The paper develops a new productive household model and a consistent household fullincome/ expenditure demand system for inputs and leisure of U.S. households. The demand system is fitted to U.S. annual aggregate data over the last half of the 20th century and findings include that the price and income elasticity of demand for food-at-home are roughly two times larger than for food-away-from-home and that food-at-home and away-from-home are substitutes. The price and income elasticity of demand for men's unpaid housework are twice as large as for women's unpaid housework and women's and men's unpaid housework are shown to be complements.


Aggregators are platforms that also control a marketplace for the suppliers' innovations. Suppliers competing within aggregators are limited by the technology and governance rules of the platform owner. As a consequence, aggregators influence the type and complexity of competitive moves suppliers can implement. Our research investigates the drivers of suppliers' competitive advantage. We incorporate existing literature on competitive action to identify the categories of moves available to suppliers. Furthermore, we identify three types of orthogonal moves that are unique to competition within aggregators. Finally, we illustrate our advanced categorization in the context of a major food delivery platform. Our preliminary results confirm that suppliers, while bounded to resources exposed by the aggregator, have the opportunity to implement an heterogenous portfolio of moves in their pursuit of competitive advantage. This result calls for empirical research in the context of competition within aggregators in general, and food delivery platforms specifically.


Analyses have been widely applied in production forecasting of oil/gas production in both conventional and unconventional reservoirs. In order to forecast production, traditional regression and machine learning approaches have been applied to various reservoir analysis methods. Nevertheless, these methods are still suboptimal in detecting similar production trends in different wells due to data artifacts (noise, data scatter, outliers) that obscure the reservoir signal and leading to large forecast error, or fail due to lack of data access (inadequate SCADA systems, missing or abhorrent data, and much more). Furthermore, without proper and complete integration into a data system, discipline silos still exist reducing the efficiency of automation.
 This paper describes a recent field trial conducted in Australia's Cooper Basin with the objective to develop a completely automated end-to-end system in which data are captured directly from the field/SCADA system, automatically imported/processed, and finally analyzed entirely in automated system using modern computing languages, modern devices incl. IoT, as well as advanced data science and machine learning methods. This was a multidisciplinary undertaking requiring expertise from petroleum, computing/programming, and data science disciplines.
 The back-end layer was developed using Wolfram's computation engine, run from an independent server in Australia, while the front-end graphical user interface (GUI) was developed using a combination of Wolfram Language, Java, and JavaScript – all later switched to a Python-React combination after extensive testing. The system was designed to simultaneously capture data real-time from SCADA Historians, IIoT devices, and remote databases for automatic processing and analysis through API's. Automatic processing included "Smart Filtering" using apparent Productivity Index and similar methods. Automated analysis, including scenario analysis, was performed using customized M/L and statistical methods which are then applied to Decline curve analysis (DCA), flowing material balance analysis (FMB), and Water-Oil-Ratio (WOR). The entire procedure is automated, without need for any human intervention.


Developing an economical, highly active and durable material to replace the conventional, expensive noble metal electrocatalyst is an important milestone in the development of fuel cell technology. Nanocarbon materials are considered as promising catalysts toward the oxygen reduction reaction (ORR) in fuel cells, due to their reasonable balance between low-cost, long-life durability and high catalytic activity in alkaline media. In this work, we present the fabrication of N,S-co-doped nanocarbon derived from a metal-organic framework (MOF) precursor for use as an electrocatalyst towards ORR. High resolution transmission electron microscopy (HRTEM) mapping demonstrates the uniform distribution of N and S atoms into the nanocarbon skeleton. The nitrogen absorption–desorption isotherms indicate that the MOF-derived N,S-co-doped nanocarbon has a high specific surface area (2439.9 m2 g−1) and a porous structure. Importantly, the N,S-co-doped nanocarbon exhibits higher catalytic activity toward ORR, better long-term stability and methanol tolerance than commercial Pt/C catalyst. First-principles calculations demonstrate that the remarkable electrochemical properties of N,S-co-doped nanocarbon are mainly attributed to the synergistic effect from the N and S dopants. Moreover, for the first time, it is revealed that the N,S-coupled dopants in nanocarbon can create active sites with higher catalytic activity for ORR than the isolated N and S-dopants. This finding on the structure–performance relationship of the co-doped nanocarbon provides guidelines for the design of high performance electrocatalysts.


Ecotoxicology aims at protecting ecosystems and populations. Population level is rarely studied in ecotoxicity tests. However, the population level can be monitored with high realism relative to ecosystems through experiments in outdoor mesocosms. At INERIS, we focus on the three-spined Stickleback, Gasterosteus aculeatus, because it is a well-studied species, autochthonous in French rivers, and a promising species to assess the impact of contaminant. All studies already performed in mesocosms suffer from an important variability between replicates for a same treatment (more than 50 % of variation is generally observed on biological variables). Temporal replicability of mesocosms' outcomes is also an issue. In our study, we aimed at identifying the major causes of inter and intra annual variability in control conditions. Thus ten populations per year, for two years experiments were monitored between March and October 2010 and 2011. At the beginning of experiments, each compartment of the ecosystem (weight of macrophytes, number and masse of invertebrates, number, length and sex ratio of fish...) were introduced in standardized conditions. At the end of the experiments, all populations were defined by characteristics such as total number of fish, sex ratio, and percentage of mature organisms. We found that, in 2010, the proportion of males and females fish introduced in the system was the most influent parameter to account for the population characteristics (total number of fish and structure of the population) at the end of the experiment. Inter-annual variability was mainly due to differences in water temperature profiles. Intra-annual variability can be reduced through a better sex determination of the fish introduced at the beginning of the experiment. We developed an original methodology to achieve that (see another poster of de Kermoysan et al. : "A non-invasive method based on head morphology to sex mature three-spined Stickleback (Gasterosteus aculeatus) in rearing conditions"). Inter-annual variability, in link with temperature, could be quantified provided the influence of temperature on the main components of G. aculeatus population dynamics are understood and modelled.


Hemodynamic evaluation is an essential component in diagnosing cardiovascular disorders and managing patient care. There are numerous invasive, semi-invasive, and noninvasive methods available for evaluating hemodynamic function, which vary widely in equipment, procedural complexity, cost, quality of data, and risks. This paper summarizes information needed for administrative decision-making about employing one method--ICG hemodynamic monitoring--and provides an overview of the technology, its accuracy and reproducibility, clinical applications, financial consideration and references for further evaluation of the technology.


Despite the significant improvement in accuracy supervised learning has brought into person re-identification (re-id), the availability of sufficient fully annotated data from concerned camera-views poses a problem for real-life applications. To alleviate the burden of intensive data annotation, one way is to resort to unsupervised methods. This has motivated us to propose a novel algorithm for unsupervised video-based person re-id applications. To achieve this, the frames of a person video tracklet are divided into a set of clusters that are subsequently matched using a distance measure based on the Naive Bayes nearest neighbor algorithm and Spearman distance. Knowing that person's sequences may suffer from substantial changes in viewpoint, pose, and illumination distortions, our technique allows the rejection of poor and noisy clusters while retaining the most discriminative ones for matching. Experiments on three widely used datasets for video person re-id PRID2011, iLIDS-VID and MARS have been carried out, and the results demonstrate the superiority of the proposed approach.


This body of work presents the research and publications undertaken under a general theme of minimal access colorectal surgery. Papers are presented on surgery for colon cancer, rectal cancer, splenic flexure, emergency surgery, and complications after laparoscopic surgery, outcomes, training in minimal access surgery and robotic surgery. The work highlights my own personal contributions and publications under this theme, as well as collaborations and output emanating from multi-centre trials. Presentations include video, oral and poster presentations at national and international meetings. With my background experience of laparoscopic surgery, the focus has been on applications of laparoscopy for the management of colorectal cancer, role of laparoscopy in emergency settings, and complications of colorectal surgery. With a significant experience in robotics, I have shared the published data from management of rectal cancers and the techniques of single docking total mesorectal excision and flexure mobilization. A particular focus has been on teaching and training in minimal access surgery. My publication record comprises; pathfinder and seminal papers; papers from co-supervised MD/MSc; international collaborations; technical authorship and support; other published contributions; guideline development and technical reports and internal briefing papers.


There are challenges faced by the profit-and-loss sharing (PLS) financing in Islamic banking institutions in Malaysia. PLS financing is comprised of mudharabah and musharakah contracts. This study  evaluated the application and modus operandi of mudharabah and musharakah contracts before dwelling into the challenges.  While musharakah contract involves contribution of capital and labor by both the investor and the entrepreneur, mudharabah contract allows the investor to provide the capital and only the entrepreneur operates the business.  In terms of return on investment, both partners share the profit or loss based on the pre-agreed ratio for musharakah; but only the capital provider bears the loss for mudharabah as the entrepreneur already forgone his or her effort for the project. In examining the challenges, we had conducted several interview sessions with Malaysian Islamic banks that offer PLS financing.  The findings showed that there were four major obstacles to PLS financing such as high risk of investment; difficulty in selecting appropriate partners; demand comes from low credit worthiness customers; and lack of capital security.  Keywords: capital security,  challenges, Islamic banking, mudharabah,  musharakah, profit and loss sharing financing


A quantitative inversion procedure is developed and applied to determine the dominant scattering mechanism (surface roughness and/or volume scattering) from seabed scattering-strength data. The classification system is based on trans-dimensional Bayesian inversion with the deviance information criterion used to select the dominant scattering mechanism. Scattering is modeled using first-order perturbation theory as due to one of three mechanisms: Interface scattering from a rough seafloor, volume scattering from a heterogeneous sediment layer, or mixed scattering combining both interface and volume scattering. The classification system is applied to six simulated test cases where it correctly identifies the true dominant scattering mechanism as having greater support from the data in five cases; the remaining case is indecisive. The approach is also applied to measured backscatter-strength data where volume scattering is determined as the dominant scattering mechanism. Comparison of inversion results with core data indicates the method yields both a reasonable volume heterogeneity size distribution and a good estimate of the sub-bottom depths at which scatterers occur.


