Purpose: The aim of this study is to formulate a novel nanoemulsion of doxorubicin to enhance the therapeutic efficacy of the drug. Method: Four different multiple emulsions (W 1 /O/W 2 ) were prepared (A, B, C, and D) by homogenization of a mixture of aqueous and oil phases. The resultant primary emulsions were later pass through a high pressure homogenization to further reduce the globules size to nanometer range. The formulation A is a control nanoemulsion, consisted of only deionized water as W 1 phase. The W 1 phase of the other three formulations (B, C, and D) consisted of aqueous solution of BSA (as an emulsion stabilizer), doxorubicin, and a mixture of BSA and doxorubicin, respectively. For all four formulations, the oil phase (O) consisted of a 2:1 mixture of soyabean oil and Span 80, and the outer aqueous phase (W 2 ) consisted of prolaxamer P-85 and Vitamin E TPGS. The nanoemulsions were evaluated for stability, polydispersity index, size, and viscosity. Anticancer efficacy of these formulations was evaluated by Alamar Blue Assay and Colony Forming Assay using MCF-7 cells as a model malignant breast cancer cell line. Results: The stability of nanoemulsions was found to be significantly better for the formulations containing BSA. Presence of BSA or doxorubicin resulted in a significant increase in viscosity from 2.09 to 10.6 cP. Cell culture studies showed that doxorubicin nanoemulsions had higher localization in cytoplasm as compared to the nucleus. In regard to cellular uptake (intracellular quantification of doxorubicin), the following results were obtained at 2h, 24h, 48h, and 120h post-incubation, respectively: 42%, 30%, 37%, and 22% with doxorubicin solution; 12%, 19%, 21%, 33% with formulation C; and 0.25%, 6%, 10%, 19% with formulation D. The results of Alamar Blue Assay showed IC 50 values of 0.97μM (solution), 1.62μM (formulation C) and 1.91μM (formulation D). The results of Colony Forming Assay (12days-post-treatment with equivalent to 0.86 μM doxorubicin) showed 74% (solution), 86% (formulation C) and 92.6% (formulation D) growth inhibitions. Conclusions: The presence of BSA within the aqueous phase enhances the stability of nanoemulsions. In comparison to doxorubicin solution, the nanoemulsions produce higher anticancer efficacy. This exploratory study will be followed by more detailed studies to confirm this preliminary finding. Acknowledgements: This work was funded in part by the NASA grant # NCC3-946-S4, Louisiana Board of Regents RC/EEP (2007-10), NIH grant# 5P20CA118768-02, and Louisiana Cancer Research Consortium. We are thankful to Dr. Thomas Wiese of the College of Pharmacy, XULA, for providing the Cell culture lab facilities. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5531.


The advancement of Deep Learning (DL) is driven by efficient Deep Neural Network (DNN) design and new hardware accelerators. Current DNN design is primarily tailored for general-purpose use and deployment on commercially viable platforms. Inference at the edge requires low latency, compact and power-efficient models, and must be cost-effective. Digital processors based on typical von Neumann architectures are not conducive to edge AI given the large amounts of required data movement in and out of memory. Conversely, analog/mixed-signal in-memory computing hardware accelerators can easily transcend the memory wall of von Neuman architectures when accelerating inference workloads. They offer increased area-and power efficiency, which are paramount in edge resource-constrained environments. In this paper, we propose AnalogNAS, a framework for automated DNN design targeting deployment on analog In-Memory Computing (IMC) inference accelerators. We conduct extensive hardware simulations to demonstrate the performance of AnalogNAS on State-Of-The-Art (SOTA) models in terms of accuracy and deployment efficiency on various Tiny Machine Learning (TinyML) tasks. We also present experimental results that show AnalogNAS models achieving higher accuracy than SOTA models when implemented on a 64-core IMC chip based on Phase Change Memory (PCM). The AnalogNAS search code is released1


A monitoring tool of a complex Grid system can gather a huge amount of information that have to be presented to the users in the most comprehensive way. Moreover different types of consumers could be interested in inspecting and analyzing different subsets of data. The main goal in designing a Web interface for the presentation of monitoring information is to organize the huge amount of data in a simple, user-friendly and usable structure. One more problem is to consider different approaches, skills and interests that all the possible categories of users have in looking for the desired information. Starting from the Information Architecture guidelines for the Web, it is possible to design Web interfaces towards a closer user experience and to deal with an advanced user interaction through the implementation of many Web standard technologies. In this paper, we will present a number of principles for the design of Web interface for monitoring tools that provide a wider, richer range of possibilities for what concerns the user interaction. These principles are based on an extensive review of the current literature in Web design and on the experience with the development of the GridICE monitoring tool. The described principles can drive the evolution of the Web interface of Grid monitoring tools.


This full paper outlines the role of the DEIS Department, Cork Institute of Technology (DEIS CIT), Ireland in the European project, Remote-labs Access in Internet-based Performance-centred Learning Environment for Curriculum Support (RIPLECS). The Multimedia for Information and Communication Systems (ICS) module developed by DEIS CIT for the RIPLECS project integrates the fundamentals of current user generated web content with remote delivery over a cloud infrastructure. The module provides students with theoretical and technical skills in various areas of multimedia technology and design, and incorporates assessment methods with these practical elements. Students are offered a basic introduction to four multimedia subjects; 3D animation, video editing, web development using HTML5 and content management systems. The students are then required to complete tasks as part of a continuous assessment for each of the four subjects. This paper outlines the design of the Multimedia module, describes the structure and scheduling of the module for delivery, the set-up of the remote laboratory in Cork Institute of Technology (CIT) and the role of DEIS CIT in the delivery of the course, both academically and administratively. It pays particular attention to the planned piloting of the course and the remote labs infrastructure, which is scheduled to take place in early 2013.


My research explores the relationship between crowd-funding and online community. My research hypothesis is that association with an online community can impact the success of crowdfunding projects. In the case of my research, success will be defined in financial terms, such as funding of projects by deadline, as well as in non-financial terms, including networking, collaboration and feedback. Furthermore, I'm investigating the reverse hypothesis suggesting that crowdfunding projects and platforms could help establish, grow, or sustain online community. My research will use qualitative research methods involving crowdfunding stakeholders, including funders, creators and platform managers.


