With the advent of phage display antibody libraries, humanization of murine antibodies can be achieved by epitope guided selection. In present study, guided selection was applied to the humanization of the mouse mAb Z8 that is directed to human TNF-alpha and can neutralize the cytotoxicity of TNF-alpha. First, the Z8 Fd gene was paired as a template with a repertoire of human kappa chains, and displayed on the filamentous phage, forming a hybrid phage antibody library. Selected by four rounds of panning against TNF-alpha, hybrid antibody fragments that bound to TNF-alpha and contained human kappa chains were obtained. Meanwhile human Fd genes were selected by pairing the human Fd repertoire with the Z8 kappa chain and performing the same procedure of panning. One of the isolated human Fd genes (huFd2), which showed the strongest reactivity, was chosen to pair with 12 of selected human kappa chains. Two of the resulting human Fabs (huFd2-hukappa1 and huFd2-hukappa2), with same Fd and different kappa chains, bound to TNF-alpha specifically. Their human origin was proved by ELISA and sequencing analysis. The human Fabs competitive ELISA and in vitro TNF-alpha neutralization assay demonstrated that the human Fabs resembled its parental mouse mAb Z8 in that they both recognized the same epitope and neutralized the cytotoxicity of TNF-alpha. These results suggest that guided selection is a promising strategy in murine mAb humanization.


This paper poses the challenges that is facing the accounting profession in the information technology era of today and the future. The organizational information that is needed by management must be of value and substance and this requires the use of computer technology by the accountants. Thus, time has come for the accountants to check their functions and roles in the information- based management. The accounting profession like any other is cautious in undertaking drastic changes to their accounting skills and curriculum and this might endanger their existence in the not distant future.


At the end of 2002 there were nine W501G engines in commercial operation, with the lead engine having accumulated 13,000 operating hours and the total fleet about 50,000 operating hours. By the end of 2003 we expect to double the number of operating engines. This paper describes the advanced design features incorporated into the W501G engine, technology/component verification programs carried out in its development, extensive field verification tests, and engine operational experience since its introduction in 1999. The W501G is the latest in a series of successful heavy duty frames developed by Siemens Westinghouse. It is the most powerful and most efficient operating 60 Hz gas turbine, with combined cycle net LHV based efficiency of 58%. Its design is based on viscous 3-D aerodynamics, advanced cooling and sealing, ultra lean premixed combustion, and proven aero engine materials and coatings. It is the first operating engine with closed-loop steam cooling in the transition. Its compressor aerodynamics and mechanical integrity were verified in a full scale test. Numerous rig tests were carried out on its cooling designs, sealings, combustion system, and coatings. An extensive field test program, including telemetry, pyrometry and thermal paint tests, was carried out to verify its performance, emissions and mechanical integrity.Copyright © 2003 by ASME


Web 2.0 may be an elusive concept, but one thing is certain: using the Web as merely a means of retrieving and displaying information is history. Today?s Web is immediate, interactive, innovative. It is user-controlled and community-driven. Organizations, marketers, application developers, and communicators must be ready to respond and to innovate or be left behind, and the experts featured on these pages are leading the charge. Their ideas are fresh, sometimes experimental, necessarily flexible, and always on the leading edge to prepare you for a Web where users rule.


Semiconductor laser diodes (SLDs) have been widely used in wavelength-divisionmultiplexing (WDM) systems due to small size, low power consumption, fast response,and its ability to perform direct modulation at moderate bit rates. A major obstacle preventing closer channel spacing is the drift of emission wavelength with ambient temperature variation. Therefore, with the development of dense WDM (DWDM)
systems, lasers with narrow linewidth, high side mode suppressed ratio (SMSR), low chirp, low cost, and stable dynamic single-mode operation are indispensable.
In recent years, fiber grating Fabry-Perot (FGFP) laser is proposed as an alternative light source for WDM systems, which can generate light with highly stable wavelengths. This is because; the emission wavelength of such laser depends only on the Bragg wavelength of fiber grating (FG), thus, independent of chip temperature and injection current. However, FGFP laser output experiences phase fluctuations due to the quantum nature of the light. In addition, ambient temperature variation causes fluctuation in the gain spectrum, threshold current, and other cavity parameters. Furthermore, external optical feedback (OFB) level (i.e. the light reflected back from grating fiber) significantly affects the performance of FGFP laser, which may fluctuate the FGFP light intensity and varies the dynamical and spectral behaviors of the laser. These will produce unwanted effect such as mode hopping and/or the coherence collapse.
In this thesis, the performance of the FGFP laser is enhanced by optimizing parameters in its original model. The effect of ambient temperature variation, OFB, injection
current, cavity volume, nonlinear gain compression factor, spontaneous emission factor, linewidth enhancement factor, antireflection (AR) coating reflectivity, external cavity
length, amplitude coupling coefficient, and fiber Bragg grating (FBG) parameters on the performance characteristics of the FGFP laser, namely dynamic response (transient
response, turn-on time delay, relaxation oscillation frequency), modulation responses (intensity modulation, frequency modulation) and noise characteristics (relative intensity noise, phase noise, linewidth characteristics) has been demonstrated. In this study, we modeled FGFP laser based on the three-mirror laser cavity model. The reflection from the external mirror is combined with the reflection of the laser end front facet, ending up
with a complex-valued effective reflection coefficient, which is equivalent to two-mirror cavity. The expressions that describe the laser characteristics have been modified by considering the effect of temperature, external OFB and other external cavity parameters.
This thesis is presented based on the alternative format which has been approved by University Putra Malaysia's Senate, which is the manuscript-based format. The major
difference between this alternative format and the conventional ones is that, this format uses published papers in place of the regular chapters on the results and discussion. The first paper, which deals with the turn-on time delay characteristics of the semiconductor diode lasers, is a comment paper, contains new results of the effect of the carrier recombination rate coefficients on the laser turn-on time delay which is published
in Optics and Laser Technology. This journal in indexed by ISI Thomson Scientific with 2010 impact factor of 1.616. The results in this paper corrected the misconception to the behavior of the carrier recombination rate coefficients on the laser turn-on time delay, which has been published by Zhang et al, Opt. & Laser Technol. 39 (2007) 997–
1001. This paper is based on a numerical closed-form equation for turn-on time delay in terms of all carrier recombination rate coefficients. The comparison between our results and those that has been published was based on the practical and physical concepts for the operation principle of semiconductor lasers. It has been shown that the main effect of increasing any of the carrier recombination rate coefficients is to increase the turn-on time delay (not to decrease, as in original report), which is due to increase of the carrierrecombination rate. This fact has been supported further by investigating the effect of carrier recombination rate coefficients on the laser threshold current.
The second paper contains a comprehensive analysis on FGFP laser peak intensity modulation and relaxation oscillation frequency (ROF) characteristics, which is published in Optical Review, the Japan Society of Applied Physics. This journal in indexed by ISI Thomson Scientific with 2010 impact factor of 0.55. The frequency of the relaxation oscillation plays an important role in determining laser response. The study is performed by modifying the general expression of ROF equation, which is often expressed in terms of the carrier and photon lifetimes. It is demonstrated that by optimizing design parameters, ROF increased significantly to produce high flat frequency operation.
 The third paper investigated the FGFP laser modulation response characteristics, which is published in Optics and Laser Technology. This journal in indexed by ISI Thomson Scientific with 2010 impact factor of 1.616. In this paper, a unified and comprehensive study on the small-signal intensity modulation (IM) and frequency modulation (FM)
characteristics of FGFP laser have been numerically conducted. This study has been presented by developing the general expressions of the intensity and frequency
modulations response using the single-mode laser rate equation. It was shown that with laser dimension optimization, IM and FM responses with low peak amplitude, high flat frequency operation and high temperature stability can be obtained.
The most important feature of a semiconductor laser used in optical communication systems is the ability to operate with low relative intensity noise. In the fourth paper, we
present a comprehensive analysis on the FGFP laser relative intensity noise (RIN) characteristics, which is published in IEEE Journal Quantum Electronics. This journal is
indexed by ISI Thomson Scientific with 2010 impact factor of 2.48. In this paper, the analysis has been performed numerically by developing a set of nonlinear single-mode
laser rate equations. It is shown that by laser optimization, the relative intensity noise level of FGFP laser can be reduced significantly.
Finally, the phase noise characteristics of a semiconductor laser are of interest in evaluating the performance of a coherent optical communication system. Because of the
quantum nature of the lasing process, the laser output exhibits phase as well as intensity fluctuations. The fifth paper discussed the phase noise characteristics of FGFP laser,which is published in the Journal of Modern Optics. This journal in indexed by ISI Thomson Scientific with 2010 impact factor of 0.988. In this paper, the analysis was
performed numerically by modifying the general expression of the laser phase noise equation. Through a comprehensive analysis, the results clearly show that by laser optimization, the FGFP laser phase noise performances significantly improved.


The acoustic emission extraction experiment of rotor crack fault has done on the rotor comprehensive fault simulation test-bed. Characteristics of acoustic emission signal of different crack rotors in various depth and conditions are analyzed. The noise-disturbing problems and the noise-eliminating methods of the acoustic emission signal were researched in the paper, and the comparison has been done with the vibration method of crack fault diagnosis by the experiment. The advantages of acoustic emission technique has been highlighted in the early period crack fault diagnosis. The wavelet packet technique was applied to obtain the characteristics of acoustic emission signal of the rotor crack propagation. the diagnosis results are shown to be quite clear, reliable and accurate.


To reasonablely assess the residual fatigue life of aged existing reinforced concrete(RC) bridges, axial tensile fatigue tests were conducted on fifteen naturally carbonation-induced corrosion steel bars. The fatigue test results indicate that the existence of corrosion pits reduces the fatigue life of steel bars significantly under the same fagitue stress; with the development of corrosion, the fatigue life of steel bars decays according to negative power exponent law approximately and the attenuation rate increases with stress level augment. The fatigue deterioration law of natural corrosion steel bars is similar to that of accelerated corrosion steel bars, but the attenuation rate is different from that of accelerated corrosion steel bars, and also the influence of stress level on the attenuation rate is just cross to that of accelerated corrosion steel bars. For the complexity of fatigue and corrosion, further pertinent conclusions remain to be confirmed.