As web search providers seek to improve both relevance and response times, they are challenged by the ever-increasing tax of automated search query traffic. Third party systems interact with search engines for a variety of reasons, such as monitoring a website's rank, augmenting online games, or possibly to maliciously alter click-through rates. In this paper, we investigate automated traffic in the query stream of a large search engine provider. We define automated traffic as any search query not generated by a human in real time. We first provide examples of different categories of query logs generated by bots. We then develop many different features that distinguish between queries generated by people searching for information, and those generated by automated processes. We categorize these features into two classes, either an interpretation of the physical model of human interactions, or as behavioral patterns of automated interactions. We believe these features formulate a basis for a production-level query stream classifier.


Purpose: Road accidents are the leading cause of non-disease-related deaths among teenagers in Cambodia. However, Cambodian schools continue to lack road safety education programmes and standardised guidelines. This study evaluated the effects of a customised comprehensive road safety educational programme for older elementary school students in Cambodia. Design: We conducted a road safety educational programme at an elementary school in Cambodia. The programme consisted of seven parts and included content related to pedestrian and vehicle (car, motorcycle and bike) safety. Methods: We used a mixed method to evaluate changes in knowledge, attitudes and practices following the programme. For the quantitative evaluation, we conducted a quasi-experimental study using a nonequivalent control group pre-test–post-test design involving 52 students. The experimental group comprised fourth graders (aged 10 years) and the control group consisted of fifth graders (aged 11 years). For the qualitative evaluation, we conducted focus group interviews with six participants from the experimental group. Results: Post-test road safety knowledge (Z = −2.79; p = .005) and attitudes (Z = −2.05, p = .041) improved significantly in the experimental group. Qualitatively, three themes were identified: participants acquired new insights into road safety, they adopted more positive attitudes and they made an effort to practise road safety. Conclusion: This pilot study demonstrated a possible positive effect of a road safety educational programme, suggesting that, following additional verification, it could be used to improve road safety for older elementary school students in Cambodia.


In this paper efforts have been made to estimate coarse rice exchange entitlement of agricultural labour. Rice entitlement has been calculated for male and female in terms of labour wage earned by selling their labour power that they own. Sharp gender disparity is observed in rice exchange entitlement. The sharpest decline in entitlement is observed in 2008. Seasonality in rice exchange entitlement of labour power has also been examined.


The overarching aim of this thesis was to develop a method of enhancing adhesive performance by introducing a self-repair capability into it. It was envisaged that such a capability would act to mitigate against degradation through environmental attack. Specifically it was desirable for the adhesive to be able to repair damage to the interface region of the joint, where defect formation may include zero-volume unbonds (ZVU) or similar artefacts. To achieve this, a means of introducing a repair material into the adhesive during manufacture. Encapsulation technology was seen as a means of achieving this, allowing the repair component to be introduced during manufacture, yet partitioned away from the reactive adhesive components and held in storage until triggered by a damage related event. The optimum trigger in this case would be the presence of moisture i.e. release would occur in response to the ingression of moisture into the adhesive joint. A review of encapsulation technologies and applications was therefore undertaken and a number of techniques identified as means of encapsulating potential repair materials, which were also identified in this study. The selected techniques were coacervation, emulsion-solvent evaporation and interfacial polymerisation, while three adhesive monomers were selected as repair materials - methyl methacrylate (MMA), 2-ethyl hexyl methacrylate and 2-ethyl cyanoacrylate. A series of experiments were attempted to encapsulate these repair materials, with limited success. Only MMA was successfully encapsulated, but the shell material was not ideal for the envisaged trigger described. A novel technique was eventually developed and employed to encapsulate 2-EHMA and MMA. Encapsulation of MMA was not achieved, though some interesting properties of the resultant microspheres were observed. 2-EHMA was encapsulated within a shell of PECA, which proved amenable to moisture triggered release of the methacrylate. Thermal analysis of these particles and adhesive components indicated that stability would be poor at high cure temperatures and that reactions may take place between shell (PECA) and adhesive components, specifically the amine hardener employed. Nether the less, incorporation of capsules into a basic epoxide adhesive was achieved, albeit at low cure temperatures. This raised a number of problems, such as achieving adequate dispersion of the capsules and preventing separation during adhesive cure. It was not possible to address these questions within the timescale of the project, but recommendations for future study have made.


Cochlear implants (CIs) in small children who do not yet have a firm footing in first language acquisition are an on-going experiment with human subjects, in the sense that the risks involved have not been properly identified, much less assessed, due to the failure to focus on the biology of language and its role in first language acquisition. Too often, the developmental cognitive milestones of the deaf child and the right to language are not considered, and we risk contributing to cases of linguistic deprivation with all the ensuing consequences. We propose an immediate remedy: to teach deaf children a sign language, along with training in speech and speech-reading. For many families, such as those that live far from a Deaf community, as in a rural situation, this presents practical problems, which we address.


Type 2 diabetes mellitus (T2DM) is a complex group of disorders, characterized by hyperglycemia, insulin resistance and insulin deficiency. In human blood, hyperglycemia ultimately results in the enhancement of glycation – a posttranslational modification formed by the interaction of protein amino groups with glucose. The resulting fructosamines (Amadori compounds) readily undergo further degradation resulting in advanced glycation end products (AGEs), known to be pro-inflammatory in humans. These compounds are highly heterogeneous and characteristic of advanced stages of the disease, whereas fructosamines are recognized markers of early diabetes stages (HbA1C, glycated albumin). Recently, individual plasma protein glycation sites were proposed as promising T2DM biomarkers sensitive to short-term fluctuations of plasma glucose. However, corresponding absolute quantification strategies, applicable in regular clinical practice, are still not established. Therefore, here we propose a new analytical approach aiming at reproducible and precise quantification of multiple glycated peptides in human plasma tryptic digests. Thereby, the standard peptides comprised a 13C,15N-labeled lysyl residue, a dabsyl moiety for determination of standard amounts, and a cleavable linker. Known amounts of these peptides were spiked to plasma samples prior to tryptic digestion, quantification relying on stable isotope dilution. The method was demonstrated to be applicable for quantification of individual glycated sites in T2DM patients and non-diabetic controls.


The politics and music of the sixties and early seventies have been the subject of scholarship for many years, but it is only very recently that attention has turned to the cultural production of African American poets. In "After Mecca," Cheryl Clarke explores the relationship between the Black Arts Movement and black women writers of the period. Poems by Gwendolyn Brooks, Ntozake Shange, Audre Lorde, Nikki Giovanni, Sonia Sanchez, Jayne Cortez, Alice Walker, and others chart the emergence of a new and distinct black poetry and its relationship to the black community's struggle for rights and liberation. Clarke also traces the contributions of these poets to the development of feminism and lesbian-feminism, and the legacy they left for others to build on. She argues that whether black women poets of the time were writing from within the movement or writing against it, virtually all were responding to it. Using the trope of "Mecca," she explores the ways in which these writers were turning away from white, western society to create a new literacy of blackness. Provocatively written, this book is an important contribution to the fields of African American literary studies and feminist theory.


With the explosive growth of the Internet, fundamental content management needs have also grown. No longer can information be published online in a manual process and be left unattended. A content management system (CMS) represents a revolutionary way to manage online content when
compared to traditional methods. A CMS is the tool that allows us to collect, manage and publish information to a variety of medium in an efficient, timely, and duplicable manner. CMS can be categorized into File-Based Content Management for Sharing, Web-Site Content Management for Publishing and Enterprise-wide Content Management for Integration and Publishing. The functionalities of a generic CMS can be broken into Content Collection or Authoring, Workflow, Storage or Management and Publishing. The need for a CMS can be gauged by the huge amount of content, the enormous amount of change in the content, and the massive number of publications to create. The use of CMS promises many advantages in the form of empowering content, decrease cost, increase revenue, improve accountability, and maintain consistency.


Three cases of bovine gamma(delta) T-cell lymphoma without skin involvement are described. Case 1 was a 17-month-old Holstein heifer with generalized lymphadenopathy. Case 2 was a 4-year-old Holstein cow that had multiple tumour masses in the uterine body and horns. Case 3, a 23-month-old Holstein bull was presented with generalized tremor, nystagmus and hyperesthaesia, and there were several tumour masses in the meninges. Cases 1 and 2 had epitheliotropic neoplastic infiltrates in the tonsillar epithelium and endometrial glands, respectively. Immunohistochemistry showed CD3+, WC1+, CD79a- lymphoma cells in all cases, and perforin was positive in two cases. Electron-dense granules were present in many neoplastic cells of all cases. These findings supported the cytotoxic gamma(delta) T-cell origin of the present lymphomas. Bovine gamma(delta) T-cell lymphoma may originate in a wide variety of anatomical sites and may be classified into several histological subtypes.


New regulations are emerging in response to historic groundwater depletion and widespread groundwater quality degradation in California. They aim at long-term preservation of groundwater resources for use in agriculture, in urban areas and for the support of ecosystems in streams dependent on groundwater. The regulations are driving a historic shift in the way the agriculture sector is engaged in managing and protecting groundwater resources in California. A review and synthesis of these recent regulatory developments — the Sustainable Groundwater Management Act and new policies under the California Porter-Cologne Water Quality Control Act — clarifies key challenges for farmers, scientists and regulators and points to the need for continuing innovation in agricultural practices as well as in planning and policy.


