The catalytic subunit of telomerase, human telomerase reverse transcriptase (hTERT), plays an essential role in telomere maintenance to oppose cellular senescence and, is highly regulated in normal and cancerous cells. Regulation of hTERT occurs through multiple avenues, including a unique pattern of CpG promoter methylation and alternative splicing. Promoter methylation affects the binding of transcription factors, resulting in changes in expression of the gene. In addition to expression level changes, changes in promoter binding can affect alternative splicing in a cotranscriptional manner. The alternative splicing of hTERT results in either the full length transcript which can form the active telomerase complex with hTR, or numerous inactive isoforms. Both regulation strategies are exploited in cancer to activate telomerase, however, the exact mechanism is unknown. Therefore, unraveling the link between promoter methylation status and alternative splicing for hTERT could expose yet another level of hTERT regulation. In an attempt to provide insight into the cellular control of active telomerase in cancer, this review will discuss our current perspective on CpG methylation of the hTERT promoter region, summarize the different forms of alternatively spliced variants, and examine examples of transcription factor binding that affects splicing.


Object recognition and localization are important tasks in computer vision. The focus of this work is the incorporation of contextual information in order to improve object recognition and localization. For instance, it is natural to expect not to see an elephant to appear in the middle of an ocean. We consider a simple approach to encapsulate such common sense knowledge using co-occurrence statistics from web documents. By merely counting the number of times nouns (such as elephants, sharks, oceans, etc.) co-occur in web documents, we obtain a good estimate of expected co-occurrences in visual data. We then cast the problem of combining textual co-occurrence statistics with the predictions of image-based classifiers as an optimization problem. The resulting optimization problem serves as a surrogate for our inference procedure. Albeit the simplicity of the resulting optimization problem, it is effective in improving both recognition and localization accuracy. Concretely, we observe significant improvements in recognition and localization rates for both ImageNet Detection 2012 and Sun 2012 datasets.


A theoretical model of temperature for Al2O3 ceramics during micro-detonation of arc strike machining was established. Based on finite element theory, the temperature of Al2O3 ceramics during micro-detonation of arc strike machining was simulated with the aid of Ansys software, combined with the actual processing, the width and depth of cavity impacted by micro-detonation were calculated. The simulation results show that the highest temperature of Al2O3 ceramics is over 13435 °C in a given processing parameters, while the high-temperature zone is quite small. With the increase of pulse width and electricity, the temperature within the machined zone increases rapidly, but the outside area kept a low temperature; and with the increase of nozzle radius, the diameter to depth ratio of the distribution of temperature is increasing gradually. The data gained from the simulation is proved to be accordant with the data gained from experiments.


The purpose of this study was to assessment of the effect of strength training (isotonic) like Nautilus equipment (in water and on land) on quadriceps muscles in knee extension to 45 and 90 degree.175 older men (50-60 ages) participated in this research that 60 subject selected between them and then divided to three groups: control, training on land and training in water. The subjects volunteer to participate in study. The essential purpose of this research was to assessment of the effect isotonic training on static strength quadriceps muscle and the study about the effect isometric training was performed in the past. Muscle strength was measured by tensiometer (pre test and post test) in the 45 and 90 degree of extension of knee. exercise program included: 3 sessions in a week and for 5 continuous week (15 sessions) and three sets per-session with ten repetition (Mac Kwien).Before beginning any exercise(with Mac Kwien method)subjects performed callisthenics and stretching exercise as warm-up, and consulted with his personal physician before of test program (during tests physician presented). The results from the t test student and ANOVA indicated: 1) Training on the land and in water had significant effect on quadriceps muscle strength extension 45 and 90 degree of the knee and 2) Training on the land had more effect on quadriceps muscle strength on extension of knee joint. The comparison of the water group shows a little increasing in post test phase which is not statistically significant. Our finding suggest that isotonic strength training may also induce central nervous system changes, which can increase the number of motor units recruited, alter motor neuron firing rates, enhance motor unit synchronization during a particular movement pattern and result in the removal of neural inhibition. So we need more studies details about isotonic exercises its effect and its various methods.


Study of the human proteome has given rise to the appearance of abundant and increasing scientific literature. This has resulted in the proposal to use proteomic techniques in the management of some diseases and the suggestion of its future use in clinical laboratories. In order to identify which proteomic techniques are being used or may be used in the near future in the clinical practice, a survey was made to experts in proteomics and the bibliometric study was done. Concordance between this study and a survey was observed. However, in general, standardized uses of proteomic techniques in the current clinical practice were not found. In regards to possible applications in the short-middle term, the experts have different opinions, from those who mention specific techniques (coinciding with the most repeated aspects of the bibliometric study) to those who think that its use in a near future is unlikely.


Activation of the sympathetic nervous system and renin-angiotensin system has been suggested to contribute to the hypertension caused by chronic nitric oxide synthase inhibition. The aim of the present study was to determine whether angiotensin within the nucleus tractus solitarii (NTS) plays a role in activation of the sympathetic nervous system in this model. Rats were treated with N(omega)-nitro-L-arginine methyl ester (L-NAME, 100 mg. kg(-1). d(-1) in drinking water) for 2 weeks. Experiments were performed on anesthetized rats with denervated arterial and cardiopulmonary baroreceptors. Arterial pressure, heart rate, and renal sympathetic nerve activity (RSNA) were measured. Microinjection of an angiotensin II type 1 (AT(1)) receptor antagonist (CV11974) or an angiotensin II type 2 (AT(2)) receptor antagonist (PD123319) into the depressor region within the NTS (identified by prior injection of L-glutamate) was performed. Microinjection of CV11974, but not of PD123319, produced greater decreases in arterial pressure, heart rate, and RSNA in L-NAME-treated rats than in control rats. The administration of hexamethonium resulted in a larger fall in arterial pressure in L-NAME-treated rats than in control rats. The ACE mRNA level in the brain stem was greater in L-NAME-treated rats than in control rats. These results suggest that increased sympathetic nerve activity plays a role in hypertension caused by chronic nitric oxide synthase inhibition and that activation of the renin-angiotensin system in the NTS is involved at least in part in this increased sympathetic nerve activity via AT(1) receptors.


Connexin-43 (Cx43) is the most abundant protein forming gap junction channels (GJCs) in cardiac ventricles. In multiple cardiac pathologies, including hypertrophy and heart failure, Cx43 is found remodeled at the lateral side of the intercalated discs of ventricular cardiomyocytes. Remodeling of Cx43 has been long linked to spontaneous ventricular arrhythmia, yet the mechanisms by which arrhythmias develop are still debated. Using a model of dystrophic cardiomyopathy, we previously showed that remodeled Cx43 function as aberrant hemichannels (non-forming GJCs) that alter cardiomyocyte excitability and, consequently, promote arrhythmias. Here, we aim to evaluate if opening of remodeled Cx43 can serve as a general mechanism to alter cardiac excitability independent of cellular dysfunction associated with a particular cardiomyopathy. To address this issue, we used a genetically modified Cx43 knock-in mouse (S3A) that promotes cardiac remodeling of Cx43 protein without apparent cardiac dysfunction. Importantly, when S3A mice were subjected to cardiac stress using the β-adrenergic agonist isoproterenol (Iso), they displayed acute and severe arrhythmias, which were not observed in WT mice. Pretreatment of S3A mice with the Cx43 hemichannel blocker, Gap19, prevented Iso-induced abnormal electrocardiographic behavior. At the cellular level, when compared with WT, Iso-treated S3A cardiomyocytes showed increased membrane permeability, greater plasma membrane depolarization, and Ca2+ overload, which likely caused prolonged action potentials, delayed after depolarizations, and triggered activity. All these cellular dysfunctions were also prevented by Cx43 hemichannel blockers. Our results support the notion that opening of remodeled Cx43 hemichannels, regardless of the type of cardiomyopathy, is sufficient to mediate cardiac-stress-induced arrhythmogenicity.


Carbon doped LiFePO4 precursor particles were successfully prepared by spray pyrolysis. The saccharides such as monosaccharide and disaccharide or organic acid were used as carbon source. SEM observation showed that as-prepared particles had spherical morphology with narrow size distribution. XRD analysis revealed that olivine phase was obtained by heating at 700°C under the atmosphere of argon/hydrogen (5%). Electrochemical measurement revealed that the discharge capacity of LiFePO4 was improved by the addition of carbon. The addition of citric acid was most effective for the stabilization of cycle life.


Animals may update their assessment of predation risk according to how a potential predator approaches them. For example, the predator's head and gaze orientation (direction of attention) may reveal its intentions, and faster-approaching predators are likely to represent greater risk. We examined the reactions of hadeda ibises Bostrychia hagedash. These large birds demonstrate a wide repertoire of responses to being approached (e.g. continuing to forage, slow walking, rapid escape walking, flight and alarm calling). Birds were approached tangentially 112 times by a human who either had the head and eyes directed towards (65 approaches) or directed away from (47 approaches) the birds to test the hypothesis that the direction of the observer's attention informs alert distance (AD) and flight initiation distance (FID) in these birds. Direction of attention had a significant effect on AD and FID as well as the likelihood of taking flight and alarm calling by hadedas, with birds appearing to associate attention directed towards them as an indication of increased risk. Hadedas were able to differentiate between the direction of attention of an approaching human, whether or not there were multiple other humans in the near vicinity. We also examined whether the observer's approach speed altered the birds' responses. Approach speed affected the birds' FID, suggesting that they perceive greater danger in a faster-approaching intruder compared with a slower-walking one. These results support the predictions of optimal escape theory and emphasize the high resolution of anti-predatory awareness in these birds. The marked success of hadeda ibises in urban environments may be due to their ability to become habituated to human presence and to modify their antipredator behaviour in response to subtle cues. These may be common traits of bird species that successfully adapt to urban environments.


