The Effect of a DNA Damaging Agent on Embryonic Cell Cycles of the Cnidarian Hydractinia echinata

The onset of gastrulation at the Mid-Blastula Transition can accompany profound changes in embryonic cell cycles including the introduction of gap phases and the transition from maternal to zygotic control. Studies in Xenopus and Drosophila embryos have also found that cell cycles respond to DNA damage differently before and after MBT (or its equivalent, MZT, in Drosophila). DNA checkpoints are absent in Xenopus cleavage cycles but are acquired during MBT. Drosophila cleavage nuclei enter an abortive mitosis in the presence of DNA damage whereas post-MZT cells delay the entry into mitosis. Despite attributes that render them workhorses of embryonic cell cycle studies, Xenopus and Drosophila are hardly representative of diverse animal forms that exist. To investigate developmental changes in DNA damage responses in a distant phylum, I studied the effect of an alkylating agent, Methyl Methanesulfonate (MMS), on embryos of Hydractinia echinata. Hydractinia embryos are found to differ from Xenopus embryos in the ability to respond to a DNA damaging agent in early cleavage but are similar to Xenopus and Drosophila embryos in acquiring stronger DNA damage responses and greater resistance to killing by MMS after the onset of gastrulation. This represents the first study of DNA damage responses in the phylum Cnidaria

Anticancer Gene Transfer for Cancer Gene Therapy

Gene therapy vectors are among the treatments currently used to treat malignant tumors. Gene therapy vectors use a specific therapeutic transgene that causes death in cancer cells. In early attempts at gene therapy, therapeutic transgenes were driven by non-specific vectors which induced toxicity to normal cells in addition to the cancer cells. Recently, novel cancer specific viral vectors have been developed that target cancer cells leaving normal cells unharmed. Here we review such cancer specific gene therapy systems currently used in the treatment of cancer and discuss the major challenges and future directions in this field

The Effort of Increasing Reynolds Number in Projection-Based Reduced Order Methods: From Laminar to Turbulent Flows

We present in this double contribution two different reduced order strategies for incompressible parameterized Navier-Stokes equations characterized by varying Reynolds numbers. The first strategy deals with low Reynolds number (laminar flow) and is based on a stabilized finite element method during the offline stage followed by a Galerkin projection on reduced basis spaces generated by a greedy algorithm. The second methodology is based on a full order finite volume discretization. The latter methodology will be used for flows with moderate to high Reynolds number characterized by turbulent patterns. For the treatment of the mentioned turbulent flows at the reduced order level, a new POD-Galerkin approach is proposed. The new approach takes into consideration the contribution of the eddy viscosity also during the online stage and is based on the use of interpolation. The two methodologies are tested on classic benchmark test cases

Non-intrusive polynomial chaos method applied to full-order and reduced problems in computational fluid dynamics: A comparison and perspectives

In this work, Uncertainty Quantification (UQ) based on non-intrusive Polynomial Chaos Expansion (PCE) is applied to the CFD problem of the flow past an airfoil with parameterized angle of attack and inflow velocity. To limit the computational cost associated with each of the simulations required by the non-intrusive UQ algorithm used, we resort to a Reduced Order Model (ROM) based on Proper Orthogonal Decomposition (POD)-Galerkin approach. A first set of results is presented to characterize the accuracy of the POD-Galerkin ROM developed approach with respect to the Full Order Model (FOM) solver (OpenFOAM). A further analysis is then presented to assess how the UQ results are affected by substituting the FOM predictions with the surrogate ROM ones

Three-dimensional printing of porous load-bearing bioceramic scaffolds

This article reports on the use of the binder jetting three-dimensional printing process combined with sintering to process bioceramic materials to form micro- and macroporous three-dimensional structures. Three different glass-ceramic formulations, apatite–wollastonite and two silicate-based glasses, have been processed using this route to create porous structures which have Young’s modulus equivalent to cortical bone and average bending strengths in the range 24–36 MPa. It is demonstrated that a range of macroporous geometries can be created with accuracies of ±0.25 mm over length scales up to 40 mm. Hot-stage microscopy is a valuable tool in the definition of processing parameters for the sintering step of the process. Overall, it is concluded that binder jetting followed by sintering offers a versatile process for the manufacture of load-bearing bioceramic components for bone replacement applications

Administrators in higher education: organizational expansion in a transforming institution

Recent European research has revealed growth in the number of administrators and professionals across different sections of universities—a long established trend in US universities. We build on this research by investigating the factors associated with variation in the proportion of administrators across 761 Higher Education Institutions (HEIs) in 11 European countries. We argue that the enactment of expanded and diversified missions of HE is one of the main factors nurturing universities’ profesional and administrative bodies. Our findings support such an assertion; regardless of geographical and institutional differences, HEIs with high levels of “entrepreneurialism” (e.g. in service provision and external engagement) are characterized by a larger proportion of administrative staff. However, we find no empirical support for arguments citing structural pressures and demands on HEIs due to higher student enrolments, budget cuts or deregulation as engines driving such change. Instead, our results point towards, as argued by neo-institutionalists, the diffusion of formal organization as a model of institutional identity and purpose, which is especially prevalent at high levels of external connectedness

