Studies indicate that more than 90% of human genes are alternatively spliced, suggesting the complexity of the transcriptome assembly and analysis. The splicing process is often disrupted, resulting in both functional and non-functional end-products (Sveen et al. 2016) in many cancers. Harnessing the immune system to fight against malignant cancers carrying aberrantly mutated or spliced products is becoming a promising approach to cancer therapy. Advances in immune checkpoint blockade have elicited adaptive immune responses with promising clinical responses to treatments against human malignancies (Tumor Neoantigens in Personalized Cancer Immunotherapy 2017). Emerging data suggest that recognition of patient-specific mutation-associated cancer antigens (i.e. from alternative splicing isoforms) may allow scientists to dissect the immune response in the activity of clinical immunotherapies (Schumacher and Schreiber 2015). The advent of high-throughput sequencing technology has provided a comprehensive view of both splicing aberrations and somatic mutations across a range of human malignancies, allowing for a deeper understanding of the interplay of various disease mechanisms. Meanwhile, studies show that the number of transcript isoforms reported to date may be limited by the short-read sequencing due to the inherit limitation of transcriptome reconstruction algorithms, whereas long-read sequencing is able to significantly improve the detection of alternative splicing variants since there is no need to assemble full-length transcripts from short reads. The analysis of these high-throughput long-read sequencing data may permit a systematic view of tumor specific peptide epitopes (also known as neoantigens) that could serve as targets for immunotherapy (Tumor Neoantigens in Personalized Cancer Immunotherapy 2017). Currently, there is no software pipeline available that can efficiently produce mutation-associated cancer antigens from raw high-throughput sequencing data on patient tumor DNA (The Problem with Neoantigen Prediction 2017). In addressing this issue, we introduce a R package that allows the discoveries of peptide epitope candidates, which are the tumor-specific peptide fragments containing potential functional neoantigens. These peptide epitopes consist of structure variants including insertion, deletions, alternative sequences, and peptides from nonsynonymous mutations. Analysis of these precursor candidates with widely used tools such as netMHC allows for the accurate in-silico prediction of neoantigens. The pipeline named neoantigeR is currently hosted in https://github.com/ICBI/neoantigeR.


We present a reduction from reinforcement learning (RL) to no-regret online learning based on the saddle-point formulation of RL, by which "any" online algorithm with sublinear regret can generate policies with provable performance guarantees. This new perspective decouples the RL problem into two parts: regret minimization and function approximation. The first part admits a standard online-learning analysis, and the second part can be quantified independently of the learning algorithm. Therefore, the proposed reduction can be used as a tool to systematically design new RL algorithms. We demonstrate this idea by devising a simple RL algorithm based on mirror descent and the generative-model oracle. For any $\gamma$-discounted tabular RL problem, with probability at least $1-\delta$, it learns an $\epsilon$-optimal policy using at most $\tilde{O}\left(\frac{|\mathcal{S}||\mathcal{A}|\log(\frac{1}{\delta})}{(1-\gamma)^4\epsilon^2}\right)$ samples. Furthermore, this algorithm admits a direct extension to linearly parameterized function approximators for large-scale applications, with computation and sample complexities independent of $|\mathcal{S}|$,$|\mathcal{A}|$, though at the cost of potential approximation bias.


Humanitarian, development and peacebuilding work has become increasingly
 dangerous in recent decades. The securitisation of aid has been critiqued,
 alongside the racialised and gendered dynamics of security provision for aid
 actors. What has received less attention is how a range of intersectional
 marginalisations – gender, racialisation, sexuality, nationality and
 disability – play out in constructions of security, danger and fear in
 aid deployments. Focusing on sexual harassment, abuse and violence as threats to
 safety and security, the article examines how in training and guidance for
 deployment to 'the field' (itself a problematically securitised
 notion), danger is projected onto sexualised and racialised
 'locals', often overlooking the potentially far greater threat
 from colleagues. Here, we employ a review of security guidance, social media
 groups, interviews with aid staffers and reflections on our own experiences to
 explore how colonialist notions of security and 'stranger danger'
 play out in training. We argue that humanitarianism is still dominated by the
 romanticised figure of the white, male humanitarian worker – even if this
 problematic imaginary no longer reflects reality – and a space where
 those questioning exclusionary constructs of danger are quickly silenced and
 even ridiculed, even in the age of #MeToo and #BlackLivesMatter.


The Coastal Data Information Program (CDIP) has been collecting data on ocean wave conditions since late 1975, first using arrays of pressure sensors, and more recently directional buoys. Fourier analysis of the data reveals the spectral and directional content of the wave-driven motions measured by the buoy. Shifting the spectrum to an audible range and synthesizing a time-domain signal creates an aurally interesting and illuminating sonification of ocean wave dynamics. The work done so far has been guided by artistic curiosity; but input from a senior oceanographer has given guidance toward interpretation and elaboration of the methodology. Examples of ocean buoy spectral data sonification are presented, each illustrating important aspects of physical oceanography. Three forms of the data are sonified, from the least detailed to the most. The obvious sonic events are the effects of energy from storms, both local and far away. From the sonification one can estimate the energy of the storm, and the distance it originated. Entire years of data have been sonified in one to thirty minute durations for buoys in different regions, which demonstrate dramatic seasonal and regional differences. Also displayed are the time-lags of South moving storm energies at three distantly separated points on the West Coast of the United States.


The greater part of my childhood was spent in Captains Flat, a small mining town in the Monaro District of NSW. The prosperity of the town was short-lived and like so many other communities its inhabitants became victims of the Great Depression in 1929. The Lake George Mining Company that had economically sustained our little community ceased production and the clang of the ore buckets, the shrill call of the mine whistle, that had segmented our lives into day, afternoon and dingo shift, fell silent. Machinery rusted and rotted on the mine lease. Notices threatening any trespasser with prosecution were affixed to the heavy padlocked gate leading onto the mine site. Despondency and hopelessness settled into the hearts of the unemployed, and anyone with the means to do so left the town in search of work. Those who remained behind shared a common, soul-destroying poverty that would persist for many years. Lacking the means to leave our family remained waiting for the good times to return. This journal article is available in Illawarra Unity Journal of the Illawarra Branch of the Australian Society for the Study of Labour History: http://ro.uow.edu.au/unity/vol7/iss1/4


Background: Radiobiological models for normal tissue complication probability (NTCP) are more and more commonly used in order to estimate the clinical outcome of radiation therapy. A normal tissue complication probability model to be considered a good and reliable one should fulfill the following two requirements: (a) it should predict the sigmoid shape of the dose-response curve as well as possible and (b) it should duly handle the volume effect. In the work from 2005 (IJROBP 61(3):892-900, 2005) P. van Luijk et al. suggest that none of the existing NTCP models is able to describe the volume effects present in the rat spinal cord during irradiation with small proton beams and they indicate the need for developing such new models.Methods: We have used the experimental data from H. Bijl et al. (IJROBP 52(1):205-211, 2002) to try explaining the change in the fifty percent effective dose (ED50) for different field sizes. We initiated this study to evaluate whether the induction of white matter necrosis in rat spinal cord after irradiation with small proton beams could be explained independent of used NTCP model. We therefore introduced a new concept of effective FSU dose, where a convolution of the original dose distribution with a function describing the effective size of a single FSU results in the average doses in a functional subunit. Such procedure allows determining the ED50 in an FSU of a certain size, within the irradiation field. We have also looked at non uniform dose distributions to see whether using a similar method we can explain the so called "bath and shower experiments" (IJROBP 57(1): 274-281, 2003).Results: Using the least square method to compare the effective doses for different sizes of functional subunits with the experimental data we observe the best fit for about 8 mm length. It seems that this length could be understood as an effective size of functional subunits in rat spinal cord, explaining what is otherwise interpreted as a volume effect. For the non uniform dose distributions an effective FSU length of 5 mm gives the optimal fit with the Probit dose-response model.Conclusions: The concept of an effective FSU length seems to explain at least part of the effects seen when small portions of the rat spinal cord are irradiated. The most likely FSU length for the shower and bath experiments is 5 mm according to these calculations.


The D-Wave 2000Q (www.dwavesys.com) is a physical implementation of the quantum annealing algorithm based on the transverse Ising model. It is built using 2048 superconducting flux qubits operated at a temperature of 10 millikelvin. While much work using the D-Wave 2000Q has focused on the application of the quantum annealing algorithm to attack classical optimization problems, we have recently been investigating its use as a tool for quantum simulation. I will present two experiments using the quantum processor as a quantum simulator. First, we measured a Kosterlitz-Thouless phase transition in a 2D lattice of 1800 qubits, induced by the interplay between quantum fluctuations and geometrical frustration. Second, we studied a prototypical quantum magnetic system, an 8x8x8 cubic lattice of effective Ising spins: by tuning the transverse magnetic field and the degree of disorder, we demonstrate transitions between paramagnetic, antiferromagnetic, and spin glass phases. Finally, I will discuss work on our next generation quantum annealing processor focusing on improved coherence and connectivity. Nanoscience and Quantum Physics


The purpose of this paper is to demonstrate the potential of an electrical signal processing technique to mitigate the effect of intersymbol interference in metro optical networks, using optical coherent detection. Intersymbol interference in fiber-optic systems can severely degrade the system performance and subsequently limit both the maximum transmission distance and data rate. The main sources of intersymbol interference include chromatic dispersion (CD) and polarization mode dispersion (PMD). The typical reach for 10 Gb/s metro optical systems is on the order of 300 km. To bridge this distance either with or without repeaters, we demonstrate the potential use of 10 Gb/s differential phase-shift keying (DPSK) modulation format in conjunction with an optical coherent receiver with a built-in switchable electrical dispersion compensator. The overall performance of the optical coherent receiver is compared with that of the corresponding direct detection (DD) receiver based on Mach-Zehnder delay interferometer. The optical signal-to-noise (OSNR) required to operate the optical coherent receiver at the enhanced forward error correction (EFEC) threshold of 2.1 X 10-3 is 6 dB/0.1 nm resolution bandwidth. The optical coherent receiver outperforms in absolute required OSNR by 0.5 dB at the EFEC threshold when compared to a DD receiver. A four position switchable CD compensator compensates up to ?5100 ps/nm of CD, using the method of heterodyne detection. The optical coherent receiver has a first-order PMD tolerance of 36.2 ps for 1 dB OSNR penalty. The utility of our optical coherent receiver is demonstrated by doing transmission experiments over 304 km of standard single-mode fiber (SSMF) in both repeatered (multiple spans) and repeaterless (single span) to measure the self-phase modulation (SPM) tolerance of 10 Gb/s nonreturn-to-zero (NRZ)-DPSK. The measured SPM tolerance of NRZ-DPSK over 304 km of SSMF in three spans of ~100 km each is +8.8 dBm fiber launch power for 1.5 dB OSNR penalty. In addition, the best Q factor of ~12 dB is obtained for the fiber launch power of +18 dBm over single repeaterless span of 304 km of SSMF, which gives ~3 dB of system margin at the second generation EFEC threshold of 9.1 dB.


