Increasing the physical activity (PA) levels of inactive older adults to promote healthy aging and to reduce preventable health conditions is a public health priority. However, there remains uncertainty on what constitutes the most important components and characteristics of effective PA interventions for older adults, and previous research has largely focused on the cognitive and behavioral strategies they adopt to increase uptake and adherence to PA. This narrative review puts forward the novel idea, with supporting evidence, that the strength, quality, and collaborative nature of the professional-client relationship, a concept drawn from the field of psychotherapy and known as therapeutic alliance, may be a vital and foundational element of effective PA interventions. This article will offer a new understanding, and a new direction of research to aid the future conceptualization, design, and development of interventions that aim to increase the PA levels of older adults.


The current conventional electricity model based on a central national power generation and long-distance transmission grids with its attendant losses is no longer sustainable particularly in isolated rural communities where the cost of building transmission lines and transporting fuels is high. The utilization of minigrids to provide an efficient source of power in Nigeria with a population of over 200 million people have begun. However, it appears this is not sufficient to stimulate the growth of minigrid adoption in Nigeria especially as there is a large disparity between the present minigrid and the national grid price of electricity (N250 - N300/kWh versus N53-N76/kWh), this currently serves as a deterrent to minigrids adoption, viability, and sustainability in Nigeria.
 This paper examined the factors that contribute to the high cost of electricity generation from minigrids as well as provided recommendations to reduce the cost of electricity generation from minigrids by carrying out a technical and economic simulation of an existing 85KW solar based renewable energy minigrid project in Nigeria. This paper used HOMER software for the simulation using Solar PV (PV), Storage Battery(B), Diesel Generator (DG) and Converter as the basecase scenario and other alternative scenarios were also modelled using CNG (Compressed Natural Gas) and LPG (Liquified Petroleum Gas) as alternate sources of fuel
 A structured analysis of the results obtained from the model show that fuel costs accounts as one of the key drivers of the minigrid systems tariff cost, the use of LPG as a source of fuel reduced the tariff cost by about 14% and CNG by about 38%. Based on these findings, this paper proposes the use of LPG and CNG as substitute fuels instead of diesel to reduce the current minigrid systems tariff costs.


A diverse set of hazards are posed by the world's 1500 subaerial volcanoes, yet the majority of them remain unmonitored. Measurements of deformation provide a way to monitor volcanoes, and synthetic aperture RaDAR (SAR) provides a powerful tool to measure deformation at the majority of the world's subaerial volcanoes. This is due to recent changes in how regularly SAR data are acquired, how they are distributed to the scientific community, and how quickly they can be processed to create time series of interferograms. However, for interferometric SAR (InSAR) to be used to monitor the world's volcanoes, an algorithm is required to automatically detect signs of deformation-generating volcanic unrest in a time series of interferograms, as the volume of new interferograms produced each week precludes this task being achieved by human interpreters. In this thesis, I introduce two complementary methods that can be used to detect signs of volcanic unrest.

The first method centres on the use of blind signal separation (BSS) methods to isolate signals of geophysical interest from nuisance signals, such as those due to changes in the refractive index of the atmosphere between two SAR acquisitions. This is achieved through first comparing which of non-negative matrix factorisation (NMF), principal component analysis (PCA), and independent component analysis (ICA) are best suited for solving BSS problems involving time series of InSAR data, and how InSAR data should best be arranged for its use with these methods. I find that NMF can be used with InSAR data, providing the time series is formatted in a novel way that reduces the likelihood of any pixels having negative values. However, when NMF, PCA, and ICA are applied to a set of synthetic data, I find that the most accurate recovery of signals of interest is achieved when ICA is set to recover spatially independent sources (termed sICA). I find that the best results are produced by sICA when interferograms are ordered as a simple ``daisy chain'' of short temporal baselines, and when sICA is set to recover around 1-3 more sources than were thought to have contributed to the time series. However, I also show that in cases such as deformation centred under a stratovolcano, the overlapping nature of a topographically correlated atmospheric phase screen (APS) signal and a deformation signal produces a pair of signals that are no longer spatially statistically independent, and so cannot be recovered accurately by sICA.

To validate these results, I apply sICA to a time series of Sentinel-1 interferograms that span the 2015 eruption of Wolf volcano (Galapagos archipelago, Ecuador) and automatically isolate three signals of geophysical interest, which I validate by comparing with the results of other studies. I also apply the sICA algorithm to a time series of interferograms that image Mt Etna, and through isolating signals that are likely to be due to instability of the east flank of the volcano, show that the method can be applied to stratovolcanoes to recover useful signals. Utilising the ability of sICA to isolate signals of interest, I introduce a prototype detection algorithm that tracks changes in the behaviour of a subaerial volcano, and show that it could have been used to detect the onset of the 2015 eruption of Wolf.

However, for use in an detection algorithm that is to be applied globally, the signals recovered by sICA cannot be manually validated through comparison with other studies. Therefore, I seek to incorporate a module into my detection algorithm that is able to quantify the significance of the sources recovered by sICA. I achieve this through extensively modernising the ICASO algorithm to create a new algorithm, ICASAR, that is optimised for use with InSAR time series. This algorithm allows me to assess the significance of signals recovered by sICA at a given volcano, and to then prioritise the tracking of any changes they exhibit when they are used in my detection algorithm.

To further develop the detection algorithm, I create two synthetic time series that characterise the different types of unrest that could occur at a volcanic centre. The first features the introduction of a new signal, and my algorithm is able to detect when this signal enters the time series by tracking how well the baseline sources are able to fit new interferograms. The second features the change in rate of a signal that was present during the baseline stage, and my algorithm is able to detect when this change in rate occurs by tracking how sources recovered from the baseline data are used through time. To further test the algorithm, I extended the Sentinel-1 time series I used to study the 2015 eruption of Wolf to include the 2018 eruption of Sierra Negra, and I find that my algorithm is able to detect the increase in inflation that precedes the eruption, and the eruption itself.

I also perform a small study into the pre-eruptive inflation seen at Sierra Negra using the deformation signal and its time history that are outputted by ICASAR. A Bayesian inversion is performed using the GBIS software package, in which the inflation signal is modelled as a horizontal rectangular dislocation with variable opening and uniform overpressure. Coupled with the time history of the inflation signal provided by ICASAR, this allows me to determine the temporal evolution of the pre-eruptive overpressure since the beginning of the Sentinel-1 time series in 2014. To extend this back to the end of the previous eruption in 2005, I use GPS data that spans the entire interruptive period. I find that the total interruptive pressure change is ~13.5 MPa, which is significantly larger than the values required for tensile failure of an elastic medium overlying an inflating body. I conclude that it is likely that one or more processes occurred to reduce the overpressure within the sill, and that the change in rate of inflation prior to the final failure of the sill is unlikely to be coincidental.

The second method I develop to detect volcanic deformation in a time series of interferograms uses a convolutional neural network (CNN) to classify and locate deformation signals as each new interferogram is added to the time series. I achieve this through building a model that uses the five convolutional blocks of a previously state-of-the-art classification and localisation model, VGG16, but incorporates a classification output/head, and a localisation output/head. In order to train the model, I perform transfer learning and utilise the weights made freely available for the convolutional blocks of a version of VGG16 that was trained to classify natural images. I then synthesise a set of training data, but find that better performance is achieved on a testing set of Sentinel-1 interferograms when the model is trained with a mixture of both synthetic and real data. I conclude that CNNs can be built that are able to differentiate between different styles of volcanic deformation, and that they can perform localisation by globally reasoning with a 224 x 224 pixel interferogram without the need for a sliding window approach.

The results I present in this thesis show that many machine learning methods can be applied to both time series of interferograms, and individual interferograms. sICA provides a powerful tool to separate some geophysical signals from atmospheric ones, and the ICASAR algorithm that I develop allows a user to evaluate the significance of the results provided by sICA. I incorporate these methods into an deformation detection algorithm, and show that this could be used to detect several types of volcanic unrest using data produced by the latest generation of SAR satellites. Additionally, the CNN I develop is able to differentiate between deformation signals in a single interferogram, and provides a complementary way to monitor volcanoes using InSAR.


Purpose: This paper seeks to explore the effect of emotions on sustainable purchasing in Arab countries, mainly Qatar and Egypt.
Design/methodology/approach: The current investigation will empirically examine the effects of self-conscious emotions (private and public) on consumers' 'green' purchasing behavior and test whether these actions are mediated by the following emotions: empathy, pride, and guilt. An online self-report survey was employed to collect data from 234 students and faculty members who are affiliated with Qatar University (Qatar) and Tanta University (Egypt). A Confirmatory Factor Analysis (CFA) was used to determine what factors directly and indirectly influence one's Willingness To Pay (WTP) for sustainable products.
Findings: The results showed that private self-consciousness was significantly related to feelings of pride, while public self-consciousness was more closely associated with empathy. Feelings of guilt and pride were more likely to encourage participants to pay greater for sustainable products and services.
Originality/value: The link between emotions and sustainable purchasing remains novel in Arab countries. Previous research has found that having ethical awareness toward sustainable purchasing does not amount to purchasing 'green' products. This will be the first study to explore the impact emotions can have on sustainable purchasing.


Bayesian
inference method has been presented in this paper for the modeling of
operational risk. Bank internal and external data are divided into defined loss
cells and then fitted into probability distributions. The distribution
parameters and their uncertainties are estimated from posterior distributions
derived using the Bayesian inference. Loss frequency is fitted into Poisson
distributions. While the Poisson parameters, in a similar way, are defined by
a posterior distribution developed using Bayesian inference. Bank operation
loss typically has some low frequency but high magnitude loss data. These heavy
tail low frequency loss data are divided into several buckets where the bucket
frequencies are defined by the experts. A probability distribution, as defined
by the internal and external data, is used for these data. A Poisson
distribution is used for the bucket frequencies. However instead of using any
distribution of the Poisson parameters, point estimations are used. Monte
Carlo simulation is then carried out to calculate the capital charge of the in-
ternal as well as the heavy tail high profile low frequency losses. The output
of the Monte Carlo simulation defines the capital requirement that has to be
allocated to cover potential operational risk losses for the next year.


