted in 1996, the Criminal Law (Sexual Offences and Related Matters) Amendment Act (32 of 2007) came into effect in December 2007. Law-makers proudly lauded sections 28 and 29 of the Act, which set out how post-exposure prophylaxis (PEP) to prevent HIV infection should be made available to rape survivors. These clauses are, however, neither particularly novel nor innovative, Cabinet having already approved (in April 2002) the provision of antiretroviral drugs to prevent HIV infection following rape.
Subsequent to Cabinet's decision, a few studies were conducted examining various facets of providing PEP as part of a health response to rape. In theory, these findings should have provided legislators with some insight into what was required by rape survivors from a PEP service, particularly in relation to psycho-social support. This was not the case, as we will show in this article, which draws on unpublished findings from 67 interviews with rape survivors exploring their adherence to PEP.


Yogurts flavored with instant coffee (0.5, 0.7 and 0.9%) and sweetened with sugar (4 or 5%) and a control yogurt (no coffee or sugar) were evaluated for chemical, physical, microbiological and sensory properties. The added ingredients generally had no effect on the chemical, physical and microbiological quality of yogurts at day 1 after preparation as compared to the control. During 15 days at 5-7C, pH and lactic acid bacteria counts decreased (P < 0.05) and titratable acidity increased (P < 0.05) in all samples. Yogurts with 0.5% coffee flavoring and 4 and 5% sugar met Turkish Institute Standards for yogurt sensory quality when evaluated by a trained 10-member panel. Yogurt flavored with 0.5% coffee and containing 5% sugar had most attributes rated in the "like" category by 50% or more of 51 consumer panelists.


Background: Inflammation is hypothesized to play a role in colorectal tumorigenesis. Circulating levels of C-reactive protein (CRP), a serologic marker of the inflammatory response, have been positively associated with colorectal cancer development in some studies; however, there are limited data on the relation of CRP with colorectal adenomas, established precursors of colorectal cancer. Methods: A nested case–control investigation of CRP levels and incident colorectal adenoma was conducted in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, a randomized trial of 154,942 individuals designed to test the efficacy of flexible sigmoidoscopy on colorectal cancer mortality when performed once, and then repeated 3 to 5 years later. Serum CRP levels were measured in baseline blood specimens from participants who were free of polyps in the left-sided colorectum at the baseline screening procedure, but who were found at the subsequent screen to have at least one colorectal adenoma (n = 356), and in a set of polyp-free, frequency-matched controls (n = 396). Results: In a multivariable logistic regression model that included established colorectal adenoma risk factors, a 1-unit increase in log CRP level was associated with a 15% reduction in risk of developing colorectal adenoma (OR = 0.85, 95% CI, 0.75–0.98, Ptrend = 0.01). This association did not differ according to body size, smoking behavior, gender, use of nonsteroidal antiinflammatory drugs, or adenoma location. Conclusions: High circulating CRP levels may be protective against colorectal adenoma development. Impact: Though at contrast with mechanistic data on inflammation and colorectal tumorigenesis, this finding is not inconsistent with prior results on CRP and colorectal adenoma and warrants further investigation. Cancer Epidemiol Biomarkers Prev; 20(3); 537–44. ©2011 AACR.


We propose an integrated all-optical switch with a low operating power that allows continuous wave operation. To achieve switching in an efficient way, we use the free carrier dispersion effect in a III-V multi-quantum well layer bonded on a Silicon on Insulator ring resonator. Using Mach-Zehnder interferometers for coupling light in and out the ring, we theoretically show that switching with an extinction ratio of 10dB at a pump power of only 300μW is achievable.


Pretreatment of straw separated from cattle and horse manure using N-methylmorpholine oxide (NMMO) was investigated. The pretreatment conditions were for 5 h and 15 h at 120 °C, and the effects were evaluated by batch digestion assays. Untreated cattle and horse manure, both mixed with straw, resulted in 0.250 and 0.279 Nm3 CH4/kgVS (volatile solids), respectively. Pretreatment with NMMO improved both the methane yield and the degradation rate of these substrates, and the effects were further amplified with more pretreatment time. Pretreatment for 15 h resulted in an increase of methane yield by 53% and 51% for cattle and horse manure, respectively. The specific rate constant, k0, was increased from 0.041 to 0.072 (d-1) for the cattle and from 0.071 to 0.086 (d-1) for the horse manure. Analysis of the pretreated straw shows that the structural lignin content decreased by approximately 10% for both samples and the carbohydrate content increased by 13% for the straw separated from the cattle and by 9% for that separated from the horse manure. The crystallinity of straw samples analyzed by FTIR show a decrease with increased time of NMMO pretreatment.


In certain five dimensional gauge theories compactified on the orbifold $S^1/Z_2$ the Standard Model Higgs doublet is identified with the zero mode of the fifth component of the gauge field. This gauge-Higgs unification scenario is realized at high energies, and the Standard Model as an effective theory below the compactification scale satisfies the boundary condition that the Higgs quartic coupling vanishes at the compactification scale (gauge-Higgs condition). This is because at energies above the compactification scale, the five dimensional gauge invariance is restored and the Higgs potential vanishes as a consequence. We consider scenario where top quark Yukawa and weak gauge coupling unification can be realized and identify the compactification scale as one at which this two coupling couplings have the same value. Taking into account the experimental uncertainties in measurements of the top quark mass and the QCD coupling constant, the Higgs mass prediction of 119-126 GeV from the gauge-Higgs unification scenario is consistent with the experimentally measured value of 125-126 GeV. More precise measurements of the top quark mass and the QCD coupling constant are crucial to reduce the interval of the Higgs mass prediction and thereby test the feasibility of the gauge-Higgs unification scenario.


Columbus crabs, Planes minutus (L.) (Crustacea: Brachyura) are often found on the postero-ventral surfaces of sea turtles, particularly the loggerhead Caretta caretta (L.) (Testudines: Cheloniidae). There has been a general acceptance of a hypothesis that the crabs feed upon turtle faeces. However, evidence is presented here to demonstrate that Planes has a 'cleaning' role, feeding on other epibionts (e.g. barnacle cyprids, parasitic amphipods) during daylight hours. At night it is likely that the crabs feed on neustonic animals (e.g. euphausids). The species is also cannibalistic.


Trade unions face multiple challenges at the beginning of the twenty-first century, including increased inward migration. The accession of eight countries from Central and Eastern Europe to the EU in 2004 in particular has created a new dynamic of labour migration in Europe, sometimes raising concerns about social dumping and a 'race to the bottom'. In the context of the weakening of organised labour, the deregulation of national labour markets and the spread of rather precarious employment relationships, including irregular migrants, unions increasingly struggle to secure 'equal pay for equal work'. Attempts to organise migrants are made further difficult not only by language barriers, but also by the fact that migrants are over-represented in those sectors of the economy where union support is traditionally weak. Thus, contemporary labour migration poses many challenges to trade unions, including intra- and extra-European migration, an increase in precarious forms of migrant labour and the task of organising migrants.

This thesis seeks to examine how trade unions in four Western European countries, Austria, Germany, Ireland and the UK, respond to these challenges. With Germany and Austria on the one hand and the UK and Ireland on the other, two pairs of countries have been selected that are classified as coordinated market economies (CMEs) and liberal market economies (LMEs). Therefore, the thesis seeks to establish whether unions in CMEs respond differently to the challenge of contemporary labour migration than unions in LMEs, and if so, how possible differences can be accounted for. The main findings of the study suggest that there is considerable variation in union attitudes towards migrant labour. Broadly speaking, unions in LMEs like Britain and Ireland appear to be more open towards migrant labour than unions in CMEs like Germany and Austria. In particular labour market factors and the structure of collective bargaining in each 'variety of capitalism' appear to be of considerable importance in accounting for the variation in union attitudes towards migrants. However, while union policies are certainly influenced by such 'structural' factors, they are not wholly determined by them as unions have some agency in the way they frame issues such as immigration.


In this paper we present new implementation details and benchmarking results for our parallel portfolio solver \topo. In particular, we discuss ideas and implementation details for the exchange of learned clauses in a massively-parallel SAT solver which is designed to run more that 1,000 solver threads in parallel. Furthermore, we go back to the roots of portfolio SAT solving, and discuss the impact of diversifying the solver by using different restart- , branching- and clause database management heuristics. We show that these techniques can be used to tune the solver towards different problems. However, in a case study on formulas derived from Bounded Model Checking problems we see the best performance when using a rather simple clause exchange strategy. We show details of these tests and discuss possible explanations for this phenomenon.As computing times on massively-parallel clusters are expensive, we consider it especially interesting to share these kind of experimental results.


Economists seem to be everywhere in the media these days. But what exactly do today's economists do? What and how are they taught? Updating David Colander and Arjo Klamer's classic The Making of an Economist , this book shows what is happening in elite U.S. economics Ph.D. programs. By examining these programs, Colander gives a view of cutting-edge economics--and a glimpse at its likely future. And by comparing economics education today to the findings of the original book, the new book shows how much--and in what ways--the field has changed over the past two decades. The original book led to a reexamination of graduate education by the profession, and has been essential reading for prospective graduate students. Like its predecessor, The Making of an Economist, Redux is likely to provoke discussion within economics and beyond. The book includes new interviews with students at Harvard, Princeton, Stanford, MIT, Chicago, and Columbia. In these conversations, the students--the next generation of elite economists--colorfully and frankly describe what they think of their field and what graduate economics education is really like. The book concludes with reflections by Colander, Klamer, and Robert Solow. This inside look at the making of economists will interest anyone who wants to better understand the economics profession.