The purpose of this study was to examine the extent to which character familiarity and game interactivity moderate preschoolers' learning and transfer from digital games. The games were based on a popular television show and designed to test skills related to STEM (science, technology, engineering, mathematics): numerical cognition (quantity of different sets) and knowledge of a biological concept (growth). Preschoolers (3.0–5.5 years, N = 44) were assigned to play one game and watch a recording of an experimenter playing the other game. Learning was assessed during pre-test and post-test using screenshots from the game. Transfer was assessed using modified screenshots (near) and real-life objects (far). Familiarity was assessed by asking children to identify the television characters and program. Findings indicate that the effectiveness of the games varied by age and condition: younger children learned from the quantity game, but only when they watched (rather than played) the game. They did not transfer this information in either condition. Conversely, older children learned from the growth game regardless of whether they played or watched. However, older children only demonstrated far transfer if they watched (rather than played) the growth game. Thus, preschoolers may benefit more by watching a video than by playing a game if the game is cognitively demanding, perhaps because making decisions while playing the game increases cognitive load. Character familiarity did not predict learning, perhaps because there was little overlap between the lessons presented in the television program and game. Findings from the current study highlight the need for more research into educational games and applications designed for preschoolers in order to establish whether, how, and for whom screen media can be educationally valuable.


Volcanic Ash (V.A) is one of Pozzolanas natural occurring material that has been tested for partial replacement of cement for production of concrete. With respect to reduction of cement consumption for sustainable construction (i.e. reducing gas emission), evaluation of the strength reduction is crucial as it has a severe impact on the structure under construction. Therefore, this paper examines the effects of replacing cement by using Tanzanian Volcanic Ash on the strength of concrete (i.e. concrete grade). The research aims to determine the optimal amount of V.A for production of high-grade concrete. The samples of V.A received from Holili, Kilimanjaro were prepared in five different proportions (0, 10, 20, 30 & 40 wt %) to make concrete cubes. Uniaxial compressive tests were used to examine the strength of concrete achieved after 7 and 28 days of curing. Results revealed the grade of concrete is significantly affected by adding more than 30 wt% of the V.A (i.e. optimal amount of V.A is 30%). For high-grade concrete, 20 wt% replacement provides less than 10% reduction in strength relative to reference concrete strength (i.e. 0% of V.A). This maintained the desired strength of concrete structure for construction. Hence, a partial replacement of cement can be allowed for 20 to 25 wt% of V.A.


BACKGROUND
Increases in the prevalence of resistance to nonnucleoside reverse transcriptase inhibitors (NNRTIs) have been observed among previously untreated individuals in all areas of sub-Saharan Africa. We aimed to examine whether first-line use of 2 NRTIs plus a boosted protease inhibitor (bPI) could protect against emergence of NRTI resistance mutations, compared to the use of 2 NRTIs plus 1 NNRTI.

METHODS
We carried out a weighted meta-analysis of randomized clinical trials comparing bPI- with NNRTI-based first-line antiretroviral therapy regimens using random effects modeling.

RESULTS
In intention to treat analyses, there was no difference in the risk of viral failure at week 48 between NNRTI and bPI (P = .19). At week 48, the overall difference between NNRTI- and PI-based regimens in selection of any major NRTI resistance mutation (crude unweighted prevalence 3.3% vs 1.6%) was 1.7% (95% confidence interval [CI], .4-3.0; P = .00927). There was a statistically significant difference in prevalence of K65R when comparing NNRTI (1.3%) with PI (0.67%); absolute weighted difference 1.0% (95% CI, .3-1.7; P = .00447). There was also a significant difference in prevalence of M184V/I between NNRTI and PI (crude unweighted prevalence 3.2% vs 1.4%); difference 1.6% (95% CI 0.1-3.1; P = .0368).

CONCLUSIONS
Despite the equivalent efficacy and more favorable resistance implications of PI- versus NNRTI-based first line therapy, widespread use of PI-based first-line therapy is not warranted at this time, due to resource limitations and predicted increased risk of resistance-related failure of NNRTI/NRTI second-line regimens. PI-based first-line therapy could be reconsidered when antiretroviral agents from other classes become available for second-line regimens in resource-limited settings.


A long-lived qubit is usually well-isolated from all other systems and the environments, and so is not easy to couple with measurement apparatus. It is sometimes difficult to implement reliable projective measurements on such a qubit. One potential solution is spin amplification with many ancillary qubits. Here, we propose a spin amplification technique, where the ancillary qubits state changes depending on the state of the target qubit. The technique works even for an inhomogeneous system. We show that fast and accurate amplification is possible even if the coupling and frequency of the ancillary qubits is inhomogeneous. Since our scheme is robust against realistic imperfections, this could provide a new mechanism for reading out a single spin that could not have been measured using the previous approaches.


Biliary stent migration occurs in about 5% of patients. The most common complications secondary to stent migration are pancreatitis, small bowel perforation and peritonitis. We report the case of a patient presenting with an abdominal wall abscess secondary to migration of a biliary stent. Direct abdominal radiography, abdominal ultrasound and CT scan have proved very useful in the diagnosis, providing the correct localisation of the stent in the left rectus muscle of the abdominal wall that led to a surgical approach under local anaesthesia for the removal, and abscess formation surrounding the stent. The patient was discharged on the day after surgery. After reviewing the literature concerning this rare complication, the Authors conclude that closer monitoring of patients with biliary prostheses is needed to prevent the migration and the consequent serious complications.


CO/sub 2/-laser-induced photovoltaic and photoconductive effects have been studied experimentally in silicon junctions. The response is slightly nonlinear or linear for the lower excitation intensities used, in opposition to the extremely nonlinear high-excitation-intensity regime. Abrupt changes in the slope of the growing response in the induced voltage pulsewidth and in the dependence on the junction temperature cause the difference in behavior. While the high-excitation-intensity response is strongly temperature dependent, the low excitation response is practically independent of the temperature. >


A negatively supercoiled plasmid DNA containing autonomously replicating sequence (ARS) 1 from Saccharomyces cerevisiae was replicated with the proteins required for simian virus 40 DNA replication. The proteins included simian virus 40 large tumor antigen as a DNA helicase, DNA polymerase alpha.primase, and the multisubunit human single-stranded DNA-binding protein from HeLa cells; DNA gyrase from Escherichia coli, which relaxes positive but not negative supercoils, was included as a "swivelase." DNA replication started from the ARS region, proceeded bidirectionally with the synthesis of leading and lagging strands, and resulted in the synthesis of up to 10% of the input DNA in 1 h. The addition of HeLa DNA topoisomerase I, which relaxes both positive and negative supercoils, to this system inhibited DNA replication, suggesting that negative supercoiling of the template DNA is required for initiation. These results suggest that DNA replication starts from the ARS region where the DNA duplex is unwound by torsional stress; this unwound region can be recognized by a DNA helicase with the assistance of the multisubunit human single-stranded DNA-binding protein.


We hereby state that the above clarifications are in compliance with the principles set forth in the Decree No 54 Series No VIII of the Capital Market Board, that it fully reflects the information we have received in this respect, that the information is compliant with the books, records and our documents, that we have accomplished our best in order to obtain the accurate and correct information, and that we are responsible for this clarification hereby.