This paper, via a case study of two hackspace events, elucidates how a hands-on collaborative, experiential learning approach may be beneficial in understanding emergent technologies both practically and conceptually. A hackspace is a location where people with common interests, usually in computers, technology, science and/or digital and electronic art can meet, socialise and/or collaborate. At Hackspace events participants who surface from mainly online communities, come from all over the world to meet up in real life (IRL) and learn about emergent technologies. Specifically the events I point to start with a course in basic hardware. These real life events are important as the organisers' predominantly only interact on line. The experiential approach is accessible and it encourages the participant to be an amateur in the realm of a technical professional, but instead of the constraint of the later, the former allows them to follow their own enthusiasms that open up new possibilities. I introduce the notion of 'engaged autonomy' referring Charles Esche's (2004) proposal as a way to think of autonomy not as something that is invested in the object itself but rather as an action or a way of working, through thinking things otherwise. Hackspace events pose a new radical set of models, which in turn provides inspiration and new insights to creative learning and engagement with technology and tools.


Sandwich panels using fibre-reinforced composite skins and low-density cores are being increasingly used in the aerospace industry due to their superior specific strength and stiffness, and increased design flexibility over traditional metallic and composite structures. However, it is well-known that sandwich panels are highly vulnerable to the effects of impact damage, with even low-energy impacts potentially causing very severe reductions in the in-plane compressive strength of these structures. The objective of this project was to produce a faithful and reliable numerical model for the simulation of the compression-after-impact strength of composite sandwich panels. An in-depth literature review revealed that delamination within the skins of a sandwich panel is a damage mechanism that has gone almost entirely neglected in previous efforts at modelling this problem, despite the proven significance of this mechanism in the failure of impact damaged sandwich panels in compression. Consequently, the use of the cohesive zone model for delamination initiation and propagation is the key unique feature of this model, with Hashin s criteria being used for intra-laminar damage formation, and a simple plasticity response capturing core crushing. An experimental study is performed to produce a thorough dataset for model validation, featuring differing levels of damage induced via quasi-static indentation, and novel asymmetric panels with skins of unequal thickness (the thinner skin being on the unimpacted side).

The experimental study revealed that the use of a thinner distal (undamaged) skin could improve the strength of mildly damaged sandwich panels over undamaged sandwich panels using the same asymmetric configuration. It is believed that this effect is due to the movement of the neutral plane of the sandwich panel caused by the reduction in the stability of the damaged skin through stiffness reduction and geometric imperfections. This removes the eccentricity of the compressive loading that exists in the undamaged asymmetric panels, which has mismatched axial stiffness between the indented skin and the thinner distal skin, and thus a noticeably lower ultimate strength than the undamaged symmetric panels.

The sandwich model is developed using pre-existing experimental and material data, and trialled for a variety of different skin lay-ups, core thicknesses and indenter sizes. The numerical model generally agreed well with the ultimate stress found in the experiments for these different configurations, but is quite poor at estimating the magnitude of the damage induced by the indentation. When used to model the experimental study, the model gave generally good, conservative estimates for the residual compressive strength of both the symmetric and asymmetric panels. The tendency of the asymmetric panels to become stronger with mild damage was not captured by the model per se, with the numerical results instead showing an insensitivity to damage in the asymmetric panels, which was not shared by the symmetric panels. However, the numerical model did exhibit erroneous strain-stress responses for both panel configurations, particularly for the undamaged and mildly damaged cases. Investigations revealed that this erroneous behaviour was caused by inconsistency in the material data, which had been collected partially via experimentation and partly from literature sources. Overall, the model developed here represents a promising advancement over previous efforts, but further development is required to provide accurate damage states.


Pervasive Internet of Things (IoT) is a research paradigm that has attracted considerable attention nowadays. The main aim of pervasive IoT is that in the future, the everyday objects (devices) would be accessible, sensed, and interconnected inside the global structure of the Internet. But in most of the pervasive IoT applications, the resources of an IoT device such as storage, processing, and energy are limited; as such there is a need for management of resources in such applications. Multiple aspects related to the data such as the type of data, size of data, number of transmission and reception of data packets, the structure of data, etc are taken into consideration while managing the resources of pervasive IoT applications. Therefore data management is essential for the management of limited resources in such applications. This paper presents the recent studies and related information in data management for pervasive IoT applications having limited resources. This paper also proposes a parallelization based data management framework for resource-constrained pervasive applications of IoT. The comparison of the proposed framework is done with the sequential approach through simulations and empirical data analysis. The results show an improvement in energy, processing, and storage requirements for the processing of data on the IoT device in the proposed framework as compared to the sequential approach.


Oxidative phosphorylation in the rat liver mitochondria was studied as affected thiophosphamide 1, 6 and 24 h 3, 7, 15 and 30 days after administration of the chemopreparation. Considerable changes were found in oxidative phosphorylation. The degree of disturbances is different depending on the period which passed after radiomemetics administration. During the first hours and days oxidative phosphorylation is inhibited more and more, reaching the maximum three days later. In subsequent periods of the studies a gradual restoration of this bioenergetic index is observed. When oxidizing alpha-ketoglutarate by mitochondria the inhibition of respiration and phosphorylation is more profound than in case with succinate oxidation.


This project focuses on the synthesis of novel dienes containing dicarboxylic acid and dipyridyl groups and their use in constructing metal organic frameworks (MOFs) and coordination polymers. Dicarboxylate and dipyridyl ligands are commonly used when forming these supramolecular structures. Many examples of MOFs exist the literature where the bridging ligands are terephthalic acid, muconic acid, and 4,4'-bis-pyridyl-1,2-ethyelene. The ligands used in this study are analogous to the previously mentioned ligands and should form similar MOF architectures and coordination polymers. These diene ligands could theoretically give us the ability to modify the pores contained within the metal organic frameworks. If successful, this could enable the size of the pore to be altered and is also a means to add different functional groups inside the pores. These MOFs could potentially be tailored for use in specific applications ranging from gas storage to semiconductors.


The growth factor midkine (MK) has been reported to bind heparan sulfate and nucleolin, two components of the cell surface implicated in the attachment of HIV-1 particles. Here we show that synthetic and recombinant preparations of MK inhibit in a dose-dependent manner infection of cells by T-lymphocyte- and macrophage-tropic HIV-1 isolates. The binding of labeled MK to cells is prevented by excess unlabeled MK or by the anti-HIV pseudopeptide HB-19 that blocks HIV entry by forming a stable complex with the cell-surface-expressed nucleolin. MK mRNA is systematically expressed in adult peripheral blood lymphocytes from healthy donors, while its expression becomes markedly but transiently increased upon in vitro treatment of lymphocytes with IL-2 or IFN-gamma and activation of T-lymphocytes by PHA or antibodies specific to CD3/CD28. In MK-producing lymphocytes, MK is detectable at the cell surface where it colocalizes with the surface-expressed nucleolin. Finally, by using MK-producing CD4(+) and CD4(-) cell clones we show that HIV infection in cell cultures could be inhibited in both an autocrine and a paracrine manner. The potent and distinct anti-HIV action of MK along with its enhanced expression in lymphocytes by various physiological stimuli suggests that MK is a cytokine that could be implicated in HIV-induced pathogenesis.


This article addresses the everyday technologies of 'extraction and redistribution' that young women and men use in order to adapt to a situation of increasing unemployment in Maputo, Mozambique and other African cities. In this neoliberal economy informal and illicit trade with sex, stolen goods and counterfeit products are on the rise and the article shows how technologies of survival are highly gendered and reconfigure masculinities and femininities. In this article I argue that technologies of survival in urban Africa are based on logics of extraction–of money, goods and other valuables from the well off - as an alternative to wage labor, salaries and more respected sources of income and redistribution of incomes to kin and social networks. Technologies of extraction are highly gendered and a division of "informal labor" exists in this shadow economy where many young women enter into transactional sex with sugar-daddies, called sponsors or patrons, who provide for them in exchange for sex while male peers often become street vendors, street artists or petty criminals engaged in the so-called 'black' markets of theft, sale of counterfeits, and circulation of stolen goods, alcohol and drugs. As I show, these gendered markets are highly entangled and interdependent, and as I argue, male and female markets use many of the same technologies, sources and circuits of exchange.


Clinical diagnosis can be influenced and delayed when patients with mental disorders cannot provide reliable medical history and cooperate with physical examinations, as well as their family members cannot evaluate the progress of the disease accurately. We present a case report of a female with schizophrenia who was admitted with convulsion and fever accompanied by skin ecchymosis of the upper limbs. She was initially diagnosed as "septic shock", had been treated with antibiotics and fluid resuscitation in a local hospital for five days, and then was transferred to our hospital because of continuing confusion and low-grade fever. After repeatedly checking medical history and detailed physical examinations, the patient was eventually diagnosed as multiple fractures with the upper limbs and shoulders, and recovered a few days later after necessary surgical intervention.


Background: This study explored the experience of nurses encountering challenging patient behaviour while working at a rural hospital-based haemodialysis unit. Methods: Focus groups were conducted with haemodialysis nurses at a rural hospital. Five participants across two focus groups were asked questions regarding their experiences of challenging patients, including impacts that the experiences may have had on their ongoing professional practice. Transcripts of the focus groups were analysed thematically. Findings: Three themes arose from the focus group discussion - experiencing challenging behaviour, long-term relationships with patients, and nursing professionalism. Participants described challenges arising when caring for patients who were aggressive, did not comply with self-management, or caused avoidable logistical challenges. Long-term caring relationships presented challenges as patients could become emotionally dependent upon one nurse, making it difficult to share workloads with other nurses. Participants reported decreased confidence, being near tears, being angry, and experiencing 'burnout' when caring for patients with difficult behaviour over extended periods. Participants managed challenging behaviours by identifying triggers, allocating staff to specific patients, and trying to understand the patient's motivation for action. 'Not taking work home' and 'not taking things personally' were ways in which nurses attempted to look after their own wellbeing, although this was not always possible. Participants stressed the importance of working as a team and having supportive management and inter-professional relationships. Significance: Participants' perceptions of working in the nursing profession were more related to their ability to work as a team and manage challenging behaviour exhibited by patients in a supportive environment than the presence of patients exhibiting challenging behaviour.