The study sought to determine the influence of entrepreneurial strategies on customer satisfaction in water providers in Kenya as the general objective. The study was guided by four objectives: To identify organizational networking challenges faced by ELDOWAS in improving customer satisfaction; To establish money management strategies with the highest returns investment in ELDOWAS; To examine technological strategies adopted by ELDOWAS to improve customer satisfaction and To establish planning strategies used by ELDOWAS in improving customer satisfaction. The study adopted a descriptive research design to collect data. The study covered a sample size of 69 drawn from a population of 230 employees of Eldoret Water and Sanitation Company Limited. The sample was selected through stratified random sampling technique. The main data collection instrument was questionnaire which contained both open ended and closed ended question. Descriptive statistics data analysis method was applied to analyze data aided by Statistical Package for Social Sciences (SPSS) version 23 to complete response of mean, frequencies, percentages and standard deviation results. Quantitative data was analyzed using descriptive of tables and bar charts. Finally, Multiple Linear Regression model was used to determine the significance of the independent variable in the dependent variable. The study concluded money management followed by organizational networking then planning and lastly technology influenced customer satisfaction in ELDOWAS differently. The study recommended that the ministry of water and stakeholders responsible in water industry should train all employees involved in water provision and customer satisfaction. The training should emphasis on improving leadership management of top managers, shaping organizational culture affecting employees and focus on improving organizational objective in order to get good returns.


This article explores cross-cultural challenges that arise when university and community members collaborate in community-based participatory research. As part of a project for primary prevention of human immunodeficiency virus (HIV) infection, researchers trained community leaders to jointly develop a research question and conduct a pilot qualitative study in a Puerto Rican community in Massachusetts. Different priorities of the community and university members about HIV as a research topic underscored the need to continuously reflect on developing a research question in community-based participatory research. Recognizing the cultural assumptions of both university and community members is an important component of capacity building among collaborative research teams.


Abstract — This study describes the methodology for the development of a validated in-vitro in-vivo correlation (IVIVC) for metoprolol tartrate modified release dosage forms with distinctive release rate characteristics. Modified release dosage forms were formulated by microencapsulation of metoprolol tartrate into different amounts of ethylcellulose by non-solvent addition technique. Then in-vitro and in-vivo studies were conducted to develop and validate level A IVIVC for metoprolol tartrate. The values of regression co-efficient (R 2 -values) for IVIVC of T2 and T3 formulations were not significantly (p<0.05) different from 1 while the values of R 2 for IVIVC of T1 and Mepressor ® were significantly (p<0.05) different from 1. Internal prediction errors of IVIVC, calculated from observed Area under Curve (AUC) and predicted AUC, were less than 10%. This study successfully presents a valid level A IVIVC for metoprolol tartrate modified dosage forms. Keywords — Metoprolol tartrate, Dissolution, Bioavailability, Validated in-vitro in-vivo correlation.I.


BACKGROUND
This study aimed to investigate the neuromuscular effects of 0.6 mg/kg rocuronium under desflurane anesthesia in patients with and without renal failure.

METHODS
The neuromuscular effects of rocuronium 0.6 mg/kg under desflurane anesthesia were investigated in 20 patients with renal failure undergoing renal transplantation surgery and in 20 patients with normal renal function. Neuromuscular transmission was monitored using acceleromyography with single stimuli at 0.1 Hz. The onset and 25%, 75%, and 95% twitch recovery times, the recovery of the train-of-four ratio to 70% (TOF70), and the recovery index (25-75%) were recorded.

RESULTS
Block onset was similar in the groups. The 25%, 75% and 95% twitch recovery times, the TOF70 time, and the recovery index were found to be prolonged in patients with renal failure compared to those with normal renal function (e.g. TOF70: 123.1 +/- 49.1 vs. 68.7 +/- 15.5 min) (P<0.001). A very strong association between the time to TOF70 and the diagnostic duration of renal failure was found (R2 = 0.79, P<0.001).

CONCLUSIONS
The duration of action of a bolus dose of 0.6 mg/kg rocuronium under desflurane anesthesia was increased significantly in patients with end-stage renal failure compared to that of healthy controls and was prolonged according to the duration of renal failure.


The increasing availability of data has generated unprecedented prospects for network analyses in many biological fields, such as neuroscience (e.g., brain networks), genomics (e.g., gene-gene interaction networks), and ecology (e.g., species interaction networks). A powerful statistical framework for estimating such networks is Gaussian graphical models, but standard estimators for the corresponding graphs are prone to large numbers of false discoveries. In this paper, we introduce a novel graph estimator based on knockoffs that imitate the partial correlation structures of unconnected nodes. We show that this new estimator guarantees accurate control of the false discovery rate in theory, simulations, and biological applications, and we provide easy-to-use R code.


PURPOSE
To explore possible correlation between CT image-based texture and histogram features and time-to-local-failure in early stage non-small cell lung cancer (NSCLC) patients treated with stereotactic body radiotherapy (SBRT).

METHODS AND MATERIALS
From an IRB-approved lung SBRT registry for patients treated between 2009-2013 we selected 48 (20 male, 28 female) patients with local failure. Median patient age was 72.3±10.3 years. Mean time to local failure was 15 ± 7.1 months. Physician-contoured gross tumor volumes (GTV) on the planning CT images were processed and 3D gray-level co-occurrence matrix (GLCM) based texture and histogram features were calculated in Matlab. Data were exported to R and a multiple linear regression model was used to examine the relationship between texture features and time-to-local-failure.

RESULTS
Multiple linear regression revealed that entropy (p=0.0233, multiple R2=0.60) from GLCM-based texture analysis and the standard deviation (p=0.0194, multiple R2=0.60) from the histogram-based features were statistically significantly correlated with the time-to-local-failure.

CONCLUSION
Image-based texture analysis can be used to predict certain aspects of treatment outcomes of NSCLC patients treated with SBRT. We found entropy and standard deviation calculated for the GTV on the CT images displayed a statistically significant correlation with and time-to-local-failure in lung SBRT patients.


We describe the antenatal diagnosis of a fetus with mirror-image dextrocardia, complete situs inversus and Turner's mosaicism (45,XO/46,XY) that was artificially terminated at 19 weeks. Autopsy confirmed our initial findings. This case represents an unusual combination of anomalies rarely encountered in clinical practice.


Our laboratory has a long-standing interest in understanding the involvement of Rho GTPases in cell growth and migration, which recently led to our discovery of a novel signaling connection between these GTPases and elevated glutamine metabolism in cancer cells. This was based on our identification of a small molecule inhibitor that blocks the transformation of fibroblasts by oncogenic Dbl (for Diffuse B cell lymphoma), a Rho GTPase-activator, as well as inhibits the growth of human breast cancer and B lymphoma cells, and shrinks tumors induced by these cancer cells in mice. The effects of the small molecule inhibitor are specific for transformed/cancer cells, as it does not inhibit the growth of normal fibroblasts or mammary epithelial cells. We identified the target of this inhibitor to be an isoform of the metabolic enzyme glutaminase (GLS1), which catalyzes the hydrolysis of glutamine to glutamate. Transformed/cancer cells show markedly elevated levels of GLS1 activity, due to post-translational modifications (phosphorylation) that are dependent on the activation of Rho GTPases and NFκB, and are blocked by the small molecule inhibitor. Recently, we have shown that an important outcome of the metabolic changes exhibited by cancer cells, that can be prevented by the inhibitor, is the generation of vesicular structures (oncosomes) that contain signaling proteins, metabolic enzymes, RNA transcripts and microRNA. Oncosomes, by transferring these components to recipient cells, are capable of conferring transformed properties on to their acceptor cells and thus have been suggested to play important roles in cancer progression. Collectively, these results shed new light on how glutamine metabolism is elevated during tumorigenesis in order to satisfy the 'glutamine addiction' of cancer cells, as well as demonstrate the consequences of such metabolic changes and how they might be interrupted. The hope is that these insights will highlight new strategies for therapeutic intervention. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr PL08-04.


AIMS AND OBJECTIVES
To explore decision processes and types of decisions made by heart failure specialist nurses.

BACKGROUND
Heart failure specialist nurses are key to the management of patients with heart failure in the community. In previous studies heart failure specialist nurses have reported difficulty in developing decision making skills. Cognitive continuum theory can be used to examine the relationship between decision tasks and the processes used by heart failure specialist nurses to make decisions.

DESIGN
A qualitative study using non-participant observation and semi-structured interviews.

METHODS
Six heart failure specialist nurses were observed while they carried out consultations with three patients each (n = 18). Twelve heart failure specialist nurses were interviewed about their decision making in practice. Data were analysed using thematic content analysis.

RESULTS
Two areas of decision making were identified by heart failure specialist nurses as key; pharmacological management and managing patients in the palliative phase of their condition. Pharmacological management decisions involved the trading off of risks and benefits of titrating medication, with nurses using internalised guidelines to inform their practice. In contrast, nurses relied on support from other health care professionals when making decisions about a patient's need for palliative care.

CONCLUSIONS
Medication titration decisions have a mixture of intuition and analysis inducing features making them amenable to the use of decision tools. The timing of the need for palliative care is less predictable, suggesting an intuitive approach to decision making may be more appropriate.

RELEVANCE TO CLINICAL PRACTICE
There are several strategies that could be used to improve the match between the decisions that heart failure specialist nurses take and the decision processes they use. These include the development of more tailored decision support tools for medication titration decisions and the provision of structured decision aids for assessing patients' need for palliative care.


