AS THE UNITED STATES considers, adopts, and implements preemptive national security policy for the 21st century, it is important to ensure that we maintain a broad policy that not only keeps America secure, but also demonstrates a realistic and moral approach to solving national security challenges--challenges that can no longer be answered by the cold war policies and paradigms of containment, detente, and peaceful coexistence. A genuinely preemptive strategy shouldn't just "defend the peace against threats from terrorists and tyrants"; it should attack the causes and conditions that give rise to terrorists and tyrants. Our "gravest dangers to freedom" do not come from "the perilous crossroads of radicalism and technology"; they come from the crossroads of ignorance and poverty. (1) National security policy in the latter half of the 20th century changed dramatically. Following the fall of the Berlin Wall in 1989, it moved from addressing a bipolar, international power struggle between NATO-allied countries led by the United States and Warsaw Pact countries led by the former Soviet Union, to assuming U.S. hegemony. Geopolitical fault lines that had defined international politics seemed to melt away. (2) The first Gulf War set the precedent for a benevolent superpower leading an international coalition against tyranny. With Operation Iraqi Freedom, however, that paradigm was soon replaced by the precedent of a unilateral superpower leading a "coalition of the willing." Many historians now believe that the bipolar, international security framework of the cold war provided a more stable, secure, and predictable strategic framework. But living in the past is not an option. Interestingly, some students of international relations see a new paradigm forming in the 21st century that bears some resemblance to the cold war. For example, former Iranian President (1997-2005) Mohammad Khatami postulates that the world order is morphing, once again, into a bipolar struggle. In this instance, the struggle will entail a global conflict between NATO-allied countries led by the United States and Islamic-based, theocratic states. (3) Similar hypotheses in elite foreign relations circles suggest that the new security paradigm will probably pit the haves against the have-nots, or, as Samuel Huntington has posited, civilization against civilization. Either way, the great clash will not be between states. (4) Even our own president, George W. Bush, seems to refer to the U.S. "War on Terror" as being a "war of ideas," not a contest between states. If the world order has indeed changed in any of these ways, the implications for how the United States formulates its forward-looking national security policy will be profound. Containment, detente, and peaceful coexistence will not work. To ensure its long-term national security, America will have to remain decisively engaged, with the full understanding that in a global economy its security and prosperity are both directly and indirectly linked to the most remote regions of the world. A national security policy best disposed to meet this challenge must be considered in the guise of "enlightened self-interest" and human security; in effect, we must broaden our past definition of national security to meet the challenges and threats that lie ahead. I am proposing here that we build the future framework of U.S. national security policy around a new paradigm: "human security." First, however, we must understand where the term "human security" comes from. Some would argue that justification for a policy based on human security is a priori rational. Through our study of history and our most recent national experiences, we see that the concept can also be proven a posteriori. Background Following the fall of the Wall, a community of political scientists, academics, and leaders of international governmental organizations and nongovernmental/humanitarian assistance organizations began to talk about changing the way "we" think about national security. …


Sustainable wood products and their value chains can play a fundamental role in achieving the objectives stated in the 2030 Agenda and the Paris Agreement, delivering a wide range of benefits to populations in remote forest areas as well as to local, regional and global society. Generation of income and employment, disaster risk reduction, and reduction of the material and carbon footprint of the planet are some of the direct contributions sustainable forest products can provide to the SDGs and the climate change commitments. Furthermore, sustainable management of natural forests reduces forest degradation and forest production can increase the opportunity cost for deforestation, while generating revenues for conservation strategies.These Voluntary Guidelines for forest concessions focus on concessions as a forest policy instrument for the delivery of sustainable forest management in the tropics, building on lessons learned from success and failures in implementing forest concession. The guidelines offer a practical participatory management approach to support forest concession regimes to be reliable sources of sustainable wood and non-wood forest products and contribute to realizing the full contribution of forestry to the 2030 Agenda.


Abstract : Analysis work by the SEI on data collected from more than 100 Independent Technical Assessments (ITAs) of software-reliant acquisition programs has produced insights into some of the most common ways that programs encounter difficulties. This report describes work done at the SEI that is based on these insights, and intends to mitigate the effects of both misaligned acquisition program organizational incentives, and adverse software-reliant acquisition structural dynamics, by improving acquisition staff decision-making. The research presented here uses a preliminary system dynamics model to analyze a specific adverse acquisition dynamic concerning the poorly controlled evolution of small prototype efforts into full-scale systems that is called ?The Evolution of a Science Project.? The report provides a narrative from an actual acquisition program that exemplifies the dynamic, qualitatively describes its key aspects, and presents some of the most relevant prior research done on one of those aspects, project rework. The system dynamics model of the behavior is described in detail, along with the process by which it was developed, and the results of simulations run using the model. The report concludes with a set of lessons learned about system dynamics modeling, as well as potential future research directions.


Nummulitidae are the largest extant calcareous Foraminifera, and are widely distributed in tropical and subtropical shallow-water seas. Classical morphology-based taxonomy divides the Nummulitidae in two subfamilies, the Nummulitinae and Heterostegininae, according to the presence or absence of secondary septa. To test the evolutionary importance of this morphological feature, phylogenetic relationships of five Recent nummulitid genera were investigated by sequencing fragments of the SSU and LSU rRNA gene. According to our results, species characterized by septate chambers ( Heterostegina depressa, Planostegina operculinoides , and Cycloclypeus carpenteri ) either group with species lacking septate chambers ( Operculina ammonoides, Nummulites venosus ) or branch separately. This suggests that chamber subdivisions developed several times independently in the evolutionary history of the Nummulitidae, providing an example of parallel evolution in Foraminifera.


AbstTact. Scarlet Macaws from northern Middle America (Mexico through Nicaragua) differ from those occurring from Costa Rica southward throughout the species' range in South America. This new subspecies (ATa macav cyanoptera)differs in having yellow wing covert feathers tipped with blue, but with no green band separating the yellow from the blue tip, and in being larger than South American birds. The new subspecies is already in danger of extinction, because of habitat loss and internal trade within its home range countries. Protection of the species in the wild can be best afforded by protecting its remaining habitat in Middle America and by reducing the internal market for pets in those countries. Many Scarlet Macaws, including more than 400 ATa macao cyanoptera, were imported into the developed countries between 1976 and 1986. Captive breeding of these individuals, keeping the subspecies. bloodlines separate, can contribute to conservation of the subspecies. Accepted 18 November 1994.


This study examined the effects of differentiating instruction in a sixth grade earth science classroom. During three lessons within one unit of study, tiered instructional materials were utilized and students were assigned to tiered learning groups. Likert-style surveys, student interviews, teacher observations, open-ended survey questions and unit test scores were used to collect data about the impact on student achievement, engagement and attitudes. Journal entries and teacher observations were used to determine how differentiating instruction impacted the teacher. Differentiating instruction improved the achievement of previously low-achieving students, but had mixed results for other students. Student attitudes were more negative following differentiated instruction. This treatment has mixed effects on student engagement and on the teacher.


The media coverage of sport events in relation to athletes' sex has been extensively analyzed in the scientific literature. Apart from sports mega-events such as the Olympic Games, the findings of these studies seem consistent in that female participants are systematically underrepresented in sports media coverage. However, much of the research in this area relates to North America. Therefore, the aim of this study was to examine sex equity in the coverage of the Sochi 2014 Winter Olympics by French, British and Spanish newspapers to provide new insights in this research field from a different cultural perspective. A content analysis was carried out and mixed results were found. French coverage shows significant discrimination of female athletes on most of the variables analyzed. Conversely, British coverage shows significant discrimination of male athletes on most of the variables studied. Finally, Spanish coverage is fair. These mixed results show the value of conducting such studies in geographical are...


Tree declines have been recorded across forests and woodlands on most continents, causing tree mortality over thousands of square kilometres, yet the impact of tree declines upon mammals have only rarely been quantified. Once the dominant tree over the western parts of the Swan Coastal Plain in Western Australia, tuart (Eucalyptus gomphocephala) forest has been reduced to less than a third of its former range through clearing for agriculture and urban development. Additionally, over the last 30 years, the remnant population has been heavily impacted by a decline that has an unknown cause, but is likely related to a root pathogen coupled with abiotic factors (reduced rainfall, increased salinity and elevated temperatures). Tuart decline is evident as marked canopy dieback, replacement with epicormic growth and increasing bare branches, while leaf litter is lost from the tree surrounds. We examined the effect of tuart decline and other vegetation measures upon bat activity using auditory monitoring. Vegetation structure was correlated with Vespertilionidae bat activity. Falsistrellus mackenziei were more likely to forage around healthy canopies (activity positively correlated with tuart crown density and negatively correlated with tuart crown dieback). By contrast, the other three taxa were more often encountered in declining rather than healthy tuart sites. Chalinolobus gouldii was positively associated with tuart crown dieback. Activity of Vespadelus regulus and Nyctophilus spp. (species not distinguishable from their calls) were significantly positively correlated with an open tall canopy (positively with cover of plants >10 m tall and negatively with overall canopy cover density). There were no vegetation measurements that were strong predictors of activity of two Molossidae species (Ozimops kitcheneri and Austronomus australis), which intercept insects above the forest canopy. This study clearly reveals different factors influencing the activity of bat taxa, which are likely related to where they feed and their manoeuvrability around tree canopies.


