The past year alone has seen unprecedented leaps in the area of learning-based image translation, namely Cycle-GAN, by Zhu et al. But experiments so far have been tailored to merely two domains at a time, and scaling them to more would require an quadratic number of models to be trained. And with two-domain models taking days to train on current hardware, the number of domains quickly becomes limited by the time and resources required to process them. In this paper, we propose a multi-component image translation model and training scheme which scales linearly - both in resource consumption and time required - with the number of domains. We demonstrate its capabilities on a dataset of paintings by 14 different artists and on images of the four different seasons in the Alps. Note that 14 data groups would need (14 choose 2) = 91 different CycleGAN models: a total of 182 generator/discriminator pairs; whereas our model requires only 14 generator/discriminator pairs.


Keystroke biometrics, as an authentication method with advantages of no extra hardware cost, easy-to-integrate and high-security, has attracted much attention in user authentication. However, a mass of researches on keystroke biometrics have focused on the fixed-text analysis, while only a few took free-text analysis into consideration. And in the field of free-text analysis, most researchers usually devote their efforts to extracting the most appropriate keystroke features on their own experience. These methods were inevitably questionable due to their strong subjectivity. In this paper we proposed a multi-user keystroke authentication scheme based on CNN model, which can automatically figure out the appropriate features for the model, adjust and optimize the model constantly to further enhance the performance of model. In the experiment on a small sample set, the performance is improved more than 10% compared with the benchmark. Our model achieves an average recognition accuracy of 92.58%, with FAR of 0.24% and FRR of 7.34%.


Background Skin tests have an important place in the diagnosis of hypersensitivity. Because of a lack of precise skin tests procedures, drug skin tests are often not carried out. However, they could help to determine the cause of hypersensitivity and help in the choice of therapeutic strategy. In our hospital, a dermatologist required us to produce skin tests with cytotoxic and anti-HER2 antibody agents (docetaxel, pertuzumab, trastuzumab) in order to evaluate the hypersensitivity of a patient who developed a photosensitive dermatosis after a second cycle of chemotherapy. Purpose The aim of this project was to produce a feasibility study for the production of skin tests with these three molecules. Material and methods A literature review was performed to find data about skin tests, and more particularly about safety and non-irritant drug concentrations. Because of a lack of data, we also decided to realise an investigation near the others hospital centres. Chemical tests were carried out such as the measure of the drug pH and the miscibility between the diluant and the medicine. Results According to the literature, the pH drug must be between 6 and 9 to avoid skin injuries. By its acidic pH, docetaxel could not be used to produce a patch test (non-diluated drug pH=3, diluated with 0.9 per cent sodium chloride drug pH=4). The pH of the two other agents and of the diluant was acceptable (pH=7). In most of the publications, the excipient used for the preparation of patch tests was petroleum jelly. In cooperation with the doctor, we decided to produce a prick test with docetaxel, prepared by diluting the drug to 5 mg/ml in an aqueous solution of 0.9% sodium chloride. Concerning pertuzumab and trastuzumab, patch tests were obtained by realizing an homogeneous preparation, with a concentration of 30% in petrolatum. Conclusion The literature deals mainly with a platinum agent, and more often with skin prick tests and intradermal tests. We were confronted with the difficulty of possessing poor data when facing the request of the dermatologist. Moreover, according to the literature, patch tests commonly reveal false negative results. This activity necessitates the development of a local thesaurus and an economic study. References and/or acknowledgements No conflict of interest.


The aim of this study was to assess the toxic effects of chronic exposure to fluphenazine in liver and kidney of rats, as well as the possible protective effect of diphenyl diselenide on the fluphenazine-induced damage. Long-term treatment with fluphenazine caused an increase in lipid peroxidation levels in liver and kidney homogenates. Diphenyl diselenide treatment did not affect delta-aminolevulinate dehydratase (delta-ALA-D) activity, but fluphenazine alone or in combination with diphenyl diselenide showed an inhibitory effect on delta-ALA-D activity in liver. Diphenyl diselenide plus fluphenazine treatment increased the reactivation index of hepatic delta-ALA-D by approximately 80%. Superoxide dismutase activity decreased in liver of rats treated with fluphenazine alone. The combined treatment with fluphenazine and diphenyl diselenide was able to ameliorate superoxide dismutase activity in liver of rats. Catalase activity was augmented in liver from rats treated with fluphenazine, and this increase was prevented when diphenyl diselenide was co-administered. Taken together, these results indicate that the association of diphenyl diselenide with fluphenazine could protect the liver from lipid peroxidation and ameliorate superoxide dismutase and catalase activities. Moreover, our data point to the relationship between the oxidative stress and fluphenazine treatment in liver and kidney of rats.


A high-capacity dense wavelength-division multiplexing/subcarrier multiplexing (DWDM/SCM) network based on a self-healing star-bus-ring architecture (SBRA) is proposed and demonstrated. This architecture has a star subnet on the upper level to be a high-capacity infrastructure for the network, several bus subnets on the middle level to offer broad-band channels for multiwavelength signals, and many ring subnets on the lower level to serve a number of nodes. We design remote nodes and bidirectional wavelength add-drop multiplexers (WADMs) by using simple optical switches to reconfigure the network under link failure. We further employ M-quadrature amplitude modulation (M-QAM) and frequency shift-keyed (FSK) signals for downstream and upstream channels, respectively. The SBRA ensures an optical-beat-interference-free (OBI-free) and high-reliability optical network. Finally, we set up an experimental network to demonstrate the feasibility of the proposed architecture.


In the numerical simulation of mold filling process, the calculation efficiency has been a key point for practical applications due to the complexity and thin-section of die castings. In current research work, a fractional step method was applied in the solution of the unsteady Navier-Stokes equations, which can be implemented with a single solution to the momentum/pressure equations at each time step. This method may avoid the decrease in efficiency induced by iteration. A water analog system was designed and developed to simulate the die casting process. The flow patterns were recorded by a high speed camera with a capturing rate of 500 frames per second. The simulation results were consistent with the experimental ones. Besides, the fluid flow patterns of several components were simulated by the fractional step and VOF algorithm, and the SOLA-VOF algorithm respectively. The simulation results showed that the combination of the fractional step method and VOF method can improve the computational efficiency to some extent in numerical simulation of mold filling process.


Three-dimension scene simulation technology of virtual environment maybe widely applied in many fields such as virtual battlefield, tourist industry and city planning. The technique has been applied to the research of "Virtual Battlefield" which provides a new research topic in the today's world. And simulation training system of cruise missile is very important in the whole R&D (Research and Development) process because of the complexity and uncertainty of the real battlefield environment. In this paper, in allusion to the problem of simulation training system of cruise missile GUI, some key technologies about how to realize the system are introduced, including 3D modeling, object picking up, multi-channel comparison, object hierarchical display and so on. Accordingly, the six freedom motion simulation system is presented, which was established by Visual C++. Secondly, establishing cruise missile entity model in Multigen Creator and putting it into the vision simulation system that is build up by Vega Prime. At lastly, combining two simulation systems into an integrity one. The integrity simulation system performed well in test.


Title of Thesis: Convexification and Deconvexification for Training Artificial Neural Networks Yichuan Gui, Degree of Philosophy, 2016 Thesis directed by: Dr. James Ting-Ho Lo, Professor Department of Mathematics and Statistics Dr. Yun Peng, Professor Department of Computer Science and Electrical Engineering The purpose of this dissertation research is to overcome a fundamental problem in the theory and application of artificial neural networks (ANNs). The problem, called the local minimum problem in training ANNs, has plagued the ANN community since the middle of 1980s. ANNs trained with backpropagation are extensively utilized to solve various tasks in artificial intelligence fields for decades. The computing power of ANNs is derived through its particularly distributed structure together with the capability to learn and to generalize. However, application and further development of ANNs have been impeded by the local minimum problem and attracted much attention for a very long time. To represent high-level abstractions, ANNs with deep architectures, called deep neural networks (DNNs), have recently been extensively studied. Training DNNs involves significantly intricate difficulties, prompting the development of the method of unsupervised layer-wise pre-training and many ingenious heuristic techniques. Although such methods and techniques have produced impressive results in solving famous machine learning tasks, more serious problems originated from the essence of local minimum in high-dimensional non-convex optimization still remain. A primary difficulty of solving the local minimum problem lies in the intrinsic nonconvexity of the training criteria of the ANNs, which usually contain a large number of non-global local minima in the weight space of the ANNs. As the standard optimization methods perform local search in the parameter (e.g., weight) space, they cannot consistently guarantee a satisfactory performance of the resultant ANN even with a large number of training sessions. Although an enormous amount of solutions have been developed to optimize the free parameters of the objective function for consistently achieving a better optimum, these methods or algorithms are unable to solve the local minimum problem essentially with the intricate presence of the non-convex function. To alleviate the fundamental difficulty of the local minimum problem in training ANNs, this dissertation proposes a series of methodologies by applying convexification and deconvexification to avoid non-global local minima and achieve the global or near-global minima with satisfactory optimization and generalization performances. These methodologies are developed based on a normalized risk-averting error (NRAE) criterion. The use of this criterion removes the practical difficulty of computational overflow and ill-initialization existed in the risk-averting error criterion, which was the predecessor of the NRAE criterion and has benefits to effectively handle non-global local minima by convexifying the non-convex error space. The effectiveness of the method based on the NRAE criterion is evaluated in training multilayer perceptrons (MLPs) for function approximation tasks, demonstrating the optimization advantage as compared to training with the standard mean squared error criterion. Moreover, numerical experiments also illustrate that the NRAE-based training methods applied to train DNNs, such as convolutional neural networks and deep MLPs, for recognizing handwritten digits in the MNIST dataset achieve better optimization and generalization results than many benchmark performances. At last, to enhance the generalization of the ANNs obtained with the NRAE-based training, a statistical pruning method that prunes redundant connections of the ANNs is implemented and confirmed for further improving the generalization ability of the ANNs trained by the NRAE criterion.