The negative stock price reaction to bad news disclosures is much larger in magnitude than the positive stock price reaction to good news disclosures. Diamond and Verrecchia (1987) posit that short-selling restrictions cause this asymmetry while Kothari, Shu, and Wysocki (2009) interpret it as evidence that managers withhold bad news and leak good news. This study explores the merits of these two explanations in a joint framework. Two popular measures of short-sale constraints based on institutional ownership and short interest ratios have no incremental power in explaining the asymmetry when factors that influence managers' incentives to disclose news in a timely fashion are controlled for. Only, the Prob-measure advocated by Ali and Trombley (2006) is incrementally significant in explaining the larger stock price reaction to bad news. Moreover, the fraction of bad news reflected in stock prices prior to bad news disclosures is significantly higher for more short-sale constrained stocks.


Cloud computing is promising technology to manage and improve utilization of computing center resources to deliver various computing and IT services. For the purpose of energy saving there is no need to unnecessarily operate many servers under light loads, and they are switched off. On the other hand, some servers should be switched on in heavy load cases to prevent very long delays. Thus, waiting times and system operating cost can be maintained on acceptable level by dynamically adding or removing servers. One more fact that should be taken into account is significant server setup costs and activation times. For better energy efficiency, cloud computing system should not react on instantaneous increase or instantaneous decrease of load. That is the main motivation for using queuing systems with hysteresis for cloud computing system modelling. In the paper, we provide a model of cloud computing system in terms of multiple server threshold-based infinite capacity queuing system with hysteresis and noninstantanuous server activation. For proposed model, we develop a method for computing steady-state probabilities that allow to estimate a number of performance measures.


For better or worse, the global financial system went through remarkable change over the last decades. Cross-border banking giants emerged; many countries opened up their banking systems welcoming foreign ownership; government ownership in banking, which is deemed to be vicious, declined globally. The financial crisis of 2007-2009, however, changed our understanding of the global financial system and provided renewed impetus to some crucial debates, which may inform the policy-makers to avoid future crises. The chapters of this thesis contribute the ongoing discussions by providing empirical evidence on some crucial aspects. Chapter 2 analyzes the transmission of real estate price changes through multinational banks by investigating the credit supply of banks in response to national and foreign real estate price changes. In Chapter 3, we focus on the internationalization of banks and possible roles of financial safety nets and market discipline related to internationalization. Chapter 4 provides empirical evidence regarding countercyclical behavior of government owned banks, which may be useful during bad times. Finally, in Chapter 5 we focus on the macroeconomic effects of securitization at the aggregate level and show that securitization may have a negative impact on real economic outcomes by changing the credit composition towards consumption.


For the purposes of starting to tackle, within artificial intelligence (AI), the narrative aspects of legal narratives in a criminal evidence perspective, traditional AI models of narrative understanding can arguably supplement extant models of legal narratives from the scholarly literature of law, jury studies, or the semiotics of law. Not only: the literary (or cinematic) models prominent in a given culture impinge, with their poetic conventions, on the way members of the culture make sense of the world. This shows glaringly in the sample narrative from the Continent-the Jama murder, the inquiry, and the public outcry-we analyse in this paper. Apparently in the same racist crime category as the case of Stephen Lawrence's murder (in Greenwich on 22 April 1993) with the ensuing still current controversy in the UK, the Jama case (some 20 years ago) stood apart because of a very unusual element: the eyewitnesses identifying the suspects were a group of football referees and linesmen eating together at a restaurant, and seeing the sleeping man as he was set ablaze in a public park nearby. Professional background as witnesses-cum-factfinders in a mass sport, and public perceptions of their required characteristics, couldn't but feature prominently in the public perception of the case, even more so as the suspects were released by the magistrate conducting the inquiry. There are sides to this case that involve different expected effects in an inquisitorial criminal procedure system from the Continent, where an investigating magistrate leads the inquiry and prepares the prosecution case, as opposed to trial by jury under the Anglo-American adversarial system. In the JAMA prototype, we tried to approach the given case from the coign of vantage of narrative models from AI.


Understanding the ingredients (APIs), in particular insight into the relationships between crystal structure and the thermodynamics of polymorph stability, is vital for the production of more stable drugs and better therapeutics, and for the economics of the pharmaceutical industry in general. In this paper, we report a detailed study of the structure-property relationships among the polymorphs of the model API, Sulfamerazine. Detailed experimental characterization using synchrotron radiation is complemented with computational modelling of the lattice-dynamics and mechanical properties, to study the origin of differences in millability and to investigate the thermodynamics of the phase equilibria. Good agreement is observed between calculated phonon density of states curves and mid-infrared and Raman spectra. The presence of slip planes, evident in the low-frequency lattice vibrations, explains the higher millability of Form I compared to Form II. Energy/volume curves for the three polymorphs, together with the temperature dependence of the thermodynamic free energy computed from the phonon frequencies, explains why Form II converts to Form I at high temperature, whereas Form III is a rare polymorph which is difficult to isolate. Moreover, the combined experimental and theoretical approach employed here should be generally applicable to the study of other systems which exhibit polymorphism, potentially helping to deliver better, more active forms of drugs at lower costs.


Along with the angiotensin-converting enzyme inhibitors (ACEIs), the β-adrenergic receptor blockers have gradually emerged to be standard in the therapy of heart failure. Individual β-blockers that have been shown to reduce all-cause mortality in patients with heart failure include bisoprolol, metoprolol and carvedilol. Carvedilol distinguishes from the other β-blockers as being a non-selective 1- and 2-receptor blocker with 1-receptor blockade effect and anti-oxidant properties. The drug does not have sympathomimetic activity and has vasodilatory effects attributable to its 1-receptor blockade property. Experimental and clinical studies have confirmed carvedilol's vasodilator, anti-oxidant and anti-apoptotic properties, which may contribute to its effect in reversing cardiac remodelling in animal models and patients with heart failure. These pharmacological properties render carvedilol a potentially useful agent in the treatment of patients with heart failure. Early studies of carvedilol in heart failure have reported beneficial haemodynamic effects but variable effects on exercise tolerance and clinical well being. The large-scale US Carvedilol Heart Failure Program and the Australian/New Zealand Heart Failure Collaborative Research Group reported beneficial effects of carvedilol on mortality, morbidity and clinical well being in patients with mild-to-moderate heart failure. The recently reported but yet unpublished preliminary results of the COPERNICUS study suggest that carvedilol improves mortality and morbidity in patients with advanced heart failure and severe symptoms. At this time, it is unclear whether the ancillary pharmacological properties of carvedilol can be translated to more superior clinical benefit compared to the other β-blockers. Preliminary studies examining surrogate end points suggest that carvedilol may improve left ventricular ejection fraction (LVEF) more than metoprolol. More conclusive information regarding their relative effects of clinical outcomes will await the completion of the COMET study, which compares the effect of metoprolol and carvedilol on mortality and morbidity, expected at the end of the year 2002.


Abstract The hospital-to-community transition is fraught with risks for patients, with 30-day readmission rates of 20% for Medicare patients. Poorly coordinated transitions of care translate to unplanned readmission costs to Medicare of more than $17 billion/year. Calls for better physician communication to improve care coordination abound; however, primary care physicians cannot better coordinate care when, in many cases, they are not even aware that their patients have been admitted to the hospital. During the past 30 years, we have made little progress in systematically improving communication between hospital and posthospital providers to coordinate postdischarge care. Hospitals and physicians need better tools to coordinate care transitions. It is time to automate the hospital discharge notification process, notify practice staff, and stop expecting physician-to-physician communication. Notification can be efficiently supported by computerized systems that do not rely on physicians to "close the loop" back to primary care. We present four clinical programs in which automated notification of primary care staff was used to ensure appropriate follow-up and coordination of care for patients. These automated systems use a secure online Web site or an encrypted e-mail notification system that alerts clinicians and practice staff to hospital registration of the patient. In each program, notification triggers a nurse-directed clinical assessment and care coordination plan and helps ensure timely primary care follow-up. We believe automated notification is a necessary tool to support coordination of care in the new delivery models such as the patient-centered medical home.


Background. Maternal mortality has continued to escalate in Kenya inspite of all the efforts being made by the government, non-governmental organization and the community. The purpose of the study was to establish the antecedent factors predisposing women to maternal death using the three delays model. Methodology: Retrospective 72 maternal death cases which occurred between January 01, 2009 and June 30, 2010 were reviewed by an independent gynecologist/obstetrician. Interviews were conducted with kins of the deceased women using a confidential questionnaire for female death based on distal as well as proximal factors that may have had a bearing on maternal death. Health care workers were likewise interviewed using a formulated questionnaire to assess the ability and readiness of the hospital to offer emergency obstetric care. Results: A record of 72 maternal deaths occurred during the study period thus between January 1, 2009 and June 30. 2010. Out of 72, 42 maternal deaths were as a result of direct obstetric complications which include hemorrhage, post-partum sepsis, pre-eclampsia and abortion. Post partum hemorrhage was the most common complication which contributed to maternal deaths. Again out of 72 maternal deaths, 33 were as a result of indirect causes with peritonitis, heart disease, HIV/AIDS, anemia, and convulsive disorder respectively. Delayed access to transport, lack of money for user fees, and hospital distance were challenges that led to delay in accessing care. Hospital experiences included; delay in service provision by staff, delayed quality emergency obstetric care and delayed care while at the hospital, unavailability of blood for transfusion, and lack of money for drugs, were reported as major challenges which attributed to maternal death. Conclusion: The study suggests maternal mortality occurs as a result of lack of access to quality healthcare facility poor health seeking behavior and poor socio-economic factors.