The exit burr generated in the face milling operation at the edge of the workpiece usually requires deburring processes to enhance the level of precision of the parts. This paper is to geometrically understand the formation of the exit burr in the face milling operation on the arbitrary shaped workpiece with multiple feature such as hole, spline, and arc so that we can suggest the cutting conditions and tool path to minimize the burr formation on the given workpiece in the early design stage. The burr formation mechanism in each type of burr is classified based on the experimental results. A database is developed to store and predict burr formation results. A Windows based program is developed with the algorithm including three steps, i.e., the feature identification, the cutting condition identification, and the analysis on exit burr formation. We can predict which portion of the workpiece would have the exit burr in advance so that we can manage to find a way to minimize the exit burr formation in an actual cutting. Here, the idea of critical burr length is introduced as a criterion in optimization.


Abstract Motivated by a question of Hirzebruch on the possible topological types of cusp cross-sections of Hilbert modular varieties, we give a necessary and sufficient condition for a manifold M to be diffeomorphic to a cusp cross-section of a Hilbert modular variety. Specialized to Hilbert modular surfaces, this proves that every Sol 3–manifold is diffeo morphic to a cusp cross-section of a (generalized) Hilbert modular surface. We also deduce an obstruction to geometric bounding in this setting. Consequently, there exist Sol 3–manifolds that cannot arise as a cusp cross-section of a 1–cusped nonsingular Hilbert modular surface.


In recent years, with the rapid development of network information technology and the surge in the number of Internet users, e-financial innovation has become an essential part of daily life. Credit scoring is a numerical expression of the credit worthiness of an individual. In this paper, we propose a credit scoring model, which is defined as a piecewise-function. Different scoring function is for different types of customers. Experiments on UCI datasets are conduct and the results shows that the performance of the model is very effective for the different types of customers. Indexing terms/


ESI-MS is a powerful/sensitive detector for CE in metabolomics. For trace analysis of certain metabolites, off-line sample preparation will be required prior to CE-ESI-MS. An alternative and complementary sample preparation approach is stacking, which was initially developed for CE with UV detection to improve detection sensitivity. Stacking also offers the possibility of sample clean-up during analyte focusing, providing the opportunity to improve the tedious and long analysis commonly associated with bioanalysis. This chapter introduces the different stacking techniques developed in CE-UV, and their evolution into CE-ESI-MS with special emphasis on applications for metabolomics. The nature of metabolites (typically charged small molecules) makes it easy to apply the different stacking techniques currently available in the literature. However, it seems like stacking in CE-ESI-MS for metabolomics is still in its development/testing stage, and hopefully younger scientists will pursue research in this relevant area of study.


Polymers are versatile materials with wide use in several industry fields, such as engineering, textile, automobile, packaging and biomedical. In the pharmaceutical industry, both natural and synthetic polymers have been largely used with different applications for the development and production of cosmetics and traditional dosage forms and novel drug delivery systems. For instance, a number of polymers are used as fillers, lubricants, disintegrants, binders, glidants, solubilizers, and stabilizers in tablets, capsules, creams, suspensions or solutions. Additionally, biodegradable and bioadhesive polymers may play an important role in the development of novel drug delivery systems, especially for controlled drug release.


Presents a visualization technique based on particle tracking. The technique consists in defining a set of points distributed on a closed surface and following the surface deformations as the velocity field changes in time. Deformations of the surface contain information about dynamics of the flow; in particular, it is possible to identify zones where flow stretching and foldings occur. Because the points on the surface are independent of each other, it is possible to calculate the trajectory of each point concurrently. Two parallel algorithms are studied; the first one for a shared memory Origin 2000 supercomputer and the second one for a distributed memory PC cluster. The technique is applied to a fluid moving by natural convection inside a cubic container.


In order to prevent hyperacute rejection in pig-to-human xenotransplantation, it would be very useful to be able to down-regulate the Gal alpha1-3 Galbeta 1-4 GlcNAc-R (alpha-Gal epitope) in mouse and swine tissues. When the beta-D-mannoside beta-1,4-N-acetylglucosaminyl-transferase III (GnT-III) gene was introduced into mouse aorta endothelial cells (MEC) their susceptibility to complement-mediated cell lysis by normal human serum (NHS) was reduced. Expression of GnT-III also suppressed the antigenicity of MEC to human natural antibodies as shown by binding of Griffonia simplicifolia 1 isolectin (GS1B4 lectin) to the alpha-Gal epitope. Western blot analysis indicated that the reactivity of the glycoproteins of the transfectants to NHS and GSIB4 lectin was reduced to approximately the same extent. Thus GnT-III, a key enzyme involved in the formation of branched N-linked sugars, reduces the expression of xenoantigens, suggesting that this approach may be of value in clinical xenotransplantation.


The previous work of the authors indicated that the fluid–solid coupling effect of the magneto-rheological fluid and the brake disc is a necessary focus during braking process. In this study, a novel design of magneto-rheological fluid brake was proposed and studied theoretically and numerically, aiming to solve the prominent problem of heat dissipation, especially in the case of single emergency braking. First, based on the modified Bingham model, a parameter defined as the apparent equivalent viscosity was utilized to represent the relationship of magnetic field, flow field, and temperature field. The braking torque and the formula for calculating the impact factor of fluid–solid coupling employed for characterizing the associations among the thermal field and the stress field were established based on fluid–solid coupling. With a detailed explanation of simulation method, the distribution disciplinarian's numerical simulation of each field was analyzed using COMSOL software. To validate the accuracy of the established model on the designed magneto-rheological fluid brake, the prototype was also manufactured, and results achieved experimentally which were measured on inertia test system of brake, for braking torque, motion parameters, and surface temperature in braking process, were compared with simulations. Simulation results manifested that the designed magneto-rheological fluid brake's magnetic circuit structure is feasible based on magnetic induction intensity distribution. Finally, it has been shown that the simulations appear to be basically consistent with the experimental results, and the heat dissipation of the designed magneto-rheological fluid brake is partially improved. These results might contribute to the structure design, optimization, and improvement of magneto-rheological fluid products, extending the previous work on fluid–solid coupling analyses.


The memory system of a modern embedded processor consumes a large fraction of total system energy. We explore a range of different configuration options and show that a reconfigurable design can make better use of the resources available to it than any fixed implementation, and provide large improvements in both performance and energy consumption. Reconfigurability becomes increasingly useful as resources become more constrained, so is particularly relevant in the embedded space.
For an optimised architectural configuration, we show that a configurable cache system performs an average of 20% (maximum 70%) better than the best fixed implementation when two programs are competing for the same resources, and reduces cache miss rate by an average of 70% (maximum 90%). We then present a case study of AES encryption and decryption, and find that a custom memory configuration can almost double performance, with further benefits being achieved by specialising the task of each core when parallelising the program.


