Background and Aim: Heavy metals have been recognized as very poisonous elements and their discharge into water sources can cause damaging effects on human and environmental health. The present study aimed at producing activated carbon from scrap tires and using it in removing Pb +2 from synthetic aqueous solutions. Materials and Methods: In this experimental study, activated carbon powder was derived from scrap tires under laboratory conditions. The effect of Pb (II) ions with the concentration 10-100mg/l, pH 2-8, contact time 3 hs , and the adsorbent dosage 0.1-0.6 g were investigated in batch adsorption system. Besides, the chemical composition and solid structure of the derived activated carbon were analyzed using Scanning Electron Microscopy (SEM) coupled with energy dispersive spectrometry (EDS). The surface area of derived activated carbon was calculated by Brunauer-Emmett-Teller (BET) and Barret-Joyner-Halenda (BJH) isotherms. The experimental data was analyzed using Langmuir and Freundlich isotherm models. Results: It was found that the main component of activated carbon was Carbon element (83.276%). BET and BJH Surface areas of activated carbon were approximately 185.046 and 146.443 m 2 /g, respectively. It was discovered that activated carbon dosage increasing leads to decreasing in q max , while with increasing of pH of Pb +2 ions adsorption increased. The experimental adsorption isotherm complied with Freundlich equation model (R 2 =0.982) and the maximum amount of adsorption (q max ) was 8.695 mg/g. Conclusion: The present study showed that derived activated carbon from scrap tires is highly effective in Pb removal from aqueous solutions. In addition, producing activated carbon from scrap tire can provide a two-fold green and cost-effective advantage and it can be a suitable recycling method for scrap tires.


White sharks are highly migratory and segregate by sex, age and size. Unlike marine mammals, they neither surface to breathe nor frequent haul-out sites, hindering generation of abundance data required to estimate population size. A recent tag-recapture study used photographic identifications of white sharks at two aggregation sites to estimate abundance in "central California" at 219 mature and sub-adult individuals. They concluded this represented approximately one-half of the total abundance of mature and sub-adult sharks in the entire eastern North Pacific Ocean (ENP). This low estimate generated great concern within the conservation community, prompting petitions for governmental endangered species designations. We critically examine that study and find violations of model assumptions that, when considered in total, lead to population underestimates. We also use a Bayesian mixture model to demonstrate that the inclusion of transient sharks, characteristic of white shark aggregation sites, would substantially increase abundance estimates for the adults and sub-adults in the surveyed sub-population. Using a dataset obtained from the same sampling locations and widely accepted demographic methodology, our analysis indicates a minimum all-life stages population size of >2000 individuals in the California subpopulation is required to account for the number and size range of individual sharks observed at the two sampled sites. Even accounting for methodological and conceptual biases, an extrapolation of these data to estimate the white shark population size throughout the ENP is inappropriate. The true ENP white shark population size is likely several-fold greater as both our study and the original published estimate exclude non-aggregating sharks and those that independently aggregate at other important ENP sites. Accurately estimating the central California and ENP white shark population size requires methodologies that account for biases introduced by sampling a limited number of sites and that account for all life history stages across the species' range of habitats.


Environmental organic pollutants are mineralized to harmless final-products such H2O and CO2 by photocatalytic advanced oxidation processes (AOPs). In photocatalytic-AOPs, an appropriate concentration of p-Cresol was mixed with certain amount of ZnO in 500 mL deionized water according to an experimental-design. Then the mixture was irradiated by UV-A lamp at different pH for 6 h. At specific time intervals, the sampling was carried out to calculate the efficiency of the photodegradation. Therefore, the photodegradation as a system consists of four input variables such irradiation time, pH, amount of ZnO and p-Cresol's concentration while the only output was the efficiency. In this work, the system was modeled and optimized by semi-empirical response surface methodology. To obtain the empirical responses, the design was performed in laboratory. Then observed responses were fitted with several well-known models by regression process to suggest a provisional model. The suggested model which was validated by several statistical evidence, predicted the desirable condition with higher efficiency. The predicted condition consisted of irradiation time (280 min), pH (7.9), photocatalyst (1.5 g L−1), p-Cresol (95 mg L−1) and efficiency (95%) which confirmed by further experiments. The closed confirmation results has presented the removal (efficiency = 94.7%) of higher p-Cresol concentration (95 mg L−1) at shorter irradiation time in comparison with the normal photodegradation efficiency (97%) which included irradiation time (300 min), pH (7.5), photocatalyst amount (1.5 g L−1) and p-Cresol (75 mg L−1). As a conclusion, the modeling which is able to industrial scale up succeeded to remove higher concentration of environmental organic pollutants with ignorable reduction of efficiency.


There is a causal relationship between obesity-associated diabetes and an increased risk of infection. The ability of obese (fa/fa) Zucker rats, a model for non-insulin-dependent diabetes mellitus (NIDDM), to clear Candida albicans from the circulation and tissues was compared to that of lean (Fa/fa, Fa/Fa) Zucker rat controls as a measure of immune function. The ID50 necessary to establish tissue colonisation in lean Zucker rats was 1.18 log10 times greater than that determined for the obese Zucker rats. Nine days after intravenous (i.v.) injection of a yeast suspension, the organs of obese rats had a 10-fold greater yeast/g organ burden than did lean rats. The kidney was determined to be the primary target organ for colonisation. Germ-tube formation by C. albicans occurred at a rate 1.5 times faster in serum from obese rats than in serum from lean rats. Peritoneal polymorphonuclear leucocytes, resident macrophages and thioglycollate-elicited macrophages from lean Zucker rats displayed a significantly higher ability to kill ingested yeast cells than analogous cell populations from obese Zucker rats.


No issue is more controversial in U.S. education than mandatory statewide or nation-wide testing (Fordham Report, 1998). Many people believe it is an essential ingredient of reform while others feel it is a menace and a distraction to quality teaching and learning. To better understand the issues that the Bush Administration will support, one must first be familiar with the history George W. Bush brings to the presidency. The accountability system in Texas is one of the nation's toughest, according to Education Weekly (Brooks, 1999). The system began under Governor Ann Richards. Although President Bush did not create the system his administration has expanded and increased the expectations of students as well as school districts and teachers. For the past decade, as required by state statute, Texas has assessed minimum basic skills in reading, mathematics, and writing, first with the Texas Assessment of Basic Skills (TABS) tests and then with the Texas Educational Assessment of Minimum Skills (TEAMS) examinations. Changes in state law required the implementation of a new criterionreferenced program. This changed occurred at the end of 1990 and the concept of the Texas Assessment of Academic Skills, or TAAS tests was born. (TEA, 2001) Each year the 7,053 public schools and 1,042 school districts are ranked based largely on scores from the TAAS (TEA, 2001). The primary purpose of the state student assessment program is to provide an accurate measure of student achievement in the areas of reading, writing, mathematics, social studies, and science. The scores on these tests are the backbone of the Texas Education Agency's accountability system. This system rates schools as exemplary, recognized, acceptable, or low performing. Bonuses, pay raises, cash incentives, and public pressure are used to motivate administrators and teachers to teach the skills necessary for success on the tests. Several shifts in philosophy have occurred since the dawn of the Texas testing program and several new assessments have been developed as a result of legislative requirements or actions by the State Board of Education (SBOE). Additionally the state has stipulated that end-of-course tests be administered in selected high school courses. Currently students must take an exit level test and those not meeting the minimum expectations must retake those sections of the assessment instrument on which they had not performed satisfactorily. Students cannot receive a diploma until they have passed this exit level assessment. Even with a decade of statewide testing, all is not well. "Schools in Texas hold distinction for one of the lowest graduation rates in the nation coupled with one of the lowest ratings in the nation for college preparation," according to a report written by education research analyst Chris Patterson. Furthermore. As TAAS scores continue to rise, the percentage of Texas students who require remediation in college has grown 16 percent. Additionally, the SAT scores of students in Texas remain below the national average. The Texas Public Policy Foundation (TPPF) claims that the focus on TAAS is getting as many students as possible to achieve at a very basic level. TPPF concludes that since so much hinges on these scores promotions, hiring and firing decisions, financial incentives - school administrators are foolish if they don't reallocate time and substantial resources from higher-achieving children whom they know will pass the test to lower-achieving children who might not. Many schools have developed specialized classes during which lower-achieving students learn skills to help them master the TAAS. These classes are mandatory and in many cases the student must give up an elective class in order to stay on track and pass the TAAS. With the ramifications of doing poorly on these tests, school districts use a wide variety of motivational techniques to encourage students to do their best during test day. …


We demonstrate transverse-magnetic (TM) dominant deep-ultraviolet (DUV) stimulated emission from photo-pumped AlGaN multiple-quantum-well lasers grown pseudomorphically on an AlN/sapphire template by means of photoluminescence at room temperature. The TM-dominant stimulated emission was observed at wavelengths of 239, 242, and 243 nm with low thresholds of 280, 250, and 290 kW/cm2, respectively. In particular, the lasing wavelength of 239 nm is shorter compared to other reports for AlGaN lasers grown on foreign substrates including sapphire and SiC. The peak wavelength difference between the transverse-electric (TE)-polarized emission and TM-polarized emission was approximately zero for the lasers in this study, indicating the crossover of crystal-field split-off hole and heavy-hole valence bands. The rapid variation of polarization between TE- and TM-dominance versus the change in lasing wavelength from 243 to 249 nm can be attributed to a dramatic change in the TE-to-TM gain coefficient ratio for the sa...