The following contribution is concerned with the particularities of theatre translation, a discipline at the crossroads of Translation Studies and Theatre Studies. More specifically, it is a case-study on the translation of the literary dialect which functions as a dramatic instrument in Eugene O'Neill's Desire under the elms (1924). The particular idiom which characterizes the play's protagonists is not only marked by its vernacular linguistic markers, but also by its remarkably unruly, fragmentary and dissonant rhythm, promoting the performative faculty. It was Arne Sierens who, in 1992 and at the request of theatre company Het Zuidelijk Toneel, brought the text to the Low Countries. An analysis of the specific considerations which Sierens had to take into account when translating for this linguistically and culturally diverse area, as well as the translation strategies applied, is followed by a look into the collaborative translation process between translator, director, dramaturge and actors, which theatre translation today essentially is. The findings reassert why drama translation deserves its place as an autonomous field within academic research. Keywords: drama translation, literary dialect, collective authorship, Arne Sierens, Eugene O'Neill


INTRODUCTION
Repetitive transcranial magnetic stimulation (rTMS) is a method of brain stimulation which is increasingly used in both clinical practice and research. Up-to-date studies have pointed out a potential antidepressive effect of rTMS, but definitive superiority over placebo has not yet been confirmed.

OBJECTIVE
The aim of the study was to examine the effect of rTMS as an adjuvant treatment with antidepressants during 18 weeks of evaluation starting from the initial application of the protocol.

METHODS
Four patients with the diagnosis of moderate/severe major depression were included in the study.The protocol involved 2000 stimuli per day (rTMS frequency of 10 Hz, intensity of 120% motor threshold) administered over the left dorsolateral prefrontal cortex (DLPFC) for 15 days. Subjective and objective depressive symptoms were measured before the initiation of rTMS and repeatedly evaluated at week 3, 6, 12 and 18 from the beginning of the stimulation.

RESULTS
After completion of rTMS protocol two patients demonstrated a reduction of depressive symptoms that was sustained throughout the 15-week follow-up period. One patient showed a tendency of remission during the first 12 weeks of the study, but relapsed in week 18. One patient showed no significant symptom reduction at any point of follow-up.

CONCLUSION
Preliminary findings suggest that rTMS has a good tolerability and can be efficient in accelerating the effect of antidepressants, particularly in individuals with shorter duration of depressive episodes and moderate symptom severity.


Due to substantial changes in society and reform processes in health care, Professional Nursing practice today is facing great challenges. Nursing Sciences can be considered as an answer to these challenges. One of Nursing Sciences' pressing tasks is the discussion of the relationship between nursing and technology in a health care environment with an ever increasing level of technology. A detailed discussion and analysis of this problem in the German speaking countries is yet to happen. This article's intent is to summarize critically the current state of the international debate on the relationship between technology and nursing and thus to stimulate the discussion. While the paper's first part focused on traditional, essentialist interpretation this second part depicts the current international arguments in view of the dialectic relationship between nursing and technology.


Unlike the current measures in the literature, where corruption is constructed as an index, this paper provides a formula for quantifying corruption. By using option pricing techniques, the paper shows that the monetary value of a corrupt activity is equivalent to a regular bond and an embedded European call option. This formula is very important because it could be used to gauge the level resources lost to corrupt activities, and also to determine the level of "tax" that could be levied at corrupt-government officials. Results in the paper show that a government committed to reducing corruption should institute measures that will reduce the level and the volatility of the price of the goods in the parallel markets. The paper also finds that a government could reduce corruption by cutting interest rates, which would spur growth and render corruption as an unprofitable exercise.


The automated documentation of work steps is a requirement of many modern manufacturing processes. Especially when it comes to important procedures such as safety critical screw connections or weld seams, the correct and complete execution of certain manufacturing steps needs to be properly supervised, e.g., by capturing video snippets of the worker to be checked in hindsight. Without proper technical and organizational safeguards, such documentation data carries the potential for covert performance monitoring to the disadvantage of employees. Naïve documentation architectures interfere with data protection requirements, and thus cannot expect acceptance of employees. In this paper we outline use cases for automated documentation and describe an exemplary system architecture of a workflow recognition and documentation system. We derive privacy protection goals that we address with a suitable security architecture based on hybrid encryption, secret-sharing among multiple parties and remote attestation of the system to prevent manipulation. We finally contribute an outlook towards problems and possible solutions with regards to information that can leak through accessible metadata and with regard to more modular system architectures, where more sophisticated remote attestation approaches are needed to ensure the integrity of distributed components.


Hydrogen peroxide (H2O2) and nitric oxide (NO) are key signaling molecules in cells whose levels are increased in response to various stimuli and are involved in plant secondary metabolite synthesis. In this paper, the roles of H2O2 and NO on salvianolic acid B (Sal B) production in salicylic acid (SA)-induced Salvia miltiorrhiza cell cultures were investigated. The results showed that H2O2 could be significantly elicited by SA, even though IMD (an inhibitor of NADPH oxidase) or DMTU (a quencher of H2O2) were employed to inhibit or quench intracellular H2O2. These elicited H2O2 levels significantly increased NO production by 1.6- and 1.46 fold in IMD+SA and DMTU+SA treatments, respectively, and induced 4.58- and 4.85-fold Sal B accumulation, respectively. NO was also markedly elicited by SA, in which L-NNA (an inhibitor of NO synthase) and cPTIO (a quencher of NO) were used to inhibit or quench NO within cells, and the induced NO could significantly enhance H2O2 production by 1.92- and 1.37-fold in L-NNA+SA and cPTIO+SA treatments, respectively, and 3.27- and 1.50-fold for Sal B accumulation, respectively. These results indicate that elicitation of SA for either H2O2 or NO was independent, and the elicited H2O2 or NO could act independently or synergistically to induce Sal B accumulation in SA-elicited cells.


Polar lows (PLs) are intense maritime mesoscale cyclones that can pose hazards to coastal communities and marine operation in the Arctic. This study examines the impacts of sudden stratospheric warmings (SSWs) on PL activity in the subarctic North Atlantic. The 20 days following SSWs are characterized by tropospheric circulation anomalies resembling the negative phase of the North Atlantic Oscillation. PL activity decreases significantly over the Labrador Sea, which can be attributed to seldom occurrence of low static stability and strong environmental baroclinicity, as well as reduced surface turbulent heat fluxes. These results suggest that a skillful prediction of SSWs can improve the extended-range forecast of PL activity over the Labrador Sea. For the Nordic Seas, the results imply that the spatial structure of an SSW event is important for the PL modulation through different tropospheric circulation patterns. Situations with increased PL frequency in the Nordic Seas are characterized by SSWs centered close to Northern Greenland occurring over a smaller area, and a tropospheric response featuring enhanced cold-air outbreaks over the Norwegian Sea. Conversely, PL activity is suppressed over the Nordic Seas when the SSW favors the formation of a tropospheric anticyclone above Greenland and Scandinavia.


An experimental investigation of the lubricated steady sliding contact for elastically soft solids is reported. We show that the anisotropic character of the surface roughness has a strong influence in determining the transition from boundary lubrication, where the normal load is fully supported by the asperity-asperity interactions, to the hydrodynamic regime, where a thin fluid layer completely separates solid surfaces from direct contact. In particular, tests have been carried out using a ball-on-flat test configuration to measure the friction coefficient at the contact between a smooth steel ball and a rough PDMS as a function of the sliding speed. The most noteworthy result is that the presence of roughness anisotropy strongly modifies the classical shape of the Stribeck curve as a consequence of local micro-EHL conditions which occur at the contact interface.


Time-frequency distributions that evaluate the signal's energy content both in the time and frequency domains are indispensable signal processing tools, especially, for nonstationary signals. Various short-time energy computation schemes are used in practice, including the mean squared amplitude and Teager-Kaiser energy approaches. Herein, we focus primarily on the short- and medium-term properties of these two energy estimation schemes, as well as, on their performance in the presence of additive noise. To facilitate this analysis and generalize the approach, we use a harmonic noise model to approximate the noise component. The error analysis is conducted both in the continuous- and discrete-time domains, deriving similar conclusions. The estimation errors are measured in terms of normalized deviations from the expected signal energy and are shown to greatly depend on both the signals' spectral content and the analysis window length. When medium- and long-term analysis windows are employed, the Teager-Kaiser energy operator is proven superior to the common squared energy operator, provided that the spectral content of the noise is more lowpass than the corresponding signal content, and vice versa. However, for shorter window lengths, the Teager-Kaiser operator always outperforms the squared energy operator. The theoretical results are experimentally verified for synthetic signals. Finally, the performance of the proposed energy operators is evaluated for short-term analysis of noisy speech signals and the implications for speech processing applications are outlined.


This article provides radiological safety professionals at nuclear power plants with information on the prevention, mitigation, and control of discrete radioactive particles (DRP). In 1990, a health physicist from the ALARA Center at Brookhaven National Laboratory searched the literature, communicated with nine health physicists involved with DRP protection, and visited Southern California Edison Company's San Onofre Nuclear Station, and Arizona Public Service Company's Palo Verde Generating Station to collect data and information on DRPs. A root cause analysis then was performed on how discrete radioactive particles escape from the reactor and coolant system and either irradiate the skin of workers or get inadvertently released off-site. This article organizes the root causes and corrective actions into four categories: discrete radioactive particle production; work environment; worker; and off-site environment. A bibliography of related papers and reports is also included.


Effect of somatostatin infusion (100 ng/min-61 pmol/min) on organ blood flow was studied in anaesthetized cats. Total blood flow in the superior mesenteric, left renal, lienal, inferior caval veins and the sagittal sinus was measured by the H2-clearance method. Vascular resistance decreased in the small intestine, in the hind limb and in the kidney due to somatostatin infusion. Somatostatin seems to have direct vasodilatory effect in different vascular beds.