Microphysical properties of cirrus clouds largely influence their atmospheric radiative forcing. However, uncertainties remain in simulating/parameterizing the evolution of ice crystals. These uncertainties require more analyses in the Lagrangian view, yet most in situ observations are in the Eulerian view. Here we demonstrate a new method to separate out five phases of ice crystal evolution, using the horizontal spatial relationships between ice supersaturated regions (ISSRs) and ice crystal regions (ICRs). Based on global in situ data sets, we show that the samples of clear‐sky ISSRs, ice crystal formation/growth, and evaporation/sedimentation are ~20%, 10%, and 70% of the total ISSR + ICR samples, respectively. In addition, the variance of number‐weighted mean diameter (Dc) becomes narrower during the evolution, while the distribution of ice crystal number density (Nc) becomes wider. The new method helps to understand the evolution of ICRs and ISSRs on the microscale by using in situ Eulerian observations.


We develop a new analysis approach towards identifying related radio components and their corresponding infrared host galaxy based on unsupervised machine learning methods. By exploiting PINK, a self-organising map algorithm, we are able to associate radio and infrared sources without the a priori requirement of training labels. We present an example of this method using $894,415$ images from the FIRST and WISE surveys centred towards positions described by the FIRST catalogue. We produce a set of catalogues that complement FIRST and describe 802,646 objects, including their radio components and their corresponding AllWISE infrared host galaxy. Using these data products we (i) demonstrate the ability to identify objects with rare and unique radio morphologies (e.g. 'X'-shaped galaxies, hybrid FR-I/FR-II morphologies), (ii) can identify the potentially resolved radio components that are associated with a single infrared host and (iii) introduce a "curliness" statistic to search for bent and disturbed radio morphologies, and (iv) extract a set of 17 giant radio galaxies between 700-1100 kpc. As we require no training labels, our method can be applied to any radio-continuum survey, provided a sufficiently representative SOM can be trained.


Vitamin D plays an important role in immune function and inflammation and the physical activity demonstrate relationship near to syntheses of vitamin D, considering to necessary to factors immunologics, environmental and physical. We searched five databases through February 20, 2021. Two reviewers screened the studies, collected data, assessed the risk of bias, and ranked the evidence for each outcome across the studies, independently and in duplicate. The prespecified endpoints of interest were Cardiorespiratory Fitness; Sunlight Exposure; Body Mass Index (BMI). We only included data from peer-reviewed articles in our primary analyses. In our primary analysis, there was a positive trend between serum 25(OH)D <20 ng/ml and body mass index, this result should be interpreted with caution, considering confidence intervals (RR 1.10 95% CI 0.37 to 1.83. We identified 4 high quality evidence that vitamin D levels and high physical activity required a direct relationship considering (four trials with 2,253) ; RR 0. (RR 0.0; 95% CI -0.15 to 0.15) (RR 0.59; 95% CI 0.43 to 0.75. Although the evidence available so far, from observational studies of medium quality, can be seen as showing a trend towards an association between sufficient serum levels of 25(OH)D and physical activity, this relationship has been shown. have a stimulating effect on vitamin D synthesis, the relationship of low body mass index with sufficient vitamin D levels is not based on solid evidence. We await results from ongoing studies to determine this effectiveness.


Traditional human computer interfaces are not intuitive and natural for the choreography of human motions in the field of VR and video games. In this paper we present a novel approach to control virtual humans performing sports with a motion-based user interface. The process begins by asking the user to draw some gestures in the air with a Wii Remote. The system then recognizes the gestures with pre-trained hidden Markov models. Finally, the recognized gestures are employed to choreograph the simulated sport motions of a virtual human. The average recognition rate of the recognition algorithm is more than 90% on our test set of 20 gestures. Results on the interactive simulation of several kinds of sport motions are given to show the efficiency and interestingness of our system, which is easy-to-use especially for novice users


Kinetic parameter is a basis for design and optimization of activated sludge POME treatment. In fact, most of the kinetic parameter value used in design and optimization are default values taken from municipal wastewater. The kinetic parameters for POME treatment have not been thoroughlystudied and most of the system is using the Activated Sludge Models (ASM), either in modelling or design. Thus, the kinetic study of POME treatment by activated sludge system were carried out to obtain the kinetic parameters  for  the  POME  treatment  plant  design calculation.In  this  study,  POME treatment was carriedout in batch studiesinto 14 L aeration tank with activated sludge for the biological oxidation process with optimum pH at 6.5 ± 0.1, MLVSS of 2000 ± 200 mg/Lfor HRT of 48 h and feeding with 650 ± 20 mg BOD3/L of anaerobic treated POME, while SRT was controlled at a range of 10 days to 20 days with interval of 2 days for the kinetic study experiment. From this kinetic study, the kinetic parameters for COD and BOD basis had been determined for maximum yields coefficient (Y), endogenous decay coefficient (kd), maximum specific substrate utilization rate (k) and half-velocity constant (Ks) at 0.2369 mg VSS/mg COD, 0.1060 day-1, 2.2717 day 1 and 758.7705 mg/L for COD basis whilst the kinetic parameters value for BOD basis were 0.6718 mg VSS/mg BOD3, 0.0658 day-1, 1.4136 day-1 and 556.1526 mg/L, respectively. Since the BOD is one of the discharge parameters in discharge regulatory, thus kinetic parameters for BOD basis will be used for the system design of POME treatment.


Objectives: Bone trauma is a common occurrence in human skeletal remains. Macroscopic and imaging scrutiny is the approach most currently used to analyze and describe trauma. Nevertheless, this line of inquiry may not be sufficient to accurately identify the type of traumatic lesion and the associated degree of bone healing. To test the usefulness of histology in the examination of bone healing biology, we used an integrative approach that combines gross inspection and microscopy. Materials and Methods: Six bone samples belonging to 5 adult individuals with signs of bone trauma were collected from the Human Identified Skeletal Collection from the Museu Bocage (Lisbon, Portugal). Previous to sampling, the lesions were described according to their location, morphology, and healing status. After sampling, the bone specimens were prepared for plane light and polarized light analysis. Results: The histological analysis was pivotal: (1) to differentiate between types of traumatic lesions; (2) to ascertain the posttraumatic interval, and (3) to diagnose other associated pathological conditions. Conclusion: The outer surface of a bone lesion may not give a complete picture of the biology of the tissue's response. Accordingly, microscopic analysis is essential to differentiate, characterize, and classify trauma signs.


This paper studies a time-varyingSIS(i.e.containing susceptible and infected populations) propagation disease model exhibiting a nonlinear incidence rate and impulsive eventual culling of both populations so that the individuals recover with no immunity to the disease. The nonlinear incidence rate consists of two time-varying additive terms proportional to the susceptible and infected populations normalized to the total population.