Background: Mild cognitive impairment (MCI) is characterized by a decrease in cognitive abilities that does not affect the ability to perform activities of daily living (ADLs). Therefore, this condition is easily overlooked. The prevalence and factors of influence for MCI in older people living in publicly managed congregate housing are currently unknown. Purpose: This study investigated the prevalence and distribution of MCI in older people living in publicly managed congregate housing and assessed the correlations among quality of life (QoL), ADL, and MCI. Methods: This study applied a correlational study design. The participants were older people who met the study criteria and who lived in public housing in Wanhua District, Taipei City, Taiwan. One-on-one interviews were conducted to measure the cognitive abilities of the participants, and 299 valid samples were collected. Results: The prevalence of MCI in older people living in publicly managed congregate housing was 16.1%. The &khgr;2 test was employed to evaluate the distribution of MCI prevalence and indicated that the group with higher MCI prevalence exhibited the following characteristics: older than 81 years; married; lived in public housing for more than 20 years; cohabiting; had a history of drinking; and exhibited severe memory regression, physical disabilities, psychological distress, and low QoL. The difference between the groups achieved statistical significance (p < .05). After performing logistical regression analysis to control demographic variables, we found that QoL and ADL were critical for predicting MCI. Conclusions/Implications for Practice: This study confirmed that QoL and ADL correlate significantly with MCI in older people. Maintaining an open and supportive community enables older people to maintain sufficient mental activity, which has been shown to reduce MCI. These findings may provide an important reference for policy makers, educators, researchers, and community practitioners in their development of service strategies for older people.


The consumption of animal products in South Africa is projected to 2020 and used to derive protein feed usage. A spreadsheet model, developed for this purpose, has the following novel features:- it is interactive and readily allows for scenario analysis; the price of protein is endogenous in the South African model as it is generated by an international model; income elasticities of demand are permitted to decline with GNP growth; it incorporates estimated rates of technological progress in livestock production, and predicts the resulting real price change. Total protein consumption is projected at 1.54 million tons by 2010, a 24% increase from 2000, and 1.96 million tons by 2020, a 58% increase from 2000, under base population growth and low income growth. Broiler, egg and pork product prices (projected to decline in real terms because of expected technological advances) contribute to increasing protein usage even in the absence of significant real income growth rates. Population growth remains the most important demand driver and scenario analysis reveals that alternative population growth rates impact significantly on projections. The negative effect of HIV/AIDS on population growth and the subsequent restriction on potential protein use is evident.


Species distribution models can be used to direct early detection of invasive species, if they include proxies for invasion pathways. Due to the dynamic nature of invasion, these models violate assumptions of stationarity across space and time. To compensate for issues of stationarity, we iteratively update regionalized species distribution models annually for European gypsy moth (Lymantria dispar dispar) to target early detection surveys for the USDA APHIS gypsy moth program. We defined regions based on the distances from the invasion spread front where shifts in variable importance occurred and included models for the non-quarantine portion of the state of Maine, a short-range region, an intermediate region, and a long-range region. We considered variables that represented potential gypsy moth movement pathways within each region, including transportation networks, recreational activities, urban characteristics, and household movement data originating from gypsy moth infested areas (U.S. Postal Service address forwarding data). We updated the models annually, linked the models to an early detection survey design, and validated the models for the following year using predicted risk at new positive detection locations. Human-assisted pathways data, such as address forwarding, became increasingly important predictors of gypsy moth detection in the intermediate-range geographic model as more predictor data accumulated over time (relative importance = 5.9%, 17.36%, and 35.76% for 2015, 2016, and 2018, respectively). Receiver operating curves showed increasing performance for iterative annual models (area under the curve (AUC) = 0.63, 0.76, and 0.84 for 2014, 2015, and 2016 models, respectively), and boxplots of predicted risk each year showed increasing accuracy and precision of following year positive detection locations. The inclusion of human-assisted pathway predictors combined with the strategy of iterative modeling brings significant advantages to targeting early detection of invasive species. We present the first published example of iterative species distribution modeling for invasive species in an operational context.


In this letter, we propose a lateral asymmetric strain profile in a silicon nanowire or ultrathin silicon film as a key technology booster for the performance of all-silicon tunnel FETs. We demonstrate by simulation that a Gaussian tensile-strain profile with a maximum placed at the source side of a nanowire tunnel FET with a 50-nm channel length provides an optimized solution for a low-standby-power switch. This leads to the following: (1) ultralow I off (more than three decades lower than in the case of a device on uniformly strained silicon); (2) boosting of I on (more than one decade higher compared to a silicon reference); and (3) an average subthreshold swing S avg of 48 mV/dec at room temperature. Furthermore, the inherent finite drain threshold voltage of the tunnel FET, which could be a disadvantage for logic design with tunnel FETs, is exponentially reduced with the strain-induced bandgap shrinkage at the source side.


This study looked at the role of the integration of online activities in overall course satisfaction and interactive learning experiences in a web-enhanced, traditional teacher education course. Data were collected over two semesters from two graduate and two undergraduate classes. The analysis demonstrated that a majority of the students held positive views of these learning experiences: student-centered flexible learning environment, student-student interactions, and the connection between web-based activities and face-to-face (FTF) learning. These findings suggested that integration of online activities into traditional teacher education courses can shift some of the power, authority, and control from the instructor to the learner while providing the interaction and connection that are central and valuable to traditional classrooms.


cases thus remain not classifiable (PTCL Not Otherwise Specified, NOS) and there is an important need for alternative diagnostic strategies. Here, we developed a parsimonious GEP assay applicable to a routine diagnostic workflow to differentiate the main PTCL entities and characterize the heterogeneity of PTCL‐NOS. A Reverse Transcriptase‐Multiplex Ligation dependant Probe Amplification (RT‐MLPA) assay was designed to evaluate the expression of 20 markers. It simultaneously addresses the expression of 18 genes routinely tested by immunohistochemistry (IHC) or selected from GEP studies. It also assesses the EBV infection status (EBER1) and the presence of RHOAG17 V and IDH2R172K/T mutations. Unsupervised hierarchical clustering of RT‐MLPA data from 102 control cases validated the capacity of our assay to identify the main PTCL entities. All Angioimmunoblastic T‐cell lymphomas (AITL; n = 29), Anaplastic largeT‐cell lymphomas (ALCL; n = 23) ALK+, NK/T‐cell lymphomas (NKTCL; n = 16), Hepatosplenic T‐cell lymphomas (HSTL; n = 6) and Adult T‐cell Leukemia/Lymphomas (ATLL; n = 12) were correctly identified. AITLs classified according to the expression of Tfh markers (CXCL13, CXCR5, ICOS, BCL6) and RHOA mutations (n = 18); NKTCLs according to EBER1, GZMB and Th1 markers (TBX21, IFNγ); HSTLs to CD56, GATA3, TBX21 and BCL6; ALCL ALK+ according to CD30, ALK and cytotoxic markers (PRF, GZMB); ATLLs to ICOSand Th2 markers (GATA3, CCR4). Interestingly, ALCL ALK‐ cases (n = 16) divided into two CD30+ subgroups: one associated with expressions of cytotoxic markers which clustered with ALCL ALK+ cases (n = 10), and a second which did not expressed PRF and GZMB but the two GATA3 and CCR4 Th2 markers (n = 6). We next developed a support vector machine based predictor combined with a centroid categorization. Applied to a series of 125 PTCL‐NOS, this algorithm reclassified 36 Tfh (AITL‐ like), 6 CD30/Th2, 6 ALCL ALK‐ like, 3 HSTL‐like and 5 NKTCL‐like PTCLs. After exclusion of these cases, unsupervised clustering analysis identified 17 cytotoxic/Th1 (GZMB, PRF,TBX21, IFNγ) cases, 14 Th2 (GATA3, CCR4) cases and 14 TH2/Tfh (GATA3, CCR4, CXCR5, ICOS) cases. Finally, 24 cases (10.5% of the cohort) did not show any recognizable signature. This study demonstrates the applicability of a robust RT‐MLPA classifier for the classification of PTCLs. Its simplicity and its applicability on FFPE samples makes it an attractive alternative to high throughout GEP approaches. In combination with conventional pathological evaluation and IHC, it may participate to improve the classification of PTCLs and the management of these aggressive tumors.


It is well known that instrumental variables (IV) estimation is sensitive to the choice of instruments both in small samples and asymptotically. Recently, Donald and Newey (2001) suggested a simple method for choosing the instrument set. The method involves minimising the approximate mean square error (MSE) of a given IV estimator where the MSE is obtained using refined asymptotic theory. An issue with the work of Donald and Newey (2001) is the fact that when considering large sets of valid instruments, it is not clear how to order the instruments in order to choose which ones ought to be included in the estimation. The present paper provides a possible solution to the problem using nonstandard optimisation algorithms. The properties of the algorithms are discussed. A Monte Carlo study illustrates the potential of the new method.


Autologous adipose stem cells owing to its pluripotent nature offer a valuable source for pancreatic beta cell replacement in the treatment of diabetes mellitus. However, maintaining longevity and functionality of stem cell-derived islet-like cells for long-term in vitro culture is challenging. Signaling interaction between islets and surrounding extracellular matrix (ECM) is an important factor for islet survival and function. Tissue engineering strategy to use scaffolds as substitute for ECM is a key to the problem. In the present study, we fabricated a three-dimensional (3D) biodegradable scaffold comprised of natural polymers dextran and gelatin (DEXGEL) for differentiation of adipose stem cells to islet-like clusters (ILCs). Adipose stem cells derived from subcutaneous fat of New Zealand white rabbits were differentiated to ILCs on DEXGEL scaffold and two-dimensional (2D) culture plates via three stage protocol using cocktail of growth factors. The ILCs differentiated on DEXGEL scaffold exhibited characteristic islet morphology, and expressed islet-specific hormones (insulin, glucagon, and somatostatin). The insulin secretion in response to glucose challenge and viability of ILCs on DEXGEL scaffold were significantly higher in comparison to ILCs on 2D culture. Our results demonstrated for the first time that DEXGEL scaffold simulated an extracellular environment for effective differentiation of rabbit adipose stem cells to ILCs.