We introduce the proximity rank join problem, where we are given a set of relations whose tuples are equipped with a score and a real-valued feature vector. Given a target feature vector, the goal is to return the K combinations of tuples with high scores that are as close as possible to the target and to each other, according to some notion of distance or dissimilarity. The setting closely resembles that of traditional rank join, but the geometry of the vector space plays a distinctive role in the computation of the overall score of a combination. Also, the input relations typically return their results either by distance from the target or by score. Because of these aspects, it turns out that traditional rank join algorithms, such as the well-known HRJN, have shortcomings in solving the proximity rank join problem, as they may read more input than needed. To overcome this weakness, we define a tight bound (used as a stopping criterion) that guarantees instance optimality, that is, an I/O cost is achieved that is always within a constant factor of optimal. The tight bound can also be used to drive an adaptive pulling strategy, deciding at each step which relation to access next. For practically relevant classes of problems, we show how to compute the tight bound efficiently. An extensive experimental study validates our results and demonstrates significant gains over existing solutions.


The dynamic responses of reserve carbohydrates with respect to shortage of either carbon or nitrogen source was studied to obtain a sound basis for further investigations devoted to the characterization of mechanisms by which the yeast Saccharomyces cerevisiae can cope with nutrient limitation during growth. This study was carried out in well‐controlled bioreactors which allow accurate monitoring of growth and frequent sampling without disturbing the culture. Under glucose limitation, genes involved in glycogen and trehalose biosynthesis (GLG1, GSY1, GSY2, GAC1, GLC3, TPS1 ), in their degradation (GPH1, NTH1 ), and the typical stress‐responsive CTT1 gene were coordinately induced in parallel with glycogen, when the growth has left the pure exponential phase and while glucose was still plentiful in the medium. Trehalose accumulation was delayed until the diauxic shift, although TPS1 was induced much earlier, due to hydrolysis of trehalose by high trehalase activity. In contrast, under nitrogen limitation, both glycogen and trehalose began to accumulate at the precise time when the nitrogen source was exhausted from the medium, coincidentally with the transcriptional activation of genes involved in their metabolism. While this response to nitrogen starvation was likely mediated by the stress‐responsive elements (STREs) in the promoter of these genes, we found that these elements were not responsible for the co‐induction of genes involved in reserve carbohydrate metabolism during glucose limitation, since GLG1, which does not contain any STRE, was coordinately induced with GSY2 and TPS1. Copyright © 1999 John Wiley & Sons, Ltd.


Data availability for small area level is one of the keys to the success of regional development. However, direct estimation of small areas can produce high error due to inadequate sample sizes so the estimation is not reliable. One of alternative solution to this problem is to use the Small Area Estimation (SAE) method which can improve precision by "borrows strength" of the corresponding region information or auxiliary variable information that is strongly related to the response variable. This study uses two SAE models, namely SAE EBLUP Fay-Herriot model with auxiliary variables Podes data and SAE with Error Measurement with auxiliary variable Twitter data. Estimation results using the SAE method are better than direct estimates. This is shown by the RSE value which produced from SAE method, both the EBLUP model and Measurement Error, is smaller than the direct estimate. Therefore, big data can be used as an alternative variable in the SAE model because the data is available in real-time, covers up to the smallest area, and relatively low cost.


In order to shed light on the principal irregularities found in various optical crystals for infrared detectors, their origins, and their influence on device performance, we have carried out high resolution monochromatic synchrotron X-ray diffraction imaging of triglycine sulfate (TGS) crystals. Images of crystals grown during the First International Microgravity Laboratory (IML-1) flight in 1992 were taken and compared with others of terrestrially-grown crystals. The local acceptance angle for diffraction from the uncut TGS crystal grown on the IML-1 mission was found to be 1-2 arc seconds, indicating extraordinary crystal uniformity. The only inclusions visible in the topographs were polystyrene particles intentionally introduced into the growth solution of the space crystal. No demarcation was seen between the terrestrial seed and the new growth of the crystal grown in space. TGS crystals grown on the ground were found to have edge dislocations near the cleaved surface. The results of the topographic studies of the space- and ground-grown crystals are discussed and their implications identified.


Relationship between the registration and right change of housing land use right is not clearly stipulated in the Property Law. Land registration involves functions of private law and public law. It is partial to only considering private rights dimension when deciding whether registration validity doctrine or registration confrontation doctrine should be implemented in housing land use right. Compilation of land use planning, implementation of land use control and promotion of arrangement project in rural residential area all rely on sound and complete housing land registration data. To clarify housing land right adscription, eliminate hidden troubles causing housing land dispute and promote the establishment of harmonious countryside can never be achieved without housing land registration data. To carry out registration validity doctrine of housing land use right can effectively guide farmers' registration behavior and thus build a perfect registration information system of housing land use right. After the cross-village and even cross-town arrangement in rural residential areas, rural acquaintance society has transformed into semi-acquaintance society and even stranger society. Therefore, housing land use right commending its existence with registration in public form has been a necessary choice in legislation.


In Part 1 of this paper, we introduced a coding-based proactive network protection scheme, named Coded Path Protection (CPP). In CPP, a backup stream of the primary data is encoded with other data streams, resulting in capacity savings. In addition to being a systematic approach of building valid coding structures, CPP is an optimal and simple capacity placement and coding group formation algorithm. It converts the sharing structure of any solution of a Shared Path Protection (SPP) technique into a coding structure with minimum extra capacity. In this Part 2 of the paper, we describe the implementation of our algorithm using Integer Linear Programming (ILP), its timing and synchronization requirements, and implementation issues in networks. We present simulation results which confirm that CPP provides faster link failure recovery than SPP while it incurs marginal extra capacity beyond that of SPP.


In these pages, I seek to advance two arguments, a negative and a positive. The negative one is that leading accounts of foreseeability in duty-of-care-analysis fail to make sense of the requirement in question. And affirmatively, I shall argue that the foreseeability requirement reflects a concern for the distinctively social form of interaction between risk-creator and risk-taker, namely, that the former could form a respectful interaction with the latter. This reconstruction of the foreseeability requirement may express the view that its moral center may be a thin form of recognition between members of a liberal society.


A stratified random sample of 307 young farm operators from the five farming areas of Iowa were interviewed to; (1) ascertain factors influencing the establishment of young farm operators, (2) estimate the number of young farm operators becoming established each year, (3) determine their agricultural education needs, (4) examine differences among the farming areas, and (5) determine the background and personal characteristics of young farm operators. Individuals between the ages of 18 and 30 were included in the sample population. Some findings were: (1) The population of youna farmers in Iowa was estimated to be 13,630, (2) Their mean age was 26.2 years, 6) Three-fourths were high school graduates, (4) 88.7 percent participated in high school vocational agriculture programs, (5) Young farmers held an average ot two occupations prior to farming, and (6) Participation in educational programs varied by farming area. Implications for education were derived in areas of educational needs, content of educational programs, methods in instructional programs, education for off-farm income and recommendations for young farmer education. This report is a consolidation of a doctoral theses submitted to the Iowa State University of Science and Technology. (DM)


Codium recurvatum is described from material collected on a Tanzanian reef slope. The diminutive species is easily recognized by its unusual morphology, as its thallus consists of several dorsiventrally flattened lobes originating from a central holdfast and curving back towards the substratum. DNA barcodes (rbcL exon 1 and tufA) confirm the distinctness of the species and the phylogenetic placement of the new species is inferred from a concatenated alignment of rbcL and rps3–rpl16 sequences.


Modern software packages have become increasingly complex with millions of lines of code and references to many external libraries. Redundant operations are a common performance limiter in these code bases. Missed compiler optimization opportunities, inappropriate data structure and algorithm choices, and developers' inattention to performance are some common reasons for the existence of redundant operations. Developers mainly depend on compilers to eliminate redundant operations. However, compilers' static analysis often misses optimization opportunities due to ambiguities and limited analysis scope; automatic optimizations to algorithmic and data structural problems are out of scope. We develop LoadSpy, a whole-program profiler to pinpoint redundant memory load operations, which are often a symptom of many redundant operations. The strength of LoadSpy exists in identifying and quantifying redundant load operations in programs and associating the redundancies with program execution contexts and scopes to focus developers' attention on problematic code. LoadSpy works on fully optimized binaries, adopts various optimization techniques to reduce its overhead, and provides a rich graphic user interface, which make it a complete developer tool. Applying LoadSpy showed that a large fraction of redundant loads is common in modern software packages despite highest levels of automatic compiler optimizations. Guided by LoadSpy, we optimize several well-known benchmarks and real-world applications, yielding significant speedups.


Background: Contact lens wear has become a trend recently. It enhances one's physical appearance without the need of glasses and boost self-confidence. However,
improper usage of contact lens with insufficient hygienic of lens care may lead to serious vision-threatening complications. Purpose: This research was conducted to
assess the level of awareness of contact lens complications among contact lens users in UiTM Puncak Alam Campus. Methods: This is a cross-sectional descriptive study. 60 regular contact lens users from UiTM Puncak Alam Campus were identified and enquired about the awareness of contact lens complications through a structured questionnaire. The questionnaire also asked regarding risk factors and knowledge of contact lens complications. Results: 60 regular contact lens users which were 57 female and 3 male participants had completed the questionnaire. The average age was 22.38 years. There was lack level of awareness assessed regarding the contact lens complications. The highest awareness of complication was allergy (45%) followed by corneal ulcer (41.7%), conjunctivitis (40%), corneal vascularization (28.3%), corneal opacities (26.7%) and corneal distortion (25%).
Majority of the participants aware of the risk factors of contact lens complications but their knowledge was significantly low. Conclusion: Significant number of regular
contact lens users in UiTM Puncak Alam Campus did not aware and know about contact lens complications. However, there was high awareness of risk factors of
contact lens complications. In the future, more exposure and continuous contact lens education needed to be enhanced among the contact lens users in UiTM Puncak
Alam Campus.