PURPOSE
Hormone treatment in trans women in Europe usually consists of the administration of estrogens and antiandrogens, for example, cyproterone acetate (CPA). Mild serum prolactin elevations during follow-up are attributed to estrogen therapy. This analysis evaluates whether CPA contributes to the elevation of prolactin in trans women receiving gender affirming hormones.

METHODS
This study is part of the endocrine part of the European Network for the Investigation of Gender Incongruence (ENIGI). Belgian data were selected for this substudy. Trans women who initiated gender affirming hormone treatment and underwent orchiectomy were prospectively evaluated. Trans women were treated with oral CPA 50 mg in combination with estrogen substitution. Postsurgery, estrogen was reinitiated in an unchanged dose. Sex steroids, gonadotropins, and prolactin were compared at baseline, pre- and postsurgery in patients receiving orchiectomy, and at baseline, 12, and 18 months in patients who did not undergo orchiectomy.

RESULTS
One hundred and seven trans women participated in this analysis, with a mean age of 31.5 years. An increase in serum prolactin levels was seen in the group undergoing orchiectomy (23.72 μg/L) and not undergoing orchiectomy (23.05 μg/L) at the preoperative and 12-month visit, compared with baseline (9.42 μg/L, P = 0.002 and 9.94 μg/L, P < 0.001, respectively). After orchiectomy, a decline in prolactin levels (10.17 μg/L, P < 0.001) occurred.

CONCLUSIONS
CPA is likely to cause a temporary increase in serum prolactin, with prolactin levels returning to normal after orchiectomy and CPA discontinuation.


Background: Although current treatment strategies for ulcerative colitis have been fairly effective, many ulcerative colitis patients do not respond to such treatments and require a colectomy. Development of new therapeutics is indeed necessary to fulfill unmet medical needs. PDE4 (phosphodiesterase 4) inhibitors, including apremilast and roflumilast, have been demonstrated to be useful in treatment of ulcerative colitis in the pre-clinical animal models, and apremilast is under evaluation in clinical trials for treating ulcerative colitis. However, dose-limiting side effects on the central nervous system (CNS) and gastrointestinal tract (GI), including nausea, emesis, headache, and diarrhea, might impede the establishment of an appropriate therapeutic index for the treatment of ulcerative colitis in a safe and efficacious manner. Given the anti-inflammatory effect of PDE4 inhibitors relies on the suppression of inflammation in various immune cells, all of which express CD11a, we have now developed a targeted therapeutic antibody drug conjugate (ADC), consisting of &agr;CD11a antibody and an analog of a highly potent PDE4 inhibitor GSK256066, to specifically deliver this small molecule into immune cells sparing the neuronal cells of the CNS and GI. This targeted delivery method could be a potential therapeutic strategy for treating ulcerative colitis. Methods: We generated both human and mouse &agr;CD11a-PDE4 inhibitor ADC, consisting of human &agr;CD11a antibody (Efalizumab) or mouse &agr;CD11a antibody (M17), and an analog of a highly potent PDE4 inhibitor GSK256066. The effect of the ADC in inhibiting inflammation was assessed both in primary human and mouse immune cells in vitro, and in a carrageenan-induced air pouch inflammation mouse model in vivo. Results: We show herein human and mouse &agr;CD11a-PDE4 inhibitor ADC suppressed LPS-induced TNF&agr; secretion in human primary monocytes and mouse primary peritoneal cells, respectively. This inhibition of TNF&agr; secretion by mouse &agr;CD11a-PDE4 inhibitor ADC in mouse peritoneal cells was mediated through CD11a, as treatment with excess &agr;CD11a antibody abrogates the ADC's effect and this ADC did not reduce TNF&agr; secretion in MEF cells that were negative for CD11a. In a carrageenan-induced air pouch inflammation mouse model, treatment with the ADC significantly reduced inflammatory cytokine production in the air pouch exudate. In addition, mouse &agr;CD11a-PDE4 inhibitor ADC bound to the lamina propria mononuclear cells and reduced TNF&agr; and IFN&ggr; production in these cells isolated from DSS-induced colitis mouse colons. Conclusions: These results provide evidence for the feasibility of specifically-delivering immune suppressants to immune compartment and the development of PDE4 inhibitor ADC as a promising therapeutic for treating ulcerative colitis.


OBJECTIVE
To investigate the role of human estrogen receptor-related receptors (ERRs) in ovarian cancer.

METHODS
A green fluorescent protein (GFP) reporter plasmid of ERRalpha was constructed and transfected into ovarian cancer cell lines SKOV3 and OVCAR3. RT-PCR was used to analyze the expression of ERRalpha, ERRbeta, and ERRgamma mRNA in 33 primary ovarian cancer samples and 12 normal ovarian epithelial cells. Progression-free survival time and overall survival time of patients with different expression of ERRs were analyzed by Kaplan-Meier method.

RESULTS
GFP-ERRalpha fusion protein showed ERRalpha expressed in the ovarian cancer cell nucleus. Expressions of the ERRalpha and ERRgamma were increased in the ovarian cancers (58% and 48%) compared with the normal ovarian tissues (P < 0.05); ERRbeta was weakly expressed in the ovarian cancer (9%) as well as in the normal tissues (0). Expression of ERRalpha was positively correlated with the International Federation of Gynecology and Obstetrics (FIGO) stage (r = 0.639, P = 0.017) and cell grading (r = 0.520, P = 0.022). Survival analysis showed that ERRalpha positive group had a poorer overall survival (19.0 months vs. 31.5 months, P < 0.05) and ERRgamma positive group had a longer progression-free survival (18.0 months vs. 13.5 months, P < 0.05).

CONCLUSIONS
ERRalpha chiefly expresses in the cell nucleus. ERRalpha and ERRgamma may play important roles in ovarian cancer.


The factors that increase the risk of development of endometrial cancer are reviewed. Many of these conditions are frequently associated with an elevated production of estrone in peripheral (nonendocrine) tissues from circulating androstenedione. Elevated estrone production may occur in young, anovulatory or postmenopausal women whose ovaries secrete higher than normal amounts of androstenedione. Alternatively, conditions such as obesity and liver disease are associated with higher than normal rates of conversion of androstenedione to estrone, resulting in high estrone levels. Neither the exact tissue site(s) of conversion nor the normal function of this process has yet been established. Much less information concerning steroid hormone receptor measurements in endometrial cancer than in breast cancer is available. However, it seems certain that measurement of progesterone receptors will provide a useful guide in the selection of progestational therapy.


Fire is one of the main agents controlling composition, structure, and function of mixed conifer forests in the Sierra Nevada, CA. Over the past century, there has been a dramatic shift in the role of fire in these forests as fire regimes shifted from low intensity, frequent fires prior to European settlement in the region, to extended periods of fire exclusion due to a policy of active fire suppression. This led to many unintended consequences such as increased stand density, shifts in species composition towards more shade tolerant species such as white fir, and an increase in fire severity and extent when fires do occur due to increased fuels and changing climate. In the past several decades, prescribed fire has become one of the most important tools for forest restoration and management, yet its effects are still not fully understood. This uncertainty is especially true for sugar pine, a species that is being affected not only by changing forest conditions, but also by the introduced pathogen white pine blister rust. These multiple factors, and potential interactions among them, have led to population declines of sugar pine in some areas and have raised concerns about potential mortality during prescribed fire. The goal of this research was to better understand what processes were most important in controlling post-fire mortality of sugar pine, use this information to produce more accurate predictive models of post-fire mortality, and to evaluate simple management actions that could ameliorate the risk of mortality following fire.The first chapter serves as an introduction to the mixed conifer ecosystem and sugar pine in particular. It discusses the main factors that control mortality following prescribed fire and highlights some of the main findings of this research. In the second chapter, structural equation modeling (SEM) was used to assess the direct and indirect effects of multiple variables related to tree health, beetle activity, blister rust, and fire effects and their relative importance in controlling sugar pine mortality following prescribed fire in Sequoia and Kings Canyon National Parks. Multiple factors are known to influence mortality following fire including fuel loads, fire intensity, beetle activity, and tree size, yet little is known about how these factors interact to control post-fire mortality. A total of 436 sugar pine were measured within three separate prescribed fires in Sequoia and Kings Canyon National Parks. SEM was used to evaluate a network of causal relationships between factors that affect post-fire mortality of sugar pine and to assess both direct and indirect effects. Several factors were found to significantly influence post-fire mortality, with crown volume scorch, diameter at breast height (dbh), and post-fire beetle activity showing the strongest effects; though the magnitude of these effects differed among sites. Other factors such as blister rust infection and pre-fire beetle activity had little impact on post-fire mortality. A causal model was developed that considered both indirect and direct effects of multiple factors associated with post-fire mortality while demonstrating the variability in the relative strength of these causal relationships based on specific attributes. This model can be used in forest management to provide a clear understanding of how fire effects interrelate with multiple processes to control post fire sugar pine mortality. The third chapter examined whether the inclusion of pre-fire tree health (based on tree ring records) in models looking at post-fire sugar pine mortality improved model fit over models based on measures of fire effects alone. This study was conducted within an old-growth mixed-conifer forest in Sequoia National Park that had been prescribed burned during 2001 or 2002. Fire effects measured by percent crown volume scorched and stem char height, and pre-fire tree health measured by multiple indices of growth calculated from tree cores and measures of crown health were assessed for 105 sugar pine. Health status (live or dead) was observed prior to the fire, immediately post-fire and five years post-fire. Logistic regression models were used to evaluate the effects of fire and pre-fire tree health on post-fire mortality. Models based only on tree size and fire effects were compared to models that included fire effects and measures of pre-fire tree health using AICc. Five years following fire, the model that best predicted mortality included dbh, crown volume scorch, 30 year growth trend, and count of sharp declines over a 30 year period. The inclusion of long-term measures of growth markedly improved model fit compared to models based only on fire effects (ΔAICc = 26.4). However, immediately after fire, models that included measures of pre-fire tree health resulted in only marginal improvements over models based only on measures of fire effects (ΔAICc = 2.1). These results imply that multiple processes, in addition to fire, are functioning to influence delayed mortality and that the inclusion of measures of tree health can provide more accurate predictions of post-fire mortality.Finally, chapter four tests whether raking away duff and litter from the base of the stem can be used as an effective means of reducing sugar pine mortality following prescribed fire. This study was conducted in three prescribed fires in Sequoia and Kings Canyon National Parks and included 457 trees, half of which were raked to mineral soil to 0.5 m away from the stem. Fire effects were assessed and tree mortality was followed for three years after prescribed fires. Overall, raking had no detectable effect on mortality as raked trees averaged 30 % mortality compared to 36 % for unraked trees. There was a significant interaction, however, between raking and average pre-treatment forest floor fuel depth: The predicted probability of survival of a 50 cm dbh tree was 0.94 vs. 0.96 when average pre-treatment fuel depth was 0 cm for a raked and unraked tree, respectively. When average pre-treatment forest floor fuel depth was 30 cm, the predicted probability of survival for a raked 50 cm tree was 0.60 compared to only 0.07 for an unraked tree. Raking did not affect mortality when fire intensity, measured as percent crown volume scorched, was very low (0 % scorch) or very high (>80 % scorch), but the raking treatment significantly increased the proportion of trees that survived by 9.6 % for trees that burned under moderate fire intensity (1 % to 80 % scorch). Raking significantly reduced the likelihood of bole charring and bark beetle activity three years post-fire. This implies that raking can be an effective management tool to reduce tree mortality following prescribed fire under specific fuel and burning conditions.