Starting from an original framework based on four dimensions and thirteen objectives of sustainable urban mobility policies, this paper advocates the selection of a core set of performance indicators founded on a participative procedure. Citizen participation and stakeholder involvement is made possible by a national sample survey and a deliberative multi-criteria analysis, respectively. Such a procedure is applied to the Italian case and it shows that the set of indicators based on citizen evaluations radically differs from that based on stakeholders' opinions - citizens are more oriented towards reducing private transport costs, air pollution and traffic accidents; stakeholders are more in favour of improving car-free accessibility and reducing the consumption of land and public space generated by urban mobility. For further testing at a local scale, a more articulated procedure is proposed in order to increase the role of citizens and to help generate unequivocal results.


The potential availability of forage feed is high, but in reality this potential has not been able to meet the requirement of feed both in sustainable quantity and quality. Silage made with the use of liquid fermentation additive (FA) can be a solution for those problems. The use of  different levels of FA and addition of Lactobacillus plantarum bacteria as well as formic acid were expected to improve the nutritive quality of napier grass silage. The first experiment was designed to measure the fermentative quality of napier grass silage. The treatments used were the levels of FA, L. plantarum, and formic acid supplementations. The experiment used a completely randomized design with a 3x2x2 factorial arrangement with 3 replications. The first factor was the level of liquid FA (5%, 7.5%, and 10%), and the second factor was the inoculation of L. plantarum (without and with inoculation of the L. plantarum), and the third factor was the addition of formic acid (without and with the addition of 0.15% formic acid). The second experiment was aimed to evaluate chemical and microbiological characteristics, and in vitro digestibility of selected napier grass silage. The results showed that napier grass silage from all treatments showed good qualities. There were interactions between FA, L. plantarum, and formic acid on DM content (P<0.05) and ammonia production (P<0.01). The use of FA showed an interaction (P<0.01) with the addition of L. plantarum and formic acid in Fleigh point. Ammonia production in rumen (P<0.01), total VFA (P<0.05), and in vitro digestibility (P<0.01) were significantly affected by the treatments. The optimal level of liquid FA was 7.5%. Based on the nutritive quality of silage, L. plantarum addition was as effective as control treatment to improve nutritive quality of napier grass silage through the increased  of fermentation characteristics i.e., low pH, high DM product, high fermentation product (VFA), and digestible on rumen. Formic acid reduced ammonia production during ensiling and fermentation in rumen, but it was less effective in inhibiting the fermentation process when it was combined with L. plantarum.


Problem statement: The urban view area's extent is an arena for the classification of Tehran's governmental and non-governmental squares creating different similarities and dissimilarities in this regard. The analysis of the similarities and dissimilarities can reveal the special and general properties of Tehran's governmental and non-governmental squares in the urban view area. The comparative study can provide a solution for analyzing the quality and the origins of the differences between Tehran's governmental and non-governmental squares in the urban view extent even with the existence of similarities. Adopting landscapebased approaches, the other researchers of the urban view areas have not so far made use of a comparative study in regard to Tehran's squares. Research method: The present study has made use of a qualitative research method andit is applied research in terms of objectives. The present research paper has for the first time investigated Tehran's governmental and non-governmental squares in the area of urban view based on a comparative research method. The study was, on the one hand, based on the library data and it was, on the other hand, drawn on the field data. Thus, after obtaining the data, the various forms and shapes used in the architectural structures and façades have been compared in terms of the arrangement at one another's side in longitudinal and transversal proportions and the effects of these shapes have been obtained for the squares' facades. Research objective: The present study is aimed at analyzing the quality and the origins of the differences and similarities created in the area of urban view. Conclusion: The performed analyses made it clear that the systems forming the square stemmed from the proportions between the dimensions and levels of the openings, positioning of them and façade's geometry, which was per se influenced by the squares' positioningand function. Although these systems may have undergone changes in the course of the history of Iranian squares, their contents have lasted till the several recent decades and can be applied as a collection of designing indices by the landscape architects and urban engineers.


With Hit Me, Fred , sensational sideman Fred Wesley Jr. moves front and center to tell his life story. A legendary funk, soul, and jazz musician, Wesley is best known for his work in the late sixties and early seventies with James Brown and as the leader of Brown's band, Fred Wesley and the JB's. Having been the band's music director, arranger, trombone player, and frequent composer, Wesley is one of the original architects of funk music. He describes what it was like working for the Godfather of Soul, revealing the struggle and sometimes stringent discipline behind Brown's tight, raucous tunes. After leaving Brown and the JB's, Wesley arranged the horn sections for Parliament, Funkadelic, and Bootsy's Rubber Band, and led Fred Wesley and the Horny Horns. Adding his signature horn arrangements to the P-Funk mix, Wesley made funk music even funkier.

Wesley's distinctive sound reverberates through rap and hip-hop music today. In Hit Me, Fred , he recalls the many musicians whose influence he absorbed, beginning with his grandmother and father—both music teachers—and including mentors in his southern Alabama hometown and members of the Army band. In addition to the skills he developed working with James Brown, George Clinton, Bootsy Collins, and the many talented musicians in their milieu, Wesley describes the evolution of his trombone playing through stints with the Ike and Tina Turner Revue, Hank Ballard, and Count Basie's band. He also recounts his education in the music business, particularly through his work in Los Angeles recording sessions.

Wesley is a virtuoso storyteller, whether he's describing the electric rush of performances when the whole band is in the groove, the difficulties of trying to make a living as a rhythm and blues musician, or the frustrations often felt by sidemen. Hit Me, Fred is Wesley's story of music-making in all its grit and glory.


Background: One of the most known reasons of the majority of diseases is oxidative stress, created by free radicals, and the most important defensive factors against these free radicals are antioxidants that can be naturally found in most herbs; hence, we studied antioxidant activity of Matricaria chamomilla L. hydroalcoholic extract (MCHAE) and compared it to lovastatin in Wistar rats. Materials and Methods: In this research, 30 Wistar rats (165 ± 15 g) were used that were randomly put in the control group (common diet), sham group (high cholesterol diet [2%]), experimental Groups of 1 and 2 (high cholesterol diet 2%) and arrangement with 0.55 and 1.1 mg/ml doses of M. chamomilla L. extract), and experimental Group 3 (high cholesterol diet [2%] and 10 mg/kg lovastatin). At the beginning and end of the study, blood sampling was performed on the rats, and plasma serum malondialdehyde (MDA) and red blood cell (RBC) superoxide dismutase (SOD) concentrations were measured. The results were analyzed by SPSS 16 software and P < 0.05 was considered as the limit of statistical inference. Results: The amount of SOD in RBC and plasma MDA in control group did not show a significant difference. In addition, the levels of these two enzymes in experimental Groups of 1 and 3 that, respectively, received 0.55 mg/ml MCHAE and 10 mg/kg lovastatin drug did not show a significant difference at the beginning and end of the study and were in normal level, "in spite of receiving high cholesterol (2%) diet. But 1.1 mg/ml dose of hydroalcoholic extract of Matricaria chamomilla L. that experimental group 2 was treated by it, could not prevent increase of Superoxide Dismutase in Red Blood Cell and Malondialdehyde in plasma at the end of the study compared to its beginning. Conclusion: The results of this research indicate that M. chamomilla L. has good antioxidant activity and can contrive making natural antioxidant compounds to prevent diseases caused by oxidative stress.


Sir (William) Richard Shaboe Doll (1912–2005), described by the British Medical Journal as "perhaps Britain's most eminent doctor", ushered in a new era in medicine: the intellectual ascendancy of medical statistics. Doll was the giant of Oxford medicine who, with Austin Bradford Hill, not only helped determine the link between smoking and lung cancer, but also helped integrate a statistical approach into both public health and patient care.

Many eloquent obituaries have been written,1–3 but in this detailed, forthright and authorized biography of Doll, Conrad Keating, the writer in residence at the Wellcome Unit for the History of Medicine at Oxford University, also opens a window on social conditions throughout 20th-century Britain. This book would appeal to anyone with an interest in scientific, medical and social history, public health, epidemiology, cancer, tobacco or Oxford University.

Doll became a non-conformist early and remained so until his death. By the time he finished school he was already turning away from religion and towards pacifism and socialism. Despite coming from an "establishment" (upper-class) background, as a young man in the 1930s, he was deeply affected by the suffering, mass unemployment and malnutrition he witnessed. His antifascist politics led to him joining the Communist party and he described himself as a "democratic communist". He became increasingly aware that much disease and premature death could be prevented by social change.

He studied medicine at St Thomas's Hospital, London (1931–7) and, after service in the Second World War, became an epidemiologist – an ideal vocation for a numerate doctor with a social conscience, since it permitted him to apply his talents to major public health problems around the world. He eventually researched an extraordinary range of health issues including smoking, asbestos, the oral contraceptive pill, HIV/AIDS, radiation and fluoridation.

At the end of the Second World War, Britain had the highest incidence of lung cancer in the world – and no one knew why. Doll himself originally thought the increase might be due to occupational factors, or to the tarring of roads, as there were known carcinogens in tar.

By the end of 1950, studies from different countries had linked smoking and lung cancer, the best being those by Doll & Hill and by Wynder & Graham. Doll and his mentor Bradford Hill went on to show that smoking caused not only lung cancer but also many other diseases. Even with solid science, it was many frustrating years before the medical profession, politicians and the public really accepted the evidence.

Doll and Hill chose the path of acting only as scientists, presenting the evidence and allowing others to act upon it. They were concerned that if they campaigned, it could lead to their scientific objectivity being questioned. But, increasingly in his later years, Doll testified in court against the tobacco industry and advocated bans on tobacco promotion.

Oxford medicine may owe more to Doll than to anyone else in the 20th century, according to Keating. He moved to Oxford in 1969 as Regius Professor of Medicine, where he helped train many of the next generation of medical researchers and became the founder of Green Templeton College. Doll made Oxford a world centre for epidemiology and his techniques have been widely adopted by his students across the world.