Access to sufficient amounts of energy is a prerequisite for the development of human well-being. The Sustainable Development Goals (SDGs) recognize the interconnectedness of climate change, energy access and development. However, not all SDG targets are quantified, leaving room for ambiguity in fulfilling, for example, the goal of ensuring access to affordable, reliable, sustainable and modern energy for all (SDG7). We show how specific sustainable development targets for health indicators are strongly correlated with electricity consumption levels in the poorest of countries. Clear thresholds in per capita electricity consumption of a few hundred kWh per year are identified by analyzing SDG indicator data as a function of per capita country electricity consumption. Those thresholds are strongly correlated with meeting of SDG 3 targets-below the identified thresholds, countries do not meet the SDG targets, while above the threshold there is a clear relationship between increasing consumption of electricity and improvement of SDG indicators. Electricity consumption of 400 kWh per capita is significantly higher than projections made by international agencies for future energy access, but only 5%–10% that of OECD countries. At the very least, the presence of thresholds and historical data patterns requires an understanding of how SDG targets would be met in the absence of this threshold level of electricity access.


The boundary layer dynamics are significantly responsible for the friction behavior of a tribo contact. A test bench to investigate the processes in the boundary layer was introduced in [1]. The so-called Wear Debris Investigator (WDI) of the Institute of Dynamics and Vibrations (IDS) forms a friction gap between a rotating and a fixed disc. For a measurement, artificial wear particles are added into the friction gap. The rotating disc of the friction contact consists of a transparent material. This allows the boundary layer to be observed in situ using a high-resolution camera. The obtained image data is used, i. a., to make statements about the formation and destruction processes of contact patches. With the measurement data of an implemented force and torque sensor, correlations between the boundary layer dynamics and the occurring friction forces can be made. This requires a high-precision measurement setup. A large number of measurements at the WDI revealed that precision and force measurement are not sufficient for all dynamic phenomena. For this reason, an innovative measuring system has been developed within the framework of this paper, which allows accurate statements to be made about the interactions of the third body with the first bodies. One major advantage of the new measuring device is that there are almost no drift effects observed during the measurement of the normal forces and friction moments. System-related normal force fluctuations are countered by a force adjustment with three adjustable elasticities, whereby the fluctuations are almost eliminated. This design allows to precisely adjust the normal forces in a wide range. Even measurements with smallest load ranges are provided by the innovative test design. First measurements using the new measuring device are presented in this paper.


The whitefly Bemisia tuberculata has caused serious damage to cassava producing areas in the state of Mato Grosso do Sul. However, little is known about the biological characteristics of this species. The objective of this study was therefore, to monitor the development of this species bred on cassava plants under controlled greenhouse conditions, and to determine its most vulnerable stages and its reproductive capacity, as well as measuring the length and width each stage of development. To obtain these data, adult individuals were kept in voile traps on cassava leaves of five different plants, totalling ten leaves. After 24 hours the leaves were removed from the traps thus making each egg-laden leaf an experimental unit. The lowest mortality rate was record in the last nymphal stage ('pupae) compared with the other development stages. The highest mortality occurred in the nymphs at the 2nd and 3rd instars. Each female laid an average of 6.3 eggs in 24 hours. Thirteen days after egg laying, every one of the nymphs was fixed on the leaves of cassava plants. From the egg laying stage up until the adult stage, the process took 26 days. The proportion of females was 73.5%. The average size of the B. tuberculata egg was 163.22 µm in length and 72.39 µm in width and the "pupae" is 915.82 µm in length and 628.71 µm in width. The measurements of males were 797.16 µm in length and 200.81 µm in width and the length females 916.12 µm in length and 338.99 µm in width. The parasitoid Encarsia porteri (Mercet, 1928) (Hymenoptera, Aphelinidae) was found in the insect stock culture.


INTRODUCTION AND OBJECTIVE: Reconstructive urologists often place both a urethral catheter (UC) and suprapubic (SP) catheter intraoperatively to prevent extravasation of undrained urine across anastomosis sutures after various urethroplasty surgeries. Postoperatively, many surgeons leave one catheter to gravity drainage and cap the other. As no consensus exists on which catheter drains the bladder more completely, we sought to identify differences in urine outflow and if both catheters should be opened to maximize bladder drainage. METHODS: Urine output (UOP) records from patients who underwent Stage II Phalloplasty with urethral lengthening from 5/2017 to 11/2020 were retrospectively reviewed. Both a UC and SP catheter were placed to gravity drainage postoperatively. UOP (ml) from each catheter was recorded separately, twice daily, through discharge. Mixed model regression modeling tested for differences in UOP by catheter French (Fr) and time. RESULTS: In total, 18 patients were identified. In 14 of 18 patients (78%) a 16 Fr UC and SP catheter were placed intraoperatively. Median length of stay was 5.0 days (range: 1.5, 7.0). The aggregate number of 12-hour shift UOP observations was 331 (165 for UC, 166 for SP catheter). SP catheters had a mean 308 ml higher output than UCs per 12-hour shift (p[0.004; 95% CI: 116, 501 ml). Multivariable analysis (Table 1) considering time of day (p[0.149) and catheter Fr (p[0.118) shows that SP catheters had an estimated 345 ml higher output than UCs per 12-hour shift (p[0.001; 95% CI: 174, 517 ml). CONCLUSIONS: Simultaneous bladder drainage by both a UC and SP catheter is associated with significantly greater drainage from the SP catheter (59.7% vs 40.3%). The difference in urinary drainage is likely explained by the SP catheter tip and drainage inlet residing in a more gravity-dependent location, within the funnel-shaped bladder neck (Figure 1). These findings suggest that when using two catheters, both should be placed to gravity drainage. For drainage with a single catheter, SP catheters will likely drain the bladder more completely than UCs. Source of Funding: NIH R01 Grant #CA20170901 (PI: Maurice Garcia). Research funding support from the Dr. Richard Onofrio Research Grant to the Cedars-Sinai Transgender Surgery and Health Program


A series of new 5-Chloroisatin derivates have been synthesized by the method of N-alkylation at room temperature, in the presence of a base and a catalyst with good yields. The chemical structures of these compounds were confirmed by NMR ( 1 H & 13 C), these new compounds obtained were evaluated for their antibacterial activity. The final results revealed that the majority of the compounds exhibited good antimicrobial activity against various organisms.


The present stage of development of nuclear power plants with helium turbine and high temperature reactor is reported and a description given of the first plant of this type, the Geesthacht KSH plant (Kernkraftwerk Schleswig-Holstein) in Germany. Particular stress is laid on the control of closed-cycle gas turbines. The special cases of reactor scram, shutdown of the turbine and load release as well as starting up and turning off of the plants are taken into consideration. The design of the turboset and the arrangement of the components of helium turbines of high output are described. Furthermore results of calculations for optimum layout of helium turbine plants with regard to simultaneous power and process heat generation are given.Copyright © 1969 by ASME


The application of viral vectors for gene expression and delivery is rapidly evolving, with several entering clinical trials. However, a number of issues, including safety, gene expression levels, cell selectivity and antivector immunity, are driving the search for new vector systems. A number of replicon-based vectors derived from positive-strand RNA viruses have recently been developed, and this paper reviews the current knowledge on the first flavivirus replicon system, which is based on the Australian flavivirus Kunjin (KUN). Like most replicon systems, KUN replicons can be delivered as DNA, RNA or virus-like particles, they replicate their RNA in the cytoplasm and direct prolonged high-level gene expression. However, unlike most alphavirus replicon systems, KUN replicons are non-cytopathic, with transfected cells able to divide, allowing the establishment of cell lines stably expressing replicon RNA and heterologous genes. As vaccine vectors KUN replicons can induce potent, long-lived, protective, immunogen-specific CD8+ T cell immunity, a feature potentially related to extended production of antigen and double-stranded RNA-induced 'danger signals'. The identification of KUN replicon mutants that induce increased levels of IFN-α/β has also spawned investigation of KUN replicons for use in cancer gene therapy. The unique characteristics of KUN replicons may thus make them suitable for specific protein production, vaccine and gene therapy applications.


The time-course association of soil physicochemical properties and fate of CeO2 nanoparticles (NPs) is not well understood. This study for the first time investigated the dissolution and retention of CeO2 NPs (<25 nm) during soil short-term (6 h) and long-term (30 d) aging processes with dynamic redox conditions. Under the additional reductant-induced initial reductive condition, theoretically, up to 220‰ of Ce(IV) was temporarily reductively dissolved within 10 min, accompanied by a slow retention process (180 min) of Ce species in soil solutions. Conversely, the dissolution and slow retention of Ce species were not significant in soil solutions without added reductant. X-ray absorption near edge spectroscopy (XANES) shows that most of Ce species were present as Ce(IV) (94.0%-97.8%) in all soils after a long-term aging process. These results indicate that the soil dynamic redox conditions induced by oxidant/reductant intrinsically determined the different time-course dissolution and retention of CeO2 NPs, highlighting the occasional reductive condition in soil solution that may contribute to the migration and diffusion of Ce species. The time-course study should be also adopted to develop a comprehensive understanding of the nano-soil interactions.


Optical studies of semiconductors under intense femtosecond laser pulse excitation suggest that an ultrafast phase transition takes places before the electronic system has time to thermally equilibrate with the lattice. The excitation of a critical density of valence band electrons destabilizes the covalent bonding in the crystal, resulting in a structural phase transition. The deformation of the lattice leads to a decrease in the average bonding-antibonding splitting and a collapse of the band-gap. Direct optical measurements of the dielectric constant and second-order nonlinear susceptibility are used to determine the time evolution of the phase transition.