The abundance of services offered by cloud providers raises the need for Quality of Service (QoS) monitoring to enforce Service Level Agreements (SLAs). In this paper, we propose a cloud-monitoring scheme, which offers flexible and dynamically reconfigurable QoS monitoring services to adapt to various cloud based service characteristics. We propose to grant cloud service consumers the option to decide whether to switch to another service provider, if the current provider frequently violates the corresponding SLA contract. For cloud service providers, the monitoring scheme provides dashboard-like indicators to continuously manage the performance of their SaaS platform and visualise the monitoring data. Our experimental evaluation involves a real cloud platform to illustrate the capability of our monitoring scheme in detecting and reporting violations of SLAs for both single and composite SaaS services. A particular emphasis on visualisation options is highlighted when revealing and reconfiguring monitoring data in a user-friendly display.


Ge2Sb2Te5 is a phase change material candidate to constitute the active element of future nonvolatile memory devices. The evolution of the thermal resistance at the interface between an aluminum thin layer and Ge2Sb2Te5 is studied using the time resolved pump probe technique from room temperature to 400 °C. The thermal resistance is influenced by the amorphous to crystalline phase change occurring in Ge2Sb2Te5. The decrease in the thermal resistance from the amorphous to the crystalline phase is well explained by the diffuse mismatch model asymptotic form for high temperature. The large increase of the interface thermal resistance between fcc and hcp crystalline states is explained by the fast and significant grain growth and species inter-diffusion during this second phase change. This leads to the formation of an interfacial layer whose chemical and mechanical intrinsic properties have been measured in order to model the thermal resistance in the hcp state.


Over the past two decades, donors increasingly link foreign aid to democracy objectives in subSaharan Africa. Yet systematic research on this topic typically focuses on how aid influences democratic transitions. This chapter investigates whether and how foreign aid affects the process of democratic consolidation in Sub-Saharan Africa by examining two potential mechanisms: (1) the use of aid as leverage to buy political reform and (2) investment in the opposition. We test these mechanisms using three dependent variables that capture different aspects of democratic consolidation. Using survival analysis for the period from 1991 to 2008, we find that democracy and governance aid has a positive effect on democratic consolidation. Economic aid, on the other hand, has little effect on democratic consolidation.


Solar radiation is a primary driver for many physical, chemical, and biological processes on the earth's surface. Solar energy engineers, architects, agriculturists, hydrologists, etc. often require a reasonably accurate knowledge of the availability of the solar resource for their relevant applications at their local. In solar applications, one of the most important parameters needed is the long-term average daily global irradiation. For regions where no actual measured values are available, a common practice is to estimate average daily global solar radiation using appropriate empirical correlations based on the measured relevant data at those locations. These correlations estimate the values of global solar radiation for a region of interest from more readily available meteorological, climatological, and geographical parameters. The present study aimed to calibrate existing models and develop a new model for estimating global solar radiation data using available measured meteorological records such as precipitation or temperature. Fifteen empirical global radiation models based on meteorological variables were generated and validated using daily data in the period of January 2007 to December 2011 at Hebron city meteorological station in Palestine. Validation criteria included coefficient of determination, root mean square error, mean bias error, mean absolute bias error, mean percentage error, and mean absolute percentage error. The best result was derived from the model proposed, which uses extraterrestrial solar radiation, saturation vapor pressures, transformed rainfall data and daily minimum relative humidity as predictors. The new multiple regression relation giving accurate estimates of daily global solar radiation was suggested. It has a high coefficient of determination R = 0.94. The results showed that the suggested model can estimate the global solar radiation with acceptable values of RMSE, MBE and MABE (2.38, 0.08, 1.75 MJ m day, respectively); and MPE and MAPE (-6.49%, 19.32%). Temperature based models provided less accurate results, of which the best one is the Bristow and Campbell model (R = 0.89). The Hargreaves and Samani model is simple and are recommended to estimate the daily global radiation when only temperature data are available and when the coefficients cannot be determined. Based on overall results it was concluded that the meteorological based method provides reasonably accurate estimates of global solar radiation, for the site where coefficients of the model were developed.


Many fundamental processes that govern the function of biological cells occur on or immediately under the cell membrane. Fluorescence marking of specific sites has had a large impact in the recognition of these processes. In addition, observation in an appropriate ionic buffer is required in many cases to preserve a reliable dynamics of the cell. Artificial membranes, used as a model for biological ones, can provide fundamental parameters connected to the composition and the molecular organization in natural membranes. Near field optical microscopy offers a valid possibility to obtain spectroscopic information at subwavelength scale, performing observation also in native liquid environment. This thesis is focused on the study and the improvements of different aspects of this technique to the observation of fluorescently labelled thin lipid films in different environments. More specifically, three fundamental issues have been addressed in this work: the implementation of a homemade SNOM in liquid, the near field fluorescence observation of Langmuir-Blodgett monolayers, and the study of probe-sample interaction forces on flat lipid films. Near field imaging in water is a critical instrumental aspect due to high drag forces generated in the liquid medium by the vibrating tip. These forces, that can induce a significant indentation of a compliant sample, have been minimized by a specific set up. The near field probe minimally interacts with the surrounding medium, being protected by a capillary tube. This dispositive has allowed measurements on thin lipid films immersed in water. However, measurements on fixed cell in water have induced indentation of the sample. The boundary transition width of non fluorescent liquid condensed domain surrounded by a liquid expanded fluorescent matrix, in a thiolipid Langmuir-Blodgett monolayer, has been studied in the near field. The optical image gives interesting insights on the molecular organization within the liquid condensed domain, showing in the central part a different molecular organization with respect to the rest of the domain. Force mapping of the sample in air predicts a contrast between the two phases that does not correspond to the topological relief of the film. Measurements in water show an inverted contrast with respect to the one recorded in air. To better identify the different forces that contribute to the shear force contrast when scanning a lipid film, the dynamics of Al-coated and probes bearing chemically functional groups has been examined in the interaction with two different systems. Interfacial forces on self assembly monolayer, micropatterned with molecules exhibiting opposite water affinity, have been investigated with Al-coated and hydrophobic functionalized near field probe. These experiments indicate that the tip dynamics in the sample vicinity is critically dependent on the wettability properties of both interfaces. The contrast observed when scanning a thiolipid monolayer is, also in this case, tightly linked with the surface properties of the probe. In particular, hydrophilic probes are totally insensitive to the different packing of alkyl chains in the two phases. The dynamics of fluorinated surface probes shows the very interesting feature of not being influenced by the drag forces of the surrounding liquid medium. This result opens up the possibility to employ such a tip, whose mechanical properties are equivalent in air and in water, to scan very compliant samples in liquid environment.


Geneticists have sequenced the first prehistoric genome from Africa: that of Mota, a hunter-gatherer man who lived 4500 years ago in the highlands of Ethiopia. Named for the cave that held the remains, the Mota genome gives scientists their first glimpse into what an African genome looked like prior to many recent migrations in Africa. This ancient Ethiopian highlander is most closely related to the Ari, an ethnic group that speaks Omotic languages in the Ethiopian highlands today. And when researchers compared Mota9s genome to that of other Africans, Europeans, and Asians, they got a surprise: Africa is usually seen as a source of outward migrations, but the genomes suggest a major migration into Africa by farmers from the Middle East, possibly about 3500 years ago. These farmers9 DNA reached deep into the continent, spreading even to groups considered isolated such as the Khoisan of South Africa and the pygmies of the Congo.


This is a systematic review on how innovations in health service practice and organisation can be disseminated and implemented. This is an academic text, originally commissioned by the Department of Health from University College London and University of Surrey, using a variety of research methods. The results of the review are discussed in detail in separate chapters covering particular innovations and the relevant contexts. The book is intended as a resource for health care researchers and academics. © 2005 by Blackwell Publishing Ltd.


The University of Alberta Libraries (UAL) is delighted to have the blessing of Dr Andrea Deakin and the Okanagan College Library to assume all responsibilities of the eponymous "Deakin Newsletter" (www.okanagan.bc.ca), which is now renamed "The Deakin Review of Children's Literature". An enthusiastic team of book reviewers and editors from UAL will review English language children's books and publish thoughtful reviews and recommendations using a four star system (four stars: highly recommended; three stars: recommended; two stars: recommended with reservations; one star: not recommended). With so many children's books published each year we know that it can be a dizzying task to find the good ones, so we will make every effort to review at least 25 books in each issue (published quarterly), including pop-ups, ABCs, young adult fiction, picture books, ebooks, board books, and works of non-fiction. Nearly a year ago I had the opportunity to meet Dr Andrea Deakin over lunch and we talked for hours about children's books. Her enthusiasm was infectious and I was in awe when I learned that she had been reviewing children's literature in Canada for nearly half a century. She explained that her career as a teacher and book reviewer had offered so many rewarding opportunities to promote children's literature, and in retirement she continued her prolific book reviewing activities in an electronic newsletter hosted by the Okanagan College Library. She was recognized for her exemplary contribution to the humanities when Okanagan College awarded her an honorary Doctor of Letters degree in 2004. Dr Deakin has earned her reputation as one of the great champions of children's literature and we are greatly honoured that she has given us this wonderful opportunity to launch a new journal in her honour. The reviewed books will be catalogued and processed as a non-circulating special collection, The Dr Andrea Deakin Collection of Children's Literature , which will be stored at the University of Alberta's Book and Record Depository, and made available to researchers in the reading room of the Bruce Peel Special Collections Library. We welcome your comments and suggestions about our publication, so please send me an email if you wish to get in touch. Best wishes for a pleasant summer, filled with splendid children's books! Robert Desmarais Managing Editor


Multipath I/O is the ability to provide increased performance and fault tolerant access to a device by addressing it through more than one path. For storage devices, Linux has seen several solutions that were of two types: high-level approaches that live above the I/O scheduler (BIO mappers), and low-level subsystem specific approaches. Each type of implementation has its advantage because of the position in the storage stack in which it has been implemented. The authors focus on a solution that attempts to reap the benefits of each type of solution by moving the kernel's current multipath layer, dm-multipath, below the I/O scheduler and above the hardware-specific subsystem. This paper describes the block, Device-mapper, and SCSI layer changes for the solution and its effect on performance.


