Analysis of alternative signaling pathways of endoderm induction of human embryonic stem cells identifies context specific differences

Background: Lineage specific differentiation of human embryonic stem cells (hESCs) is largely mediated by specific growth factors and extracellular matrix molecules. Growth factors initiate a cascade of signals which control gene transcription and cell fate specification. There is a lot of interest in inducing hESCs to an endoderm fate which serves as a pathway towards more functional cell types like the pancreatic cells. Research over the past decade has established several robust pathways for deriving endoderm from hESCs, with the capability of further maturation. However, in our experience, the functional maturity of these endoderm derivatives, specifically to pancreatic lineage, largely depends on specific pathway of endoderm induction. Hence it will be of interest to understand the underlying mechanism mediating such induction and how it is translated to further maturation. In this work we analyze the regulatory interactions mediating different pathways of endoderm induction by identifying co-regulated transcription factors.Results: hESCs were induced towards endoderm using activin A and 4 different growth factors (FGF2 (F), BMP4 (B), PI3KI (P), and WNT3A (W)) and their combinations thereof, resulting in 15 total experimental conditions. At the end of differentiation each condition was analyzed by qRT-PCR for 12 relevant endoderm related transcription factors (TFs). As a first approach, we used hierarchical clustering to identify which growth factor combinations favor up-regulation of different genes. In the next step we identified sets of co-regulated transcription factors using a biclustering algorithm. The high variability of experimental data was addressed by integrating the biclustering formulation with bootstrap re-sampling to identify robust networks of co-regulated transcription factors. Our results show that the transition from early to late endoderm is favored by FGF2 as well as WNT3A treatments under high activin. However, induction of late endoderm markers is relatively favored by WNT3A under high activin.Conclusions: Use of FGF2, WNT3A or PI3K inhibition with high activin A may serve well in definitive endoderm induction followed by WNT3A specific signaling to direct the definitive endoderm into late endodermal lineages. Other combinations, though still feasible for endoderm induction, appear less promising for pancreatic endoderm specification in our experiments. © 2012 Mathew et al.; licensee BioMed Central Ltd

Numerical studies towards practical large-eddy simulation

Large-eddy simulation developments and validations are presented for an improved simulation of turbulent internal flows. Numerical methods are proposed according to two competing criteria: numerical qualities (precision and spectral characteristics), and adaptability to complex configurations. First, methods are tested on academic test-cases, in order to abridge with fundamental studies. Consistent results are obtained using adaptable finite volume method, with higher order advection fluxes, implicit grid filtering and "low-cost" shear-improved Smagorinsky model. This analysis particularly focuses on mean flow, fluctuations, two-point correlations and spectra. Moreover, it is shown that exponential averaging is a promising tool for LES implementation in complex geometry with deterministic unsteadiness. Finally, adaptability of the method is demonstrated by application to a configuration representative of blade-tip clearance flow in a turbomachine

Quantum nondemolition measurement of mechanical motion quanta

The fields of opto- and electromechanics have facilitated numerous advances in the areas of precision measurement and sensing, ultimately driving the studies of mechanical systems into the quantum regime. To date, however, the quantization of the mechanical motion and the associated quantum jumps between phonon states remains elusive. For optomechanical systems, the coupling to the environment was shown to preclude the detection of the mechanical mode occupation, unless strong single photon optomechanical coupling is achieved. Here, we propose and analyse an electromechanical setup, which allows to overcome this limitation and resolve the energy levels of a mechanical oscillator. We find that the heating of the membrane, caused by the interaction with the environment and unwanted couplings, can be suppressed for carefully designed electromechanical systems. The results suggest that phonon number measurement is within reach for modern electromechanical setups.Comment: 8 pages, 5 figures plus 24 pages, 11 figures supplemental materia

Probing the Role of Magnetic-Field Variations in NOAA AR 8038 in Producing Solar Flare and CME on 12 May 1997

We carried out a multi-wavelength study of a CME and a medium-size 1B/C1.3 flare occurring on 12 May 1997. We present the investigation of magnetic-field variations in the NOAA Active Region 8038 which was observed on the Sun during 7--16 May 1997. Analyses of H{\alpha} filtergrams and MDI/SOHO magnetograms revealed continual but discrete surge activity, and emergence and cancellation of flux in this active region. The movie of these magnetograms revealed two important results that the major opposite polarities of pre-existing region as well as in the emerging flux region (EFR) were approaching towards each other and moving magnetic features (MMF) were ejecting out from the major north polarity at a quasi-periodicity of about ten hrs during 10--13 May 1997. These activities were probably caused by the magnetic reconnection in the lower atmosphere driven by photospheric convergence motions, which were evident in magnetograms. The magnetic field variations such as flux, gradient, and sunspot rotation revealed that free energy was slowly being stored in the corona. The slow low-layer magnetic reconnection may be responsible for this storage and the formation of a sigmoidal core field or a flux rope leading to the eventual eruption. The occurrence of EUV brightenings in the sigmoidal core field prior to the rise of a flux rope suggests that the eruption was triggered by the inner tether-cutting reconnection, but not the external breakout reconnection. An impulsive acceleration revealed from fast separation of the H{\alpha} ribbons of the first 150 seconds suggests the CME accelerated in the inner corona, which is consistent with the temporal profile of the reconnection electric field. In conclusion, we propose a qualitative model in view of framework of a solar eruption involving, mass ejections, filament eruption, CME, and subsequent flare.Comment: 8 figures, accepted for publication in Solar Physic

