Modulatory roles of microRNAs in the regulation of different signalling pathways in large bowel cancer stem cells

There are emerging data to suggest that microRNAs (miRNAs) have significant roles in regulating the function of normal cells and cancer stem cells (CSCs). This review aims to analyse the roles of miRNAs in the regulation of colon CSCs through their interaction with various signalling pathways. Studies showed a large number of miRNAs that are reported to be deregulated in colon CSCs. However, few of the studies available were able to outline the function of miRNAs in colon CSCs and uncover their signalling pathways. From those miRNAs, which are better described, miR-21 followed by miR-34, miR-200 and miR-215 are the most reported miRNAs to have roles in colon CSC regulation. In particular, miRNAs have been reported to regulate the stemness features of colon CSCs mainly via Wnt/B-catenin and Notch signalling pathways. Additionally, miRNAs have been reported to act on processes involving CSCs through cell cycle regulation genes and epithelial-mesenchymal transition. The relative paucity of data available on the significance of miRNAs in CSCs means that new studies will be of great importance to determine their roles and to identify the signalling pathways through which they operate. Such studies may in future guide further research to target these genes for more effective cancer treatment. miRNAs were shown to regulate the function of cancer stem cells in large bowel cancer by targeting a few key signalling pathways in cells.

Influence of tool rake angle on the quality of pure magnesium chip-consolidated product

Chips were produced by orthogonal Cutting of cast pure magnesium billet with three different tool rake angles viz., -15 degrees, -5 degrees and +15 degrees on a lathe. Chip consolidation by solid state recycling technique involved cold compaction followed by hot extrusion. The extruded products were characterized for microstructure and mechanical properties. Chip-consolidated products from -15 degrees rake angle tools showed 19% increase in tensile strength, 60% reduction ingrain size and 12% increase in hardness compared to +15 degrees rake chip-consolidated product indicating better chip bonding and grain refinement. Microstructure of the fracture specimen Supports the abovefinding. On the overall, the present work high lights the importance of tool take angle in determining the quality of the chip-consolidated products. (C) 2009 Elsevier B.V. All rights reserved.

A Low-Complexity Near-ML Performance Achieving Algorithm for Large MIMO Detection

In this paper, we present a low-complexity, near maximum-likelihood (ML) performance achieving detector for large MIMO systems having tens of transmit and receive antennas. Such large MIMO systems are of interest because of the high spectral efficiencies possible in such systems. The proposed detection algorithm, termed as multistage likelihood-ascent search (M-LAS) algorithm, is rooted in Hopfield neural networks, and is shown to possess excellent performance as well as complexity attributes. In terms of performance, in a 64 x 64 V-BLAST system with 4-QAM, the proposed algorithm achieves an uncoded BER of 10(-3) at an SNR of just about 1 dB away from AWGN-only SISO performance given by Q(root SNR). In terms of coded BER, with a rate-3/4 turbo code at a spectral efficiency of 96 bps/Hz the algorithm performs close to within about 4.5 dB from theoretical capacity, which is remarkable in terms of both high spectral efficiency as well as nearness to theoretical capacity. Our simulation results show that the above performance is achieved with a complexity of just O(NtNt) per symbol, where N-t and N-tau denote the number of transmit and receive antennas.

Additively manufactured device for dynamic culture of large arrays of 3D tissue engineered constructs

The ability to test large arrays of cell and biomaterial combinations in 3D environments is still rather limited in the context of tissue engineering and regenerative medicine. This limitation can be generally addressed by employing highly automated and reproducible methodologies. This study reports on the development of a highly versatile and upscalable method based on additive manufacturing for the fabrication of arrays of scaffolds, which are enclosed into individualized perfusion chambers. Devices containing eight scaffolds and their corresponding bioreactor chambers are simultaneously fabricated utilizing a dual extrusion additive manufacturing system. To demonstrate the versatility of the concept, the scaffolds, while enclosed into the device, are subsequently surface-coated with a biomimetic calcium phosphate layer by perfusion with simulated body fluid solution. 96 scaffolds are simultaneously seeded and cultured with human osteoblasts under highly controlled bidirectional perfusion dynamic conditions over 4 weeks. Both coated and noncoated resulting scaffolds show homogeneous cell distribution and high cell viability throughout the 4 weeks culture period and CaP-coated scaffolds result in a significantly increased cell number. The methodology developed in this work exemplifies the applicability of additive manufacturing as a tool for further automation of studies in the field of tissue engineering and regenerative medicine.

