A workflow for the automatic segmentation of organelles in electron microscopy image stacks

pre-printElectron microscopy(EM) facilitates analysis of the form,distribution, and functional status of key organelle systems in various pathological processes,including those associated with neurodegenerative disease.Such EM data often provide important new in sights into the underlying disease mechanisms. The development of more accurate and efficient methods to quantify changes in subcellular microanatomy has already proven key to understanding the pathogenesis of Parkinson's and Alzheimer's diseases,as well as glaucoma. While our ability to acquire large volumes of 3D EM data is progressing rapidly, more advanced analysis tools are needed to assist in measuring precise three-dimensional morphologies of organelles within data sets that can include hundreds to thousands of whole cells. Although new imaging instrument throughputs can exceed teravoxels of data per day, image segmentation and analysis remain significant bottlenecks to achieving quantitative descriptions of whole cell structural organellomes. Here, we present a novel method for the automatic segmentation of organelles in 3D EM image stacks. Segmentations are generated using only 2D image information, making the method suitable for anisotropic imaging techniques such as serial block-face scanning electron microscopy (SBEM). Additionally, no assumptions about 3D organelle morphology are made, ensuring the method can be easily expanded to any number of structurally and functionally diverse organelles. Following the presentation of our algorithm, we validate its performance by assessing the segmentation accuracy of different organelle targets in an example SBEM dataset and demonstrate that it can be efficiently parallelized on supercomputing resources, resulting in a dramatic reduction in runtime

A workflow for the automatic segmentation of organelles in electron microscopy image stacks.

Electron microscopy (EM) facilitates analysis of the form, distribution, and functional status of key organelle systems in various pathological processes, including those associated with neurodegenerative disease. Such EM data often provide important new insights into the underlying disease mechanisms. The development of more accurate and efficient methods to quantify changes in subcellular microanatomy has already proven key to understanding the pathogenesis of Parkinson's and Alzheimer's diseases, as well as glaucoma. While our ability to acquire large volumes of 3D EM data is progressing rapidly, more advanced analysis tools are needed to assist in measuring precise three-dimensional morphologies of organelles within data sets that can include hundreds to thousands of whole cells. Although new imaging instrument throughputs can exceed teravoxels of data per day, image segmentation and analysis remain significant bottlenecks to achieving quantitative descriptions of whole cell structural organellomes. Here, we present a novel method for the automatic segmentation of organelles in 3D EM image stacks. Segmentations are generated using only 2D image information, making the method suitable for anisotropic imaging techniques such as serial block-face scanning electron microscopy (SBEM). Additionally, no assumptions about 3D organelle morphology are made, ensuring the method can be easily expanded to any number of structurally and functionally diverse organelles. Following the presentation of our algorithm, we validate its performance by assessing the segmentation accuracy of different organelle targets in an example SBEM dataset and demonstrate that it can be efficiently parallelized on supercomputing resources, resulting in a dramatic reduction in runtime

Synchronization in a ring of pulsating oscillators with bidirectional couplings

We study the dynamical behavior of an ensemble of oscillators interacting through short range bidirectional pulses. The geometry is 1D with periodic boundary conditions. Our interest is twofold. To explore the conditions required to reach fully synchronization and to invewstigate the time needed to get such state. We present both theoretical and numerical results.Comment: Revtex, 4 pages, 2 figures. To appear in Int. J. Bifurc. and Chao

Chronic environmental perturbation influences microbial community assembly patterns

Acknowledgements Next-generation sequencing and library construction was performed by NCIMB Ltd., Aberdeen and CGEBM, Aberdeen. The authors would like to acknowledge the support of the Maxwell computer cluster funded by the University of Aberdeen. Dr Axel Aigle is acknowledged for assistance in molecular analysis. This work was supported by the Natural Environment Research Council [NE/L00982X/1] with financial support from BP UK Ltd and Intertek Group PLC. CGR was supported by a University Research Fellowship from the Royal Society [UF150571]Peer reviewedPostprin

Ultrathin a-Si:H/Oxide transparent solar cells exhibiting UV-Blue selective-like absorption