Many developing countries face severe challenges with the reliability of water supplies. These supplies are often characterised by intermittence, low pressure and poor water quality. Despite its contribution towards water-related illness and the significant coping burden it imposes on households, water supply reliability remains a difficult attribute to measure. A key challenge is the lack of a universal definition of water supply reliability. The issue of unreliability in water supply and the financial cost it imposes on households is of profound relevance in South Africa – a country whose social policies include a Free Basic Water policy which entitles all households to a free lifeline supply of 6,000 litres per month. This thesis examines household experiences of unreliable water supplies and in particular, explores the question as to what constitutes a reliable water supply, and household responses to unreliable water supplies.
The analysis draws on literature reviews and a household survey conducted in peri-urban communities in the Limpopo Province of South Africa in 2012. A systematic review of definitions and assessment criteria used in studies of water supply reliability demonstrates that there is no consensus on what constitutes a reliable water supply. Assessment criteria also vary greatly, with the most common criterion in urban settings being the duration and/or continuity of supply in hours per day. In rural settings, the proportion of functional water systems is commonly assessed. A discrete choice experiment was conducted to elicit households' preferences for a reliable water supply. Results indicate that overall, households value notification of interruptions and having water available for longer durations during the day, and would be willing to pay for these improvements. However, there is some heterogeneity in these preferences as wealthier households, who have drilled their own wells and are no longer dependant on the public supply are less willing to pay for improvements in the water supply.
Findings from a systematic review of household strategies to cope with unreliability reveal that relatively wealthy households incur significant direct costs from strategies such as drilling wells and installing water storage tanks, poor households expend time and energy in collecting water from other sources. Income, level of education, land tenure and extent of unreliability are the main determinants of which strategies are adopted. Results from the survey in Limpopo highlight that Free Basic Water is not actually free; households spend significant proportions of their income on buying water,
ii
drilling wells and treating the water prior to consumption. Coping costs increase with wealth status and are higher in communities without alternative water sources such as springs. Notably, for many households the lifeline supply of 6,000 litres per month is unmet.
The findings from this thesis highlight the need for consensus on the definition, and assessment approach for water supply reliability. Further, the analysis of households' responses to unreliable water supplies in South Africa draws attention to how poor reliability negates the Free Basic Water policy. Without reliable water supply services, the objectives of improving public health and promoting equity cannot be met.


It is best that the concern of having a healthy child starts before its conception and addresses the health of both parents on the physical, mental and emotional levels. This training will be useful both to the baby— who benefits from the mother's strong and healthy body — and to the parents who will deal with the physical and psycho-emotional changes more easily, since these changes are triggered by pregnancy in both parents.
The homeopathic treatment can be administered both to pregnant and breastfeeding mothers, as well as to newborns. This article provides several ways of homeopathic approach in specific pregnancy disorders, without exhausting the subject since having a treatment individualized by a homeopathic doctor can offer many other recommendations.


Abstract
 Territoriality and the factors that influence the outcome of animal contests are easy to study in a lab using convict cichlid fish (Archocentrus nigrofasciatus). I present a two-week laboratory experiment suitable for high school and college students. In the first week, students observe resident and intruder convict cichlids interacting in the presence of flowerpot territories, allowing them to develop hypotheses about factors that might determine the outcome of contests over resources, including relative size of competitors ("resource holding potential" hypothesis) and ownership ("resource value" hypothesis). They then work with their teacher to design and set up an experiment to test these two hypotheses, providing specific predictions that would support each hypothesis. In the second week, students observe contests between each owner and a larger or smaller intruder. The winner is defined as the individual that spends the most time in the pot and bites more. Students graph their data and decide what statistics are most appropriate for analyzing their results. They determine which hypothesis is supported by their findings and present their findings in scientific paper format.


Heparin is an anticoagulant medicine that prevents the formation of harmful blood clots in the vessels. Following the outbreak of the novel coronavirus disease 2019 (COVID-19), heparin has helped to improve the health of affected patients beyond its anticoagulant effects. The potential antiviral activity of heparin has attracted speculation due to its highly sulfated profile, which allows it to have a high binding affinity to a wide range of viral components. Heparin's successful binding to the ZIKA virus, human immunodeficiency virus, as well as the SARS CoV and MERS CoV spike proteins have demonstrated its potential to inhibit the entry of SARS-CoV-2 into the body. A high degree of sequence homology also enables heparin to have inhibitory binding potential on viral components. The SARS-CoV-2 virus exhibits significant differences in its spike glycoprotein (SGP) sequence compared to other coronaviruses. The SGP sequence in SARS-CoV-2 contains additional potential glycosaminoglycan (GAG) binding domains that may drive differences in the attachment and entry process of the virus. Findings from unbiased computational ligand docking simulations, pseudotyped spike protein experiments, and cell to cell fusion assays have also opened possibilities to investigate the antiviral properties of heparin in clinical trials


Maintenance of bridges is becoming increasingly important in Japan. In the maintenance of bridges, it is necessary to evaluate the current load carrying capacity of a deteriorated structure by the use of design equations or numerical analyses. However, the design drawings are often missing, thereby input parameters such as material properties and internal reinforcement arrangements for the equations and analyses are not available. In such a case, it is necessary and important to determine the input parameters by destructive or nondestructive tests (NDT) or rational judgements and to estimate the load carrying capacity of a deteriorated structure with a rational analytical model. In this study, using NDT results, the structural performance of SRC deep beams is evaluated by FEA, where the evaluation processes are examined as well. Considering that the material properties from NDT has some ranges and may contain errors, their values are adjusted referencing the design of similar beams from some papers and then input for FEA. In terms of concrete, a nonlinear stress-strain relation is employed for compression. Under tension, the concrete is assumed to behave linear elastically before the tensile strength is reached. After that, a linear softening behavior is assumed for cracked concrete. As for steel reinforcements, i.e. embedded I-beam and rebars, the stress-strain relation is assumed as elastoplastic. The steel/concrete interface is regarded as rigidly connected. In addition to FEA, hand calculation using empirical equations is conduced as well to examine the predictions. Finally, the predictions such as internal structure, material properties and load carrying capacity are compared with their corresponding experimental results which have been closed until this step. From this comparison, the employed performance evaluation processes are examined.


The rapidly evolving crisis of antibiotic resistance among microorganisms has contributed to the rise of patient morbidity and mortality from nosocomial and community-acquired infections. Therefore, innovative antimicrobial technology targeting mechanisms to which the bacteria are unlikely to evolve resistance is urgently needed. We have previously described a nitric oxide-releasing nanoparticle (NO-np) with efficacy against methicillin-resistant Staphylococcus aureus (MRSA) and Acinetobacter baumannii in vitro and in murine wound and abscess models. Although the prior findings suggest that the NO-np can be a useful therapeutic for skin and soft tissue infections, the antimicrobial spectrum of NO-np has yet to be fully elucidated. In the current study, we investigated the efficacy of a NO-np against several Gram-positive and -negative clinical isolates. We found that the NO-np were uniformly active against all of the Streptococcus pyogenes, Enterococcus faecalis, Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa clinical isolates examined, including strains that were both sensitive and resistant to commonly used antibiotics. We concluded that the NO-np have the potential to serve as a novel broad spectrum antimicrobial agent.


Firefighters serve as first responders and encounter a wide variety of hazards while performing their job tasks. They also perform an array of movements when responding to emergencies. It is thus critical that their personal protective equipment allow firefighters to perform their duties with minimal limitations and maximum safety. This research explored the issues firefighters experience when wearing their gear to identify areas needing improvement. Researchers conducted focus groups of male firefighters throughout the country to identify areas of concern for firefighters regarding their gear. Data were analyzed using an interpretive thematic analysis method that revealed three main problem areas: gear function, wearer comfort, and protection provided. Specific issues related to these problem areas are discussed, and suggestions are made for ways to improve firefighter gear to enhance the experience of the end user. Findings from this study serve as a guide for future researchers and manufacturers creating new gear, as well as developing enhanced education and training of firefighters regarding their gear.


This issue of Sisyphus draws on work in the research project 'Governing By inspection: school inspection and education governance in England, Scotland and Sweden'. That research seeks to fill a gap in the literature on the governing of education by examining the ways in which inspection regimes may be understood as governing education-in this case in the three national education systems of Sweden, England and Scotland. (...)


