Spectral properties of microwave graphs with local absorption

The influence of absorption on the spectra of microwave graphs has been studied experimentally. The microwave networks were made up of coaxial cables and T junctions. First, absorption was introduced by attaching a 50 Ohm load to an additional vertex for graphs with and without time-reversal symmetry. The resulting level-spacing distributions were compared with a generalization of the Wigner surmise in the presence of open channels proposed recently by Poli et al. [Phys. Rev. Lett. 108, 174101 (2012)]. Good agreement was found using an effective coupling parameter. Second, absorption was introduced along one individual bond via a variable microwave attenuator, and the influence of absorption on the length spectrum was studied. The peak heights in the length spectra corresponding to orbits avoiding the absorber were found to be independent of the attenuation, whereas, the heights of the peaks belonging to orbits passing the absorber once or twice showed the expected decrease with increasing attenuation.Comment: 7 pages, 7 figure

Proton and carbon ion radiotherapy for primary brain tumors delivered with active raster scanning at the Heidelberg Ion Therapy Center (HIT): early treatment results and study concepts

<p>Abstract</p> <p>Background</p> <p>Particle irradiation was established at the University of Heidelberg 2 years ago. To date, more than 400 patients have been treated including patients with primary brain tumors. In malignant glioma (WHO IV) patients, two clinical trials have been set up-one investigating the benefit of a carbon ion (18 GyE) vs. a proton boost (10 GyE) in addition to photon radiotherapy (50 Gy), the other one investigating reirradiation with escalating total dose schedules starting at 30 GyE. In atypical meningioma patients (WHO °II), a carbon ion boost of 18 GyE is applied to macroscopic tumor residues following previous photon irradiation with 50 Gy.</p> <p>This study was set up in order to investigate toxicity and response after proton and carbon ion therapy for gliomas and meningiomas.</p> <p>Methods</p> <p>33 patients with gliomas (n = 26) and meningiomas (n = 7) were treated with carbon ion (n = 26) and proton (n = 7) radiotherapy. In 22 patients, particle irradiation was combined with photon therapy. Temozolomide-based chemotherapy was combined with particle therapy in 17 patients with gliomas. Particle therapy as reirradiation was conducted in 7 patients. Target volume definition was based upon CT, MRI and PET imaging. Response was assessed by MRI examinations, and progression was diagnosed according to the Macdonald criteria. Toxicity was classified according to CTCAE v4.0.</p> <p>Results</p> <p>Treatment was completed and tolerated well in all patients. Toxicity was moderate and included fatigue (24.2%), intermittent cranial nerve symptoms (6%) and single episodes of seizures (6%). At first and second follow-up examinations, mean maximum tumor diameters had slightly decreased from 29.7 mm to 27.1 mm and 24.9 mm respectively. Nine glioma patients suffered from tumor relapse, among these 5 with infield relapses, causing death in 8 patients. There was no progression in any meningioma patient.</p> <p>Conclusions</p> <p>Particle radiotherapy is safe and feasible in patients with primary brain tumors. It is associated with little toxicity. A positive response of both gliomas and meningiomas, which is suggested in these preliminary data, must be evaluated in further clinical trials.</p

On the Link between Gaussian Homotopy Continuation and Convex Envelopes

Abstract. The continuation method is a popular heuristic in computer vision for nonconvex optimization. The idea is to start from a simpli-fied problem and gradually deform it to the actual task while tracking the solution. It was first used in computer vision under the name of graduated nonconvexity. Since then, it has been utilized explicitly or im-plicitly in various applications. In fact, state-of-the-art optical flow and shape estimation rely on a form of continuation. Despite its empirical success, there is little theoretical understanding of this method. This work provides some novel insights into this technique. Specifically, there are many ways to choose the initial problem and many ways to progres-sively deform it to the original task. However, here we show that when this process is constructed by Gaussian smoothing, it is optimal in a specific sense. In fact, we prove that Gaussian smoothing emerges from the best affine approximation to Vese’s nonlinear PDE. The latter PDE evolves any function to its convex envelope, hence providing the optimal convexification

Inferring latent task structure for Multitask Learning by Multiple Kernel Learning