Drilling challenging wells requires a combination of drilling analytics and comprehensive simulation to prevent poor drilling performance and avoid drilling issues for the upcoming drilling campaign. This work focuses on the capabilities of a drilling simulator that can simulate the directional drilling process with the use of actual field data for the training of students and professionals. This paper presents the results of simulating both rotating and sliding modes and successfully matching the rate of penetration and the trajectory of an S-type well.
 Monitored drilling data from the well were used to simulate the drilling process. These included weight on bit, revolutions per minute, flow rate, bit type, inclination and drilling fluid properties. The well was an S-type well with maximum inclination of 16 degrees. There were continuous variations from rotating to sliding mode, and the challenge was approached by classifying drilling data into intervals of 20 feet to obtain an appropriate resolution and efficient simulation. The simulator requires formation strength, pore and fracture pressures, and details of well lithology, thus simulating the actual drilling environment. The uniaxial compressive strength of the rock layer is calculated from p–wave velocity data from an offset field. Rock drillability is finally estimated as a function of the rock properties of the drilled layer, bit type and the values of the drilling parameters. It is then converted to rate of penetration and matched to actual data.
 Changes in the drilling parameters were followed as per the field data. The simulator reproduces the drilling process in real-time and allows the driller to make instantaneous changes to all drilling parameters. The simulator provides the rate of penetration, torque, standpipe pressure, and trajectory as output. This enables the user to have on-the-fly interference with the drilling process and allows him/her to modify any of the important drilling parameters. Thus, the user can determine the effect of such changes on the effectiveness of drilling, which can lead to effective drilling optimization.
 Certain intervals were investigated independently to give a more detailed analysis of the simulation outcome. Additional drilling data such as hook load and standpipe pressure were analyzed to determine and evaluate the drilling performance of a particular interval and to consider them in the optimization process.
 The resulting rate of penetration and well trajectory simulation results show an excellent match with field data. The simulation illustrates the continuous change between rotating and sliding mode as well as the accurate synchronous matching of the rate of penetration and trajectory. The results prove that the simulator is an excellent tool for students and professionals to simulate the drilling process prior to actual drilling of the next inclined well.


We examined how voting behavior in the European Parliament changed after the European Union added ten new member-states in 2004. Using roll-call votes, we compared voting behavior in the first half of the Sixth European Parliament (July 2004-December 2006) with voting behavior in the previous Parliament (1999–2004). We looked at party cohesion, coalition formation, and the spatial map of voting by members of the European Parliament. We found stable levels of party cohesion and interparty coalitions that formed mainly around the left-right dimension. Ideological distance between parties was the strongest predictor of coalition preferences. Overall, the enlargement of the European Union in 2004 did not change the way politics works inside the European Parliament. We also looked at the specific case of the controversial Services Directive and found that ideology remained the main predictor of voting behavior, although nationality also played a role.


Background: Cough variant asthma (CVA) is characterized by prolonged non productive cough which responds to bronchodilator therapy. None of herbal drug is reported to possess pharmacological activity against CVA. Objective: To investigate the pharmacological potential of ethanolic extract of Woodfordia fruticosa (L.) Kurz (EEWF) against CVA as well as to develop an efficient screening model for CVA. Material and Method: Anti-tussive effect of EEWF was evaluated against nebulized aqueous solution of 0.1 g/ml of citric acid to determine the cough response. EEWF potential was finally accessed against aerosolic mixture of 0.3 g/ml of citric acid mixed with 0.1% histamine and 2% acetylcholine chloride to evaluate the convulsive latency, percentage protection and cough frequency against CVA. Results: EEWF at aerosolic dose of 6% w/v exhibit decrease in of the average coughs frequency (4.83 ± 0.30) which is quite significant effect as compared to standard drug codeine. EEWF against aerosol induced CVA was found to exhibit a significant bronchoprotection of 41.75% and decreases number of coughs (7.16 ± 0.47) at 200 mg/kg as compared to control (14.16 ± 0.60). Conclusion: EEWF at 200 mg/kg dose exhibited bronchoprotective and anti-tussive effects against aerosol induced CVA.


The Supreme Court is currently reviewing the Second Circuit's decision in Kiobel v. Royal Dutch Petroleum, a case holding that federal courts lack jurisdiction under the Alien Tort Statute ("ATS") over claims against corporations. Although the parties have focused on issues of corporate liability under the ATS, there is a logically antecedent question of subject matter jurisdiction that the Court should decide before considering corporate liability. All of the parties in Kiobel — whether corporate or individual — are aliens. Understood in its full legal and historical context, the ATS was a jurisdictional statute that did not apply to suits between aliens. The First Congress enacted the ATS as a species of foreign diversity jurisdiction to satisfy the United States' obligation under international law to redress violence by U.S. citizens against foreign citizens. Accordingly, the ATS was originally understood to give federal courts jurisdiction only over claims by aliens against U.S. citizens for intentional torts to person or personal property. In Sosa v. Alvarez-Machain, the Supreme Court sought to interpret the ATS in accordance with the expectations of the First Congress. If the Court adheres to this goal in Kiobel, then it should conclude that it lacks statutory subject matter jurisdiction over the case. If the Court decides that the ATS does not apply to suits between aliens, then the Court likely will never have occasion to decide the thorny question of corporate liability under the ATS. Under the express terms of 28 U.S.C. §1332, federal courts already have jurisdiction over suits by aliens against U.S. corporations provided that the amount in controversy is greater than $75,000.00 — a condition easily met in cases against large corporations.


As phosphorus deficiency limits the productivity of many plantation forests in Asia, there is considerable interest in developing phosphorus-efficient clones for the region through targeted breeding programs. Therefore, we determined growth, nutrient concentrations and nutrient absorption and utility efficiencies of four Betula alnoides clones (C5, C6, 1-202 and BY1) in response to six phosphorus levels of 0, 17, 52, 70, 140 and 209 mg P plant-1 coded as P1 to P6, respectively. Maximum growth occurred in the P4, P5 and P6 plants since they had the largest height, biomass, leaf area and branch number. Phosphorus application increased the phosphorus concentrations of all clones. Nutrient loading was achieved with the P6 treatment because growth and biomass were not significantly higher, but root, stem and leaf phosphorus concentrations were approximately twice those of P4 plants. Clone BY1 had the highest phosphorus-efficiency, and is recommended for field application due to its maximum root collar diameter, biomass, root/shoot ratio, leaf area, nutrient absorption and utility efficiency among the four clones. The findings will help to improve the nutrient efficiency of this species in plantation forestry in Asia.


Purpose: Multiple methods of accelerating fracture healing have been proposed and some are approved for use in the clinical settings. A low intensity (30 nW/cm 2 ) pulsed ultrasound (LIPUS) signal will promote fracture healing. This study is conducted to determine the effect of LIPUS on fresh fracture healing. Materials and Methods: Out of the 60 patients with diaphyseal fractures of the tibia and femur fixed with an interlocking nail, 33 received LIPUS and 27 were kept as control. Ultrasound treatment was started three days after surgery, 20 minute sessions each day, for 30 days. The rate of fracture healing in the LIPUS group was compared with that of the control group. Six orthopedic surgeons and two radiologists analyzed the follow-up x-rays. Results: Five out of the six surgeons interpreted that there was significantly more callus formation and union in the LIPUS group compared to the control group, especially in the initial stage of healing. The need for dynamization decreased by 50% in the LIPUS group. Both radiologists interpreted that there was significantly more callus in the case where ultrasound was administered, when they evaluated the same with an diagnostic ultrasound scan at the fracture site. Conclusion: The present study establishes the relation between low intensity pulsed ultrasound therapy and fresh fracture healing, especially in the early stages. We strongly recommend the use of LIPUS as an adjunct therapy where the surgeon anticipates delayed union of the fracture.


The coronavirus outbreak has challenged and continues to challenge every aspect of the supply chain within the AEC industry, forcing stakeholders to cope with increasing uncertainties and continuous change. The notion of resilience is especially salient now. While the need for the AEC industry to focus on resilience has been highlighted in recent articles, there is a need for a comprehensive discussion on what resilience means for the AEC industry and how companies can create built-in resilience. This paper takes the form of a high-level overview of where the industry is headed and aims to establish eleven propositions for a resilient, post-COVID-19 future, for practitioners working in the design and construction industry. Moreover, this paper proposes a 'decentralization of workforce and integration of data' model in which the established propositions are manifested to support a resilient AEC industry.