On 25 March 2015, the Enlarged Board of Appeal of the European Patent Office (EBA) finally delivered its' much awaited decisions on the consolidated referrals G2/12 ("Tomato II") and G2/13 ("Broccoli II"). The EBA affirmed that products, namely plants or parts thereof, obtained by essentially biological processes are – unlike individual plant varieties – principally patentable under the European Patent Convention (EPC). This decision leaves considerable leeway for patenting novel and inventive plants and products thereof, which have been produced by "conventional" methods including breeding steps. The EBA has also clarified that this applies irrespective of if such claims are formulated in a product-by-process format or as a per se product . Moreover, the combined effect of Broccoli & Tomato I & II opens new opportunities for patenting GMOs - provided that all other patent criteria are also met. This generally appears to be "good news" for innovative plant breeders and agrochemical companies. However, caveat needs to be added: Major industry players had challenged the relevant patent-claims and the EBA's decision(s) remain very controversial. It is, for example, very uncertain how the CJEU would decide if confronted with similar issues in the context of national implementations of the Biotech Directive, which have taken a very different view than the EBA. Moreover, the fierce European opposition against genetically modified organisms (GMOs) and Synthetic Biology remains a major challenge to the industry, research and innovation in an increasingly significant area of science and debate.Post scriptum (!) : After completion of this paper, the European Commission expressed that it did not share the opinion of the EPO's Enlarged Board of Appeal (cf. the Interpretative Notice from November 2016). Like several EU member states, such as France, Germany, Italy and Netherlands, the Commission found that under the EU Biotech Directive products obtained by essentially biological processes should not receive patent protection. This intervention by the Commission, the divergences between the interpretation of the EPC and the Biotech Directive, and the need for legal certainty and harmonization, led the EPO to stay ex officio all the proceedings in which the decision depended entirely on the patentability of a plant or animal obtained by an essentially biological process. Then, on June 29, 2017, the Administrative Council of the EPO decided to amend Rules 27 and 28 of the Implementing Regulation. According to these amendments products (animals or plants) obtained exclusively from essentially biological process are now effectively excluded from patentability. Notwithstanding that this contradicts the earlier decisions by the Enlarged Board of Appeal, these amendments apply to European patent applications filed on or after July 1, 2017, as well as to European patent applications and European patents pending at that time.This paper has also been published as a working paper on SSRN, see: Minssen, Timo and Nordberg, A., The Impact of Broccoli II & Tomatoes II on European Patents in Conventional Breeding, GMO's and Synthetic Biology: The Grand Finale of a Juicy Patents Tale? (May 19, 2015). Univ. of Copenhagen Dept. of Economics Discussion. Available at SSRN: http://ssrn.com/abstract=2607865 or http://dx.doi.org/10.2139/ssrn.2607865 (Less)


This paper deals with continuous-time Markov decision processes with the unbounded transition rates under the strong average cost criterion. The state and action spaces are Borel spaces, and the costs are allowed to be unbounded from above and from below. Under mild conditions, we first prove that the finite-horizon optimal value function is a solution to the optimality equation for the case of uncountable state spaces and unbounded transition rates, and that there exists an optimal deterministic Markov policy. Then, using the two average optimality inequalities, we show that the set of all strong average optimal policies coincides with the set of all average optimal policies, and thus obtain the existence of strong average optimal policies. Furthermore, employing the technique of the skeleton chains of controlled continuous-time Markov chains and Chapman-Kolmogorov equation, we give a new set of sufficient conditions imposed on the primitive data of the model for the verification of the uniform exponential ergodicity of continuous-time Markov chains governed by stationary policies. Finally, we illustrate our main results with an example.


Background Low back pain (LBP) is a common disabling condition. Lumbar disc degeneration (LDD) may be a contributing factor for LBP. Modic change (MC), a distinct phenotype of LDD, is presented as a pathological bone marrow signal change adjacent to vertebral endplate on MRI. It is strongly associated with LBP and has heritability around 30%. Our objective was to identify genetic loci associated with MC using a genome-wide meta-analysis. Methods Presence of MC was evaluated in lumbar MRI in the Northern Finland Birth Cohort 1966 (n=1182) and TwinsUK (n=647). Genome-wide association analyses were carried out using linear regression model. Inverse-variance weighting approach was used in the meta-analysis. Results A locus associated with MC (p<5e-8) was found on chromosome 9 with the lead SNP rs1934268 in an intron of the PTPRD gene. It is located in the binding region of BCL11A, SPI1 and PBX3 transcription factors. The SNP was nominally associated with LBP in TwinsUK (p=0.001) but not associated in the UK Biobank (p=0.914). Suggestive signals (p<1e-5) were identified near XKR4, SCIN, MGMT, DLG2, ZNF184 and OPRK1. Conclusion PTPRD is a novel candidate gene for MC that may act via the development of cartilage or nervous system; further work is needed to define the mechanisms underlying the pathways leading to development of MC. This is the first genome-wide meta-analysis of MC, and the results pave the way for further studies on the genetic factors underlying the various features of spine degeneration and LBP.


For any code C defined over an equal energy constellation, it is first shown that at any time instance, the problem of determining codewords of C with high peak-to-average power ratios (PAPR) in a multicarrier communication system is intimately related to the problem of minimum-distance decoding of C. Subsequently, a method is proposed for computing the PAPR by minimum-distance decoding of C at many points of time. Moreover an upper bound on the error between this computed value and the true one is derived. Analogous results are established for codes defined over arbitrary signal constellations. As an application of this computational method, an approach for reducing the PAPR of C proposed by Jones and Wilkinson (1996) is revisited. This approach is based on introducing a specific phase shift to each coordinate of all the codewords where phase shifts are independent of the codewords and known both to the transmitter and the receiver. We optimize the phase shifts offline by applying our method for computing the PAPR for the coding scenario proposed by the ETSI BRAN Standardization Committee. Reductions of order 4.5 dB can be freely obtained using the computed phase shifts. Examples are provided showing that most of the gain is preserved when the computed optimal phase shifts are rounded to quantenary phase-shift keying (PSK), 8-PSK, and 16-PSK type phase shifts.


In this paper new techniques are proposed for the handling of multimedia traffic in a hierarchical multi-tier system involving microcellular, macrocellular and satellite coverage. In this environment, efficient channel assignment and hand-off management techniques become critical issues to fully exploit the benefits of the multi-layered architecture. The traffic flow control between layers has to maximise the system capacity without degrading the traffic QoS. This task is particularly hard when in the presence of multimedia calls, which ask for large amount of bandwidth and are characterised by the combination of traffic of different nature. The proposed algorithms differ from the traditional ones as they adopt a multi-bearer transport approach to carry multimedia traffic over the air-interface, coupled with suitable strategies for the allocation of each traffic component at the best layer. This leads to better resource utilisation and multimedia QoS guarantees, while minimising new call blocking and hand-off failure probabilities.


Practical Applications In Business Cycle–Related Timing of Alternative Risk Premia Strategies, from the Spring 2020 issue of The Journal of Alternative Investments, Bernd Scherer and Matthias Apel relate how they developed a business cycle model to explore its predictive power in a tactical allocation framework. They created an aggregate of economic indicators that identifies economic regimes in order to determine the sensitivities of a host of risk premia strategies across various business cycle phases. Many of these sensitivities, measured as conditional Sharpe ratios, are statistically different from their unconditional, overall risk-adjusted returns. During each regime, a long–short tactical overlay strategy takes a long position in the four alternative risk premia strategies with the highest Sharpe ratios and shorts the four with the lowest. The authors show that the overlay strategy improves the performance of a risk-parity portfolio and provide evidence that the observed return patterns are not a beta-driven result. While their primary interest lies within a universe of investable alternative risk premia strategies, cross-validation tests also applied the model within three additional investment universes: global asset classes, smart betas, and Fama–French risk factors.


Comparisons of ground motions from two widely used point-source and finite-source ground-motion simulation programs (SMSIM and EXSIM) show that the following simple modifications in EXSIM will produce agreement in the motions from a small earthquake at a large distance for the two programs: 1) base the scaling of high frequencies on the integral of the squared Fourier acceleration spectrum; 2) do not truncate the time series from each subfault; 3) use the inverse of the subfault corner frequency for the duration of motions from each subfault; and 4) use a filter function to boost spectral amplitudes at frequencies near and less than the subfault corner frequencies. In addition, for SMSIM an effective distance is defined that accounts for geometrical spreading and anelastic attenuation from various parts of a finite fault. With these modifications the Fourier and response spectra from SMSIM and EXSIM are similar to one another, even close to a large earthquake (M 7), when the motions are averaged over a random distribution of hypocenters. The modifications to EXSIM remove most of the differences in the Fourier spectra from simulations using "pulsing" and "static" subfaults, and they also essentially eliminate any dependence of the EXSIM simulations on the number of subfaults. Simulations with the revised programs suggest that the results of Atkinson and Boore (2006), computed using an average stress parameter of 140 bars and the original version of EXSIM, are consistent with the revised EXSIM with a stress parameter near 250 bars.


In this paper, we present a system generating free-viewpoint video in real-time using multiple cameras and a PC cluster. Our system firstly reconstructs a shape model of objects by the visual cone intersection method, secondly transforms the shape model represented in terms of a voxel form into a triangular patch form, thirdly colors vertexes of triangular patches, and finally displays the shape-color model from the virtual viewpoint directed by a user. In this paper, we describe implementation details of our system and show some experimental results.