The importance of context in engaging students large first year management classes: A case study

Engaging large first year classes in tertiary education poses a number of significant challenges, most of which have been discussed by others. One area that has not received the kind of attention that it warrants is the context within which the engagement activities take place. This paper examines both the processes used to engage a large first year management class in a major city university and how the context of the classes shaped activities and student responses to these activities. It was recognised that students had certain types of learning styles, but given the total number of students (in excess of 1200) it was realised that is would be impossible to cater to all possibilities. A key outcome of the exercise was the importance of context in shaping student behaviours.

Heritability analysis of surface-based cortical thickness estimation on a large twin cohort

The aim of this paper is to assess the heritability of cerebral cortex, based on measurements of grey matter (GM) thickness derived from structural MR images (sMRI). With data acquired from a large twin cohort (328 subjects), an automated method was used to estimate the cortical thickness, and EM-ICP surface registration algorithm was used to establish the correspondence of cortex across the population. An ACE model was then employed to compute the heritability of cortical thickness. Heritable cortical thickness measures various cortical regions, especially in frontal and parietal lobes, such as bilateral postcentral gyri, superior occipital gyri, superior parietal gyri, precuneus, the orbital part of the right frontal gyrus, right medial superior frontal gyrus, right middle occipital gyrus, right paracentral lobule, left precentral gyrus, and left dorsolateral superior frontal gyrus.

Structure of polyamidoamide dendrimers up to limiting generations: A mesoscale description

The polyamidoamide (PAMAM) class of dendrimers was one of the first dendrimers synthesized by Tomalia and co-workers at Dow. Since its discovery the PAMAMs have stimulated many discussions on the structure and dynamics of such hyperbranched polymers. Many questions remain open because the huge conformation disorder combined with very similar local symmetries have made it difficult to characterize experimentally at the atomistic level the structure and dynamics of PAMAM dendrimers. The higher generation dendrimers have also been difficult to characterize computationally because of the large size (294852 atoms for generation 11) and the huge number of conformations. To help provide a practical means of atomistic computational studies, we have developed an atomistically informed coarse-grained description for the PAMAM dendrimer. We find that a two-bead per monomer representation retains the accuracy of atomistic simulations for predicting size and conformational complexity, while reducing the degrees of freedom by tenfold. This mesoscale description has allowed us to study the structural properties of PAMAM dendrimer up to generation 11 for time scale of up to several nanoseconds. The gross properties such as the radius of gyration compare very well with those from full atomistic simulation and with available small angle x-ray experiment and small angle neutron scattering data. The radial monomer density shows very similar behavior with those obtained from the fully atomistic simulation. Our approach to deriving the coarse-grain model is general and straightforward to apply to other classes of dendrimers.

Why do birds participate in mixed-species foraging flocks? A large-scale synthesis

Mixed-species flocks of foraging birds have been documented from terrestrial habitats all over the world and are thought to form for either improved feeding efficiency or better protection from predators. Two kinds of flock participants are recognized: those that join other species ('followers') and are therefore likely to be the recipients of the benefits of flock participation and those that are joined ('leaders'). Through comparative analyses, using a large sample of flocks from around the world, we show that (1) 'followers' tend to be smaller, more insectivorous, and feed in higher strata than matched species that participate in flocks to a lesser extent and (2) 'leaders' tend to be cooperative breeders more often than matched species that are not known to lead flocks. Furthermore, meta-analyses of published results from across the world showed that bird species in terrestrial mixed-species flocks increase foraging rates and reduce vigilance compared to when they are solitary or in conspecific groups. Moreover, the increase in foraging rates is seen only with flock followers and not flock leaders. These findings suggest a role for predation in the evolution of mixed-species flocking. Species that are vulnerable to predation follow species whose vigilance they can exploit. By doing so, they are able to reduce their own vigilance and forage at higher rates. (C) 2009 The Association for the Study of Animal Behaviour. Published by Elsevier Ltd. All rights reserved.