Doll was knighted in 1971 and made a Companion of Honour in 1996. He received numerous honorary doctorates and fellowships from around the world. I and many others felt that he should have received a Nobel Prize.

The 25 years after Doll's retirement in 1979 as regius professor were amazingly productive. He wrote, travelled, lectured and collaborated with many others in new research. Until weeks before his death in 2005, Doll continued working daily in the Cancer Epidemiology Unit (directed since 1989 by Valerie Beral) or the Clinical Trial Service Unit (co-directed since 1985 by Rory Collins and Richard Peto).He enjoyed a long and happy marriage to Joan Faulkner, who had worked at the Medical Research Unit (and had led Doll into his first job) until her death in 2001.

Doll thought, wrote, and spoke clearly. Keating describes him as often perceived as an elegant and austere intellectual, but with a dry and mischievous sense of humour. I remember him with much respect and fondness. In the early 1990s, Doll attended a lecture I gave on the tobacco epidemic in Asia. I introduced the epidemiology, then spoke of the "scientific evidence". After the talk, Doll said to me, politely but firmly: "Epidemiology is science". I never dared make that mistake again!

One twist in the tale was an uncannily-targeted e-mail that I received after his death, supposedly written by a chaplain who claimed to be an executor of his will, informing me that Doll had left me £400 000 for my work on tobacco control in Asia and asking me to contact a "lawyer" for my bank details. The giveaway was the description of Doll as "always a Christian gentleman…" The writer had not, like Doll, been meticulous in checking his facts.


Abstract: Speech is the most natural means of communication between humans. Speech signals carry various levels of information, such as linguistic content, emotion, the acoustic environment, language, the speaker's identity and their health condition, etc. Automatic speaker recognition technologies aim to verify or identify a speaker using recordings of his/her voice. In practice, automatic speaker verification (ASV) systems should be robust to nuisance variation such as differences in the microphone and transmission channel, intersession variability, acoustic noise, speaker ageing, etc. Significant effort invested over the last three decades has been tremendously successful in developing technologies to compensate for such nuisance variation, thereby improving the reliability of ASV systems in a multitude of diverse application scenarios. In a number of these, specifically those relating to authentication applications, reliability can still be compromised as a result of spoofing attacks whereby fraudsters can gain illegitimate access to protected resources or facilities through the presentation of specially crafted speech signals that reflect the characteristics of another, enrolled person's voice. ASV systems should be resilient to such malicious spoofing attacks. This tutorial presents a treatment of the issues concerning the robustness and security of an ASV system in the face of spoofing attacks. We also discuss current research trends and progress in developing anti-spoofing countermeasures to protect against attacks derived from voice conversion, speech synthesis, replay, twins (which has more malicious nature in attacking ASV systems and also called as twin's fraud in biometrics literature) and professional mimics. The tutorial will give an overview of the risk and technological challenges associated with each form of attack in addition to an overview of the two internationally competitive ASVspoof challenges held as special sessions at INTERSPEECH 2015 and INTERSPEECH 2017. The tutorial will conclude with a summary of the current state-of-the-art in the field and a discussion of future research directions.


Food still is, and will continue to be, a basic issue at every day decision process in human behavior. Food consumption has been a problematic issue in human history and today is also recognized as a basic pilar for human health and welfare/quality of life. From a global problem up to the middle of the eighties, right now food security is mainly a local issue (however a macro-level approach continued to be necessary for long run perspective and food safety concerns in trade and commercialization). Food and nutritional concerns today still are unforgetable issues on a local base perspective in many regions: the most common problems are related to the access and consumption to achieve the minimum nutritional requirements, but also other dimension such as production, transformation, distribution and logistic aspects of the "food equation", mainly in less developed countries, are crucial aspects to be taken into consideration. Economic effciency from a production perspective in the food sector, measured in terms of output per unit of input (technical and technologial innovation) achieved one of the best performances in terms of development in the last 30 years. The same can not be refered in regard to markets and institutional innovations. In fact, looking at institutions including markets and governments, it is necessary to explore and identify the several observed failures (institutional and governance failures: markets, governmental and others) were science can make a contribution. This is the main purpose of the current research, which is starting based on observed problems and applied solutions with good results in many situations, but also pointing out many other situations were solutions are needed based on the old instruments, but also based on innovative procedures. The methodoly followed explores the basic theorectical approach in production theory and in consumption micro-economic concepts, allowing the introduction of some new purposals in regard to efficiency measures. Adding to those aspects some new questions and models are discussed in regard to the "institutional/organizational economics" in the actual world, providing support for improvement measures ( and policy suggestions). The Brasilien case is explored in more detail ( the "Fome Zero Program"), but also some african examples are used to ilustrate that many solutions will have to rely on technological changes, but also on institutional innovations.


In this paper, we present an agent-based model for exploring the interplay of basic structural and socio-cognitive factors and conventional water saving measures in the evolution of domestic water use in metropolitan areas. Using data of Barcelona, we discuss three scenarios that involve plausible demographic and cultural trends. Results show that, in the three scenarios, aggregate outcomes are consistent with available conventional modelling (while total water use grows, per capita water use declines); however, the agent-based simulation also reveals, for each scenario, the different dynamics of simple policy measures with population growth, cultural trends and social influence; thus providing unexpected insights for policy design.


This paper introduces AC, a set of language constructs for composable asynchronous IO in native languages such as C/C++. Unlike traditional synchronous IO interfaces, AC lets a thread issue multiple IO requests so that they can be serviced concurrently, and so that long-latency operations can be overlapped with computation. Unlike traditional asynchronous IO interfaces, AC retains a sequential style of programming without requiring code to use multiple threads, and without requiring code to be "stack-ripped" into chains of callbacks. AC provides an "async" statement to identify opportunities for IO operations to be issued concurrently, a "do..finish" block that waits until any enclosed "async" work is complete, and a "cancel" statement that requests cancellation of unfinished IO within an enclosing "do..finish". We give an operational semantics for a core language. We describe and evaluate implementations that are integrated with message passing on the Barrelfish research OS, and integrated with asynchronous file and network IO on Microsoft Windows. We show that AC offers comparable performance to existing C/C++ interfaces for asynchronous IO, while providing a simpler programming model.


Infinity is surely the strangest idea that humans have ever had. Where did it come from and what is it telling us about our Universe? Can there actually be infinities? Can you do an infinite number of things in a finite amount of time? Is the Universe infinite? Infinity is also the place where things happen that don't. What is it like to live in a Universe where nothing is original, where you can live forever, where anything that can be done, is done, over and over again? These are some of the deep questions that the idea of the infinite pushes us to ask. Throughout history, the infinite has been a dangerous concept. Many have lost their lives, their careers, or their freedom for talking about it. The Infinite Book will take you on a tour of these dangerous questions and the strange answers that scientists, mathematicians, philosophers and theologians have come up with to deal with its threats to our sanity.


The malleefowl Leipoa ocellata Gould, 1840, has declined substantially since European settlement of Australia just over 200 years ago. The species is now vulnerable and is threatened by the loss and degradation of suitable habitat by grazing, fire, and clearing, by the insidious effects of fragmentation of their populations that has resulted from clearing, and by predation by introduced foxes. Accordingly, a National Malleefowl Recovery Plan is being prepared to outline actions that are needed to both secure the species and provide the information necessary for effective management. Conserving malleefowl will require improved management throughout its range and on a diversity of land tenures. Improving habitat quality is crucial and may be achieved by reducing grazing pressure from commercial stock and feral goats, by preventing the catastrophic effects of large wildfire, and by reducing the size and frequency of intentional fires. Reducing the abundance of foxes may also assist malleefowl recovery, particularly where the birds' populations are small and isolated or declining. Remaining malleefowl populations are highly fragmented, and there is a need in many areas for habitat links to facilitate dispersal of the species between nearby habitat patches. The retention and revegetation of habitat links would also slow the degradation of remnant habitats due to increasing soil salinity. Considering the vulnerability of the species, it is especially important to monitor the distribution and abundance of malleefowl across Australia and over a number of years. Effective conservation will also require a better understanding of the species' population dynamics, habitat preferences and genetic variability. Local communities have made a major contribution to protecting and understanding the malleefowl and interest in this popular species is growing rapidly. Many of the projects outlined in the Recovery Plan are suitable for community involvement, and the time is ripe to further encourage and promote this interest in malleefowl conservation.