Oncogenic signalling and metabolic reprograming are hallmarks of tumour progression, yet little is known about the regulatory elements that coordinate their interface. Aberrant choline and phospholipid metabolism are strongly correlated to malignant progression in NSCLC and provide the essential components required by both hallmarks and yet mechanistic links to either remain scarce. Choline kinase alpha (ChoKα) regulates the conversion of choline to phosphocholine and although its regulatory cascade has not been described, it is thought to act in conjuction with EGFR. We used an integrated systems approach and queried whether pharmacoproteomic pathway mapping could identify regulators of the cholinic phenotype. Proteomic and phosphoproteomic Stable isotope labelling by amino acids in cell culture (SILAC) analysis was used to describe the interactome following ChoKα or EGFR inhibition. Bioinformatic analysis was used to identify the significant (Significance-B test) subset of targets for each condition. These subsets were clustered according to GeneOntology, Reactome and KEGG databases and the resulting maps identifed the potential regulators of choline metabolism. Choline uptake, phosphorylation and efflux were further evaluated in vitro in response to erlotinib, cisplatin, pemetrexed and paclitaxel using radio-labelled Choline analogues. Derived metabolites were characterised using radio-HPLC. Uptake was further characterised under hypoxic and nutrient deficient conditions. In vivo, [18F]-D4-Choline PET dynamic imaging was performed following treatment. Pharmacoproteomic analysis revealed a 40% overlap between ChoKα and EGFR inhibition providing direct evidence of the pathways and targets involved in, mostly, biosynthesis. Rapid modulation of the cholinic phenotype was directly dependent on ChoKα activity. Intracellular uptake was induced by nutrient deprivation, hypoxia and reversed through second messenger signalling or growth factor stimulation. Choline uptake within 3 hours of treatment correlated to survival at 72 hours. In vivo, [18F]-D4-Choline tracer kinetics were diagnostic of choline kinase expression and sensitive to treatment. Significant correspondence between ChoKα and EGFR inhibition provided mechanistic evidence that ChoKα and lipid metabolism are effectors of the EGFR signalling cascade in NSCLC. Choline can act as a sensor by synchronizing the survival response via metabolic and signalling reprograming and is thus an early predictor of therapeutic efficiency in vitro and in vivo. Citation Format: Rosy Favicchio, Nicos Angelopoulos, Diana Brickute, Robin Fortt, Frazer Twyman, Georgios Giamas, Juan Carlos Lacal, Eric O. Aboagye. Choline metabolism is an early predictor of EGFR-mediated survival in NSCLC. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4235.


The development and maintenance of quality software involves the effective use of software engineering standards. The development of national and international software engineering standards began in the early 1970s. Since that time more than 300 standards have been developed. From a user's perspective, there is duplication, inconsistencies, overlap and omissions. In the 1980s the two major international standards organizations formed a joint technical committee on information technology to deal with a range of standards including those for software. A market-driven architecture for software engineering standards has been developed to: guide the development and organization of international software engineering standards; position those standards in relation to standards for quality systems (ISO 9000 series) and system-related standards dependability (IEC TC56), safety-critical (IEC SC65A), and security (ISO/IEC JTC1/SC27); and promote the adoption of software engineering standards in the marketplace.


The intermittent nature of millimeter wave (mmWave) links caused by human-body blockage is an intrinsic property of the 5G New Radio (NR) technology that may cause drops of sessions already accepted for service. To improve the session continuity, multiconnectivity and guard capacity mechanisms have been proposed recently. Multiconnectivity enables dynamic handover between multiple pre-established spatially-diverse links, while guard capacity reserves a fraction of radio resources for the already accepted sessions by ensuring that they will have sufficient provisions in case of link blockage. In this study, we combine the tools of queuing theory and stochastic geometry to develop a mathematical framework for capturing the joint operation of these two schemes as well as the features of mmWave radio propagation. The metrics are related to user- and system-centric performance including the system resource utilization and the new and ongoing session drop probabilities. Our results show that multiconnectivity benefits all of the considered parameters. However, the range of performance boost remains limited by the deployment density and the maximum supported degree of multiconnectivity. In its turn, guard capacity allows to further decrease the ongoing session drop probability at the expense of the new session drop probability and the system resource utilization. When implemented jointly with multiconnectivity, guard capacity does not produce noticeable negative effects on the system resource utilization as compared to its standalone use. Hence, one may prefer a joint implementation of these mechanisms for preserving the session continuity of users without compromising the resource utilization.


Abstract:The Tudor period saw a revolution in antiquarian histories of Britain. Their networks of transmission largely circle around major collectors such as Matthew Parker and William Cecil. One prominent figure in Cecil's orbit was Laurence Nowell, the antiquarian whose name is famously associated with the Beowulf manuscript (the "Nowell Codex"). Nowell made copies of the Itinerarium Kambriae and Descriptio Kambriae, both texts by Giraldus Cambrensis, from differing sources, resulting in the defective manuscript London, British Library Additional MS 43706. His colleague William Lambarde used the Add. MS 43706 as the basis for his copy of Descriptio Kambriae. However, before Lambarde finished his transcription, he made annotations in Nowell's copy. This paper will examine the marginal annotations in Add. MS 43706, which include several annotations in Nowell's hand too. Nowell and Lambarde must have exchanged the manuscript back and forth, as demonstrated by their crossing out and correcting of each other's annotations. This correspondence on the physical pages of the manuscript speaks to their differing attitudes towards prominent aspects of Giraldus's text, including how to read and interpret marvels, natural history, and the twelfth-century discord between Wales and Anglo-Norman England. Nowell's more conservative attitude led him to derisively identify many of the anecdotes as "superstitio", "ridiculum", and "fabula", whereas Lambarde resists such disparaging comments by crossing them out and then justifying them with notes such as "mais miraculu[m]". This article ultimately argues that reading conflict in the margins highlights the value of studying marginalia in order to better understand the transmission practices of the antiquarians, including how they read medieval texts and how they interpret, translate, excerpt, and summarize them.


Diel cycles are known to occur in all types of waters, and increasing studies indicate routine water samples may not provide an accurate snapshot in concentrations of trace elements and nutrients. Diel behavior in neutral to alkaline pH ranges is independent of streamflow variability and concentration. Extensive historical U.S. Geological Survey (USGS) water-quality data have been collected in the Eagle River Basin during daylight hours, which is defined as the period of time between one-half hour prior to sunrise and one-half hour after sunset. However, no USGS data have been collected throughout the nighttime, defined as the time between one-half hour after sunset and one-half hour prior to sunrise, making the evaluation of diel cycles impossible. To assess the importance of diel cycling within the Eagle River Basin, the USGS, in cooperation with Eagle River Watershed Council, developed a study to assess the mechanisms, patterns, and magnitude of change during the diel cycle for selected constituents. Water-quality monitors at five USGS streamgage sites (09065500, Gore Creek at Upper Station, near Minturn, Colorado, 09063000, Eagle River at Red Cliff, Colorado, 09064600, Eagle River near Minturn, Colorado, 09066325, Gore Creek above Red Sandstone Creek at Vail, Colorado, and 394220106431500, Eagle River below Milk Creek near Wolcott, Colorado) were deployed in 2017 to evaluate the water-quality field parameters and to determine if water conditions were favorable for the diel cycling of nutrients and trace elements. Based on the evaluation of water-quality parameters, three of the five sites were sampled for nutrient and traceelement concentrations in 2018 to confirm the presence and magnitude of diel cycling. Historical data were also analyzed to assess the effect of time of day on measured nutrient and trace-element concentrations. An assessment of the effect of land use on diel cycling was also investigated. Measurable nutrients displayed a diel cycle at all three sites with the largest percentage change at the most downstream site (394220106431500), located on the Eagle River. More notable diel cycles at this site include filtered nitrate plus nitrite, which varied 179 percent, with concentrations from 0.24 to 0.67 milligrams per liter (mg/L) and filtered orthophosphate, which varied 71 percent, with concentrations from 0.07 to 0.12 mg/L. Filtered nitrate plus nitrite at site 09066325 varied 57 percent, ranging from 0.14 to 0.22 mg/L. Maximum concentrations occurred prior to noon, decreased through the afternoon (between noon and sunset), and increased during the night (between sunset and sunrise). That pattern is consistent with nutrient uptake in response to daytime (between sunrise and sunset) photosynthesis along with biologically driven denitrification and nitrification cycles. Nutrient concentrations at sites 09064600 and 09066325 were generally low and below laboratory reporting limits, which is the smallest measured concentration that nutrients could be measured by a given analytical method. Trace-element concentrations were detectable at all sites with the largest percentage change at the most downstream site (394220106431500) and exhibited diel concentration variation from 11.6 to 284 percent. Appreciable diel cycles included filtered copper (0.98–1.40 micrograms per liter [μg/L], 42.9 percent), filtered zinc (less than [<] 4.00–5.50 μg/L, greater than [>] 37.5 percent), total manganese (9.70–19.5 μg/L, 101 percent), and total arsenic (0.30–0.40 μg/L, 33.3 percent). The largest percentage change in concentration was filtered manganese (2.84–10.9 μg/L, 284 percent). Diel cycles at site 09064600 ranged from 9.1 to 64.5 percent across the trace elements measured. Dissolved trace elements with appreciable diel cycles during the sampling period include filtered cadmium (0.09–0.12 μg/L, 33.3 percent), filtered copper (0.99–1.40 μg/L, 41.4 percent), and total arsenic (0.20–0.30 μg/L, 50 percent). The largest percentage change was filtered zinc (38.3–63.0 μg/L, 65 percent). Trace-element concentrations at site 09066325 were below laboratory reporting limits for many parameters, and no diel cycle could be assessed for these parameters. However, total recoverable iron, filtered barium, filtered manganese, and filtered selenium exhibited changes in concentrations of <10.0–19.4 μg/L (>94 percent), 115–121 μg/L (5 percent), 1.44–1.72 μg/L (19.4 percent), and 0.25–0.28 μg/L (12 percent), respectively. At sites 09064600 and 394220106431500, maximum trace-element concentrations occurred during nighttime with some variation regarding the timing of the peak. The exceptions to this were filtered copper, total arsenic, and filtered selenium, which had maximum concentrations around noon or as the sun disappeared below the horizon. The timing of minimum concentrations occurred in the afternoon for many trace elements, with 2 Assessment of Diel Cycling in Nutrients and Trace Elements in the Eagle River Basin, 2017–18 filtered copper, total arsenic, and filtered selenium having minimum concentrations in the morning or just prior to the appearance of the sun. Analysis of historical data also showed evidence of diel cycling. Historical samples collected from July through October were used to identify diel cycling in base-flow conditions. The resulting diel pattern in the median concentration for filtered manganese, filtered zinc at water-quality site 09064600, and filtered manganese and filtered nitrate plus nitrite at water-quality site 39422016431500 were consistent with the diel pattern in the September 2018 samples, and indicate time of day can bias sampling results even during daylight hours. Diel cycling in the Eagle River Basin appears to be driven primarily by instream, biological processes. However, land use, particularly human effects downstream from urban areas, mining, and agriculture, may affect these processes. At some locations, diel variations in nutrient and trace-element concentrations are small enough to be of low concern. At other locations, however, variations in concentrations up to 284 percent in the data collected for this study and 214 percent in base-flow historical data, indicate daytime-only sampling, particularly in late afternoon, can underestimate daily average nutrient and trace-element concentrations. When feasible, the potential of diel cycling warrants consideration in sample design to account for the potential of diel cycles, or at a minimum, be recognized as a component of the river dynamic and the potential consequences that diel cycles may have in data interpretation and river management decisions.