Background. Eighty percent of beef produced in Mexico is consumed domestically. However, in recent years per capita domestic consumption has gradually decreased. Identifying consumer preferences and their perspectives on beef quality could provide information for the design of programs focused on the improvement of beef production chain and encourage meat consumption. Objective. In this study the definition of quality is provided and discussed and the published evidence on the main attributes considered by the Mexican consumer at the time of  beef purchase are revised, providing a critical perspective on beef quality appreciation and to identify some implications and limitations. Methodology. Was performed a bibliographic search of available literature including the Mexican consumer perspective on beef quality attributes published in peer reviewed papers from international and national indexed journals. Main findings. Evidences on the main criterions that Mexican consumer considers as indicators for beef quality during de beef purchase are presented, and some implications and perspectives for the future adoption of more complex systems to guarantee beef quality and add value to the entire production chain are discussed. Implications. This study provide some directions on the establishment of proposals to adequately define the Mexican beef consumer preferences focused on quality and consistency of product, favorable for the whole beef industry. Conclusions: The price of beef was identified as the main criterion considered for Mexican consumer for purchasing of beef, and secondarily, his perspective include intrinsic attributes generically describing the beef quality. More studies are necessary for the identification of factors affecting the beef consistency and to adequately define the most important attributes that satisfy the Mexican consumer perspective on beef quality.


This paper discusses the challenges that SSA countries face in implementing financial regulation. It looks in particular at the issue of capacity (human, technical) for effective regulation and supervision. It argues that the benchmark for capacity assessment in the region is being set too high and inappropriately, and that SSA countries can settle on simpler rules in line with their specific needs. From this perspective, the analysis, based on a number of sources, is that SSA is making significant progress in acquiring capacity and resources, as well as gradually putting in place rules and tools for effective regulation and supervision, although challenges remain, for example regarding what capital adequacy framework to adopt and how to regulate foreign banks.


A key problem under imperfect power control in multimedia DS-CDMA networks is how to guarantee the differentiated outage probabilities of different traffic classes resulted from the uncertainty of received powers. In addition, in order to utilize the scarce wireless resource efficiently, as many users as possible should be admitted into the network while providing guaranteed quality-of-service support for them. In this work, a call admission control scheme, differentiated outage probabilities CAC or DOP-CAC, is proposed to achieve the above goals for imperfectly power controlled multimedia CDMA networks. Two important features of CDMA system are considered in our scheme: one is the power multiplexing among bursty traffic and the other is the power allocation scheme employed at the physical layer. The validation and efficiency of DOP-CAC are verified by numerical examples.


The paper folding task is commonly used for the evaluation of nonverbal, spatial reasoning skills. In this paper, we present a computational model that attempts to use visual-imagerybased representations and operations to solve this task. The model was tested against all problems from the standard paper folding task and achieved a perfect score, illustrating that visual-imagery-based representations and operations are sufficiently expressive to capture at least one successful solution strategy. Although the model does not closely resemble human cognitive processing, and thus should not be considered in its current form to be a plausible psychological model of human task performance, the assumptions made and their implications for our understanding of human cognition on the paper folding task point to fruitful lines of future work towards this goal.


Nowadays organ transplantation is a life-saving procedure, or anyhow it can considerably improve the life quality of patients suffering from irreversible organ impairment. Monitoring transplantation outcome is the last step of a long process that starts with cadaver donor identification, selection and clinical management, and continues with organ allocation, patient evaluation, surgical operation and clinical follow-up. The National Transplantation Committee has been discussing many of these items and, in 1995, it set up two protocols, one on liver exchange for urgent patients and the other on transplantation in the pediatric patient. The protocols application has met many difficulties, mainly due to the uneven behaviours of the different inter-regional organizations. In this paper we comment on the two main aspects to be submitted to the next National Committee: organ allocation and transplantation outcome. As far as the last point is concerned, the enclosed data are based on the experience of the North Italy Transplant program (NITp), and on that of the major international registries. Without any doubt these data demontrate that organ transplantation is to be ascribed among the successes of medicine in the just closed century.


74 patients with chronic salpingo-oophoritis (CS) in remission were assessed as to effects of classic massage of the uterine and epoöphoronic reflexogenic zones on clinical pattern of the disease, bioelectric activity of the abdominal muscles, spine and pelvis, blood coagulation. The combined massage produced a more potent effect on electric activity of the above muscles and blood coagulation than massage on a single area. It is better to start massage from the abdomen and continue in the lumbosacral area.


The progression of technology constitutes the learning acquisition which is one of the pillars of education. Researches showed that it gives profound influence in reshaping learning and teaching mode in the schools like Learning Management System (LMS) tool. This study aimed to evaluate whether school-related personal background, study habit or frequency of studying, computer and online technology experience, problems encountered in the subject, and difficulties faced in the LMS environment are the determinants of students' performance exposed to LMS. A descriptive survey method was used that includes a researcher-made questionnaire, which was pilot-tested, and interviews. The questionnaire was designed base on the variables reflected as useful data from the respondents. There were ninety (90) Bachelor of Science in Information Technology student-respondents. Results show that most of the students have less access to technology. It implies that students are inexperienced and are not exposed to computer and new technologies hence they experience problems in using LMS that also affect their study habit. The school-related personal backgrounds, study habitand computer and online technology experience effect differently with the performance of the students exposed to LMS. Teachers may be considerate in introducing LMS to minimize time pressure and adjustment issues.


Agriculture expansion is a major contributor to wildlife habitat loss in the ecological frontier areas. However, little is known about the contribution of different crops to wildlife habitat loss.
In this study we evaluated the relative contribution of changes in farming practices, particularly the introduction of cotton (Gossypium hirsutum L) to the loss of wildlife habitat with specific
focus on the African elephant (Loxodonta africana) in the mid- Zambezi Valley, Zimbabwe.
First, we developed a remote sensing method based on normalised difference vegetation index (NDVI) derived from 16 day multi-temporal Moderate Resolution Imaging Spectroradiometer (MODIS) remotely sensed data for the 2007 growing period, to test whether cotton (Gossypium hirsutum L) fields can significantly (p < 0.05) be distinguished from maize (Zea mays L) fields, as well as sorghum (Sorghum bicolor) fields. Second, we tested whether woodland fragmentation in the study area was best explained by the areal extent of cotton fields than the areal extent of cereal fields. Finally, we tested whether woodland fragmentation resulting from cotton fields explains elephant distribution better than woodland fragmentation resulting from the extent of cereal fields. Results show that multi-temporal remotely sensed data can be used to distinguish
and map cotton and cereal fields. Cotton fields contributed more to woodland fragmentation than cereal fields. Also, we found out that woodland fragmentation from cotton fields significantly
explained elephant distribution in the mid- Zambezi Valley. These results indicate that the areal extent of cotton fields explains elephant habitat fragmentation more than the areal extent of
cereal fields. Thus, we conclude that the expansion of cotton fields contributes most to elephant habitat loss in the Mid-Zambezi Valley. These results imply that elephant conservation policy needs to address the reduction of the negative impact of cash crops such as cotton on the habitat particularly their threat to wildlife habitat which may eventually lead to loss these wild animals.
Thus it is important to strike a balance between wildlife habitat conservation and agricultural production as advocated through the Communal Areas Management Programme For Indigenous
Resources (CAMPFIRE) policy.