During the 19th century, poor and orphan Swedish children were boarded out. The foster-parents' compensation was determined in English auctions. Some children were re-auctioned. We use historical data from such auctions to study whether informational asymmetry and possibly adverse selection affected the outcome in the market for re-auctioned children. The empirical findings are consistent with adverse selection.


A 57-year-old man was directly transported to our emergency department via the emergency medical service. The patient was found lying on the floor after a trauma. The initial chest computed tomography (CT) scan showed a suspicious diaphragm injury (Fig. 1.) with thoracic aortic injury. The trauma team called an intervention radiologist who performed emergency thoracic endovascular aortic repair for aortic rupture. A follow-up abdominal CT scan for liver injury was performed to obtain more detailed information regarding a suspicious diaphragm injury. The herniated liver dome was more prominent (Fig. 2.), and we decided on surgical repair of the injured diaphragm. The patient was sent to the operating room and underwent thoracoscopic examination under double-lumen general endotracheal anesthesia. We found traumatic diaphragm injury and herniation of the liver dome (Fig. 3.). The herniated liver dome was strangulated and had superficial laceration on the surface without active bleeding. We performed a lateral thoracotomy and repaired the injured diaphragm with nonabsorbable sutures in an airtight manner (Fig. 4.). The rightsided traumatic diaphragm injury was found incidentally through serial coronal views of chest and abdomen CT scans for evaluation of multiple severe injuries. The traumatic diaphragm injury was successfully managed through thoracoscopy and lateral thoracotomy under doublelumen general endotracheal anesthesia. The ruptured diaphragm could be tightly repaired without any


The management of urban development projects in the Netherlands has changed significantly in recent years. These projects have become mainly 'led' by developers as they manage the entire life cycle of development projects, while public actors mainly facilitate development projects. This changes the way projects are organized and managed and might resolve in different outcomes. Therefore, this research aims at understanding the roles of public and private actors in private sector-led urban development projects and aims at determining the effects of their cooperation by conducting empirical research in different contexts. This paper provides a method for academic scholars to study the management of urban development projects, as management has been underestimated in theory as a way to influence project outcomes. A conceptual steering model is introduced which provides opportunities to describe, analyze and compare complex urban development cases. Furthermore, empirical findings from case studies in the Netherlands and England are presented and compared with each other to indicate how the conceptual model can be used.


Face information processing relies on the quality of data resource. From the data modality point of view, a face database can be 2D or 3D, and static or dynamic. From the task point of view, the data can be used for research of computer based automatic face recognition, face expression recognition, face detection, or cognitive and psychological investigation. With the advancement of 3D imaging technologies, 3D dynamic facial sequences (called 4D data) have been used for face information analysis. In this paper, we focus on the modality of 3D dynamic data for the task of facial expression recognition. We present a newly created high-resolution 3D dynamic facial expression database, which is made available to the scientific research community. The database contains 606 3D facial expression sequences captured from 101 subjects of various ethnic backgrounds. The database has been validated through our facial expression recognition experiment using an HMM based 3D spatio-temporal facial descriptor. It is expected that such a database shall be used to facilitate the facial expression analysis from a static 3D space to a dynamic 3D space, with a goal of scrutinizing facial behavior at a higher level of detail in a real 3D spatio-temporal domain.


Abstract. We use observations of surface and top-of-the-atmosphere (TOA) broadband radiation fluxes determined from the Atmospheric Radiation Measurement programme mobile facility, the Geostationary Earth Radiation Budget (GERB) and Spinning Enhanced Visible and Infrared Imager (SEVIRI) instruments and a range of meteorological variables at a site in the Sahel to test the ability of the ECMWF Integrated Forecasting System cycle 43r1 to describe energy budget variability. The model has daily average biases of −12 and 18 W m−2 for outgoing longwave and reflected shortwave TOA radiation fluxes, respectively. At the surface, the daily average bias is 12(13) W m−2 for the longwave downwelling (upwelling) radiation flux and −21(−13) W m−2 for the shortwave downwelling (upwelling) radiation flux. Using multivariate linear models of observation–model differences, we attribute radiation flux discrepancies to physical processes, and link surface and TOA fluxes. We find that model biases in surface radiation fluxes are mainly due to a low bias in ice water path (IWP), poor description of surface albedo and model–observation differences in surface temperature. We also attribute observed discrepancies in the radiation fluxes, particularly during the dry season, to the misrepresentation of aerosol fields in the model from use of a climatology instead of a dynamic approach. At the TOA, the low IWP impacts the amount of reflected shortwave radiation while biases in outgoing longwave radiation are additionally coupled to discrepancies in the surface upwelling longwave flux and atmospheric humidity.


Purpose: We investigated the feasibility of detecting aberrant DNA methylation of some novel and known genes in the serum of lung cancer patients. Experimental Design: To determine the analytic sensitivity, we examined the tumor and the matched serum DNA for aberrant methylation of 15 gene promoters from 10 patients with primary lung tumors by using quantitative methylation-specific PCR. We then tested this 15-gene set to identify the more useful DNA methylation changes in the serum of a limited number of lung cancer patients and controls. In an independent set, we tested the six most promising genes (APC, CDH1, MGMT, DCC, RASSF1A, and AIM1) for further elucidation of the diagnostic application of this panel of markers. Results: Promoter hypermethylation of at least one of the genes studied was detected in all 10 lung primary tumors. In majority of cases, aberrant methylation in serum DNA was accompanied by methylation in the matched tumor samples. In the independent set, using a single gene that had 100% specificity (DCC), 35.5% (95% CI: 25–47) of the 76 lung cancer patients were correctly identified. For patients without methylated DCC, addition of a logistic regression score that was based on the five remaining genes improved sensitivity from 35.5% to 75% (95% CI: 64–84) but decreased the specificity from 100% to 73% (95% CI: 54–88). Conclusion: This approach needs to be evaluated in a larger test set to determine the role of this gene set in early detection and surveillance of lung cancer. Clin Cancer Res; 17(13); 4494–503. ©2011 AACR.


Noninvasive glutamate brain imaging (GluCEST) can localize seizure foci to one hemisphere in patients with temporal lobe epilepsy. Toward visualizing the focus Many seizures, especially those that originate in the brain's temporal lobe, start at a single spot in the brain. If drugs fail, excision of this region can often provide relief from seizures. A new imaging method that harnesses the power of a 7-T magnet shows promise in locating hard-to-find epileptic foci by visualizing the neurotransmitter glutamate. In a pilot study, the authors used glutamate chemical exchange saturation transfer (GluCEST), a very high resolution magnetic resonance imaging contrast method, to measure how much glutamate was in the hippocampi of four patients with epilepsy. Glutamate is elevated in epileptic foci. The amount of glutamate was clearly higher in one of the hippocampi in all four patients, and confirmatory methods (electroencephalography or magnetic resonance spectra) verified independently that the hippocampus with the elevated glutamate was located in the same hemisphere as the epileptic focus. Although the authors have only taken a first step toward noninvasively finding epileptic foci, their demonstration that GluCEST can localize small brain hot spots of high glutamate is promising. This approach can potentially allow a higher rate of successful surgeries in this difficult disease. When neuroimaging reveals a brain lesion, drug-resistant epilepsy patients show better outcomes after resective surgery than do the one-third of drug-resistant epilepsy patients who have normal brain magnetic resonance imaging (MRI). We applied a glutamate imaging method, GluCEST (glutamate chemical exchange saturation transfer), to patients with nonlesional temporal lobe epilepsy based on conventional MRI. GluCEST correctly lateralized the temporal lobe seizure focus on visual and quantitative analyses in all patients. MR spectra, available for a subset of patients and controls, corroborated the GluCEST findings. Hippocampal volumes were not significantly different between hemispheres. GluCEST allowed high-resolution functional imaging of brain glutamate and has potential to identify the epileptic focus in patients previously deemed nonlesional. This method may lead to improved clinical outcomes for temporal lobe epilepsy as well as other localization-related epilepsies.


Concussions in soccer are often coincident with the act of heading the ball, and some researchers have reported that soccer heading is associated with neurocoginitive decrements. This study aimed to understand (a) the personality factors that may predict frequent soccer heading, and (b) how knowledge of players' personality traits might help sport counselors persuade neurologically at-risk players to moderate their heading behavior. Sixty elite male soccer players (ages 16-34) completed structured self-report interviews, the NEO-FFI personality inventory, and the Arnett Inventory of Sensation Seeking. Players who headed most had significantly higher extraversion scores than comparison athletes and soccer players who headed less. Physical height was the best predictor of heading frequency but was not correlated with extraversion, which was also a significant predictor. Players with the typical profile of the high heading group may be more resistant to suggestion that they alter their style of play for safe...


Several projects are underway currently in the UK to promote the production, management and use of theses in electronic format. Funding from the Joint Information Systems Committee (JISC) is enabling three project teams to address key issues which to date have held back e-theses development in this country, including the lack of models suitable for use at national level. In order to appreciate the context within which the (Glasgow, Edinburgh and RGU led) projects are operating, this paper includes a brief history of the development of e-theses in the UK. It has taken a considerable length of time for the present, positive, situation to materialise in the UK. However, it is hoped that by highlighting the stages of development, the paper will serve to encourage others to persevere with attempts to obtain funding, and change attitudes, in order to achieve acceptance of electronic theses in their own institutions. The formation of the University Theses Online Group (UTOG), in the mid 1990s, may be considered the first milestone in the UK. Over the years, members of UTOG have worked hard to ascertain the views of students and researchers and to raise awareness of the advantages of having theses available in electronic format. At times the slow rate of progress has been dispiriting, but individual achievements have been significant. The paper explores the difficulties associated with maintaining interest in the subject of e-theses over a lengthy period during which there were few major breakthroughs - and it explains how this has been achieved in the UK. Finally, the paper examines the value of having easy access, via Web pages, to information about international e-theses projects and developments. Persuasive arguments can be made at home when details about progress, achievements and increased usage statistics elsewhere can be cited.