Aim: A prospective study to establish the reliability of a self-completion version of the Office for National Statistics (ONS) questionnaire for assessing drug dependence of substance misuse clients. Method: A total of 47 treatment seeking opioid-dependent clients completed the self-complete version of the ONS questionnaire (ONS-sc) followed by the interviewer-administered ONS questionnaire (ONS-ia) at a single clinic appointment. Scores for four Class A drugs (heroin, methadone, speed and crack/cocaine) from both formats were compared. Results: The observed agreement was 87% or more and Cohen's kappa was 0.7 (p < 0.001) or more for all four Class A drugs. Sensitivity for each Class A drugs was 56% or higher and specificity was 87% or higher. Sensitivity for severe heroin dependency was 98% (CI 89–100%). There was a 100% correlation between the ONS-sc and positive urine analysis for heroin use. However, methadone and crack/cocaine drug use appeared under reported. Conclusion: ONS-sc is a feasible, practical and time-saving alternative to a detailed interview on drug dependence. Further research with a larger sample size and non-opiate-dependent clients are needed, as this could prove a useful tool for monitoring clients in everyday practice, or for survey purposes where interviews are impractical.


The migration flows to and from the four largest Dutch municipalities (Amsterdam Rotterdam The Hague and Utrecht) show a number of similarities. During the past few decades internal migration has been characterized by a move away from the large cities while the much smaller international migration flow had an opposite direction. This has resulted in a net decrease of the total population in the largest cities. (SUMMARY IN ENG) (EXCERPT)


Within an authentic learning framework, second year pre-service teachers were introduced to LAMS (the Learning Activity Management System) as part of one of the information and communication technology (ICT) units they are required to complete as part of their course. Using case study methodology, the students returned some interesting results: LAMS helped the students plan all aspects of their lesson and allowed them to preview their lesson from the learner's perspective. Additionally, the software provided a visual overview of the lesson which assisted them to identify the learning styles that were addressed with the activities employed. Students also saw the benefit in the production of standardised templates of activities that could easily be modified for future re-use.


A surgeon faced with a patient presenting with an open tibial/fibular fracture in combination with severe damage of the surrounding soft tissues, has to make the difficult decision whether to attempt salvage or to perform an immediate amputation of the leg.

Until late in the nineteenth century the mortality from open fractures was high - mainly due to sepsis after infection. Theodor Billroth, the famous surgeon, reported in 1881 that 46 of 93 patients with an open fracture of the lower leg whom he treated in Zurich, died. Gunshot wounds were particularly notorious and though generally treated with immediate amputation, most of these victims did not survive. It is recorded that in the American Civil War (1861-1865), the overall mortality rate after nearly 30.000 amputations was in the order of 30%, for above-knee amputations it reached 54%. In the Franco-Prussian War (1870-1871), the death rate from open fractures was 41%, while for open fractures of the knee this rate was even 77%. With the growing understanding of bacterial contamination and cross infection, the introduction of antisepsis and aseptic surgery, the advances in operative fracture stabilisation and, more recently, the various options for bone and soft-tissue reconstruction, the problems from open fractures have been greatly reduced. The emphasis came from life saving via limb salvage on restoration of limb function and preservation of quality of life.

At the present time, the majority of open tibial fractures are caused by traffic accidents. In the Netherlands, approximately 5.000 patients annually are admitted to hospital with a lower leg fracture - both as an isolated injury and as part of "polytrauma". It is estimated that open fractures account for 10% of this total. The improvements in treatment of mangled lower legs have opened the door to therapeutical options, previously unavailable to the surgeon. Nowadays, attempt at salvage is frequently chosen, because due to modern reconstructive techniques this is successful in the majority of cases. However, in some patients - for example due to persisting ischemia of the lower leg or to concomitant life-threatening injuries - it is obvious that immediate (primary) amputation is the option of choice. Unfortunately, in some of these cases nevertheless salvage is attempted - mainly due to a combination of wrong clinical judgement and optimistically thinking of the surgeon. Although these attempts seem successful eventually, after a long period of untreatable infections and other complications (secondary) amputation has to be performed as yet. These patients generally undergo more and more complex operations, and suffer more from complications than patients with a primary amputation. It is clear that it should be avoided that a patient will end up in such a situation.

In this thesis, we tried to clarify several aspects of this difficult clinical problem by answering the following questions:
1. Is it possible to predict outcome in individual patients with a mangled lower leg?
2. What are the short-term consequences of the chosen treatment?
3. How is the long-term outcome of successful salvage and amputation?
4.What are the influences of smoking on the healing of open tibial fractures?
5. How are the results of treatment of infected segmental defect pseudarthrosis of the tibia?


ABSTRACT Contemporary phenotypic trends associated with global change are widely documented, but whether such trends always denote trait optimization under changed conditions remains obscure. Natural selection has shaped the wings of long-distance migratory birds to minimize the costs of transport, and new optimal wing shapes could be promoted by migration patterns altered due to global change. Alternatively, wing shape could vary as a correlated response to selection on other traits favored in a changing environment, eventually moving away from the optimal shape for migration and increasing transport costs. Data from 20 yr of monitoring 2 Common Nightingale (Luscinia megarhynchos) populations breeding in central Spain, where environmental conditions for breeding have deteriorated during recent decades due to increased summer drought, show that birds have reduced wing length relative to body size over the period 1995–2014. However, long-winged nightingales survived their first round-trip migration better, and the shorter the average wing length of individuals, the stronger the survival-associated natural selection favoring longer wings. Maladaptive short wings may have arisen because the mortality costs of migration are outweighed by reproductive benefits accrued by short-winged nightingales in these populations. Assuming that the phenotypic integration of morphological and reproductive adaptations of migratory birds has a genetic basis, we hypothesize that the maladaptive trend towards shorter wings may be a correlated response to selection for moderate breeding investment in drying habitat. Our results provide evidence that contemporary phenotypic change may deviate average trait values from their optima, thereby increasing our understanding of the ecological constraints underpinning adaptation to rapid global change.


An increasing number of projects in neuroscience requires the statistical analysis of high dimensional data sets, as, for instance, in predicting behavior from neural firing or in operating artificial devices from brain recordings in brain-machine interfaces. Linear analysis techniques remain prevalent in such cases, but classical linear regression approaches are often numerically too fragile in high dimensions. In this paper, we address the question of whether EMG data collected from arm movements of monkeys can be faithfully reconstructed with linear approaches from neural activity in primary motor cortex (M1). To achieve robust data analysis, we develop a full Bayesian approach to linear regression that automatically detects and excludes irrelevant features in the data, regularizing against overfitting. In comparison with ordinary least squares, stepwise regression, partial least squares, LASSO regression and a brute force combinatorial search for the most predictive input features in the data, we demonstrate that the new Bayesian method offers a superior mixture of characteristics in terms of regularization against overfitting, computational efficiency and ease of use, demonstrating its potential as a drop-in replacement for other linear regression techniques. As neuroscientific results, our analyses demonstrate that EMG data can be well predicted from M1 neurons, further opening the path for possible real-time interfaces between brains and machines.


This paper presents the COMBINA-PT project, a study of corpus-extracted Portuguese Multiword (MW) expressions. The objective of this on-going project is to compile a large lexical database of multiword (MW) units of the Portuguese language, automatically extracted from a balanced 50 million word corpus, and manually validated with the help of lexical association measures. MW expressions considered in the database include named entities and lexical associations with different degrees of cohesion, ranging from frozen groups, which undergo little or no variation, to lexical collocations composed of words that tend to occur together and that constitute syntactic dependencies, although with a low degree of fixedness. This new resource has a two-fold objective: (i) to be an important research tool which supports the development of MW expressions typologies and their lexicographic treatment; (ii) to be of major help in developing and evaluating language processing tools able of dealing with MW expressions.


defined and illustrative examples given, as well as the meaning of "retardations". Later chapters are devoted to "neutral" and "advanced type" equations like those of Chapter 3, to linear systems of such equations, to their asymptotic behaviour and stability of solutions. Non-linear differential-difference equations are also treated for stability and asymptotic behaviour. The book ends with two chapters on the zeros of "exponential polynomials", again considering asymptotic location and stability properties respectively. A final application of Laplace transform techniques is given in the renewal equation


INCREASING ATTENDANCE OF EWU STUDENTS AT CHENEY MAYFEST: DOES SOCIAL MEDIA PLAY A ROLE? by Kyra M. Phelps Spring 2017 The non-profit organization, Cheney Mayfest, puts on an event each year to promote the community and its local businesses. Most of the Cheney community is Eastern Washington University (EWU) students. Cheney Mayfest's goal is to have an increase in EWU student attendance at Mayfest each year. In order to examine the best way to reach them, this study examines what motivates EWU students to attend and the barriers as to why they do not attend. Findings from this study indicate that most students do not know what Cheney Mayfest is and have not seen any marketing for the event. Understanding the different motivations and barriers for why they do not attend could help find a way to enhance the attendance of EWU students at Mayfest. This thesis seeks to identify why there is a low attendance of EWU students and whether a social media marketing plan can play a role in enhancing student attendance.