In this thesis, a new digitally tunable UWB pulse generator for an impulse type of pulse generator is developed. The pulse generator is realized with a low cost simple circuitry by using Step Recovery Diode (SRD), PIN diodes and microstrip transmission lines which are employed in the many basic UWB pulse generation circuits. During the pulse generation process, the generator initially generates sharp edges by using a Step Recovery Diode (SRD) from an applied low frequency input sinusoidal signal, and then the sharp edges are converted into short pulses with desired durations by utilizing parallel short-circuited stub with variable lengths. These variable length stubs are acquired by PIN Diodes and microstrip transmission line sub-sections. By adjusting the lengths of the microstrip transmission line, variable duration UWB pulses can be obtained. Also by controlling stub with the N sub-sections digitally, 2N variable duration UWB pulses can be obtained that is a significant improvement in UWB pulse generation. The digitally tunable UWB pulse generator has been designed, implemented during the studies by using microstrip line technology and yielded reasonable performance. Typical pulse durations varying from 550 to 1750 psec and from 900 to 2500 psec have been obtained experimentally for 2-bit and 4-bit pulse generator, respectively. Experimental results are also duplicated using simulations based on Agilent Advance Design System (ADS) platform.


Citizens who share close, important relationships with non-citizens often face significant obstacles if they wish to continue these relationships on a permanent basis within the United States. In order to lawfully immigrate to the United States, non-citizen loved ones must fit within one of the narrowly defined admission categories established by the Immigration and Nationality Act. The majority of individuals able to immigrate can do so because they share relationships with United States citizens that render them eligible under the "family reunification" admission category. Unfortunately, immigration law's definition of family includes only relationships that could fit within the "traditional family unit." Thus, many citizens find themselves unable to reunite with the people they value most. This Article proposes adding a new category to immigration law's current family reunification scheme. The "Plus One Policy" would allow an adult United States citizen to sponsor one important individual in her life who does not fit within any of the pre-existing family reunification provisions. The Plus One Policy seeks to supplement the current purely "bounded model" of family reunification, in which the government categorically decides which relationships are most valuable to its citizens, with an "autonomous model," whereby citizens decide for themselves which relationships they value most. Not only would such a model demonstrate that the United States recognizes and respects the wide variety of domestic and global conceptions of family, it would also further the humane and practical goals of family reunification law.


Due to the recent power events in Texas, power forecasting has been brought national attention. Accurate demand forecasting is necessary to be sure that there is adequate power supply to meet consumer's needs. While Texas has a forecasting model created by the Electricity Reliability Council of Texas (ERCOT), constant efforts are required to ensure that the model stays at the stateof-the-art and is producing the most reliable forecasts possible. This research seeks to provide improved shortand medium-term forecasting models, bringing in state-of-the-art deep learning models to compare to ERCOT's forecasts. A model that is more accurate than ERCOT's own models during certain time periods was found. To have the most accurate energy forecasts in Texas, it is recommended that ERCOT investigate using different models in their Coast, Far West, North, North Central and West zones specifically. No models produced in this analysis accurately predicted the actual load that the state experienced during Winter Storm Uri due to the predicted load exceeding the practical grid capacity given the extreme weather. Synthetic data that simulates these types of extreme weather events could aid in training models for prediction in the future.


As a sport that partly owes its existence to the issue of 'broken time', the working life of professional players outside the game is a highly symbolic issue in rugby league. In England financial reality meant that until the 1990s most players at professional level had to combine their career with full time employment away from the sport, often in the communities they represented on the field. To many this helped create a strong communal bond between those who played and watched rugby league and this perception has become a key cultural narrative in the sport's 'collective' memory. This article uses individual narratives from oral history interviews which relate to the working life of professional players outside rugby league to examine the contention advanced by the sociologist Maurice Halbwachs and others that recollections of personal experience are always shaped to fit within the accepted public discourse. A wide range of personal testimonies are considered in order to illustrate how far, as some oral historians have argued, individuals are able to reflect upon the significance of shared experiences in ways which offer alternative perspectives to dominant cultural scripts.


Electronic correlation energies from the random-phase approximation converge slowly with respect to the plane wave basis set size. We study the conditions under which a short-range local density functional can be used to account for the basis set incompleteness error. Furthermore, we propose a one-shot extrapolation scheme based on the Lindhard response function of the homogeneous electron gas. The different basis set correction methods are used to calculate equilibrium lattice constants for prototypical solids of different bonding types.


This paper develops a dynamic, stochastic, general-equilibrium model to analyze and derive simple budget rules in the face of volatile public revenue from natural resources in a low-income country like Niger. The simulation results suggest three policy lessons or rules of thumb. When a resource price change is positive and temporary, the best strategy is to save the revenue windfall in a sovereign fund and use the interest income from the fund to raise citizens' consumption over time. This strategy is preferred to investing in public capital domestically, even when private investment benefits from an enhanced public capital stock. Domestic investment raises the prices of domestic goods, leaving less money for government to transfer to households; public investment is not 100 percent effective in raising output. In the presence of a negative temporary resource price change, however, the best strategy is to cut public investment. This strategy dominates other methods, such as trimming government transfers to households, which reduces consumption directly, or borrowing, which incurs an interest premium as debt rises. In the presence of persistent (positive and negative) shocks, the best strategy is a mix of public investment and saving abroad in a balanced regime that provides a natural insurance against both types of price shocks. The combination of interest income from the sovereign fund, transfers to households, and output growth brought about by public investment provides the best protective mechanism to smooth consumption over time in response to changing resource prices.


We examine Kreps' conjecture that optimal expected utility in the classic Black–Scholes–Merton (BSM) economy is the limit of optimal expected utility for a sequence of discrete‐time economies that "approach" the BSM economy in a natural sense: The nth discrete‐time economy is generated by a scaled n‐step random walk, based on an unscaled random variable ζ with mean 0, variance 1, and bounded support. We confirm Kreps' conjecture if the consumer's utility function U has asymptotic elasticity strictly less than one, and we provide a counterexample to the conjecture for a utility function U with asymptotic elasticity equal to 1, for ζ such that E[ζ3]>0 .


Background: Studies have indicated a relationship between hypertension and cognitive function. The possible effect of antihypertensive therapy on cognitive disorders is therefore a matter of interest. Materials and methods: The Observational Study on Cognitive function And SBP Reduction (OSCAR) was an open-label, multinational trial designed to evaluate the impact of eprosartan-based antihypertensive therapy on cognitive function in patients with essential hypertension. Eprosartan 600 mg/day for 6 months (with provision for additional medication as needed) was initiated in hypertensive subjects aged $ 50 years. A total of 853 patients in an intention-to-treat cohort from seven countries of the Middle East was identified for subgroup analysis. Results: Arterial blood pressure was reduced significantly ( P , 0.001) during the study: At the end of 6 months of eprosartan-based therapy, the mean ( ± SD) reduction from baseline was 32.1 ± 14.3/14.6.3 ± 8.6 mmHg ( P , 0.001). Mean pulse pressure was reduced by 18.3 ± 13.1 mmHg ( P , 0.0001 vs baseline). Blood pressure was normalized (systolic , 140 mmHg and diastolic , 90 mmHg) in 68.2% of patients. The overall mean Mini-Mental State Examination (MMSE) score after 6 months of eprosartan-based therapy was one-point higher than at baseline ( P , 0.001). MMSE score on completion of 6 months' follow-up was either unchanged or increased from baseline in 793 (93%) individuals and decreased in 60 (7%). Factors associated with stability of or improvement in cognitive function included MMSE score at baseline, diastolic blood pressure (DBP) at baseline, and treatment-induced change in DBP. Conclusion: Results from the Middle East subgroup of OSCAR are supportive of the hypothesis that antihypertensive therapy based on angiotensin-receptor blocker therapy with eprosartan may be associated with preservation or improvement of cognitive function.