Licensed warehousing system plays a very important role in all transfers of food products from the place of origin to ultimate users in developed countries. Public warehouses, operated as an independent business offering a range of services, such as storage, handling and transportation. Licensed Warehousing Law, was accepted on 10.02.2005 and this is a new subject in Turkey. In this research, the licensed warehousing system in Turkey is evaluated from the point of view of industrial and agriculture officials. Confidential face to face interviews were held with the authorities of Industry and Trade Ministry in Ankara. The very new licensed warehousing law connote many questions. Who will be getting the benefits of qualified storing, small-sized enterprises or big ones? What will be benefits to producers, product markets, and government? Are all the necessary legal, institutional, and technical enabling ready? During the study, authorities of Industry and Trade Ministry has met, qualified storing law and its system, function, benefits, world samples information were given by using literatures, then action of the qualified storing system in Turkey and its possible problems were discussed.


The Labrador Trough contains world-class iron deposits which have been mined since 1954. The direct shipping of Knob Lake ores were mined at Schefferville from 1954 to 1982. Concentrate production began in 1961 in the southwest end of the Trough, with three mines currently producing concentrate and pellets at a rate of 35 Mt per year. West and north of Schefferville, several billion tonnes of taconite have been outlined in fine-grained, cherty magnetite iron formation. Several deposits of highly metamorphosed magnetite-specularite iron formation are located west of Ungava Bay. Numerous studies have shown that this medium- to fine-grained iron formation can be beneficated to 66% to 68% iron. In the area from Wabush Lake to Mont-Wright, a medium- to coarse-grained friable specularite-quartz iron formation is repeated by folding to form several large deposits. In this area, three mining operations are located with reserves and resources in the order of 5 billion tonnes. The iron deposits occur within iron formation in sediments in the extensive Proterozoic geosyn-cline called the Labrador Trough. Several facies of iron formation within the Sokoman Formation reflect variations in chemical composition and depositional conditions. The correlation between the mineralogy and textures is discussed to illustrate the development of different types of iron ores. This band extends for about 1100 km southeast of Ungava Bay through both Quebec and Labrador. Further south, it turns southwest past the Wabush and Mont-Wright areas to within 300 km of the St. Lawrence River. The iron formation is essentially folded and faulted along most of its length. The degree of metamorphism is variable, ranging from intense in the northern and southern portions to greenschist facies in the central portion. The stratigraphy, structure and mineralogy of the producing mines are described along with the history of discoveries. Geological input is required to achieve the strict specifications of the international iron ore market.


We tested the hypothesis that inhibition of synthesis of either nitric oxide (NO) or vasodilating prostaglandins (PGs) would not alter exercise hyperaemia significantly, but combined inhibition would synergistically reduce the hyperaemia. Fourteen subjects performed 20 min of moderate rhythmic forearm exercise (10% maximal voluntary contraction). Forearm blood flow (FBF) was measured by Doppler ultrasound. Saline or study drugs were infused (2 ml min−1) into the forearm via a brachial artery catheter to locally inhibit synthesis of NO and PGs during steady state exercise (NG‐nitro‐L‐arginine methyl ester (L‐NAME), 25 mg over 5 min to inhibit NO synthase (NOS); and ketorolac, 3 mg over 5 min to inhibit cyclooxygenase (COX)). After achieving steady state exercise over 5 min (control), L‐NAME was infused for 5 min, followed by 2 min saline, then by a 5 min infusion of ketorolac, and finally by 3 min of saline (n= 7). Drug order was reversed in seven additional subjects, such that single inhibition of NOS or COX was followed by combined inhibition. FBF during exercise decreased to 83 ± 2% of control exercise (100%) with NOS inhibition, followed by a transient decrease to 68 ± 2% of control during COX inhibition. However, FBF returned to levels similar to those achieved during NOS inhibition within 2 min (80 ± 3% of control) and remained stable through the final 3 min of exercise. When COX inhibition was performed first, FBF decreased transiently to 88 ± 4% of control (P < 0.01), and returned to control saline levels by the end of ketorolac infusion. Addition of L‐NAME reduced FBF to 83 ± 3% of control, and it remained stable through to the end of exercise. Regardless of drug order, FBF was ∼80% of steady state control exercise (P < 0.01) during the last 30 s of exercise. We conclude that (1) NO provides a significant, consistent contribution to hyperaemia, (2) PGs contribute modestly and transiently, suggesting a redundant signal compensates for the loss of vasodilating PGs, and (3) NO and PG signals appear to contribute independently to forearm exercise hyperaemia.


Bradykinin (BK)- or acetylcholine (ACh)-mediated vasodilation has only rarely been observed in fish. This suggests that many fish vessels lack the endothelium-dependent relaxing mechanisms recently identified in mammals. To examine this hypothesis, isolated vascular rings were prepared from trout ventral aortas (VA), efferent branchial and celiacomesenteric (CM) arteries, and anterior cardinal veins (CV) and examined for endothelium-mediated responses. A doubly perfused trunk preparation was also used to evaluate the response of the microcirculation. ACh produced dose-dependent contractions in all vascular rings and increased vascular resistance when perfused into the CM but had no affect when perfused into the dorsal aorta. Neither ACh nor BK relaxed precontracted vessels or lowered resting tone. Removal of the endothelium did not affect ACh or BK responses. The calcium ionophore A23187 produced an endothelium-dependent relaxation of precontracted VA, CM, and CV. The A23187 response was abolished by indomethacin, indicating that a prostanoid was involved in the relaxation. ATP contracted and/or relaxed precontracted CM and CV. ATP effects were independent of an intact endothelium. Sodium nitroprusside and atrial natriuretic factor partially or completely relaxed all vessels, indicating the presence of soluble and particulate guanylate cyclases, respectively. These results suggest that nonprostanoid endothelium-derived relaxing factors (EDRFs) or EDRF-like vasodilator mechanisms are not present in trout vessels or, if they are, they are not released by classical agonists.


This study analyzed labour utilization issues in the rural farm households of Imo state. Data were collected with a structured questionnaire and personal observations from 120 stratified randomly selected rural farm households in Imo state, and analyzed using descriptive statistics and ordinary least squares regression technique. Results showed that the amount of labour used per hectare of cultivated area was estimated at about 186.5 mandays. Farm size, state of infrastructure, difference in income and household capital are key determinants of the share of household labour time devoted to farming by male and female household heads, while farm size, state of infrastructure, difference in income, household capital, dependency ratio and gender explain the share of labour time spent on non – farm income generating activities by male and female household heads in Imo State. There is need for policy actions to improve the agricultural product markets if rural households in Imo state are to allocate more labour time to farming activities.


Silk fibroin (SF), a natural protein biopolymer, exhibits a favorable structure due to the existence of alternative hydrophilic and hydrophobic domains in its molecular chains, and it shows good intrinsic mechanical properties, biocompatibility, biodegradability and low immunogenicity. The properties and functions of SF can be further enhanced and enriched through its synergetic combination with graphene-based nanomaterials (GBNs), which are two-dimensional carbon nanomaterials with impressive mechanical properties, adjustable electrical conductivity, and anticipated biocompatibility. The combination of SF and GBNs can result in fantastic properties and functions upon optimizing the interactions between them, and they can be processed into various formats to tailor them for specific applications. This review presents the structures and properties of SF and GBNs, summarizes recent progress related to assemblies of SF and GBNs, and then focuses on their interfacial interactions during the process of building high performance composites with good mechanical or conductive properties. The unique interactions provide potential ideas for designing novel composites of SF and GBNs with enhanced mechanical or conductive properties. Then, we provide the latest developments related to the applications of composites of SF and GBNs in different fields, emphasizing their applications in tissue engineering and wearable devices. Some challenges and potential measures are also suggested in relation to constructing composites of SF and GBNs to widen their future applications in biomedical fields.


Establishment of an efficient transformation system is a prerequisite for genetic improvement of Jatropha curcas , a promising biodiesel feedstock plant, by transgenic approach. In this study an efficient Agrobacterium-mediated transformation protocol using cotyledon explants from J. curcas seeds was developed. The integration and expression of the transgenes in the putatively transformed J. curcas plants was confirmed by polymerase chain reaction (PCR), Southern blot analysis and β- glucuronidase (GUS) activity staining. In the protocol used, the critical step for successful transformation is that the selective agent kanamycin (20 mg/L) is not included in the callus-inducing medium within the first 4 weeks after co-cultivation with Agrobacterium . Keywords : Agrobacterium-mediated transformation, biofuel, Jatropha curcas, kanamycin, physic nut, plant regeneration, transgenic plants.


BACKGROUND
Complex anatomy of intra-cardiac structures requires spatial orientation of image in three dimensions for better understanding and enhanced image interpretation. We evaluated the feasibility and efficacy of the emerging 'real-time three-dimensional transthoracic echocardiography' technique for comprehensive assessment of cardiac anatomy, physiology, pathomorphology and pathophysiology in patients with structural heart disease.

METHODS AND RESULTS
Patients with structural heart disease (n=152) were evaluated by conventional two-dimensional transthoracic echocardiography and real-time three-dimensional transthoracic echocardiography using standard protocol. Fifty-six cases were of rheumatic etiology with multi-valvular involvement (mitral stenosis: 32; mitral regurgitation: 29; tricuspid regurgitation: 8; aortic valve disease: 11) and 21 cases of non-rheumatic valvular heart disease. A total of 38 congenital heart disease patients were examined including 23 patients with atrial septal defect. Left ventricular function (n=20) and right ventricular function (n=10) were also assessed using dedicated software.