The habitats of the real biological populations and community generally are fragmented. They can be presented as the system of local populations coupled by migration. Such system of subpopulations is called metapopulation. Here the population dynamics is more complicated than a single local population or biological community. For study of a spatiotemporal dynamics of metapopulation it can be used coupled map lattices. Multistability, synchronization, intermittency and clustering are observed in these models. Furthermore, process of clustering or forming synchronous element groups looks like a core-satellite distributions in metapopulation. The paper investigates the phenomenon of clustering in such model. A local population dynamic is described by Riker's model. The coupling between subpopulations apparently cannot be global and represents a seasonal movement or migration of individuals into neighboring patches. To construct attraction basins for some phases of clustering we propose a method based on estimation of statistic distances between initial state and the states on stable attraction. It is used the coefficient of determination as a distance measure. This method too enables one to identify parameter regions of stable clustering phase. This technique has been successfully tested on an example of formation two-cluster states. As result it is shown the forming of clusters is complex depends on initial distribution of individuals on flat area. In the case of forming two equal clusters, comparabled with ordered phase, the attraction basins coincide only partially with basins of antiphase modes in system of two coupled Riker's map. The bifurcation scenario is described for this phase. It is shown the first bifurcation is always the period-doubling. It is arising of synchronous 2-cycle with only coherent phase. With increasing reproductive rate there is antiphase 2-cycle coexistsing with synchronous cycles of different lengths in the system. The existing of nonsynchronous modes makes possible emergence of stable order, partially order and turbulent phases. However, the bifurcation boundaries of coherent and not coherent phases are different. With growth of reproductive rate the coherent phase basin is transformed from simply connected and two-dimensional domains to univariate regions. The univariate region is the part of the first quadrant bisector of the phase space. Here it is formed the dynamic mode closed to chaotic synchronization. This happens when the order phase gets the multistable nature and 2-cycle coexists with 4-cycle. The basin of 4-cycle has a heavily trimmed or an even fractal view. In area of Arnold's tongues the coherent phase basins again takes the form of the two-dimensional areas. A decreasing the rate of individual movement leads to the emergence of two closed limiting invariant curves around of 2-cycle elements. Both clusters have quasiperiodic antiphase dynamics. The destruction of invariant curves produces 4-cycle. In the case of form not equal clusters, the complexity of dynamic is realized by only Feigenbaum's scenario. Also for such clusters we shown the basins of attraction are qualitatively similar to basins nonsynchronous modes of nonidentical asymmetrically coupled Riker's map in asymptotic behavior. The study was supported by RFBR, research project No. 14-01-31443 mol_a.


Obtaining full DNA profiles from bone can be challenging due to the inherently low quantity and quality of DNA. An efficient extraction protocol is required to maximize DNA recovery from bone samples while minimizing the coextraction of the PCR inhibitors naturally present in bone.DNA extraction from bone involves three discrete steps: demineralization, lysis, and purification. Demineralization involves incubating bone that has been pulverized into a powder in a chelating agent in order to sequester the divalent metal cations that comprise the mineral matrix of bone tissue. This is followed by a lysis step, in which the demineralized bone material is incubated in a buffer that disrupts the cellular membrane, releasing the DNA and intracellular components. Purification is performed after lysis to separate the DNA from proteins and cellular debris, as well as to remove PCR inhibitors.Several variables were examined in this study, including the use of three different lysis buffers, two different bone types, two different materials for the end caps and impactor bar used in the pulverization process, and the interactions between these variables. The effectiveness of each modification in the procedure was assessed using qPCR, which was used to measure mtDNA recovery in copies of mtDNA per gram of bone material, as well as by the assessment of inhibition using an internal positive control. The actual effectiveness of each lysis buffer varied considerably with bone types examined. In addition, a novel modification to the pulverization step was found to significantly enhance mtDNA recovery by reducing inhibition detected in samples.The findings of this work suggest that the current methodology is not fully optimized, and additional emphasis needs to be placed upon removing inhibitors but also investigating the effects of the bone lysate on the pH and ionic strength on the recovery of DNA from bone material. Preliminary work is presented from this study in developing a method for DNA extraction from human bone and elucidating the sources of inhibition that are introduced via the extraction method itself as well as those naturally present in bone tissue.


The relation between death from acute myocardial infarction and the level of magnesium in drinking water was examined using mortality registers and a case-control design. The study area comprised 17 municipalities in the southern part of Sweden that have different magnesium levels in the drinking water. Cases were men in the area who had died of acute myocardial infarction between ages 50 and 69 years during the period 1982-1989 (n = 854). The controls were men of the same age in the same area who had died from cancer during the same time period (n = 989). In both groups, only men who consumed water supplied from municipal waterworks were included in the study. The subjects were divided into quartiles according to the drinking water levels of magnesium and calcium and the quotient between magnesium and calcium. The odds ratios for death from acute myocardial infarction in the groups were inversely related to the amount of magnesium in drinking water. For the group with the highest levels of magnesium in drinking water, the odds ratio adjusted for age and calcium level was 0.65 (95 percent confidence interval 0.50-0.84). There was no such relation for calcium. For the magnesium/calcium quotient, the odds ratio was lower only for the group with the highest quotient. These data suggest that magnesium in drinking water is a important protective factor for death from acute myocardial infarction among males.


This paper describes a statistical signal-processing method for exploiting narrowband bistatic RF measurements to detect and track moving people (hereafter referred to as "dismounts"). In our approach, RF measurements are made by a constellation of narrowband radar units, arranged around a surveillance region. There are several benefits of narrowband radar in this application, which we describe in the paper. However, the narrow bandwidth means that individual measurements only yield coarse information about target state. We show that by fusing measurements from multiple bistatic sensors over time with a Bayesian nonlinear-filteri ng algorithm, we can effectively estimate dismount position and velocity using as little as 5-10 m bistatic range resolution. We illustrate the algorithm's efficacy with an experiment where a moving person is detected and tracked from a constellation of four narrowband bistatic sensors.


This article reports on several industrial applications of a visually guided system for robot grasping using an inexpensive two-finger gripper. In all cases, the robot uses visual information as input and is able to reason about the shapes of objects in a scene in order to decide the best stable grasp online. The first version of this system was able to grasp rectangular parts in arbitrary positions in the scene and was successfully deployed. New applications in industry have been addressed that must cope with the cost, time, and reliability requirements imposed by the industrial process. The results show that the capabilities of the underlying methodology make it feasible to deal with more complex shapes, even a priori unknown, opening up new possibilities within industrial domains, such as the food industry, that has traditionally not been fully automated due to a large variability in the shaper of the objects to be handled.


The 14.6 miles of the Colorado River bounded by Parker Dam and Head gate Rock Dam has been referred to as the Parker Strip. This river reach has become a high use recreation area during the past decade with 4,000 permanent residents and as many as 120,000 water enthusiasts on long weekends. The riparian area of the river is heavily clustered with mobile homes, marinas and public beaches. The means of sewage disposal is exclusively via septic tanks. Recent surveys by the Environmental Protection Agency, Arizona State Department of Public Health and the University of Arizona have localized surface water bacteria levels that may indicate a developing groundwater problem. The geohydrology of the area indicates that the septic tanks are located in Post -Pliocene Colorado River deposits. The deposits are quite thin and relatively narrow. Since the deposits are locally derived sands and gravels, the horizontal hydraulic conductivities are such that a relatively short flow time to the river may result. Intensive evaluation of the degradation of the water quality in these deposits is needed to determine if the ground water supply was jeopardized by septic tank systems.


This book provides a nice balance between describing the mathematical fundamentals and offering practical advice on how to solve a crystal structure. It is a very good translation of the original German text. The book is appropriate for an undergraduate audience (particularly in chemistry) and for graduate students or researchers who ®nd they need a better grasp of the subject. Students seeking a rigorous treatment of the theoretical basis of many concepts in crystallography will need to supplement this book with other sources, some of which are listed in a useful bibliography. Students whose main interest is macromolecular crystallography will ®nd it inadequate in certain places. For instance, the sections describing crystallization experiments and on preparing the crystal sample for data collection make no mention of standard procedures for dealing with macromolecular crystals. To keep the size of the book small, there is no mention of the accumulated results of diffraction experiments ± the many interesting known structures and what we can learn from them. However, the various small-molecule databases are mentioned, together with some useful Internet addresses, in a short chapter towards the end of the book. The ®rst six chapters deal with geometric fundamentals of lattices, symmetry and X-ray diffraction. One of the strengths of the text is that the author tries to clarify many of the topics that frequently cause confusion to the new student of crystallography. For example, he gives a clear explanation of the differences between the trigonal, hexagonal and rhombohedral crystal systems when initially de®ning lattice symmetry in Chapter 2. From my perspective in teaching, Chapter 5, on structure factors, might be better placed if it came immediately before Chapter 8, on structure solution. Chapter 7, one of the lengthiest, describes the various experimental methods and is quite complete and very readable. The next three chapters, devoted to structure solution, re®nement and the determination of absolute con®guration, include de®nitions of a variety of terms used by commonly available software programs. The description of how hydrogen atoms are treated is useful ± particularly for a novice who may not be aware of the different ways used to report their positions. There are also hints and advice on how to deal with problem structures. The use of the Rietveld method for structure re®nement based on powder data (as opposed to singlecrystal data) is also brie ̄y described. The book is clearly a useful reference to have around when performing an X-ray diffraction experiment. Another strength of the book is Chapter 11 entitled `Errors and Pitfalls'. The content is self-explanatory from the title and Massa points out potential errors in the interpretation of crystal data and experimental results. It covers important topics such as disorder, twinning and quasicrystals. Chapter 12 discusses the results obtained from a structure determination. It contains equations for calculating bond distances, angles, torsion angles and best planes. Also useful for a novice is a description of the different types of structural diagrams used to display the results, including the polyhedral drawings used for inorganic and materials science applications. These threedimensional drawings are usually incomprehensible when seen for the ®rst time by a chemistry undergraduate student. To my way of thinking, this chapter should precede Chapter 9, on structure re®nement. Given that it describes the important results of the experiment, its placement after the `Errors and Pitfalls' chapter seems a bit pessimistic! Chapter 14 offers a useful and fairly detailed outline of the various stages of a crystal structure determination with references to the appropriate section in the text where the particular topic is discussed. Chapter 15 includes a worked and annotated crystal structure determination, using SHELX, that is very useful for the new student. I only wish that the space group of the example had not been chosen as I2=a, which is a non-standard space group in the monoclinic system. However, Chapter 2, on crystal lattices, has an illustration showing the relationship between the monoclinic I and C centering. A bibliography lists other crystallography texts and a score of software packages, though none relating to macromolecular applications. Overall, the book is a helpful addition to the collection of introductory texts in X-ray crystallography, especially for its treatment of common errors in the collection of intensity data and in the interpretation of results. This feature is particularly important in a book directed at non-specialist users of this powerful method.