Designed paper is focused on the analysis of public goods in the form of greenhouse gas emissions in livestock production in Czechia. The main aim of the paper is to quantify the amount and valuation of greenhouse gas emissions produced in beef cattle breed (dairy and meat), pig breed, and poultry breed (meat and eggs). The partial aim of this paper is to compare greenhouse gas emissions production across sectors of livestock production and to evaluate a development of volume, value and share of emissions as a form of public goods. The methodology is based on the conceptual model MITERRA-Europe (The model was developed to assess the effects and interactions of policies and measures in agriculture on N losses and P balances at a regional level in EU-27), which is partly based on the CAPRI (Common Agricultural Policy Regionalised Impact) and the GAINS (Greenhouse Gas and Air Pollution Interactions and Synergies) models using the tools for quantification of the emission factors indicators defined by the IPCC (Intergovernmental Panel for Climate Change) organizations. Part of the solution is to determine the value of public goods quantified through a European platform for carbon emissions trading with its futures contract based on the EU Allowances. The result of this paper is quantified emission value of public goods in livestock production in Czechia and their appreciation in the period 2000-2014. In the final consequence is quantified the proportion of the value of public goods in the total production of the analyzed livestock sector.


Electron microscopy of thin-sectioned Spirillum volutans (ATCC 19554) showed that at the insertion site of the flagellum there was a cylindrical structure with a diameter of ca. 36 nm which extended ca. 19 nnm into the cytoplasm. This structure, termed a cytoplasmic flagellar base, enclosed a central rod which was continuous with the hook. There was a continuation of the flagellar base into the peptidoglycan layer, enclosing ringlike structures and the central rod. The flagellar hook and proximal part of the flagellar filament contained a central channel which was large enough to accomnmodate the flagellin subunit. The flagella of fixed cells may project perpendicularly from the outer membrane in a position corresponding to a trailing, swimming orientation or may bend almost parallel to the membrane in a leading orientation. Maximum bending occurred in the hook region, which may be the structure responsible for executing changes in swimming direction.


ME-344 is a second-generation cytotoxic isoflavone with anticancer activity promulgated through interference with mitochondrial functions. Using a click chemistry version of the drug together with affinity-enriched mass spectrometry, voltage-dependent anion channels (VDACs) 1 and 2 were identified as drug targets. To determine the importance of VDAC1 or 2 to cytotoxicity, we used lung cancer cells that were either sensitive (H460) or intrinsically resistant (H596) to the drug. In H460 cells, depletion of VDAC1 and VDAC2 by small interfering RNA impacted ME-344 effects by diminishing generation of reactive oxygen species (ROS), preventing mitochondrial membrane potential dissipation, and moderating ME-344–induced cytotoxicity and mitochondrial-mediated apoptosis. Mechanistically, VDAC1 and VDAC2 knockdown prevented ME-344–induced apoptosis by inhibiting Bax mitochondrial translocation and cytochrome c release as well as apoptosis in these H460 cells. We conclude that VDAC1 and 2, as mediators of the response to oxidative stress, have roles in modulating ROS generation, Bax translocation, and cytochrome c release during mitochondrial-mediated apoptosis caused by ME-344. SIGNIFICANCE STATEMENT Dissecting preclinical drug mechanisms are of significance in development of a drug toward eventual Food and Drug Administration approval.


According to stipulations in the Water Framework Directive economic analyses of water use in different sectors are required. The aim is to assess the possibilities to reach the targets for water quality by 2015 at reasonable costs, and to develop cost-effective programs for restoration and management that will be part of the management plans in 2009. By 2010 pricing of water services should give full coverage of costs. A pilot study in the Motala River Basin has shown, that for the implementation of the Directive there is a need of tools by which large amounts of data can be coordinated. Information about socio-economic conditions are now collected mainly on a municipal or county basis, while data on hydrology and substance flows are organised on a catchment level. We also need a set of general estimations of various types of costs that are not too site specific. Further, reliable forecasts of future development are demanded, both for society (demography, economic growth, environmental policy, CAP, ...) and for global climate changes. Finally, the issue of public participation should be considered.


Applying an appropriate roughness model is one of the most effective ways to improve the accuracy of the numerical simulation for centrifugal compressors, and it is also the key to the study of surface deterioration such as compressor fouling and corrosion. The basis for using the roughness model is to determine the conversion relation between physical roughness and equivalent roughness. In this paper, numerical and experimental studies on the roughness conversion relation for the centrifugal compressors were performed by means of a unique self-developed "pseudo front stage (PFS)" device. An equivalent roughness conversion coefficient of 8.5 was determined on the basis of fitting performance of the U-bend and return channel model. The validity of the conversion coefficient in improving the performance prediction accuracy of the centrifugal compressors was verified by three centrifugal compressor models. The concept of weighted average roughness was proposed to quantify the roughness sensitivity and roughness level of the centrifugal compressor. Quantitative research on the roughness effect of centrifugal compressors indicated that the peak efficiency degradation due to the roughness effect in the compressors was linearly associated with the logarithm of the relative roughness when the impeller of the centrifugal compressor was in the hydraulically rough regime. Doubling or halving the roughness value of all components of a centrifugal compressor in the hydraulically rough flow regime will result in a change in the peak efficiency of the compressor by about 1.72%.


Coronary artery calcification is increasingly prevalent in our patient population. It significantly limits the procedural success of percutaneous coronary intervention and is associated with a higher risk of adverse cardiovascular events both in the short-term and long-term. There are several modalities for modifying calcified plaque, such as balloon angioplasty (including specialty balloons), coronary atheroablative therapy (rotational, orbital, and laser atherectomy), and intravascular lithotripsy. We discuss each modality's relative advantages and disadvantages and the data supporting their use. This review also highlights the importance of intravascular imaging to characterize coronary calcification and presents an algorithm to tailor the calcium modification therapy based on specific coronary lesion characteristics.


The goal of the gelatin manufacturer is to partial hydrolyze the covalent cross-linkages that organize the collagen molecules into a quarter staggered arrangement found in connective tissue, to minimize the hydrolysis of the peptide bonds and to obtain the appropriate molecular weigh distribution (MWD) for a specific application. The mechanical properties of the resulting gelatin are known to be influenced by the tissues and species from which it is produced as well as the pretreatment and extraction procedures. Cold water fish gelatins from saithe (Pollachius virens) skins were in this work extracted at different temperatures, by different acetic acid concentrations and in different extraction times. Size-exclusion chromatography coupled to multi-angle laser light scattering (SEC-MALLS), small-strain oscillatory measurements and optical rotation measurements were used to characterize the resulting gelatins according to their molecular weight, mechanical and structural properties. Saithe gelatins with high weight average molecular weight (Mw) and excellent gel forming properties were produced during the extractions made at low temperature while highly hydrolyzed gelatins with reduced mechanical properties were extracted under harsher conditions. Gelatins from cold water fish species, acid porcine skin gelatins (type A) and lime bovine bone gelatins (type B) were compared on the basis of low deformation mechanical properties, Bloom value, Mw, MWD and polydispersity index (PI). The Bloom value and dynamic storage modulus (G') for all types of gelatin increased with increasing Mw. Cold water fish gelatins and mammalian gelatins exhibit comparable Bloom values at different Mw and different PI. The Bloom values for gelatins extracted at room temperature (22 C) from haddock (Melanogrammus aeglefinus), saithe and cod (Gadus morhua) were determined to be 200, 150 and 100 g from a linear correlation between G' and Bloom. Acid porcine skin gelatins and lime bovine bone gelatins with similar Mw exhibited different G' and Bloom values, most likely due to varying MWD and PI. Removing low molecular weight (LMW) molecules from a gelatin sample improved the mechanical properties whereas adding LMW gelatin molecules had the opposite effect on the mechanical properties of the resulting gel. Based on principal component analysis (PCA) and partial least squares regression (PLSR), two linear relationships between the mechanical properties and the MWD were suggested. Both the G' value for cold water fish gelatin and the Bloom value for mammalian gelatin were positively correlated with their corresponding fractions of β - chains and high molecular weight (HMW) molecules and negatively correlated with the fractions of LMW molecules. In contrast to the Bloom value for mammalian gelatin, the G' value for cold water fish gelatin was negatively correlated with the fractions of α - chains.


Fair trial is recognized as a fundamental human right in the modern criminal justice system. Consequently, the war crime tribunals of former Yugoslavia (ICTY) and Rwanda (ICTR) fully adopted the due process rights and incorporated it in their respective statutes. However, the international crimes tribunal Bangladesh (ICTB) follows its own special procedure which is lacking the fair trial guarantees as promised. With reference to the fair trial guarantees, governing statutes and its working, there are vast disparities found between the ICTB and the other internationally recognized tribunals (ICTY and ICTR). The ICTY and the ICTR appeared to be more transparent than the ICTB. The ICTB has repeatedly deviated from the international norms and principals of a just trial. Moreover, non-compliance with the ICCPR, violations of the domestic laws and other serious irregularities make the ICTB illegal and unjust. The legal analysis of the ICTB unfolds the entire discourse from a comparative perspective to identify the flaws in the International Crimes Tribunal Bangladesh legislation.


The property of two nitrate transporters suggests a new strategy to enhance nitrate supply into developing tissues with low transpiration rate by redistributing xylem-borne nitrate. This study of the Arabidopsis (Arabidopsis thaliana) nitrate transporters NRT1.11 and NRT1.12 reveals how the interplay between xylem and phloem transport of nitrate ensures optimal nitrate distribution in leaves for plant growth. Functional analysis in Xenopus laevis oocytes showed that both NRT1.11 and NRT1.12 are low-affinity nitrate transporters. Quantitative reverse transcription-polymerase chain reaction and immunoblot analysis showed higher expression of these two genes in larger expanded leaves. Green fluorescent protein and β-glucuronidase reporter analyses indicated that NRT1.11 and NRT1.12 are plasma membrane transporters expressed in the companion cells of the major vein. In nrt1.11 nrt1.12 double mutants, more root-fed 15NO3− was translocated to mature and larger expanded leaves but less to the youngest tissues, suggesting that NRT1.11 and NRT1.12 are required for transferring root-derived nitrate into phloem in the major veins of mature and larger expanded leaves for redistributing to the youngest tissues. Distinct from the wild type, nrt1.11 nrt1.12 double mutants show no increase of plant growth at high nitrate supply. These data suggested that NRT1.11 and NRT1.12 are involved in xylem-to-phloem transfer for redistributing nitrate into developing leaves, and such nitrate redistribution is a critical step for optimal plant growth enhanced by increasing external nitrate.