The Baseport system is a system introduced by Stora in year 2000 for the distribution of
its paper products. Some characteristics of the system includes the concentration of flows
to systemtransports between Stora's production units in Sweden and the port of
Gothenburg, where the transport passes on its way towards the continent. Also, the
Baseport system includes the development of loading units to facilitate heavier and more
voluminous transports. At the same the capacity of the train infrastructure increased.
The purpose of the study is to investigate the evolution of the Baseport system, to
investigate the effects when changes in the Baseport system's environment also affects
the transport flows in the whole transport system and finally to investigate what space of
action to reduce the environmental impact that existed during the same time.
The study uses actor-network theory to describe this evolution, together with
Hagerstrands "process landscape-framework". The study makes judgements on the
effects of the Baseport system with the help of a framework, developed in other repots,
investigating the indirect effects of changes in infrastructure. Finally a proposal is made
on the use of space of action to reduce the environmental impact in the context of the
transportsystem and a judgement is made on what space of action to reduce
environmental impact that existed in the case in point.
The study concludes that through the evolution of the Baseport system regional
imbalances in transport flows has been further conserved or reinforced; the possibilities
for co-loading has reduced; and the risk for higher transport flows has increased, which
among other things relates to the increased infrastructural capacity.
Some actors have, through their relations, to a particular extent and through their
functioning enabled or restricted the space of action to reduce the environmental impact.
Stora has played the enabling role when they have optimized their transports and reduced
the need for energy. The state has also played an enabling role by promoting train as a
transport mode by reduced fees for using the train infrastructure. Three restricting aspects
are brought out. Fysical relations such as the localization of the raw material, affecting
the localization of production units, just admits certain possibilities to change transport
distances when at the same time localization of customers often are far from the raw
material. The second aspect is changed institutions. The opening of a European market
without the introduction of regulations for transport-related activities cross national
borders have had a negative impact on transport distances. Changed institutions leads to
the third aspect, growing markets and the increased specialization of the production,
which contributes to increased regional imbalances and increased transport distances.
The report is written in Swedish


S. Davison & M. J. Hambrey reply: We thank A.D. Stewart for his stimulating comments regarding our recent paper on Torridonian glacial deposits. However, there are several differences of observations and interpretations which need to be resolved. (i) Roches moutonnées and stratigraphic relationships. The gneiss ridges shown in Stewart's fig. 1 are not, as he correctly observes, parallel and are not aligned in the direction of the proposed ice-flow. However, roches moutonnées do not necessarily have to be parallel to flow direction; indeed many are transverse. The critical observation is the contrast between up-glacier facing slopes, which are relatively smooth, and down-glacier slopes which are fractured. There is also a marked difference in clast size between the two slopes, those on the up-glacier side being generally smaller than those on the down-glacier side. We are unsure of the purpose of Stewart's fig. 2. It certainly shows the irregular nature of the Stoer Group/Lewisian contact, but this is a reflection of differential weathering/erosion of a foliated gneiss, whereas our photograph (fig. 3a) illustrates the form more clearly. The suggestion that the ice smoothed surface in our fig. 3a is 'far from smooth' is, we feel, misleading. Whilst it is not flat and polished, it is rounded and, in a geomorphological sense, is smooth. It is certainly of a much smoother and lower profile than the surface on the SW side of this feature, which is brecciated with a matrix of Torridonian sediments. The interpretation of these features as roches moutonnées is


The article reviews the origins, precursors, and main proponents of climate change tipping points, and the debates that the tipping point concept has occasioned. The importance of dynamical systems theory, GAIA theory, and abrupt climate change to the main proponents of tipping point warning systems is noted and situated in historical context. The 'semantic confusion' that animates contemporary debates, it is suggested, results not simply from a narrow conception of tipping points, but from inattention to the way metaphor was used to reshape climate policy. A deeper understanding of dynamical systems theory and its origins (both mathematical and metaphorical) is recommended for addressing the value of tipping points in policy. WIREs Clim Change 2015, 6:427–434. doi: 10.1002/wcc.344


In medical research, repeated questionnaire data is often used to measure and model latent variables across time. Through a novel imputation method, a direct comparison is made between latent growth analysis under classical test theory and item response theory, while also including effects of missing item responses. For classical test theory and item response theory, by means of a simulation study the effects of item missingness on latent growth parameter estimates are examined given longitudinal item response data. Several missing data mechanisms and conditions are evaluated in the simulation study. The additional effects of missingness on differences in classical test theory- and item response theory-based latent growth analysis are directly assessed by rescaling the multiple imputations. The multiple imputation method is used to generate latent variable and item scores from the posterior predictive distributions to account for missing item responses in observed multilevel binary response data. It is shown that a multivariate probit model, as a novel imputation model, improves the latent growth analysis, when dealing with missing at random (MAR) in classical test theory. The study also shows that the parameter estimates for the latent growth model using item response theory show less bias and have smaller MSE's compared to the estimates using classical test theory.


Some new N-acyclic pyridazine nucleosides 2-5 and S-acyclic pyridazine nucleosides 8-10 were prepared from compounds 4,6-diphenyl-2H-pyridazin-3-one (1) and 4,6-diphenyl-2H-pyridazin-3-thione (7), respectively. Also, the hydrazino derivative 11 was prepared and used as a key compound for the preparation of some [1,2,4]triazolo[4,3-b]pyridazines 12-15. Moreover, the cytotoxicity and in vitro anticancer evaluation of some prepared compounds have also been assessed against different cancer cells including Lung (A594), Colon (HCT116), Breast (MCF-7), Liver (HepG2) and Prostate (PC3) as well as normal Melanocyte (HFB4). The results revealed that compounds 3 and 10 have moderate anticancer activities; while compounds 1, 2, 8, and 11 possess promising anticancer activities against breast MCF-7 and liver HepG2 cancer cell lines compared to the activity of the commonly used anticancer drug, doxorubicin. Otherwise, the results revealed that the previous compounds have no toxic effect against the normal HFB4 cells.


We propose a configuration of signal multiplexing with four polarization states, and investigate its transmission performance over single-mode-fiber links. Assisted by coherent detection and digital signal processing (DSP), the demodulation of four-polarization multiplexed (4PM) on-off-keying (OOK) and phase-shift-keying (PSK) signals are achieved. We then discuss the impact of the crosstalk from polarization mode dispersion (PMD) on 4PM systems. The transmission distance is extended from ~50-km to ~80 km by employing feedback-decision-equalizers. We also compare the back-to-back characteristics of the 40-Gbit/s 4PM-OOK system and 40-Gbit/s PDM-QPSK system with the same spectral efficiency. The results show that the performance of 4PM systems is comparable to that of PDM-QPSK systems, which indicates that the proposed scheme is a potentially promising candidate for future optical networks.


The Snowden leaks, first published in June 2013, provided unprecedented insights into the operations of state-corporate surveillance, highlighting the extent to which everyday communication is integrated into an extensive regime of control that relies on the 'datafication' of social life. Whilst such data-driven forms of governance have significant implications for citizenship and society, resistance to surveillance in the wake of the Snowden leaks has predominantly centred on techno-legal responses relating to the development and use of encryption and policy advocacy around privacy and data protection. Based on in-depth interviews with a range of social justice activists, we argue that there is a significant level of ambiguity around this kind of anti-surveillance resistance in relation to broader activist practices, and critical responses to the Snowden leaks have been confined within particular expert communities. Introducing the notion of 'data justice', we therefore go on to make the case that resistance to surveillance needs to be (re)conceptualized on terms that can address the implications of this data-driven form of governance in relation to broader social justice agendas. Such an approach is needed, we suggest, in light of a shift to surveillance capitalism in which the collection, use and analysis of our data increasingly comes to shape the opportunities and possibilities available to us and the kind of society we live in.


This case describes business issues at an organic farm. The people and places are real, and the quantitative data is based on actual observations, although some detail has been omitted for pedagogical purposes. This case was developed for use in an integrated course in the first year of an MBA program. Two academic disciplines are covered in the case: management accounting and quantitative methods. Once the technical aspects of the case analysis have been covered, class sessions have produced rich managerial discussions. Brett Grohsgal, a former chef from Washington, DC, started an organic farm in southern Maryland after creating a network of contacts in restaurants and observing the restaurant demand for organic vegetables grow over the years. He soon added a pair of local farmers' markets and a co-op subscription service as additional sales channels. These channels were added opportunistically, without any formal analysis. At the time of the case, the vegetables for the year have already been planted. Furthermore, Brett has come to realize that potential demand across his three sales channels outstrips his expected current season supply. However, he has no idea as to the relative profitability of the three distribution channels and, therefore, does not know the how he should plan his sales effort. The price of each type of produce is different in each of the different channels, as are the spoilage rates. In addition, entering each channel is associated with an entry cost, as well as with variable selling and distribution costs that scale with the amounts sold through each channel. Brett's immediate need is to figure out which channels to use, and how much of each produce to sell in each channel. Beyond the current season, Brett also needs to adjust his planting next year, not only to increase supply, but to find the best "production mix" of vegetables. The primary teaching objectives for this case are to explore distribution channel profitability and to introduce the concept of integer programming. The case requires students to set up a differential analysis across the three different distribution channels. This highlights the "off/on" nature of certain costs in each channel. In addition, students have to cope with harvest yields (anticipated production output), channel demand limits, and within-channel spoilage rates. Nonetheless, the setting is a simple one which all students can readily visualize.