The genus Micranthus (Pers.) Eckl., has traditionally been treated as comprising three species, all with virtually identical, bilaterally symmetric, deep or pale blue to white flowers arranged in crowded, 2-ranked spikes and with divided style branches, but differing in their foliage. Examination of plants in the field and herbarium shows that there are four additional species. M. filifolius Goldblatt & J.C.Manning, from the Caledon District of the southwestern Western Cape, has up to six, filiform leaves, the blades of at least the lowermost terete and cross-shaped in section, and usually pale blue-mauve flowers. M. simplex Goldblatt & J.C.Manning from high elevations on Zebrakop, Piketberg, has the smallest flowers in the genus, white but tinged lilac as they age, linear leaves up to 1.5 mm wide, and undivided style branches. M. cruciatus Goldblatt & J.C.Manning, from the northern Cedarberg and Bokkeveld Mtns, has up to four leaves, the lower with linear or terete blades with heavily thickened margins and central vein and relatively large flowers, unusual in having the style dividing at the mouth of the perianth tube into particularly long branches, these deeply divided as is typical of the genus. M. thereianthoides Goldblatt & J.C.Manning, from the Paardeberg south of Malmesbury, is unique in the genus in having flowers with an elongate perianth tube. We also document the occurrence of large populations of putative hybrids at some sites. We provide a complete revision of Micranthus with original observations on leaf anatomy, pollen morphology and reproductive biology and discuss its confused taxonomic and nomenclatural history and that of the three common species of the genus, known for over 150 years. In so doing, we neotypify Gladiolus alopecuroides L. (1756) [= Micranthus alopecuroides (L.) Eckl. (1827)], type of the genus, and choose lectotypes for M. plantagineus Eckl. var. junceus Baker (1892) and Gladiolus fistulosus Jacq. Now with seven species, Micranthus remains endemic to the Cape flora region, extending from its extreme northern limit in the Bokkeveld Mtns south-eastwards to Port Elizabeth. We also deal with the genera Paulomagnusia Kuntze and Beilia Kuntze with which Micranthus has sometimes been associated, although both are nomenclatural synonyms of Thereianthus G.J.Lewis, a genus close allied to Micranthus .


The success of transplantation of the urinary bladder en bloc with pediatric kidneys remains undetermined. We transplanted a large portion of the bladder with en bloc kidney allografts from a 13‐month‐old donor into a 45‐year‐old adult male. The recipient, who was on long‐term hemodialysis, had a small urinary bladder consistent with long‐standing anuria. Informed consent was given and bilateral kidneys were transplanted en bloc with both ureters and bladder. The patient's bladder was augmented with the donor bladder and bilateral ureteroneocystotomies of small ureters was avoided. At 3 and 18 months post‐transplantation, cystoscopies revealed a viable bladder with new vessels and normal donor bladder. Cystogram revealed no reflux. The bladder segment was reperfused via blood supply from both ureters and then from the recipient's bladder. It seems that bladder transplantation en bloc with pediatric kidneys is a viable option for augmentation of a small recipient bladder that allows avoidance of very small bilateral ureteroneocystotomies.


The effectiveness of vibrational energy in promoting dissociation of molecules colliding with surfaces can be measured through the so-called vibrational efficacy. It is thought by many to be a pure "energetic" measure and therefore believed to be limited from below by zero (in the case that there is no increase in dissociation probability upon vibrational excitation) and from above by one (in the case that all of the vibrational excitation energy is used to promote reaction). However, the quantity vibrational efficacy is clearly linked to the detailed dynamics of the system, and straightforward considerations lead to the conclusion that it is not limited either from below or above. Here we discuss these considerations together with a quasiclassical dynamics study of a molecule-surface system, N(2)/Ru(0001), for which a vibrational efficacy bigger than one has been found both experimentally and theoretically. We show that an analysis of the vibrational efficacy only in terms of energy transfer from vibration to translation can be too simple to describe the behavior of systems for which the potential energy surfaces present (high) reaction barriers, potential corrugation and anisotropy, and curved reaction paths.


Less attention has been paid for the effects of surfactant on the hydrolysis of chitosan. This paper presents the influence of the surfactant Tween 80 addition on the chitosan hydrolysis catalyzed by cellulase enzyme. The hydrolyzed chitosan was characterized by measuring its reducing sugar content, its chemistry by Fourier transforms infrared spectroscopy (FTIR), its formation of aldehyde groups by ultraviolet visible spectra (UV-Vis), and its crystallinity degree by X-ray diffraction (XRD). The results showed that Tween-80 could increase the hydrolysis rate and decrease the crystallinity of chitosan. The formation of reducing sugar increased by increasing reaction time up to 24 hours and then leveled off. A more significant effect of surfactant was observed when the hydrolysis was performed at a low surfactant concentration and a low substrate concentration. IR spectra showed that both raw and hydrolyzed chitosan have similar chemical structure.


Since becoming a nation-state in 1970, Oman's expanding heritage industry has included the restoration of castles and citadels, including the fort at Nizwa. The fort was once the administrative and juridical center of the Ibadi Imamate (1913–58). As the site of sharia adjudication, it sanctioned a past of primarily moral nature, oriented toward God and salvation and grounded in Ibadi doctrine and practice. This mode of history implied that everyday interactions and relationships could be assessed through exemplary forms of morality, as embodied by virtuous forbears. Yet the heritage project in modern Oman has treated history and Islam as seemingly separate, erasing formal awareness of the sociopolitical and ethical relationships that once characterized Ibadi rule. Today, the historical work done by the fort as a heritage site entails a progress-oriented future, reconfiguring Ibadi Islam in the process.


This report has been commissioned by Friends of the Earth England Wales and Northern Ireland (FoE) to independently review evidence on key issues relating to the potential new fleet of nuclear power stations that may be built in the UK over the period 2017 to 2030. The report draws primarily on peer-reviewed academic literature although this is supplemented with ?grey? literature from credible government, consultancy and policy sources. It is not an exhaustive review of all the issues and writing concerning civil nuclear power but has a specific scope outlined below (see Annex 1 for full Terms of Reference). Nuclear power is quite unlike both fossil fuels and renewable sources of electricity generation with a particular set of characteristics that may be beneficial or problematic. The main purpose of this report is to provide a succinct appraisal of key issues relevant to the plans for a new generation of reactors in the UK, namely:? safety? radioactive waste disposal? proliferation of nuclear weapons? economics of nuclear power? siting and planning of low carbon generation? employment ? issues in managing a low carbon grid? interactions between nuclear power and other low carbon technologiesThese issues are presented in separate sections as reviews of existing primary research and not as new research findings. The penultimate section, Chapter 11, presents new work by Tyndall Manchester on the carbon dioxide emissions implications of using gas rather than building a new series of nuclear power stations. We calculate the emissions output if the shortfall in electricity generation were to be met by the use of combined cycle gas turbines (CCGT). Alternative renewable energy sources are not considered as their direct emissions are negligible and similar to those from nuclear stations. A range of scenarios is presented for different combinations of rates and extent of nuclear construction and the availability and performance of carbon capture and storage technology. This report is intended for detailed consideration by the staff and members of Friends of the Earth and does not include an executive summary. Direct recommendations as to the appropriateness of a new fleet of nuclear stations in the UK have not been made by the authors. It is also important to note that some key aspects are highly contextual and contingent upon future circumstance.


This article describes the results of a research in Information Science field that aimed to verify how System Dynamics could be applied to manage, in a systemic perspective, the information of risk factors in Pension Fund"s assets and liabilities management (ALM) processes. Delphi technique was used to get data and to identify risk factors with two financial managers and actuaries from 20 Brazilian Pension Funds. By system dynamics, system thinking and agent based modelling techniques it was possible to represent factors cause and effect relations in order to get a function of their expenses and the actual and future payments of the retirements. The conclusions propose a methodology combining these three approaches and show some particularities and benefits of system dynamics to model financial and actuarial assumptions in such organizations and in Information Science research.


OBJECTIVE
To study the regulation role of with neutral property to cAMP-PKA pathway in the rats with cold and heat blood stasis syndromes and it's mechanism.

METHODS
60 rats were randomly divided into normal control group, model control group, Semen Persicae group, radix salvia miltiorrhiza group, rhizoma chuanxiong group, 12 rats per group. The three herb groups were orally given relative herbs decoction, whose dosages were equal to 10 times the human clinical dose, normal and model control groups were orally given water, 2 times/day, 20 mL/kg, for 7 days. Experiments in rats with cold and heat blood stasis syndromes were carried on respectiverly. In heat blood stasis syndromes, except normal control group, the other groups were intraperitoneally injected 10% carrageenan, 5 mL/kg, 1 times/day, for 3 days;24 hours after the last injection, subcutaneously injected 20% dry yeast suspension, 10 mL/kg. In cold blood stasis syndromes, except normal control group, the other groups were put into fridge, temperature--(18 +/- 2) degrees C, 2 hours/ times, 2 times/day, for 7 days. Separately draw 5 ml abdominal aortic blood and taken abdominal aorta, 6 hours and 12 hours after finishing the model in the two syndromes. Tested the cAMP content by elisa, tested the PKA protein expression by Western blot.

RESULTS
Semen Persicae with neutral property, could decrease the content of cAMP in plasma (P < 0.01), inhibit the expression of protein PKA (P < 0.05) in rats with heat stagnation and blood stasis syndrome, increase the plasma content of cAMP (P < 0.01) and increase the expression of protein PKA (P < 0.01) in rats with cold stagnation and blood stasis syndrome. Semen Persicae had two-way adjustment action on CAMP-PKA signal pathway.

CONCLUSION
In different internal environment of heat stagnation and blood stasis syndrome, cold stagnation and blood stasis syndrome, Semen Persicae with neutral property has two-way adjustment to cAMP-PKA signaling channel, which may be one of the mechanism of it's two-way application.