Simulating the Software Development Lifecycle: The Waterfall Model

(1) Background: This study employs a simulation-based approach, adapting the waterfall model, to provides estimates for projects and individual phase completion times. Additionally, it pin-points potential efficiency issues stemming from a suboptimal resource level. It further demonstrates how one can go on to identify a resource level that effectively eliminates bottlenecks and curtails the idle time of resources. (2) Methods: We implement our software development lifecycle using SimPy, a discrete-event simulation framework written in Python. Our model is executed on 100 projects of varying sizes over three stages. The first, pre-optimization, provides insight based on the initial set of resources. This is followed by the optimization stage, which serves to identify the optimal number of resources to eliminate bottlenecks and minimize idle time. The third stage, post-optimization, evaluates the resource optimized model. (3) Results: The analysis of the simulation-generated data reveals the presence of resource bottlenecks during the pre-optimization stage, particularly in the implementation phase. These dissipate after optimization. (4) Conclusions: The findings emphasize the advantage of using simulation as a safe and effective way to experiment and plan for software development projects. Such simulations also allow those man-aging software development projects to make accurate, evidence-based projections as to phase and project completion times and identify optimal resource levels and their interplay. In particular, understanding the tradeoffs between experiencing delayed completion times and procuring additional resources to alleviate any bottlenecks

Dynamic biospeckle analysis, a new tool for the fast screening of plant nematicide selectivity

Background: Plant feeding, free-living nematodes cause extensive damage to plant roots by direct feeding and, in the case of some trichodorid and longidorid species, through the transmission of viruses. Developing more environmentally friendly, target-specific nematicides is currently impeded by slow and laborious methods of toxicity testing. Here, we developed a bioactivity assay based on the dynamics of light 'speckle' generated by living cells and we demonstrate its application by assessing chemicals' toxicity to different nematode trophic groups.Results: Free-living nematode populations extracted from soil were exposed to methanol and phenyl isothiocyanate (PEITC). Biospeckle analysis revealed differing behavioural responses as a function of nematode feeding groups. Trichodorus nematodes were less sensitive than were bacterial feeding nematodes or non-trichodorid plant feeding nematodes. Following 24 h of exposure to PEITC, bioactivity significantly decreased for plant and bacterial feeders but not for Trichodorus nematodes. Decreases in movement for plant and bacterial feeders in the presence of PEITC also led to measurable changes to the morphology of biospeckle patterns.Conclusions: Biospeckle analysis can be used to accelerate the screening of nematode bioactivity, thereby providing a fast way of testing the specificity of potential nematicidal compounds. With nematodes' distinctive movement and activity levels being visible in the biospeckle pattern, the technique has potential to screen the behavioural responses of diverse trophic nematode communities. The method discriminates both behavioural responses, morphological traits and activity levels and hence could be used to assess the specificity of nematicidal compounds.</p

Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition

Multiwavelength studies of MHD waves in the solar chromosphere: An overview of recent results

The chromosphere is a thin layer of the solar atmosphere that bridges the relatively cool photosphere and the intensely heated transition region and corona. Compressible and incompressible waves propagating through the chromosphere can supply significant amounts of energy to the interface region and corona. In recent years an abundance of high-resolution observations from state-of-the-art facilities have provided new and exciting ways of disentangling the characteristics of oscillatory phenomena propagating through the dynamic chromosphere. Coupled with rapid advancements in magnetohydrodynamic wave theory, we are now in an ideal position to thoroughly investigate the role waves play in supplying energy to sustain chromospheric and coronal heating. Here, we review the recent progress made in characterising, categorising and interpreting oscillations manifesting in the solar chromosphere, with an impetus placed on their intrinsic energetics.Comment: 48 pages, 25 figures, accepted into Space Science Review

Defining the local nerve blocks for feline distal thoracic limb surgery: a cadaveric study

Though controversial, onychectomy remains a commonly performed distal thoracic limb surgical procedure in cats. Peripheral nerve block techniques have been proposed in cats undergoing onychectomy but evidence of efficacy is lacking. Preliminary tests of the described technique using cadavers resulted in incomplete staining of nerves. The aim of this study was to develop nerve block methods based on cadaveric dissections and test these methods with cadaveric dye injections

Electron beam-formed ferromagnetic defects on MoS2 surface along 1T phase transition

1 T phase incorporation into 2H-MoS2 via an optimal electron irradiation leads to induce a weak ferromagnetic state at room temperature, together with the improved transport property. In addition to the 1T-like defects, the electron irradiation on the cleaved MoS2 surface forms the concentric circletype defects that are caused by the 2 H/1 T phase transition and the vacancies of the nearby S atoms of the Mo atoms. The electron irradiation-reduced bandgap is promising in vanishing the Schottky barrier to attaining spintronics device. The simple method to control and improve the magnetic and electrical properties on the MoS2 surface provides suitable ways for the low-dimensional device applications.ope