Background: Cataract is a leading cause of childhood visual impairment in developing countries. Cataract in children causes the blurring of retinal images and therefore disrupts the development of the immature visual pathways in the central nervous system with subsequent development of amblyopia if there is no timely surgical intervention. There are several associations of pediatric cataract- both systemic and ocular which have considerable consequences on the management and post operative outcomes. Aim: To identify the systemic and ocular associations of childhood cataract presenting in Evangelical church of West Africa (ECWA) Eye Hospital, Kano, Nigeria from 2006 to 2014. Methods: This was a prospective study of 694 children (1388 eyes) with 881 lens opacity seen at Original Research Article ECWA Eye Hospital, from January 2006 to December 2014. One hundred and eighty-seven children (26.9%) had bilateral cataract. All the patients had comprehensive paediatric review and their parents interviewed. Results: Seven hundred and thirty eyes (82.8%) had cataract with associated ocular abnormalities: Nystagmus (22.5%), Squint (17.3%), Corneal opacity (8.8%), Microcornea (2.7%), Megalocornea (8.2%), Vascularized cornea (0.8%), Congenital glaucoma (10.4%), Iris coloboma (1.6%), Peripheral synaechiae (3.7%), Abnormal lens anatomy (6.6%). Ninety-eight children (14.1%) had various forms of associated systemic abnormality: Congenital Health Diseases, Deafness, Mentally Retarded, Cerebral Palsy, Down's Syndrome, Failure to Thrive, Mumps and Asthma.


New methods for controlling blowfly strike will be needed when mulesing is phased out and the availability or efficacy of insecticides for control of fly strike decreases. The Australian Sheep Industry CRC has pursued two approaches for the development of new methods to help control blowfly strike. In the first, genetic resistance of sheep to survival and growth of blowfly larvae was examined. Resistance to growth of larvae was heritable (0.29 ± 0.22). The trait was not associated with resistance to internal parasites, nor was it influenced by wool characteristics such as fibre diameter or coefficient of variation of fibre diameter. This new trait differs from resistance to fly strike associated with resistance to fleece rot. Because measurement of the trait is labour intensive, gene markers or correlated measures are needed before it will be suitable for industry adoption. The second approach examined the impact of larval products on the immune system of the sheep. Larvae suppress the sheep immune system and thereby limit the ability of the sheep to reject the larvae. The immunosuppressive agent is being purified and strategies to abolish its activity are being explored. Abolition of immunosuppression would create opportunities for the development of new vaccines against blowfly strike.


In order to evaluate the effect of ducks number on weeds diversity and density in paddy fields, an experiment was conducted at Sari Agricultural Sciences and Natural Resource University during growing season of 2011-2012. Experiment was arranged in split plot based on complete randomized block design with four replications. Main factors were duck number at three levels (consisting of control, 400 and 800 ducks.ha-1) and sub plots were three contrast cultivars (including Tarom as a traditional, and Shirodi and Ghaem as improved cultivars). Results of ANOVA showed highly significant differences between ducks, cultivars and ducks × cultivar interaction in terms of weeds density including nutsedge (Cyperus spp. L.), common Water-plantain (Alisma plantago-aquatica L.), barnyard grass (Echinochloa crus-galli L.), duckweed (Lemna minor L.), azolla (Azolla pinata R.Br.) and paddy yield. Accordingly, the lowest weed density and diversity were recorded at 800 and 400 ducks.ha-1, respectively. Among rice cultivars Tarom and Ghaem had the minimum and the maximum weeds density and diversity. The highest nutsedge density (67 plant.m-2) was related to Ghaem cultivar in control (without duck) plots as much as 97% higher than 800 ducks.ha-1. Maximum paddy yield was observed in 800 ducks.ha-1 in Shirodi (5.3 t.ha-1), Ghaem (4.3 t.ha-1) and Tarom (3.6 t.ha-1) as much as 23, 7 and 20% higher than those cultivars in 400 ducks.ha-1, respectively. Finally, in the current research conditions using 800 ducks.ha-1and Tarom cultivar resulted the best performance because of the lowest weed diversity and density as compared to other treatments.


Over the past decades, group-based control has become one of the most popular signal technologies being applied in many cities around the world. LHOVRA control is one of such group-based controls widely employed in Scandinavian countries. While several previous studies showed that group-based control outperforms stage-based control in many aspects, implementation and evaluation of signal controllers are complicated in a real application. In addition, little effort has been put in optimizing such group-based controllers in traffic management practice. This study implements generic group-based control in an object-oriented software framework, while a software-in-the-loop simulation is developed to integrate the signal controller with an open-source traffic simulator, SUMO. Also, stochastic optimization is applied to generate optimal signal parameters according to different settings of objective. In particular, part of the study is to improve the computational performance of the optimization process by parallelized simulation runs. Test-based experiments are finally carried out to evaluate traffic and optimize its impact on a small traffic network in Stockholm.


endothelial cell internalization of insulin. Conclusions: Globular adiponectin increases muscle insulin uptake by recruiting muscle microvasculature, which contributes to its insulin-sensitizing action. ( Circ Res . 2013;112:1263-1271.) (0.1, 1, 2, 3 µ g/mL) at 37°C for 15 minutes. The reaction was stopped by transferring the culture plates onto ice. Cells were washed once with ice-cold HEPES-binding buffer, then twice with ice-cold acid solution (0.5 mol/L NaCl, 0.2 mol/L acetic acid, pH 3.0) to remove surface-bound 125 I-insulin, and then lysed with 0.5 mL 1 mol/L NaOH on ice for 1 hour. Aliquots of cell lysate were used for protein content determination and radioactivity quantification using a gamma counter. After subtracting the nonspecific binding, endothelial insulin uptake was calculated and expressed as cpm/ µ g protein.


By applying planar optodes and imaging techniques to a benthic photosynthetic mat, we demonstrated an extensive vertical and horizontal variation in O2 concentrations, O2 consumption, and O2 production. In light, the oxic zone could be divided into three horizons: 1) an upper zone dominated by diatoms that had a moderate net O2 production, 2) another zone dominated by Microcoleus‐like cyanobacteria with a high net O2 production, and 3) a lower zone with disintegrating microalgae and cyanobacteria with a high O2 consumption rate. From the O2 images, the net O2 production/consumption was calculated at a spatial resolution of 130 μM. This allowed us to identify microsites with high rates of O2 turnover within the photic zone. Sites with high net O2 consumption (>1.5 nmol·cm−3·s−1) were typically situated next to sites with a relatively high net production (>2 nmol·cm−3·s−1), revealing a mosaic in which the highest O2 consumption sites were surrounded by the highest O2 production sites. This suggested a tight spatial coupling between production and consumption of O2 within the photic zone. Light stimulated the O2 consumption within the photic zone. At irradiances above 400 μmol photons·m−2·s−1, the stimulated O2 production was almost completely balanced by enhanced O2 consumption at microsites exhibiting net consumption of O2 even at maximum irradiance (578 μmol photons·m−2·s−1). Our observations strongly supported the idea that light‐stimulated respiration was caused by stimulated heterotrophic activity fueled by organic carbon leakage from the phototrophs. Despite microsites with high net O2 consumption, anoxic microniches were not encountered in the investigated mat. Images of gross photosynthetic rates also revealed an extensive horizontal variation in gross rates, with microsites of low or no photosynthesis within the otherwise photic zone. Calculations based on the obtained images revealed that at maximum light (578 μmol photons·m−2·s−1), 90% of the O2 produced was consumed within the photic zone. The presented data demonstrate the great potential offered by planar optode for studies of benthic photosynthetic communities.