Edith H. Jones* Why write about a bankruptcy law proposal in a Symposium to honor Charles Alan Wright? This is a sensible question, as Professor Wright has written little on bankruptcy,1 and bankruptcy law is hardly visible from the commanding heights of the American legal system, dominated by federal civil procedure and constitutional law, where Professor Wright reigns. But bankruptcy law has been conducting a stealthy approach on those heights for nearly two decades, and it is time someone at the top posted a lookout. I can think of no better place to begin assessing the impact of bankruptcy on federal courts, federalism, and even the Constitution, than in the company of the contributors to and the honoree of this Symposium. And no subject better illustrates the incursion of bankruptcy into traditional federal and state court territory than that of mass tort litigation. The National Bankruptcy Review Commission ("Commission") was set up by Congress in 1994 and charged with recommending reform of bankruptcy laws. Its report, issued in October 1997, proposes codifying authority in bankruptcy courts to reorganize or liquidate companies exposed to mass future claims.2 Unfortunately, the Commission had neither the time nor the expertise to compare carefully its recommendation with the precise problems imposed by mass product liability litigation on nonbankruptcy courts.3 Notwithstanding these deficiencies, the Commission proposal enthusiastically promotes a bankruptcy alternative, which, because of the Commission's endorsement, may soon appear in omnibus bankruptcy legislation. The purpose of this article is to urge caution before bankruptcy courts enter deeper into the mass tort litigation fray. The Commission's proposals, in my view, beg the essential questions regarding class membership and adequacy of representation. They also fail to offer a significantly superior means to resolve mass tort litigation, instead distending and distorting bankruptcy practice to accomplish their goal. These conclusions are reached by comparing the Commission's proposal with the problems that have beset Rule 23 class actions, a currently popular federal court device for resolving mass tort litigation. I take no pleasure in criticizing the Commission's proposal, for I was a member of the Commission and participated in the working group that formulated the mass future claims recommendation. If our proposal is lacking, it marks one more blow against rational treatment of mass tort litigation, a phenomenon which has sturdily resisted judicial management efforts. But despite the inadequacy of current judicial approaches, there is no progress or honor in simply changing the forum for mass tort litigation without solving its inherent problems. Had the Commission learned from the specialists in federal civil procedure, its endorsement that bankruptcy take over mass tort litigation might have been more restrained. I. Federal Courts and Mass Future Claims Mass tort litigation is the vexing product of an extravagant tort law, the decline of limits on barratry, and enhanced lawyer networking-both literally and figuratively. While mass litigation has been spawned because of industry's perceived inability to mass produce safe or effective products, the federal courts' attempts to mass produce justice have also routinely fallen short. For nearly two decades, as waves of product liability litigation have assaulted civil courts, the same questions have continued to arise and yet defy solution.4 Even the question of the defendants' liability, which should be a critical matter in the fashioning of a just solution, becomes submerged beneath the overwhelming volume of claims and the huge transactional costs of defending them. In mass litigation, it is difficult to distinguish valid claims from frivolous or false ones. Transfer of cases to one forum for more "efficient" processing does not necessarily result in their expeditious conclusion. …


The production of oxygen free radicals has been strongly implicated as an important pathophysiological mechanism mediating myocardial ischemia/reperfusion (I/R) injury. Various antioxidants have cardioprotective effects. Melatonin, an indoleamine synthesized by the pineal gland, is a potent antioxidant and a direct free radical scavenger. This is the first in vivo study to evaluate the effect of melatonin (0.5, 1.0, and 5.0 mg/kg, i.v. bolus) on myocardial I/R injury in anesthetized Sprague–Dawley rats. Results demonstrate that pretreatment with intermediate or high doses of melatonin (1.0 and 5.0 mg/kg) at 10 min before left coronary artery occlusion markedly suppressed ventricular tachycardia (VT) and ventricular fibrillation (VF), while reducing the total number of premature ventricular contractions and total duration of VT and VF that occurred during the 45‐min ischemic period. Pretreatment with melatonin dramatically improved survival rate of rats when compared with the I/R‐only group. After 1‐hr reperfusion, melatonin caused a significant reduction in infarct size when compared with I/R‐only group. Meanwhile, pretreatment with melatonin (1.0 mg/kg) significantly reduced superoxide anion production and myeloperoxidase activity; the latter is an index of neutrophil infiltration in the ischemic myocardium. Additionally, pretreatment with melatonin (1.0 and 5.0 mg/kg) significantly attenuated ventricular arrhythmias and mortality elicited by reperfusion following 5‐min ischemia. In conclusion, melatonin suppresses ischemia‐ and reperfusion‐induced ventricular arrhythmias and reduces infarct size resulting from I/R injury. The pronounced cardioprotective activity of melatonin may be mediated by its antioxidant activity and by its capacity for neutrophil inhibition in myocardial I/R.


A general equilibrium search model makes layoff costs affect the aggregate unemployment rate in ways that depend on equilibrium proportions of frictional and structural unemployment that in turn depend on the generosity of government unemployment benefits and skill losses among newly displaced workers. The model explains how, before the 1970s, lower flows into unemployment gave Europe lower unemployment rates than the United States and also how, after 1980, higher durations have kept unemployment rates in Europe persistently higher than in the United States. These outcomes arise from the way Europe's higher firing costs and more generous unemployment compensation make its unemployment rate respond to bigger skill losses among newly displaced workers. Those bigger skill losses also explain why U.S. workers have experienced more earnings volatility since 1980 and why, especially among older workers, hazard rates of gaining employment in Europe now fall sharply with increases in the duration of unemployment.


Houghton (2010) believes that housing is a profoundly important issue like food and
water and without housing humans' life becomes unsustainable. Housing is a basic
need for communities and part of everyday life. Too often, progressive politicians
have launched house-building programmes in the name of delivering social justice.
Affordable housing problems are increasing rapidly with almost 2 billion people, or
32% of the world's urban population, living in slums, the majority of which are in
the developing world (UN-Habitat 2003 and UN-IRIN 2008). The main reasons that
have forced people to live under extreme conditions in slums are the lack of
governments' commitment, resources and ineffective strategic planning
techniques/tools (Tibaijuka, 2009; Hull, 1998; Yao, 2010).
Setting strategies and policies for the housing industry can be a very delicate,
confusing and unpredictable process for decision makers and government officials.
Scholars, researchers and prominent international figures such as Tibaijuka (2009),
Porter (1998), Davis (2000) etc. argue that the housing industry in developing
countries is suffering from insufficient and ineffective strategic planning. Moreover,
Tibaijuka (2009) states that given what is now know of the housing, building and
planning sectors, collectively known as the real estate sector, it is evident that it has
failed to meet its goals in macroeconomic planning and policy formulation,
particularly in developing countries. In addition, the present unsatisfactory state of
housing in developing countries is the result of wilful neglect by government
economic planners and political decision-makers and the lack of clear understanding,
strategies and policies of the nature and functioning of the sector itself (ibid). In
other words, the insufficient and ineffective strategic planning of the housing
industry, among other reasons has forced billions of people worldwide to live in
slums and shanty towns.
This research focuses on addressing the housing problems in developing countries
from the strategic planning point of view and the techniques/tools available that can
be used and implemented to drive forward and improve the performance of the
housing industry. Effective techniques/tools (Interpretive Structural Model "ISM"
and Decision Support System "DSS" Model) are realised through this research and
will be used, adopted and implemented based on the major housing industry factors
that have been identified.
A total of 94 factors and sub-factors were identified through profound investigation
of literature. The number of housing industry factors was reduced to 14 major factors
using Entity Relations Model (ERM) based on logical and contextual relations
established through literature in order to reduce the work load and therefore to
remain within the time and cost limits and constrains of this research. The 14 major
factors (tangible and non-tangible) of the housing industry were then prioritised
using the ISM in order to indicate to decision makers what is the most important
factor(s) to start with the process of improving the performance of the housing
industry and makes it meets its targets. The tangible/measurable factors were then
used to develop the DSS Model/engines based on MS Excel/Spreadsheet to provide
estimates on the housing finances and costs of the housing industry to assist decision
makers setting realistic and sound strategies and policies.
Finally, the DSS Model was tested/validated by running scenarios and simulations
using data from the case study of the Iraq housing industry provided by the Iraqi
Institute for Economic Reform (HER) in order to confirm the DSS Model integrity
and correctness. The HER is an official body directly linked to the Office of Prime
Minister. The evaluation process however was conducted by seeking Subject Matter
Experts (SMEs)/stakeholders' opinions to evaluate the DSS Model quality,
functionality, integrity, acceptance, effectiveness, reliability, usability, etc. via
observations and interviews. Subject Matter Experts (SMEs)/stakeholders were
recruited from developing countries (Malaysia and Sri Lanka), developed countries
(UK), financers (World-Bank) and Non-Governmental Organisations "NGOs" (UN)
which involved a total of six Subject Matter Experts (SMEs)/stakeholders. The result
of the evaluation process was overall very positive with the DSS Model being widely
accepted by all stakeholders as a novel approach and tool which is perceived can
make a great impact on the housing industry strategic planning in both developing
and also developed countries. Finally, according to the evaluation process of this
research, all Subject Matter Experts (SMEs)/stakeholders confirmed the
ORIGINALITY and GENERALIZABILITY of the DSS Model.

Appendices
Attached are the Appendices of this research which helped achieving its aims and
objectives.
1. Appendix One: Results of testing the DSS model
2. Appendix Two: Interview Questionnaire with the Participants/
Stakeholders
3. Appendix Three: Consent Form Signed by the Participants/
Stakeholders.


We have produced interleukin-6 (IL-6)-deficient mice to examine, in vivo, the wide variety of biological activities attributed to this multifunctional cytokine. To investigate the role of IL-6 during infectious disease, IL-6-deficient mice were challenged with sublethal doses of Listeria monocytogenes, a facultative intracellular bacterium. While normal control animals were able to clear the infection, mutant animals exhibited a high mortality rate and showed uncontrolled replication of the bacteria in the spleen and liver at 2 and 3 days postinfection. Sections of infected tissues showed an increase in the number and severity of inflammatory foci. All aspects of this phenotype in the mutant animals were completely reverted upon administration of recombinant murine IL-6 (rIL-6). Various parameters of natural killer (NK) cell and macrophage function were unaffected in the challenge of the mutant animals. However, IL-6-deficient animals failed to mount peripheral blood neutrophilia in response to listeriosis, whereas control animals displayed a prominent neutrophilia in the blood at 24 and 48 h postinfection. Additionally, we analyzed the efficacy of rIL-6 in protecting animals devoid of lymphocytes or devoid of neutrophils during listeriosis. Administration of rIL-6 was protective to animals devoid of lymphocytes, suggesting that the rIL-6 protective effect was not mediated through lymphocytes. In contrast, control and mutant animals depleted of neutrophils were refractory to the rIL-6 protective effect. These data suggest that IL-6 is critical early during listeriosis, perhaps acting by stimulating neutrophils either directly or indirectly. Additionally, these data show a promising therapeutic potential for rIL-6 administration during opportunistic infection.