Within twenty years of one another, Bacon and Descartes proposed cosmologies which relied heavily on matter theory. In both, the distribution of matter in the cosmos determined what centers of rotation there were, and rotating bodies were carried around by the motion of an all-encompassing celestial fluid in which they were embedded. But the role of matter theory in the two accounts is very different, both in motivation and in the level at which it is active in guiding physical theory. Matter theory in Baconian cosmology stands as a foundational discipline, being virtually constitutive of physical theory, as it had been for natural philosophers from Thales onwards, whereas in Descartes it is subservient to the needs of his optics and his mechanics. Comparison of the two cases shows how the role of matter theory came to be radically modified in seventeenth-century cosmology.


A training program was designed and developed for school-going children of 7-12 years old in order to help them improve their understanding of safety rules at critical street-crossing scenarios. The training is constructed of two modules that take place on two different platforms. The first one is a bilingual instruction-based video presentation that demonstrates street crossing safety rules and is viewed on a digital display. The second one (virtual "game" ) takes place in a virtual environment (VE), and the trainee wears a virtual reality (VR) head-mounted device (Oculus Quest) to physically walk on 30-ft long marked and unmarked crosswalks to put the lesson into practice. Eight types of scenarios called "levels" were developed to test and improve the player's decision-making ability. In addition, an experiment was designed to test the efficacy of the program. Trials were run, where a participant watched the video presentation between the two times they were allowed to play the game. The process required an average of 40 minutes per participant to complete. No participants went through simulation sickness according to the Simulation Sickness Questionnaire provided, and an experience survey conducted at the end of the trials showed that all participants found the training program natural and informative.


This work aims to detect the presence of Babesia canis vogeli in dogs from Recife, Pernambuco via molecular and parasitological detection methods, and to assess the risk factors associated with this parasite. A total of 146 dogs (male and female) of varying breeds and ages that presented clinical symptoms of babesiosis were assessed at a clinical care center in the Veterinary School Hospital. Blood was obtained via venopuncture for hemoparasite detection and polymerase chain reaction (PCR). Using a commercial kit, DNA was extracted from blood samples. For the PCR reaction, an approximately 590 base pair long genetic sequence was used to detect the presence of B. canis vogeli . The forward primer, denoted as BAB1 (5'-GTG AAC CTT ATC ACT TAA AGG-3'), was specific for a conserved region on the 18S rRNA gene of Babesia spp., and the antisense primer was denoted as BAB4 (5'-CAA CTC CTC CAC GCA ATC G-3'). PCR results suggested that the percentage of Babesia canis vogeli infection was 4.8%. Through descriptive statistical analysis of the data, we observed that there was higher frequency of parasite infection associated with male dogs above two years of age, with a defined breed, from the countryside, are domiciled, and also suffer from tick infestation. We conclude that regardless of the type of risk factor, babesiosis can be found throughout Recife, Pernambuco, and its prevalence does not vary in most regions of Brazil. Our results indicate that PCR is a sensitive test for the detection of blood parasites, and should be performed as a clinical routine.


Certificate revocation is an important security component in mobile ad hoc networks (MANET). Securing network from various kinds of Attacks (MANET) plays an important role. Certificate revocation mechanisms play an important role in securing a network. The main challenge of certificate revocation is to revoke certificates of malicious nodes promptly and accurately. In this paper we use Cluster based certificate Revocation with vindication capability (CCRVC) scheme. It's possible to identify attackers from the network and permanently revoke the Certificate of Attacker node. And it revokes the accused node based on a single node's accusation. However the certificate accusation and recovery mechanisms have some limitations. The number of nodes capable of accusing malicious nodes decreased over time. It eventually lead to case malicious nodes can no longer be revoked in timely manner. To overcome this problem we propose Threshold based mechanism approach to vindicate warned nodes as legitimate nodes or not. And it enhances effectiveness and efficiency. By this scheme we improve the reliability and accuracy.


This article aims to analyse ethnolinguistic vitality of pupils from schools where they are taught in the Lithuanian language in terms of the Lithuanian language usage, proficiency and language assessment. The survey was aimed at assessing the following ethnolinguistic vitality indexes of the analysed group of respondents: (1) language use and domination,(2) language proficiency and motivation to learn, (3) the attitude to the Lithuanian language, and (4) creative powers of language. Ethnolinguistic vitality of different age group pupils is analysed on the basis of an empirical study on the impact of other languages on the Lithuanian language of third- and fourthformers conducted in 2018–2019. The relevance of the study rests on the fact that ethnolinguistic vitality, as ethnic vitality of the Lithuanian linguistic community, has never been analysed before. For the first time, the article sequentially and systematically analyses ethnolinguistic vitality of a group of pupils through the aspects of the relation to language, which allows predicting perspectives of sustainability and continuity of the Lithuanians as an ethnic community. The study data show the tendency that, according to all the aspects studied, as the pupils become older, their vitality as members of an ethnolinguistic group decreases. Moreover, a foreign (English) language is becoming more and more dominant in the pupils' language as they grow older. When assessing the pupils' ethnolinguistic vitality in terms of language proficiency, it turned out that the pupils' learning achievements decreased from the fifth form. As the data show, the majority of the pupils (more than 70 per cent) claim that they are proud of the Lithuanian language as their language, they indicate the connection between the Lithuanian language and their ethnic identity, and they relate the sustainability of the ethnic identity to the language strength – its usage in the ethnolinguistic community. However, the data also reveal the following tendency: the older the respondents are, the fewer of them have an opinion about the significance of the language to the identity of an ethnolinguistic community (from 7.3 per cent in the fourth form to 26 per cent in the eighth form). It can be assumed that a part of the respondents, especially the ones in senior forms, have weak ethnic identity self-concept and linguistic identity, and therefore the native language is being assessed only as the instrument of communication, the same as any other language. Assessment of the pupils' ethnolinguistic vitality in terms of their linguistic powers and linguistic potential revealed that only a half of the respondents assess the Lithuanian language as a modern language. Weak linguistic self-awareness of pupils is observed in their attitude towards the strengthening of the Lithuanian language powers: less than a half of the respondents agree that the Lithuanian language resources must be expanded. The study data reveal that pupils' ethnolinguistic vitality in terms of trust in the creative powers of their language, their attitudes to the expansion of the Lithuanian language resources, and giving priority to the use of the Lithuanian language decrease with age.


Abstract Motivation RNA 5-methylcytosine (m5C) is a type of post-transcriptional modification that may be involved in numerous biological processes and tumorigenesis. RNA m5C can be profiled at single-nucleotide resolution by high-throughput sequencing of RNA treated with bisulfite (RNA-BisSeq). However, the exploration of transcriptome-wide profile and potential function of m5C in splicing remains to be elucidated due to lack of isoform level m5C quantification tool. Results We developed a computational package to quantify Epitranscriptomal RNA m5C at the transcript isoform level (named Episo). Episo consists of three tools: mapper, quant and Bisulfitefq, for mapping, quantifying and simulating RNA-BisSeq data, respectively. The high accuracy of Episo was validated using an improved m5C-specific methylated RNA immunoprecipitation (meRIP) protocol, as well as a set of in silico experiments. By applying Episo to public human and mouse RNA-BisSeq data, we found that the RNA m5C is not evenly distributed among the transcript isoforms, implying the m5C may subject to be regulated at isoform level. Availability and implementation Episo is released under the GNU GPLv3+ license. The resource code Episo is freely accessible from https://github.com/liujunfengtop/Episo (with Tophat/cufflink) and https://github.com/liujunfengtop/Episo/tree/master/Episo_Kallisto (with Kallisto). Supplementary information Supplementary data are available at Bioinformatics online.


The challenge of accessing, maintaining, sharing and preserving massive datasets, generally referred to as data curation, has been a direct result of computational e-science. Although scientists and engineers recognized the problem, the solution was not apparent. The principles that underlay library science are not widely understood or appreciated by those outside librarianship. The theory and principles behind librarianship are obscured by historical application primarily to print materials – books and journals – however, the same principles that apply to organization, retrieval, and preservation of print materials apply to the digital realm as well. The National Science Foundation (NSF) in the United States is concerned that much of its funding was committed to creating datasets, used for a specific research project, and then discarded. The question was: couldn't a dataset be "mined" for more than one research project? The NSF has begun to assess and research the issues associated with "archiving" datasets for present and future research use. Purdue University Libraries, after having observed the need that domain researchers have, determined that the creation of a center to focus on and research these issues while fostering collaboration between librarians and domain researchers was needed. The Distributed Data Curation Center (D2C2) was created at the end of 2006.