Widespread sensorimotor and frontal cortical atrophy in Amyotrophic Lateral Sclerosis

BACKGROUND: Widespread cortical atrophy in Amyotrophic Lateral Sclerosis (ALS) has been described in neuropathological studies. The presence of cortical atrophy in conventional and scientific neuroimaging has been a matter of debate. In studies using computertomography, positron emission tomography, proton magnetic resonance spectroscopy and conventional T2-weighted and proton-weighted images, results have been variable. Recent morphometric studies by magnetic resonance imaging have produced conflicting results regarding the extent of grey and white matter involvement in ALS patients. METHODS: The authors used optimized voxel-based morphometry as an unbiased whole brain approach to detect differences between regional grey and white matter volumes. Seventeen patients with a diagnosis of ALS according to El-Escorial criteria and seventeen age-matched controls received a high resolution anatomical T1 scan. RESULTS: In ALS patients regional grey matter volume (GMV) reductions were found in the pre- and postcentral gyrus bilaterally which extended to premotor, parietal and frontal regions bilaterally compared with controls (p < 0.05, corrected for the entire volume). The revised ALS functional rating scale showed a positive correlation with GMV reduction of the right medial frontal gyrus corresponding to the dorsolateral prefrontal cortex. No significant differences were found for white matter volumes or when grey and white matter density images were investigated. There were no further correlations with clinical variables found. CONCLUSION: In ALS patients, primary sensorimotor cortex atrophy can be regarded as a prominent feature of the disease. Supporting the concept of ALS being a multisytem disorder, our study provides further evidence for extramotor involvement which is widespread. The lack of correlation with common clinical variables probably reflects the fact that heterogeneous disease processes underlie ALS. The discrepancy within all published morphometric studies in ALS so far may be related to differences in patient cohorts and several methodological factors of the data analysis process. Longitudinal studies are required to further clarify the time course and distribution of grey and white matter pathology during the course of ALS

First narrow-band search for continuous gravitational waves from known pulsars in advanced detector data

Spinning neutron stars asymmetric with respect to their rotation axis are potential sources of continuous gravitational waves for ground-based interferometric detectors. In the case of known pulsars a fully coherent search, based on matched filtering, which uses the position and rotational parameters obtained from electromagnetic observations, can be carried out. Matched filtering maximizes the signalto- noise (SNR) ratio, but a large sensitivity loss is expected in case of even a very small mismatch between the assumed and the true signal parameters. For this reason, narrow-band analysis methods have been developed, allowing a fully coherent search for gravitational waves from known pulsars over a fraction of a hertz and several spin-down values. In this paper we describe a narrow-band search of 11 pulsars using data from Advanced LIGO’s first observing run. Although we have found several initial outliers, further studies show no significant evidence for the presence of a gravitational wave signal. Finally, we have placed upper limits on the signal strain amplitude lower than the spin-down limit for 5 of the 11 targets over the bands searched; in the case of J1813-1749 the spin-down limit has been beaten for the first time. For an additional 3 targets, the median upper limit across the search bands is below the spin-down limit. This is the most sensitive narrow-band search for continuous gravitational waves carried out so far

Using Transcription Modules to Identify Expression Clusters Perturbed in Williams-Beuren Syndrome

The genetic dissection of the phenotypes associated with Williams-Beuren Syndrome (WBS) is advancing thanks to the study of individuals carrying typical or atypical structural rearrangements, as well as in vitro and animal studies. However, little is known about the global dysregulations caused by the WBS deletion. We profiled the transcriptomes of skin fibroblasts from WBS patients and compared them to matched controls. We identified 868 differentially expressed genes that were significantly enriched in extracellular matrix genes, major histocompatibility complex (MHC) genes, as well as genes in which the products localize to the postsynaptic membrane. We then used public expression datasets from human fibroblasts to establish transcription modules, sets of genes coexpressed in this cell type. We identified those sets in which the average gene expression was altered in WBS samples. Dysregulated modules are often interconnected and share multiple common genes, suggesting that intricate regulatory networks connected by a few central genes are disturbed in WBS. This modular approach increases the power to identify pathways dysregulated in WBS patients, thus providing a testable set of additional candidates for genes and their interactions that modulate the WBS phenotypes

An agent based decentralized matching macroeconomic model

In this paper we present a macroeconomic microfounded framework with heterogeneous agents-individuals, firms, banks-which interact through a decentralized matching process presenting common features across four markets-goods, labor, credit and deposit. We study the dynamics of the model by means of computer simulation. Some macroeconomic properties emerge such as endogenous business cycles, nominal GDP growth, unemployment rate fluctuations, the Phillips curve, leverage cycles and credit constraints, bank defaults and financial instability, and the importance of government as an acyclical sector which stabilize the economy. The model highlights that even extended crises can endogenously emerge. In these cases, the system may remain trapped in a large unemployment status, without the possibility to quickly recover unless an exogenous intervention takes place