Solar thermal concentrating solar power (CSP) plants, because of their capacity for large‐scale generation of electricity and the possible integration of thermal storage devices and hybridization with backup fossil fuels, are meant to supply a significant part of the demand in countries of the solar belt. Nowadays, the market penetration of solar thermal electricity is steeply increasing, with commercial projects in Spain, USA, and other countries, being the most promising technology to follow the pathway of wind and photovoltaics to reach the goals for renewable energy implementation in 2020 and 2050. In the first commercial projects involving parabolic‐trough technology, some improvements are being introduced like the use of large molten‐salt heat storage systems able to provide high degrees of dispatchability to the operation of the plant, like the plants Andasol in Guadix, Spain, with 7.5 h of nominal storage, or the use of direct steam generation loops to replace thermal oil at the solar field. In the near future, the research and innovation being conducted within the field of linear Fresnel collectors may lead to high temperature systems able to operate up to 500°C and produce cost‐effective superheated steam. Central receiver systems are opening the field to new thermal fluids like molten salts (Gemasolar tower plant in Seville, Spain) with more than 14 h of nominal storage and air, and new solar receivers like volumetric absorbers, allowing operation at temperatures above 1000°C. All these factors can lead to electricity generation cost reduction of CSP plants by 30–40% for the period 2010–2020, according to public roadmaps and cost analysis made by the International Energy Agency in 2010. WIREs Energy Environ 2014, 3:42–59. doi: 10.1002/wene.79


Leaf area index (LAI) is a key variable for the understanding and modeling of several ecophysiological processes within a vegetation canopy. The LAI could thus provide vital information for the management of the environment and agricultural practices when estimated continuously over time and space thanks to remote sensing sensors such as CHRIS/PROBA. The spaceborne ESA-mission CHRIS/PROBA provides multi-temporal observations of the land surface in the spectral and directional information dimensions. This system represents a rich source of information for Earth observation purposes specifically adapted for monitoring the high dynamic of agricultural crops. For this purpose a radiative transfer model (RTM) is coupled to a canopy structure dynamic model (CSDM). The coupled models are used to exploit the complementary content of the spectral and temporal information dimensions for LAI estimation over a maize canopy. The resulting estimation of the temporal and spatial variation of LAI is improved by integrating multi-temporal CHRIS/PROBA data and ground meteorological observations. Further, the presented method provides the continuous LAI time course over the season, which is required by crop growth and land surface process models.


BACKGROUND
In this article, we review a diverse body of research and draw conclusions about the usefulness, or lack there-of, of specific antioxidants in the prevention of Alzheimer's disease (AD).

METHODS
The National Library of Medicine's database was searched for the years 1996-2004 using the search terms "Alzheimer's, anti-oxidants, antioxidants."

RESULTS
Over 300 articles were identified and 187 articles were selected for inclusion based on relevance to the topic. Agents that show promise in helping prevent AD include: 1) aged garlic extract, 2) curcumin, 3) melatonin, 4) resveratrol, 5) Ginkgo biloba extract, 6) green tea, 7) vitamin C and 8) vitamin E.

CONCLUSIONS
While the clinical value of antioxidants for the prevention of AD is often ambiguous, some can be recommended based upon: 1) epidemiological evidence, 2) known benefits for prevention of other maladies, and 3) benign nature of the substance. Long-term, prospective studies are recommended.


Several empirical studies have shown that formative assessment improves student learning. We build on those studies by reporting the results of a natural experiment at The Ohio State University Moritz College of Law. Students in one of three first-year sections had the opportunity to complete a formative assessment in their spring-semester Constitutional Law course. The assessment consisted of an essay question that the professor had used on a prior exam. Students who submitted an essay answer received prompt, extensive written feedback; they also had the chance to discuss their answer with the professor.
Over the course of three years, about half of the students enrolled in the section took advantage of the formative assessment. Those students achieved significantly higher grades on the final exam even though the assessment score did not factor into their course grade. Notably, students receiving this formative feedback also secured a significantly higher GPA in their other spring-semester classes. Both of these effects persisted after controlling for LSAT score, UGPA, gender, race, and fall-semester grades. These controls helped reduce any effect of selection bias on our findings.
In addition to exploring these relationships between formative assessment and academic achievement, we discuss several race and gender effects that emerged in our analyses. Women, for example, were significantly more likely than men to complete the formative assessment. Women also received significantly higher grades than men in a spring-semester course on Legal Analysis and Writing; men, conversely, received significantly higher grades than women in a Legislation course. A race effect, meanwhile, emerged for students with LSAT scores at or above the school median: Among those students, nonwhite students who completed the formative assessment achieved significantly higher grades in Constitutional Law than white students who submitted the same exercise.
All of these relationships deserve further empirical study. In particular, our results suggest the importance of examining the transfer effects of formative feedback, gender differences in law school learning, and paths for improving the academic experience of minority students.


The historical role that the Catholic Church has played in oppressing many different groups is clear: for example, the oppression of women, children, LGBTQ people, and people of Color. Equally clear is the choice many churches and congregants make today to remain silent and inert when it comes to prioritizing the dignity of all marginalized populations, even those sitting beside them in the pews. Specifically, the White, Catholic community of faith is significantly absent in the work to challenge institutions that oppose the liberation of Black communities. However, this reality is inconsistent with the most faithful demands of Catholic scripture and tradition. From the Old Testament to Jesus of Nazareth and his apostles to Pope Francis, one core principle of Catholicism is the priority God places on the lives and dignity of the most oppressed. By exploring the compendium of Catholicism, White Catholics can find an appropriate framework for considering how to engage the work for racial justice. Additionally, those of White identity have a unique responsibility to explore the realities of their racial identity. By taking intentional action and heeding the call that so many others before them have taken up, they can find that it is very much in the lexicon of God to loudly proclaim the Gospel truth, "Black lives matter!" This is a personal self-reflection, and I envision the primary audience for this article to be privileged White Catholics who impose their social and political beliefs about the Black Lives Matter movement on their faith. The aim is to provide pushback to those who would argue that this social movement, along with others, is contrary to the Catholic faith and hopefully serve as a call to embolden them to action.   Note: UDP is a platform for voices to be heard. Therefore, this is a personal, self-reflection article for a specific population, and is not a reflection of the beliefs of UDP.


Despite the brutal nature of the Civil War, the Confederate cavalry has a storied and generally favourable relationship with its history. However, sometimes the whiff of romance present obscures history. Failure in the Saddle is the first study of its kind to examine the impact of the Confederate Cavalry on the larger Chickamauga campaign. David A. Powell draws upon a massive array of primary accounts, many previously unpublished, for his richly detailed study full of insightful tactical commentary, new perspectives on the strategic role of the Rebel horsemen, and fresh insights on every engagement of the campaign. The 1863 battle of Chickamauga was one of the largest and bloodiest combats of the war. The intricate engagement between the Union Army of the Cumberland and the Confederate Army of Tennessee ended success for the Southern Army. Yet despite this, the main prize of Chattanooga would still elude them. Within months, Federal counterblows reversed all that had been so dearly purchased. With two full cavalry corps under legendary commanders Nathan Bedford Forrest and Joe Wheeler, should the outcome have been different? Failure in the Saddle is a judiciously reasoned and carefully crafted study and an essential book for readers of Civil War battle and campaign histories. About the Author David A. Powell has a BA in history from the Virginia Military Institute. He has published numerous books and articles, more than fifteen historical simulations of various battles, and regularly leads tours to Civil War battlefields including the epic field of Chickamauga.


ABSTRACT Amino-bis-phosphonates (N-BPs) such as zoledronate (Zol) have been used in anticancer clinical trials due to their ability to upregulate pyrophosphate accumulation promoting antitumor Vγ9Vδ2 T cells. The butyrophilin 3A (BTN3A, CD277) family, mainly the BTN3A1 isoform, has emerged as an important structure contributing to Vγ9Vδ2 T cells stimulation. It has been demonstrated that the B30.2 domain of BTN3A1 can bind phosphoantigens (PAg) and drive the activation of Vγ9Vδ2 T cells through conformational changes of the extracellular domains. Moreover, BTN3A1 binding to the cytoskeleton, and its consequent membrane stabilization, is crucial to stimulate the PAg-induced tumor cell reactivity by human Vγ9Vδ2 T cells. Aim of this study was to investigate the relevance of BTN3A1 in N-BPs-induced antitumor response in colorectal cancer (CRC) and the cell types involved in the tumor microenvironment. In this paper, we show that (i) CRC, exposed to Zol, stimulates the expansion of Vδ2 T lymphocytes with effector memory phenotype and antitumor cytotoxic activity, besides sensitizing cancer cells to γδ T cell-mediated cytotoxicity; (ii) this effect is partially related to BTN3A1 expression and in particular with its cellular re-distribution in the membrane and cytoskeleton-associated fraction; (iii) BTN3A1 is detected in CRC at the tumor site, both on epithelial cells and on tumor-associated fibroblasts (TAF), close to areas infiltrated by Vδ2 T lymphocytes; (iv) Zol is effective in stimulating antitumor effector Vδ2 T cells from ex-vivo CRC cell suspensions; and (v) both CRC cells and TAF can be primed by Zol to trigger Vδ2 T cells.


On the basis of predecessors' researches, this paper introduces service cost as a factor that influences bank service capability, and considers customers and service quality as well, to build a bank service capability decision-making model based on stochastic service system. We subdivide customers into different types according to their different concerns about service quality, use Activity Based Costing to analyze the factors of service cost, transfer waiting time which is the most important factor of service quality that priority customers consider to cost by adopting Delay Cost Theory. At last, the paper use Matlab to verify this model through adjusting the value of service rate and the number of servers to optimize service capability in a multi-server setting, help banks find the most reasonable way of optimizing service capability. This paper finds that bank managers need to consider customers, service quality and service cost together when optimize service capability, and that a bank can reduce waiting time by choosing staffs with high service rate and by increasing the number of servers.