Recent work has established an association between overweight/obesity and sleep duration, suggesting that short sleep duration and timing of sleeping may lead to overweight. Most of these studies considered sleep-length rather than any other aspects associated with the sleep and wake rhythm, e.g. chronotype, which is a measure of timing of sleeping ('when to sleep'; based on the midpoint of sleep). The objective of this study was to assess the influence of different factors of the sleep-wake cycle and of co-variates on the Body Mass Index in a cross-sectional questionnaire study. Nine hundred and thirteen pupils (406 boys, 507 girls) from Southwestern Germany participated in this study. Mean age was 13.7 ± 1.5 (SD) years and range was between 11 – 16 years. We found that chronotype (β = .079) and social jetlag (β = .063) showed a significant influence on Body Mass Index (BMI), while sleep duration did not. Social jetlag is the absolute difference between mid-sleep time on workdays and free days. Further, screen time (in front of TV, computer, β = .13) was positively related with BMI. Self-efficacy on nutrition (β = -.11), a psychological variable important in health-behaviour models, showed an influence with high scores on self-efficacy related to lower BMI. A high BMI was correlated with low fast-food consumption (β = -.12) suggesting that adolescents with high BMI may exert some control over their eating.


We present results of a randomized trial testing the impact on academic outcomes of providing free eyeglasses to junior high school students in a poor rural area of western China. We find that providing free prescription eyeglasses approximately halves dropout rates over a school year among students who did not own eyeglasses at baseline. Effects on dropout are mirrored by improvements in student performance on standardized exams in math and aspirations for further schooling.


Glutaredoxin (Grx) is a small, heat-stable protein acting as a multi-functional glutathione-dependent disulfide oxidoreductase. In this work, a gene encoding the monothiol glutaredoxin Grx4 was cloned from the genomic DNA of the fission yeast Schizosaccharomyces pombe. The determined DNA sequence carries 1706 bp, which is able to encode the putative 244 amino acid sequence of Grx with 27 099 Da. It does not contain an intron, and the sequence CGFS is found in the active site. Grx activity was increased 1.46-fold in S. pombe cells harboring the cloned Grx4 gene, indicating that the Grx4 gene is in vivo functioning. Although aluminum, cadmium, and hydrogen peroxide marginally enhanced the synthesis of beta-galactosidase from the Grx4-lacZ fusion gene, NO-generating sodium nitroprusside (0.5 mmol/L and 1.0 mmol/L) and potassium chloride (0.2 mol/L and 0.5 mol/L) significantly enhanced it. The Grx4 mRNA level was also enhanced after the treatment with sodium nitroprusside and potassium chloride. The synthesis of beta-galactosidase from the Grx4-lacZ gene was increased by fermentable carbon sources, such as glucose (lower than 2%) and sucrose, but not by nonfermentable carbon sources such as acetate and ethanol. The basal expression of the S. pombe Grx4 gene did not depend on the presence of Pap1. These results imply that the S. pombe monothiol Grx4 gene is genuinely functional and regulated by a variety of stresses.


Steel bearings have plenty of usages in manufacturing different kinds of ball bearings, bearings and cold rolling rollers. Heat treatment has an important role in the properties of this group of steels. Therefore, in current research the effect of tempering temperature on the microstructure, hardness, impact energy and wear resistance in forged steel containing Chrome, Manganese and Molybdenum will be studied. For this purpose, the samples were tempered after austenitizing at 900oC and quenching in the oil at 6 temperatures of 150, 250, 350, 450, 550 and 650 oC for an hour. Then microstructural studies and mechanical properties of the samples including hardness, impact energy and wear resistance were surveyed on the samples. The results showed that the hardness was gradually decreased (impact energy gradually increased) at the temperature range of 150 - 250 ˚C and at temperature range of 350 -650oC, the hardness would decrease and the impact energy would increase. Also, the wear resistance would decrease with an increase in the tempering temperature. The result should be justified considering the softening of the structure and the reduction in martensite tetragonality which stems from an increase in the tempering temperature. The study of the wear surface of the samples indicated that the dominant wear mechanism was adhesive wear in which with an increase the tempering temperature due to a reduction in the hardness of the samples, more sever adhesive wear was observed. DOI: http://dx.doi.org/10.5755/j01.mech.24.6.22478


Background Road accidents are one of the main causes of death around the world and yet, from a time-space perspective, they are a rare event. To help us prevent accidents, a metric to determine the level of concentration of road accidents in a city could aid us to determine whether most of the accidents are constrained in a small number of places (hence, the environment plays a leading role) or whether accidents are dispersed over a city as a whole (hence, the driver has the biggest influence). Methods Here, we apply a new metric, the Rare Event Concentration Coefficient (RECC), to measure the concentration of road accidents based on a mixture model applied to the counts of road accidents over a discretised space. A test application of a tessellation of the space and mixture model is shown using two types of road accident data: an urban environment recorded in London between 2005 and 2014 and a motorway environment recorded in Mexico between 2015 and 2016. Findings In terms of their concentration, about 5% of the road junctions are the site of 50% of the accidents while around 80% of the road junctions expect close to zero accidents. Accidents which occur in regions with a high accident rate can be considered to have a strong component related to the environment and therefore changes, such as a road intervention or a change in the speed limit, might be introduced and their impact measured by changes to the RECC metric. This new procedure helps us identify regions with a high accident rate and determine whether the observed number of road accidents at a road junction has decreased over time and hence track structural changes in the road accident settings.


Objective In this brief report, we characterize pediatric primary care service utilization in metropolitan Chicago over the first 24 weeks of the COVID-19 pandemic response in relation to the comparable time period in 2019. Methods We examined retrospective visit and billing data, regardless of payer, from 16 independent pediatric practices that utilize a common electronic medical record platform within an Accountable Care Organization of 252 pediatricians in 71 offices throughout metropolitan Chicago. We categorized visits as Well-Child and Immunization-Only (WC-IO) or Other types and identified visits with a telemedicine billing modifier. Diagnoses for Other visits were tallied and categorized using the Agency for Healthcare Research and Quality Clinical Classification System. We summarized counts of visits and the proportion of visits with a telemedicine billing modifier in one-week epochs for 2020 compared with 2019. Results There were 102 942 total visits (72 030 WC-IO; 30 912 Other) in 2020 and 144 672 visits (80 578 WC-IO; 64 094 Other) in 2019. WC-IO visits in 2020 were half of 2019 visits at the start of the Illinois Stay-at-Home Order and returned greater than 90% of 2019 visits in 8 weeks. Other visit types have remained below 70% of 2019 visits. A telemedicine billing modifier peaked in mid-April (21% of all visits) and declined to <10% of all visits in June (Phase 2 reopening). The top 10 most common diagnoses differed between years. Conclusions Recovery of well child and immunization visits suggests that practice-level efforts and policy change can ensure children receive recommended care as the pandemic evolves.


Purpose - Several types of entrepreneurship with a societal purpose coincide in Sweden today, some stemming from older domestic traditions, others being more recent foreign influences. This paper aims to interrelate social, civic, community, and other entrepreneurships in search of a more unifying concept of societal entrepreneurship for Sweden and beyond. Design/methodology/approach - As part of a larger study, Swedish researchers and practitioners promoting some kind of entrepreneurship with societal purpose, are interviewed and asked for examples and literature references. Altogether 176 actors are identified and 59 are interviewed. The main distinguishing factors between different discourses of entrepreneurship are accounted for as well as results from workshops where actors representing different discourses partook. Findings - Seven societally oriented entrepreneurship discourses are distinguished, with different foreign or domestic origins. Key characteristics for interrelating different discourses are the type of actor (individual and/or collective) and purpose (social/ecological and/or economic) emphasized in a discourse. Interactions documented from workshops indicate a potential in unifying different entrepreneurships within a widened understanding of societal entrepreneurship. Research limitations/implications - The field of entrepreneurship emphasizing societal utility is fragmented with many parallel discourses. The conceptual analysis and empirical findings imply that there is potential in a more unifying concept. Furthermore, in the limited Swedish setting, collective dimensions of entrepreneurship stand out. This nevertheless implies that collective engagements into entrepreneurship of any kind are worthy of more research and recognition. Practical implications - Implications are primarily limited to societal entrepreneurship within uncontested welfare states, such as Sweden, where most established societal needs are taken care of through taxes utilized by a public sector. Societal entrepreneurship in such a setting becomes a mechanism for renewal and experimentation. Originality/value - The paper is original in its approach to identifying and interrelating current discourses in Sweden.


Abstract This article argues that high levels of government regulation of religion help to explain the "democracy gap" in majority Muslim countries. Controlling for previously hypothesized determinants of democracy, it finds that as levels of regulation increase, levels of democracy decline. Examination of specific types of religious regulation in Muslim-majority countries uncovers a pattern of repression of religious expression that may be used to mobilize citizens politically. These regulations are targeted more often at Muslims who seek independence from state-controlled religion or who wish to challenge authoritarian governments, rather than at non-Muslim minorities or at religious worship more generally. Thus, authoritarian and semi-authoritarian regimes in Muslim-majority states successfully use policies toward religion to restrict political competition and inhibit democratic transition.


Every day, millions of users log on to their favorite online forums and interact with others to get advice and discuss everything from the latest news and trends to their hobbies, professions, and whatever else strikes their fancy. Administrators have to lead these communities, deal with difficult users, and choose moderators. Legal constraints, spammers, and technical issues can turn the excitement of running an online community into chaos. With the right guidance, however, running forums can be a pleasure. Patrick O'Keefe has spent years developing and managing online communities. Now, he shows readers how to make the right decisions about every aspect of their forums, including: • choosing a name and domain name • picking the right software • deciding on user options like avatars and private messaging • setting guidelines and dealing with violators • ensuring that posts stay on topic • settling online disputes among users • involving users and keeping the site interesting Managing Online Forums is the one book that shows site owners and administrators how to create a safe and entertaining community that users will return to again and again.