The aberrations of lenses containing spherical index gradients are considered. Coordinate transformations from spherical to rectangular geometry are presented. These transformations enable calculation of the index polynomial in rectangular coordinates and subsequent calculation of aberration coefficients and ray trace data. The ability to alter the sign of the gradient aberration contribution by simply changing the curvature of the gradient is demonstrated.


Minimum wage increases are not a very effective mechanism for reducing poverty. They are not related to decreases in poverty rates. They can cost some low-income workers their jobs. And most minimum wage earners who gain from a higher minimum wage do not live in poor (or near-poor) families. A better tool for reducing poverty, and at lower cost, is the earned income tax credit. It is a much more targeted way to provide income to workers in poor families. It raises the wages of only workers in low-income families and rises with the number of dependent children in a family.


Nutrigenomic studies were conducted to uncover the
mechanism of action for the hypoglycemic and insulin sensitizing effects of
UP780. From high fat diet-induced obesity mouse model for UP780, livers and
white adipose tissues (WAT) from groups of lean control, high fat diet (HFD), and HFD treated with UP780
were collected for microarray study. Microarray generated gene
expression changes were applied to Ingenuity Pathway Analysis for changes in
canonical metabolic and signaling pathways. Microarray was validated by
quantitative reverse transcriptase-polymerase chain reaction (QPCR), Western
blots, liver triglyceride, liver cholesterol, liver steatosis, and insulin
ELISA. UP780 treatment decreased liver gene expressions for multiple enzymes
involved in fatty acid biosynthesis and triglyceride production. UP780 treatment increased gene expressions globally for the insulin receptor signaling
pathway in WAT. Both liver triglyceride and liver cholesterol levels were significantly reduced by UP780 over HFD. The reduction of liver fat was confirmed by
microscopic analysis of liver steatosis. Finally, UP780 significantly
decreased fasting plasma insulin level over HFD. The mechanism of action for
UP780 indicated a reduction of liver fat accumulation and an enhancement in
adipose tissue insulin signaling pathway. This provided mechanistic
explanation for the in vivo UP780
effects of enhanced insulin sensitiveity and decreased blood glucose in
mouse diabetes and prediabetes models.


Summary Many aquatic crustaceans pass through a complex life cycle comprising a benthic juvenile-adult and a pelagic larval phase. In the study of aquatic ecology, meroplanktonic larvae are therefore considered as principal components of benthic-pelagic coupling processes. As a consequence of radical transitions of life style, larvae differ from conspecific adults in their ecology, behaviour, nutrition, morphology, and physiology. Ontogenetic changes of these traits, as well as carry-over effects of larval condition on postmetamorphic fitness of benthic juveniles, are subjects of the interdisciplinary field of larval biology. Larval biology is thus not only an intrinsic part of lifehistory studies, but contributes essential information also to various other biological disciplines, including the broad area of crustacean research. For economically important species, it provides critical information for the development of aquaculture techniques or for the management of sustainable fisheries. Inferring from heritable ontogenetic patterns, comparative studies of larval morphology also aid the identification of phylogenetic relationships within and among higher taxa ("Evo-Devo" perspective). On the other hand, larval traits may be modified by environmental factors, which link larval ecology to developmental biology ("Eco-Devo" approach). Patterns of larval dispersal, mortality, and recruitment are crucial for the stability of benthic populations and communities. These aspects of "supply-side ecology" have also consequences for patterns of biogeographic distribution, population connectivity, genetic diversity, and the formation of metapopulations. In addition, the spread of introduced species in recipient regions may be explained or predicted through developmental and ecophysiological traits of their larvae. In evolutionary biology, knowledge of reproductive and developmental adaptations is crucial for the understanding of limnic and terrestrial invasions by originally marine crustaceans.


A 9-year-old Pemon girl visited the primary healthcare outpatient clinic at Wonken, a Pemon village in the Gran Sabana region of Bolivar state, in southeastern Venezuela. Wonken is located within the Canaima National Park, a tropical rainforest region at 844 m above sea level. The average temperature is 20 C. The patient presented a 4-week history of discomfort, itching, redness, and secretion in theback of her left thigh. She reported feeling movement inside the lesion, described as a "screwdriver being turned." Despite living in the village, she indicated recent visits to Araparitá, a remote community south of Wonken. She was afebrile and with stable vital signs. She presented a non-painful furuncle at the back of her left thigh, surrounded by an erythematous area of approximately 10 cm (Figure 1A). On close examination, a pair of moving respiratory spiracles werevisiblewithin thecenterof the lesion (SupplementalVideo). Suspecting a case of furuncular myiasis, a soap paste was applied on the lesion and covered in gauze to asphyxiate the fly larvae. After 3 hours, the gauze was removed, and the posterior end of the larva was clearly visible. A single live larva was successfully extracted (Figure 1B) and subsequently identified as a third instar stage larva (L3) of Dermatobia hominis, the human botfly. The gross morphological characteristics that allowed for identification of the extracted larva included the cylindrical body shape with narrowed posterior end, and the backward-facing, coarse cuticular spines present on all but the posterior three body segments (Figures 1C and D). The anterior mandibles (Figure 1E) were also clearly visible. Even though posterior spiracles were not examined (straight spiracular slits in a deepcavity are characteristic of this species), the gross morphologic appearance in the setting of furuncular myiasis in Venezuela is diagnostic of D. hominis infestation.


Point of view: Each of the creators are university researcher/professors of engineering; Linda is Eurasian/Latina and transgender, with a background in metallurgical engineering and materials science and engineering acquired in United States institutions; Nicola is a cis-gender woman, with a background in environmental engineering and educational research, who moved to the U.S. from Australia after completing her doctoral studies. Ruth is a cis-gender woman, born and raised in the U.S., of Western-European ancestry, with an educational background in biology and educational psychology. Although these identities do not represent the totality of what has shaped our view, we believe they have strongly influenced our experience of the field of engineering.

Value of submission: This piece raises what we believe are important questions about our current education for engineers that are arising from the implications of recent neuroscience findings.
Abstract
According to the National Society of Professional Engineers' (NSPE) creed, engineers are members of a profession who "dedicate [their] professional knowledge and skill to the advancement and betterment of human welfare." Although the educational process of developing one's engineering cognition has regional differences, by and large it derives from a core content that requires mechanical reasoning about the physical world. Results emerging from cognitive neuroscience imply that regions of the brain that function for mechanical reasoning have antagonistic relationships with regions that are active during moral and social reasoning, and vice versa. Their findings raise important questions for engineering education: How are we ensuring the balanced cognitive development necessary for the essential social and moral reasoning required of our profession? Can integrating Phenomenal activities with Physical activities serve holistic developmental aims? Can we envision integrative alternatives to present incarnations of engineering curricula? The intent of this paper is to offer reflections and speculations on the implications of these emerging neuroscientific findings on the dynamics of brain functioning for learning engineering.


OBJECTIVE Smaller LDL particles are associated with an increased risk for coronary artery disease and have been found predominantly in subjects with the insulin resistance syndrome. Although insulin resistance has been suggested to be a basic defect, little is known about the relation between this predisposing factor (and associated metabolic disturbances) and LDL size distribution in young and metabolically healthy subjects. In the present study, we investigated the relation between insulin sensitivity, lipoprotein distribution, and LDL patterns in young adults to increase the understanding of the development of metabolic risk factors in an early phase of the life span. RESEARCH DESIGN AND METHODS Young, clinically healthy subjects (n = 50; age 21.1–30.6 years) were enrolled in the study. Glucose metabolism was characterized by peripheral insulin sensitivity assessed by a hyperinsulinemic-euglycemic clamp and by levels of fasting insulin, C-peptide, and glucose. Lipoproteins were measured, and LDL fractions were additionally characterized by the diameter of the major LDL peak, estimated by 2–16% polyacrylamide gradient gel electrophoresis. Cholesterol ester transfer was estimated with a fluorescent spectroscopic method that measures the transfer of fluorescent cholesteryl linoleate between exogenous donor and acceptor particles. In this assay system, cholesterylester transfer protein (CETP) activity was only influenced by the plasma CETP concentration therefore reflecting more likely the CETP mass. RESULTS In the entire study group, 47 subjects had LDL phenotype A (LDL diameter >25.75 nm) and 3 subjects had an intermediate phenotype (25.50–25.75 nm). An interrelation between LDL size and LDL triglyceride (LDL-TG) per apolipoprotein (apo) B (Spearman's rank correlation analysis; r = −0.78; P < 0.001) or LDL cholesterol ester (CE) per apoB (r = 0.58, P < 0.001) was found, and 39% of the plasma samples studied were characterized by a monodispersed LDL pattern. Furthermore, LDL diameters correlated negatively with total TGs (men: r = −0.52, P < 0.001; women: r = −0.61, P < 0.001) and positively with insulin sensitivity (total population: r = 0.54, P < 0.001). In addition, LDL size was inversely related to the [VLDL + LDL cholesterol (CH)]/HDL-CH ratio and positively to the HDL-CE/TG ratio, which were both related vice versa to CETP activity levels. A direct relation between CETP activity levels and LDL size or composition was not observed. In a linear regression analysis including parameters of lipoprotein metabolism (TG, HDL cholesterol, CETP activity level), glucose metabolism (insulin sensitivity, fasting insulin), and sex, only TGs predicted significantly for 62% of LDL size variability. If the total study population was evaluated according to quintiles of insulin sensitivity, increasing TGs (analysis of variance, Scheffe test; P < 0.05) and CETP activitiy levels (P < 0.05) were combined with decreasing LDL particle diameters (P < 0.05) and with a preponderance of a monodispersed LDL pattern (60%) in the most insulin-resistant group. CONCLUSIONS Among parameters of the lipoprotein and glucose metabolism, total TG is the single most important factor affecting LDL size variability, even in young adults. If the study population is evaluated according to insulin sensitivity, lipoprotein pattern is altered in a more atherogenic manner in the most insulin-resistant subjects. In this group, increasing TG and CETP activity levels are associated with decreasing LDL particle diameters and preponderance of a monodispersed LDL pattern. Although increasing CETP levels are combined with this particular lipoprotein profile, a direct relation to LDL size and composition is not found.