Donald Trump has consistently performed better politically than his negative polling indicators suggested he would. Although there is a tendency to think of Trump support as reflecting ideological conservatism, we argue that part of his support during the election came from a non-ideological source: The preponderant salience of norms restricting communication (Political Correctness – or PC – norms). This perspective suggests that these norms, while successfully reducing the amount of negative communication in the short term, may produce more support for negative communication in the long term. In this framework, support for Donald Trump was in part the result of over-exposure to PC norms. Consistent with this, on a sample of largely politically moderate Americans taken during the General Election in the Fall of 2016, we show that temporarily priming PC norms significantly increased support for Donald Trump (but not Hillary Clinton). We further show that chronic emotional reactance towards restrictive communication norms positively predicted support for Trump (but not Clinton), and that this effect remains significant even when controlling for political ideology. In total, this work provides evidence that norms that are designed to increase the overall amount of positive communication can actually backfire by increasing support for a politician who uses extremely negative language that explicitly violates the norm.


A method for the functionalization of surfaces within soft glass microstructured optical fibers has been developed, using self assembled monolayers (SAMs) of silane coupling agents. We demonstrate the use of measurements of the fiber capillary fill rate, as a positive test for a functionalized internal surface. A simple theoretical model is used for comparison with measured fill rates. During this work, adsorption kinetics for SAMs of octadecyltrichlororsilane onto lead silicate glass has been investigated. This work is a critically important first step for a plethora of applications in biophotonics, chemical fiber sensing as well offering promise for protecting fiber glass from degradation.


OF DISSERTATION THE DEPARTMENTAL WORK LIVES OF FULL-TIME NON-TENURE TRACK FACULTY This qualitative phenomenological dissertation explored The Departmental Work Lives of Full-Time Non-Tenure Track Faculty (FTNTT) at two public four-year universities located in the Southeastern region of the United States. This study is based on interviews with twelve (FTNTT) faculty members representing departments traditionally associated within the College of Arts and Sciences. This study found FTNTT faculty participants highly credentialed and reasonably satisfied in their positions. This study adds the descriptor heterogeneous to FTNTT faculty members' job roles, work environments, daily engagements, and work experiences and contradicts existing literature that finds FTNTT faculty positions to be resource deficit and administratively non-supporting. Literature surrounding FTNTT faculty, Agency Theory, and the concepts of Agency of Perspective, Agency of Action, and Action of Avoidance informed this study. This study extended Agency of Action to include intentional, strategic behaviors of inactions (coined within this study as Action of Avoidance) toward the departmental contexts of policies and practices concerning discipline, employability, employment longevity, and personal FTNTT faculty career trajectories. Agency Theory, Agency of Perspective, Agency of Action, and Action of Avoidance, as identified by the researcher, emerged as strong frameworks used by FTNTT faculty to construct behaviors to successfully navigate long-term careers under short-term conditions. Based on FTNTT faculty responses, this study outlines policies and practices that are perceived as supportive or non-supportive. Policymakers may use this data to inform strategies for improving support among FTNTT faculty members.


In a water-wet petroleum reservoir with a water-wet seal, a continuous water phase will extend from the reservoir into the seal, and the pressure difference between the water phase in the uppermost pores of the reservoir and the water phase in the lowermost pores of the seal can therefore only be of an infinitesimal magnitude. This implies that any overpressure in a water-wet reservoir will not contribute to pushing the hydrocarbons through a water-wet seal, and overpressured water-wet reservoirs should therefore not be considered more prone to capillary leakage than normally pressured reservoirs. Within a water-wet petroleum reservoirs, the overpressure in the hydrocarbon phase relative to the water phase is balanced by the elastic forces at the fluid interface (interfacial tension). The overpressure in the hydrocarbon phase relative to the water phase therefore does not increase the risk of hydrofracturing the reservoir's seal. This implies that the risk of hydrofracturing should not be increased as a function of hydrocarbon column height, and should not be considered to be higher for gas than it is for oil. When an upward-directed hydraulic gradient is present from a reservoir unit into the overlying seal, water will continuously move upwards from the reservoir unit and into the seal if both rocks are water-wet. This movement of water may lead to exsolution of gas above the reservoir unit, and the presence of free gas may be detected as gas chimneys on seismic sections. This mechanism will operate regardless of whether or not a hydrocarbon accumulation is present below the gas chimneys, and fracturing of the reservoir unit's seal or capillary leakage of hydrocarbons are therefore not necessary conditions for the development of gas chimneys.


Premature chromatin condensation (PCC) is a hallmark of mammalian cells that begin mitosis before completing DNA replication. This lethal event is prevented by a highly conserved checkpoint involving an unknown, caffeine-sensitive mediator. Here, we have examined the possible involvement of the caffeine-sensitive ATM and ATR protein kinases in this checkpoint. We show that caffeine's ability to inhibit ATR (but not ATM) causes PCC, that ATR (but not ATM) prevents PCC, and that ATR prevents PCC via Chk-1 regulation. Moreover, mimicking cancer cell phenotypes by disrupting normal G1 checkpoints sensitizes cells to PCC by ATR inhibition plus low-dose DNA damage. Notably, loss of p53 function potently sensitizes cells to PCC caused by ATR inhibition by a small molecule. We present a molecular model for how ATR prevents PCC and suggest that ATR represents an attractive therapeutic target for selectively killing cancer cells by premature chromatin condensation.


Search-based methods for hard combinatorial optimization are often guided by heuristics. Tuning heuristics in various conditions and situations is often time-consuming. In this paper, we propose NeuRewriter that learns a policy to pick heuristics and rewrite the local components of the current solution to iteratively improve it until convergence. The policy factorizes into a region-picking and a rule-picking component, each parameterized by a neural network trained with actor-critic methods in reinforcement learning. NeuRewriter captures the general structure of combinatorial problems and shows strong performance in three versatile tasks: expression simplification, online job scheduling and vehicle routing problems. NeuRewriter outperforms the expression simplification component in Z3; outperforms DeepRM and Google OR-tools in online job scheduling; and outperforms recent neural baselines and Google OR-tools in vehicle routing problems.


The collisional dynamics of equal-sized water and normal-alkane droplets, in the 150 μm radius range, have been experimentally studied for situations involving 0(1) droplet Weber numbers and head-on to grazing impact parameters. Results show that in the parametric range investigated the behaviour of hydrocarbon droplets is significantly more complex than that of water droplets. For head-on collisions, while permanent coalescence always results for water droplets, the outcome is quite nonmonotonic for the hydrocarbon droplets in that, with increasing droplet Weber number, the collision can result in permanent coalescence, bouncing, permanent coalescence again, and coalescence followed by separation with or without production of satellite droplets. Similar complexities exist for off-centre collisions. Phenomenological explanations are offered for these observations based on the material properties of the fluids, the relative influences of the normal and shearing aspects of the collision, and the nature and extent of energy dissipation due to droplet deformation during collision.


Computer simulations are important to increase the knowledge of the processes involved in paper making. Because of the complexity of the paper processes the development of simulation tools requires models and numerical methods which capture as much as possible of the real physical phenomena. In this paper a framework for simulation of fiber suspension flow is presented. The framework is founded on a fluid solver for the Navier-Stokes equations and a fiber model based on finite strain beam theory including shearing. Moreover, the coupling between fibers and fluid is resolved with the immersed boundary method and the interaction between the fibers is calculated using a model based on DLVO-theory.


Minnesota's local highway agencies are tasked with maintaining their low-volume road networks with available financial resources, prompting increased interest in lower-cost pavement rehabilitation alternatives. In-place cold recycling technologies, such as cold in-place recycling (CIR) and full-depth reclamation (FDR), provide lower-cost opportunities to renew deteriorated roads than traditional rehabilitation methods, particularly if surfaced with a thin surface treatment such as a chip seal (seal coat) or microsurfacing rather than hot-mix asphalt. However, the resulting road surface may not meet some road users' expectations. This study investigated the performance and economics of four pavement rehabilitation alternatives involving recycling technologies. The alternatives included CIR and FDR treatments with either an asphalt overlay or thin surface treatment. Fifteen case study sections in Minnesota and neighboring states were selected for performance evaluation and life cycle cost analysis (LCCA). Pavement condition surveys were performed to evaluate the study sections' pavement distresses and roughness. The results indicated satisfactory performance for fourteen sections, while a CIR section with a chip seal surface using quartzite as cover aggregate had extensive transverse cracking. The cause of the distress is not clear. The LCCA results indicate a 14% to 42% lower life cycle cost for CIR and FDR treatments with chip seal surfaces. Costs savings may be achieved if asphalt overlay thicknesses are reduced, though chip seal surfaces may be rougher and nosier and require more maintenance than asphalt overlays. A decision tree was developed to aid local agencies during the treatment selection process.


Author(s): Smoodin, Eric | Abstract: In Paris in the Dark Eric Smoodin takes readers on a journey through the streets, cinemas, and theaters of Paris to sketch a comprehensive picture of French film culture during the 1930s and 1940s. Drawing on a wealth of journalistic sources, Smoodin recounts the ways films moved through the city, the favored stars, and what it was like to go to the movies in a city with hundreds of cinemas. In a single week in the early 1930s, moviegoers might see Hollywood features like King Kong and Frankenstein, the new Marlene Dietrich and Maurice Chevalier movies, and any number of films from Italy, Germany, and Russia. Or they could frequent the city's cine-clubs, which were hosts to the cinephile subcultures of Paris. At other times, a night at the movies might result in an evening of fascist violence, even before the German Occupation of Paris, while after the war the city's cinemas formed the space for reconsolidating French film culture. In mapping the cinematic geography of Paris, Smoodin expands understandings of local film exhibition and the relationships of movies to urban space.


We have recently proposed in a blind frame synchronization method based on a maximum a posteriori (MAP) approach. In this letter, we study the properties of this method and show that this synchronization technique is well suitable for codes having a sparse parity check matrix, such as low-density parity-check (LDPC) codes. We also find the probability distributions involved in our synchronization criterion and expand the analytical expression of the probability of false synchronization. Through computer simulations we validate our theoretical results and show that this synchronization technique has excellent performance when applied to LDPC codes. We also show that this method outperforms another approach of blind frame synchronization that computes hard values of the syndrome instead of its log-likelihood ratios (LLR).