CONCLUSIONS
Results of real-time three-dimensional transthoracic echocardiography mitral valve area assessment by planimetery are comparable to two-dimensional transthoracic echocardiography with additional information about surface anatomy of leaflets and the subvalvular apparatus in real time with clear demarcation of commissural fusion and scallops of leaflets. Enface view of atrial septal defect with direct visualization of shape, size and number of defects, tricuspid valve area by planimetery, right ventricular shape, objective assessment of ventricular volumes and regurgitation vena contracta area are the fields where three-dimensional transthoracic echocardiography was of additive value to conventional two-dimensional transthoracic echcardiography. This study proves clinical feasibility of real-time three-dimensional transthoracic echocardiography but requires further validation of quantitative observations.


Situated in a Mediterranean landscape, the Maeght Foundation is a unique Modernist museum, product of an extraordinary collaboration between the architect, Jose Luis Sert, and the artists whose work was to be displayed there. The architecture, garden design and art offer a rare opportunity to see work in settings conceived in active collaboration with the artists themselves. By focusing on the relationship between this art foundation and its Arcadian setting, including Joan Miro's labyrinth, George Braque's pool, Tal-Coat's mosaic wall and Giacometti's terrace, Jan K. Birksted demonstrates how the building articulates many of the ideas that preoccupied this group of artists during the culminating years of their lives. The study pays special attention to the ways in which architecture can shape the experience of time, and addresses the Modernist desire for wilderness and its problematic roots in the classical Mediterranean ideal. In showing how the design of the Maeght Foundation is a Modernist representation of Mediterranean culture, the author has developed an interpretation of architecture that accommodates not only the architect's handling of material or function, but shows as well how it can be the embodiment of a particular vision of space and time. Contents Preface; Introduction: The Commission: 'A moment of Euphoria'; The labyrinth: The labyrinth; Knossos; The Mediterranean: The Mediterranean; Narratives; The Pools: The pools; Reflections; Conclusion: The Aftermath: 1974; Academic envoi: Spatial temporality; Bibliography; Index. Reviews 'Jan Birksted has responded with passion and ingenuity to a marvellous subject. Sert's Maeght Foundation fulfils the criteria for an exemplary Gallery of Modern Art, but in this account it becomes a site of deconstruction. Using a mass of archival material from Sert and the Maeght family, he explores the relationship between patron, artists and architect, and between the built form of the gallery and the surrounding Mediterranean world.' Stephen Bann, University of Bristol, UK 'Jan Birksted's unravelling of the design process of the Maeght Foundation reads like a thriller where the corpse is only discovered at the very last line. It unwraps one layer of intentions after another, revealing the fascinating potentials of architectural modernism beyond the stereotypes of the International Style. It brings to light the surprising reinvention of architecture as landscape, and garden as architecture, begot by the dance of Modernism and Surrealism under the timely skies of the Mediterranean. A marvellous promenade architecturale.' Michel Conan, Dumbarton Oaks, US 'This book is a handsome object... Birksted has accomplished a rare task. He has written a book of fine scholarship; he has managed to make it read like a gripping story; and he draws us into a world of reflection upon the nature of landscape and architecture... When Birksted leaves scholarship behind and moves into the space of argumentative speculation he treats us to rich, rewarding and exigent thought.' Edward Winters, The Architects' Journal 'The author's style manages to be both readable and scholarly, and the notes and bibliography are exhaustive...' Sandy McLendon, Modernism Magazine '... this is a beautiful, many-layered book that greatly deepens our understanding and knowledge of the building's whole design and methodology and has many fascinating details.' Twentieth Century Society Newsletter 'Though of particular interest to landscape historians, this book would also be useful to scholars of modernist art and architecture.' Katie Campbell, The Art Book


Recently, nanostructured materials have received tremendous attention because of their exceptional properties and great potential in applications. In this thesis, we investigated the thermoelectric transport properties of Si and Ge nanomembranes and nanowires as well as silica nanoclusters by using density functional theory calculations combined with Landauer-Buttiker formalism in the linear response regime. We also investigated the thermoelectric coefficients for quantum devices in the Coulomb blockade regime. The thesis is organized as follows.We first investigated the thermoelectric properties in one- and two-dimensional Si and Ge nanomembranes, i.e., silicene and germanene. We found that the figure of merit ZT in the one-dimensional zigzag-edged silicene and germanene nanoribbons decreases monotonously when the width of the nanoribbons increases. The decreasing figure of merit can be attributed to the rapid rising of the thermal conductance. Broader nanoribbons have more phonon modes contributing to the transport than those of the narrow nanoribbons, while electron conduction does not change so much. For armchair-edged silicene and germanene nanoribbons, ZT as a function of ribbon width shows an oscillating behavior. To improve the thermoelectric performance, we mixed the Si and Ge in the nanoribbons to enhance the lattice scattering. We found that the figure of merit at room temperature for hybrid narrow silicene and germanene nanoribbons is remarkably high, up to 2.5.Secondly, we investigated the thermoelectric energy conversion efficiency of Si and Ge nanowires, and in particular, that of SiGe core-shell nanowires. We showed how the presence of a thin Ge shell on a Si core nanowire increases the overall figure of merit. We found the optimal thickness of the Ge shell to provide the largest figure of merit for the devices. We also considered the Ge-core/Si-shell nanowires. Here, we found that an optimal thickness of the Si shell does not exist, since the figure of merit is a monotonically decreasing function of the radius of the nanowire. Moreover, we considered the nanowire in which the shell is an alloy of Si and Ge. We verified the empirical law relating the electron energy gap to the optimal working temperature, at which the efficiency of the device is maximized.Thirdly, we investigated the heat transfer between two silica nanoclusters. We found that when the gap between two neighboring clusters is in the range 4 A to 3 times the cluster size, the thermal conductance decreases due to the surface charge-charge interaction. When the gap is further increased to 5 times the cluster size, the volume dipole-dipole interaction dominates. On the other hand, when the gap is smaller than 4 A, quantum effects dominate, where electrons of both clusters are shared. This quantum interaction leads to the dramatic increase of thermal coupling between neighboring clusters when the gap distance decreases. This study provides a description of the transition between radiation and heat conduction in gaps smaller than a few nanometers.Finally, we investigated the thermoelectric coefficients, in particular the Seebeck efficient, for strongly interacting electrons in the Coulomb blockade regime. The Seebeck coefficient plays a fundamental role in identifying the efficiency of a thermoelectric device. Its theoretical evaluation for atomistic models is routinely based on density functional theory calculations combined with the Landauer-Buttiker approach to quantum transport. This combination, however, suffers from serious drawbacks for devices in the Coulomb blockade regime. We showed how to cure the theory through a simple correction in terms of the temperature derivative of the exchange-correlation potential. We also compared our results with those obtained from both rate equations and experimental measurements on carbon nanotubes, and we found good qualitative agreement in all cases.Our results are expected to be beneficial for the understanding of material performance and for designing future nanodevices.


This paper presents a graphical user interface, based on modified long-wavelength approximation method (MLWA) to compute the optical properties of core-shell nanoparticles. The validity of this technique is verified by comparison to the exact solution (Mie theory). For core-shell nanoparticles, when the shell thickness of a core-shell particle is decreased, the plasmon resonance shifts to longer wavelengths. This red shift is accompanied by an increase in peak intensity. For coated spherical particles, we confirm that our approach yields a correspondence with Mie theory and gives an approximation error of less than 2.8% for silica-gold and silica-silver particles with outer diameters approaching 40nm and 26nm and inner diameters approaching 38nm and 24nm respectively. Also the MLWA can give an acceptable degree of accuracy 4.92% for larger particles of silica-gold with (innerouter) diameters 68-70nm at surface plasmon resonance wavelength 1573nm. For this simulation run, the computation time was less than 150.050 ms (Intel Pentium 4 CPU at 3GHz, 1.00GB of RAM), which includes calculation of the polarizability and all three cross-section plots of absorption, scattering and extinction. This simulator provides a useful guide tool for optical characterization experiments.


SYNOPSIS: Extant literature finds mixed evidence on the association between audit market concentration and audit fees. We re-examine this issue using a large sample of U.S. audit clients covering 90 metropolitan statistical areas (MSAs) spanning 2000–2013. We find that audit market concentration is associated with significantly higher audit fees, consistent with the concerns of regulators and managers. We also find that increases in audit market concentration are associated with fewer initial engagement fee discounts (i.e., reduced lowballing), particularly for non-Big 4 clients. We reconcile our findings with those of prior research and find that our divergent findings are attributable to controls for MSA fixed effects. In supplemental analyses, we find that audit market concentration is associated with higher audit quality. We also find that concentration is associated with higher audit quality for first-year engagements, but only if the auditor does not lowball on the engagement. Our results are releva...


A patient with blue-gray discoloration of the skin of her face, neck, and hands is described. She was a patient with rheumatoid arthritis who had received a large total cumulative dose of gold. Light microscopy of skin biopsy tissue from the forehead revealed deposits of heavy metal in macrophages. On electron microscopy, the particles were found in the lysosomes of the cell. X-ray microanalysis confirmed the presence of gold. This condition, which is called chrysiasis, may be incorrectly diagnosed as cyanosis.


The speedy augmentation of the market in every sector is leading to superior subscriber base for service providers. Added competitors, novel and innovative business models and enhanced services are increasing the cost of customer acquisition. In such a tedious set up service providers have realized the importance of retaining the on hand customers. It is therefore mandatory for the service providers to inhibit churn- a phenomenon which states that customer wishes to quit the service of the company. To prevent the churn many approaches are used by the researchers. This paper reviews the different approaches used by researchers not only in communication sector but also other sectors which highly depends on customer participation.