Evaluation of Moderate-Resolution Imaging Spectroradiometer (MODIS) collection 004 (C004) aerosol retrievals at Kanpur, Indo-Gangetic basin

[1] We have compared the spectral aerosol optical depth (AOD, tau lambda) and aerosol fine mode fraction (AFMF) of Collection 004 (C004) derived from Moderate-Resolution Imaging Spectroradiometer (MODIS) on board National Aeronautics and Space Administration's (NASA) Terra and Aqua platforms with that obtained from Aerosol Robotic Network (AERONET) at Kanpur (26.45 degrees N, 80.35 degrees E), India for the period 2001-2005. The spatially-averaged (0.5 degrees x 0.5 degrees centered at AERONET sunphotometer) MODIS Level-2 aerosol parameters (10 km at nadir) were compared with the temporally averaged AERONET-measured AOD (within +/- 30 minutes of MODIS overpass). We found that MODIS systematically overestimated AOD during the pre-monsoon season (March to June, known to be influenced by dust aerosols). The errors in AOD at 0.66 mu m were correlated with the apparent reflectance at 2.1 mu m (rho*(2.1)) which MODIS C004 uses to estimate the surface reflectance in the visible channels (rho(0.47) = rho*(2.1)/ 4, rho(0.66) = rho*(2.1)/ 2). The large errors in AOD (Delta tau(0.66) > 0.3) are found to be associated with the higher values of rho*(2.1) (0.18 to 0.25), where the uncertainty in the ratios of reflectance is large (Delta rho(0.66) +/- 0.04, Delta rho(0.47) +/- 0.02). This could have resulted in lower surface reflectance, higher aerosol path radiance and thus lead to overestimation in AOD. While MODIS-derived AFMF has binary distribution (1 or 0) with too low (AFMF < 0.2) during dust-loading period, and similar to 1 for the rest of the retrievals, AERONET showed range of values (0.4 to 0.9). The errors in tau(0.66) were also high in the scattering angle range 110 degrees - 140 degrees, where the optical effects of nonspherical dust particles are different from that of spherical particles.

Kernels for large margin time-series classification

In this paper we propose a novel family of kernels for multivariate time-series classification problems. Each time-series is approximated by a linear combination of piecewise polynomial functions in a Reproducing Kernel Hilbert Space by a novel kernel interpolation technique. Using the associated kernel function a large margin classification formulation is proposed which can discriminate between two classes. The formulation leads to kernels, between two multivariate time-series, which can be efficiently computed. The kernels have been successfully applied to writer independent handwritten character recognition.