This thesis considers two difficult combinatorial optimization problems for request routing and client assignment in content distribution networks. The aim is to introduce lower and upper bounds to estimate optimal solutions. Existing solution methods and techniques for similar problems have been reviewed. The first problem consists of minimizing the total network cost for request routing with no origin server by considering the delay function. The second problem is cache allocation problem. Lagrangian relaxation and two perspective cuts are used to linearize first problem and to find valid lower bounds. Two different linearization methods are implemented for cache allocation problem. Iterated Variable Neighborhood Descent and Tabu Search are two solution methods which are suggested to find best upper bounds. Different local search operators are introduced to improve objective function values as follows: swap, remove-insert, insert from origin server to a proxy, insert from one proxy to another proxy, swap between origin server and a proxy, swap between two proxies and cyclic exchange. All computational results are presented on randomly generated instances


Generating functions for a complete collection of symmetries of the multiphased averaged KdV equation are constructed. The isospectral generating function has a potential form with one of the canonical basis holomorphic differentials as a potential and possesses some remarkable properties at double points of the hyperelliptic Riemann surface. A new representation for the characteristic speeds of the Whitham-KdV hierarchy is obtained. A global solution to the Whitham system is constructed in an effective form for the case of smooth decreasing initial data with a finite number of inflection points. The large time asymptotics of this solution implies the single-phase limiting behaviour of the oscillations to correlate with the asymptotic predictions of the Lax-Levermore theory. PACS: 03.40.Kf: 04.20.Jb


The form factor and the effective mass are shown to be significantly altered in narrow quantum wells owing to the extension of the wavefunction into the barrier layers. The mobility is found to change as a result by a large factor (a factor of 12 for a well width of 0.5 nm). Modifications caused by the band non-parabolicity are also discussed.


Background Bladder cancer (BLCA) is the 11th most common malignancy worldwide. Although significant improvements have been made in screening, diagnosis, and precise management in recent years, the prognosis of BLCA remains bleak. Objectives This study aimed to investigate the prognostic significance of tumor-infiltrating immune cells and construct ceRNA networks in BLCA patients. Methods The expression data of BLCA patients were obtained from The Cancer Genome Atlas (TCGA) database. A competing endogenous RNA (ceRNA) network was constructed to identify the hub genes involved in the prognosis of BLCA. The CIBERSORT algorithm was utilized to investigate the infiltration levels of 22 subsets of immune cells. Ultimately, the nomogram was generated to visualize the survival probability of each patient, with the calibration curve being performed to assess its performance. Furthermore, the Pearson correlation test was used to explore the correlation between the identified hub genes in the ceRNA network and the prognostic-related immune cells. Results A total of eight elements in the ceRNA network were considered as key members and correlated with the prognosis of BLCA, including ELN, SREBF1, DSC2, TTLL7, DIP2C, SATB1, hsa-miR-20a-5p, and hsa-miR-29c-3p. T cells CD8, T cells follicular helper (Tfh), and neutrophils were identified as independent prognostic factors in BLCA. The co-expression analysis showed that there was a significant correlation between the identified hub genes and immune cells. Conclusion Our results suggest that the mechanism of hsa-miR-29c-3p regulates the expression of ELN and DSC2, and the infiltration of Tfh and neutrophils might play pivotal roles in the progression of BLCA.


Ionospheric data from several stations are used to verify that, at any given local time, the mid-latitude F2 peak tends to lie at fixed values of atmospheric pressure, as expected from theory. The pressure values are found empirically to be about 2 × 10−10 atmosphere at noon, 2 × 10−11 atmosphere at midnight. Given that the global Mass Spectrometer/Incoherent Scatter (MSIS) model of the neutral thermosphere is now readily available, we suggest that the "constant pressure" approach provides a simple way of modeling the height hmF2 for practical purposes, for a wide range of solar and geomagnetic activity, with better consistency than is given by methods based on ionosonde data alone.


In mammals, glucose-dependent insulinotropic polypeptide (GIP) is synthesized predominately in the small intestine and functions in conjunction with insulin to promote nutrient deposition. However, little is known regarding GIP expression and function in early vertebrates like the zebrafish, a model organism representing an early stage in the evolutionary development of the compound vertebrate pancreas. Analysis of GIP and insulin (insa) expression in zebrafish larvae by RT-PCR demonstrated that although insa was detected as early as 24 h postfertilization (hpf), GIP expression was not demonstrated until 72 hpf, shortly after the completion of endocrine pancreatic development but prior to the commencement of independent feeding. Furthermore, whole mount in situ hybridization of zebrafish larvae showed expression of GIP and insa in the same tissues, and in adult zebrafish, RT-PCR and immunohistochemistry demonstrated GIP expression in both the intestine and the pancreas. Receptor activation studies showed that zebrafish GIP was capable of activating the rat GIP receptor. Although previous studies have identified four receptors with glucagon receptor-like sequences in the zebrafish, one of which possesses the capacity to bind GIP, a functional analysis of these receptors has not been performed. This study demonstrates interactions between the latter receptor and zebrafish GIP, identifying it as a potential in vivo target for the ligand. Finally, food deprivation studies in larvae demonstrated an increase in GIP and proglucagon II mRNA levels in response to fasting. In conclusion, the results of these studies suggest that although the zebrafish appears to be a model of an early stage of evolutionary development of GIP expression, the peptide may not possess incretin properties in this species.


In this paper a prediction model is proposed for estimation of furan content in transformer oil using oil quality parameters and dissolved gases as inputs. Multi-layer perceptron feed forward neural networks were used to model the relationships between various transformer oil parameters and furan content. Seven transformer oil parameters, which are breakdown voltage, water content, acidity, total combustible hydrocarbon gases and hydrogen, total combustible gases, carbon monoxide and carbon dioxide concentrations, are proposed to be predictors of furan content in transformer oil. The predictors were chosen based on the physical nature of oil/paper insulation degradation under transformer operating conditions. Moreover, stepwise regression was used to further tune the prediction model by selecting the most significant predictors. The proposed model has been tested on in-service power transformers and prediction accuracy of 90% for furan content in transformer oil has been achieved.


Abstract Significant uncertainty remains regarding the exact timing and nature of subduction events during the closure of the Tethyan seas in what is now NW Iran. This study thus presents new geochemical compositions and U–Pb ages for a suite of volcanic rocks emplaced during Cenozoic volcanism in the west Alborz Magmatic Assemblage, which is commonly regarded as the back-arc of the Neotethyan magmatism in Central Iran. The subalkali basalts and andesites are dated to 57 ± 1.2 Ma, and are likely derived from a supra-subduction mantle wedge. Later, trachytic A-type rocks erupted from ∼42 to 25 Ma during an anorogenic (extensional) stage triggered by slab retreat and associated asthenospheric mantle influx. A-type melts were at least partly concurrent with lithospheric mantle magmatism implied by eruption of subalkali basalts–andesites around 26–24 Ma. Next, Amp-Bt trachybasaltic volcanism with high-Nb basaltic affinity at ∼19 Ma likely records slab deepening and slab partial melting, which reacted with the mantle wedge to produce the source material for the high-Nb basalts. Sr–Nd isotopic ratios for SE Ahar mafic as well as A-type rocks imply rather enriched mantle source(s). Some crustal contamination is implied by the presence of inherited zircons dominated by those derived from Neoproterozoic–Cambrian basement rocks and Carboniferous magmatism. Rhyolitic rocks with adakitic affinity probably mark the final volcanism in the study area. The adakitic rocks show crustal signatures such as high K and Th, probably formed as a consequence of higher temperature gradients, at crustal levels, imposed by both slab and mantle partial melts.


Minimally invasive neurological surgeries are increasingly being sought after for treatment in neurological pathologies and oncology. A critical limitation in these minimally invasive procedures is lack of specialized tools that allow for space-time controlled delivery of sufficient energy for coagulation and cutting of tissue. Advent of fiber-lasers provide high average power with improved beam quality (lower M2), biocompatible silica fiber delivery, reduced cost of manufacturing, and radiant output stability over long operating periods. Despite these advancements, no fiber-laser based surgical tools are currently available for tissue resection in vivo. Here we demonstrate a first to our knowledge, fiber-laser platform for performing precise brain surgery in a murine brain model. In this study, our primary aims were to first demonstrate efficacy of fiber-lasers in performing precise blood-less surgery in a murine brain with limited non-specific thermal damage. Second, fiber-lasers' ability to deliver radiant energy through biocompatible silica fibers was explored in a murine brain model for blood less resection. A bench-top optical coherence tomography (OCT) guided fiber-laser platform was constructed with a stereotactic stage for performing precision brain surgery. A pulsed quasi-continuous wave ytterbium (Yb) fiber-laser (1.07 µm) was used to perform vascular specific coagulation while a pulsed nanosecond thulium fiber-laser (1.94 µm) was used to conduct bloodless cutting, all under the guidance of a swept-source OCT system centered at 1310 +/- 70 nm. Specialty linear and circular cuts were made in an in vivo murine brain for bloodless brain tissue resection. The two fiber-lasers were combined into a single biocompatible silica fiber to conduct brain surgery resection under the bench-top OCT system's imaging microscope. Vascular specific coagulation was demonstrated in all five mice studied. Bloodless linear cuts and point cuts were demonstrated in vivo. Histologically, thermal injury was measured to be less than 100 µm while a removal rate of close to 5 mm3/s was achieved with an average Tm fiber-laser power of 15 W. To the authors' knowledge, this is the first demonstration of a fiber-laser platform for conducting in vivo bloodless brain tissue resection with a pulsed thulium (Tm) fiber-laser and a quasi-continuous wave (QCW) Yb fiber-laser. The demonstrated fiber-laser platform, if successfully configured for use in the operating room (OR), can provide surgeons a tool for rapid removal of tissue while making surgical resections of brain regions more precise, and can be basis for a flexible cutting tool capable of reaching hard-to-operate regions.


The kinetics of complex formation between recombinant hirudin or recombinant hirudin mutants with thrombin were analyzed. In order to elucidate the inhibitor's reactive site peptide bond predetermined amino acid substitutions were introduced at positions of basic amino acid residues by means of site-directed mutagenesis of a hirudin gene. In comparison to recombinant hirudin (Ki = 19 pM) only those mutant inhibitors which were modified at amino acid position Lys47 showed a higher Ki value for their complexes with thrombin. The observed effects are mainly due to increased koff rate constants.