Direction fields and vector fields play an increasingly important role in computer graphics and geometry processing. The synthesis of directional fields on surfaces, or other spatial domains, is a fundamental step in numerous applications, such as mesh generation, deformation, texture mapping, and many more. The wide range of applications resulted in definitions for many types of directional fields: from vector and tensor fields, over line and cross fields, to frame and vector‐set fields. Depending on the application at hand, researchers have used various notions of objectives and constraints to synthesize such fields. These notions are defined in terms of fairness, feature alignment, symmetry, or field topology, to mention just a few. To facilitate these objectives, various representations, discretizations, and optimization strategies have been developed. These choices come with varying strengths and weaknesses. This report provides a systematic overview of directional field synthesis for graphics applications, the challenges it poses, and the methods developed in recent years to address these challenges.


Core competencies are the crown jewels of a company and, therefore, should be carefully nurtured and developed. Companies can determine their future business directions based on the strengths of competencies. However, because generalized terms such as resource, asset, capability, and competence are not clearly explained in connection with competence theory, these posing difficulties in understanding many contemporary management concepts. In this paper, the authors provide a summary of the recent management theories by comparing their salient features. They then propose a linking mechanism between assets, resources, capabilities, competencies, and core competencies. They provide a methodology to identify core competencies by isolating unique and flexible capabilities of the firm. They use this framework to identify the core competencies of a UK manufacturing company. The results of their analyses are used to help the company to make more informed strategic management decisions regarding capability development, outsourcing, focusing, or diversification, with regards to new products, services, or markets. The framework is generic in nature and is applicable to benchmark a manufacturing, public, or service sector organization.


An analytical expression was proposed to analyze the influence of group-delay ripple (GDR) on timing jitter induced by self-phase modulation (SPM) and intra-channel cross-phase modulation (IXPM) in pseudo-linear transmission systems when dispersion was compensated by chirped fiber Bragg grating (CFBG). Effects of ripple amplitude, period, and phase on timing jitter were discussed by theoretical and numerical analysis in detail. The results show that the influence of GDR on timing jitter changes linearly with the amplitude of GDR and whether it decreases or increases the timing jitter relies on the ripple period and ripple phase. Timing jitter induced by SPM and IXPM could be suppressed totally by adjusting the relative phase between the center frequency of the pulse and the ripples.


This article appears in the Hofstra Law Review symposium issue on the Supplementary Guidelines for the Mitigation Function of Defense Teams in Death Penalty cases.Capital defense counsel have a duty at every stage of the case to take advantage of all appropriate opportunities to argue why death is not a suitable punishment for their particular client. But that duty can hardly be discharged effectively if the arguments are made in ignorance of available information concerning how persuasive they are likely to be to their audience. Heeding that simple proposition we present lessons from the work of the Capital Jury Project, an ongoing empirical research effort built upon extended interviews with people who have actually sat on capital juries. We find that the standards for mitigation investigations contained in the ABA's Guidelines for the Appointment and Performance of Defense Counsel in Death Penalty Cases reprinted in 31 Hofstra L. Rev. 913 (2003) and in the Supplementary Guidelines that are the subject of this issue are on firm empirical ground, both in their specific aspects and in their overall approach of encouraging counsel to be creative in building a coherent mitigation theory that is advanced consistently throughout the proceedings. We then describe particular defense themes and approaches that Project data show are likely to resonate favorably with jurors as well as the most potent prosecution arguments for death and how they might be most effectively rebutted. We conclude by describing the current research findings on the demographic and attitudinal characteristics of those jurors most likely to vote for life, and offering pointers on how to best ameliorate the scandalous but well-documented reality that many jurors simply do not understand the task they are being called upon to perform.


This volume includes fifteen research papers to celebrate Luiz Carlos Pereira's 60th birthday. Among the authors contributing to the volume we find colleagues, friends - including his PhD advisor - and admirers. Similar to Luiz Carlos Pereira's intellectual interests and work, the contributions range from Philosophy to Mathematics, from Mathematics to Logic, and from Logic to Philosophy, passing through Computer Science. They are the result of current research by well-known scholars in these fields. Proof Theory is, maybe, the Ariadne's thread that unite the different subjects treated. Questions around the nature of proofs are often present in Luiz Carlos' formal and informal talks and publications. Of course, he was not the first to dedicate himself to these questions, but he always raises and deals with them enthusiastically. This enthusiasm, together with his intellectual perspicacity, has allowed us to enjoy a wonderful journey into the world of proofs. Although not all contributions focus directly on proof theory, we can feel its echos in all of them.


Recent studies suggest that Italian population shows a higher degree of internal genomic variability than other European populations. This scenario is the result of complex demographic dynamics, dating back mainly from Late Palaeolithic and Neolithic, but also dating to Metal Ages. In fact, numerous population movements occurred between the Mediterranean basin and the Middle East during the Metals Ages, a period that has determined the transformation of the first social organizations in ancient civilizations. During the 1st millennium BC, Italy appeared as a patchwork of different peoples, either whose origin remain still largely unresolved (e.g. Ligures, Veneti and, Etruscans), or that are known to have originated from specific migration processes (e.g. Celts in North-Western Italy; Greeks and Phoenician-Punic in Southern Italy, Sardinia, and Sicily). In this thesis, I focused my attention on the Italian Iron Age period, in particular on the ancient 'Piceni' (Case Study I) and 'Punic' (Case Study II) populations, and I analysed the ancient DNA (aDNA) of skeletal remains coming from the Novilara necropolis located in Central Italy (Case Study I), and from Tharros (Capo San Marco - Sardinia, IT) and Lilybaeum (Corso Gramsci - Sicily, IT) necropolises (Case Study II). I have applied different aDNA protocols and methods in order to obtain ancient mitochondrial DNA (HVS-I) (Case Study I and II) or complete genome (Case Study II). This research provides a pioneering survey on the ancient genetic diversity of Italy, contributing to disentangle the migration patterns and the relationships between ancient and presentday populations of the Mediterranean basin.


The study is the first to analyze genetic and environmental factors that affect brain fiber architecture and its genetic linkage with cognitive function. We assessed white matter integrity voxelwise using diffusion tensor imaging at high magnetic field (4 Tesla), in 92 identical and fraternal twins. White matter integrity, quantified using fractional anisotropy (FA), was used to fit structural equation models (SEM) at each point in the brain, generating three-dimensional maps of heritability. We visualized the anatomical profile of correlations between white matter integrity and full-scale, verbal, and performance intelligence quotients (FIQ, VIQ, and PIQ). White matter integrity (FA) was under strong genetic control and was highly heritable in bilateral frontal (a2 = 0.55, p = 0.04, left; a2 = 0.74, p = 0.006, right), bilateral parietal (a2 = 0.85, p < 0.001, left; a2 = 0.84, p < 0.001, right), and left occipital (a2 = 0.76, p = 0.003) lobes, and was correlated with FIQ and PIQ in the cingulum, optic radiations, superior fronto-occipital fasciculus, internal capsule, callosal isthmus, and the corona radiata (p = 0.04 for FIQ and p = 0.01 for PIQ, corrected for multiple comparisons). In a cross-trait mapping approach, common genetic factors mediated the correlation between IQ and white matter integrity, suggesting a common physiological mechanism for both, and common genetic determination. These genetic brain maps reveal heritable aspects of white matter integrity and should expedite the discovery of single-nucleotide polymorphisms affecting fiber connectivity and cognition.


Mediated responses to reports of abuse during the Global War on Terror are puzzling. Few of the many revelations of abuse prompted concerted reactions (e.g. scandals), and those that did were often very similar to reports that were ignored. This article draws from empirical research into responses to prisoner abuse at Abu Ghraib to develop new concepts that help untangle the mediatization of American wars. Feedback helps to model the variety of polemical interventions that are adopted in public discussions as a result of a scandal. The concept of feedforward, introduced here, enables us to model polemical interventions that develop within an organization in response to such feedback. Together, these concepts encourage greater sensitivity to the cultural horizon of mediated events. Further, they point to a new theoretical focus for mediatization research, namely the cycles of feedback and feedforward that help shape new forms of understanding and behaving within organizations.


This paper reviews a variety of backtests that examine the adequacy of Value-at-Risk (VaR) measures. These backtesting procedures are reviewed from both a statistical and risk management perspective. The properties of unconditional coverage and independence are defined and their relation to backtesting procedures is discussed. Backtests are then classified by whether they examine the unconditional coverage property, independence property, or both properties of a VaR measure. Backtests that examine the accuracy of a VaR model at several quantiles, rather than a single quantile, are also outlined and discussed. The statistical power properties of these tests are examined in a simulation experiment. Finally, backtests that are specified in terms of a pre-specified loss function are reviewed and their use in VaR validation is discussed.


There are many sources of outdoor pollution in Kuwait which then makes natural ventilation a poor mechanism for good Indoor Air Quality (IAQ). Therefore, a mechanical or hybrid ventilation system is necessary. First of all, Kuwait is situated in the northeast of the Arabian Peninsula in Western Asia with a desert weather climate. The prevailing wind is north and northeast and that causes sand storms. Also most of the towns and cities are situated and constructed within the vicinity of many industrial sites, petroleum downstream/upstream facilities (including Kuwait's three refineries, petrochemical complexes, crude oil production points etcetera) and many small industries. Most housing construction projects, as well as schools, commercial and governmental buildings are built in the downwind of the polluted air emitted from such plants, therefore, there is the potential for consequential health effects related to the ambient air. As a result, there is a prevalence of asthma and rhinitis among the schoolchildren in Kuwait. The estimated prevalence of asthma among school children was 22.4% and that of rhinitis was 23% (Abal et al., 2010).