<p>Abstract</p> <p>Background</p> <p>The lack of sufficient training data is the limiting factor for many Machine Learning applications in Computational Biology. If data is available for several different but related problem domains, Multitask Learning algorithms can be used to learn a model based on all available information. In Bioinformatics, many problems can be cast into the Multitask Learning scenario by incorporating data from several organisms. However, combining information from several tasks requires careful consideration of the degree of similarity between tasks. Our proposed method simultaneously learns or refines the similarity between tasks along with the Multitask Learning classifier. This is done by formulating the Multitask Learning problem as Multiple Kernel Learning, using the recently published <it>q</it>-Norm MKL algorithm.</p> <p>Results</p> <p>We demonstrate the performance of our method on two problems from Computational Biology. First, we show that our method is able to improve performance on a splice site dataset with given hierarchical task structure by refining the task relationships. Second, we consider an MHC-I dataset, for which we assume no knowledge about the degree of task relatedness. Here, we are able to learn the task similarities<it> ab initio</it> along with the Multitask classifiers. In both cases, we outperform baseline methods that we compare against.</p> <p>Conclusions</p> <p>We present a novel approach to Multitask Learning that is capable of learning task similarity along with the classifiers. The framework is very general as it allows to incorporate prior knowledge about tasks relationships if available, but is also able to identify task similarities in absence of such prior information. Both variants show promising results in applications from Computational Biology.</p

Magnetic resonance imaging, computed tomography, and 68Ga-DOTATOC positron emission tomography for imaging skull base meningiomas with infracranial extension treated with stereotactic radiotherapy - a case series

<p>Abstract</p> <p>Introduction</p> <p>Magnetic resonance imaging (MRI) and computed tomography (CT) with ⁶⁸Ga-DOTATOC positron emission tomography (⁶⁸Ga-DOTATOC-PET) were compared retrospectively for their ability to delineate infracranial extension of skull base (SB) meningiomas treated with fractionated stereotactic radiotherapy.</p> <p>Methods</p> <p>Fifty patients with 56 meningiomas of the SB underwent MRI, CT, and ⁶⁸Ga-DOTATOC PET/CT prior to fractionated stereotactic radiotherapy. The study group consisted of 16 patients who had infracranial meningioma extension, visible on MRI ± CT (MRI/CT) <it>or </it>PET, and were evaluated further. The respective findings were reviewed independently, analyzed with respect to correlations, and compared with each other.</p> <p>Results</p> <p>Within the study group, SB transgression was associated with bony changes visible by CT in 14 patients (81%). Tumorous changes of the foramen ovale and rotundum were evident in 13 and 8 cases, respectively, which were accompanied by skeletal muscular invasion in 8 lesions. We analysed six designated anatomical sites of the SB in each of the 16 patients. Of the 96 sites, 42 had infiltration that was delineable by MRI/CT and PET in 35 cases and by PET only in 7 cases. The mean infracranial volume that was delineable in PET was 10.1 ± 10.6 cm³, which was somewhat larger than the volume detectable in MRI/CT (8.4 ± 7.9 cm³).</p> <p>Conclusions</p> <p>⁶⁸Ga-DOTATOC-PET allows detection and assessment of the extent of infracranial meningioma invasion. This method seems to be useful for planning fractionated stereotactic radiation when used in addition to conventional imaging modalities that are often inconclusive in the SB region.</p

Different Rho GTPase–dependent signaling pathways initiate sequential steps in the consolidation of long-term potentiation

The releasable factor adenosine blocks the formation of long-term potentiation (LTP). These experiments used this observation to uncover the synaptic processes that stabilize the potentiation effect. Brief adenosine infusion blocked stimulation-induced actin polymerization within dendritic spines along with LTP itself in control rat hippocampal slices but not in those pretreated with the actin filament stabilizer jasplakinolide. Adenosine also blocked activity-driven phosphorylation of synaptic cofilin but not of synaptic p21-activated kinase (PAK). A search for the upstream origins of these effects showed that adenosine suppressed RhoA activity but only modestly affected Rac and Cdc42. A RhoA kinase (ROCK) inhibitor reproduced adenosine's effects on cofilin phosphorylation, spine actin polymerization, and LTP, whereas a Rac inhibitor did not. However, inhibitors of Rac or PAK did prolong LTP's vulnerability to reversal by latrunculin, a toxin which blocks actin filament assembly. Thus, LTP induction initiates two synaptic signaling cascades: one (RhoA-ROCK-cofilin) leads to actin polymerization, whereas the other (Rac-PAK) stabilizes the newly formed filaments