Detailed knowledge of radio propagation effects is a keystone for the development and performance assessment of mobile communication systems. Although a lot of investigations have already been carried out, there remains a need to gain deeper insight into the complex mechanisms which govern radio propagation. The authors first present a summary of the propagation mechanisms and discuss some issues related to radio channel parameters and measurement techniques. Then a systematic description of the propagation and simulation models developed within various European projects is given. The survey focuses on the main features of these models and the rationale behind their elaboration.


With regard to the public circulation of knowledge, universities are often regarded as privileged institutions where information and ideas are formally transmitted through regulated didactic experiences. University life, however, provided a more complex environment in which various parallel and perhaps contradictory processes of transmission were at work. In this paper, we analyse a set of 55 engravings with scientific images, which started to appear around 1670 in student notebooks at the University of Louvain. These engravings, produced and sold by the Louvain printers Michael Haye and Lambert Blendeff, were related to the philosophy curriculum of the Faculty of Arts but did not correspond entirely to the actual topics or doctrine taught. In fact, the obvious Cartesian orientation of the images was not in line with the more prudent position of the Faculty. This paper offers a preliminary analysis of the set of engravings and their role in the Cartesian reforms at Louvain.


To examine the effect of the presence of γ-hydroxymethyl groups on the rate of the β-O-4 bond cleavage during the alkaline pulping process, the rates of the β-O-4 bond cleavage of non-phenolic lignin model compounds without a γ-hydroxymethyl group, 2-(2-methoxyphenoxy)-1-(3,4-dimethoxyphenyl)ethanol (G'G) and 2-(2,6-dimethoxyphenoxy)-1-(3,4-dimethoxyphenyl)ethanol (G'S), were compared with those of analogous model compounds with a γ-hydroxymethyl group, 2-(2-methoxyphenoxy)-1-(3,4-dimethoxyphenyl)propane-1,3-diol (GG) and 2-(2,6-dimethoxyphenoxy)-1-(3,4-dimethoxyphenyl)propane-1,3-diol (GS), under alkaline pulping conditions. The disappearance of G'G or G'S was accompanied by the quantitative liberation of 2-methoxyphenol or 2,6-dimethoxyphenol, respectively, indicating that the disappearance resulted from the β-O-4 bond cleavage. The disappearance rate of G'G or G'S was in between those of the erythro and threo isomers of GG or GS, respectively. This result seems to be reasonably explained when the steric repulsions of the three staggered conformations are taken into consideration. The disappearance rate of G'G or G'S increased, but the increment became moderate with increasing hydroxide concentration.


Biopsy material from 46 cases clinically diagnosed as Mycobacterium ulcerans infection was studied. The disease was found to be most frequent in East Sepik Province, and in the first decade of life. In these 46 cases the histological features were characteristic and acid-fast bacilli were seen in tissue sections.


A 25-year-old patient with testicular teratoma (pathological stage I) relapsed with a solitary, symptomatic metastasis in the right humerus 8 months after unilateral orchiectomy and lymphadenectomy. Treatment consisted in three cycles of standard chemotherapy with etoposide, bleomycin and cisplatin (the last replaced by carboplatin in courses 2 and 3). No supplementary treatment proved necessary to achieve complete remission and complete physical rehabilitation. Only four cases of solitary bone metastasis of testicular germ cell tumors have been reported previously. The present case illustrates that, contrary to previous reports, symptomatic skeletal metastases of germ cell tumors can safely be treated with standard chemotherapy alone.


For experiments at the torque meter, flies are kept on standard fly medium at 25°C and 60% humidity with a 12hr light/12hr dark regime. A standardized breeding regime assures proper larval density and age-matched cohorts. Cold-anesthetized flies are glued with head and thorax to a triangle-shaped hook the day before the experiment. Attached to the torque meter via a clamp, the fly's intended flight maneuvers are measured as the angular momentum around its vertical body axis. The fly is placed in the center of a cylindrical panorama to accomplish stationary flight. An analog to digital converter card feeds the yaw torque signal into a computer which stores the trace for later analysis. The computer also controls a variety of stimuli which can be brought under the fly's control by closing the feedback loop between these stimuli and the yaw torque trace. Punishment is achieved by applying heat from an adjustable infrared laser.


Epilepsy is a dynamic and complex neurological disease affecting about 1% of the worldwide population, among which 30% of the patients are drug-resistant. Epilepsy is characterized by recurrent episodes of paroxysmal neural discharges (the so-called seizures), which manifest themselves through a large-amplitude rhythmic activity observed in depth-EEG recordings, in particular in local field potentials (LFPs). The signature characterizing the transition to seizures involves complex oscillatory patterns, which could serve as a marker to prevent seizure initiation by triggering appropriate therapeutic neurostimulation methods. To investigate such protocols, neurophysiological lumped-parameter models at the mesoscopic scale, namely neural mass models, are powerful tools that not only mimic the LFP signals but also give insights on the neural mechanisms related to different stages of seizures. Here, we analyze the multiple time-scale dynamics of a neural mass model and explain the underlying structure of the complex oscillations observed before seizure initiation. We investigate population-specific effects of the stimulation and the dependence of stimulation parameters on synaptic timescales. In particular, we show that intermediate stimulation frequencies (>20 Hz) can abort seizures if the timescale difference is pronounced. Those results have the potential in the design of therapeutic brain stimulation protocols based on the neurophysiological properties of tissue.


Vitex trifolia or locally known as lemuni, is well documented/or its medicinal properties including anticancer, antibacterial and wound healing. For years, the leaves and flowers were consumed for anti-aging and general well-being. It is also commonly served as nutraceuticals to post-partum women during their confinement period. Previous study showed that V. trifolia possesses high antioxidant properties that could prevent oxidative stress related diseases such as cancer, atherosclerosis, diabetes and many more. From the literature, V. trifolia leaves are used as poultice for rheumatic pains, sprains, antithelmintics and inflammations. Meanwhile, the fruits are utilised in amenorrhea. The roots, on the other hand, are used for the treatment of cough and fever. The plant is known to possess pharmacologically-active constituents such as the essential oil, halimanetype diterpenes, flavonoids, triterpenes, lignans, iridoids and ecdysteroids. Review papers were consistently published to justify the non-exhaustive biological exploration of this genus. Nevertheless, only 11 per cent of the total Vitex species were phytochemically examined. Apart from being eaten raw or blanched, Vitex is also taken as a food colourant in preparing lemuni rice. The process of making lemuni rice is quite tedious. First, the leaves and flowers are picked and washed. Both parts are then ground with water and sieved to give a bluish extract which is then mixed with rice and boiled to cook Hence, the Vitex pouch is introduced to provide an easy way to prepare lemuni rice. This packaging is designed to enclose Vitex samples in a pouch that simply can be placed together with rice and boiled to cook Such instant preparation will hopefully promote the consumption oflemuni rice among busy locals. Future plans include international marketing and production of other Vitex nutritional products.