A reconnaissance of the potential for memorializing people through online avatars was carried out by participant observation, running ancestor veneration avatars (AVAs) based on deceased members of the author's own family. First, the AVA concept is introduced in the context of the changing social status of religion in postmodern society. Then the range of possibilities is sketched through four avatars, exploring how: (1) a priest character in World of Warcraft can represent an actual deceased priest; (2) an ambivalent character in EverQuest II can represent an abstract issue about the value of religion; (3) an historically accurate gameworld like Pirates of the Burning Sea can be a good environment for commemorating a person whose life is largely unknown but took place during its historical period; and (4) a fantasy world like Lord of the Rings Online can represent a person who in life had a direct connection to that fantasy. Memorialization of one person in multiple environments illustrates that avatar-like manifestations may be created in (1) solo-player games like Elder Scrolls IV: Oblivion, (2) multiplayer games like Star Wars: The Old Republic, (3) a nongame virtual world like Second Life, and (4) a variety of other online environments where one is represented by something like an avatar, including Wikipedia.


Cat right ventricular papillary muscles responded biphasically to cumulative additions of ryanodine. A progressive and pronounced negative inotropic effect was observed with low to intermediate ryanodine concentrations (5 nM-1 muM) while a rebound or reversal of these initial changes back toward pre-drug values was obtained as the ryanodine concentration was further increased to 100 muM. Active force development (DF), the rate of force development (dF/dt), as well as the rate of relaxation all exhibited these bidirectional changes. In contrast, time to peak force underwent only a progressive prolongation over the entire concentration range tested. This response pattern was observed with both normal and K+-depolarized (isoproterenol- or dibutyryl cAMP-restored) preparations. The response to a single addition of 100 muM ryanodine, in the presence of 2.5 mM Ca++ mimicked both the qualitative and quantitative aspects of the cumulative concentration response curve. In the presence of 5.0 mM Ca++ the high concentration of ryanodine no longer caused depression but instead caused only a slowly developing, monophasic increase in DF. Ryanodine also changed the response of ventricular muscle to other inotropic interventions. Ryanodine (1 muM; 2.5 mM Ca++) abolished the normal increase in dF/dt following either paired electrical stimulation (PES) or 50 mOsM mannitol, but not that in response to a doubling of the stimulation rate (0.2--0.4 Hz). After ryanodine exposure, the potentiation of developed force by PES was shifted from the first (regular) to the second (premature) contraction, producing a summation-like waveform. Prior addition of the calcium channel antagonist D600 (1 muM) did not alter ryanodine-induced changes in PES. Caffeine (1 mM) produced alterations in the responses to PES and hyperosmolarity which were similar to those observed with ryanodine. In the presence of high concentrations of both ryanodine (100 muM) and calcium (5 mM) both the transient and steady-state responses to a doubling of the stimulation rate (0.2--0.4 Hz) were markedly depressed, whereas the decrease in DF or dF/dt normally accompanying a reduction in the rate of stimulation was attenuated. The data obtained in the present study are consistent with a functional inhibition of sarcoplasmic reticular calcium release by ryanodine.


"Talk to the hand 'cause the face ain't listening," the saying goes. When did the world get to be so rude? When did society become so inconsiderate? It's a topic that has been simmering for years, and Lynne Truss says that it has now reached boiling point. Taking on the boorish behaviour that has become a point of pride for some, Talk to the Hand is a rallying cry for courtesy. Like Eats, Shoots & Leaves, Talk to the Hand is a spirited conversation, not a stuffy guidebook. It is not about forks, for a start. Why hasn't your nephew ever thanked you for that perfect Christmas present? What makes your builder think he can treat you like dirt in your own home? When you phone a utility with a complaint (and have negotiated the switchboard), why can't you ever speak to a person who is authorised to apologise? What accounts for the appalling treatment you receive in shops? Most important, what will it take to roll back a culture that applauds rudeness and finds it so amusing? For anyone who's fed up with the brutality inflicted by modern manners (and is naturally too scared to confront the actual yobs), Talk to the Hand is a colourful call to arms - from the wittiest defender of the civilised world.


The Indonesia Archipelago is a complex region that both harbors the today's most biodiverse marine environments and plays an important role in climate and ocean regulation. Additionally, the area contains a large human population and noteworthy fossil fuel industries. However, there is a dearth of knowledge about the region's natural history. The vast majority of fossil specimens available today were collected by British and Dutch explorers in the 19th and very early 20th centuries, which are now housed in the Natural History Museum of London and Naturalis Museum of Leiden. These specimens lack modern taxonomic and environmental context that is important for judging what caused the flourishing of biodiversity and how climate events of the past influenced the biosphere. Traditionally, it was thought that sea-level fluctuations (1 Ma to 11 Ka) of the last ice ages led to the high level of species in the Indonesian area. However, recent studies show evidence that the current biodiversity hotspot was forming during the Miocene (23-5 Ma). Borneo is at the heart of the hotspot and is furthermore situated centrally within the Indonesian Throughflow (ITF), which acts as a complex 'faucet' controlling the mixing of the Pacific and Indian Oceans. Today, the ITF is a vital modulator for several globally important climate/ocean features including the Asian Monsoons and El Nino Southern Oscillation. Hence, Borneo is pivotal to understanding many mysterious about the regional and global biosphere and climate operations. Because of this, a consortium of European research institutions, funded by the EU, formed the "Throughflow project" which aimed to better understand this region's geological and biological history and how past events alterted the coarse of life on Earth. But, what good is a fantastic story without an element of timing? As part of the Throughflow project, my PhD undertook a collaborative role in adding age control and environmental context to the largely paleobiological data being collected by my fellow researchers. My research focuses on eastern Borneo during the Miocene. My PhD covered an array of studies including: paleoenvironmental reconstruction, magnetostratigraphy, strontium isotope stratigraphy, cyclostratigraphy, and paleomagnetic rotational studies. The improved dating provided by my research has helped tie down the arrival of the current biodiversity hotspot in the region to at least the middle Miocene. Furthermore, by better dating the growth of the Mahakam River Delta, it is now better realized that biodiverse reefs flourished in very dynamic tectonic and muddy environments, not typical (pehaps even antithetical) for today. My research shows that cyclic sedimentary alternations in the region match Earth's orbital oscillations which is perhaps one of the best examples globally of orbital forces manifested in an equatorial and riverine sedimentary record. It also appears that these oscilations played an important role in allowing biodiverse reefs to form or be killed. Also, a study of the microscopic magnetic minerals in rocks from eastern Borneo indicate that the island probably did not rotate drastically since at least around 40 million years ago, which is contrary to current tectonic models for the region.


The winning condition of a parity game with costs requires an arbitrary, but fixed bound on the cost incurred between occurrences of odd colors and the next occurrence of a larger even one. Such games quantitatively extend parity games while retaining most of their attractive properties, i.e, determining the winner is in NP and co-NP and one player has positional winning strategies.
We show that the characteristics of parity games with costs are vastly different when asking for strategies realizing the minimal such bound: The solution problem becomes PSPACE-complete and exponential memory is both necessary in general and always sufficient. Thus, solving and playing parity games with costs optimally is harder than just winning them. Moreover, we show that the tradeoff between the memory size and the realized bound is gradual in general. All these results hold true for both a unary and binary encoding of costs.
Moreover, we investigate Streett games with costs. Here, playing optimally is as hard as winning, both in terms of complexity and memory.


It was recently shown that inhibition or downregulation of Bcl-2 represents a new therapeutic approach to by-pass chemoresistance mechanism in cancer cells. Therefore, we explored the potential of this approach in breast cancer cells; MCF-7 (drug-sensitive; p53 wild type) and MDA-MB-231 (drug-insensitive; p53 mutant). Cisplatin and paclitaxel induced apoptosis in a dose-dependent manner in both cell lines. Furthermore, silencing of Bcl-2 remarkably increased cisplatin and paclitaxel induced apoptosis. Dose dependent induction of apoptosis by cisplatin and paclitaxel was enhanced by the pre-treatment of these cells with HA14-1, a Bcl-2 inhibitor. Although the effect of cisplatin on cell death was significant in MCF-7 and MDA-MB- 231, paclitaxel was less potent only in MDA-MB-231 cells. To further understand the distinct role of drugs in breast cancer cells which were pre-treated with HA14-1, changes in mitochondrial membrane potential, caspase activation, and Bcl-2 family protein levels, generation of reactive oxygen species and lipid peroxidation were studied. The apoptotic effect of cisplatin with or without HA14- 1 pre-treatment was shown to be caspase-dependent in both cell lines. While proapoptotic Bcl-2 proteins (Bax, Puma, Bad) were found to be up-regulated, Bcl-2 and Bcl-xL were down-regulated when cells were pre-treated with HA14-1 followed by cisplatin or paclitaxel. MCF-7 and MDA-MB-231 cells overexpressing Bcl-2 displayed different responses upon drug-treatment. Although cisplatin could still induce apoptosis in Bcl-2 overexpressing MCF-7 cells by promoting pro-apoptotic Bcl-2 family members, Bcl-2 overexpression abrogated paclitaxel induced apoptosis in MCF-7 and MDA-MB-231 breast cancer cells, respectively. In conclusion, our findings suggest two important implications for understanding cisplatin and paclitaxel induced apoptosis mechanism and the potential role of Bcl-2 in this apoptotic pathway. First, the potentiating effect of Bcl-2 inhibitor (HA14-1) is drug and cell type specific and may not only depend on the inhibition of Bcl-2. Importantly, alteration of other pro-apoptotic or anti-apoptotic Bcl-2 family members may dictate the apoptotic response when HA14-1 is combined with chemotherapeutic drugs. Second, cisplatin activated a p53- regulated pro-apoptotic pathway to overcome Bcl-2 mediated resistance. These insights may be useful for the development of novel treatments for cancer cells overexpressing anti-apoptotic Bcl-2 proteins.