Objective: To provide recommendations for preferred models of follow-up care for stage I-IV colorectal (CRC) cancer survivors in Ontario; to identify signs and symptoms of potential recurrence and when to investigate; and to evaluate patient information and support needs during the post-treatment survivorship period. Methods: Consistent with the Program in Evidence-Based Medicine's standardized approach, MEDLINE, EMBASE, PubMed, Cochrane Library, and PROSPERO databases were systematically searched. The authors drafted recommendations and revised them based on the comments from internal and external reviewers. Results: Four guidelines, three systematic reviews, three randomized controlled trials, and three cohort studies provided evidence to develop recommendations. Conclusions: Colorectal cancer follow-up care is complex and requires multidisciplinary, coordinated care delivered by the cancer specialist, primary care provider, and allied health professionals. While there is limited evidence to support a shared care model for follow-up, this approach is deemed to be best suited to meet patient needs; however, the roles and responsibilities of care providers need to be clearly defined, and patients need to know when and how to contact them. Although there is insufficient evidence to recommend any individual or combination of signs or symptoms as strong predictor(s) of recurrence, patients should be educated about these and know which care provider to contact if they develop any new or concerning symptoms. Psychosocial support and empathetic, effective, and coordinated communication are most valued by patients for their post-treatment follow-up care. Continuing professional education should emphasize the importance of communication skills and coordination of communication between the patient, family, and healthcare providers.


Abstract This paper reports the responses of nursing home residents who live in a psychogeriatric ward to the abstract interactive art installation 'Morgendauw', which was specifically designed for this study. All stakeholders were involved in designing and implementing Morgendauw. The artwork seems able to evoke responses in both the residents and their caregivers, but the amount and duration of the responses observed during the study were limited. 15 interactions over the course of 14 h were noted and almost all of them were initiated by the nursing home staff, physiotherapy students or visitors (n = 12). Interactions lasted for about 3 min on average. Although the nursing home residents initially did not seem to notice the artwork, the threshold of acknowledging and approaching the artwork was quickly overcome when staff nudged or directed the residents' attention towards the artwork. Beyond this point, nursing home residents generally needed little explanation of the interface to interact with the artwork. The location in which Morgendauw was placed during the study or the characteristics of the installation seemed to create a threshold. Further research should focus on the importance and the effects of context when designing and implementing an interactive art installation in a nursing home environment.


This report focuses on changes in the Nebraska farm sector from 1974 to 1982. Items of major interest include number, size, and types of farms; resource use and output; tenure patterns; age of farm operators; forms of farm business organization; and capital investment. A Gini Index procedure is used to measure shifts in concentration of certain structural variables. Data sources are Censuses of Agriculture, with emphasis on the 1982, 1978, and 1974 Censuses. The number of Nebraska farms declined in the period ending with the 1982 Census, a continuation of a long-term trend, both in the state and nationally. The 60,243 Nebraska farms accounted for in the latest Census represented an 11 percent decline from 1974 (Table 1). Similarly, the land in farms dropped to just under 45 million acres, down three percent from 1974. However, the value of Nebraska agricultural commodities sold jumped sharply in the eight year period - from $3.7 billion to $6.6 billion - reflecting both a larger volume of sales and inflation-driven prices, especially in the livestock sector.


Aristotle's socio-political theory emphasizes the belief that human beings are naturally political. Aristotelian ideals that the political life of a free citizen is a sovereign state which provides for the well-being of the citizenry is the highest form of life. Thus, his idea of free citizenship immediately introduces the concept of limitations between citizens—the free and the not free, the masters and the slave. The consequence of his political theory is the introduction of inequality among the members of the society but the question is: was Aristotle right in justifying social inequality? The answer to it embodies the major issues of this work. How we can evaluate Aristotle's positive and negative socio-political theories is one of the concerns of this paper. Effort will be made to critically explicate the good aspects of his theory as well as drawing a synthesis from the critique of the condemnable aspects of Aristotle's political philosophy in fashioning out a formidable route for African political leaders.


We propose a novel approach for evaluating the performance of activation detection in real (experimental) datasets using a new mutual information (MI)‐based metric and compare its sensitivity to several existing performance metrics in both simulated and real datasets. The proposed approach is based on measuring the approximate MI between the fMRI time‐series of a validation dataset and a calculated activation map (thresholded label map or continuous map) from an independent training dataset. The MI metric is used to measure the amount of information preserved during the extraction of an activation map from experimentally related fMRI time‐series. The processing method that preserves maximal information between the maps and related time‐series is proposed to be superior. The results on simulation datasets for multiple analysis models are consistent with the results of ROC curves, but are shown to have lower information content than for real datasets, limiting their generalizability. In real datasets for group analyses using the general linear model (GLM; FSL4 and SPM5), we show that MI values are (1) larger for groups of 15 versus 10 subjects and (2) more sensitive measures than reproducibility (for continuous maps) or Jaccard overlap metrics (for thresholded maps). We also show that (1) for an increasing fraction of nominally active voxels, both MI and false discovery rate (FDR) increase, and (2) at a fixed FDR, GLM using FSL4 tends to extract more voxels and more information than SPM5 using the default processing techniques in each package. Hum Brain Mapp, 2011. © 2010 Wiley‐Liss, Inc.


This paper uses qualitative methodology to explore the experience of growing old in rural Appalachia. Given the growing population of older adults seeking and utilizing services, it is important to understand the challenges and specific needs related to aging. Within the context of rural Appalachia, these challenges and needs may be different than those in urban areas or areas outside of the region itself. From interviews with 14 geriatric service providers in rural southeast Ohio, the authors were able to identity three prevalent themes associated with aging in rural North Central Appalachia: scarcity of resources, valuing neighbors and family, and the prevalence of drug use. These findings suggest that preparation and ongoing training of rural geriatric social workers should include attention to topics such as substance abuse and strengthening social support networks that often exist in these regions.


Abstract We present two rate equation models describing the effects of clusters on rare earth-doped silica fibers. The first one, valid for my cluster size, describes the interaction between clustered ions (cross relaxation) as a nonradiative process. The second model, valid only for large clusters, describes it as a cooperative upconversion process. These models are applied to both Nd- and Er-doped fibers. In the limit of large clusters, the two models predict comparable behavior, which provides the heretofore missing relationship between these two formalisms. Increasing the cluster size is found to significantly reduce the steady-state population of the metastable level and to introduce an increasingly faster and stronger fast component in its relaxation. The model is used to quantify the effect of clusters on the gain of fiber amplifiers and the threshold of fiber lasers. These results can be directly applied to study the impact of clusters of any size on doped fiber devices, as well as cooperative upconversion in highly doped materials.


CD43 is the most abundant cell surface-expressed sialoglycoprotein on T lymphocytes. Despite evidence demonstrating the activation of some signaling components by CD43, the exact function of CD43 in T cell biology remains controversial. In this study, we demonstrate that the sole ligation of CD43 in cloned Th2 cells resulted in cytokine production, cellular proliferation, and upregulation of CD25 and CD69 activation markers. Similarly, cross-linking of CD43 on naive splenic T cells led to a significant proliferative response and an enhancement of the expression of CD25 and CD69 markers. These responses required no additional signals from other T cell molecules, including TCR. In Lck-deficient Th2 cells, however, CD43 ligation led to IL-4 production and an increase in the expression of CD25 and CD69 antigens but, surprisingly, no proliferation. Analysis of signaling pathway components revealed that CD43 associates with the adaptor protein SLP-76 within 30 s of activation. This induces the tyrosine phosphorylation of SLP-76 and promotes the recruitment and phosphorylation of another adaptor, Shc. The formation of this multi-component complex was strictly dependent on Lck. In contrast, comparison of tyrosine phosphorylated proteins in whole extracts of normal and Lck-deficient cells revealed a strikingly similar pattern of phosphorylation involving two major protein bands at 26 and 78 kDa. This suggests that tyrosine kinases other than Lck are activated by CD43 ligation. Taken together, the data support the notion that CD43 ligation may induce a dual pathway leading to the activation of different effector functions in Th2 lymphocytes.


The diatoms are one of the most important groups of organisms for biomonitoring studies. In Turkey, most previous applications of diatoms to water quality monitoring have focused on the pennate diatoms, with almost no attention given to the centric forms. The paper presents the centric diatoms in some river catchments in Central Anatolia (Konya closed catchment and Kizilirmak) and Western Anatolia (Marmara, Sakarya, Susurluk, Akarcay, Kucuk Menderes, and Meric-Ergene in the Marmara and Aegean regions). The survey of these catchments is based on samples collected between 2009 and 2013 from 33 different locations, including some springs from Turkmen Mountain and Domanic forest, as well as small streams and big rivers of the Anatolian Peninsula. Altogether 30 taxa were found, of which 14 are new records for the freshwater diatom flora of Turkey.


The noncognitive features of pupils' experience of school are important: they can
affect academic attainment; they have an independent influence on outcomes in later life;
and to the extent that they are related to pupils' wellbeing they have intrinsic importance.
I present four empirical papers on the emotional health, friendships, and behaviour of
pupils in English secondary schools. The first two empirical papers present the results
of a large pragmatic controlled trial of an intervention intended to promote pupils'
resilience and mental health. I estimate the intervention impact on symptoms of poor
mental health, behaviour, absence from school, academic attainment, and popularity. I
find small and short-lived impacts on depressive symptoms, absence, and popularity,
and a small but more lasting impact on academic attainment. I find no impact on anxiety
scores or behaviour. The third paper examines behaviour incidents at school. Poor
behaviour is a major challenge to the effectiveness of schooling, and the data I have
represents a substantial improvement over previous attempts to measure pupil behaviour.
I find that demographic characteristics are strong predictors of the number of incidents
per pupil, but they do not explain much of the overall variance in incidents. Incident
rates per lesson vary strongly by context within the school, suggesting that schools
could influence behaviour by modifying the environment. However, a pupil's rank in
terms of behaviour is remarkably persistent over different contexts and through time,
suggesting that the tendency to misbehave is a stable noncognitive trait. The fourth
paper looks in detail at the impact of time of day and day of the week on behaviour. I
find that the strong and persistent day-of-the-week and time-of-day patterns I observe
are not due to selective reporting or misreporting, and are not due to endogenous
timetabling. Since schedule adjustment could be almost costless, it could be highly cost
effective even if the impact on behaviour were much smaller than estimated in my
observational data.