This book provides the authoritative history of salsa.Salsa is one of the most popular types of music listened to and danced to in the United States. Until now, the single comprehensive chronicle of the music - and the industry that grew up around it, including musicians, performances, styles, movements, and production - was available only in Spanish. This lively translation provides for English-reading and music-loving fans the chance to enjoy Cesar Miguel Rondon's celebrated El libro de la salsa.Rondon tells the engaging story of salsa's roots in Puerto Rico, Cuba, Colombia, the Dominican Republic, and Venezuela, and of its emergence and development in the 1960s as a distinct musical movement in New York. Rondon presents salsa as a truly pan-Caribbean phenomenon, emerging in the migrations and interactions, the celebrations and conflicts that marked the region. Although salsa is rooted in urban culture, Rondon explains, it is also a commercial product produced and shaped by professional musicians, record producers, and the music industry. For this first English-language edition, Rondon has added a new chapter to bring the story of salsa up to the present.


Various physicochemical characteristics of a sepiolite sample from the Eskis ehir area, Turkey, were investigated to help in making predictions about possible uses of the material. The sample was examined by chemical analysis (CA), thermal analysis (DTA/TGA), X-ray diffraction (XRD) analysis, particle-size analysis (PSA), linear dilatometry (LD), scanning electron microscopy (SEM), mercury porosimetry (Hg-Por.), and low-temperature nitrogen adsorption/desorption (N2-AD) techniques. The CA and XRD data indicated that the sepiolite contains only 6% dolomite by mass. The XRD patterns showed that sepiolite anhydride, enstatite, diopside, and opal-CT form upon heating the sepiolite above 600, 800, 900, and 1200oC, respectively. The maximum rate of endothermic changes in the DTA and TGA curves were observed at 82, 287, and 491oC, corresponding to the loss of external, zeolitic, and bound water from the sepiolite, respectively. Dehydroxylation and recrystallization of the sepiolite were fastest at 845oC and 862oC, respectively. The LD curve indicated that the shrinkage began at 800oC and reached 4.0% at 1000oC. The proportion of particles with diameters of <2 mm, and the external surface area of the long-term (24 h) water-treated sepiolite were determined by PSA as 79% by volume, and 8 mg , respectively. The SEM view revealed discrete bundles of sepiolite fibers of various lengths. The specific surface area found from adsorption data was 316 mg . The specific micro-, meso-, macro-, and total-pore volumes obtained from the combination of Hg-Por. and N2-AD results were 0.16, 0.21, 0.45, and 0.82 cm g , respectively. The average macropore and micro-mesopore radii in the sepiolite were estimated (using the Hg-Por. and N2-AD data) to be 35 and 2.4 nm, respectively. Key Words—Porosity, Sepiolite, Surface Area, Thermal Analysis, X-ray Diffraction.


There is a need within the production industry for digitalization and the development of meaningful functionality for production operation. One such industry is aggregate production, characterized by continuous production operation, where the digital transformation can bring operational adaptability to customer demand. Dynamic process simulations have the ability to capture the change in production performance of aggregate production over time. However, there is a need to develop cost-efficient methodologies to integrate calibrations and validation of models. This paper presents a method of integrating an experimental and data-driven approach for calibration and validation for crushing plant equipment and a process model. The method uses an error minimization optimization formulation to calibrate the equipment models, followed by the validation of the process model. The paper discusses various details such as experimental calibration procedure, applied error functions, optimization problem formulation, and the future development needed to completely realize the procedure for industrial use. The validated simulation model can be used for performing process planning and process optimization activities for the crushing plant's operation.


X-ray-based inspection systems are a well-accepted technique for identification and evaluation of internal defects in castings, such as cracks, porosities, and foreign inclusions. In this paper, some images showing typical internal defects in the castings derived from an X-ray inspection system are processed by some traditional methods and wavelet technique in order to facilitate automatic detection of these internal defects. An X-ray inspection system used to detect the internal defects of castings and the typical internal casting defects is first addressed. Second, the second-order derivative and morphology operations, the row-by-row adaptive thresholding, and the two-dimensional (2-D) wavelet transform methods are described as potentially useful processing techniques. The first method can effectively detect air-holes and foreign-inclusion defects, and the second one can be suitable for detecting shrinkage cavities. Wavelet techniques, however, can effectively detect the three typical defects with a selected wavelet base and multiresolution levels. Results indicate that 2-D wavelet transform is a powerful method to analyze images derived from X-ray inspection for automatically detecting typical internal defects in the casting


Surgical data science is revolutionizing minimally invasive surgery by enabling context-aware applications. However, many challenges exist around surgical data (and health data, more generally) needed to develop context-aware models. This work - presented as part of the Endoscopic Vision (EndoVis) challenge at the Medical Image Computing and Computer Assisted Intervention (MICCAI) 2020 conference - seeks to explore the potential for visual domain adaptation in surgery to overcome data privacy concerns. In particular, we propose to use video from virtual reality (VR) simulations of surgical exercises in robotic-assisted surgery to develop algorithms to recognize tasks in a clinical-like setting. We present the performance of the different approaches to solve visual domain adaptation developed by challenge participants. Our analysis shows that the presented models were unable to learn meaningful motion based features form VR data alone, but did significantly better when small amount of clinical-like data was also made available. Based on these results, we discuss promising methods and further work to address the problem of visual domain adaptation in surgical data science. We also release the challenge dataset publicly at https://www.synapse.org/surgvisdom2020.


object-oriented development, TMN, MIB, network management, information model Fusion is an object-oriented development method that provides a framework of analysis and design models and processes to support the full software development lifecycle. It was designed as a generic object-oriented method in that it assumes a green field or clean slate development, working from a set of initial requirements through to implementation. In practice, text book developments are rare. There will typically be domain specific constraints placed on the development activity which influence the way the system is developed and in some cases will require modifications to be made to the development process. In this paper we investigate extensions to the Fusion design process to support the development of TMN management applications. The Telecommunications Management Network (TMN) is an architecture for the management and control of telecommunication sever provider networks. A set of international recommendations and standards define the TMN architecture and the function of certain elements in a telecommunication network. In what follows, we show how aspects of this architecture affect the way in which management applications are developed and result in additional phases of design being required.


Global concerns over climate change and sustainability have led to recent worldwide push toward generating electricity from renewable and sustainable resources. Wind energy is a fast-growing form of renewable resources worldwide. Integration of wind resources into the power system brings new challenges to the planning, operation, and control of power system in either short-term or long-term time interval. It's an intermittent resource, which is not dispatchable in the traditional sense. Fortunately, a number of new technologies are making wind energy friendly, and promising continued growth in its share of total energy. These include better wind forecast, advanced power electronic devices, enhanced control techniques and energy storage. In this paper we discuss compressed air energy storage (CAES) as an alternative solution to store energy. After giving an overview about wind energy and CAES technology some CAES power plants in the world will be introduced and the integration of CAES with green power plant will be evaluated.


This article examines Richard Wright's Native Son - which ends with its protagonist Bigger Thomas awaiting execution for the rape and murder of a white woman - to offer three interrelated close readings that go beyond the usual law-and-literature approaches. It examines the three "real life" cases that informed Wright as he was writing Native Son - the trial of Robert Nixon, the Scottsboro Boys case, and the prosecution of Leopold and Loeb - and demonstrates that Native Son, more than simply problematizing criminal justice issues, foregrounds the way in which society and the law actively participate in the construction(s) of race and gender, and challenges the traditional utilitarian and retributive justifications for punishment. The article posits that the real crime motivating Bigger's prosecution is not murder and rape, but a violation of what the author terms the "white letter law" of "trespass." Although the text that motivates the article is Native Son, the goal of the article is significantly larger. Much of the criticism of the law-and-literature movement centers around claims that it lacks discipline and boundaries. Through its explication of Native Son, this article redirects such thinking about law-and-literature by suggesting that only wider landscapes, a new critical geography, will reinvigorate the discipline.


This work was carried out to assess the community's perception of the relative importance of various dietary, environmental and lifestyle factors as CVDs risk determinants and to investigate the beliefs of the community on issues related to CVDs. A household cluster sample survey was conducted in Alexandria city. The total sample was 600 persons aged > or = 18 years Results of this work revealed that public awareness of the magnitude of CVDs in the community was high. There appeared from the large percentages of incorrect or unsure responses that the community tended not to perceive the importance of different lifestyle habits specific to CVDs. 'Sociodemographic variables that were significantly associated with good perception were higher educational and occupational levels of the subjects. It was also revealed, that although the community has confidence in advice on preventive behaviours, it was reluctant to ask about screening tests. Moreover, the community is receiving some information about issues related to CVDs and, a desire for more health information from doctors and health agencies was evident. In spite of the majority of the subjects were willing to follow advice aimed to reduce their risk of getting CVDs, they were not sure what that advice might be. Studies of this type clearly have the ability to provide a range of information which ought to be available to those responsible for the planning of health promotion and education initiatives.