It was evident from a preliminary study that indoor air quality (IAQ) in Kuwait housing is under-researched and there is a clear lack of awareness amongst building stakeholders (Architects and Designers, M&E Engineers, User, etc.) of the harmful effects of chemicals that exist inside buildings. The risk of poor Indoor Air Quality (IAQ) is increased by a lack of proficient knowledge of how numerous factors can contribute to poor IAQ, both during design, construction and after occupancy. As a result, the study set out to: research previous related research studies in the field of IAQ, identify the current status quo of IAQ in Kuwait, conduct a survey (questionnaires and interviews) with Kuwait construction professionals regarding IAQ issues and to find the barriers to implementing IAQ best practice in all stages of the project, and then finally, to develop a framework for achieving good IAQ in Kuwait housing projects.

The findings revealed no documents written for Kuwait, that encompasses codes, standards, regulations and guidance for the implementation of good IAQ in Kuwait housing developments, or a framework for government enforcement of such. It was also revealed that there was a significant lack of awareness of indoor air pollutants and good IAQ both amongst occupants and construction professionals. The analysis also revealed that the status quo in the housing development process did not enable integration amongst the project team and stakeholders at the design stage, hence team member's valuable input on achieving good IAQ at design stage is lost. Furthermore, the process did not emphasize the following at every stage of the project to ensure good IAQ: commissioning of the ventilation design and installation, which includes value engineering, proper sequencing and scheduling of activities to avoid dust or debris from contaminating the ventilation system, proper documentation and reporting to ensure the owner's project objectives are documented, achieved, checked, and carried over to the next stage.

The findings show that the barriers to achieving good IAQ in Kuwait housing developments are; cost and budget, government enthusiasm, lack of awareness, lack of enforceable codes and standards, lack of design integration, distrust of the competence level of local IAQ companies, habit and age, low level of IAQ education, and lack of training. While, the drivers of good IAQ in Kuwait housing are; the client/end-user, the government, architects, designers, IAQ consultants, construction professional societies, contractors and manufacturers.

The developed and validated framework achieves the aim and objectives of the study by proposing strategies and actions for improving indoor air quality (IAQ) in Kuwaiti housing developments through increased integration, commissioning, proper and adequate sequencing and scheduling, and documentation at design, construction, and occupancy stages. Kuwait Environmental Protection Agency (KEPA), Kuwait Institute of Environmental Management (KIEM), Kuwait Municipality, and Kuwait Institute of Science and Research (KISR) were also suggested as the main bodies to drive the education, awareness, and training, of not only the construction industry but also the general population on good IAQ practices.


Measurements in the atmosphere and at the surface of Venus are required to understand fundamental processes of how terrestrial planets evolve and how they work today. While the European Venus community is unified in its support of the EnVision orbiter proposal for the M5 opportunity, many scientific questions also require in situ Venus exploration. ESA has already explored Venus entry / descent probe science in its Planetary Entry Probe (PEP) study [ESA PEP study, 2010], and Venus balloon science in its Venus Entry Probe Study [ESA VEP study, 2005]; Venus balloons were also explored in detail by the European Venus Explorer (EVE) M1/M2 and M3 proposals [Chassefiere et al., 2009; Wilson et al., 2012]. While those in situ mission concepts remain scientifically compelling and technically feasible, the present call requests new scientific concepts. Therefore, in the present document, we suggest a long-duration lander at Venus, which would be capable of undertaking a seismometry mission, operating in the 460{\deg}C surface conditions of Venus.


We provide elementary combinatorial proofs of several Fibonacci and Lucas number identities left open in the book Proofs That Really Count [1], and generalize these to Gibonacci sequences $G_n$ that satisfy the Fibonacci recurrence, but with arbitrary real initial conditions. We offer several new identities as well. Among these, we prove $\sum_{k\geq 0}{n \choose k}G_{2k} = 5^n G_{2n}$ and $\sum_{k\geq 0}{n \choose k}G_{qk}(F_{q-2})^{n-k} = (F_q)^n G_{2n}$.


Member-based civic associations, or citizen groups, have two crucial roles in American democracy. They advocate for members' interests in the public arena, but also operate as Tocquevillian "schools of democracy" linking citizens to politics and equipping them with the skills of democratic citizenship. Yet scant research has examined the interrelationships of these two roles. Does the work that civic associations do in developing democratic participants enhance the work they do advocating for members' interests in the public arena? We bring together two previously disparate strands of research on civic associations by arguing that a key factor affecting the political presence of civic associations is leadership quality. We focus on the relationship of leadership quality to political presence, using data from a unique 2003 study of 226 local entities of the Sierra Club. We show that organizations with more skilled and committed leaders have higher levels of political presence. This contrasts with previous research that has focused primarily on community context and resources as explanatory factors. This study shows that political presence is related to the extent to which leaders develop their skills and demonstrate commitment to the organization.


A team of cancer researchers has shown that a gene commonly lost during neuroblastoma tumor formation, one of the most aggressive cancers in babies and children, is in fact a "metastasis suppressor" gene. The researchers, from the Moores Cancer Center at the University of California, San Diego (UCSD) Medical Center and St. Jude Children's Research Hospital in Memphis, also describe how the gene, caspase 8, works. The findings, published in the January 5 issue of the journal Nature, provide important new insights into the biology of metastatic disease and lay the necessary groundwork for developing targeted therapies designed to halt the spread of neuroblastoma, and possibly other cancers. "A major problem with cancer is not necessarily the primary tumor formation, but the ability of some tumor cells within that primary tumor to metastasize, or travel to distant sites, where they develop new tumors," said David Cheresh, Ph.D., senior author on the paper and Associate Director for Translational Research at the Moores UCSD Cancer Center. Cheresh is also a professor of pathology at the UCSD School of Medicine. Caspase 8's normal role is to act as a suicide gene, killing the cell it is housed within in response to cues from the immune system. The UCSD group had previously shown, in normal human cells, that caspase 8 can be activated even without signals from the immune system, particularly when the cell is present in a foreign location. This acts as a mechanism to ensure the cells would survive only in appropriate tissues; for example, liver cells in liver tissue and skin cells in skin tissue. "The exciting point of the new research is that we are finding that even tumor cells will try to make sense of their location, and when they cannot, they will often activate this suicide pathway," said Dwayne Stupack, Ph.D., first author on the paper and assistant professor of pathology at UCSD. The team showed that when a neuroblastoma cell attempts to migrate away from the primary tumor and encounters new tissues, cell-surface molecules called integrins detect that the cell is in "foreign territory" and send "death" signals into the cell. These signals activate caspase 8, which then instructs the cell to commit suicide. The researchers have coined this mechanism "integrin-mediated death." Some cancer cells, however, have found a way to escape the normal death-promoting machinery the body has developed. These cells may suppress or even delete caspase 8, freeing themselves to become much more aggressive and survive in distant sites in the body. "We've shown now in animals and human tissue that as soon as the neuroblastoma cells lose caspase 8, suddenly you have a much more aggressive disease," said Stupack. "This explains why we see the loss of caspase 8 in 70 percent of aggressive neuroblastomas in children." Neuroblastoma is a solid tumor cancer that usually originates in the abdomen near the kidneys. In the majority of cases (about 70 percent), by the time of diagnosis the disease has already metastasized. The average age at diagnosis is two years old."It is clear this gene is a deciding factor in whether or not a cancer cell becomes metastatic, yet, surprisingly, it does not appear to be involved at all in the initial formation of the cancer," said Stupack. "As such, it is one of only a handful of true metastasis suppressor genes currently known." A number of other cancers may use this same mechanism for regulating their metastatic properties, which the researchers are now studying. Caspase 8 loss or suppression is seen in about 70 percent of small cell lung cancer, about 10 percent of colon cancer and about 35 percent of medulloblastoma. While genetic mutation will sometimes delete both copies of the caspase 8 gene, typically the gene is simply silenced. This paper opens up a new way of thinking about cancer therapy. "Now we have a roadmap for attacking not just the primary cancer but the metastatic cascade, the metastatic disease process, as well," said Cheresh. "That is new, and very exciting. We now know the Achilles heel of the metastatic tumor cell. If we can develop drugs targeted at restoring caspase 8, we may be able to stop metastasis. That now appears feasible." The study was co-authored by a team from St. Jude that included Tal Teitz, Ph.D., Peter Houghton, M.D., and Jill Lahti, Ph.D., as well as by UCSD scientists Matthew Potter, Ph.D., and David Mikolon. Lahti, the senior scientist in the St. Jude group, has collaborated with Stupack for several years. The work was funded by grants from the National Cancer Institute awarded to Cheresh, Lahti, Houghton and Stupack. Additional local funding was provided by a grant from the San Diego Padres Cindy Matters Children's Research Fund to Stupack, and by continuing ALSAC support of the St. Jude laboratories. Founded in 1979, the Moores UCSD Cancer Center is one of just 39 centers in the United States to hold a National Cancer Institute (NCI) designation as a Comprehensive Cancer Center. As such, it ranks among the top centers in the nation conducting basic, translational and clinical cancer research; providing advanced patient care; and serving the community through outreach and education programs.