There are three broad categories of hemostatic agents: 1) caustic, 2) physical, and 3) biologic. Because of the paucity of data on the use of topical hemostatic agents in gynecologic and obstetric surgery, indications for use are extrapolated from data on the use of these agents in other types of surgeries and are based on expert opinion. Topical hemostatic agents can be a useful adjunct to assist in the management of intraoperative bleeding in select circumstances. Topical hemostatic agents most commonly are used in situations where the use of electrocautery or sutures for hemostatic control of surgical bleeding is not ideal or safe, including bleeding in areas with nearby vulnerable structures or in the presence of diffuse bleeding from peritoneal surfaces or cut surfaces of solid organs. When managing intraoperative bleeding, there is no substitute for meticulous surgical technique. When possible, the surgeon should attempt to control intraoperative bleeding with sutures, clips, or electrosurgery before the use of hemostatic agents. It is essential for surgeons to understand the appropriate use, contraindications, and cost of these agents in order to make the most informed decision for patient care.


The nonlinear optical phenomena which occur in semiconductor materials on a femtosecond to picosecond timescale have recently generated much interest, especially in the field of telecommunications where the development of all-optical switching devices based on semiconductors promises a considerable reduction in the complexity of design coupled with a large increase in the speed of operation. This thesis examines the underlying ultrafast physical processes with the aim of providing a clear understanding of the mechanisms involved. The two main regimes of operation are investigated, namely off-resonance excitation where virtual processes are important and on-resonance excitation where real carriers are photogenerated, and in each case a particular system of interest is studied. For the virtual regime of operation, a recent proposal is examined which suggests the use of bandstructure engineering for a semiconductor quantum well in order to enhance the nonlinear optical response by the introduction of additional resonant transitions between subbands. A number of descriptions of the device are presented, and it is concluded that the technique does not necessarily lead to an improved response. An example of on-resonance phenomena is provided by the modelling of the fast refractive index changes in semiconductor laser amplifiers which have been observed in recent experiments. A simple physical model is developed which predicts the behaviour seen in the experimental observations. The nonlinear optical response of the laser amplifier promises the development of fast all-optical switching based on these devices. The thesis also examines the difficulties associated with describing the interaction of semiconductor material and electromagnetic field, and in particular looks at the formulation of a gauge invariant procedure for calculating values of the susceptibility. The propagation of a light beam along the plane of a semiconductor quantum well is discussed, and the gauge invariance of susceptibility calculations performed in the so called A.p and E.r gauges is explicitly demonstrated. Finally, a brief exploration is undertaken of the effects of bandstructure on the optical response of a semiconductor, and two quantum well models for the calculation of a more realistic bandstructure are presented which employ infinite and finite wells respectively.


Pickerel Lake formed on the Coteau des Prairies, northeastern South Dakota, prior to 10,670 ± 140 years ago. The lake was probably initially underlain by an ice block; it was insulated from the ice first by an undetermined thickness of outwash, and then also by sediment. Fossil pollen, spores, seeds, leaves, and mollusks of a core from Pickerel Lake were analyzed in order to work out the limnological history of the lake and the vegetational history of the nearby upland. The data were then compared with ecological data from modern vegetation and the lake. The following chronology was deduced from these studies: (1) Prior to 10,670 years ago, boreal forest existed around Pickerel Lake and on the nearby upland, the climate was cool and moist, there were a few marshes around the lake margin, and the lake was less than 3 m deep at the coring site. The lake water was alkaline but not very hard. (2) Between 10,670 and about 8000 years ago, there were mixed deciduous trees around the lake, in gullies, and on the upland; however, tree cover on the upland was less dense and had numerous prairie-like openings with grass and perhaps bracken fern. The climate was warmer than that of the previous age. The lake was probably deeper at the study site, and was probably slightly harder. (3) From about 8000 to 4000 years ago, blue-stem prairie dominated the upland. Deciduous forest was almost absent, except perhaps for a few groves around the lake or in gullies. The climate was characterized by recurring summer drought, and the level of Pickerel Lake consequently fluctuated markedly. The depth of the lake at the coring site was less than 3 m, and the water was hard with high carbonate content. Reed marshes were common around the lake margin, and during low water levels a rich herbaceous vegetation invaded the exposed lake sediments. (4) Since about 4000 years ago, the upland and lake vegetation has been about the same as now, with prairie dominating the upland and with an abundant oak and ash deciduous forest common around lakes and in gullies. Summer droughts were not so common as during the preceding period. The lake was less than 3 m deep at the study site. It was also alkaline, hard, and had reed marshes flourishing in places around its margin.


Abstract Discrete dental morphology among members of the extant Erinaceidae (Mammalia; Lipotyphla) is comprehensively reviewed in order to ascertain its phylogenetic resolving power. This analysis responds to the need to better understand the nature of the characters—discrete dental morphology—most commonly used to diagnose erinaceid fossil taxa, and reconstruct their evolutionary histories. This investigation attempts to set the parameters for a phylogenetic analysis of both fossil and living erinaceids. The first phase of this investigation reviews 246 descriptive discrete dental transformation series—the majority of which were gathered primarily from the literature and are (or have been) considered apomorphies at various taxonomic levels within the family Erinaceidae. These characters were reviewed across 10 species of hedgehogs: a minimum of two species per extant genus (excluding the rare species), of which all are represented by series of individuals. The data were compiled and analyzed for each individual for inter- and intraspecific variation (including asymmetry), and its possible covariation with sex, relative age (based on tooth eruption and wear stage), and geographic location. The second phase tests the phylogenetic resolving power of the discrete dental transformation series when considered as the sole body of evidence for hypotheses of evolutionary relationships. The discovered phylogenies of parsimony analyses of the discrete dental data are compared to previous hypotheses of relationships based on all known morphological evidence. Results suggest that dental variation is intemperant both inter- and intraspecifically within the Erinaceidae and cannot unequivocally be attributed to any one of the variables considered (see above); and, more specifically, the phylogenetic resolving power of the dental data (across the considered taxa) is contingent on the inclusion of other data (i.e., cranial and postcranial material). Consequently, the applicability of this character set to the erinaceid fossil record as the sole source of evidence for phylogenetic inference is challenged.


Scholars interested in the Christian Apocrypha (CA) typically appeal to CA collections when in need of primary sources. But many of these collections limit themselves to material believed to have been written within the first to fourth centuries CE. As a result a large amount of non-canonical Christian texts important for the study of ancient and medieval Christianity have been neglected. The More Christian Apocrypha Project will address this neglect by providing a collection of new editions (some for the first time) of these texts for English readers. The project is inspired by the More Old Testament Pseudepigrapha Project headed by Richard Bauckham and Jim Davila from the University of Edinburgh. Like the MOTP, the MCAP is envisioned as a supplement to an earlier collection of texts—in this case J. K. Elliott's The Apocryphal New Testament (Oxford 1991), the most recent English-language CA collection (but now almost two decades old). The texts to be included are either absent in Elliott or require significant revision. Many of the texts have scarcely been examined in over a century and are in dire need of new examination. One of the goals of the project is to spotlight the abilities and achievements of English (i.e., British and North American) scholars of the CA, so that English readers have access to material that has achieved some exposure in French, German, and Italian collections.


An integrated seismic–stratigraphic study of the Lower Cretaceous Cromer Knoll Group was undertaken as part of a recent comprehensive analysis of the Upper Jurassic – lowermost Cretaceous petroleum system in the Danish Central Graben. This study of the basal group of the post-rift package yielded an updated regional assessment of the distribution of the Valhall, Tuxen, Sola and Rødby Formations. This is documented by four high resolution isochore maps (presented here) that record temporal shifts in subsidence patterns from the latest Ryazanian to the earliest Cenomanian. The distribution and thickness variation of the mud-dominated Valhall Formation (latest Ryazanian – early Hauterivian) at the base of the group attests to the progressive fill of inherited syn-rift morphology. The dominant depositional theme is thus ponding in, and onlap from, the main inherited depocentres, although growth faults and incipient inversion locally controlled stratigraphic architecture, and new depocentres were initiated in the east of the graben (Ål and Outer Rough Basins). The isochores for the succeeding, increasingly chalk-rich Tuxen, Sola and Rødby Formations (Hauterivian – earliest Cenomanian) document the regional weakening of syn-rift patterns but emphasize the shift in sedimentation patterns controlled by accelerating inversion activity in the east (Adda–Tyra area, Søgne Basin) and increased local subsidence. The latter sometimes coincided with syn-rift depocentres, such as the Roar Basin and the Arne-Elin Graben, but was also significant in the new Early Cretaceous depocentres in the west of the graben, particularly the Outer Rough Basin. The evolution of the Early Cretaceous basin recorded by this dataset reveals significant shifts in the subsidence pattern in the late Valanginian – early Hauterivian, in large part due to early inversion in the east, and during the late Aptian – early Albian when subsidence was focussed in central and western sub-basins, probably locally due to salt withdrawal. These events, in combination with sea-level change, had implications for the accumulation and preservation of Barremian and early Aptian reservoir chalks.


The purpose of this article is to identify the conditions that set the stage for the secessionist movements within the Soviet Union. Using the statistical procedures of discriminant and regression analysis, the following thesis is tested: Secessionist movements are undertaken for the reason of emancipation from economic exploitation, for the purpose of maintaining or preserving an endangered culture, or for the purpose of achieving redress from some form of political grievance. An evaluation of the parameters produced by estimating linear regression models indicates that high levels of social and economic development together with concentrated populations are the structural factors that provide the contextual environments most conducive to early demands for sovereignty. Other factors that are related to separatism are pervasive international ties, Christian traditions, and relatively small populations and territory. The analysis serves to challenge widely held assumptions that a reaction against Russian settlement in minority enclaves, state-sponsored efforts at Russification, and relative deprivation were prime motivators behind secessionist activity.