Pancreatic cancer is the present third leading cause of all cancer-associated deaths with a under 9% 5-year survival rate. Aggressive tumor progression and lack of early detection technique lead to the fact that most patients are diagnosed at terminal stage - pancreatic ductal adenocarcinoma (PDAC). Despite that numerous therapeutic approaches have been introduced, most options cannot advance to or fail at the clinical trials. It has been suggested that previous failure is due to insufficient understanding of PDAC tumor microenvironment (TME). Human PDAC is composed of severely fibrotic tissue (i.e., desmoplasia) that harbors a variety of malignant cells (e.g., pancreatic stellate cells, cancer-associated fibroblasts, macrophages, etc.), excessive extracellular matrices (ECM), as well as abnormal expression of growth factors, cytokines, and chemokines. Multiple cell-cell and cell-ECM interactions jointly result in a stiffened, hypoxic, and fluid pressure-elevated PDAC tissue. The resulting pancreatic TME not only physically hinders penetration of therapeutics, but also dynamically interacts with the residing cells, regulating their behaviors.Increasing tumor tissue stiffness in PDAC is not only a passive outcome from desmoplasia, but an active environmental factor that promotes tumor survival, growth, and invasion. However, traditional in vitro cell culture systems such as two-dimensional (2D) culture plate and animal models are not ideal for mechanistic understanding of specific cell-matrix interactions. Therefore, dynamic hydrogels have been introduced as a category of advanced biomaterials that exhibit biomimetic, adaptable, and modularly tunable physiochemical property. Dynamic hydrogels can be precisely engineered to recapitulate a variety of aspects in TME, from which to investigate the role of dynamic tumor-stroma interaction in PDAC progression. The goal of this dissertation was to exploit synthetic polymers (i.e., poly(ethylene glycol) (PEG)) or natural ECM (i.e., gelatin and hyaluronic acid (HA)) as precursors to prepare the dynamic cancer-cell laden gels. The design utilized the orthogonal thiol-norbornene photopolymerization to prepare the primary homogenous xxvigel network. Next, through further functionalizing gel precursors with phenolic derivatives, enzymatic reaction (i.e., tyrosinase) or flavin mononucleotide (FMN)-mediated photochemistry could be harnessed to manipulate the dynamic changes of substrate mechanics. Experimentally, a computational model and the associated validation were presented to investigate the process of gel stiffening. Finally, these techniques were integrated to prepare cell-laden gels with spatial-temporally tunable properties that were instrumental in exploring the synergistic effects of dynamical matrix stiffening and presence of HA in promoting epithelial-mesenchymal transition (EMT) in PDAC cancer and stromal cells.


This paper builds upon previous research that examines participatory forms of "reciprocal journalism" and "public communication" led by high school and college students in Miami, Florida, USA, in the fall of 2014. In this study, the students' assessment of local and national media coverage is used to reveal greater details inherent in examining participatory methods of newswork. Collectively, students said that media coverage emphasis on local and national public officials instead of residents and community members who experience sea-level rise first-hand, combined with a lack of scientific explanation of and solutions for sea-level rise reduced the event's potential to build reciprocal relationships with younger audiences.


Two different approaches of the aerological method were used for estimating evaporation in northwestern Europe in the period 1969-1970. Daily operational aerological observations (»the synoptic approach«) gave better results for homogeneous areas (e.g. the Baltic Sea) than for a nonhomogeneous surface. One drawback in this approach was the non-uniform station network due to a lack of observations and resulting in scattered values even for monthly means. Based on annual mean moisture fluxes at the aerological stations (»the statistical approach«) the evaporation from the Bothnian Sea was estimated to be about 300 mm/year. The main convergence of the water vapor flux occurred below the 900 mb level and was largely due to the mean part of the flux. The results appeared to be quite dependent on the homogeneity of the data sample. In both approaches the main source of error is the lack and low quality of data, because divergence calculations are sensitive to errors in wind data. The linearity approximation used may also fail in low levels. Careful data checking and the use of complete data samples are needed when the aerological method is applied.


A few simple rules are sufficient to keep neighboring stomata at a safe distance from one another. The mechanisms that generate dynamic spatial patterns within proliferating tissues are poorly understood, largely because of difficulties in unravelling interactions between cell specification, polarity, asymmetric division, rearrangements, and growth. We address this problem for stomatal spacing in plants, which offer the simplifying advantage that cells do not rearrange. By tracking lineages and gene activities over extended periods, we show that limited stem cell behavior of stomatal precursors depends on maintenance of the SPEECHLESS (SPCH) transcription factor in single daughter cells. Modeling shows how this property can lead to observed stereotypical stomata lineages through a postmitotic polarity-switching mechanism. The model predicts the location of a polarity determinant BASL over multiple divisions, which we validate experimentally. Our results highlight the dynamic two-way interactions between stem cells and their neighborhood during developmental patterning.


PURPOSE
To update American Society of Hematology/American Society of Clinical Oncology recommendations for use of erythropoiesis-stimulating agents (ESAs) in patients with cancer.

METHODS
An Update Committee reviewed data published between January 2007 and January 2010. MEDLINE and the Cochrane Library were searched.

RESULTS
The literature search yielded one new individual patient data analysis and four literature-based meta-analyses, two systematic reviews, and 13 publications reporting new results from randomized controlled trials not included in prior or new reviews.

RECOMMENDATIONS
For patients undergoing myelosuppressive chemotherapy who have a hemoglobin (Hb) level less than 10 g/dL, the Update Committee recommends that clinicians discuss potential harms (eg, thromboembolism, shorter survival) and benefits (eg, decreased transfusions) of ESAs and compare these with potential harms (eg, serious infections, immune-mediated adverse reactions) and benefits (eg, rapid Hb improvement) of RBC transfusions. Individual preferences for assumed risk should contribute to shared decisions on managing chemotherapy-induced anemia. The Committee cautions against ESA use under other circumstances. If used, ESAs should be administered at the lowest dose possible and should increase Hb to the lowest concentration possible to avoid transfusions. Available evidence does not identify Hb levels ≥ 10 g/dL either as thresholds for initiating treatment or as targets for ESA therapy. Starting doses and dose modifications after response or nonresponse should follow US Food and Drug Administration-approved labeling. ESAs should be discontinued after 6 to 8 weeks in nonresponders. ESAs should be avoided in patients with cancer not receiving concurrent chemotherapy, except for those with lower risk myelodysplastic syndromes. Caution should be exercised when using ESAs with chemotherapeutic agents in diseases associated with increased risk of thromboembolic complications. Table 1 lists detailed recommendations.


This article introduces the concept of an affective disposition. An affective disposition is an individual's capacity to affect or be affected as it is framed in a specific context of affective relations. An af fective disposition is constituted by traces of past affective encounters. Such traces act as specific affective potentials in present situations. At the same time, the concrete affective dynamics, in which these potentials might actualize, are not determined by traces of the past, but modulated and coshaped by the affective dispositions of other individuals in the situation. The actualization of an affec tive disposition is thus a constitutive process. The article introduces the concept in the context of a re lational and dynamic affect theory based on Spinoza and Deleuze.


Any eLearning Management System (e-LMS) contains electronic content and many tools that are needed for running an efficient electronic management system. Some of these are related to electronic communications. Arab Open University (AOU) is one of the first organizations that used e-learning systems in the Arabic region. We present in this paper an analytical study on the effectiveness of using electronic communications within e-learning environments. This analytical study will differentiate between the synchronous and asynchronous communications in e-learning. We will focus on the most used tools in e-LMS such as Messages, Forums, and Chat Session as a part of electronic communications within the learning management system. Experimental results on AOU experience of using different types on electronic communication are presented.


High level data structures are a cornerstone of modern programming and at the same time stand in the way of compiler optimizations. In order to reason about user- or library-defined data structures compilers need to be extensible. Common mechanisms to extend compilers fall into two categories. Frontend macros, staging or partial evaluation systems can be used to programmatically remove abstraction and specialize programs before they enter the compiler. Alternatively, some compilers allow extending the internal workings by adding new transformation passes at different points in the compile chain or adding new intermediate representation (IR) types. None of these mechanisms alone is sufficient to handle the challenges posed by high level data structures. This paper shows a novel way to combine them to yield benefits that are greater than the sum of the parts.
 Instead of using staging merely as a front end, we implement internal compiler passes using staging as well. These internal passes delegate back to program execution to construct the transformed IR. Staging is known to simplify program generation, and in the same way it can simplify program transformation. Defining a transformation as a staged IR interpreter is simpler than implementing a low-level IR to IR transformer. With custom IR nodes, many optimizations that are expressed as rewritings from IR nodes to staged program fragments can be combined into a single pass, mitigating phase ordering problems. Speculative rewriting can preserve optimistic assumptions around loops.
 We demonstrate several powerful program optimizations using this architecture that are particularly geared towards data structures: a novel loop fusion and deforestation algorithm, array of struct to struct of array conversion, object flattening and code generation for heterogeneous parallel devices. We validate our approach using several non trivial case studies that exhibit order of magnitude speedups in experiments.