Ephrin-A5 Suppresses Neurotrophin Evoked Neuronal Motility, ERK Activation and Gene Expression

During brain development, growth cones respond to attractive and repulsive axon guidance cues. How growth cones integrate guidance instructions is poorly understood. Here, we demonstrate a link between BDNF (brain derived neurotrophic factor), promoting axonal branching and ephrin-A5, mediating axonal repulsion via Eph receptor tyrosine kinase activation. BDNF enhanced growth cone filopodial dynamics and neurite branching of primary neurons. We show that ephrin-A5 antagonized this BDNF-evoked neuronal motility. BDNF increased ERK phosphorylation (P-ERK) and nuclear ERK entry. Ephrin-A5 suppressed BDNF-induced ERK activity and might sequester P-ERK in the cytoplasm. Neurotrophins are well established stimulators of a neuronal immediate early gene (IEG) response. This is confirmed in this study by e.g. c-fos, Egr1 and Arc upregulation upon BDNF application. This BDNF-evoked IEG response required the transcription factor SRF (serum response factor). Notably, ephrin-A5 suppressed a BDNF-evoked neuronal IEG response, suggesting a role of Eph receptors in modulating gene expression. In opposite to IEGs, long-term ephrin-A5 application induced cytoskeletal gene expression of tropomyosin and actinin. To uncover specific Eph receptors mediating ephrin-As impact on neurotrophin signaling, EphA7 deficient mice were analyzed. In EphA7 deficient neurons alterations in growth cone morphology were observed. However, ephrin-A5 still counteracted neurotrophin signaling suggesting that EphA7 is not required for ephrin and BDNF crosstalk. In sum, our data suggest an interaction of ephrin-As and neurotrophin signaling pathways converging at ERK signaling and nuclear gene activity. As ephrins are involved in development and function of many organs, such modulation of receptor tyrosine kinase signaling and gene expression by Ephs might not be limited to the nervous system

EMC ASPECTS OF TURBULENCE HEATING OBSERVER (THOR) SPACECRAFT

Turbulence Heating ObserveR (THOR) is a spacecraft mission dedicated to the study of plasma turbulence in near-Earth space. The mission is currently under study for implementation as a part of ESA Cosmic Vision program. THOR will involve a single spinning spacecraft equipped with state of the art instruments capable of sensitive measurements of electromagnetic fields and plasma particles. The sensitive electric and magnetic field measurements require that the spacecraft-generated emissions are restricted and strictly controlled; therefore a comprehensive EMC program has been put in place already during the study phase. The THOR study team and a dedicated EMC working group are formulating the mission EMC requirements state of its EMC requirements

Quantitative Analysis of the Effect of Cancer Invasiveness and Collagen Concentration on 3D Matrix Remodeling

Extracellular matrix (ECM) remodeling is a key component of cell migration and tumor metastasis, and has been associated with cancer progression. Despite the importance of matrix remodeling, systematic and quantitative studies on the process have largely been lacking. Furthermore, it remains unclear if the disrupted tensional homeostasis characteristic of malignancy is due to initially altered ECM and tissue properties, or to the alteration of the tissue by tumor cells. To explore these questions, we studied matrix remodeling by two different prostate cancer cell lines in a three-dimensional collagen system. Over one week, we monitored structural changes in gels of varying collagen content using confocal reflection microscopy and quantitative image analysis, tracking metrics of fibril fraction, pore size, and fiber length and diameter. Gels that were seeded with no cells (control), LNCaP cells, and DU-145 cells were quantitatively compared. Gels with higher collagen content initially had smaller pore sizes and higher fibril fractions, as expected. However, over time, LNCaP- and DU-145-populated matrices showed different structural properties compared both to each other and to the control gels, with LNCaP cells appearing to favor microenvironments with lower collagen fiber fractions and larger pores than DU-145 cells. We posit that the DU-145 cells' preference for denser matrices is due to their higher invasiveness and proteolytic capabilities. Inhibition of matrix proteases resulted in reduced fibril fractions for high concentration gels seeded with either cell type, supporting our hypothesis. Our novel quantitative results probe the dynamics of gel remodeling in three dimensions and suggest that prostate cancer cells remodel their ECM in a synergistic manner that is dependent on both initial matrix properties as well as their invasiveness