1. The synthesis of dibutylchloromethyltin chloride, a new covalent inhibitor of the mitochondrial ATP synthase [oligomycin-sensitive ATPase (adenosine triphosphatase)] complex is described, together with a method for preparing dibutylchloro[(3)H]methyltin chloride. 2. Studies with the yeast mitochondrial oligomycin-sensitive ATPase complex show that dibutylchloromethyltin chloride inhibits both the membrane-bound enzyme and also the purified Triton X-100-dispersed preparation. 3. F(1)-ATPase is not inhibited even at 500nmol of dibutylchloromethyltin chloride/mg of protein, and the general inhibitory properties are similar to those of triethyltin, oligomycin and dicyclohexylcarbodi-imide, known energy-transfer inhibitors of oxidative phosphorylation. 4. Binding studies with yeast submitochondrial particles show that dibutylchloromethyltin chloride antagonizes the binding of triethyl[(113)Sn]tin, indicating that there is an interaction between the two inhibitor-binding sites. 5. Unlike triethyltin, inhibition by dibutylchloromethyltin chloride is due to a covalent interaction which titrates a component of the inner mitochondrial membrane present at a concentration of 8-9nmol/mg of protein. 6. All of the labelled component can be extracted with chloroform/methanol (2:1, v/v), and sodium dodecyl sulphate/polyacrylamide-gel electrophoresis of the chloroform/methanol extract indicates that the labelled component has an apparent mol.wt. of 6000-8000. However, t.l.c. reveals the presence of only one labelled component which is lipophilic and non-protein and is distinct from the free inhibitor, mitochondrial phospholipids and the dicyclohexylcarbodi-imide-binding protein (subunit 9). 7. Inhibition of mitochondrial ATPase and oxidative phosphorylation is correlated with specific interaction with a non-protein lipophilic component of the mitochondrial inner membrane which is proposed to be a co-factor or intermediate of oxidative phosphorylation.


In order to investigate the importance of the host microbiota on differentiation of T cell subsets in response to infection, Swiss/NIH germ-free mice and conventional (microbiota-bearing) mice were infected with Leishmania major, and lesion development, parasite loads, and cytokine production were assessed. Germ-free mice failed to heal lesions and presented a higher number of parasites at the site of infection than their conventional counterparts. In addition, histopathological analysis indicated a higher density of parasitized macrophages in lesions from germ-free mice than in conventional mice. The initial production of interleukin (IL)-12 and interferon-gamma (IFN-γ) in germ-free mice was comparable to the conventional controls. Also, germ-free mice produced elevated levels of IFN-γ and lower levels of IL-4 throughout the course of infection, suggesting the development of a Th1 response. Macrophages from germ-free mice exposed to IFN-γ and infected with amastigotes in vitro were not as efficient at killing parasites as macrophages from conventional animals. These observations indicate that the microbiota is not essential for the development of Th1 immune responses, but seems to be important for macrophage activation.


After a young girl's father is deported, she and her family have had to tighten their belts, and now they've had to move in with family. The girl misses Papi at their soccer games and on her birthday, and she's upset when "a mean boy at school" says her father was taken away because he did something bad. Her mother explains that that's not true and that none of the rest of the family will be deported; the girl still misses her father, though, and thinks about the two of them in different places looking up at the same bright orange full moon. This is a sincere and sympathetic look at the kids left behind when deportation takes their parents; it is, however, unambiguously programmatic, and the full-moon framing is more poetic than effective. The thickly painted art is atmospheric and smoothly textured, but the drafting is sometimes stiff and awkward, and our protagonist's facial expressions are severely limited. This has most potential for introducing the personal impact of deportation to kids who don't live with its possibility and for opening up discussions of family immigration history then and now. A Spanish-language edition is also available. DS


This paper adopts a case-study approach to illuminate some core features of assessment models that engage learners and supports learning. It explores the student perspective on assessment and feedback processes in four modules delivered by the author. Initially, the assessment literature is reviewed to identify good practice. Based on this review, key features that were implemented include the use of criteria; exemplars, model answers and assessment workshops to communicate the criteria and standard; feedback to support learning; and, in most cases, opportunities to apply the feedback in their final assignment. A student questionnaire was used to collect data. As the student intake in individual modules is low (13 – 60 students) a longitudinal approach – over the years 2011 to 2015 - was used to increase the validity of the study. An analysis of the quantitative survey data reveals that students are highly satisfied with the assessment methodology. The qualitative data identifies feedback as a key feature of the assessment environment. The analysis also reveals that students identify with feedback that corrects, guides and motivates students. This feedback, when incorporated into a feedback-on-draft assessment model, engages students with the assessment process. The main issue reported revolved around making the assessment criteria sufficiently explicit. A significance of the study is that it illustrates how both student satisfaction and engagement with assessment can be enhanced by evidence-based assessment practices.


As our previous issue 8:2, this issue of Erasmus Law Review addresses the problem of incorporating insights from non-legal disciplines into legal research. Whereas the articles in issue 8:2 focused on more general and theoretical questions with regard to the incorporation problem, this issue contains a number of case studies. The first four articles reflect on concrete research projects conducted by legal researchers in which they include a form of interdisciplinarity. The final article takes a different approach, by using Ph.D. theses, scholarly articles, and Law Reform Commission reports, analyzing whether and how legal researchers do interdisciplinary research.


Titanium dioxide/poly(methyl methacrylate) (TiO2/PMMA) hybrid films with various amounts of TiO2 containing PMMA resin on PMMA sheets were produced by a tape casting method. TiO2 nanocrystals were prepared using electrospraying process at 400oC under high electric field of 3 kV/cm. The as-sprayed and annealed TiO2 powders were characterized by Raman spectroscopy, XRD, SEM and TEM. The UV absorption for both pristine PMMA sheet and TiO2/PMMA hybrid film on PMMA sheet was measured using UV-Vis spectroscopy. The as-sprayed and annealed TiO2 powders showed anatase preferred orientation. They have higher UV absorption in the range of wavelength between 230 and 370 nm than commercial anatase TiO2 nanopowders. Moreover, the visible light transmittances of anatase TiO2/PMMA hybrid films on PMMA sheets in the range of wavelength between 400 and 800 nm was comparable with those derived from pristine PMMA sheets. Therefore, the resulting hybrid films can block out the UV rays, but are transparent to visible light.


The town of Kilis in Kilis province, south-central Turkey is harboring about 100.000 urban Syrian refugees from the three-year-old Syrian conflict alongside its 82,000 Turkish residents. Malteser International and International Blue Crescent implemented mental health/psychosocial support intervention with the objective to improve well-being and resilience of urban Syrian refugee population. In this study, the authors presented and evaluated the effectiveness of this intervention. It was delivered to Syrian refugees in the field hospital, outpatient health centre and community skills centre in the town of Kilis. Data collection methods included HESPER survey and quantitative surveys using well-being and resilience scale. The results showed improvement of resilience and well-being of the targeted population. The intervention was effective in an urban context. Further evaluation of this intervention is needed, preferably in a form of prospective longitudinal cohort study with a control group of Syrian refugees that receives no intervention.

 Key words: Turkey, community-based MHPSS intervention, urban Syrian refugees, project description, project evaluation, well-being, resilience.


Literature Review: Pathways to social anxiety often reflect a set of complex and interacting factors including intrinsic and environmental factors. Theoretical models of social anxiety have highlighted that children and adolescents' peer experiences can increase risk for social anxiety. This systematic review explored the role of peers in the development of social anxiety in adolescent girls. It aimed to identify peer-related risk factors (i.e., peer acceptance, peer attachment, friendship quality, peer support, and victimisation) that place adolescents at risk for social anxiety, including those specific to girls. The results showed that while some peer experiences were relevant to understanding risk across genders, others placed girls at increased risk. For example, low peer acceptance was significantly associated with increased social anxiety in boys and girls, both concurrently and over time. Those factors that placed girls at increased risk of social anxiety and avoidance, relative to boys, included limited close friendships, negative friendship experiences and relational victimisation. The review suggested that researchers might usefully start to develop frameworks that capture generic as well as gender-specific risk for social anxiety. These will facilitate the development of prevention and intervention methods to support girls at increased risk, that focus on improving the quality of their peer relationships. Empirical Paper: The onset of adolescence represents an age where young people are at risk for the development of social anxiety. Increasingly, research has highlighted an increased risk of social anxiety in girls with Autism Spectrum Disorders (ASD). However, there remains a lack of understanding of their experiences and the extent to which they are consistent with current models of anxiety in ASD. This qualitative study aimed to develop an understanding of the experience of social anxiety in adolescent girls with ASD from the perspective of young people themselves, their parents and teachers. Semi-structured interviews were conducted with four triads, with girls interviewed using an 'ideal classroom' activity to explore their perception of school-based social situations. Four interrelated themes emerged from the data across all four triads including (1) barriers to social situations, (2) quality of relationships, (3) coping with social situations, and (4) desire to 'fit in'. The results found that girls' experiences were underpinned by factors present in typical pathways to social anxiety (e.g. negative peer experiences and poor social skills) and that girls' sensory sensitivity to noise acted as an autism-specific pathway. Implications for professionals who work with adolescent girls diagnosed with ASD were discussed, including the delivery of targeted training and workshops to increase staff understanding and raise peer acceptance.


In this paper we explore techniques for 8T SRAM that allow near threshold voltage (NTV) operation as well as improved functionality across a wide voltage range. Operating in these voltage regimes will be crucial for emerging hardware paradigms, such as IoT (internet-of-things) and throughput oriented accelerators, e.g., deep learning accelerators, that will target lower voltages than conventional processors. We present several programmable enhancements to the recently proposed voltage supply boosting technique for further reducing Vmin as well as adapting to various operating conditions. These enhancements allow for a reduction in the power required for boosting through optimizing boost buffer sizes and shaping the boost pulse width. Furthermore, adjusting the boost pulse phase allows for additional Vmin reduction as well as faster read access times. These programmable booster techniques are demonstrated in a 2nd generation test chip in 14nm FinFET SOI technology.