This study is motivated by the development of credit-related instruments and signals of stock price movements of large banks during the recent financial crisis. What is common to most of the empirical studies in this field is that they concentrate on modeling the conditional mean. However, financial time series exhibit certain stylized features such as volatility clustering. But very few studies dealing with credit default swaps account for the characteristics of the variances. Our aim is to address this issue and to gain insights on the volatility patterns of CDS spreads, bond yield spreads and stock prices. A generalized autoregressive conditional heteroscedasticity (GARCH) model is applied to the data of four large US banks over the period ranging from January 01, 2006, to December 31, 2009. More specifically, a multivariate GARCH approach fits the data very well and also accounts for the dependency structure of the variables under consideration. With the commonly known shortcomings of credit ratings, the demand for market-based indicators has risen as they can help to assess the creditworthiness of debtors more reliably. The obtained findings suggest that volatility takes a significant higher level in times of crisis. This is particularly evident in the variances of stock returns and CDS spread changes. Furthermore, correlations and covariances are time-varying and also increased in absolute values after the outbreak of the crisis, indicating stronger dependency among the examined variables. Specific events which have a huge impact on the financial markets as a whole (e.g. the collapse of Lehman Brothers) are also visible in the (co)variances and correlations as strong movements in the respective series.


Acute chest pain remains one of the most difficult challenges for the clinician. Nowadays, chest pain and its related complaints account for up to 10% of the adult emergency admissions and around 25% of all hospital admissions.w1 Notably, the number of patients presenting with complaints of chest pain is rising.w2 In a typical population of patients presented for the evaluation of acute chest pain in emergency departments, about 20% will have an acute coronary syndrome (ACS).w3 w4 The principal pathophysiological mechanism of an ACS is one of myocardial underperfusion resulting from either atherosclerotic plaque rupture or from erosion with different degrees of superimposed thrombus.1 ,2 A minority of patients, estimated to be around 10% of those who presented with chest pain, will not have an ACS but another life threatening problem such as a pulmonary embolism or an acute aortic dissection.w1 Most patients are discharged with the diagnosis of a non-cardiac condition. These non-cardiac conditions include musculoskeletal syndromes, gastrointestinal syndromes, and psychological disorders.

When evaluating cardiac chest pain, an ECG provides the initial classification. Patients are subdivided into those with a persistent ST segment elevation and those without a persistent ST segment elevation. The latter is called a non-ST elevation ACS (NSTE-ACS). The concentration of the biomarkers of necrosis above a certain prespecified threshold differentiates NSTE-ACS patients into those with a non-ST elevation myocardial infarction (NSTEMI) as opposed to those with unstable angina (Ofigure 1). This article focuses on the timing of invasive evaluation in those patients with a suspected NSTE-ACS.

Figure 1
Diagnostic approach to the patient with chest pain. NSTE-ACS, non-ST elevation acute coronary syndrome; NSTEMI, non-ST elevation myocardial infarction; STEMI, ST elevation acute myocardial infarction; UAP, unstable angina pectoris.

In patients presenting with a suspected NSTE-ACS, the first hurdle is to confirm …


The influence of NH3 input partial pressure on N-polarity InGaN grown by tri-halide vapor phase epitaxy was investigated. It was found that surface morphology, solid composition and optical properties were affected by NH3 input partial pressure. As shown in thermodynamic analyses, the indium content increased due to an increase in the driving force for InN deposition caused by increased NH3 input partial pressure. In addition, the deep level emission around 2.1 eV in photoluminescence measurements drastically decreased at higher NH3 input partial pressures. Ab initio calculations and subsequent secondary ion mass spectrometry measurements suggested the reduction of metal-vacancies and/or carbon impurity incorporation in the InGaN layers.


O18/O16 and D/H measurements were made on a
variety of sedimentary rocks and minerals, with special emphasis on the fine-grained, predominantly clay mineral fraction of the sediments. The interlayer water was removed from clay minerals prior to the isotopic analyses. Precision of the measurements was generally ± 0.2 permil for oxygen and ± 0.3 percent for hydrogen. In the case of zeolites the reproducibility was less constant because of difficulty encountered in removing zeolitic water. Listed in order of decreasing tendency to concentrate O18, the sedimentary minerals for which such data are available and their approximate isotopic fractionation factors relative to water at sedimentary temperatures are: [See abstract for table]. Mineral - water fractionations are related to
the types of chemical bonds in the minerals. Clay minerals which form under sedimentary conditions
appear to form in isotopic equilibrium with their
environments. Subsequent isotopic exchange may occur
easily at elevated temperatures, but only extremely slowly
at low temperatures. Ocean sediments which are detrital in origin
have isotopic compositions reflecting the fresh water origin
of their clay minerals. There is no evidence for any isotopic
exchange of detrital clay minerals with the marine
environment in any of the ocean cores studied. (The sediments
could be as old as 250,000 years as determined by
ionium-thorium method.) Marine sediments which have large
authigenic components are generally enriched in O18, reflecting
the presence of phillipsite (δ O18 = +34 permil
and montmorillonite δ O18 = +29 permil)e However, those
containing a high concentration of iron and manganese
oxide may be isotopically light. (A manganese nodule had
δ O18 = +15 permil.) The isotopic compositions of the clay minerals
of ocean sediments are compatible with a weathering origin
for a kaolinite and a metamorphic or diagenetic origin for
chlorite. Montmorillonite and illite are primarily of
weathering origin but both of these minerals may have
diagenetic components. There is no evidence for any isotopic exchange of
sand-sized quartz or feldspar in the sedimentary environment
and these minerals may be used as indicators of provenance
in sediments. The presence of a large authigenic feldspar
or quartz component may be readily detected by oxygen isotopic
analysis. An authigenic feldspar had an O18/O16 ratio
ten permil greater than igneous feldspars. Calculations have been performed to determine
the effect of weathering and the formation of sediments on
the isotopic composition of the hydrosphere. It is concluded
that those processes could have depleted the hydrosphere
3 permil in O18 and enriched it 0.03 percent in
deuterium through the course of geologic time.


In this study, surface error calculations and stability conditions are presented for milling operations in case of slender parts. The dynamic behavior of the flexible beam-type workpiece is modeled by means of finite element method (FEM), while the varying dynamical properties related to the feed motion as well as the material removal process are incorporated in the model. The FEM-generated direct frequency response function is verified through a closed-form solution based on the distributed transfer function method. Relative errors and convergence of the FEM are investigated based on the analytical solutions of the continuum model, from which appropriate element size and mode number can be selected for modal coordinate transformations. The pattern in the variation of the natural frequencies is explored using the analytical model in case of high radial depth of cut relative to the original cross section of the beam-like workpiece. Both the stability conditions and the resulted surface errors are predicted as a function of the tool position. The presented approach and the results are validated by laboratory tests. [DOI: 10.1115/1.4045418]


Multiple myeloma (MM) is a haematological malignancy characterized by terminally differentiated plasma cells and their accumulation in the bone marrow (BM). Despite significant advances in therapeutic strategies it currently remains incurable. The interactions between the BM microenvironment and malignant plasma cells have been pivotal to understanding this disease. Previous reports have shown that patients with a haematological malignancy sustain "damage" to their BM, but how much of this is due to the disease and/or the treatment is currently unknown. Furthermore MM plasma cells have been documented to harness the BM microenvironment to their advantage, improving their growth and survival. However, little is known about the functionality of BM mesenchymal stem cells (MSC) in patients with MM disease which form an essential compartment of the BM microenvironment. It was hypothesised that MSC altruistically protect MM cells from therapy and consequently become phenotypically and genetically compromised.
To facilitate the study of the effects of chemotherapeutic agents and MM cells on MSC, a non-contact co-culture model was developed that allowed the investigation of functional and genetic damage. In line with previous studies, U266 cells were found to be protected from drug-induced cell death when in co-culture with the stromal cell line HS5. However, the promoting effects of the BM appear to be at the detriment to their own survival. HS5 cells were found to have lower viability, altered morphology and disrupted differentiation when in a non-contact co-culture with U266 cells.
Results from this study have revealed that interactions of MSC with MM cells lead to an altruistic protection of MM cells by the BM. This work demonstrates that U266 cells have an improved viability following exposure to chemotherapy when in a non-contact co-culture with MSC/HS5. Furthermore, genotoxic assays also revealed that HS5/MSC interactions with U266 cells protect U266 from the genotoxic effects of melphalan in co-culture, whilst for the first time HS5 morphology was shown to be severely altered following exposure to chemotherapy and when in co-culture with U266 cells.
This work has demonstrated, for the first time, the cytotoxic effects of novel agents bortezomib and carfilzomib on HS5 cells when in co-culture with U266 cells. Results from this study also demonstrate that melphalan severely effects the ability of HS5 cells to differentiate in an osteogenic lineage with a further deficiency in differentiation when in co-culture with U266. Adipogenic differentiation of HS5 was unable to take place when in co-culture with MM cells and was again further impaired by chemotherapy. This is the first study to reveal that primary MSC secrete significantly high concentrations of IL-6 compared to the stromal cell line HS5. A further increase in expression of IL-6 was also shown when in co-culture with U266 cells.
Increased multi-nucleation was also identified in both HS5 and U266 cells when exposed to either thalidomide, lenalidomide and bortezomib with abnormalities providing possible explanations for the therapy related malignancies and neurotoxicity that is seen in some patients. Genotoxicity to the MSC/HS5 compartment of the co-culture measured by the micronucleus assay was also found to be reduced suggesting that the BM is protected from the DNA damaging effects of some agents when in co-culture with MM cells.
Combined work on the functionality and genotoxicity of the interactions between the BM and MM reveal a tropism of MSC and HS5 towards the MM cell line U266. With this research being conducted in a non-contact co-culture, it has indicated that cell-cell contact is not essential to provide protection of both the BM and MM cells against chemotherapy. This research provides further understanding of the MSC and MM interactions' impact on the functionality of the BM and their protection from genotoxic damage. Elucidating the consequence of cytotoxic and genotoxic damage to MSC via chemotherapy treatment and/or through haematological disease may allow for the development of effective therapies and improve the quality of life for patients with MM.