This is the peer reviewed version of the following article: Lopez-Garcia, A. [et al.]. Ultrathin a-Si:H/Oxide transparent solar cells exhibiting UV-Blue selective-like absorption. "Solar RRL", April 2023, which has been published in final form at https://onlinelibrary.wiley.com/doi/10.1002/solr.202200928. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.Herein, the fabrication of transparent solar cells based on nanometric (8 and30 nm) intrinsic hydrogenated amorphous siliconfilms (a-Si:H) and using oxidethinfilms as transparent carrier selective contacts are reported. The ultrathindevices present photovoltaic effect and high average visible transmittance (AVT).Additionally, they display a shifted spectral response toward short wavelengths.Glass/fluorine-doped tin oxide (FTO)/aluminum-doped zinc oxide (AZO)/a-Si:H/MoO3/indium tin oxide (ITO) prototypes are shown, presenting AVT=35% andphotovoltaic conversion efficiency (PCE)=2% for a device with a 30 nm a-Si:Hfilm. This yields a light utilization efficiency (LUE) of 0.7%, a record up to this datefor inorganic oxide-based transparent solar cells. For devices including an 8 nma-Si:Hfilm, the AVT reaches 66% with a PCE=0.6% (LUE=0.4%). These highAVT values are comparable or even superior in some cases to those achieved forpure oxide devices. Thesefindings confirm the potential of the proposedarchitectures for the development of highly transparent energy harvesters asfunctional components in building-integrated photovoltaics (BIPV), agrophoto-voltaics (APV), sensors and other low-power devices. In addition, these devicesare fabricated with earth-abundant materials and with up-scalable techniquesthat can allow for a feasible implementation.Peer ReviewedPostprint (published version

The Influence of Physiological Status on age Prediction of Anopheles Arabiensis Using Near Infra-red spectroscopy

Determining the age of malaria vectors is essential for evaluating the impact of interventions that reduce the survival of wild mosquito populations and for estimating changes in vectorial capacity. Near infra-red spectroscopy (NIRS) is a simple and non-destructive method that has been used to determine the age and species of Anopheles gambiae s.l. by analyzing differences in absorption spectra. The spectra are affected by biochemical changes that occur during the life of a mosquito and could be influenced by senescence and also the life history of the mosquito, i.e., mating, blood feeding and egg-laying events. To better understand these changes, we evaluated the influence of mosquito physiological status on NIR energy absorption spectra. Mosquitoes were kept in individual cups to permit record keeping of each individual insect’s life history. Mosquitoes of the same chronological age, but at different physiological stages, were scanned and compared using cross-validations. We observed a slight trend within some physiological stages that suggest older insects tend to be predicted as being physiologically more mature. It was advantageous to include mosquitoes of different chronological ages and physiological stages in calibrations, as it increases the robustness of the model resulting in better age predictions. Progression through different physiological statuses of An. arabiensis influences the chronological age prediction by the NIRS. Entomologists that wish to use NIR technology to predict the age of field-caught An. gambiae s.l from their study area should use a calibration developed from their field strain using mosquitoes of diverse chronological ages and physiological stages to increase the robustness and accuracy of the predictions.\u

Universality in the Screening Cloud of Dislocations Surrounding a Disclination

A detailed analytical and numerical analysis for the dislocation cloud surrounding a disclination is presented. The analytical results show that the combined system behaves as a single disclination with an effective fractional charge which can be computed from the properties of the grain boundaries forming the dislocation cloud. Expressions are also given when the crystal is subjected to an external two-dimensional pressure. The analytical results are generalized to a scaling form for the energy which up to core energies is given by the Young modulus of the crystal times a universal function. The accuracy of the universality hypothesis is numerically checked to high accuracy. The numerical approach, based on a generalization from previous work by S. Seung and D.R. Nelson ({\em Phys. Rev A 38:1005 (1988)}), is interesting on its own and allows to compute the energy for an {\em arbitrary} distribution of defects, on an {\em arbitrary geometry} with an arbitrary elastic {\em energy} with very minor additional computational effort. Some implications for recent experimental, computational and theoretical work are also discussed.Comment: 35 pages, 21 eps file

MAGY: an innovative high voltage - low current power supply for gyrotron

From the electrical point of view, the body and the anode of high power gyrotrons behave as capacitive loads. A highly dynamic power supply is, therefore, hard to achieve. The MAGY concept (Modulator for the Anode of a triode type GYrotron) embodies an innovative solution to manage the capacitive current ensuring a very low ripple on the output voltage. It consists of a series of independent, bi-directional and regulated DC sources. Compared to existing topologies, this solution requires a smaller number of power modules. It avoids internal high frequency modulation and simultaneously offers high resolution of the output voltage and a wide range of operating scenarios. (C) 2011 Elsevier B.V. All rights reserved

A pharmacogenetic intervention for the improvement of the safety profile of antipsychotic treatments