The papers and abstracts in this volume are the outcome of the conference on Island Invasives: Eradication and Management, held at Tamaki Campus, University of Auckland, New Zealand. This conference had "islands" and "eradication of invasive species" as the focus, with emphasis on the work done and results or learning achieved. The conference endeavoured to cover the full breadth of this work by breaking the subject down to: gaining political, community, financial and physical support; eradication techniques tested and used; the immediate results of eradication operations; the longer-term outcomes as seen in the biota of the island and among communities involved; and biosecurity measures for such islands from planning to implementation.


Intertextual war: Edmund Burke and the French Revolution in the writings of Mary Wollstonecraft, Thomas Paine, and James Mackintosh. By Steven Blakemore. Cranbury, NJ: Associated University Presses, 1997. Pp. 256. ISBN 0-8386-3751-5. £32. Radical expression: political language, ritual, and symbol in England, 1790–1850. By James Epstein. Oxford: Oxford University Press, 1994. Pp. xi+233. ISBN 0-19-506550-6. £30. Tom Paine: a political life. By John Keane. London: Bloomsbury, 1996. Pp. xxii+644. ISBN 0-7475-2543-9. £8.99. Gothic images of race in nineteenth-century Britain. By H. L. Malchow. Stanford, CA: Stanford University Press, 1996. Pp. xii+335. ISBN 0-8047-2664-7. £35 (hb). ISBN 0-8047-2793-7. £12.95 (pb). Popular contention in Great Britain, 1758–1834. By Charles Tilly. Cambridge, MA: Harvard University Press, 1995. Pp. xvii+476. ISBN 0-674-68980-1. £31.50. Radical culture: discourse, resistance and surveillance, 1790–1820. By David Worrall. Hemel Hempstead: Harvester Wheatsheaf, 1992. Pp. ix+236. ISBN 0-7450-0960-3. £40. Most of these books are influenced by current philosophical or methodological concerns which might be labelled, according to taste, as poststructuralism, postmodernism, or the linguistic turn; but they are influenced to very varying degrees. At one end of the spectrum stands Tilly's substantial study, essentially modernist, rejecting the latest fashions. At the other stand the books by Blakemore and Malchow, their colours firmly nailed to the mast of deconstruction. Blakemore teaches in a department of English, and although Malchow's institutional affiliation is as an historian, his book is a hermeneutic of literary texts. The great majority of 'postmodern' analyses of texts from this period have come from the stable of literary studies, perhaps especially from scholars concerned, as Malchow is, with the construction of gender, that great growth area of the present time. None of these books subscribes in practice to a postmodern relativism, declaring itself to be merely a construction or representation of the past: all arrive at some kind of closure, explicitly or implicitly asserting the truth of their interpretations. Historians concerned to justify their subject to funding bodies may judge this to be prudent; nevertheless a greater degree of reflexivity, of self-doubt, would have been welcome in some instances, as we shall see.


Absfruct-A systematic design methodology is described for the rapid derivation of %SI architectures for implementing high performance recursive digital filters, particularly ones based on most significant digit (msd) first arithmetic. The method has been derived by undertaking theoretical investigations of msd first multiplyaccumulate algorithm and by deriving important relationships governing the dependencies between circuit latency, levels of pipelining and the range and number representations of filter operands. The techniques described are general and can be applied to both bit parallel and bit serial circuits, including those based on on-line arithmetic. The method is illustrated by applying it to the design of a number of highly pipelined bit parallel IIR and wave digital filter circuits. It is shown that established architectures, which were previously designed using heuristic techniques, can be derived directly from the equations described.


Atrial septal defects (ASDs) are the most common congenital cardiac abnormalities in adults. Patients frequently present with symptoms for the first time at adult age. One of the most common late complications of an ASD is the development of atrial tachyarrhythmias (ATs), especially atrial fibrillation (AF). In a large population-based study from Ontario, the prevalence of AT was 19% in adult patients with ASD, which is fourfold higher than that in the general population.1 The incidence of AT continues to increase with age.2 ,3 This vulnerability to AT is not surprising considering the long-standing haemodynamic derangements due to left-to-right shunting causing atrial stretch, RV dilatation, elevated pulmonary arterial pressure and atrioventricular valve regurgitation. The resultant atrial electrical remodelling with increased dispersion of atrial refractoriness may predispose to AT. Furthermore, in surgically corrected patients, the presence of patches and suture lines may create the substrate for macroreentry AT.

The current guidelines recommend closure of an ASD when there are signs of RV volume overload (in the absence of pulmonary hypertension) or if there is a suspicion of paradoxical embolism. In earlier studies, the prevalence of prior AT at the time of surgical closure at adult age is approximately 20%.2 ,3 ASD closure is associated with reduction in right atrial and ventricular volume and an increase in RVEF. However, atrial electrical and structural remodelling …


We propose a new threshold quantity for the analysis of the epidemiology of infectious diseases. The quantity is similar in concept to the familiar basic reproduction ratio, R0, but it singles out particular host types instead of providing a criterion that is uniform for all host types. Using this methodology we are able to identify the long–term effects of disease–control strategies for particular subgroups of the population, to estimate the level of control necessary when targeting control effort at a subset of host types, and to identify host types that constitute a reservoir of infection. These insights cannot be obtained by using R0 alone.


Organizations dedicated to applying engineering solutions to improve health in developing countries may lack sufficient expertise in the public health aspects of these efforts to ensure successful project design and implementation. The occupational hygienist is a valuable complement to the efforts needed for development-oriented public health engineering projects.


Masson, Sophie.  The Phar Lap Mystery .  Sydney, Aust.:  Scholastic, 2010.  Print The end notes of this historical novel describe the details of the remarkable Australian racehorse, Phar Lap, who, in the difficult times of the Great Depression, gave Australians something positive to think about.  The cover image, from the collection of the State Library of Victoria, shows the big red horse in full stride, tail flying, jockey crouched behind his neck, reigns pulled tight. While the novel tracks alongside the historical story, it is a delightfully written account presented as a two-year diary of an eleven year-old girl.  Diarist, Sally Fielding, is very conscious of the fact that she is writing for posterity.  She begins her September 19, 1931 entry with "Hill Stakes Day, and the best day ever!  I want to write down absolutely everything, to remember it all." Author, Sophie Masson, who has written more than fifty juvenile novels, gives the reader a good snapshot of life in the 1930's in urban Eastern Australia.   From the "chooks" in the back yard, to the fancy hats of the well-to-do ladies at the Rosehill racecourse, to the seedy characters from the underbelly of the racing industry, Masson's detailed descriptions help to draw us into Sally's world.   Aussie slang is sprinkled throughout the book to add to the "down-under" flavour.  "Strewth", which is a mild oath like "crikey" appears often.  Sally refers to a young man with whom she is not impressed, as a "real mick", denies that she's a "stickybeak" when she really has been snooping and has a "slap up" lunch, which is a very good one. The story stretches over two years beginning with Sally's private detective father first being engaged to try to find out who took a shot at Phar Lap and ends with Sally and her father going to America when Phar Lap is taken there  to race.  Sally's diary chronicles her reactions to the various dangerous twists and turns of the case, her father's on-again, off-again romance, and Sally's general chatter about friends and events around her.  The family's economic struggles are ever-present.  Occasionally readers are treated to a facsimile of a real newspaper article or a letter, which is "glued" into the volume, reinforcing the illusion that you really are reading someone's diary. Overall this is a thoroughly enjoyable read that captures your attention and holds it through to the surprising ending.  The Phar Lap Mystery will appeal to readers from pre-teens through adults and especially to readers who love horses. Highly recommended for junior high and high school libraries, as well as public libraries everywhere. Reviewer: Sandy Campbell Highly recommended:  4 out of 4 stars Sandy is a Health Sciences Librarian at the University of Alberta, who has written hundreds of book reviews across many disciplines.  Sandy thinks that sharing books with children is one of the greatest gifts anyone can give.


The extended fuzzy rules for image segmentation (EFRIS) algorithm initially splits all segmented regions into mutually exclusive 4-connected objects, from which the largest one in each region is designated as its main object. A drawback of this approach is that it is less effective when the main objects are relatively small and some of the minor objects are completely surrounded and connected to the main object of another region. Besides, defining insufficient merging rules, EFRIS also only considers the surrounding main objects in the original order that the regions were segmented, which is undesirable. In this paper, a new general segmentation algorithm called modified extended fuzzy rules for image segmentation (MEFRIS) is presented, which addresses these problems and whose improved segmentation performance is analysed and numerically evaluated. The results are also contrasted with both the original generic fuzzy rule-based image segmentation (GFRIS) and EFRIS algorithms.


Parameter inference in mathematical models of complex biological
systems, expressed as coupled ordinary differential equations (ODEs), is a challenging problem. These depend on kinetic parameters, which cannot all be measured and have to be ascertained a different way. However, the computational
costs associated with repeatedly solving the ODEs are often staggering, making
many techniques impractical. Therefore, aimed at reducing this cost, new concepts using gradient matching have been proposed. This paper combines current
adaptive gradient matching approaches, using Gaussian processes, with a parallel tempering scheme, in order to compare 2 different paradigms using the same
nonlinear regression method. We use 2 ODE systems to assess our technique,
showing an improvement over the recent method in Calderhead et al. (2008).


Dynamic Programming (DP) over tree decompositions is a well-established method to solve problems - that are in general NP-hard - efficiently for instances of small treewidth. Experience shows that (i) heuristically computing a tree decomposition has negligible runtime compared to the DP step; (ii) DP algorithms exhibit a high variance in runtime when using different tree decompositions; in fact, given an instance of the problem at hand, even decompositions of the same width might yield extremely diverging runtimes. We thus propose here a novel and general method that is based on a selection of the best decomposition from an available pool of heuristically generated ones. For this purpose, we require machine learning techniques based on features of the decomposition rather than on the actual problem instance. We report on extensive experiments in different problem domains which show a significant speedup when choosing the tree decomposition according to this concept over simply using an arbitrary one of the same width.