Sea surface salinity is a key oceanographic parameter that can be measured by means of L-band microwave radiometry. The measured brightness temperatures over the ocean are influenced by the sea state, which can entirely mask the salinity signature. Sea-state corrections parameterized in terms of wind speed and/or significant wave height have proven not to be fully satisfactory. In 2003, it was proposed to use reflectometry using navigation opportunity signals [Global Navigation Satellite System Reflectometer (GNSS-R)] for sea-state determination and correction of the measured L-band brightness temperature changes associated to the sea state. The novelty of the approach relies in the measurement of the whole Delay-Doppler Map that captures the scattering of the GNSS signals in the whole glistening zone. In this framework, the "Advanced L-BAnd emissiviTy and Reflectivity Observations of the Sea Surface" (ALBATROSS) field experiments were undertaken in 2008 and 2009, collecting an extensive data set of collocated radiometric and reflectometric measurements over the Atlantic Ocean, as well as oceanographic and meteorological data. In this paper, the experimental results and conclusions of the ALBATROSS 2009 field experiment are compiled and presented, showing the great potential of this technique to perform the necessary corrections in future salinity missions. Empirical relationships are derived among measured brightness temperature variations due to the sea-state effect and direct GNSS-R observables, and the sea surface correlation time at L1 band, a key parameter for GNSS-R data processing since it determines the maximum coherent integration time, was experimentally determined.


Ultrasound‐driven microbubbles produce mechanical forces that can disrupt cell membranes (sonoporation). However, it is difficult to control microbubble location with respect to cells. This lack of control leads to low sonoporation efficiencies and variable outcomes. In this study, aqueous two‐phase system (ATPS) droplets are used to localize microbubbles in select micro‐regions at the surface of living cells. This is achieved by stably partitioning microbubbles in dextran (DEX) droplets, deposited on living adherent cells in medium containing polyethylene glycol (PEG). The interfacial energy at the PEG‐DEX interface overcomes microbubble buoyancy and prevents microbubbles from floating away from the cells. Spreading of the small DEX droplets retains microbubbles at the cell surface in defined lateral positions without the need for antibody or cell‐binding ligand conjugation. The patterned microbubbles are activated on a cell monolayer exposed to a broadly applied ultrasound field (center frequency 1.25 MHz, active element diameter 0.6 cm, pulse duration 8 μs or 30 s). This system enables efficient testing of different ultrasound conditions for their effects on sonoporation‐mediated membrane disruption and cell viability. Regions of cells without patterned microbubbles show no injury or membrane disruption. In microbubble patterned regions, 8 μs ultrasound pulses (0.2‐0.6 MPa) produce cell death that is primarily apoptotic. Ultrasound‐induced apoptosis increases with higher extracellular calcium concentrations, with cells displaying all of the hallmarks of apoptosis including annexinV labeling, loss of mitochondrial membrane potential, caspase activation and changes in nuclear morphology.


Telepresence robots offer presence, embodiment, and mobility to remote users, making them promising options for homebound K-12 students. It is difficult, however, for robot operators to know how well they are being heard in remote and noisy classroom environments. One solution is to estimate the operator's speech intelligibility to their listeners in order to provide feedback about it to the operator. This work contributes the first evaluation of a speech intelligibility feedback system for homebound K-12 students attending class remotely. In our four long-term, in-the-wild deployments we found that students speak at different volumes instead of adjusting the robot's volume, and that detailed audio calibration and network latency feedback are needed. We also contribute the first findings about the types and frequencies of multimodal comprehension cues given to homebound students by listeners in the classroom. By annotating and categorizing over 700 cues, we found that the most common cue modalities were conversation turn timing and verbal content. Conversation turn timing cues occurred more frequently overall, whereas verbal content cues contained more information and might be the most frequent modality for negative cues. Our work provides recommendations for telepresence systems that could intervene to ensure that remote users are being heard.


Indoor combustion of solid fuel such as coal may generate respirable particles containing polycyclic aromatic hydrocarbons (PAH) that may adhere to settled dust. Dust might therefore present a major source of PAH exposure in humans. This study evaluated the in vitro and in vivo genotoxicity of PAH mixtures extracted from house dust samples. Four dust samples (E1–4) were collected from houses in Shanxi, China, where coal is heavily used for heating and cooking. For comparison, a coal sample was also collected from one of the houses and included in the analyses. The samples were extracted with methylene chloride:acetone (95:5 v/v), dried, and redissolved in appropriate solvents for assessment in genotoxicity assays. Samples were evaluated for their ability to induce point mutations in bacteria and DNA adducts in vivo. DNA adduct levels were analyzed by nuclease P1-enhanced 32P-postlabeling. PAH were quantified using gas chromatography/mass spectrometry. Based on chemical analysis, sample E1 had the highest concentration by sampling area of benzo[a]pyrene (BaP) (181 μg/m2) and total PAH (10100 μg/m2). However, based on the microbial genotoxicity assay, sample E3, with the highest carcinogenic PAH/total PAH ratio (26%), produced the greatest number of revertants. In mice, administration of the extract of coal induced more adducts (9.81 adducts per 109 nucleotides) than dust extracts. The results of this study confirm the presence of genotoxic chemicals in residential dust. Inhalation of respirable particles containing similar mixtures of PAH represents a cancer risk for humans.


ABSTRACT Substance use disorder (SUD) stigma persists in society despite a movement toward people-first language in the mental health field. Stigma creates barriers to treatment and marginalizes already at-risk populations. Opioid use disorder (OUD) is of particular relevance to this discussion because recent increases in OUD can be traced to iatrogenic origins, and as such, power differentials between prescriber and patient may complicate stigma and/or create additional barriers for those who develop opioid dependence. We examine the shift to use destigmatizing language surrounding OUD, explores the unique power dynamics associated with the rise of OUD prevalence, and presents a manifest content analysis of phrases related to OUD to observe the emergence of opioid use as a public health issue. Whereas SUD has long had visibility in public health discourse, OUD has emerged as a major theme in this discourse as its prevalence and mortality rate reached epidemic levels. We advocate for public health practice and research discourse to more uniformly adopt destigmatizing language alongside clinical SUD practitioners toward the goal of reducing stigma and barriers to treatment seeking for OUD.


This paper examines whether first-time exporters achieve productivity improvements through learning-by-exporting effects. The results suggest that the start of exporting to North America/Europe has a strong positive effect on sales and employment growth, R&D activity, and productivity growth. On the other hand, the start of exporting to Asia does not have any strong productivity-enhancing effects, although it does tend to boost the growth rates of sales and employment and to be associated with an increase in R&D expenditure. However, even considering these variables, the positive impact from the start of exporting to North America/Europe is much larger. Further analysis shows that export starters to North America/Europe are larger, more productive, more R&D intensive, and more capital intensive than export starters to Asia even before they start exporting, suggesting that the former are potentially better performers than the latter. Moreover, export starters to North America/Europe become more innovative than export starters to Asia after the start of exporting. The results obtained here imply that potentially innovative non-exporters should be supported through an export-promotion policy.


This dissertation is an interdisciplinary examination of the history and theory of adolescence. I draw on a variety of materials, from both Britain and the United States, including nineteenth- and early twentieth-century newspapers and periodicals, literary texts, educational treatises, advertisements, pamphlets, and medical discourse which reveal the term and the category of adolescence as it has been put into service by fields like medicine, psychology, education, and public policy. Methodologically, I use this range of materials to look for patterns, tracing not only the word and concept of adolescence, but the construction and circulation of social meanings associated with adolescence. Queer theory understands categories of gender and sexuality as unstable, shifting, malleable, contextual—and this project understands that theorized complexity as belonging to the past as well as the present, in the movement of adolescence as a term and a concept. Among constructivist studies of adolescence, scholars often cite G. Stanley Hall's exhaustive two-volume work Adolescence (1904) as a point of origin, the beginning of what we recognize today as adolescence. This project maps out a trajectory of fragmented, multi-purposed conceptualizations of adolescence, one that precedes Hall and continues after him, a mapping that brings to light the surprising movement and instability of this trajectory over time. If we understand language and meaning as having a certain flexibility, as moving with each iteration and reiteration, then my framing historical question is not whether adolescence existed in earlier centuries, but how the concept existed, and more specifically, how it existed in shifting and interconnected discourses, such as nineteenth-century American newspapers and British sex education pamphlets from the 1930s and 40s. This methodology allows me to speak to the perplexing question of how language constitutes social realities and modes of knowledge. My research encompasses a wide range of materials and historical moments to explore the ideological dimensions of adolescence, ones that circulate and reappear in very specific, located contexts. This project brings to light a nonlinear history that reframes present assumptions about adolescence and opens up the category as a powerful site for work in queer theory, cultural studies, and literary studies.


While increasing attention is being paid to the feasibility of incorporating quality of life investigations into cancer clinical trials, and QOL data have played a prominent role in some recent trials, such studies remain the exception rather than the rule. This paper addresses a number of measurement, research design, and implementation issues surrounding clinical-trial-based quality of life studies. These include: the appropriate source of quality of life data; global versus multidimensional approaches to conceptualizing quality of life; the feasibility and desirability of a quality of life measurement "gold standard;" generic versus disease-specific measures; the role of psychometrics in selecting quality of life measures; the frequency and timing of data collection; and patient accrual and differential loss to follow-up. Where appropriate, areas of real or potential consensus on the methods of conducting quality of life investigations are highlighted.