It has been generally hypothesized that habituation mediates the effects of pheromone‐based disruption strategies used in the management of moth pests. The current study demonstrates that pheromone‐mediated sexual response in the tobacco budworm moth, Heliothis virescens (F.) (Lepidoptera: Noctuidae), can in fact be modulated by conditions consistent with the production of habituation. An ethogram was used to measure response strength in a wind tunnel experiment where male moths were allowed to respond freely to one of two different blends of female pheromone in 16 trials over 4 days. Post‐test measures were collected to investigate stimulus specificity and long‐term effects. In conditions appropriate to the formation of habituation, habituation will develop and disrupt male sexual response to female sex pheromone. Males repeatedly exposed to plumes of synthetic pheromone blends display a habituated response lasting up to 96 h. Habituation rate and spontaneous recovery of response strength are greater with less intense stimuli. Additionally, males habituated to one blend express no habituation of sexual response when exposed to a different blend. This indicates a high degree of stimulus specificity, which could facilitate outbreeding, and that moths attend to the configuration of the pheromone blend, not simply to its elements.


Novel rGO–KTaO3 composites with various graphene content were successfully synthesized using a facile solvothermal method which allowed both the reduction of graphene oxide and loading of KTaO3 nanocubes on the graphene sheets. The as-prepared photocatalysts were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM) with energy dispersive X-ray analysis (EDX), Fourier transform infrared spectroscopy (FT-IR), Brunauer–Emmett–Teller (BET) specific surface area, X-ray photoelectron spectroscopy (XPS), thermogravimetric analysis (TGA), UV-Vis diffuse reflectance spectroscopy (DRS) and photoluminescence (PL) emission spectroscopy. The obtained rGO–KTaO3 composites showed greatly improved photocatalytic performance for degradation of phenol under visible light irradiation (λ > 420 nm) over pristine KTaO3 which could be related to the photosensitizer role of graphene in the rGO–KTaO3 composites as well as the formation of p–n heterojunctions between KTaO3 nanocubes and rGO sheets. The highest photocatalytic activity in phenol degradation reaction was observed for rGO–KTaO3 hybrid with 30 wt% graphene. The enhanced photoactivity of this composite could be attributed to the synergistic effect of several factors such as: small crystallite size, extended absorption range in the visible spectrum and intimate contact between graphene and KTaO3 cubes.


Neascus -type metacercariae in Geophagus brasiliensis (Perciformes: Cichlidae) of Peixe river, Juiz de Fora, Brazil. Neascus -type metacercariae, which cause the black spot disease, are described in specimens collected from 33 samples of Geophagus brasiliensis from the Peixe river, in Monte Verde, Juiz de Fora, state of Minas Gerais, Brazil, during March and May 2006. The main morphological features of these metacercariae are: genital primordia composed of three cell masses located in the hind body, and a median dorsal vessel of the reserve bladder around the acetabulum. Thirty fish specimens (90.9%) were parasitized by metacercariae, with mean infection intensity of 15.6 ± 16.1 (1-75). Also, a positive correlation was detected between G. brasiliensis total length and the parasite abundance (r = 0.459; p < 0.01).


Objective: The purpose is to determine some clinical features of self-injurious behavior, family functions and self-esteem in self-injurious adolescents in comparison to a control group. Apart from that, one purpose is to evaluate the relationships between self-esteem and some clinical features regarding self-injurious behavior in the case group. Methods: A group of 70 adolescents with self-injurious behavior who admitted to the child and adolescent psychiatry outpatient clinic were included in the study as well as another group of 70 adolescents with similar age and gender distribution to the case group who does not have self-injurious behavior. Self-Injurious Behavior Information Form, Piers-Harris Children\'s Self-Concept Scale and Family Assessment Device are applied to both the case and control groups. Results: The present study suggests that low self-esteem, unhealthy family functions and smoking are independent risk factors for self-injurious behavior. It has been found out that the adolescents who injure themselves more frequently and more seriously in the case group have lower self-esteem. It has been found out that the presence of self-injurious family member or friend does not create a significant difference in the Piers-Harris Children\'s Self-Concept Scale total point average of the adolescents in the case group. Besides, it has been revealed that alcohol consumption and smoking in the adolescents in the case group do not create a significant difference in the Piers-Harris Children\'s Self-Concept Scale total point averages. Discussion: There is a need for studies that assess the main factors related to the association of self-injurious behavior with smoking and self-esteem, and that determine the direction of causality between them. In our study, the findings that are related to family functions seem to suggest that self-injurious behavior in adolescents might be related to unhealthy family environment. This finding shows the importance of assessing family functions along with the characteristics of the adolescent and the family.


Abstract. We derive trends and monthly anomalies in global and regional sea-level and solid-earth deformation that result from mass redistribution observed by GRACE and an ensemble of GIA models. With this ensemble, we do not only compute mean changes, but we also derive uncertainty estimates of all quantities. We find that over the GRACE era, the trend in land mass change has led to a sea-level trend of 1.28–1.82 mm/yr, which is driven by ice mass loss, while terrestrial water storage has increased over the GRACE period, causing a sea-level drop of 0.11–0.47 mm/yr. This redistribution of mass causes sea-level and deformation patterns that do not only vary in space, but also in time. The temporal variations affect GNSS-derived vertical land motion (VLM) observations, which are now commonly used to correct tide-gauge observations. We find that for many GNSS stations, including GNSS stations in coastal locations, solid-earth deformation resulting from present-day mass redistribution causes trends in the order of 1 mm/yr or higher. Since GNSS records often only span a few years, these trends are generally not representative for the tide-gauge records, which often span multiple decades, and extrapolating them backwards in time could cause substantial biases. To avoid this possible bias, we computed trends and associated uncertainties for 8228 GNSS stations after removing deformation due to GIA and present-day mass redistribution. With this separation, we are able to explain a large fraction of the discrepancy between observed sea-level trends at multiple long tide-gauge records and the reconstructed global-mean sea-level trend from recent reconstructions.


Coal Bottom Ash (CBA) is the waste material produced by coal-based power plants, particularly in Malaysia around 1.7 million tons of CBA was produced annually, which is major environmental concern. Therefore, the use of CBA as a partial replacement of cement in concrete is a possible solution for that pollution; this approach also creates a new corridor in the field of concrete production. However, this study aims to evaluate the effects of CBA as cementitious material on the concrete properties. This study incorporated 10% CBA as a cement replacement by weight method in concrete. However, concrete samples were prepared with and without CBA and immersed in water for 7, 28, 56 and 90 days. Next, the performances of concrete with and without CBA were evaluated in terms of workability, compressive strength, and rapid chloride permeability test. It was found that due to presence of CBA in concrete, workability reduces; no substantial growth in compressive strength at the early ages but substantial rise in strength was noticed after 56 days. Almost 4.7% higher strength was recorded than the control specimens at 90 days. Besides that, concrete containing CBA has lower chloride penetration as compared to the control specimen, which shows its better durability performance. It can be concluded that CBA has an enormous potential to be utilized as a cementitious material in durable concrete production.


As the use of fiber-reinforced polymer-matrix composites gains momentum in automotive designs, there is a need to characterize the composite properties at low strain rates, such as below 100/s. In performing such low strain rate tests, the commonly used split Hopkinson's pressure bar for high strain rates should become overqualified. A high-speed hydraulic testing machine may be suitable for the low strain rate testing. However, due to its high cost, it is not necessarily available to general laboratories. Based on a conventional drop weight impact tester (DWIT), this study presents an affordable testing technique for characterizing a glass woven composite at low strain rates, such as up to 100/s.


Problem statement: The activated sludge system is a complex dynamic process and must account for a large number of reactions between large numbers of components. There is necessity for simulation models which describe the dynamic behavior of the activated sludge process. The application of the models in most treatment plants is limited due to lack of appropriate data acquisition and parameters identification studies. To realize this, an improvement of the operating strategies of Waste-Water Treatment Plants (WWTP) is required. The objectives of this study were to: (i) To build a process model considering mass transfer limitations and simulate an existing plant (Helwan WWTP) and validate the results using data from another existing plant with (Zenine WWTP). (ii) To adjust the model kinetic parameters of the biochemical reactions under the effect of mass transfer conditions to be prepared for simulation purposes. (iii) Study the effect of the operating conditions on the removal efficiency of both substrate and ammonia. Approach: A process model of the process was built considering mass transfer limitations and the three growth processes: Carbon oxidation, nitrification and denitrification. Helwan WWTP was used in order to extract the suitable stoichiometric and kinetic parameters to be used for the simulation. Helwan WWTP was used through the simulation results of the substrate (BOD) and ammonia. Egyptian Zenine WWTP was used for the testing and validation of the process model through predicting the response of substrate. Results: The average error of the removal efficiency in Helwan WWTP reached 3.3% for the substrate and 12.5% for the ammonia while the average error of the removal efficiency in Zenine WWTP of substrate reached 4.6%. The effects of recycle ratio, flow rate and influent substrate concentrations on the removal efficiency of the aeration tank were studied. It was found that the removal efficiency of substrate and ammonia was increased by increasing the recycle ratio, influent substrate concentrations and also increased by decreasing influent flow rates. It was found also that the sludge age increased by increasing the recycle ratio and decreased by decreasing the influent flow rates. Conclusion: The heterogeneous process model was able to describe the characteristics and reflects the real phenomena existing in activated sludge processes.