Thought you couldnt learn statistics? You can and you will! Even You Can Learn Statistics and Analytics, Third Edition is the practical, up-to-date introduction to statistics for everyone! Now fully updated for "big data" analytics and the newest applications, it'll teach you all the statistical techniques youll need for finance, marketing, quality, science, social science, and more one easy step at a time. Simple jargon-free explanations help you understand every technique, and extensive practical examples and worked problems give you all the hands-on practice you'll need. This edition contains more practical examples than ever all updated for the newest versions of Microsoft Excel. You'll find downloadable practice files, templates, data sets, and sample models including complete solutions you can put right to work! Learn how to do all this, and more: Apply statistical techniques to analyze huge data sets and transform them into valuable knowledge Construct and interpret statistical charts and tables with Excel or OpenOffice.org Calc 3 Work with mean, median, mode, standard deviation, Z scores, skewness, and other descriptive statistics Use probability and probability distributions Work with sampling distributions and confidence intervals Test hypotheses with Z, t, chi-square, ANOVA, and other techniques Perform powerful regression analysis and modeling Use multiple regression to develop models that contain several independent variables Master specific statistical techniques for quality and Six Sigma programs Hate math? No sweat. Youll be amazed at how little you need. Like math? Optional "Equation Blackboard" sections reveal the mathematical foundations of statistics right before your eyes. If you need to understand, evaluate, or use statistics in business, academia, or anywhere else, this is the book you've been searching for!


Abstract Medical genetics is an exponentially progressing field. In less than a decade, the increase in our understanding of genetics, particularly Molecular genetics has exceeded that achieved over the previous 4 decades marked by Watson and Crick's specification of the double helix structure of DNA in 1953. Since then the genetic code has been deciphered, the nature of the gene was clarified and many of the intricacies of its function became overt. Genetics has a long tradition of merging clinical observation with basic laboratory investigation. This has culminated in the emergence of molecular biology in which biological processes are understood from the level of the gene through proteins that direct the development and function of the creature. Genetics is therefore playing an increasingly central role in the medical field, and no physician can remain ignorant of its fundamental principles and practice.


BACKGROUND
Menopausal women are at high risk for cardiovascular diseases and osteoporosis. However, for so long, women have devoted much of their time and energy to family, children, and work such that they could not regularly exercise. There are few studies addressing the experiences of Taiwanese women who regularly exercise.

OBJECTIVES
The aim of this study was to explore the experiences of regularly exercising, defined as thoughts or actions by menopausal women who did not regularly exercise before menopause, but who now exercise regularly.

DESIGN
A grounded theory research design was used.

METHODS
In-depth interviews were undertaken with a purposive sampling of 12 menopausal women who began to do regular exercises after menopause and who have continued exercising for more than 6 months. The constant comparative method was used to analyse the interview data.

RESULTS
'Perceiving Continuous Power' was the core category during the process of regularly exercising. Every participating woman perceived that her body and mind were filled with continuous power including the subcategories of 'Overcoming the initial discomfort', 'Experiencing Benefits to Body and Mind' and 'Broadening' during the process. 'Awareness of Health Crisis', which included the subcategories of 'Cureless Chronic Disease', 'Mood Swings', and 'Conflict on Medication', was identified as occurring when these women first began regularly exercising. Throughout the process of perceiving continuous power, women experienced the following interactive behaviour categories: 'Exercise Selection' with subcategories of 'Self-Evaluation', 'Seeking and Fitting', 'Comparing' and 'Health Becoming' with the subcategories of 'Releasing Health Crisis', 'Regaining Flowering Life', and 'Self-Fulfilling'.

CONCLUSIONS
Regular exercises provided continuous power for menopausal women.

RELEVANCE TO CLINICAL PRACTICE
The experiences with exercise we uncovered in this study can provide a reference for nurses to guide menopausal women with their regular exercise plans.


This paper is concerned to the segmentation of heart sounds by using Radial-Basis Functions for acoustical modelling, combined with a Hidden Markov Model for heart sounds sequence modelling. The idea behind the use of RBF's is to take advantage of the local approximations using exponentially decaying localized nonlinearities achieved by the Gaussian function, which increases the clustering power relatively to MLP's. This neural model can be advantageous over the global approximations to nonlinear input-output mappings provided by Multilayer Perceptrons (MLP's), especially when non-stationary processes need to be accurately modelled.

The above described RBF's properties combined with the non-stationary statistical properties of Hidden Markov Models can help in the detection of the T-wave which is fundamental for the detection of the second heart sound.

The feature vectors are based on a MFCC based representation obtained from a spectral normalisation procedure, which showed better performance than the MFCC representation alone, in an Isolated Speech Recognition framework. Experimental results were evaluated on data collected from five different subjects, using CardioLab system and a Dash family patient monitor. The ECG leads I, II and III and an electronic stethoscope signal were sampled at 977 samples per second.


Background A 2015, Hockey Calgary body checking (BC) policy change disallowed BC from non-elite Bantam (ages 13–14, lower 60% of divisions). This was informed by evidence that disallowing BC in Pee Wee (ages 11–12) reduced the risk of injury, specifically concussion, by >3-fold. Objective To compare the frequency of type and intensity of player-to-player contacts (PC) and head contact in non-elite Bantam ice hockey games in leagues allowing BC (2014–15) compared with leagues disallowing BC (2015–16). Design Cohort study. Setting Ice-hockey arenas in Calgary, Canada. Participants Non-elite Bantam players in 2014–15 (n=348 players) and 2015–16 (n=309 players) seasons. Interventions In the 2014–15 season, non-elite Bantam leagues allowed BC. In 2015–2016, BC was disallowed. Main Outcome Measurements Thirteen games pre-policy change (2014–2015) and 13 post-policy change were video recorded. Analysis using validated methodology was used to compare the frequency, type (i.e., trunk, head and other types of PC with limb/head/stick), and intensity (trunk contacts level 1–5 with increasing intensity) of PCs. Incidence rate ratios (IRR) were estimated using Poisson regression (controlling for cluster by team, offset by player minutes). Results There were a total of 3485 trunk contacts and 1395 other contacts in 26 games. The overall risk of trunk PCs was lower post-policy change (IRR=0.50, 95% CI; 0.45–0.56). Post-policy change, high intensity (body checking - level 4,5) contacts decreased (IRR4=0.19, 95% CI; 0.13–0.26 IRR5=0.11, 95% CI; 0.03–0.51), lower intensity (level 2,3) PCs were less frequent (IRR2=0.45, 95% CI; 0.40–0.50 and IRR3=0.47, 95% CI; 0.35–0.63), and other contacts made with the limb/stick also decreased (IRR=0.60, 95% CI; 0.48–0.73). Head contact decreased (IRR=0.40, 95% CI; 0.25–0.61). Conclusions Post-policy change disallowing BC in non-elite Bantam, incidence of high intensity (level 4,5) PCs decreased 82%. Head contact decreased 60% and stick/limbs contact decreased 40%. These findings inform the mechanisms of injury explaining concussion risk reduction post-BC policy change.


model the optimal Bayesian foraging strategy in environments with only two patch qualities. That is, all patches either belong to one rich type, or to one poor type. This has been a situation created in several foraging experiments. In contrast, previous theories of Bayesian foraging have dealt with prey distributions where patches may belong to one out of a large range of qualities (binomial, Poisson and negative binomial distributions). This study shows that two-patch systems have some unique properties. One qualitative difference is that in many cases it will be possible for a Bayesian forager to gain perfect information about patch quality. As soon as it has found more than the number of prey items that should be available in a poor patch, it "knows" that it is in a rich patch. The model generates at least three testable predictions. 1) The distribution of giving-up densities, GUDs, should be bimodal in rich patches, when rich patches are rare in the environment. This is because the optimal strategy is then devoted to using the poor patches correctly, at the expense of missing a large fraction of the few rich patches available. 2) There should be a negative relation between GUD and search time in poor patches, when rich patches are much more valuable than poor. This is because the forager gets good news about potential patch quality from finding some food. It therefore accepts a lower instantaneous intake rate, making it more resistant against runs of bad luck, decreasing the risk of discarding rich patches. 3) When the energy gains required to remain in the patch are high (such as under high predation risk), the overuse of poor patches and the underuse of rich increases. This is because less information about patch quality is gained if leaving at high intake rates (after short times). The predictions given by this model may provide a much needed and effective conceptual framework for testing (both in the lab and the field) whether animals are using Bayesian assessment. (Less)


Synthesis of a series of pyrenesulfonamide-labeled polyelectrolytes with varied label proximities has been accomplished by a micellar polymerization technique. The solution properties of these terpolymers consisting of acrylamide (AM), acrylic acid (AA), and N-[(1-pyrenylsulfonamido)ethyl]-acrylamide (APS) are examined using viscometry, light scattering, and fluorescence spectroscopy. Classical light scattering indicates high molecular weights (>1 x 10 6 ) and very good polymer solvation even at high NaCl concentrations (A 2 ∼10 4 cm 3 mol/g 2 ). Viscometry and dynamic light scattering studies indicate no interpolymer aggregation of the hydrophobic APS labels. Also, no intermolecular associations are evident through measurement of I E /I M as a function of terpolymer concentration in 0.5 M NaCl or at pH 3 and 7. Further photophysical results are interpreted on the basis of intramolecular excimer formation. Steady-state fluorescence emission studies indicate that I E /I M scales with the surfactant to APS ratio (SMR) in polymerizations. Also, I E /I m is a linear function of n, the initial number of APS monomer molecules per micelle. Steady-state excitation and time-resolved fluorescence emission studies have been utilized to probe the microenvironment surrounding the APS labels at varying polymer concentration, electrolyte concentration, and pH values.