In a previous paper we provided guidelines for scholars on optimizing research articles for academic search engines such as Google Scholar. Feedback in the academic community to these guidelines was diverse. Some were concerned researchers could use our guidelines to manipulate rankings of scientific articles and promote what we call 'academic search engine spam'. To find out whether these concerns are justified, we conducted several tests on Google Scholar. The results show that academic search engine spam is indeed— and with little effort—possible: We increased rankings of academic articles on Google Scholar by manipulating their citation counts; Google Scholar indexed invisible text we added to some articles, making papers appear for keyword searches the articles were not relevant for; Google Scholar indexed some nonsensical articles we randomly created with the paper generator SciGen; and Google Scholar linked to manipulated versions of research papers that contained a Viagra advertisement. At the end of this paper, we discuss whether academic search engine spam could become a serious threat to Web-based academic search engines.


The Commonwealth Treasury has recently held consultations concerning the Australian Taxation Office's discretion to withdraw the administrative concession for tax advice provided by accountants. One matter commonly overlooked in this consultation process was the vulnerability of claims for client legal privilege in respect of legal advice provided by legal practitioners to be abrogated in circumstances where Pt IVA of the Income Tax Assessment Act 1936 may apply. This article examines the circumstances in which client legal privilege may be abrogated by reason of the potential application of Pt IVA. The author suggests that the ATO should take appropriate steps to clarify the position and provide certainty to taxpayers. In the interim, practitioners should consider the potential implications of these issues in respect of both tax and non-tax advice and take prudent steps to preserve any right that their clients may have to claim client legal privilege.


Antimicrobial resistance is a challenge facing the world in the twenty-first century with an estimated 10 million deaths by 2050 if no actions are taken. Microbial resistance to drugs is a natural consequence when bacteria develop and adapt genetically to face new challenges including antibiotics. Currently, this development occurs at a higher rate than drug discovery. Hence there is a need for a new generation of antibiotics that kill pathogenic bacteria. Nature itself provides inspiration for such new antibiotics. For example, our immune system secretes antimicrobial peptides (AMPs), which have been successful agents in killing pathogens with no reported bacterial resistance. Compared with conventional antibiotics, these peptides are larger and more sophisticated biological molecules, which disturb the bacterial membrane, leading to cell lysis. It is currently costly to extract AMPs from natural resources to be used for fighting infections. Alternatively, synthetic AMPs that mimic natural ones could provide a sustainable cheap weapon against such thread. This also provides a unique opportunity to understand the structure–function relationships of such molecules to optimise these effective, non-toxic antimicrobial properties. Our collaborators at National Physical Laboratory have designed and synthesised new AMPs from their essential building blocks (amino acids). This thesis describes the use of atomic force microscopy (AFM) as a nanoscale imaging technique for characterising and imaging membrane poration mechanisms of four new AMP systems. Two of these systems are helical peptides, explained in chapter 3. The third system, explained chapter 4, is a triskelion with three arms of antimicrobial β-sheet peptide that co-assemble to form a hollow antimicrobial capsules. The latter has two possible functions: gene delivery and bactericidal effects. The fourth system, explained in chapter 5, contains two peptide monomers that are designed to co-assemble and form antimicrobial hollow capsids, inspired by the natural viral capsids. Finally, chapter 6 is a plan for taking these AMPs a step closer to commercialisation, including a business plan for one potential application.


Design Thinking (DT) has been applied to the corporate world with elan, and organizations have made DT their mainstay. Tourism in its Sustainable avatar can be seen in Community Based Ecotourism (CBE) which has brought to the forefront the Community who live in the forest fringes to adopt to business opportunities with support from the Government, primarily the Forest Departments (FD) across various states in India, and helped in the creation of special purpose vehicles (SPV) which have provided for livelihood options, income generating opportunities at the same point in time to preserve and conserve the ecology, environment, the flora and fauna, which is the mandate of the FD. The researcher paper talks about the efforts of applying DT to community-based business activities and with a population which may not be able to appreciate the larger nuances of business, as we seen in the modern contemporary term. The adoption of DT to businesses and organization, was easily juxtaposed on account of the understanding the associates/employees already had about DT. But when it came to the community helping them to understand the facets was tough, but once they understand that this is for their betterment, they have never looked back. We realized that the experiences provided by the communities were not short of the corporate world and look forward to implement this further as best practices.


The federal government's voice on the subject of parenting has become much more audible over the past several decades. Because opinions about the normative good of the unitary family (i.e. adults related to one another by marriage, and related biologically to each of their children) are in flux both at the state and the federal level, the federal voice is important. Taken together, federal parenting policies, programs and rhetoric do not exhibit a robust preference for the unitary family. Rather, they vigorously promote economically self-sufficient parenting, and involved fathers. They weakly support parenting within marriage. And they discount or dismiss biological parent-child ties in favor of the good of individual adults' choices about parenting -- both about the form of adults' intimate association and whether or not there will be a biological relationship with the children they rear. This article describes how the federal government exhibits these preferences. It also affirms the benefits of federal policies highlighting fatherhood, and the link between non-marital births, poverty and diminished child welfare. It critiques federal policies along two lines: first, the failure to affirm more explicitly the good of biological parenting, and the link between marriage and effective fathering; and second, the absence of reflection upon the long-run failure of its birth control strategy to curb single parenting and associated poverty. It finally suggests that politics and ideology -- as distinguished from concern for children and for the welfare of women and vulnerable populations -- might be influencing federal parenting policy unduly.


The disintegration rates of 222Rn and its daughters in natural water were determined successfully by the use of the integral counting method with a liquid scintillation spectrometer. A significant advantage of this method is its freedom from the quenching effect. Moreover, when plural alpha-, and beta-emitters are present, their total amounts can be determined. The simple extrapolation of integral counting curve to zero pulse-height, however, do not give the true disintegration rate for the soft beta-emitters (Emax < 200 keV), because the liquid scintillator (LS) has a relatively high detection threshold. Therefore, the zero detection threshold of the liquid scintillation spectrometer was determined by measuring standard 3H samples, and a modified integral counting method which extrapolates the integral counting curve to the zero detection threshold was proposed. The method has been successfully applied to various beta-emitters, 222Rn samples, and coloured samples of beta-emitters, giving more accurate absolute disintegration rate than the conventional integral counting method and the efficiency tracing method. In the course of the study determining 222Rn by liquid scintillation counting, we observed unexpected phenomena; the air luminescence from gaseous space above LS, and the temperature dependence of pulse-height spectra. As for the former phenomenon, we proposed a method for correcting errors due to air luminescence, a method for determining alpha-emitters by the air luminescence, and a rapid calibration method for 222Rn detectors. As for the latter phenomenon, we observed that the pulse-height spectra for alpha, and beta-emitters in LS are shifted toward higher pulse-height with decreasing temperature. We found that the fluorescence intensities of the solvent of LS (toluene) is promoted at lower temperatures, and that not only toluene, but also the fluorescence intensity of a number of aromatic hydrocarbons and aliphatic hydrocarbons show the same effect as toluene. Other unexpected results are existence of metals in number of enzymes, and discrepancies between the experimental value for Kurie plot of allowed beta-emitters and the value which would be expected according to Fermi's theory, the results of which would affect the transmission probability of potential barrier for alpha-particles.


"What is strikingly new about Miss Siegel's achievement is that she goes beyond the usual kind of historical reassessment...She performs on behalf of this most evanescent of the arts an act of significant recovery. By tracking down - often in rare stage revivals, on film or on videotape - as many of the works by major creators of the last half century as survive, and by describing them ...in a manner that combines accuracy and imagination, she has enriched our knowledge of the past and added immeasurably, to our resent stock of critical resources." (Dale Harris, New York Times Book Review). "Siegel has a gut feeling for dance and a razor-sharp intelligence about it. It's an irresistible combination." (Margaret Pierpont, Dance Magazine). "After you've seen and felt dance this deeply--even vicariously--your way of looking at dance will never be the same." (William Albright, Houston Post). "She sees, acutely, with her muscles as well as her eyes. She thinks about dance as much as she experiences it...This is dance choreography reconstituted. Dances leap off the page...The ability to do that is extraordinary." (Jean Bunke, Des Moines Sunday Register). "The sections in which she describes the dances themselves make up the bulk of the book and they are profoundly illuminating...These descriptions represent an amazing literary, as well as critical, accomplishment, for they are both accurate and resonant, both objective and enlightening, both formal and personal." (Laura Shapiro, The Real Paper). "Siegel draws on her years of experience as a working dance critic, a profession she has helped to shape, and brings to a range of American dance a sense of honesty and a mind that wants to understand the antecedents of what is currently in vogue as the dance explosion." (Iris M. Fanger, The Christian Science Monitor).