The knowledge of consumer perception of meat tenderness and taste is essential to forecast a Brazilian quality value-based beef market. This study aimed to verify perception of tender (WBSF 4.8 kg) strip loin steak or uncharacteristic (calcium-treated/Ca-IM) and normal (non-calcium/NO-Ca) meat taste by consumers according to gender, age, education and income levels. Steaks were previously classified by shear force measurements as tender or tough. Each consumer was served a paired sample of one tender and of one tough steak, which were either Ca-IM or NO-Ca treated before tenderness classification. Three hundred and eight consumers answered a nine-point intensity (tenderness) and hedonic (taste) scales evaluation questionnaire. Among consumers, 82.2% indicated beef as first choice meat products, 75.3% had beef at least four times a week; 39.3% considered taste as the most important meat attribute and 30.2% considered tenderness; 75.8% were males; 73.6% were 21 to 55 years old; 56.7% had college education; 76.6% had monthly income higher than US $ 435,00. Tender steaks were scored highest (P < 0.01), independently of gender, age and income. However, elderly consumers gave higher scores to tender steaks in comparison to middle age consumers (P < 0.05). In the lower education level, scores given to tender and tough meat did not differ. The higher income level responders assigned lower tenderness scores within tender or tough meat (P = 0.10). Differences in taste were perceived by both genders, and by consumers in every income and education level. Males gave higher scores (dislike less) within Ca-IM steaks. Consumers in the lower education level scored taste higher (like most) within untreated samples. The elderly people could not differentiate taste between the Ca-IM and NO-Ca steaks. These are the first indications that Brazilian consumers perceive tender from tough or uncharacteristic taste of beef, but palatability is evaluated differentially depending on gender, age, education and income level.


Probabilistic model checking is a powerful formal verification method that can ensure the correctness of real-life systems that exhibit stochastic behaviour. The work presented in this thesis aims to solve the scalability challenge of probabilistic model checking, by developing, for the first time, fully-automated compositional verification techniques for probabilistic systems. The contributions are novel approaches for automatically learning probabilistic assumptions for three different compositional verification frameworks. The first framework considers systems that are modelled as Segala probabilistic automata, with assumptions captured by probabilistic safety properties. A fully-automated approach is developed to learn assumptions for various assume-guarantee rules, including an asymmetric rule Asym for two-component systems, an asymmetric rule Asym-N for n-component systems, and a circular rule Circ. This approach uses the L* and NL* algorithms for automata learning. The second framework considers systems where the components are modelled as probabilistic I/O systems (PIOSs), with assumptions represented by Rabin probabilistic automata (RPAs). A new (complete) assume-guarantee rule Asym-Pios is proposed for this framework. In order to develop a fully-automated approach for learning assumptions and performing compositional verification based on the rule Asym-Pios, a (semi-)algorithm to check language inclusion of RPAs and an L*-style learning method for RPAs are also proposed. The third framework considers the compositional verification of discrete-time Markov chains (DTMCs) encoded in Boolean formulae, with assumptions represented as Interval DTMCs (IDTMCs). A new parallel operator for composing an IDTMC and a DTMC is defined, and a new (complete) assume-guarantee rule Asym-Idtmc that uses this operator is proposed. A fully-automated approach is formulated to learn assumptions for rule Asym-Idtmc, using the CDNF learning algorithm and a new symbolic reachability analysis algorithm for IDTMCs. All approaches proposed in this thesis have been implemented as prototype tools and applied to a range of benchmark case studies. Experimental results show that these approaches are helpful for automating the compositional verification of probabilistic systems through learning small assumptions, but may suffer from high computational complexity or even undecidability. The techniques developed in this thesis can assist in developing scalable verification frameworks for probabilistic models.


In Norway, environmental education (EE) has been part of schools' curricula since the 1970s. The concept of education for sustainable development (ESD) was introduced after Agenda 21 was introduced at the UN conference on environment and development held in Rio in 1992. The article shows there has been little change in the geography curricula since the concept ESD was introduced, and no important differences are found between curricula for mandatory schooling (classes 1–10) and curricula for upper secondary schools. ESD is mentioned in the geography curricula but without explanation and implementation. Core goals in the general national core curricula may indicate a change to ESD, but they have not been followed in the development of geography curricula in Norway.


Nonclassical structures of permanent-magnet cylindrical air-gap couplings with progressive magnetization are studied. In these couplings, parallelepiped magnets with nonclassical magnetization direction are used and stuck in ironless cores. The magnetization direction of each magnet is chosen to provide an optimal repartition of the induction in the air gap. This progressive magnetization allows very high values of pullout torque. The use of this type of structure with ironless cores and very high pull-out torque seems to be an advantageous way to minimize the inertia and maximize the pullout torque of a magnetic coupling. An efficient method to calculate the torque of such a coupling is presented, based on analytical formulas for forces between magnets. It allows the exact evaluation of the performance of the studied couplings when the main dimensions of the coupling are varying with small calculation time. In this paper the influence of the number of pole pairs, the influence of the number of magnets per pole, the influence of the magnets' thickness, the influence of the air-gap radius, and the influence of the length of the structure are studied and discussed. Then some general rules are presented for efficient design of such a coupling.


The adsorption, photo- and thermal- chemistry of adsorbates, and the photoactivation of TiO2(110) single crystalline surfaces are the central topics investigated and presented in this thesis. The hole-induced photodesorption of chemisorbed O2 from a defective TiO2(110) surface was studied to monitor the kinetics of electron-hole pair formation, recombination and hole-trapping. Two distinct O2 desorption processes are found which are characteristic of low and high photon fluxes. At a critical photon flux, the slow O2 desorption process converts to a fast process as a result of the saturation of hole trapping sites in the TiO2 crystal. Both the slow and fast O2 desorption processes are governed by the flux of UV radiation, Fhv1/2, indicating that the steady state concentration of photogenerated holes can be described by second-order electron-hole pair recombination kinetics. A hole scavenger is used to probe the role of added hole trap centers on the photodesorption rate.The photodesorption for O2 from TiO2(110) was found to exhibit fractal kinetic behavior where the photodesorption process is described by a rate coefficient that varies throughout the measurement. A model is proposed in which the electrons associated with O-vacancy defects on the surface percolate from vacancy site to vacancy site via the filled orbitals at these sites to neutralize photo-produced holes. This electron percolation, causing e-h recombination, reduces the efficiency of charge transfer between a photoproduced hole and an O2-(a) species localized at a vacancy defect site, causing the rate of O2 photodesorption to follow a fractal rate law. We postulate that the fractal electron conduction path across the surface is one-dimensional.The adsorption and thermal desorption of CO2 on TiO2(110) was investigated as a probe of the concentration of oxygen vacancy defects. For the stoichiometric and fully oxidized surface, a single thermal desorption feature (Ed = 48.5 kJ/mol) is measured and is attributed to CO2 bound to regular 5-fold coordinated Ti4+ atoms. For the partially reduced TiO2(110) surface, CO2 binds not only to regular sites, but also to oxygen vacancy sites (Ed = 54.0 kJ/mol), created by thermal annealing. The variation in the characteristic CO2 desorption kinetics was measured as a function of the surface reduction temperature and the systematic production of increasing levels of surface defects is observed in the temperature range of 600K- 1100K.The effect of impurity doping on the photoactivity of TiO2 rutile single crystals was subjected to a combined surface science and bulk analysis study. Two approaches were taken: First, the incorporation of nitrogen ions, N-, into TiO2 single crystals was achieved by sputtering with N2+/Ar+ mixtures and subsequent annealing to 900 K under ultra high vacuum conditions; Secondly, a chemical doping method where TiO2(110) single crystals were exposed to gaseous NH3 at 870 K was used. The nitrogen implantation method employed in the first study resulted in an unexpected blueshift of the photoexcitation threshold energy for the doped material compared to undoped TiO2. For crystals doped using the second chemical doping method, a decrease in the required photoactivation energy was observed when compared to undoped TiO2 crystals.Finally, the thermal- and photo- chemistry of the mustard gas simulant molecule, 2-chloroethyl ethyl sulfide (2-CEES), was investigated on both TiO2(110) single crystals and TiO2 powdered materials. 2-CEES decomposition occurs through the incorporation of lattice oxygen from the TiO2 material into the oxidized products.A review of aspects of photochemistry on TiO2 surfaces forms the concluding chapter of the thesis.


Fish is an important source of animal protein for billions of people and in some tropical countries like Bangladesh, the Pacific islands, and the Maldives, fish provides more than 60% of animal protein supply. Climate change [the rise in temperatures (T°C), ocean acidification (OA), sea-level rise (SLR) and extreme events (EE)] is an additional threat and risk to world fisheries, aquaculture, and seafood security, in addition, to existing threats posed by other stressors. The T°C will have both the negative and positive effects on fisheries and aquaculture, of which, the temperate areas/countries will benefit, while the tropical regions/countries will be losers due to shifting in fish species from the tropical areas to the temperate areas to escape the warmer water. The T°C would cause coral bleaching and mortalities and may enhance seafood contamination (by algal toxins and metals). The OA would adversely affect many organisms that use calcium carbonate for their skeletons and would cause a decrease in abundance of commercially exploited seafood organisms (shellfish and finfish). SLR would cause salinisation of freshwater fisheries and aquaculture facilities and would damage or destroy many coastal ecosystems including mangroves and salt marshes, which are essential habitat for wild fish stocks. Climate change is projected to increase the frequency and intensity of EE. Besides, EE would destroy seagrass and seaweed beds and mangroves (which are important nursery areas for fishes). The economic loss and impacts on fisheries, aquaculture and seafood security due to T°C, OA, SLR, EE could be substantial in both tropical and temperate areas/countries. To achieve sustainability in fisheries and aquaculture in line with the new global sustainable development goals (2016-2030), it will be essential to identify appropriate adaptation and mitigation measures. Such measures may include promotion of climate-smart fisheries and clim


People talk about politics with others who may or may not share their views. These conversations shape their understanding and engagement with politics. However, studies have resulted in a conundrum in the relationship between disagreeable discussion and participation. Some studies suggest that the relationship is likely contingent on the type of participation. In addition, considering the characteristics of one's social networks alongside exposure to disagreement serves to extend our understanding of how communication matters for political engagement. Our results suggest that episodic forms of participation, such as voting or protesting, are not directly impacted by exposure to disagreement, whereas iterative forms, including certain forms of civic engagement and expressive behaviors, are enhanced by exposure to political disagreement, particularly among those with larger discussion networks.