Cell migration and invasion is a central process in embryonic development, wound healing and immune responses. Errors during this process have serious consequences, including mental retardation, vascular disease, tumor formation and metastasis. An understanding of the mechanism by which cells migrate and invade may lead to the development of novel therapeutic strategies for controlling, for example, cancer metastasis.

Fascin is an actin-bundling protein involved in filopodia assembly and cancer invasion and metastasis of multiple epithelial cancer types. In this thesis, I have investigated the role of fascin in invadopodia formation, which are invasive finger-like protrusions that cancer cells use to invade into and degrade extracellular matrix. I demonstrated that fascin and its actin bundling activity are required for the assembly of the actin cytoskeleton at invadopodia as well as for the degradation of matrix. Fascin is a very stable component of invadopodia and its presence enhance the stability of actin structures at invadopodia. Furthermore, fascin is required for invasive migration into collagen I-Matrigel gels particularly in cell types that use an elongated mesenchymal type of motility in 3D. These data provide a potential molecular mechanism for how fascin increases the invasiveness of cancer cells.

During embryogenesis, melanoblasts proliferate and migrate ventrally through the developing dermis and epidermis as single cells. In the second part of this thesis, I examined the importance of small Rho GTPase Rac1 on melanoblast migration during development. I demonstrate that targeted deletion of Rac1 in the melanoblasts of developing mice causes defects in migration, cell cycle progression and cytokinesis. Rac1 null cells migrate markedly less efficiently, but surprisingly global steering, crossing the dermal/epidermal junction andhoming to hair follicles are normal. Melanoblasts navigate in the epidermis using two classes of protrusion: short stubs and long pseudopods. Short stubs are driven by actin assembly, but unexpectedly are independent of Rac1, Arp2/3 complex, myosin or microtubules. Rac1 positively regulates
the frequency of initiation of long pseudopods, which promote migration speed and directional flexibility. Scar/WAVE and Arp2/3 complex drive actin assembly for long pseudopod extension, which is also microtubule dependent. Myosin contractility balances the extension of long pseudopods by effecting retraction and allowing force generation for movement through the complex 3D epidermal environment. In addition, I demonstrated that expression of activated N-Ras did not affect migration and proliferation of melanoblast during embryogensis. However, Rac1 is required for constitutively active N- Ras induced dermal melanocytes survival in mice.


While the role of negatively charged axial ligands (e.g. Cl−, Br− and I−) in tuning the reactivity and stability of molecular Ru water oxidation catalysts was well-documented, less was explored when axial ligands are neutral molecules. In this work, we reported the synthesis and full characterization of [Ru(NCNHCO)(bpy)L]+ complexes (L = DMSO, 1; L = 4-picoline, 2), where L is a neutral axial ligand. The effects of these axial ligands on the stability and reactivity of the catalysts were thoroughly investigated. Both complexes were competent to oxidize water with turnover numbers up to 463 and 107, respectively. Complex 1 initiated the water oxidation involving a PCET process. It was found that complex 2 afforded its corresponding Ru–aqua complex owing to the carboxylate dissociation, while complex 1 exhibited considerable stability in acidic aqueous solutions. On the other hand, in the presence of an oxidant, for complex 1 DMSO/H2O exchange occurred, facilitating water oxidation. In contrast, the Ru–O bond cleavage of complex 2 was inhibited, leading to an inferior catalytic performance.


We describe a wavelet-based series expansion for wide-sense stationary processes. The expansion coefficients are uncorrelated random variables, a property similar to that of a Karhunen-Loeve (KL) expansion. Unlike the KL expansion, however, the wavelet-based expansion does not require the solution of the eigen equation and does not require that the process be time-limited. This expansion also has advantages over Fourier series, which is often used as an approximation to the KL expansion, in that it completely eliminates correlation and that the computation for its coefficients are more stable over large time intervals. The basis functions of this expansion can be obtained easily from wavelets of the Lemaire-Meyer (1990) type and the power spectral density of the process. Finally, the expansion can be extended to some nonstationary processes, such as those with wide-sense stationary increments. >


The sintered neodymium-iron-boron (Nd-Fe-B) material is used in most of PM machines. The kind of PM materials has small tensile strength and cannot withstand large centrifugal force due to high rotational velocity. A nonmagnetic steel enclosure is needed to cover the PM material. The tensile stress of the PM can reduced by pre-pressure applied to the outer surface of the PM through shrink-fitting into the enclosure. Based on the elasticity theory and the elastic-plastic contact theory, in soft ANSYS it is feasibility to establish a finite element mechanical model of interference fit between the enclosure and motor rotor PM at high rotating speed. This paper simulates the effects of the temperature and rotating speed (centrifugal force) on the displacement and the contact pressure on the interference-fitting surfaces .By finite element non-linear contact model analysis, if setting up right fit clearance, this paper could ensure the security of the PM rotor under rotational velocity up to 300,000 r/min high and temperature up to 150°C.


Objectives Primary vaginal carcinomas are rare, accounting for 1–2% of gynaecological malignancies. This project aimed to describe a series of primary vaginal cancer cases at a single institution, identifying patient, tumour and treatment factors impacting outcomes. Methods A retrospective chart analysis was performed for all patients diagnosed with primary vaginal cancer from 2008 to 2018 at a single institution in Australia. For each case, data extracted included histopathology, staging, treatment received, socio-demographic information and patient outcomes. Overall, eight patients were eligible to be included in analysis. Results Average age at diagnosis was 59 years (34–75 years). 87.5% were in the most socially disadvantaged quintile of the Index of Socio-Economic Disadvantage. Overall, 75% of patients had squamous cell carcinoma and 25% had melanoma. Stage at presentation: FIGO stage one (n=3), stage two (n=2) and stage three (n=3). The average Body Mass Index was 26.2 kg/m2 and Charlson Comorbidity Score of 4.75. Treatment received included: surgery alone (n=2), primary chemo-radiotherapy (n=3), surgery and adjuvant radiation (n=1), surgery and adjuvant immunotherapy (n=1), and chemotherapy alone (n=1). With median 39 months follow-up (11–113 months), 2 of 6 patients with SCC have relapsed and 2 of 2 patients with melanoma have relapsed. Conclusions This study indicates that outcomes for vaginal cancers are poor, and that early presentation is essential to improve outcomes. Treatment is highly individualised based on extent of disease at presentation. Due to limited literature in this area, it is difficult to compare patient demographics, tumour factors and standard treatment.


The shell of yellow-spotted Amazon turtles is well adapted to their natural surroundings: its flattened shape lets them glide through the water more easily. Their webbed feet also help them move around faster, which is useful when they are hunting for food or fleeing predators.


Experiments were performed to test whether conjugated bile acid administration would decrease bacterial overgrowth, bacterial translocation, and endotoxemia in ascitic cirrhotic rats. Cholylsarcosine, a deconjugation‐dehydroxylation resistant and cholylglycine, a deconjugation‐dehydroxylation susceptible bile acid were used. Rats with CCl4‐induced cirrhosis and ascites were fed cholylsarcosine, cholylglycine (both at 70 mg/kg/d), or placebo for 2 weeks. Healthy rats, as controls, were treated similarly. In cirrhotic rats receiving placebo, bile secretion from an acute biliary fistula was lower than in healthy rats (27.2 ± 6.5 vs. 53.0 ± 3.1 μL/kg/min; mean ± SE, P< .05). The administration of conjugated bile acids to cirrhotic rats normalized bile secretion (cholylsarcosine, 51.8 ± 6.29; cholylglycine, 52.72 ± 8.9 μL/kg/min). Total ileal bacterial content was 6‐fold higher in ascitic cirrhotic rats than in healthy rats. Conjugated bile acid administration reduced bacterial content to normal levels. Bacterial translocation was less in cirrhotic animals receiving conjugated bile acids (cholylsarcosine, 33%; cholylglycine, 26%) than in animals receiving placebo (66%). Endotoxemia was decreased in cirrhotic rats by conjugated bile acid feeding (cholylsarcosine, 0.098 ± 0.002; cholylglycine 0.101 ± 0.007 EU/mL) compared with placebo (0.282 ± 0.124, P < .001). Survival was greater in animals receiving conjugated bile acids (cholylsarcosine, 10/15; cholylglycine, 11/15; placebo, 5/15). In conclusion, the administration of conjugated bile acids to ascitic cirrhotic rats increased bile acid secretion, eliminated intestinal bacterial overgrowth, decreased bacterial translocation, decreased endotoxemia, and increased survival. Oral conjugated bile acids may be useful in preventing bacterial translocation, endotoxemia, and spontaneous bacterial perotonitis in cirrhotic patients.


A challenge facing reformers in the field of communications law is the increasingly widening gap between converging markets and services, and regulatory frameworks that continue to govern on the basis of a rigid vertical distinction between broadcasting and telecommunications. In Australia, media and communications are governed by the two distinct and largely independent statutory regimes created by the Broadcasting Services Act 1992 (Cth) and the Telecommunications Act 1997 (Cth). However, markets and services and the underlying technologies have converged. In such a context, continuing to apply vertical 'silo' laws serves to undermine established regulatory objectives of parity and technological neutrality. In 2011, the federal government announced a review of the effects of convergence. One of the issues identified in the review was to need to consider shifting from a silo model to a horizontal 'layered' model. The purpose of the present article is to analyse the merits of adopting a horizontal layered model (i.e. one which mirrors the horizontal layered architecture of modern electronic communications) as the basis for the design of an effective regulatory framework for electronic communications in Australia.