Autophagy is an essential cellular degradative process that has been implicated in the pathogenesis of several neurodegenerative diseases including Huntington's disease and Amyotrophic Lateral Sclerosis (ALS). During autophagy, autophagosomes form around cargo such as mitochondria, and subsequently fuse with lysosomes to acidify and acquire enzymes to degrade internalized cargos. In neurons, constitutive autophagosome biogenesis preferentially occurs at the axon tip, followed by the robust retrograde axonal transport of autophagosomes back to the cell body. The mechanisms regulating both the axonal transport of autophagosomes and the selective degradation of damaged mitochondria have not yet been determined. Here, I report novel roles for huntingtin and optineurin in regulating these dynamics and show that this regulation is disrupted in models of neurodegenerative disease. Using live cell imaging of primary neurons, I demonstrate that huntingtin regulates autophagosome retrograde axonal transport via its interactions with dynein and the motor adaptor protein HAP1 (huntingtin-associated protein 1). Loss of either huntingtin or HAP1 disrupts autophagosome transport. We also find that expression of the polyglutamine expansion in huntingtin (polyQhtt) which leads to Huntington's disease disrupts autophagosome transport, resulting in reduced autophagosome motility and inefficient cargo degradation. These observations support a model in which robust autophagosome transport is required for efficient lysosomal encounters along the axon; inhibition of this transport prevents efficient degradation of internalized cargos. To further explore the mechanism regulating autophagy, I also examined the dynamics of selective mitochondrial degradation during PINK1 (PTEN-induced putative kinase 1)/parkin-dependent mitophagy. These studies identified optineurin as a novel autophagy receptor for damaged mitochondria. Optineurin is recruited to the outer mitochondrial membrane (OMM) following parkin-mediated ubiquitination of OMM proteins. Optineurin binds to ubiquitinated proteins via its UBAN domain, and subsequently recruits the autophagosome protein LC3 via its LC3 interacting region (LIR). This pathway is disrupted by either loss of optineurin or an ALS-associated E478G mutation in optineurin's ubiquitin binding domain, leading to inefficient mitochondrial degradation. Together, these studies provide new insights into the mechanisms driving autophagy and mitophagy, and further demonstrate that defects in autophagy may contribute to pathogenesis in both Huntington's disease and familial ALS. Degree Type Dissertation Degree Name Doctor of Philosophy (PhD) Graduate Group Neuroscience First Advisor Erika L. Holzbaur This dissertation is available at ScholarlyCommons: http://repository.upenn.edu/edissertations/1165


Stanley Potts is just an ordinary boy, but when all the jobs in Fish Quay disappear his Uncle Ernie develops an extraordinary fascination with canning fish. Suddenly their home is filled with the sound of clanging machinery and the stench of mackerel, and Uncle Ernie's obsession reaches such heights that he would even can Stan's beloved goldfish! Stan, however, has his own destiny, which leads him - via a hook-a-duck stall - to Pancho Pirelli, the blue-caped madman who swims with piranhas. And as Stan delves into the waters, he finally discovers who he really can be.


The mechanisms of growth of silicon carbide (SiC) films by the method of substitution of atoms on macroand mesoporous silicon substrates (Si) of pand n-type conduction are investigated. Significant dependence of the rate and the mechanism of nucleation of SiC layers on Si on the type of Si doping and its crystallographic orientation is experimentally found. Comparison of the experimental data with the theoretical results obtained earlier is performed. It is shown that the presence of the system of pores on the surface allows one to significantly increase the thickness of silicon transformed into SiC during the process of synthesis by the method of substitution of atoms, which was equal to 115 microns in our experiments. The obtained samples are studied by methods of scanning electron microscopy, micro-Raman spectroscopy, and X-ray diffraction analysis. Numerical simulation of the distribution of elastic stresses caused by the difference in thermal expansion coefficients (TEC) in the heterostructures of GaN/SiC/porous Si/Si is conducted. It is revealed that the presence of pores in the near-surface layers of Si leads to considerable relaxation of elastic stresses in GaN films caused by differences in the TEC between GaN and Si.


In order to define the teaching orientation of environmental specialty in colleges and universities, this paper emphasizes the consistency and similarity between teaching and practice, and turns to promote and encourage the development of characteristics, advantages and differences of environmental specialty teaching in colleges and universities. This paper proposes a classroom teaching effect evaluation model for environmental specialty based on cognitive neural theory. According to the analysis of current environmental professional classroom teaching, the introduction of different types of colleges and universities in teaching environment in the level of the special teaching mode, using the PLS - SEM statistical techniques to determine the effect of classroom teaching evaluation, on the basis of the understanding of theory, the effect of classroom teaching evaluation model is set up, and to evaluate the effect of classroom teaching. The experimental results show that the evaluation accuracy of the model is higher.


ABSTRACT The current study investigated the effects of task-clarification, and manager verbal and graphic feedback on employee busing times at a pizza restaurant. Using an ABC design, task-clarification was provided in a memo, which described the process, priority, and goal time of busing. The busing time decreased slightly, from an average of 315 seconds during baseline to an average of 284 seconds after the task clarification memo. The majority of this change was accounted for by servers decreasing the time it took them to arrive at the table to begin busing. Subsequent to the employee memo, group feedback was administered in the form of verbal feedback and a weekly graph of average server busing times. This feedback was associated with reductions in busing time to an average 152 seconds. Changes in the feedback phase were caused almost exclusively by reductions in the time it took to clean the table once the server was there. A reversal to near-baseline busing times was observed in a follow-up phase. Prebusing and cross-busing were not associated with shorter busing times.


INTRODUCTION For more than 20 years, Caribbean leaders have pursued regional integration as a response to the challenges of globalization. The response, while consistent, has been sluggish and often wracked by nationalist politics and poor administrative procedures. As a result, the Anglophone Caribbean's experience and experimentation with regionalization has been the focus of some academic study of the politics, process, and procedure that has shaped the efforts, but the majority of the research has often ignored the role or opinion of the public about regional integration. This omission has meant the voice of the people most likely to be affected by the policies adopted by Caribbean leaders or ignored and at the least minimized. Regional integration has been an evolutionary response for the Anglophone Caribbean as it sought increased economic opportunities on the global scene. Among international organizations, regionalization is the only response. In its 2010 report, Opportunities for Convergence and Regional Cooperation, the Economic Commission for Latin America and the Caribbean (ECLAC), noted that "greater regional cooperation and closer collaboration between and within the sub regions is no longer merely a major political objective, but also an economic imperative if the region is to integrate into a global economy that is increasingly structured around regional or sub regional value chains." (1) Taking the lead on regional integration efforts has been the Caribbean Community (CARICOM). Established in 1973, CARICOM was created to pursue "the attainment of a viable, internationally competitive and sustainable Community, with improved quality of life for all." (2) CARICOM represents 15 member states that stretch from Jamaica in the northeast to Guyana in the south on the mainland of South America. It has been the premier tool through which the region has pursued integration efforts under the Caribbean Free Trade Agreement (CARIFTA), the Common Market and, most recently, the Caribbean Single Market and Economy (CSME). The CSME, the region's most ambitious effort at integration, is a vast regional agreement that calls for cooperation in seven areas, including taxes, finance, labor, laws, goods, services, and business. CARICOM leaders announced the launch of the CSME with a goal to "provide more and better opportunities to produce and sell our goods and services and to attract investment. It will create one large market among the participating member states." (3) One of the goals of the CSME was to encourage full use of labor through free movement of skills and services. Divided into two components, the Single Market and Single Economy, the CSME has challenged Caribbean leaders previous concepts about regionalization that historically have focused on trade and tax agreements. This time, CARICOM member states are pursuing unity in new areas, particularly under the Single Market that includes free movement of labor and services. Outlined in Article 46 of the Revised Treaty of Chaguaramas, the free movement of labor policy envisions a new concept of integration that relaxes employment restrictions in member states to allow certain categories of workers to move freely. This policy is likely to have the most direct impact on residents of the region as it allows initially five categories of workers to move easily among member states to seek employment without the need for work permits. Despite the consequences for employment levels, career opportunities, and migration, Caribbean leaders have done little to investigate public opinion and generate public awareness about the free movement of labor policy under the CSME. Rather, more than 10 years since member states agreed to implement the free movement of labor policy residents remain woefully unaware about the details of the policy. Additionally, CARICOM has struggled to monitor the policy in action and residents remain distrustful and misinformed about the policy. …


This paper explores the role of basin-scale fluid migration in stratiform Pb-Zn ore formation in the southern McArthur Basin, Australia. Mathematical models are presented for coupled brine migration and heat transport in the basin. The models account for: (i) topographically driven flow (forced convection) during periods when parts of the McArthur Basin were subaerial and elevated above the central Batten Fault Zone; (ii) density-driven flow (free convection) during periods when the basin was mostly submarine; and (iii) transient flows associated with fault rupture during periods of transpression. These hydrologic models help to compare and contrast a variety of hypotheses concerning deep fluid migration and the origin of base metal ores in the McArthur Basin. The numerical results exhibit a strong structural control on fluid flow caused by the north-trending fault systems that characterize the Batten Fault Zone. As a result, fluids descend to depths of a few kilometers along the western side, migrate laterally to the east through the clastic and volcanic aquifers of the upper Tawallah and lowest McArthur Groups, and then ascend along the eastern side of the fault zone. This recharge-discharge pattern dominates all of the hydrogeologic models. The basin-wide flow pattern suggests that Na-Ca-Cl brines acquired base metals in the deepest levels of the basin stratigraphy as the fluids migrated eastwards through the aquifer system. Upward flow was relatively rapid along the Emu Fault Zone, so much so that fluid temperatures likely approached 130 degrees celsius in the muddy sediments near the sea floor due to upward flow and venting at the HYC ('Here's Your Chance'). Transient pulses of flow characterized periods of transpressional stress and subsequent faulting may have punctuated the basin history. Large-scale free convection, however, characterized notably long periods of diagenesis and ore mineralization during the Proterozoic in the McArthur Basin.