Landslides in many regions constitute serious hazards that cause substantial life and financial losses. To overcome and reduce the damages, efforts to monitor landslides are developed. One such technology utilizes a wireless sensor network (WSN). Results obtained from studies conducted in the Ikanfoti village, Kupang District, Nusa Tenggara Timur (NTT) Province (S 10 o 16' 21.9" and E 123 o 40'59.8") as pilot project, give result that the application of WSN can be applied properly. We detect and measure vibrations caused by landslides by vibration sensor (accelerometer) on Micaz devices. The results of this study indicate that changes in accelerometer values ranging from 0.2 g (gravity) to 0.49 g of either the X or Y of accelerometer indicate that soil begins to move but not significantly. Value above 0.5 g is a value that indicating a significant change of ground motion. The value of 1 g and above of ground motion indicates a very strong activity and should be alarmed. It is expected that this research provides the foundation for the application of WSN in various areas in NTT Province and Indonesia in general, for establishing thorough and reliable early warning system (EWS).


The essay looks at characterization in the plays of Ben Jonson as phobic projective behaviors that can best be understood using theories of narcissism and Kleinian object-relations theory. Jonson exhibited what are today clear symptoms of narcissistic personality disorder. The essay argues that Klein's ideas on projective behavior in which the subject attempts to cast out bad partial objects (selfobjects) is more helpful in explaining self-fashioning in Jonson than Greenblatt's theory. Object-relations theory makes sense of the action and characters in several of the plays, explains Jonson's attitude to his son (another Ben), and even tells us something about his need to drop letters from his name (Johnstone). keywords: Klein, Freud, self-fashioning, object-relations, narcissism, DSM IV, depressive, paranoid-schizoid, introjective, projective selfobject, partial objects, Heidegger, Derrida, exomologesis, publicatio sui, Every Man out of His Humour, Volpone, Bartholmew Fair, Sejanus url: http://www.clas.ufl.edu/ipsa/journal/2006_donoghue01.shtml Sinne of selfe love posesseth al mine eye And all my soule and al my every part And for this sinne there is no remedie, It is so grounded inward in my heart. Shakespeare (Sonnet 62) A graphic instance of Renaissance self-fashioning occurred in 1604 when Benjamin Johnson, stepson of a Westminster bricklayer, dropped the 'h' in his name to become Ben Jonson, son of no John. The author later told Drummond that he was related to the Johnstones of Dumfries, just across the Scottish border, and that his grandfather was a gentlemen who had served Henry VIII. The Johnstones were a rocky quarry of lowland Scots ("a band of butchers and cut-throats" as Rosalind Miles puts it) who would have made colorful ancestors for Jonson, and maybe did.1 The 't' had been dropped long before, thus eliminating the masonry, and dropping the 'h' eliminated the filial note, allowing the author to spring forth parthogenetically, like Athena, from his own mind, into the footlights.2 Unfortunately the repressed masonry had already returned some time before when Johnson's mother took the bricklayer, Robert Brett, for her second husband. And one might argue that the loss of the aspirated 'h' makes no material difference. Indeed, by the time he dropped it, Jo(h)nson was already well-known, if not quite yet the poet and gentleman he envisioned. It was also about this time that he followed the fashion in Renaissance self-fashioning and purchased a coat of arms. Jonson does not make it onto the list of the fashionable in Stephen Greenblatt's "historical drama" on the topic As Greenblatt says, his is only one "narrative selection" among many that would be possible. But an equally good reason might be that while Jonson was a determined self-fashioner, and meets Greenblatt's requirement of demonstrating "profound mobility," the mobility is not upward. The figures Greenblatt focuses on were self-made men who rose in class from humble beginnings. Spenser was the son of a tailor; Marlowe the son of a shoemaker; Shakespeare the son of a glover. Spenser became a large landowner; Marlowe went to Cambridge; Shakespeare owned a large house in Stratford. Another Greenblatt choice, Sir Thomas More, was the son of a lawyer and rose to the heights of power before achieving the ultimate in upward mobility by losing his head.3 Jonson by comparison could only relieve others of theirs, of their mobility at least, which he did twice, and convert to Catholicism, which he did once. That at least got him moving, since it (probably) saved his life in prison. But it was a lateral mobility at best. So Jonson seems to require something different by way of a self-fashioning program from what Greenblatt offers-something that can describe and account for his own special kind of mobility, not to mention the mobility of those two letters. What does it mean to drop letters from one's name? …


This review article explores the aims, implementations and results of the British Imperial education policies in the Indian Subcontinent which installed English language as a measure to establish British influence and control over the colony. It looks into the historical beginnings of English in Pakistan in the postcolonial context, which resulted in the loss of Persian, the end of the indigenous system of education, formation of hybrid identities, and the establishment of elite institutions. These issues are still plaguing the education system in present day Pakistan.


Abstract Objective The objective of a study was to assess the ability of the pre-implantation genetic testing of embryos for aneuploidy (PGT-A) and Endometrial receptivity array (ERA)—alone or in combination to improve the clinical outcomes in intracytoplasmic sperm injection (ICSI) cycles in patients with repeated implantation failure (RIF). Methods This was a retrospective study of the 253 cycles with a history of the previous RIF. They were divided into four groups: Group I - frozen embryo transfers without any additional tests or procedures (pure FET), n = 72 cycles; Group II - FET with PGT-A, n = 87; Group III - FET with PGT-A and ERA, n = 72; Group IV - FET with ERA, n = 22. Results Median age of the entire study group for the females was 35 years. Only Group II (FET + PGT-A) showed statistically significant higher chance in achieving both biochemical (p = .01, OR = 5.5) and clinical pregnancy (p =.049, OR = 2.3), as compared to the Group I (FET with no additional tests). Both Group III and Group IV failed to demonstrate better clinical outcomes as compared to the Group I. Conclusions Patients with RIF can benefit from testing for embryo aneuploidy using the PGT-A method, but the ability of the ERA test to improve the clinical outcome in ICSI cycles seems to be rather limited. Although the endometrium cycle is also weakened with age, the contribution of the embryo genetic quality is evidently more important for successful implantation, although in principle both factors reflect the reproductive health.


Recently, text-based chatbots had a rise in popularity, possibly due to new APIs for online social networks and messenger services, and development platforms that help dealing with all the necessary Natural Language Processing. But, as chatbots use natural language as interface, their users may struggle to discover which sentences the chatbots will understand and what they can do. Because of that it is important to support their designers in deciding how to convey the chatbots' features, as this might determine whether the user will continue chatting or not. In this work, our goal is to analyze the communicative strategies used by popular chatbots when conveying their features to users. We used the Semiotic Inspection Method (SIM) for that end, and as a result we were able to identify a series of strategies used by the analyzed chatbots for conveying their features to users. We then consolidate these findings by analyzing other chatbots. Finally, we discuss the use of these strategies, as well as challenges for designing such interfaces and limitations of using SIM on them.


Within human-machine conversation, clarification is vital and may consist of various forms, as it is may by due to many different effects on different levels of communication. In this paper, we present a strategy for detecting situations where a need for clarification exists in a natural spoken dialogue system. We define rule sets which enable us, via an anomaly analysis, to detect these critical situations. Through the use of such rule sets, we show that ist is possible to enhance the strategy in such a manner that more different situations are detected. In a user test, we evaluate the success of the strategy and show that strategies with explicit clarification improve the naturalness of human-machine interaction.


[fre] Abstract : The ecclesiastical insinuations were created in the sixteenth century in France in order to put on end to frauds during the benefice transfers. The relating law, which has often been modified, has made it possible to register in each diocese various deeds which provide the historian with serials. The example of the 57 registers preserved for the diocese of Langres shows the abundance of documents for studying the regular and secular clergy and its origins. This documentation gives useful information about the «career» of clerics, about commendam, about the universities' graduates and so on. Above all, it allows us to analyse the benefice system from the sixteenth century up to the French Revolution. The importance of this source of information leads to make a nation-wide investigation into these documents, which has been sketched out here in the case of Burgundy and Champagne and which aims at working out a Catalogue of the ecclesiastical insinuations which could be used by researchers.


Summary In this article we summarize the theoretical arguments which led us in the German Hodgkin's Disease Study Group to introduce the BEACOPP-regimen and to initiate a large randomised trial to investigate the role of moderate dose escalation in the treatment of advanced stage Hodgkin's disease. Although some indications for a role of dose were available in the early 1990s no prospective randomised trial had been undertaken. In order to obtain an impression of the shape of the essential dose response characteristic we developed a novel statistical model that could be used to analyse a set of data in which dose variations had occured. The model took tumour growth and chemotherapy effects into account. The model could be applied to clinical data on tumour control and treatment given in a patient population. The model was fitted to the data of 706 patients which had received COPP/ABVD-like regimens. It revealed considerable heterogeneity in chemosensitivity and a positive slope of the doseresponse relationship. The model was used to simulate the effect of various treatment strategies with dose escalation and schedule changes. On the basis of such simulations we predicted that shortening cycle intervals from 4 to 3 weeks should lead to small benefits (about 3% in fiveyear tumour control rates). In contrast, we predicted that a moderate average dose escalation by 30% of a standard chemotherapy would lead to a potential benefit in the order of 10%-15% in tumour control at five years. Subsequently we searched for a treatment scheme that would permit such a dose escalation. The BEACOPP-scheme was invented to allow the three major myelotoxic substances (cyclophsphamide, adriamycin and etoposide) to be given in the beginning of a cycle. These three substances were then subject to dose escalation in a dose finding trial. G-CSF was introduced to compensate for the myelotoxic effects. The dose level found feasible for a large multicentre setting turned out to be in the required magnitude. The HD9 trial of the GHSG was then initiated to examine whether the predicted dose response curve really exists.