The products of the S-locus expressed in female tissues of Nicotiana alata are ribonucleases (S-RNases). The arrest of growth of incompatible pollen tubes in styles may result from entry of the S-RNase into the pollen tube and degradation of pollen tube RNA. We investigated the action of isolated S-RNases on pollen tubes grown in vitro and found that S-RNase is taken up by the pollen without substantial alteration. The S-RNases inhibit incorporation of exogenously added radioactive amino acids into protein by the germinated pollen. The S-RNases also inhibit in vitro translation of pollen tube RNA in a wheat germ cell-free extract. We found no evidence for a specific mRNA substrate for the S-RNases, which implies that if RNase activity is involved in the control of self-incompatibility, allelic specificity is more likely to depend on the selective uptake of S-RNases into pollen tubes or their selective activation or inactivation by pollen factors, rather than cleavage of a specific substrate. Heat treating S2-RNase largely destroys its RNase activity but increases its inhibitory effect on in vitro pollen tube growth. This effect is not due to an increased uptake of S2-RNase by the pollen but is associated with a greatly enhanced accumulation of S2-RNase on the outer surface of the pollen grains.


BACKGROUND
Extensive renal ablation is associated with progressive sclerosis of the remnant kidney. Because lymphocytes and monocytes accumulate in the remnant kidney, it is likely that they play a role in the renal scarring. Therefore, we treated rats with 5/6 nephrectomy (5/6Nx) with mycophenolate mofetil (MMF), a drug that has an antiproliferative effect and that suppresses the expression of intercellular adhesion molecules.

METHODS
Sprague-Dawley rats with 5/6Nx received MMF (30 mg. kg-1. day-1 by daily gastric gavage, N = 15) or vehicle (N = 16). Ten additional rats were sham operated. All rats were fed a 30% protein diet. Body weight, serum creatinine, and urinary protein excretion were determined weekly. Lipid peroxidation, as a measure of oxidative stress observed by urinary malondialdehyde determinations, was performed every two weeks. Histologic studies were done in the remnant kidney four weeks (9 rats from the vehicle-treated group, 7 rats from the MMF group, and 5 sham-operated rats) and eight weeks after surgery (the remaining rats). Glomerular volume, sclerosis in glomeruli (segmental and global) and interstitium (semiquantitative scale), infiltrating lymphocytes and macrophages (CD43- and ED1-positive cells), and expression of adhesion molecules (CD54, CD18, and CD11b) were analyzed.

RESULTS
MMF treatment prevented the progressive increment in serum creatinine and the proteinuria observed in the 5/6 nephrectomized rats during the eight weeks of observation (P < 0.01). Weight gain was comparable in the MMF-treated and sham-operated rats, whereas weight gain was decreased in untreated 5/6 nephrectomized rats. Excretion of malondialdehyde increased after surgery but returned sooner to control levels in the MMF-treated rats. Increments in glomerular size and mean arterial blood pressure induced by renal ablation were not modified by MMF treatment. Eight weeks after surgery, segmental sclerosis was present in 48.4 +/- 8.35% (+/- sd) glomeruli in the vehicle-treated group versus 25 +/- 10.5% in the MMF-treated group (P < 0.001). Interstitial fibrosis was reduced significantly with MMF treatment (P < 0.001). Infiltration with CD43- and ED1-positive cells in glomeruli and interstitium was two to five times lower in MMF-treated rats (P < 0.01). Expression of adhesion molecules CD18 and CD11b was similarly reduced.

CONCLUSION
MMF ameliorates the progressive renal damage in the remnant kidney after 5/6Nx. This effect is associated with a reduction in the infiltration of lymphocytes and monocytes, whereas glomerular hypertrophy and systemic hypertension are unchanged.


Background: This study was designed to quantify abdominal adipose tissue thickness in hypertensive obese subjects using ultrasound and correlate it with biochemical and anthropometric parameters to establish reference range values for adipose tissue thickness in these subjects in this locality. Materials and methods: A prospective study design was adopted in this study and it was conducted at Esteem Diagnostic Medical Services Limited (EDMSL) Lagos State, Nigeria. Ethical approval was obtained from Research Ethics Committee of EDMSL. An informed consent was also obtained from each patient. Information obtained from the patients was treated with high level of confidentiality. A convenience sample size of 112 volunteers was recruited in this study. Standard protocols and parameters were used to obtain the data. Data were processed and analyzed using SPSS version 20, descriptive and inferential statistics. Statistical significance was set at p<0.05. Results: The study population consisted of 41.96% (n=47) males and 58.04% (n=65) females with age mean of 41.4 ± 10.2 years. The Subcutaneous Adipose tissue (SAT) and Visceral Adipose tissue (VAT) mean ± SD and p-values for male and female subjects were (SAT=30.93 ± 7.97 mm, p=0.012, and SAT=37.08 ± 14.42 mm, p=0.617) for male and female respectively while the (VAT=73.00 ± 8.61 mm, p=0.214 and VAT=71.61 ± 17.40, p=0.006) for male and female respectively. The correlation of VAT with age, BMI, lipid profile and fasting blood sugar levels in male and female hypertensive subjects were assessed and the results showed VAT(Age: Male, r=0.122, p=0.416, female, r=0.082, p=0.517), VAT(LDL: Male, r=0.092, p=0.541, Female, r=0.112,p=0.375), VAT(HDL: Male, r=0.049, p=0.745, Female, r=0.198, p=0.113). Conclusion: Female preponderance was noted in this study. Male subjects had higher values of VAT thickness than their female counterparts, while females were seen with higher values of SAT thickness than their male counterparts. Higher value of blood sugar increases VAT and SAT thickness in female obese subjects more than in male obese subject.


Buffer strips with no added fertilizers are a mitigation measure to reduce P loads from agricultural land to surface water. However, the experimental evidence on their effectiveness (BSE) has been from sloping locations with shallow flow and surface runoff. The aim of this experimental study was to quantify BSE for P on flat agricultural lowland, predominantly with deep flow. We selected sites characteristic of five major hydrogeological classes in the Netherlands and in each experimental field installed paired 5‐m‐wide unfertilized grass (BS) and reference treatments (REF) that abutted the ditch. The REF treatments were managed similar to the adjacent grass or maize field, but BS treatments were only harvested. Each treatment had a reservoir in the ditch to collect and measure discharge and flow‐proportional P concentration for 3 or 4 yr. We also measured net P withdrawal, the P status of the soil and P concentration in upper groundwater. We found a significant BSE for P of 61% on the site with the shallowest flow and steepest slope (2%). At the other sites, BSE was low and statistically insignificant. We conclude that harvested unfertilized buffer strips reduce P loads from flat fields only in specific areas with high surface runoff and/or shallow flow, especially in combination with a high original soil P status.


One emerging approach to reducing the labour and costs of software development favours the specialisation of techniques to particular application domains. The rationale is that programs within a given domain often share enough common features and assumptions to enable the incorporation of substantial support mechanisms into domain-specific programming languages and associated tools. Instead of being machine-oriented, algorithmic implementations, programs in many domain-specific languages (DSLs) are rather user-level, problem-oriented specifications of solutions. Taken further, this view suggests that the most appropriate representation of programs in many domains is diagrammatic, in a way which derives from existing design notations in the domain. This thesis conducts an investigation, using mathematical techniques and supported by case studies, of issues arising from the use of diagrammatic representations in DSLs. Its structure is conceptually divided into two parts: the first is concerned with semantic and reasoning issues; the second introduces an approach to describing the syntax and layout of diagrams, in a way which addresses some pragmatic aspects of their use. The empirical context of our work is that of IEC 1131-3, an industry standard programming language for embedded control systems. The diagrammatic syntax of IEC 1131-3 consists of circuit (i.e. box-and-wire) diagrams, emphasising a dataflow view, and variants of Petri net diagrams, suited to a control-flow view. The first contribution of the thesis is the formalisation of the diagrammatic syntax and the semantics of IEC 1131-3 languages, as a prerequisite to the application of algebraic techniques. More generally, we outline an approach to the design of diagrammatic DSLs, emphasising compositionality in the semantics of the language so as to allow the development of simple proof systems for inferring properties which are deemed essential in the domain. The control-flow subset of IEC 1131-3 is carefully evaluated, and is subsequently re-designed, to yield a straightforward proof system for a restricted, yet commonly occurring, class of safety properties. A substantial part of the thesis deals with DSLs in which programs may be represented both textually and diagrammatically, as indeed is the case with IEC 1131-3. We develop a formalisation of the data-flow diagrams in IEC 1131-3 and rigorously demonstrate the match between these diagrams, their internal textual equivalents and their computational interpretation. Using the devices of universal algebra, we formulate a general, rigorous consistency criterion regarding such "dual" representations. Finally, we motivate the need to include pragmatic aspects of diagrams, such as layout, in formalisations. We demonstrate how certain classes of categories can capture both the structure and layout of graph-based notations. Use of this technique is concretely illustrated in terms of control-flow diagrams in IEC 11313, yielding a basis on which diagram-driven and layout-sensitive rules of inference can be formulated.


Type-and-effect systems are a widely used approach to program verification, verifying the result of a computation using types, and its behavior using effects. This paper extends an effect system for verifying temporal, value-dependent properties on event sequences yielded by programs, to the delimited control operators shift0/reset0. While these delimited control operators enable useful and powerful programming techniques, they hinder reasoning about the behavior of programs because of their ability to suspend, resume, discard, and duplicate delimited continuations. This problem is more serious in effect systems for temporal properties because these systems must be capable of identifying what event sequences are yielded by captured continuations. Our key observation for achieving effective reasoning in the presence of the delimited control operators is that their use modifies answer effects, which are temporal effects of the continuations. Based on this observation, we extend an effect system for temporal verification to accommodate answer-effect modification. Allowing answer-effect modification enables easily reasoning about traces that captured continuations yield. Another novel feature of our effect system is the support for dependently typed continuations, which allows us to reason about programs more precisely. We prove soundness of the effect system for finite event sequences via type safety and that for infinite event sequences using a logical relation.