Theoretical approaches to low-frequency magnetized turbulence in collisionless and weakly collisional astrophysical plasmas are reviewed. The proper starting point for an analytical description of these plasmas is kinetic theory, not fluid equations. The anisotropy of the turbulence is used to systematically derive a series of reduced analytical models. Above the ion gyroscale, it is shown rigourously that the Alfvén waves decouple from the electron-density and magnetic-field-strength fluctuations and satisfy the Reduced MHD equations. The density and field-strength fluctuations (slow waves and the entropy mode in the fluid limit), determined kinetically, are passively mixed by the Alfvén waves. The resulting hybrid fluid-kinetic description of the lowfrequency turbulence is valid independently of collisionality. Below the ion gyroscale, the turbulent cascade is partially converted into a cascade of kinetic Alfvén waves, damped at the electron gyroscale. This cascade is described by a pair of fluid-like equations, which are a reduced version of the Electron MHD. The development of these theoretical models is motivated by observations of the turbulence in the solar wind and interstellar medium. In the latter case, the turbulence is spatially inhomogeneous and the anisotropic Alfvénic turbulence in the presence of a strong mean field may coexist with isotropic MHD turbulence that has no mean field. Submitted to: Plasma Phys. Control. Fusion on 31 May 2006, now accepted and scheduled to be published in May 2007


AIMS
In our aging society, age-related hearing loss (ARHL) or presbycusis is increasingly important. Here, we study the mechanism of ARHL using the senescence-accelerated mouse prone 8 (SAMP8) which is a useful model to probe the effects of aging on biological processes.

RESULTS
We found that the SAMP8 strain displays premature hearing loss and cochlear degeneration recapitulating the processes observed in human presbycusis (i.e., strial, sensory, and neural degeneration). The molecular mechanisms associated with premature ARHL in SAMP8 mice involve oxidative stress, altered levels of antioxidant enzymes, and decreased activity of Complexes I, II, and IV, which in turn lead to chronic inflammation and triggering of apoptotic cell death pathways. In addition, spiral ganglion neurons (SGNs) also undergo autophagic stress and accumulated lipofuscin.

INNOVATION AND CONCLUSION
Our results provide evidence that targeting oxidative stress, chronic inflammation, or apoptotic pathways may have therapeutic potential. Modulation of autophagy may be another strategy. The fact that autophagic stress and protein aggregation occurred specifically in SGNs also offers promising perspectives for the prevention of neural presbycusis.


Background Angiotensin-converting enzyme (ACE) (EC 4.15.1) metabolizes many biologically active peptides and plays a key role in blood pressure regulation and vascular remodeling. Elevated ACE levels are associated with different cardiovascular and respiratory diseases. Methods and Results Two Belgian families with a 8-16-fold increase in blood ACE level were incidentally identified. A novel heterozygous splice site mutation of intron 25 - IVS25+1G>A (c.3691+1G>A) - cosegregating with elevated plasma ACE was identified in both pedigrees. Messenger RNA analysis revealed that the mutation led to the retention of intron 25 and Premature Termination Codon generation. Subjects harboring the mutation were mostly normotensive, had no left ventricular hypertrophy or cardiovascular disease. The levels of renin-angiotensin-aldosterone system components in the mutated cases and wild-type controls were similar, both at baseline and after 50 mg captopril. Compared with non-affected members, quantification of ACE surface expression and shedding using flow cytometry assay of dendritic cells derived from peripheral blood monocytes of affected members, demonstrated a 50% decrease and 3-fold increase, respectively. Together with a dramatic increase in circulating ACE levels, these findings argue in favor of deletion of transmembrane anchor, leading to direct secretion of ACE out of cells. Conclusions We describe a novel mutation of the ACE gene associated with a major familial elevation of circulating ACE, without evidence of activation of the renin-angiotensin system, target organ damage or cardiovascular complications. These data are consistent with the hypothesis that membrane-bound ACE, rather than circulating ACE, is responsible for Angiotensin II generation and its cardiovascular consequences.


Abstract. Observations of naturally enhanced ion acoustic lines (NEIALs) taken with the Poker Flat Incoherent Scatter Radar (PFISR) using a mode with very high time resolution are presented. The auroral event took place over Poker Flat, Alaska on 8 February 2007 at 09:35 UT (~22:00 MLT), and the radar data are complemented by common-volume high-resolution auroral imaging. The NEIALs occurred during only one of the standard 15-s integration periods. The raw data of this time show very intermittent NEIALs which occur only during a few very short time intervals (≤1 s) within the 15-s period. The time sampling of the raw data, ~19 ms on average, allows study of the time development of the NEIALs, though there are indications that even finer time resolution would be of interest. The analysis is based on the assumption that the NEIAL returns are the result of Bragg scattering from ion-acoustic waves that have been enhanced significantly above thermal levels. The spectra of the raw data indicate that although the up- and down-shifted shoulders can both become enhanced at the same time, (within 19 ms), they are most often enhanced individually. The overall power in the up-and down-shifted shoulders is approximately equal throughout the event, with the exception of one time, when very large up-shifted power was observed with no corresponding down-shifted power. This indicates that during the 480 μs pulse, the strongly enhanced ion-acoustic waves were only traveling downward and not upward. The exact time that the NEIALs occurred was when the radar beam was on the boundary of a fast-moving (~10 km/s), bright auroral structure, as seen in the high resolution auroral imaging of the magnetic zenith. When viewed with high time resolution, the occurrence of NEIALs is associated with rapid changes in auroral luminosity within the radar field of view due to fast-moving auroral fine structures.


Background: Cementum is a hard tissue in the root, which is deposited around dentin in layers throughout life. Under the light microscope, root cementum is seen as alternate light and dark rings known as incremental lines of cementum. In paleontology and forensic medicine, the number of these incremental lines is used to derive the age at death of an individual. Objectives: The present study was undertaken to determine if any relation exists between incremental lines of cementum and age of the individual. Materials and Methods: Twenty-five teeth from patients of known ages and devoid of any pathology such as attrition or hypercementosis were selected for this study. Ground sections were prepared manually. Nineteen of them showed visible countable annulations, while six showed indistinct, invisible annulations and hence were excluded from the study. Half of the selected teeth were sectioned longitudinally and the remainder were cross-sectioned. The mid-root region was selected for counting the annulations. Cemental annulations were counted after taking a photograph and enlarging the mid-root area. Age was then determined by adding the eruption age of the tooth to the annulations counted. Results and Conclusions: It was observed that cemental annulations, when appreciated, can be used as a reliable guide to determine the age of the patient. The age thus determined varied by about 2−3 years from the actual age of the patient. The reliability of the method was found to be 94.73%. There was good interobserver agreement in counting annulations.


High expectations of development and renewal of form and content in schools are now very common. However there seem to be no simple answers how to do. Schools are a complex organisation with many stakeholders involved. The complexity concern for example formal decisions taken on many different levels, state, municipally and in school-units, but perhaps the most important decisions are made informal in the classrooms. Schools as an organisation also seem to be hard to change. Developing processes have a tendency to take long time before there are possible to discover any results. Teachers have continuously lack of time, here and now, as there are so many things to be done. What is the role of the school-leader under these conditions? One of the problems school-leaders have to face is, as there are many expectations, the difficulty to make priorities among their work. The teachers demand the school-leaders to be "visible". Meetings take so much time those school-leaders can not take active part in the daily work as expected. They are supposed to be "pedagogical-leaders", at the same time this usually does not seem to work in practise. Politicians and the public are keen to know what the results are. The budget gives restrictions that can not be exceeded. The parents would like to have influence and so on and on. In short, the expectations of the school-leaders are high. In the paper is discussed what possibility school-leaders have to manage school-development. Following questions are raised: What kind of strategically choices do school-leaders meet when they are going to manage school-development? Is it possible to manage school-development in a long-term perspective and what may school-leaders do to make it possible to involve the personnel in an efficient way? It seems apparent that school development is a field just as complicated as one has reason to believe. It is important to give teachers a possibility to be involved in school-development processes and also the managers' choice of development strategy seems to be of importance. Managers have to be those who create necessary prerequisites and co-ordinate the activities. The accomplishment is in many aspects possible to hand over to the teachers. There is however a risk to see school-development processes as clearly defined short-term projects. When school-development on the other hand is run in a long-term perspective there seems to be possible to expect more lasting effects as a result. There are of course no simple solutions how to do, but it seems as a necessary prerequisite that school-development must be well prepared and carried out systematically, with high involvement and on the ground of dialogue. The managers have to support these processes especially when difficulties of different kinds occur and, not at least, have faith to the teachers ability.


Objective Functional dyspepsia (FD) is an extremely common functional gastrointestinal disorder, the pathophysiology of which is poorly understood. We hypothesised that impaired intestinal barrier function is involved in the onset and persistence of this disorder by inducing low-grade inflammation. Therefore, our aim was to evaluate duodenal mucosal integrity and low-grade inflammation in patients with FD. Design Duodenal biopsy specimens were obtained from 15 patients with FD fulfilling the Rome III criteria and 15 age- and gender-matched healthy volunteers. Transepithelial electrical resistance (TEER) and paracellular permeability were measured in Ussing chambers. Expression of cell-to-cell adhesion proteins was evaluated by real-time PCR, western blot and/or immunofluorescence. Numbers of mast cells, eosinophils and intraepithelial lymphocytes were assessed by immunohistochemistry. Results Patients with FD displayed lower TEER and increased paracellular passage compared with healthy controls, which is indicative of impaired mucosal integrity. In addition, abnormal expression of cell-to-cell adhesion proteins at the level of tight junctions, adherens junctions and desmosomes was shown. Furthermore, patients were characterised by the presence of low-grade inflammation, as demonstrated by increased infiltration of mucosal mast cells and eosinophils. A significant association between the expression level of several cell-to-cell adhesion proteins, the extent of increased permeability and the severity of low-grade inflammation was found. Conclusions These findings challenge the classical paradigm that patients with FD show no structural changes in the gastrointestinal tract. We suggest that impaired intestinal barrier function is a pathophysiological mechanism in FD. Thus, restoration of intestinal barrier integrity may be a potential therapeutic target for treating patients with FD.