The departure of Commissioner Mario Monti from his post as the EC Commissioner for competition policy provides a good opportunity to reflect upon the achievements and perceived failures of the European Commission in the field of antitrust law over the past five years. This paper attempts to do so on the basis of six core principles of sound competition policy. Under the first principle, it is undisputable that the Commission under Commissioner Monti's leadership has been at the forefront of the international efforts undertaken in the fight against cartels. Second, despite some weaknesses in areas such as conglomerate mergers or in its approach to the Microsoft case, the Commission's focus now appears to be in the protection of competition, not competitors. Third, after a string of annulments of Commission merger decisions by the EC judiciary, the Commission has made substantial progress toward assuring that its decisions are based on sound economics and hard evidence (including consideration of efficiencies). Fourth, recent Commission policy confirms that the Commission is ready to limit intervention to those cases that really cause harm to the competition process. Fifth, despite some concerns arising from the reform of the merger review process, the Commission is working hard to ensure that competition laws do not become bureaucratic roadblocks to efficient transactions. Sixth, Commissioner Monti has been instrumental in promoting international initiatives designed to promote a better understanding of competition policy. Competition Policy International VOLUME 1 NUMBER 1 SPRING 2005 eSapience knowledge shaping markets Mario Monti's Legacy: A U.S. Perspective


Stream sediment geochemical data are usually subjected to methods of multivariate analysis (e.g. factor analysis) in order to extract an anomalous geochemical signature (factor) of the mineral deposit-type sought. A map of anomalous geochemical signature can be used as evidence, in combination with other layers of evidence, for mineral prospectivity mapping (MPM). Because factor analysis may yield more than one factor in a stream sediment dataset, it raises the challenge of how to recognize the factor that best indicates presence of the mineral deposit-type sought. In addition, MPM is faced with the challenge of how to assign weights to classes in a geochemical evidence map. Accordingly, a new approach is discussed in this paper for the extraction of significant anomalous geochemical signature of the mineral deposit-type sought and for assigning weights to anomaly classes in a geochemical evidence map. In this approach, we used a staged factor analysis and then applied a logistic function to transform factor scores representing an anomalous geochemical signature in order to derive a map of geochemical mineralisation prospectivity indices (GMPI) as a spatial evidence layer for MPM based on the theory of fuzzy sets and fuzzy logic. The GMPI is a fuzzy weight in the [0,1] range. We demonstrate the application of the GMPI for mapping prospectivity for Mississippi valley-type fluorite deposits in the Mazandaran province, north of Iran, which is a greenfield area.


The article presents a comparative study of shale gas media debates in Germany and Poland. Drawing from the Sociology of Knowledge Approach to Discourse (SKAD), it addresses discursive conflicts over the use of hydraulic fracturing and its environmental impacts in both countries. The authors relate their analysis to the theoretical debate that emerged in the 1990s in French sociology concerning the question of "green justifications" that form a specific way of how social actors intervene, dispute, and build compromises in public discussions to protect non-human entities. Referring to these discussions, this article identifies several ecological justification clusters and the associated social actors that are 'compromised' or enclosed in existing orders of worth.


There are key HIV prevention measures that have been proven to be the most effective for people who use drugs. For people who inject drugs, needle and syringe programmes (NSP) are the most effective intervention. For people who inject opioids, the provision of opioid substitution therapy (OST) is also critical. For all people who use drugs, condom programmes are the most effective measure for preventing the sexual transmission of HIV.It is concerning that these proven HIV prevention measures – also known as harm reduction measures – have come under threat by recent suggestions that abstinence-based drug dependence treatment is an alternative strategy for preventing HIV transmission among people who use drugs. Such suggestions are not supported by evidence and undermine basic HIV prevention messages. Abstinence- and harm reduction-based strategies are not competing alternatives – both are mutually supporting elements of a comprehensive response to drug dependence, which includes HIV prevention.The UNODC, as the lead co-sponsor with UNAIDS for HIV prevention amongst people who use drugs, must clearly promote evidence-based measures to address the HIV epidemic. The expansion of abstinence-oriented treatment at the expense of harm reduction measures must not be promoted as an alternative strategy for preventing HIV.


This paper presents the results of quasi-static and dynamic testing of glass fiber-reinforced polyester leaf suspension for rail freight vehicles named Euroleaf. The principal elements of the suspension's design and manufacturing process are initially summarized. Comparison between quasi-static tests and finite element predictions are then presented. The Euroleaf suspension have been mounted on a tipper wagon and tested dynamically at tare and full load on a purpose-built shaker rig. A shaker rig dynamic testing methodology has been pioneered for rail vehicles, which follows closely road vehicle suspension dynamic testing methodology. The use and evaluation of this methodology have demonstrated that the Euroleaf suspension is dynamically much softer than steel suspensions even though it is statically much stiffer. As a consequence, the suspension dynamic loading at laden loading conditions is reduced compared to the most advanced steel leaf suspension over shaker rig track tests.


Clifford Odets and Lillian Hellman were two of the most influential playwrights of the 1930s, which was a decade of economic instability and political unrest in the United States. Odets began his career in 1935 with his workers' theatre smash hit Waiting for Lefty. Hellman's career took off with the premiere of her drama The Children's Hour. Both playwrights generated controversy with their plays through the emphasis of Popular Front values. They were influenced by the political, social, and economic conditions in the 1930s. An in-depth analysis of their plays reveals how the interrelationship between playwright and society is best understood through an examination of the role of male and female characters and the role of class in their plays. With a look at two plays each by both Odets and Hellman, the playwrights' works offer insight into the changes in society as well as the development of the decade's cultural history.


Using data from the National Urban Employment Survey, 1988-1999, this paper tries to separate the local and the national forces behind the increasing wage inequality in Mexico. The paper analyzes the trend of 3 different inequality measures in 16 different local labor markets and shows that the rising Mexican wage inequality is concentrated in the southern and central cities, while northern border cities seem to have experienced significant drops in wage inequality. Using the variability in the inequality measures at a local level, the analysis combines cross section and time series data to understand the role that local demographic, industrial and economic characteristics have played in the rising inequality. Drops in local economic activity, employment in the service sector, and occupational opportunities for executives seem to be positively correlated with the rising wage inequality, while occupational opportunities for moderately educated workers seem to be negatively correlated with it. Specialization of the local economies in the production of tradable goods shows contradicting results and no conclusion can be drawn from them.


Manvers coal has been pyrolysed to 500oC in a stirred autoclave under various pressures of nitrogen (pyrolysis) and hydrogen (hydropyrolysis). All products were investigated. Pyrolysis of coals involves the transfer of hydrogen atoms from one part of their structure to another. In the above experiments there was no way of labelling the hydrogen or of distinguishing between hydrogen which was initially part of the coal and hydrogen originating in the external atmosphere. Consequently, Manvers coal has been pyrolysed in an atmosphere of deuterium in order to obtain greater insight into the mechanism of hydropyrolysis. In particular it was hoped to distinguish between direct hydrogenation (deuteration!) of the coal and the products of pyrolysis and the 'shuttling' of hydrogen atoms between different parts of the pyrolysing coal. The addition to the coal of 5% (wt.% of coal) of either tetralin or pyrite was also studied. A variety of techniques were used to analyse the products of pyrolysis: gas chromatography - mass spectrometry and high performance liquid chromatography for tars; thermal conductivity gas chromatography and high resolution mass spectrometry for gases; methanol densities, microporosities and diffuse reflectance infra red spectroscopy for the cokes (chars); refractive index to determine deuterium in the liquor. An attempt has been made to apply basic thermodynamics to reactions which are likely to occur in the hydropyrolysis of coals. Diffusion and effusion rates for hydrogen and tar molecules have also been estimated.


Shi, Marlene. Infectious diseases still plague much of the developing world. Rapid and accurate diagnosis of diseases such as malaria, tuberculosis, and HIV is critical for improved control and management allowing for targeted and effective treatment. The Whitesides Research Group led by George Whitesides, the Woodford L. and Ann A. Flowers University Professor at Harvard, has developed a low-cost paper based diagnostic test that follows the principles of microfludics using paper's inherent channels and natural capillary action. The first application that the Whitesides paper diagnostic test will perform is liver toxicity screening. The printing method for these diagnostic tests will model the newspaper press print format for efficient and speedy production. The Whitesides Group intends the test results to be analyzed using telemedicine. Camera phones will transmit images of the test to a lab where a doctor or a computer can make a diagnosis. The key area that has not yet been explicitly defined is the method of packaging, distribution, and portability of the paper diagnostic test squares. The proposed paper diagnostic dispenser will make the tests portable which will increase access to diagnostic tools in the developing world. Heath care volunteers will be able to carry the tests in a simple container and dispense test squares as needed. This device increases the mobility of health care workers, requires little to no training to use, and facilitates the decentralization of health care services in developing countries.