Visual exploration of scientific data in life science area is a growing research field due to the large amount of available data. The Kohonen's self organizing map (SOM) is a widely used tool for visualization of multidimensional data. In this paper we present a fast learning algorithm for SOMs that uses a simulated annealing method to adapt the learning parameters. The algorithm has been adopted in a data analysis framework for the generation of similarity maps. Such maps provide an effective tool for the visual exploration of large and multi-dimensional input spaces. The approach has been applied to data generated during the high throughput screening of molecular compounds; the generated maps allow a visual exploration of molecules with similar topological properties. The experimental analysis on real world data from the National Cancer Institute shows the speed up of the proposed SOM training process in comparison to a traditional approach. The resulting visual landscape groups molecules with similar chemical properties in densely connected regions.


The latest offering in the Poets on Poetry series from acclaimed poet, critic, and National Endowment for the Arts' chairman Dana Gioia, Barrier of a Common Language collects essays on British poets and poetry spanning the past two decades.Gioia ignited a national debate on the relevance of poetry in 1991 when he published an essay in the "Atlantic" titled "Can Poetry Matter?" The essay was expanded into a book of the same name and went on to become one of the best-selling books of contemporary poetry criticism in the 1990s.In Barrier of a Common Language Gioia addresses the current disconnect between British and American poetry, the result of America's growing postwar self-sufficiency in its intellectual concerns and concomitant patronizing attitude toward Britain. Writes Gioia, "Today . . . most American readers are not only unfamiliar with current British poetry, but modestly proud of the fact. They do not dissemble, but urbanely flourish their ignorance as an indisputable sign of discrimination."Whether British poetry ever regains the importance in Anglo-American literary traditions it had fifty years ago, Gioia believes, will depend on the quality of service it receives from critics, poets, editors, and anthologists who alone can make it accurately heard and understood.Poet, critic, and acclaimed author of "Can Poetry Matter?" Dana Gioia is one of America's leading contemporary men of letters. Winner of the American Book Award, Gioia is internationally recognized for his role in reviving rhyme, meter, and narrative in contemporary poetry."


To maintain the overall productivity of a citrus grove, dead or declining trees should be promptly removed and replaced with young, healthy trees, a practice known as resetting. Resetting presents many challenges for growers because young trees require more attention and care than more established trees. This 4-page fact sheet discusses effective resetting methods and maintenance for citrus. Written by Zekri Mongi, and published by the UF Department of Horticultural Sciences, August 2015.
HS1266/HS1266: Resetting in Citrus Groves (ufl.edu)


The electrochemical performance of Li-ion batteries (LIBs) can be highly tuned by various factors including the morphology of the anode material, the nature of the electrolyte, the binding material, and the percentage of conducting materials. Binding materials have been of particular interest to researchers over the decades as a means to further improve the cycle durability and columbic efficiency of LIBs. Such approaches include the introduction of different polymeric binders such as poly(acrylic acid) (PAA), carboxymethyl cellulose (CMC), and alginic acid (Alg) into the Si anode of LIBs. To achieve a better efficiency of LIBs, herein, we introduce a novel copolymer, poly(tert-butyl acrylate-co-triethoxyvinylsilane) (TBA-TEVS), as an efficient binder with stable cycle retention and excellent specific capacity. The binder forms a highly interconnected three-dimensional network upon thermal treatment as a result of de-protection of the tert-butyl group and the consequent inter-intra condensation reaction, which minimizes pulverization of the Si nanoparticles. Moreover, the siloxane group is expected to promote the formation of stable solid-electrolyte-interface (SEI) layers. A series of random copolymers were synthesized by varying the molar ratio of tert-butyl acrylate and triethoxyvinylsilane. Twenty-one percent of TEVS in the TBS-TEVS copolymer gave rise to a superior performance as a binder for Si anodes, where the anodes showed a stable specific capacity of 2551 mA h g(-1) over hundreds of cycles and an initial columbic efficiency (ICE) of 81.8%.


The use of Optical Coherence Tomography (OCT) in acute coronary syndromes (ACS) allows recognizing ruptured fibrous cap (RFC) and intact fibrous cap (IFC) culprit lesions. The biological differences between them, as recently pointed out in translation studies, highlight different mechanisms for a similar clinical manifestation that might deserve different therapeutic approaches. The relationship between endothelial wall shear stress (WSS) and ACS has been demonstrated, however the differences in WSS features between RFC and IFC have not been elucidated.

 The aim of this study is to provide a fluid-dynamic and biological description of unstable and stable (SA) plaques, according to OCT analysis.

 We enrolled 10 SA and 20 Non-ST Elevation Myocardial Infarction (NSTEMI)-ACS patients, with IFC (n=10) and RFC (n=10) culprit lesions according to OCT analysis. We performed Real-time PCR primer array on pooled Peripheral Blood Mononuclear Cell (PBMC) for 30 different molecules whose expression is strictly dependent on WSS. High-fidelity 3D-coronary artery models were created for 3 patients per group, applying previously validated methodologies.

 Among the groups we found a broad difference in molecular expression (Fig. 1A), with RFC displaying higher levels of molecules involved in vasoconstriction/dilatation (EDN1, NOS3), cellular adhesion (ICAM1), and peptidase inhibition (PI16). A significantly higher WSS was observed in RFC group (p<0.001, Fig 1B and C), with larger variability and larger areas exposed to both low and high WSS (Fig. 1D). Interestingly, the molecules overexpressed in RFC are known to be upregulated by high WSS.

 Our data demonstrated that IFC and RFC unstable plaques are associated with different WSS conditions, alongside with the expression of different molecular patterns specifically related to altered WSS. In the era of precision medicine these findings may have relevant therapeutical implications.

 Type of funding source: None


BACKGROUND: Limited success has been reported for matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS) differentiation of staphylococci, including methicillin resistant Staphylococcus aureus (MRSA) strains. Chemical pretreatment of cells prior to MALDI-TOF-MS analysis has not been systematically investigated for enhanced discrimination of S. aureus strains. OBJECTIVES: To evaluate various chemical pretreatment of cells for MALDI-TOF-MS discrimination of clinical staphylococcal isolates, with a focus on differentiation of MRSA from methicillin sensitive S. aureus (MSSA) strains and from other staphylococcal species. METHOD: MALDI-TOF-MS of a well-characterised S. aureus strain(s) was optimised with respect to matrix chemical(s), matrix solvent and target plating method. Various chemical pretreatments (solvents, reductants, detergents) and pretreatment application methods were then evaluated for enhancement of spectral richness. The three most promising pretreatments were applied to MALDI-TOF-MS discrimination of three set of clinical isolates comprising non-S. aureus staphylococci (77 isolates), MSSA (36) and MRSA (43), with analysis by total or set specific resolved peaks. RESULTS: The optimized MALDI-TOF-MS protocol involved α-cyano-4-hydroxycinnamic acid (CHCA) as matrix chemical (in 1:2 acetonitrile:H2O and 2% trifluoroacetic acid), with application as an overlay onto smeared cells (on-probe). Onprobe application of chemical pretreatment was most effective at enhancing MALDI-TOF-MS spectral richness. Use of reductants and detergents as pretreatments were ineffective. The three most effective solvents/acid pretreatments – ethanol:formate, ethanol:acetate and formate:isopropanol – each generated reproducible and distinct spectra over the 2,000–10,000 m/z range. For the combined sets of clinical isolates (114), all three of these pretreatments increased the total number of resolved peaks in comparison with no pretreatment controls. The ethanol:formate pretreatment gave 100% clustering of non-S. aureus staphylococci, based on total resolved peaks. The formate:isopropanol pretreatment generated the largest increase in number of MRSA set specific peaks (from 18 to 32; 78% increase) and clustered the majority (77%) of the MRSA strains together, although compete discrimination of the MSSA and MRSA was not achieved. CONCLUSION: MALDI-TOF-MS discrimination of clinical isolates of staphylococci is enhanced through chemical pretreatment of cells. Three chemical pretreatments, not previously applied to staphylococci, are highlighted for enhancing spectral richness and offering new opportunities for improved discrimination of staphylococci, including MRSA and MSSA strains.


In this paper is given the scientific explanation of the mutual interaction
 and interpenetration of geographical position, elements of the natural basis
 and the relevant socio-economic processes that led to territorial,
 demographic and functional development of the network of settlements in the
 Republic of Serbia. Chronologically is given the continuity in functional
 connections between the settlements, as well as causes, origin and legal
 development of the urban system in Serbia. Highlighting the problems in
 distribution of the settlement system of Serbia, in principle is pointed to
 possible directions of the spatial and functional organization of the network
 of settlements, in order to achieve, on the one hand, polycentric,
 sustainable and balanced regional development of Serbia, and on the other, to
 involve into the development processes of the closer and further regional
 environment.