Antipsychotic drugs fail to achieve adequate response in 30-50% of treated patients and about 50% of them develop severe and lasting side effects. Treatment failure results in poorer prognosis with devastating repercussions for the patients, carers and broader society. Our study evaluated the clinical benefits of a pharmacogenetic intervention for the personalisation of antipsychotic treatment. Pharmacogenetic information in key CYP polymorphisms was used to adjust clinical doses in a group of patients who started or switched treatment with antipsychotic drugs (PharmG+, N = 123), and their results were compared with those of a group of patients treated following existing clinical guides (PharmG−, N = 167). There was no evidence of significant differences in side effects between the two arms. Although patients who had their antipsychotic dose adjusted according to CYPs polymorphisms (PharmG+) had a bigger reduction in side effects than those treated as usual (PharmG−), the difference was not statistically significant (p > 0.05 for all comparisons). However, PharmG+ patients treated with CYP2D6 substrates that were carriers of CYP2D6 UMs or PMs variants showed a significantly higher improvement in global, psychic and other UKU side effects than PharmG− patients (p = 0.02, p = 0.05 and p = 0.01, respectively). PharmG+ clozapine treated patients with CYP1A2 or CYP2C19 UM and PMs variants also showed higher reductions in UKU scores than PharmG− clozapine patients in general. However, those differences were not statistically significant. Pharmacogenetic interventions may improve the safety of antipsychotic treatments by reducing associated side effects. This intervention may be particularly useful when considering treatment with antipsychotics with one major metabolic pathway, and therefore more susceptible to be affected by functional variants of CYP enzymes

Adjuvant chemotherapy with or without bevacizumab in patients with resected non-small-cell lung cancer (E1505): an open-label, multicentre, randomised, phase 3 trial.

BackgroundAdjuvant chemotherapy for resected early-stage non-small-cell lung cancer (NSCLC) provides a modest survival benefit. Bevacizumab, a monoclonal antibody directed against VEGF, improves outcomes when added to platinum-based chemotherapy in advanced-stage non-squamous NSCLC. We aimed to evaluate the addition of bevacizumab to adjuvant chemotherapy in early-stage resected NSCLC.MethodsWe did an open-label, randomised, phase 3 trial of adult patients (aged ≥18 years) with an Eastern Cooperative Oncology Group performance status of 0 or 1 and who had completely resected stage IB (≥4 cm) to IIIA (defined by the American Joint Committee on Cancer 6th edition) NSCLC. We enrolled patients from across the US National Clinical Trials Network, including patients from the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network (ECOG-ACRIN) affiliates in Europe and from the Canadian Cancer Trials Group, within 6-12 weeks of surgery. The chemotherapy regimen for each patient was selected before randomisation and administered intravenously; it consisted of four 21-day cycles of cisplatin (75 mg/m2 on day 1 in all regimens) in combination with investigator's choice of vinorelbine (30 mg/m2 on days 1 and 8), docetaxel (75 mg/m2 on day 1), gemcitabine (1200 mg/m2 on days 1 and 8), or pemetrexed (500 mg/m2 on day 1). Patients in the bevacizumab group received bevacizumab 15 mg/kg intravenously every 21 days starting with cycle 1 of chemotherapy and continuing for 1 year. We randomly allocated patients (1:1) to group A (chemotherapy alone) or group B (chemotherapy plus bevacizumab), centrally, using permuted blocks sizes and stratified by chemotherapy regimen, stage of disease, histology, and sex. No one was masked to treatment assignment, except the Data Safety and Monitoring Committee. The primary endpoint was overall survival, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00324805.FindingsBetween June 1, 2007, and Sept 20, 2013, 1501 patients were enrolled and randomly assigned to the two treatment groups: 749 to group A (chemotherapy alone) and 752 to group B (chemotherapy plus bevacizumab). 383 (26%) of 1458 patients (with complete staging information) had stage IB, 636 (44%) had stage II, and 439 (30%) had stage IIIA disease (stage of disease data were missing for 43 patients). Squamous cell histology was reported for 422 (28%) of 1501 patients. All four cisplatin-based chemotherapy regimens were used: 377 (25%) patients received vinorelbine, 343 (23%) received docetaxel, 283 (19%) received gemcitabine, and 497 (33%) received pemetrexed. At a median follow-up of 50·3 months (IQR 32·9-68·0), the estimated median overall survival in group A has not been reached, and in group B was 85·8 months (95% CI 74·9 to not reached); hazard ratio (group B vs group A) 0·99 (95% CI 0·82-1·19; p=0·90). Grade 3-5 toxicities of note (all attributions) that were reported more frequently in group B (the bevacizumab group) than in group A (chemotherapy alone) were overall worst grade (ie, all grade 3-5 toxicities; 496 [67%] of 738 in group A vs 610 [83%] of 735 in group B), hypertension (60 [8%] vs 219 [30%]), and neutropenia (241 [33%] vs 275 [37%]). The number of deaths on treatment did not differ between the groups (15 deaths in group A vs 19 in group B). Of these deaths, three in group A and ten in group B were considered at least possibly related to treatment.InterpretationAddition of bevacizumab to adjuvant chemotherapy did not improve overall survival for patients with surgically resected early-stage NSCLC. Bevacizumab does not have a role in this setting and should not be considered as an adjuvant therapy for patients with resected early-stage NSCLC.FundingNational Cancer Institute of the National Institutes of Health