Iodine Brachytherapy for Large Uveal Melanomas

Uveal melanoma is the most common primary intraocular malignancy in adults. Vision in the affected eye is threatened by both the tumor and side-effects from the treatments currently available. Poor prognosis for saving vision increases with tumor size and, consequently, enucleation has been the treatment of choice for large uveal melanomas in most centers. However, increasing evidence suggests that no survival benefit is gained (nor lost) by enucleation as compared to eye-conserving methods. The Helsinki University Eye Hospital has since 1990 offered episcleral iodine-125 plaque brachytherapy (IBT) for all patients unwilling to undergo enucleation for a large uveal melanoma. The primary aim of this study was to assess survival, local tumor recurrence and preservation of the eye and vision after IBT in a population-based series of 97 patients with uveal melanomas classified as large by the Collaborative Ocular Melanoma Study (COMS) criteria. Further aims included reporting the incidence of side-effects and assessing the role of intraocular dose distribution and clinical risk factors in their development. Finally, means to improve the current treatment were investigated by using computer models to compare existing plaques with collimating ones and by comparing the outcome of a subgroup of 54 IBT patients with very thick tumors with 33 patients with similarly-sized tumors managed with transscleral local resection (TSR) in Liverpool, United Kingdom. Kaplan-Meier estimates of all-cause and melanoma-specific survival at 5 years after IBT were 62% and 65%, respectively, and visually comparable with the survival experience of patients reported after enucleation by the COMS. Local recurrence developed in 6% of eyes and 84% of eyes were conserved at 5 years. Visual prognosis was guarded with 11% avoiding loss of 20/70 vision and 26% avoiding loss of 20/400 vision in the tumor eye at 2 years. Large tumor height and short distance from the posterior pole were independently associated with loss of vision. Using cumulative incidence analysis to account for competing risks, such as enucleation and metastatic death, the 5-year incidence of cataract after IBT was 79%, glaucoma 60%, optic neuropathy 46%, maculopathy 52%, persistent or recurring retinal detachment (RD) 25%, and vitreous hemorrhage 36%. In multivariate competing risks regression models, increasing tumor height was associated with cataract, iris neovascularization and RD. Maculopathy and optic neuropathy were associated with distance from the tumor to the respective structure. Median doses to the tumor apex, macula and optic disc were 81 Gy (range, 40-158), 79 Gy (range, 12-632), and 83 Gy (range, 10-377), respectively. Dose to the optic disc was independently associated with optic neuropathy, and both dose to the optic disc and dose to the macula predicted vision loss after IBT. Simulated treatment using collimating plaques resulted in clinically meaningful reduction in both optic disc (median reduction, 30 Gy) and macular (median reduction, 36 Gy) doses as compared to the actual treatment with standard plaques. In the subgroup of patients with uveal melanomas classified as large because of tumor height, cumulative incidence analysis revealed that while long-term preservation of 20/70 vision was rare after both IBT and TSR, preservation of 20/400 vision was better after TSR (32% vs. 5% at 5 years). In multivariate logistic regression models, TSR was independently associated with better preservation of 20/400 vision (OR 0.03 at 2 years, P=0.005) No cases of secondary glaucoma were observed after TSR and optic neuropathy was rare. However, local tumor recurrence was more common after TSR than it was after IBT (Cumulative incidence 41% vs. 7% at 5 years, respectively). In terms of survival, IBT seems to be a safe alternative to enucleation in managing large uveal melanomas. Local tumor control is no worse than with medium-sized tumors and the chances of avoiding secondary enucleation are good. Unfortunately, side-effects from radiotherapy are frequent, especially in thick tumors, and long-term prognosis of saving vision is consequently guarded. Some complications can be limited by using collimating plaques and by managing uveal melanomas that are large because of tumor height with TSR instead of IBT. However, the patient must be willing to accept a substantial risk of local tumor recurrence after TSR and it is best suited for cases in which the preservation of vision in the tumor eye is critical.

On the mechanical behavior of compacted pack ice : A theoretical and numerical investigation