On a regional scale, we compared the local adaptive patterns of soil mycobiota revealed in four 'Evolution Canyons' located in the northern and southern parts of Israel. These microsites were chosen according to the framework of the Institute of Evolution, University of Haifa programme, focusing on the effect of interslope environmental divergence on biodiversity patterns. The comparative analysis demonstrated remarkable differences in spatiotemporal structure of the microfungal communities and their biodiversity level (species richness, heterogeneity and equitability). In the desert 'Evolution Canyon', stress-selected, slow-reproducing, dark-coloured species with large, multicelled conidia were dominant. At the same time, in the forest localities of the northern canyons, as well as in the agriculturally disturbed locality with soil degradation, ruderal-selected, fast-reproducing Penicillium species predominated. Environmental natural selection appeared to be the major factor affecting adaptive diversity patterns of soil microfungi in the studied area. © 2008 The Linnean Society of London, Biological Journal of the Linnean Society, 2008, 93, 157–163.


To mitigate negative impacts of drought stress in the face of climate change, mixtures of tree species such as those between European beech (Fagus sylvatica) and silver fir (Abies alba) are assumed to lower risks in forest management. This study investigates the influence of mixing beech and fir on tree growth in general and in particular on tree species responses to the extreme drought event of 2003. For this purpose, we analyzed basal area increment series and carbon isotope composition (δ13C) in the wood of ~160 trees from three mixed-species sites in Germany and one site in Croatia. Overall growth performance for both fir and beech increased with proportions of the admixed species when accounting for the interactions with tree size and competition intensity. Mixing improved growth of large trees for both species irrespective of neighborhood density, whereas smaller trees benefitted only in denser neighborhoods. Positive mixing effects on radial growth were more pronounced in fir compared to beech, yet the latter benefitted by the admixture of fir with regard to growth recovery following drought. Both the resistance of radial growth against reduction during drought as well as the variation of isotopic composition throughout the drought period were not affected by mixing, indicating that water-use in these two species was not complementary under drought stress. Although trees from both species exhibited growth reductions during the drought, fir maintained higher absolute growth levels than beech during the drought. Both species benefited from growing in mixed neighborhoods but complementary effects depended on tree size and neighborhood density. Mixing fir and beech leads to positive or neutral effects on growth performance of trees, also in response to an extreme drought event. Since increasing tree species richness also spreads the risks associated with extreme events, mixtures of beech and fir can be recommended as a possible alternative for more drought-sensitive stands such as spruce monocultures.


Abstract Depth of burrowing in bivalves presents the individual with a trade-off: burrowing more deeply increases safety against predators but shallow burrowing increases food intake. Large variation in burrowing depth exists both between and within species. This study investigated whether part of this variation in depth in the tellinid Macoma balthica can be attributed to phenotypic plasticity. A predatory crab and food availability were either offered or withheld in separate aquaria and the response in burrowing depth measured. Individuals burrowed more deeply in the presence of a crab but only to shallow depths in the presence of food. This suggests that individuals can assess their environment and subsequently make decisions on their burrowing depth. Phenotypic plasticity like this flexible anti-predation behaviour in M. balthica can have farranging effects. In the presence of predators burrowing depth increases, reducing energy uptake and subsequent growth and reproduction, whereas increased burrowing depths reduces mortality by predation, further affecting prey and predator population dynamics.


The advent of network era provides a new opportunity for the development of journals.In response to this situation,an analysis is made of such aspects as the reception,processing,and administration of papers in terms of the network setting for editorial business on the basis of analyzing the requirement of editorial digitalization to editorial consciousness.Consequently,the superiority of the handling of journal papers in the network setting is revealed.


In a direct-conversion wireless receiver the baseband filter should be able to handle large blockers, resulting in a very challenging spurious free dynamic range (SFDR) requirement. In particular, the noise added in-band trades off with the linearity required to handle close out-of-band interferers [1]. Since the integrated noise generally is proportional to kT/C, once the noise floor for the filter is set, the amount of capacitance is roughly defined as well as a lower bound for area and power consumption [2]. The solution presented in this paper aims to break this trade off by inserting an in-band zero in the output noise transfer function to improve the dynamic range.


The Internet of Things (IoT) is a huge network formed by connecting various information sensing devices through the Internet. Although IoT has been popularized in many fields, connected devices can be used only when network security is guaranteed. Recently, Rana et al. proposed a secure and lightweight authentication protocol for the next-generation IoT infrastructure. They claim that their protocol can resist major security attacks. However, in this study, we prove that their protocol is still vulnerable to offline password guessing attacks and privilege internal attacks. In order to solve these shortcomings, we propose an improved protocol, which is proved to be secure by formal and informal analysis. In addition, after comparing the time and memory consumption with other protocols, we find that our protocol has more advantages.


Objectives: To determine exercise training effects on cardiac size and left ventricular (LV) diastolic function and relationships of exercise induced changes in physiological and body composition parameters with cardiac parameters. Design: Prospective, randomised controlled trial. Subjects: Men and women (63.6 (5.7) years, body mass index 29.5 (4.4) kg/m2) with untreated hypertension (systolic blood pressure (BP) 130–159 or diastolic BP 85–99 mm Hg). Main outcome measures: Cardiac size and LV diastolic function, peak oxygen uptake (Vo2), muscle strength, general and abdominal fatness, and insulin resistance. Interventions: 6 months of exercise training versus usual care. Results: When analysed by group at six months, cardiac size and LV diastolic function did not differ between exercisers (n  =  51) and controls (n  =  53), whereas exercisers had significantly higher peak Vo2 (28 v 24 ml/kg/min) and strength (383 v 329 kg), and lower fatness (34% v 37%), diastolic BP (73 v 75 mm Hg) and insulin resistance (quantitative insulin sensitivity check index 0.35 v 0.34) versus controls (all p ⩽ 0.05). By regression analysis, among six month changes, increased peak Vo2 and reduced abdominal fat were associated with increased cardiac size. Increased peak Vo2 and reduced abdominal fat, BP and insulin resistance were associated with improved LV diastolic function. r Values ranged from 0.20 to 0.32 (p ⩽ 0.05). Conclusions: When examined by group assignment, exercise had no effect on cardiac size or LV diastolic function. When individual variations in six month changes were examined, participants attaining the greatest increases in fitness and reductions in abdominal fatness, insulin resistance and BP showed a modest trend towards physiological hypertrophy characterised by increased cardiac size and improved LV diastolic function. These results suggest that decreased abdominal fatness may have a role in improving cardiovascular health.


Background Variations in patient demand increase the challenge of balancing high-quality nursing skill mixes against budgetary constraints. Developing staffing guidelines that allow high-quality care at minimal cost requires first exploring the dynamic changes in nursing workload over the course of a day. Objective Accordingly, this longitudinal study analyzed nursing care supply and demand in 30-minute increments over a period of 3 years. We assessed 5 care factors: patient count (care demand), nurse count (care supply), the patient-to-nurse ratio for each nurse group, extreme supply-demand mismatches, and patient turnover (ie, number of admissions, discharges, and transfers). Methods Our retrospective analysis of data from the Inselspital University Hospital Bern, Switzerland included all inpatients and nurses working in their units from January 1, 2015 to December 31, 2017. Two data sources were used. The nurse staffing system (tacs) provided information about nurses and all the care they provided to patients, their working time, and admission, discharge, and transfer dates and times. The medical discharge data included patient demographics, further admission and discharge details, and diagnoses. Based on several identifiers, these two data sources were linked. Results Our final dataset included more than 58 million data points for 128,484 patients and 4633 nurses across 70 units. Compared with patient turnover, fluctuations in the number of nurses were less pronounced. The differences mainly coincided with shifts (night, morning, evening). While the percentage of shifts with extreme staffing fluctuations ranged from fewer than 3% (mornings) to 30% (evenings and nights), the percentage within "normal" ranges ranged from fewer than 50% to more than 80%. Patient turnover occurred throughout the measurement period but was lowest at night. Conclusions Based on measurements of patient-to-nurse ratio and patient turnover at 30-minute intervals, our findings indicate that the patient count, which varies considerably throughout the day, is the key driver of changes in the patient-to-nurse ratio. This demand-side variability challenges the supply-side mandate to provide safe and reliable care. Detecting and describing patterns in variability such as these are key to appropriate staffing planning. This descriptive analysis was a first step towards identifying time-related variables to be considered for a predictive nurse staffing model.


Surface precipitation has been shown to occur on rapid time scales in clay and metal oxide mineral systems. The formation of surface precipitates is hypothesized to present new potential sorption sites for potassium (K), where K can become incorporated into newly formed interlayer spaces (e.g., between tetrahedral-octahedral-tetrahedral stacked sheets). The objective of this study is to determine the effects of newly formed mineral surface precipitates on K sorption. Potassium adsorption experiments were conducted by utilizing Al2O3 and SiO2 sorbents in the presence of various cations (magnesium, zinc, and nickel) that helped to catalyze the formation of surface precipitates. Dissolved concentrations of elements were monitored via inductively coupled plasma optical emission spectrometry (ICP-OES). Solids were characterized via X-ray diffraction (XRD), and K surface complexation was analyzed via X-ray absorption near edge structure (XANES) spectroscopy. X-ray diffraction analysis indicated bayerite, layered double hydroxides (LDH), and silicated LDH were formed as reaction products, thus creating new surface sites for potential K adsorption. The presence of Si increased K adsorption perhaps due to its role in the formation of LDH surface precipitates. When the differences between observed and theoretical surface area normalized K sorption densities were averaged, a 31% increase in K adsorption was observed in the presence of Si. XANES analysis indicated that the binding mechanism of K to Si is different than that of K to Al, perhaps due to the presence of inner-sphere complexation of K to Al-oxide. Samples reacted for one month versus one week yielded more intense XANES post-edge peaks which indicated that the K sorption complex changes over time. Overall, our findings provide novel insights into the mechanisms of K fixation in soil and has high implication in providing improved K fertilizer recommendation to growers.