Over the past thirty years Ariane Mnouchkine's 'Theatre du Soleil' has become one of the most celebrated companies in Europe, and Mnouchkine one of its best-known directors. Collaborative Theatre is the first in-depth sourcebook in English on 'Theatre du Soleil', providing English readers with first-hand accounts of the development of its collectivist practices and ideals. Collaborative Theatre presents critical and historical essays by theatre scholars from around the world as well as the writings of and interviews with members of le Theatre du Soleil, past and present. Projects discussed include: 1789, L'Age d'Or, Richard II, L'Indiade and Les Atriades.


Contributors to the debate on ethical rationing bring with them assumptions about the proper role of moral theories in practical discourse, which seem reasonable, realistic and pragmatic. These assumptions function to define the remit of bioethical discourse and to determine conceptions of proper methodology and causal reasoning in the area. However well intentioned, the desire to be realistic in this sense may lead us to judge the adequacy of a theory precisely with reference to its ability to deliver apparently determinate answers to questions that strike most practitioners and patients as morally arbitrary. By providing ethical solutions that work given the world as it is, work in clinical ethics may serve to endorse or protect from scrutiny the very structures that need to change if real moral progress is to be possible. Such work can help to foster the illusion that fundamentally arbitrary decisions are 'grounded' in objective, impartial reasoning, bestowing academic credibility on policies and processes, making it subsequently harder for others to criticise those processes. As theorists, we need to reflect on our political role and how best to foster virtuous, critical practice, if we are to avoid making contributions to the debate that not only do no good, but may even be harmful. A recent debate in this journal illustrates these issues effectively.


During September 2004 a total of 25 sites were sampled for fish and freshwater crayfish in Ellen Brook, Cowaramup Brook and Gunyulgup Brook. This included 11 sites on Ellen Brook, six sites on Cowaramup Brook and eight sites on Gunyulgup Brook. A total of 1270, 720 and 1450 m2 were sampled on Ellen, Cowaramup and Gunyulgup Brooks, respectively.

Five species of fish were captured in the 11 sites sampled in Ellen Brook. These included two freshwater species that are endemic to south-western Australia, i.e. the Western Pygmy Perch and the Nightfish, the marine-estuarine opportunistic Sea Mullet, the marine Zebra Fish and the introduced Mosquitofish. The only fish species captured in the six sites sampled in Cowaramup Brook was the introduced Mosquitofish. Three species of fish were captured in the eight sites sampled in Gunyulgup Brook. These include the estuarine Swan River Goby and Black Bream and the marine/estuarine opportunistic Sea Mullet. All three species were found at the mouth of the brook, with the Black Bream (1 specimen, 43 mm TL) and Sea Mullet (5 individuals, 34-43 mm TL) being small juveniles. In contrast, the 60 Sea Mullet captured at Caves Rd were much larger and ranged in length from 204 to 261 mm TL.

The largest Western Pygmy Perch captured in Ellen Brook was 78 mm TL, a size considerably longer than previously reported for the species (i.e. 68 mm TL, from almost 3000 individuals measured) (see Pen and Potter (1991) in the Collie River. Furthermore, 13 of the 268 individuals captured and measured in Ellen Brook were larger than the largest reported from the Collie River. This high proportion of large individuals is unusual in that most populations of Western Pygmy Perch are represented by the 0+, 1+ and 2+ cohorts, which comprised 99% of all fish examined in the Collie River. In the Collie River, Western Pygmy Perch attain lengths of ~42 and 51 mm TL at the end of their first and second year of life, respectively (Pen and Potter 3 1992). Based on this length at age data, almost 43% of Western Pygmy Perch in Ellen Brook would have been in their fourth, fifth or sixth year of life. The population of Nightfish in Ellen Brook is similarly dominated by larger, older fish. For example, in the Collie River 98.5% of the population is three years old (i.e. >85 mm TL) (see Pen and Potter 1990). These dramatically contrasting population demographics are important, particularly in terms of ensuring the survival of what may be an aging population. It is possible that either predation is high on juvenile fish or that the high degree of water extraction is impacting on the fishes. The considerable number of new dams in the catchment, increased land clearing and long term drought experienced in the region again may be affecting environmental flows to the degree that only the few larger fish are surviving, possibly as they are more capable of competing for habitat as it becomes limited.

Four species of endemic freshwater crayfish were captured in Ellen Brook, including the widespread smooth Marron (Cherax cainii), the common Gilgie (Cherax quinquecarinatus), the restricted Gilgie (Cherax crassimanus) and the widespread Koonac (Cherax preissii). While only two, eight and four individuals of the Marron, the restricted Gilgie and the Koonac were captured, respectively, over 500 Gilgies were found throughout Ellen Brook, with densities peaking at 3.0 Gilgies m-2 at site 10 (Garstone Rd, the second uppermost site). Only one Gilgie was found at the uppermost site (site 11) which offered little habitat or shade. The restricted gilgie in Ellen Brook represents the northern-most extent of its range and reflects its preference for small waterbodies. The overall mean density of common Gilgies throughout Ellen Brook was high, with approximately every 2 m2 of stream bed being occupied by one animal. The densities of the widespread Gilgie were highest in Cowaramup Brook, with an average mean abundance of 1.62 Gilgies m-2. A total of 963 Gilgies were captured in Cowaramup Brook and they were found in all sites, including the mouth of the brook. A total of six Marron was also captured in three of the six sites sampled. 41 Yabbies were captured in Gunyulgup Brook. There appeared to be three age cohorts (year classes) present including newly released (0+) individuals, indicating that this species was a self-maintaining population. In Gunyulgup Brook Gilgies were captured in all sites with the exception of the mouth, while Marron were only found in the large dam at site 7, where they were probably introduced. The presence of a Yabbie below this dam (site 6) suggests that this is also the most likely avenue of their introduction into this part of the brook. The fact that the majority of Yabbies were caught on another branch of the brook implies that there have been multiple introductions to the system. A wild population of Yabbies in the Hutt River (near Geraldton) has recently been found to have the serious porcelain disease caused by the microsporidian Thelohania parastaci, a disease that has also impacted on 4 the aquaculture industry in this State. This disease is contracted by a crayfish consuming infected tissue. It is possible that the endemic crayfish may be able to contract this disease by consuming infected Yabbie tissue. Therefore, the potential accompanying spread of this and other diseases by Yabbie introductions is of considerable concern in this region. The identification of this, and other diseases, in the yabbies of Gunyulgup Brook should be assessed.

The high abundance and success of Gilgies in these streams is no doubt a reflection of their adaptive life history strategy adapted to these water bodies which includes: the ability to burrow into the water table in temporary waterbodies, a relatively small size at first maturity reproducing after the first year of life, and being able to spawn multiple times over the annual breeding period (spring-summer). Therefore, the wide distribution and large abundance in all three streams in the current study reflects this species adaptiveness to such small lotic systems, subject to low summer water levels.


Internet users create social media that enable information to be transferred more efficiently. In this work we focus on a typical social media platform Wikipedia and examine how management's voluntary disclosure reacts to information arrivals on Wikipedia. In doing so, we seek to answer the question of whether social media indeed improve the information environment for investors in the financial market. Our analysis is based on a unique dataset collected from the modification history of firm entries on Wikipedia, and thus we are able to identify information arrivals on Wikipedia. We find that information arrivals on Wikipedia affect the timing of management disclosure of bad news, and the effect is in sharp contrast to the way in which traditional media affect management disclosure. Further, we find consistent evidence that information arrivals on Wikipedia preempt the negative reaction of the market to bad news. In contrast, more news coverage in traditional media exacerbates the problem of optimistic analyst forecasts. Together these findings emphasize that social media have an identifiable effect on both the management side and the investor side in the financial market.


We demonstrate the physical rearrangement of wheeled stools in a moderately cluttered indoor environment by a quadrupedal robot that autonomously achieves a user's desired configuration. The robot's behaviors are planned and executed by a three layer hierarchical architecture consisting of: an offline symbolic task and motion planner; a reactive layer that tracks the reference output of the deliberative layer and avoids unanticipated obstacles sensed online; and a gait layer that realizes the abstract unicycle commands from the reactive module through appropriately coordinated joint level torque feedback loops. This work also extends prior formal results about the reactive layer to a broad class of nonconvex obstacles. Our design is verified both by formal proofs as well as empirical demonstration of various assembly tasks.


This research studies how variations in competition and in media content characterized the use and impact of Gutenberg's printing press technology during the European Renaissance. The research constructs annual firm-level panel data on the publications produced by 7,000+ printing firms operating in over 300 European cities 1454- 1600. Evidence on the timing of the premature deaths of firm owner-managers is used to isolate shocks to competition. Firms where owner-managers died experienced large negative shocks to output. However, at the citylevel deaths of incumbent managers were associated with significant increases in entrance and with a positive and persistent impact on competition and city output. Variations in city supply induced by heterogeneous manager deaths are used to study the relationship between the diffusion of ideas in print and city growth. A uniquely strong relationship is observed between the new business education literature and local growth. This is consistent with historical research on the transformative impact business education ideas had on commercial practices and European capitalism.


Our cities are what we consume. In essence, the city is in fact nothing more than a space for consumption in which we apparently express ourselves as citizens of a consumer society. Consumption lies at the ideological core of the contemporary city and as such consumption spaces lie at the very heart of what it means to be a citizen of contemporary society. The contemporary city appears to be undergoing something of a transformation second only in scale to the onset of industrialisation. All around us are indications and representations of what has been labelled an 'urban renaissance', a period that promises good times ahead; times from which the city will emerge as the focal point for regenerative social change. Cities throughout Europe are being re-branded as places to be consumed; as tourist destinations, centres of culture and as places worthy of the cultured middle classes. But are such changes any more than purely symbolic? Do they represent a substantive shift in how we as human beings relate to the cities around us? Is the soul of the contemporary city being sold to the consumerist paymaster and if so what does this mean for the long term sustainability of our cities? 'Spaces for Consumption' is concerned with the contexts in which the omnipresent power of consumption is most powerfully expressed and in turn, how the human condition is reflected in these spaces. It therefore constitutes a contribution to key debates in sociology, human geography and cultural studies around the extent to which consumers are able to actively construct the urban environments with which they engage on an everyday basis.