Pack ice is an aggregate of ice floes drifting on the sea surface. The forces controlling the motion and deformation of pack ice are air and water drag forces, sea surface tilt, Coriolis force and the internal force due to the interaction between ice floes. In this thesis, the mechanical behavior of compacted pack ice is investigated using theoretical and numerical methods, focusing on the three basic material properties: compressive strength, yield curve and flow rule. A high-resolution three-category sea ice model is applied to investigate the sea ice dynamics in two small basins, the whole Gulf Riga and the inside Pärnu Bay, focusing on the calibration of the compressive strength for thin ice. These two basins are on the scales of 100 km and 20 km, respectively, with typical ice thickness of 10-30 cm. The model is found capable of capturing the main characteristics of the ice dynamics. The compressive strength is calibrated to be about 30 kPa, consistent with the values from most large-scale sea ice dynamic studies. In addition, the numerical study in Pärnu Bay suggests that the shear strength drops significantly when the ice-floe size markedly decreases. A characteristic inversion method is developed to probe the yield curve of compacted pack ice. The basis of this method is the relationship between the intersection angle of linear kinematic features (LKFs) in sea ice and the slope of the yield curve. A summary of the observed LKFs shows that they can be basically divided into three groups: intersecting leads, uniaxial opening leads and uniaxial pressure ridges. Based on the available observed angles, the yield curve is determined to be a curved diamond. Comparisons of this yield curve with those from other methods show that it possesses almost all the advantages identified by the other methods. A new constitutive law is proposed, where the yield curve is a diamond and the flow rule is a combination of the normal and co-axial flow rule. The non-normal co-axial flow rule is necessary for the Coulombic yield constraint. This constitutive law not only captures the main features of forming LKFs but also takes the advantage of avoiding overestimating divergence during shear deformation. Moreover, this study provides a method for observing the flow rule for pack ice during deformation.

Scattering and Refraction as Contrast Mechanisms in X-Ray Imaging

Differentiation of various types of soft tissues is of high importance in medical imaging, because changes in soft tissue structure are often associated with pathologies, such as cancer. However, the densities of different soft tissues may be very similar, making it difficult to distinguish them in absorption images. This is especially true when the consideration of patient dose limits the available signal-to-noise ratio. Refraction is more sensitive than absorption to changes in the density, and small angle x-ray scattering on the other hand contains information about the macromolecular structure of the tissues. Both of these can be used as potential sources of contrast when soft tissues are imaged, but little is known about the visibility of the signals in realistic imaging situations. In this work the visibility of small-angle scattering and refraction in the context of medical imaging has been studied using computational methods. The work focuses on the study of analyzer based imaging, where the information about the sample is recorded in the rocking curve of the analyzer crystal. Computational phantoms based on simple geometrical shapes with differing material properties are used. The objects have realistic dimensions and attenuation properties that could be encountered in real imaging situations. The scattering properties mimic various features of measured small-angle scattering curves. Ray-tracing methods are used to calculate the refraction and attenuation of the beam, and a scattering halo is accumulated, including the effect of multiple scattering. The changes in the shape of the rocking curve are analyzed with different methods, including diffraction enhanced imaging (DEI), extended DEI (E-DEI) and multiple image radiography (MIR). A wide angle DEI, called W-DEI, is introduced and its performance is compared with that of the established methods. The results indicate that the differences in scattered intensities from healthy and malignant breast tissues are distinguishable to some extent with reasonable dose. Especially the fraction of total scattering has large enough differences that it can serve as a useful source of contrast. The peaks related to the macromolecular structure come to angles that are rather large, and have intensities that are only a small fraction of the total scattered intensity. It is found that such peaks seem to have only limited usefulness in medical imaging. It is also found that W-DEI performs rather well when most of the intensity remains in the direct beam, indicating that dark field imaging methods may produce the best results when scattering is weak. Altogether, it is found that the analysis of scattered intensity is a viable option even in medical imaging where the patient dose is the limiting factor.

PROBESYNC: Platform Based Synchronization for Enhanced Life of Large Scale Wireless Sensor Networks

Optimization in energy consumption of the existing synchronization mechanisms can lead to substantial gains in terms of network life in Wireless Sensor Networks (WSNs). In this paper, we analyze ERBS and TPSN, two existing synchronization algorithms for WSNs which use widely different approach, and compare their performance in large scale WSNs each of which consists of different type of platform and has varying node density. We, then, propose a novel algorithm, PROBESYNC, which takes advantage of differences in power required to transmit and receive a message on ERBS and TPSN and leverages the shortcomings of each of these algorithms. This leads to considerable improvement in energy conservation and enhanced life of large scale WSNs.