In this paper, we employed multivariate econometric analysis approach to study the relationship between taxation and income inequality in Nigeria. The study was a country-specific appro ach using tax and macroeconomic data from 1980 to 2011. We collected data from the Central Bank of Nigeria Publications, Federal Inland Revenue Service, World Bank and Index Mundi. We estimated the data using a combination of co-integration and error correctio n model. Preliminary diagnostic analysis using Rams ey RESET test, Breuch-Pagan-Godfrey, Granger causality test and Breuch-Godfrey test of serial correlation were affected to check the accuracy of our model. T he preliminary analysis where favourable with no cases of serial correlation, non-normality, bi-dire ctional causality and model misspecification. We fo und a negative and robust relationship between total tax revenue, total tax revenue to GDP ratio and income inequality in Nigeria with t-values of (-2.748706) and (-2.287270) and negative coefficients of (-0.00 7869) and (-0.512235) respectively. We found a negative b ut insignificant relationship between GDPPC, PCREDIT/GDP, TDT/TIT*TTR while LFP and TDT/TIT had positive but insignificant relationship with income inequality with coefficients of (0.421) and (1.243794) and t-values of (1.732565) and (1.717362 ) respectively.


In recent years, there has been renewed interest in the use of industrial polices. The need for modern industrial policies has been increasingly acknowledged in the literature and by the praxis of developed and developing countries, including much of Latin America. Whether a country should have an industrial policy is no longer in question; rather, the issue is how to do it right. Nevertheless, research is still incipient on the experience with the specific institutional arrangements and governance structure required for effective modern industrial policy and the form that such institutions should take. This is especially true in large countries with developed subnational governance structures. One institutional mechanism considered vital to effective modern industrial policy is the modality of public-private dialogue and problem solving that supports a search for obstacles and solutions to agreed development objectives. This paper addresses industrial policy in general, but especially at the subnational level, with new empirical evidence from a large federal state: Mexico. It presents a detailed analysis of the governance of 32 newly created public-private State Productivity Commissions (Comisiones Estatales de Productividad, or CEPs). The analysis also is informed by new research on the longer experience of subnational public-private councils in Colombia's national system of competitiveness and innovation.


The role of psychiatry in primary care is an area of rapid expansion and increasing significance. Given the fact that inadequate diagnosis and treatment of psychiatric disorders are major public health problems, it is essential to integrate psychiatrists into multidisciplinary primary care teams. Since primary care physicians are increasingly called upon to act as "gatekeepers" in managed care programs, they will have to meet the important and growing need for broader psychiatric diagnostic and referral skills.


In the 1970s, cities across the United States and Western Europe faced a deep social and political crisis that challenged established principles of planning, economics and urban theory. At the same time, film industries experienced a parallel process of transition, the effects of which rippled through the aesthetic and narrative form of the decade's cinema. The Cinema of Urban Crisis traces a new path through the cinematic legacy of the 1970s by drawing together these intertwined histories of urban and cultural change. Bringing issues of space and place to the fore, the book unpacks the geographical and spatial dynamics of film movements from the New Hollywood to the New German Cinema, showing how the crisis of the seventies and the emerging 'postindustrial' economy brought film and the city together in new configurations.

Chapters cover a range of cities on both sides of the Atlantic, from New York, Philadelphia and San Francisco to London, Paris and Berlin. Integrating analysis of film industries and production practices with detailed considerations of individual texts, the book offers strikingly original close analyses of a wide range of films, from New Hollywood (The Conversation, The King of Marvin Gardens, Rocky) to European art cinema (Alice in the Cities, The Passenger, Tout va Bien) and popular international genres such as the political thriller and the crime film. Focusing on the aesthetic and representational strategies of these films, the book argues that the decade's cinema engaged with - and helped to shape - the passage from the 'urban crisis' of the late sixties to the neoliberal 'urban renaissance' of the early eighties. Splicing ideas from film studies with urban geography and architectural history, the book offers a fresh perspective on a rich period of film history and opens up new directions for critical engagement between film and urban studies.


Sex differences in inhibition and self‐regulation at a behavioral level have been widely described. From an evolutionary point of view, the different selection pressures placed on male and female hominids led them to differ in their behavioral strategies that allowed our species to survive during natural selection processes. These differences reflect changes in neural and structural plasticity that might be the core of sex differences, and of the susceptibility towards one psychiatric condition rather than another. The goal of the present review is to summarize current evidence for such a dichotomy in impulsive and compulsive behavior with a focus on drug addiction. Sex‐dependent differences in drug abuse and dependence will be examined in the context of pathophysiological regulation of impulse and motivation by neuromodulators (i.e. gonadal hormones) and neurotransmitters (i.e. dopamine). Advances in the understanding of the sex differences in the capability to control impulses and motivational states is key for the determination of efficacious biologically based intervention and prevention strategies for several neuropsychiatric disorders where loss of impulse control and compulsivity are the core symptoms.


The results presented in this article are related to the field of investigation defined inside the European TSER project on "Information Society, Work and Generation of New Forms of Social Exclusion " (SOWING). The thematic center of the project is connected with the question of the relations that exist between the introduction of information technologies (IT) and the changes in the waged labour as well as in the organisation of work systems. The introduction of these technologies transformed specially the activities on services as well as certain branches, where great changes of the organization of work for the next future assume, which are discussed within the margin of the debate on future forms of work. The tendencies within the occupational structures indicate an individualisation of the insecurities and an opening of the occupational carreers. For these reasons, the development of the occupational carreers is more and more bound to the biographical planning. The institutionalised occupational model is changing very strongly, which in the long term will take to social and cultural changes, not only in the professional life, but also in the private life.


In the developing world, skills in innovation and creative design have emerged as key attributes for graduating designers. Creativity is essential if we want to generate new solutions to the considerable and complex problems in architecture. Metaphor is frequently expressed as a key tool for enhancing creative design, yet little empirical research has been performed on how novice designers can use it within their design. The goal of this study is to empirically research the use of metaphor in the design studio, with a focus on its effects on design creativity and quality. A three-stage method is presented, which allows novice designers to use meanings and metaphors in the early stages of design and idea generation. This method was tested in an architectural studio with two groups as experiment and control groups. The results were evaluated using a qualitative research methodology and a questionnaire was prepared in which the students were requested to assess the use of this method in their design process. Also expert designers evaluated the design outcomes in both control and experiment groups. The results highlight that metaphor is a helpful tool for young designers to stimulate design creativity and has a noticeable effect on design quality factors such as novelty, value, flexibility, usefulness and detail. These research findings have different implication for novice architects and help them enhance creativity and quality in their design endeavors.


A flexible pedestrian legform impactor (FlexPLI) with biofidelic characteristics is aimed to be implemented within global legislation on pedestrian protection. Therefore, it is being evaluated by a technical evaluation group (Flex- TEG) of GRSP with respect to its biofidelity, robustness, durability, usability and protection level (Zander, 2008). Previous studies at the Federal Highway Research Institute (BASt) and other laboratories already showed good progress concerning the general development, but also the need for further improvement and further research in various areas. An overview is provided of the different levels of development and all kinds of evaluation activities of the Flex-TEG, starting with the Polar II full scale pedestrian dummy as its origin and ending up with the latest legform impactor built level GTR that is expected to be finalized by the end of the year 2009. Using the latest built levels as a basis, gaps are revealed that should be closed by future developments, like the usage of an upper body mass (UBM), the validation of the femur loads, injury risk functions for the cruciate knee ligaments and an appropriate certification method. A recent study on an additional upper body mass being applied for the first time to the Flex-GT is used as means of validation of recently proposed modified impact conditions. Therefore, two test series on a modern vehicle front using an impactor with and without upper body mass are compared. A test series with the Flex-GTR will be used to study both the comparability of the impact behavior of the GT and GTR built level as well as the consistency of test results. Recommendations for implementation within legislation on pedestrian protection are made. The full text of this paper may be found at: http://www-nrd.nhtsa.dot.gov/pdf/esv/esv21/09-0277.pdf For the covering abstract see ITRD E145407.


PURPOSE
To explore feasibility, maximum-tolerated dose (MTD), and recommended dose (RD) for phase II studies of weekly oxaliplatin for the treatment of relapsed or refractory pediatric solid malignancies.

PATIENTS AND METHODS
Eligible patients were 6 months to 21 years old, had a diagnosis of a solid malignancy, and had experienced treatment failure with at least two or more previous lines of therapy. The phase I study was multicentric, open-label, and nonrandomized. It foresaw two phases: a dose-escalation phase (comprising six levels) to find the RD and an extension at the RD to evaluate the cumulative toxicity. Oxaliplatin was administered intravenously over 2 hours on days 1, 8, and 15 of a 28-day cycle.

RESULTS
Forty-five patients were enrolled: 29 patients in the dose-escalation phase and 16 patients in the extension at the RD. Median age was 9.5 years (range, 2.8 to 20.0 years) and 7.8 years (range, 1.8 to 19.2 years), respectively. The dose-limiting toxicities during the first treatment cycle were grade 3 (G3) sepsis at 50 mg/m(2), G3 dysesthesia at 90 mg/m(2), and G3 dysesthesia and G3 paresthesia at 110 mg/m(2), thus the MTD and RD was 90 mg/m(2). No case of ototoxicity was reported. Stable disease was reported in seven patients (16.3%), and confirmed partial response was observed in two patients (4.7%), one with neuroblastoma and one with osteosarcoma.