Background Skin ulcers are an important cause of morbidity and mortality everywhere in the world and occur due to several causes, including diabetes mellitus, peripheral neuropathy, immobility, pressure, arteriosclerosis, infections, and venous insufficiency. Ulcers are lesions that fail to undergo an orderly healing process and produce functional and anatomical integrity in the expected time. In most cases, the methods of analysis used nowadays are rudimentary, which leads to errors and the use of invasive and uncomfortable techniques on patients. There are many studies that use a convolutional neural network to classify the different tissues in a wound. To obtain good results, the network must be trained with a correctly labeled data set by an expert in wound assessment. Typically, it is difficult to label pixel by pixel using a professional photo editor software, as this requires extensive time and effort from a health professional. Objective The aim of this paper is to implement a new, fast, and accurate method of labeling wound samples for training a neural network to classify different tissues. Methods We developed a support tool and evaluated its accuracy and reliability. We also compared the support tool classification with a digital gold standard (labeling the data with an image editing software). Results The obtained comparison between the gold standard and the proposed method was 0.9789 for background, 0.9842 for intact skin, 0.8426 for granulation tissue, 0.9309 for slough, and 0.9871 for necrotic. The obtained speed on average was 2.6, compared to that of an advanced image editing user. Conclusions This method increases tagging speed on average compared to an advanced image editing user. This increase is greater with untrained users. The samples obtained with the new system are indistinguishable from the samples made with the gold standard.


Virtual Reality (VR) and Augmented Reality (AR) have revolutionized technology and taken the world by storm. They established the foundation for numerous future innovations. Virtual and augmented reality are now widely employed to improve user experiences in various areas. Over time, more and more companies and businesses have begun to use this cutting-edge technology to improve their products and services. Recently, the attention to VR and AR has exploded with the concept "Metaverse" surfacing in mainstream media. Many major companies have already set their goals in motion and are working on building the core of their metaverses. This review paper focuses on explaining the concept of the metaverse, its history, and its associated benefits. Through a survey, it helps understand people's concerns with the metaverse and how it can impact and affect humans mentally, physically, and psychologically. The analysis of this paper can help humans prepare themselves for what the new technologies have to offer, in addition to assisting companies in building a flawless metaverse.


A retrospective review of 552 patients with clinical stage I primary cutaneous malignant melanomas was undertaken comparing margins of resection and local recurrence between 1966 and 1981. The overall local recurrence rate was 8 per 552 (1.45 percent). We observed no instances of local recurrence in lesions less than 1.40 mm thick with resection margins of at least 1 cm. A comparison of resection margins greater than 2 cm versus less than 2 cm for lesions less than 1.00 mm thick showed no difference at the 0.05 level of significance for local recurrence (0 per 228 versus 2 per 154; 1.3 percent) or survival. While narrower margins of resection for thinner, low-risk stage I malignant melanomas appear safe, the exact minimum margin of resection needed to satisfy both oncologic and cosmetic considerations, whether 1 or 2 cm, will need to be determined by a large prospective, randomized study.


Light is considered by many investigators to be the primary Zeitgeber for most physiologic rhythms. In order to study the effects on biorhythms of changing photoperiods and to provide information on the nature of the wave forms and the mechanisms of entrainment, unrestrained male monkeys (Cebus albifrons, Macaca nemestrina) were maintained in a sound-proofed environmental chamber. The Cebus was initially maintained on a 12L:12D schedule; it was subjected to a 180 degrees phase shift for 14 days, then returned to the original photoperiod. In two experiments (24 days; 27 days each) the same monkey was again maintained on a 12L:12D schedule which was gradually altered to a constant light environment. Deep body temperature (DBT) data were obtained with miniature radiotransmitters. Locomotor activity (LMA) was measured by strain gauges. Under the 12L:12D regimens the Macaca DBT cycles were uniform as to phase and wave form for over 60 weeks. These wave forms were analyzed by the use of periodogram and correlogram analyses and by fitting to the Volterra Integro-Differential Equation. Phase angle relationships between Zeitgeber and physiologic parameters were characterized. After the photoperiod phase shift the DBT cycle rephased in about 9 days. During the rephasing process the wave form changed. The shapes of the wave forms of DBT and activity were maintained with increasing light until an 18L:6D photoperiod was reached. The rhythms were entrained to the onset of darkness rather than lights on. Major and minor periods of LMA were detected. Hysteresis diagrams showed that DBT led the onset of major LA by 6 hr and the end of major activity by 2 hr.


This paper proposes two syntactic positions for the wide range of Cantonese sentence-final particles that occur in the CP domain. The first position that I argue for is identified with the Force head (SFP1) of the C space (à la Rizzi 1997) which hosts particles that express speech acts and speaker-oriented modality. The second position (SFP2) is an iterative head located lower than the higher Topic. This proposal not only captures facts about the co-occurrence and ordering restrictions of particle clusters, but also some previously unobserved behaviours of particles with quantified noun phrases and different types of questions.


BACKGROUND/AIM
Maxillofacial injuries are among the commonest forms of body injuries. There are three divisions, namely, facial bone fractures, soft tissue injuries, and dentoalveolar injuries. Etiologies include motor vehicle accidents, assaults, falls, and sporting injuries. The aim of this study was to determine the profiles including the causes of maxillofacial injuries seen in an urban government hospital in the mainland of Penang State, Malaysia.

MATERIALS AND METHODS
This was a cross-sectional study that recruited cases reported within a period of 1 year. The source population was maxillofacial injury patients presenting to the Oral and Maxillofacial Surgery Department of an urban hospital in the Penang Mainland, North Malaysia between May 2007 and May 2008. Cases of patients involved in accidents that occurred outside the reference vicinity were excluded. A case report form was developed and completed by the attending clinicians. Data were analyzed using spss version 12.0.

RESULTS
A total of 194 cases were studied, with the mean patient age being 27.8 (SD 15.20) years. The majority of patients were Malay men between 20 and 29 years of age. The main cause of injury was motorcycle accident (53.6%). The commonest injury (in isolation/combination with other injuries) involved the soft tissues (87.2%), dentoalveolar region (33.4%), and facial bones (23.9%). Laceration was the commonest soft tissue injury, and crown fracture was the most frequent dentoalveolar injury. The facial bone that was most highly involved in the injury was the zygoma. Subjects involved in motorcycle accidents had a significantly higher incidence of sustaining facial bone fractures.