Currently it is developed a certain approach to Hispanic literature of the golden age that emphasizes the relation of "coevidad" and exchange between Spain and America. Within this framework it has been tried to relate: Miguel de Cervantes and Inca Garcilaso. This study extend the approach of the Golden age to an Atlantic consideration, because while the encounter of dissimilar peoples and cultures marks from the beginning their differentiation, on the other hand it is undeniable that they have in many aspects a continuity which allows us to talk about transculturation, or mestizo identity. There is continuity and discontinuity between the Iberian peoples and their colonies across the Ocean: the languages, customs, literary genres, are the same and others in the imperial metropolis and in the West Indies.


According to the Taylor rule, the Federal Reserve sets the funds rate based on an estimate of the economy's unutilized resources and the contemporaneous behavior of inflation. The primary policy prescription deriving from this view is that the Fed has failed to control inflation when it has not responded vigorously enough to observed inflation. However, there are reasons to question this understanding of how the Fed controls inflation. If the Fed creates inflation, it is better to pursue a monetary policy that prevents inflation rather than responds to it.


AIM
A retrospective study of 69 cases of gastric cancer seen during the period from 1/1-1990 to 31/12-1994 treated in a University Hospital. The aim of the study was to describe morbidity, mortality and identify independent prognostic variables for mortality.

METHOD
Patient data were recovered from the hospital's central database. Mortality was chosen as end-parameter. Univariate log-rank-test identified statistically significant variables which were then analysed by Cox backward stepwise regressional analysis.

MATERIAL
Sixty-nine patients were available for analysis, median age 73 years. Fifty-one patients underwent operation. Eighteen patients did not have a surgical procedure due to disseminated disease. The overall postoperative morbidity was 25% and postoperative mortality 10%. The overall five-year survival rate was 8%, 12% for operated patients, 35% after radical and 0% after non-radical or omitted surgery. Age, radicality of operation, type of operation, Borrmann's tumour classification, and degree of depth of local infiltration were identified as significant factors for survival. Cox's analysis identified type of operation (p = 0.0002) and Borrmann's tumour classification (p = 0.001) as independent variables.

DISCUSSION
The overall five-year survival is low and has not changed over two decades in Denmark, whereas mortality and morbidity rates have improved. It should be recommended that: The treatment of gastric cancer must be centralised in order to develop preoperative examinations, operative technique and the necessary routine for the surgeons. All gastric ulcers must be considered malignant and biopsies taken accordingly.


Neisserial adhesin A (NadA) is a surface exposed trimeric protein present in most hypervirulent meningococcal strains and involved in epithelial cell adhesion and colonization. The expression of nadA is controlled by Neisserial adhesin regulator (NadR), a member of the MarR family, which binds to the nadA promoter and strongly represses the transcription of nadA. It was recently demonstrated that the DNA-binding activity of NadR was attenuated by 4-hydroxyphenylacetic acid (4-HPA), a natural molecule released in human saliva, thus leading to the de-repression of nadA in vivo. To elucidate the mechanism of regulation of NadR by 4-HPA, we used hydrogen-deuterium exchange mass spectrometry in association with in silico docking and site-directed mutagenesis. We show here that 4-HPA binds at the interface between the dimerization and the DNA-binding domains and stabilizes the homodimeric state of NadR without inducing large conformational changes in the DNA-binding lobes. The residues predicted to be in contact with 4-HPA were further selected for mutagenesis to assess their in vitro and in vivo functions in 4-HPA binding. Our results indicate that Arg(40) is critical for DNA-binding and reveal that Tyr(115) plays a key role in the mechanism of regulation of NadR by 4-HPA. Altogether our data suggest that the mechanism of regulation of NadR by 4-HPA mainly involves the stabilization of the dimer in a configuration incompatible with DNA binding.


This thesis explores the relationship between ideas, attitudes, and sentiments found in popular French music of the 1960s and those that would later become important during the May 1968 protests in France. May 1968 has generated an enormous amount of literature and analyses of its events, yet there has been little previous work on popular music prior to May 1968 and the events of these protests and strikes that involved up to seven million people at its height. Using data from best-selling monthly charts in France from 1963 to 1968, this thesis links particular key aspects or ideas of May with the lyrics of popular songs that were released up to years prior to the protests. With a chapter devoted to each of the four included important aspects of May, this thesis deals, in particular, with antihierarchy and anti-authority attitudes, anti-capitalist sentiments, internationalism, and opposition to the Vietnam War that appeared both in these songs and, in some form, in the events of May. These songs, through their popularity and presence in the French social discourse of the time period, give further support to the larger theory that many of the causes of May were sentiments brewing much earlier than is generally thought.


In this paper, we introduce the concept of near-field synchronization as an efficient, scalable, and robust method to synchronize a 2-D array of mutually coupled oscillators for beam-forming at frequencies above fmax of a technology. The method employs an array of on-chip sense antennas to probe electromagnetic near-fields of the on-chip radiators. These sense antennas are then coupled to each other appropriately through a network that establishes the synchronized state as the lowest energy state. A circuit-electromagnetic co-design methodology is employed to demonstrate beam-steering near 200 GHz with a synchronized 2 × 2 array. Each element of the array is a traveling-wave oscillator with the nonlinear active devices selectively radiating its second harmonic through the same electromagnetic structure. The beam-pattern can be varied by more than 70° in both azimuth and elevation. The chip is realized in 65-nm bulk CMOS.


BPR0C261 is a synthetic small molecule compound cytotoxic against human cancer cells and active prolonging the lifespan of leukemia mice. In the present study, we further investigated the mechanisms of its anticancer action and found that BPR0C261 inhibited microtubule polymerization through interacting with the colchicine binding sites on tubulins, disrupted microtubule arrangement and caused cell cycle arrest at G2/M phase in cancer cells. BPR0C261 also inhibited the clonogenic growths of cancer cells and showed cytotoxicity against human cervical cancer cells of multidrug‐resistant phenotype. In addition, BPR0C261 concentration‐dependently inhibited the proliferation and migration of HUVECs and disrupted the endothelial capillary‐like tube formations in HUVEC and rat aorta ring cultures. Given orally, BPR0C261 inhibited angiogenesis in s.c. implanted Matrigel plugs in mice. Notably, its IC50 values against the endothelial cell growths were approximately 10‐fold lower than those against the cancer cells. It was found orally absorbable in mice and showed a good oral bioavailability (43%) in dogs. BPR0C261 permeated through the human intestinal Caco‐2 cell monolayer, suggesting oral availability in humans. Orally absorbed BPR0C261 distributed readily into the s.c. xenografted tumors in nude mice in which the tumor tissue levels of BPR0C261 were found oral dose‐dependent. BPR0C261 showed in vivo activities against human colorectal, gastric, and nasopharyngeal tumors in nude mice. Most interestingly, the combination of BPR0C261 plus cisplatin synergistically prolonged the lifespans of mice inoculated with murine leukemia cells. Thus, BPR0C261 is a novel orally active tubulin‐binding antitumor agent with antimitotic, apoptosis‐inducing, and vasculature disrupting activities. (Cancer Sci 2011; 102: 182–191)


A regulator of bone morphogenetic protein switches from enhancing to inhibiting activity at high concentrations. Binding of bone morphogenetic protein 4 (BMP4) to its receptor causes phosphorylation and activation of Smad transcription factors. Low concentrations of the secreted factor BMPER (BMP-binding endothelial cell precursor–derived regulator) enhance BMP4 activity, whereas high concentrations paradoxically inhibit it. Kelley et al. now provide evidence for a mechanism underlying the dual nature of this regulation. When added to mouse endothelial cells (MECs) at concentrations equimolar to BMP4, BMPER increased Smad activation over BMP4 alone. However, high concentrations of BMPER inhibited BMP4-mediated Smad activation by triggering endocytosis of both factors through a clathrin-mediated pathway that led to the lysosomal degradation of BMP4 and BMPER. This process required the proteolytic processing of BMPER into its mature form and the binding of BMP4 to its receptor. During embryogenesis, alveoli development requires the regression of lung mesenchyme through apoptosis, which the authors proposed occurs through BMPER inhibition of BMP4 signaling. Treatment of isolated mouse embryonic lung mesenchyme with BMP4 and low concentrations of BMPER promoted fibroblast survival, whereas high concentrations of BMPER increased apoptosis. Compared with wild-type mice, the lung tissue from BMPER+/– mice exhibited reduced apoptosis and elevated BMP4 activity, as measured by the expression of Id1 (inhibitor of differentiation or inhibitor of DNA binding 1), a downstream BMP target. Two other regulators of BMP signaling, Noggin or Gremlin, also attenuated BMP4-mediated Smad phosphorylation by triggering BMP4 endocytosis in MECs; however, Chordin did not inhibit Smad activity through BMP4 internalization. In addition, Noggin and Gremlin treatment prevented BMP4-mediated Smad phosphorylation regardless of whether BMPER was also present, and BMPER induced Chordin internalization and degradation only in the absence of BMP4, hinting at a complex hierarchy among BMP inhibitors. R. Kelley, R. Ren, X. Pi, Y. Wu, I. Moreno, M. Willis, M. Moser, M. Ross, M. Podkowa, L. Attisano, C. Patterson, A concentration-dependent endocytic trap and sink mechanism converts Bmper from an activator to an inhibitor of Bmp signaling. J. Cell Biol. 184, 597–609 (2009). [Abstract] [Full Text]