CONCLUSION
Oxaliplatin administered in a weekly schedule has an acceptable safety profile, different from cisplatin and carboplatin, and shows activity in children with relapsed or refractory solid tumors, suggesting further investigation in pediatric malignancies.


Serious games are successfully applying game engines for purposes that go beyond pure entertainment However this
results in a serious game being dependent on a particular game engine. This undermines the ability to keep the serious
game up to date with the latest in gaming technology and also causes insecurity due to the possibility of the
discontinuation of a game engine or the possibility of its support dwindling. In this thesis, the 'game' is separated from
the game engine in order to make it portable between game engines. The game elements this work makes portable are
the game logic, the object model and the game state, which represent the game's brain, and which are collectively referred
to as the game factor, or G-factor. This separation is achieved by using an architecture called game space architecture
(GSA), which ,combines a variant of the model-view-controller (MVC) pattern to separate the G-factor (the model) from
the game engine (the view) with on-the-fly scripting to enable communication through an adapter (the controller). This
enables multiple views (i.e. game engines) to exist for the same model (i.e. G-factor).
The success of GSA in achieving its objective is evaluated by two types of evaluation: structured and unstructured.
The principal findings from the evaluation process reveal that GSA is capable of servicing the same G-factor to multiple
game engines and that it supports modifiability. They also reveal that GSA adds little development overhead. The ability
of GSA to scale to real world applications is demonstrated by the development of a serious game for traffic accident
investigators (SGTAI).
SGTAI itself is used to investigate the suitability of a serious game to address the Dubai police force's current traffic
accident investigation training needs. These needs were identified in a field study conducted in the summer of 2004 to
assess the current training methods oflectures and on-the-job training. SGTAI was then developed by combining game
design and instructional design to ensure the learning objectives were integral to the gameplay. To assess the learning
effectiveness of SGTAI an experiment was conducted in February and March of 2006 for fifty-six police officers from
the Dubai police force. They were divided into two groups: novices (0 to 2 years experience) and experienced
investigators (with more than 2 years e.'{perience). The experiment revealed significant performance improvements in
both groups, with the improvement reported in novices significantly higher than the one reported in experienced
investigators.


This article is a case study based on court records. What seems initially to be a petty theft gives rise to remarkable events. Affairs that are initially private later become public. Various events in and around the court throw light upon the way court and community respond to family stress in a mid-nineteenth century rural northern Swedish community. Testimonies by a large number of witnesses in court reveal a society in transition with elements of a money market, which means here a huge amount of ready money in circulation and arenas ready to shelter private transactions.


We report on a system to control the emitted wavelength of a laser independently from its pump conditions. To illustrate the concept, it is applied to III-V microdisk lasers fabricated on a CMOS pilot line for application to multicolored optical interconnections. Two different control systems are experimentally studied. The first one requires two coupling areas between the resonator and its coupled waveguide while the second solution is based on a photonic crystal mirror and a single coupling area. In both cases, the independent tuning of their emission from the pump conditions is demonstrated with a very high compacity. A controlled multimode emission in microdisk lasers is obtained for the first time.


Approaches to urban slums are a multimedia sourcebook that comprises 14 self-running audiovisual presentations and 18 video interviews. It is organized into four broad sections: adaptive approaches, proactive approaches, case profiles, and thematic interviews. The sourcebook itself, which contains more than nine viewing hours of content on CD-ROM, does not exist in printed format. This guide provides an overview of the structure and content of the CD as well as approximate running times for the various sections. Approaches to urban slums builds on an extensive body of knowledge accumulated over 35 years from a wide range of sources. The 14 self-running audiovisual presentations include photographs, illustrations, maps, graphic animations, and aerial imagery, along with voice-over narration. The sourcebook's multimedia format facilitates the presentation of a highly complex subject by adding an audiovisual and spatial dimension to the descriptive and analytical discussion. The 18 video interviews provide access to the knowledge and opinions of urban stakeholders and experts on specific issues, and from various development perspectives, including development organizations, governments, Non-governmental Organizations (NGOs), community organizations, academia, and professional urban consulting.


The theory of differential overqualification, developed by Robert Frank (1978), claims that married women in smaller labor markets have a higher risk of working in jobs for which they are overqualified. This stems from the problem of dual job search for couples which is much more difficult to optimize than single job search. Here, for several reasons husbands tend to first optimize their individual job search. Their wives are "tied movers" or "tied stayers" in the sense that their job search is undertaken under the condition that the job search of their husbands is optimized. This leads especially in smaller labor markets to a higher risk of a mismatch between formal qualifications and job requirements. The only specific empirical test of this theory, until now, has been performed by McGoldrick and Robst (1996). Their results, using US data, do not support the theory. Using German panel data (GSOEP), we also test the theory of differential overqualification. Unlike previous studies we control for commuting distances and our own results provide some mixed support for the differential overqualification hypothesis.


This article is part of a review symposium of Sheila Cavanagh's book Queering bathrooms: gender, sexuality and the hygienic imagination, 2010, Toronto, University of Toronto Press, 295 pp., £19.94 (paperback), ISBN 978-1-4426-10736


Detection of Agreement and Disagreement: An investigation of linguistic coordination and conversational features Maria Alexandropoulou Chair of the Supervisory Committee: Gina-Anne Levow, Assistant Professor Department of Linguistics The focus of this thesis is detection of agreement and disagreement in multiparty conversations using existing transcripts from the ICSI corpus. We use an unsupervised lexicon-based method to create our baseline and then follow a supervised approach to study the effect on performance of different feature sets. The feature sets we are interested in are the following: a. lexicosyntactic, b. Dialog act tag-based features, c. Linguistic style coordination features and d. Conversational features (baseline, individual and non-individual ones). The results enabled us to study the presence of coordination in agreeing and disagreeing statements and showed that the performance can improve when adding further features on top of the lexicosyntactic ones. Additionally, we saw that non-individual conversational features can improve the performance of agreement detection while individual conversational ones appear to have a similar effect on disagreement detection.


It has been previously found that fat cells release a hormone that regulates bone remodeling. The concept of homeostasis suggests that bone should be able to signal back to the tissues that regulate metabolism to establish a feedback system. Lee et al. sought such an endocrine connection and screened mice in which genes specifically expressed in osteoblasts (the cells responsible for bone deposition) were knocked out for altered metabolism. Using this approach, they identified the Esp gene, which encodes a protein tyrosine phosphatase called OST-PTP that is present only in osteoblasts and Sertoli cells. (Analysis of knockout mice or mice with targeted disruption of the gene only in osteoblasts showed the same phenotypes, and these are referred to collectively as Esp−/−.) The Esp−/− mice showed increased perinatal lethality, increased pancreatic β cell mass, increased circulating concentrations of insulin and adiponectin, decreased blood glucose concentration, and increased glucose tolerance. Adiponectin is released by adipocytes and enhances insulin sensitivity. In addition, the Esp−/− mice were resistant to obesity and glucose intolerance caused by a high-fat diet or excessive food intake (caused by lesioning the ventromedial hypothalamus). The metabolic alterations in the Esp−/− mice were reversed if the mice were heterozygous for the gene encoding osteocalcin, an osteoblast-secreted protein, suggesting that OST-PTP regulates osteocalcin. However, the concentration of circulating osteocalcin was normal in the Esp−/− mice; therefore, OST-PTP influences the bioactivity of osteocalcin. Osteocalcin is posttranslationally modified by γ-carboxylation of glutamic acid residues, and in the Esp−/− mice the abundance of uncarboxylated osteocalcin relative to carboxylated osteocalcin in circulation was increased. Coculture experiments with wild-type osteoblasts, Esp−/− osteoblasts, or warfarin-treated osteoblasts (warfarin inhibits γ-carboxylation) and adipocytes or pancreatic β cells supported the hypothesis that uncarboxylated osteocalcin is the bioactive form and that the release of the uncarboxylated form of Esp−/− osteoblasts is elevated. These results have important clinical implications (see Semenkovich and Teitelbaum). First, they point to additional targets (osteocalcin, OST-PTP, and the enzymes involved in osteocalcin γ-carboxylation) for treating obesity and diabetes. Second, warfarin is used clinically to treat thrombosis. The effect on metabolism in these patients should be investigated. Third, treatments used for osteoporosis prevention inhibit bone remodeling and may alter this homeostatic mechanism linking the skeleton to energy metabolism. Finally, this may provide a mechanistic framework for understanding the effects of glucocorticoid treatment on metabolism and bone remodeling as dependent and not independent effects. N. K. Lee, H. Sowa, E. Hinoi, M. Ferron, J. D. Ahn, C. Confavreux, R. Dacquin, P. J. Mee, M. D. McKee, D. Y. Jung, Z. Zhang, J. K. Kim, F. Mauvais-Jarvis, P. Ducy, G. Karsenty, Endocrine regulation of energy metabolism by the skeleton. Cell 130, 456-469 (2007). [Online Journal] C. F. Semenkovich, S. L. Teitelbaum, Bone weighs in on obesity. Cell 130, 409-411 (2007). [Online Journal]