CONCLUSIONS
Motorcycle accidents were the commonest cause of maxillofacial injuries in the Penang Mainland, Malaysia. Most patients were young men. Hence, it is prudent to reinforce appropriate road safety and awareness interventions particularly focusing young male motorcyclists so as to reduce the risk of accidents.


This report outlines the long-term outcome after successful sealing of a coronary perforation with a covered stent in a patient with aspirin allergy.


To the Editor.— The problem of suicide among psychiatrists deserves more serious thought than that in your admonition to the "suicide-prone healer of the mind": "Psychiatrist, Mind Thy Psyche" ( 218 :1823, 1971). Does working the specialty of psychiatry in some way predispose an individual to suicide, or does psychiatry attract more suicide-prone physicians? If the former is true, what is it that predisposes? If the latter, how can these self-assaultive people be identified among applicants for psychiatric training? Flippant cliches will not answer these questions.


Possible M-type contact binaries were investigated by selecting W UMa-type variables with orbital periods below the 0.22-day cutoff. Gaia parallaxes were combined with Gaia and 2MASS photometry to obtain G and J-band absolute magnitudes of 674 red variable stars catalogued as contact binaries in the VSX database. The absolute magnitude of main sequence cool dwarfs varies strongly with spectral type, which was used to create a selection of 218 systems with primaries potentially of spectral types M0-M3. Lightcurves of the 46 systems with lowest near-infrared luminosities were inspected individually to confirm or reject the W UMa classification where possible. The extinction limits and amplitudes were combined with the calculated absolute magnitudes in order to set upper limits for the masses of the primary components. This is achieved via the consideration that the luminosity of the primary is no less than that of a main sequence star of the same mass. For 26 possible contact binaries the mass of the primary was limited to less than 0.5 solar masses with some systems having upper limits for the primary as low as 0.35 solar masses. These rare systems are intriguing targets for more detailed observations since they are on the low-mass end of the contact binary distribution and their formation and evolution are still unclear.


This paper proposes an energy saving control method of periodic motions composed of multi-frequency components based on adaptive stiffness optimization for mechanical systems. In the case of sinusoidal motions, the concept of resonance can be easily applied to determine an optimal stiffness. This paper tries to extend resonance to deal with periodic motions composed of multi-frequency components. For this purpose, we define a cost function, which represents an amount of actuator torque. Next, an optimal stiffness is defined as the stiffness that minimizes the cost function. The relationship between the optimal stiffness and the desired motions is analytically derived. Based on the preparations, we propose two types of controller. These controllers generate the desired motions using the least amount of actuator torque as possible by optimizing the stiffness adaptively. The controllers work well without using parameters of the objective systems. Stability and effectiveness of the stiffness optimization are proved mathematically. Simulation results demonstrate the effectiveness of the proposed method.


It is important to know whether the human population includes genetically predisposed radiosensitive subsets. In vitro studies have shown that cells from individuals homozygous for ataxia telangiectasia (A-T) are much more radiosensitive than cells from unaffected individuals. Although cells heterozygous for the ATM gene (ATM+/−) may be slightly more radiosensitive in vitro, it remained to be determined whether the greater susceptibility of ATM+/− cells translates into an increased sensitivity for late effects in vivo, though there is a suggestion that radiotherapy patients that are heterozygous for the ATM gene may be more at risk of developing late normal tissue damage. We chose cataractogenesis in the lens as a means to assay for the effects of ATM deficiency in a late-responding tissue. One eye of wild-type, Atm heterozygous and homozygous knockout mice was exposed to 0.5-, 1.0-, 2.0-, or 4.0-Gy x rays. The animals were followed weekly for cataract development by conventional slit-lamp biomicroscopy. Cataract development in the animals of all three groups was strongly dependent on dose. The lenses of homozygous mice were the first to opacify at any given dose. Most important in the present context is that cataracts appeared earlier in the heterozygous versus wild-type animals. The data suggest that ATM heterozygotes in the human population may also be radiosensitive. This may influence the choice of individuals destined to be exposed to higher than normal doses of radiation, such as astronauts, and may also suggest that radiotherapy patients who are ATM heterozygotes could be predisposed to increased late normal tissue damage.


Multiple sclerosis (MS) is a chronic, inflammatory, and demyelinating disease of the central nervous system (CNS), which is likely to be mediated by autoaggressive immunity. Treatments of MS that may beneficially influence the disease course consist of Avonex (interferon-β; IFN-β), and Copaxone (glatiramer acetate; GA). Studies in experimental autoimmune encephalomyelitis (EAE), a commonly used experimental model of human MS, have demonstrated a crucial role of CD4CD25 T regulatory (Tr) cells in suppressing autoreactive T cells and promoting peripheral tolerance. Recent studies have shown that Tr cells inhibiting the proliferation and cytokine secretion by CD4 T cells, are enriched in the CD25 cells among CD4 T cells. It is not yet known if circulating CD4CD25 Tr cells are involved in MS. The aims of this study were to: 1. identify and quantify CD4CD25 and CD4CD25 Tr cells among blood CD4 T cells, and proportions of CD4CD25 Tr cells expressing cell surface and intracellular molecules in patients with untreated MS vs MS treated with either IFN1a or GA or the combination of IFN-1a+GA, vs healthy controls (HC); 2. to correlate the properties of circulating CD4CD25 Tr cells with lesion load (LL) and gadolinium (Gd) enhancement detected by magnetic resonance imaging (MRI) of the brain in untreated MS patients. 3. analyse the in-vitro influence of GA upon CD4CD25 Tr cells from MS patients vs from HC. 4. examine whether a functional deficit inherent to CD4CD25 Tr cells occurred in untreated MS patients vs HC, in terms of the ability of Tr cells to suppress the production of pro-inflammatory cytokines by blood mononuclear cells (MNC) upon autoor foreign-antigenic stimulation. These studies demonstrated that i) there are no alterations of frequency of circulating CD4CD25 and CD4CD25 Tr cells nor of the proportions of CD4CD25 Tr cells expressing CD45RO, HLA-DR, CD95, CTLA-4 or IL-10 in MS patients compared to HC; ii) the frequency of CD4CD25 Tr cells, and the proportions of IL-10 expressing CD4CD25 Tr cells are elevated in MS patients with Gd-enhancing lesions; iii) the proportion of CXCR3 CD4 T cells is lower in the group of patients with Gd-enhancing lesions on T1-weighted images, as compared to the group with no Gd-enhancing lesions; iv) GA, in vitro elevates the levels of IL-10 producing blood CD4CD25 Tr cells in both MS patients and HC, and; v) CD4CD25 Tr cells augments the secretion of Th1 cytokines IFN-γ and IL-2, but not of Th2 cytokine IL-13 in response to MBP, equally in MS patients and HC, suggesting that the functional activity of CD4CD25 Tr cells in terms of controlling Th1 and Th2 cytokine secretions in response to MBP, is not significantly altered in MS.