Human Activity Recognition (HAR) is an important application of smart wearable/mobile systems for many human-centric problems such as healthcare. The multi-sensor synchronous measurement has shown better performance for HAR than a single sensor. However, the multi-sensor setting increases the costs of data transmission, computation and energy. Therefore, the efficient sensor selection to balance recognition accuracy and sensor cost is the critical challenge. In this paper, we propose an Instance-wise Dynamic Sensor Selection (IDSS) method for HAR. Firstly, we formalize this problem as minimizing both activity classification loss and sensor number by dynamically selecting a sparse subset for each instance. Then, IDSS solves the above minimization problem via Markov Decision Process whose policy for sensor selection is learned by exploiting the instance-wise states using Imitation Learning. In order to optimize the parameters of the activity classification model and the sensor selection policy, an algorithm named Mutual DAgger is proposed to alternatively enhance their learning process. To evaluate the performance of IDSS, we conduct experiments on three real-world HAR datasets. The experimental results show that IDSS can effectively reduce the overall sensor number without losing accuracy and outperforms the state-of-the-art methods regarding the combined measurement of accuracy and sensor number.


RISC vs. CISC wars raged in the 1980s when chip area and processor design complexity were the primary constraints and desktops and servers exclusively dominated the computing landscape. Today, energy and power are the primary design constraints and the computing landscape is significantly different: growth in tablets and smartphones running ARM (a RISC ISA) is surpassing that of desktops and laptops running x86 (a CISC ISA). Further, the traditionally low-power ARM ISA is entering the high-performance server market, while the traditionally high-performance x86 ISA is entering the mobile low-power device market. Thus, the question of whether ISA plays an intrinsic role in performance or energy efficiency is becoming important, and we seek to answer this question through a detailed measurement based study on real hardware running real applications. We analyze measurements on the ARM Cortex-A8 and Cortex-A9 and Intel Atom and Sandybridge i7 microprocessors over workloads spanning mobile, desktop, and server computing. Our methodical investigation demonstrates the role of ISA in modern microprocessors' performance and energy efficiency. We find that ARM and x86 processors are simply engineering design points optimized for different levels of performance, and there is nothing fundamentally more energy efficient in one ISA class or the other. The ISA being RISC or CISC seems irrelevant.


__________________________________________________________________________________________________ Copyright © Ismail Gani 2015 iv Abstract The objective of this study is to determine whether compliance with ASX Recommendation 4.3 as part of Australia's corporate governance reforms is related to the performance of corporations. In order to investigate this matter, companies operating in the materials sector that are ranked in the top 500 companies listed on the ASX were analysed. The research question is: Among corporations that operate within the materials sector and are ranked in the top 500 companies (by market capitalisation) listed on the ASX, do those corporations that comply with ASX Recommendation 4.3, achieve higher corporate performance? This study used secondary numerical and historical data to answer the research question. The study period was derived from reports of the corporations for years ended 30 June 2006, 30 June 2007 and 30 June 2008. The data includes board characteristics, audit committee characteristics and financial data. The study included 54 corporations; 30 of them complied with Recommendation 4.3 and 24 did not. Panel data estimation regression analysis was selected as a suitable statistical technique for this study. A random effects model regression analysis was conducted (with six variables in total) for the dependent variables: Reported Net Profit (RNP), Return on Assets (ROA), Return on Equity (ROE), +/Market (M), Price Earnings Ratio (PER) and Price Cash Flow Ratio (PCFR). Conclusions and implications were only drawn for ROA and ROE as the results for the remaining variables presented a low percentage of overall fit and statistically insignificant probability values, and so statistical inferences could not be drawn. This study answered the research question by concluding that corporations that operate within the materials sector ranked in the top 500 companies (by market capitalisation) listed on the ASX that comply with ASX Recommendation 4.3, achieve higher corporate performance as measured by return on assets and return on equity.


This paper is devoted to the proof of the orbifold theorem: If O is a compact connected orientable irreducible and topologically atoroidal 3-orbifold with nonempty ramification locus, then O is geometric (i.e. has a metric of constant curvature or is Seifert fibred). As a corollary, any smooth orientationpreserving nonfree finite group action on S3 is conjugate to an orthogonal action.


Thyroid hormones (THs) are essential for the development and function of the central nervous system (CNS), not only for neuronal cells but also for glial development and differentiation. In adult CNS, both hypo- and hyper-thyroidism may affect psychological condition and potentially increase the risk of cognitive impairment and neurodegeneration including Alzheimer's disease (AD). We have reported non-genomic effects of tri-iodothyronine (T3) on microglial functions and its signaling in vitro (MORI et al., 2015). Here we report the effects of hyperthyroidism on glial cells in vivo using young and old male and female mice. Immunohistochemical analyses showed glial activation are sex- and age-dependent. We also injected fluorescent-labeled amyloid β peptide (Aβ1-42) intracranially to L-thyroxine (T4)-injected hyperthyroid model mice and observed sex-dependent microglial phagocytosis in vivo as well. These results may partly explain the gender- and age-dependent differences in neurological and psychological symptoms of thyroid dysfunction.


Negative or disturbed body perceptions are often interwoven with people's physical inactivity. While wearables can support body perception changes (body transformation), the design space of body transformation wearables supporting physical activity remains narrow. To expand this design space, we conducted an embodied co-design workshop with users. Using conceptual and tangible sensitizing tools, we explored/reflected on bodily sensations at three moments of movement execution (before/during/after). Conceptual tools were used to evoke/reflect/capture past lived experiences, while tangible tools were used as ideation probes for sensory bodystorming. Two design concepts emerged, reflecting diverging approaches to body transformation wearables: one focused on reminders and movement correction; the other on sensory augmentation and facilitation. We reflect on how each facilitates useful representations of body sensations during movement, and present methodological recommendations for designing technology for sensory augmentation in this area. Finally, we propose a preliminary prototype based on our design concepts and discuss future steps.


Desktop Virtual Reality (VR) is a simple and affordable way to implement VR technology into an organisation. With PC technology developing at a phenomenal pace fast processor speeds enable the relatively easy development of visually impressive Virtual Environments (VEs) that can be used with familiar desktop PCs for novice and expert end users alike. A need had consequently evolved to ensure that VE development is structured so that VEs can be visually impressive, usable and effective for their purpose. Interaction between the user and the VE is a distinguishing feature of VR but the importance of interaction on the effectiveness of the VE has been little explored, in particular how to measure that effectiveness with a view to providing guidance to VE developers in this case for training applications using the familiar and affordable desktop medium. The use of VR as a training tool has been widely investigated and implemented in both research and industry.

Through experimentation this thesis reviews the design of effective interaction, primarily with the design of selection hotspots (cued objects within the VE designed to prompt the user to select that object) and the importance of implementing task guided interaction into the user's experience with the VR system.

Five experiments were performed to examine the appropriate design of selection hotspots and the importance on the inclusion of a task to the effectiveness of desktop VR training. The initial experiment examined the importance of the user's ability to select within the VE, control their own navigation and the influence of visual realism on the VE's effectiveness as a training tool. The second experiment explored the importance of the user performing a task on the VE's effectiveness and the effectiveness of various selection hotspot cue designs. The third experiment examined influencing factors on the recall of non-task related aspects of the VE. Experiment four examined the effectiveness of selection hotspot cues when they are no longer congruous to the surrounding VE context and the final experiment investigated if participants perceived and recognised the cued objects or were merely responding to the cue and the influence of the inclusion of cues and their design. Effectiveness was measured using the recall of aspects of the VE by the user and measures of usability, presence and enjoyment.

Main findings were that the use of the same incongruous interaction hot spot cues throughout the VE to prompt the selection of specific points within the VE were most effective and using task directed interaction improved task related recall but significantly reduced selection within the VE. Selection significantly increased recall when in a non-task directed VE. With the application of these findings it is possible that designers can produce more effective VEs for their purpose, in this context as a training VE on a desktop VE system.


ABSTRACT Migratory fishes encounter a variety of environmental conditions, including changes in salinity, temperature and dissolved gases, and it is important to understand how these fishes are able to acclimate to multiple environmental stressors. The gill is the primary site of both acid–base balance and ion regulation in fishes. Many ion transport mechanisms involved with acid–base compensation are also required for the regulation of plasma Na+ and Cl+, the predominant extracellular ions, potentially resulting in a strong interaction between ionoregulation and acid–base regulation. The present study examined the physiological interaction of elevated dissolved CO2 (an acid–base disturbance) on osmoregulation during seawater acclimation (an ionoregulatory disturbance) in juvenile white sturgeon (Acipenser transmontanus). Blood pH (pHe), plasma [HCO3−], [Na+], [Cl−] and osmolality, white muscle water content, and gill Na+/K+-ATPase (NKA) and Na+/K+/2Cl− co-transporter (NKCC) abundance were examined over a 10 day seawater (SW) acclimation period under normocarbia (NCSW) or during prior and continued exposure to hypercarbia (HCSW), and compared with a normocarbic freshwater (NCFW) control. Hypercarbia induced a severe extracellular acidosis (from pH 7.65 to pH 7.2) in HCSW sturgeon, and these fish had a 2-fold greater rise in plasma osmolarity over NCSW by day 2 of SW exposure. Interestingly, pHe recovery in HCSW was associated more prominently with an elevation in plasma Na+ prior to osmotic recovery and more prominently with a reduction in plasma Cl− following osmotic recovery, indicating a biphasic response as the requirements of osmoregulation transitioned from ion-uptake to ion-excretion throughout SW acclimation. These results imply a prioritization of osmoregulatory recovery over acid–base recovery in this period of combined exposure to acid–base and ionoregulatory disturbances. Summary: Acidosis recovery in hypercapnic sturgeon associates with plasma Na+ accumulation prior to and plasma Cl− removal following osmotic recovery, as osmoregulatory requirements transition from ion uptake to ion excretion throughout seawater acclimation.