The two-channel quadrature mirror filter structure of Croisier and Esteban may be extended to an arbitrary number of equal bandwidth channels, given certain restrictions on the bandpass filters. The most serious restriction is that the stopband attenuation of eacli band-pass filter must be high for all frequencies outside twice the nominal 3 dB bandwidth of the filter. This restriction is not really a limiting factor for speech subband waveform coding since high adjacent channel attenuation is a necessity for the confinement of quantization noise. A key feature of our filter structure is that the number of multiplies, adds, and stored coefficients required for implementation is significantly less than those needed for the conventional QMF structure, given the same number of channels. Fortran code for a 16-channel filter structure is listed as an example of efficient implementation.


The cubic-ZrO2 (100) ‖ NiO (111) interface provides an opportunity for comparison between atomic-scale measurements, atomistic simulations, and theoretical electronic structures. High-resolution electron microscopy indicates that the oxides share a common oxygen layer and that the small lattice strain is largely taken up by NiO near the interface. Using simple Coulomb plus Buckingham-type interatomic potentials, we are able to provide a more focused picture, revealing two types of boundary. The lowest energy interface is highly planar, almost ideal in structure; there is a second interface, of higher energy, that shows a rumpled structure with strain taken up by deformation of nickel chains. Depth profiling of atomic site energies permits calculation of interface versus bulk and surface energies, and it shows that the interface effects penetrate only two to three atomic layers. Embedded cluster density functional studies of bulk and interface-region sites permit the characterization of perturbations of electronic density around the boundaries.


Abstract:  The contemporary feminist debate is characterized by the outburst of different feminist theories and movements often in conflict with each other. This plurality is a challenge for women's political subjectivity, especially since strong conservative movements are targeting women's freedom and non-normative gender identities. The essay retraces the contemporary feminist debate, focusing on the relationship between equality, women's freedom and the law. Interpreting the law as a social practice, it suggests to take stock of all the knowledge, experiences and resistances that were developed by different feminist traditions. Such differences cannot be obliterated, but they should not prevent us from preserving and enriching the toolbox we need in order to reinforce the resistance against neoliberal governamentality. Keywords : feminism, gender, women's freedom, women's human rights, neoliberalism.


This paper narrates the work of the team Amrita_CEN for the shared task on Patronizing and Condescending Language Detection at SemEval 2022. We implemented machine learning algorithms such as Support Vector Machine (SVV), Logistic regression, Naive Bayes, XG Boost and Random Forest for modelling the tasks. At the same time, we also applied a feature engineering method to solve the class imbalance problem with respect to training data. Among all the models, the logistic regression model outperformed all other models and we have submitted results based upon the same.


Video-assisted thoracic surgery is increasingly being applied to treat a variety of intrathoracic disease processes. Numerous pleural, pulmonary, esophageal, autonomic nervous system, spinal, and even cardiac procedures are now being performed using this minimally invasive approach. An overview of these thoracoscopic interventions is the focus of this review. It must be realized that although the technical feasibility of these operations has been demonstrated, their role in the practice of general thoracic surgery remains to be defined by critical scientific comparisons with established standards. Copyright © 1996 by W. B. Saunders Company


There is growing concern that rare earth elements (REEs) will become emerging soil–water contaminants because of their increased use in new technologies and products, which may lead to unavoidable release to the environment. To better understand the environmental behavior of REEs, a comprehensive set of adsorption and column transport experiments was conducted in quartz sand media. The retention and mobility of three representative REEs (La, Gd, and Er) were studied in the presence and absence of humic acid (HA; 5, 20, and 50 mg L–1) and under a range of pH conditions (5–8). Results show that REE mobility and retention are controlled by the amount of REE–HA complexes formed in a solution, which increases with increasing HA concentrations and solution pH. Gadolinium is the most mobile among the representative REEs, followed by Er and La, corresponding to the amount of (calculated) REE–HA complexes. Increasing HA concentrations in the REE solution inhibits REE retention in both the batch adsorption and column experiments. The same retardation trend was observed for lower HA concentrations (Gd > Er > La). In a fixed HA concentration, HA and REE adsorption decrease simultaneously as the solution pH increases, indicating the co-adsorption of REEs and HA on the sand. Scanning electron microscopy detection of elongated regions attached to the sand, where high REE and carbon (HA) concentrations were measured, further suggests the co-adsorption of REE–HA complexes. Modeling the column experiments shows that the time-dependent attachment is dominant at high HA concentrations, while at lower HA concentrations, both the time-dependent and spontaneous attachments play equal roles. These results provide a quantitative characterization of REE retention and mobility in sand media.


Heat disturbances, which are usually caused by nonuniformity of the conductor operating locally at overcritical currents or by resistive joints in the HTS coil, always lead to local increase in the temperature around the weak point. This may expose the coil to possible damage. Understanding the thermal behavior of the HTS coil is important when designing and operating a conduction-cooled HTS magnet. In this paper, thermal simulations were performed to analyze thermal response of the heat disturbances for a conduction-cooled HTS coil by using a model based on the heat conduction equation and solved using the finite element method. The coil is cooled by a cryocooler through a cooling plate. This study focused on the temperature profile in the coil and the heat transfer between the coil and the cooling plate. Based on the results, the issues related to thermal stability of the HTS coil are discussed.


Understanding the size-dependent electronic, structural and chemical properties of metal clusters on oxide supports is an important aspect of heterogeneous catalysis. Recently model oxide-supported metal catalysts have been prepared by vapour deposition of catalytically relevant metals onto ultra-thin oxide films grown on a refractory metal substrate. Reactivity and spectroscopic/microscopic studies have shown that these ultra-thin oxide films are excellent models for the corresponding bulk oxides, yet are sufficiently electrically conductive for use with various modern surface probes including scanning tunnelling microscopy (STM). Measurements on metal clusters have revealed a metal to nonmetal transition as well as changes in the crystal and electronic structures (including lattice parameters, band width, band splitting and core-level binding energy shifts) as a function of cluster size. Size-dependent catalytic reactivity studies have been carried out for several important reactions, and time-dependent catalytic deactivation has been shown to arise from sintering of metal particles under elevated gas pressures and/or reactor temperatures. In situ STM methodologies have been developed to follow the growth and sintering kinetics on a cluster-by-cluster basis. Although several critical issues have been addressed by several groups worldwide, much more remains to be done. This article highlights some of these accomplishments and summarizes the challenges that lie ahead.


Staphylococcal protein A (SpA) produced by Staphylococcus aureus, binds Immunoglobulin G (IgG), forming SpA-IgG immune complexes (SIC), at a ratio of 2 SpA molecules to 4 IgG molecules. In vitro, SIC have been found to inhibit human osteoclastogenesis, and reduce proinflammatory cytokine secretion by human macrophages. The targeting of both osteoclasts and macrophages together may be important in diseases such as rheumatoid arthritis (RA), where inflammation and bone erosion both play roles in disease progression; resulting in considerable pain and disability. SpA is currently in clinical trials, however, as SpA forms heterogeneous IgG complexes, SpA therapy is not optimal. The aim of this project was to produce human recombinant Fc (Fragment crystallisable) constructs using different IgG subtype(s), thus optimising the immunomodulatory properties exhibited by SIC. This could lead to the development of new therapeutics, and will also give insight into Fc-mediated inhibitory mechanisms.

In this thesis, 13 human Fc constructs (5 tetramers, 5 dimers and 3 monomers) were produced in total. The methods used to generate the human Fc constructs enabled their successful production for use in in vitro cultures. However, when investigating the structure of the IgG3 tetramer (TG3), IgG3 dimer (DG3) and IgG3 monomer (MG3), it was found that TG3 and DG3 do not appear to be polymerising in the manner that was predicted.

The IgG1 tetramer (TG1) and TG3 tetramer, alongside SIC, were found to have the ability to significantly inhibit osteoclast differentiation, and the same molarities of dimers and monomers subsequently displayed reduced levels of inhibition. In studies performed using TG3, DG3, MG3 and SIC: TG3 and SIC were both shown to significantly inhibit RANK transcript levels, although they did not significantly affect the levels of RANK protein expression on the cell surface. However, the level of RANKL-mediated phosphorylated p38 (pp38) was reduced across all donors. Interestingly, TG3 and DG3 significantly reduced cell surface expression of CD115 (c-Fms; colony stimulating factor 1 receptor (CSF1R); macrophage colony-stimulating factor receptor (M-CSFR)). SIC and TG3 were able to significantly reduce transcript levels of DCSTAMP, OCSTAMP, cathepsin K and MMP-9 at certain time points, and TG3 was also shown to significantly reduce NFATc1 transcript levels. TG3, DG3, MG3 and higher amounts of SIC all displayed binding to the surface of cells, although this was only significant for DG3 and SIC.

The mechanisms of action of the human Fc constructs and SIC have not been fully elucidated, and further work is required. However, the data in this thesis suggests that these novel human Fc constructs and SIC can exert their Fc-mediated inhibitory effects by affecting pathways essential for osteoclast differentiation and function.


Millennials are a generation of young people currently in training at universities and colleges, and entering the workforce. They have several characteristics that could potentially make them one of the most productive generations ever. On the other hand the concepts of sustainability and energy awareness are part of their vocabulary and most of the jobs will be related to these terms. This work relates an attempt to tailor a microcomputers course to appeal to this generation of students. What we have found is that the traditional teaching formulas have to be adapted to make them usable by millennials who do not know a world without internet, wireless communications and social networking.