. The term 'impact' has become the kind of word which, when it relates to the evaluation of technological advances in contemporary culture, suggests signs of erosion, debilitation and evasion. The misinformed and in-discriminate use of the term in the most varied of contexts has created an impasse in the cultural semiotic approach, where sign systems are viewed in terms of borders and relations. The objective of this article is to examine the trivialisation of the use of the ballistic metaphor in this explosive moment of the culture. For this, we will refer to the formulations presented by the semiotician, Juri Lotman, in his book, appropriately entitled Culture and Explosion . To what degree is the concept of explosion presented as a counterpart to the notion of impact? The desire to find answers to this question is what moti-vated this inquiry.


A prototype resistive superconducting fault current limiter (SFCL) was developed using single-strand round magnesium diboride (MgB2) wire. The MgB2 wire was wound with an interleaved arrangement to minimize coil inductance and provide adequate inter-turn voltage withstand capability. The temperature profile from 30 to 40 K and frequency profile from 10 to 100 Hz at 25 K were tested and reported. The quench properties of the prototype coil were tested using a high current test circuit. The fault current was limited by the prototype coil within the first quarter-cycle. The prototype coil demonstrated reliable and repeatable current limiting properties and was able to withstand a potential peak current of 372 A for one second without any degradation of performance. A three-strand SFCL coil was investigated and demonstrated scaled-up current capacity. An analytical model to predict the behaviour of the prototype single-strand SFCL coil was developed using an adiabatic boundary condition on the outer surface of the wire. The predicted fault current using the analytical model showed very good correlation with the experimental test results. The analytical model and a finite element thermal model were used to predict the temperature rise of the wire during a fault.


In this paper we describe small case study exploring how four elementary students with mathematics learning disabilities utilized mobile technology (the eWorkbook) during core math instruction in a general education setting.  The lead author designed the eWorkbook intervention to provide a flexible learning experience optimized for diverse learners.  Sophisticated video coding software was used to map the actions of the students as they engaged with the tool during the independent practice portion of math instruction.  Results related to engagement, independence, accuracy, and specific affordances and barriers to learning with mobile technology are reported.


Many small businesses closed in the pandemic, but were economic losses disproportionately felt by businesses owned by people of color? This paper provides the first study of the impacts of COVID‐19 on racial inequality in business earnings. Pandemic‐induced losses to business earnings in 2020 were 16% to 19% for all business owners. Racial inequality increased in the pandemic: Black business owners experienced larger negative impacts on business earnings of 12% to 14% relative to White business owners. Regression estimates for Latinx and Asian business owners reveal negative point estimates but the estimates are not statistically significant. Using Blinder‐Oaxaca decompositions and a new pandemic‐focused decomposition technique, I find that the industry concentrations of Black, Latinx, and Asian business owners placed each of these groups at a higher risk of experiencing disproportionate business earnings losses in the pandemic. Higher education levels among Asian business owners helped insulate them from larger losses from COVID‐19. In the following year of economic recovery, 2021, business earnings rebounded strongly for all groups except for Asian business owners, who experienced large relative losses (which were partly due to industry concentrations). State‐level variation in policies and disease spread does not explain racial differences in business earnings losses or rebounds.


Transcripts produced after injection of the Xenopus 5S RNA gene into oocyte germinal vesicles of mice migrate electrophoretically with the 5S RNA marker, an indication that the gene is transcribed and processed with considerable accuracy. Approximately two 5S RNA molecules are transcribed per gene per hour. This system may be useful in studying DNA processing and gene regulation by the mammalian ovum and might be modified to allow permanent incorporation of specific genes into mice.


As Unmanned Aerial Vehicles (UAVs) become increasingly available, pose estimation remains critical for navigation. Pose estimation is also useful for scene reconstruction in certain surveillance applications, such as surveillance in the event of a natural disaster. This thesis presents a Direct Sparse Visual-Inertial Odometry with Loop Closure (VIL-DSO) algorithm design as a pose estimation solution, combining several existing algorithms to fuse inertial and visual information to improve pose estimation and provide metric scale, as initially implemented in Direct Sparse Odometry (DSO) and Direct Sparse Visual-Inertial Odometry (VI-DSO). VIL-DSO utilizes the point selection and loop closure method of the Direct Sparse Odometry with Loop Closure (LDSO) approach. This point selection method improves repeatability by calculating the Shi-Tomasi score to favor corners as point candidates and allows for generating matches for loop closure between keyframes. The proposed VIL-DSO then uses the Kabsch-Umeyama algorithm to reduce the effects of scaledrift caused by loop closure. The proposed VIL-DSO algorithm is composed of three main threads for computing: a coarse tracking thread to assist with keyframe selection and initial pose estimation, a local window optimization thread to fuse Inertial Measurement Unit (IMU) information and visual information to pose scale and pose estimate, and a global optimization thread to identify loop closure and improve pose estimates. The loop closure thread also includes the modification to mitigate scale-drift using the Kabsch-Umeyama algorithm. The trajectory analysis of the estimates yields that the loop closure improves the pose estimation, but causes to scale estimate to drift. The scale-drift mitigation method successfully improves the scale estimate after loop closure. However, the estimation error level struggles to exceed the other state-of-the-art methods, namely VI-DSO and VI-ORB SLAM. The results were evaluated on the EuRoC MAV dataset, which contains fairly short sequences. VIL-DSO is expected to show more advantages when used on a longer dataset, where loop closure is more useful. Lastly, using the odometry as a feed, scene reconstruction and the effects of various factors regarding mapping are discussed, including the use of a monocular camera, camera angle and resolution in outdoor settings.


We consider a sensor scheduling problem where the sensors have multiple choices of communication channel to send their local measurements to a remote state estimator for state estimation. Specifically, the sensors can transmit high-precision data packets over an expensive channel or low-precision data packets, which are quantized in several bits, over some cheap channels. The expensive channel, though being able to deliver more accurate data which leads to good estimation quality at the remote estimator, can only be used scarcely due to its high cost (e.g., high energy consumption). On the other hand, the cheap channel, though having a small cost, delivers less accurate data which inevitably deteriorates the remote estimation quality. In this work we propose a new framework in which the sensors switch between the two channels to achieve a better tradeoff among the communication cost, the estimation performance and the computational complexity, where the two-channel case can be easily extended to a multiple-channel case. We propose an opportunistic sensor schedule which reduces the communication cost by randomly switching among the expensive and cheap channels, and in the meantime maintains low computational complexity while introducing data quantization into the estimation problem. We present a minimum mean square error (MMSE) estimator in a closed-form under the proposed opportunistic sensor schedule. We also formulate an optimization problem to search the best opportunistic schedule with a linear quantizer. Furthermore, we show that the MMSE estimator in the limiting case becomes the standard Kalman filter.


This paper examines the welfare implications of alternative rule-based fiscal policies in an economy with financially-constrained households. Using a New Keynesian DSGE model of a multi-sectoral small and open commodity-exporting economy, we find that adopting a welfare-maximizing fiscal policy involves an actively countercyclical response to the tax revenue gap and a procyclical response to international commodity prices. Transitioning from a procyclical stance to the optimized rule regarding the tax revenue gap leads to welfare gains of approximately 1.5% and 0.1% of permanent consumption for Non-Ricardian and Ricardian consumers, respectively. Moreover, moving from a countercyclical stance to the optimized rule concerning the commodity revenue gap results in 1% and 0.02% larger welfare gains for Non-Ricardian and Ricardian consumers, respectively. In terms of implementation, social transfers are the best instrument to implement the fiscal rule, yielding higher welfare gains, lower macroeconomic volatility, and only moderate fluctuations in government spending.


Two gradations of asphalt mixtures were conducted to short term and long term aging tests. And then, static creep test was implemented on the samples of mixture. According to creep compliance curves from the stress-strain relations, Burgers viscoelastic model parameters were got to analyze the influences of aging effect on the viscoelastic response of asphalt mixture. The results and analysis indicated that aging is an important reason introducing viscoelasticity changes of asphalt mixture. For aged asphalt mixtures, the stiffness increases, the flexibility declines, the instantaneous elastic and the viscous compliance decrease. But short-term aging and long-term aging have different effects. And the viscoelastic parameters of the asphalt mixture with large voids vary more significantly, so aging process is much faster.


X-linked lymphoproliferative disease (XLP) is a rare primary immunodeficiency characterised by severe immune dysregulation and is caused by mutations in the SH2D1A gene. Clinical manifestations vary and include haemophagocytic lymphohistiocytosis (HLH), lymphoma and dysgammaglobulinaemia, often triggered by Epstein-Barr virus (EBV) infection. SLAM-associated protein (SAP) is a key regulator of immune function in T, NK, and NKT cells and defects in this protein lead to the cellular and humoral immune defects described in patients. Treatment options for XLP are limited and currently haematopoietic stem cell transplant (HSCT) is the only curative option. Results are variable and dependent on a good donor match and absence of active infection at transplant. Somatic gene therapy is now successfully used to correct certain severe immunodeficiencies and offers a potential cure in XLP. The use of self-inactivating (SIN) lentiviral vectors with transgene expression driven by non-viral promoters has improved the biosafety profile of haematopoietic stem cell gene therapy procedures. In this study we have successfully corrected both cellular and humoral defects in a SAP deficient murine model using a SIN lentiviral vector with a codon optimised SAP transgene under the transcriptional control of the elongation factor 1α short form (EFS) promoter. Initial attempts with a non-codon optimised version of SAP led to insufficient protein expression levels to restore immune function. We also assessed the CD2 locus control region (LCR) to evaluate any lymphoid specificity to permit more regulated SAP expression but were unable to demonstrate any benefit with this regulatory element. The results presented here provide proof of concept for the development of gene therapy for XLP and further work is warranted to improve the efficiency of gene transfer, secure engraftment of long term repopulating haematopoietic stem cell progenitors and additional characterisation of immune reconstitution after gene therapy.