BACCardI - a tool for the validation of genomic assemblies, assisting genome finishing and intergenome comparison

Bartels D, Kespohl S, Albaum S, et al. BACCardI - a tool for the validation of genomic assemblies, assisting genome finishing and intergenome comparison. Bioinformatics. 2005;21(7):853-859.Summary: We provide the graphical tool BACCardI for the construction of virtual clone maps from standard assembler output files or BLAST based sequence comparisons. This new tool has been applied to numerous genome projects to solve various problems including (a) validation of whole genome shotgun assemblies, (b) support for contig ordering in the finishing phase of a genome project, and (c) intergenome comparison between related strains when only one of the strains has been sequenced and a large insert library is available for the other. The BACCardI software can seamlessly interact with various sequence assembly packages. Motivation: Genomic assemblies generated from sequence information need to be validated by independent methods such as physical maps. The time-consuming task of building physical maps can be circumvented by virtual clone maps derived from read pair information of large insert libraries

Integrated Techno-Economic Power System Planning of Transmission and Distribution Grids

The energy transition towards renewable and more distributed power production triggers the need for grid and storage expansion on all voltage levels. Today’s power system planning focuses on certain voltage levels or spatial resolutions. In this work we present an open source software tool eGo which is able to optimize grid and storage expansion throughout all voltage levels in a developed top-down approach. Operation and investment costs are minimized by applying a multi-period linear optimal power flow considering the grid infrastructure of the extra-high and high-voltage (380 to 110 kV) level. Hence, the common differentiation of transmission and distribution grid is partly dissolved, integrating the high-voltage level into the optimization problem. Consecutively, optimized curtailment and storage units are allocated in the medium voltage grid in order to lower medium and low voltage grid expansion needs, that are consequently determined. Here, heuristic optimization methods using the non-linear power flow were developed. Applying the tool on future scenarios we derived cost-efficient grid and storage expansion for all voltage levels in Germany. Due to the integrated approach, storage expansion and curtailment can significantly lower grid expansion costs in medium and low voltage grids and at the same time serve the optimal functioning of the overall system. Nevertheless, the cost-reducing effect for the whole of Germany was marginal. Instead, the consideration of realistic, spatially differentiated time series led to substantial overall savings

Abnormal synchrony and effective connectivity in patients with schizophrenia and auditory hallucinations

[EN] Auditory hallucinations (AH) are the most frequent positive symptoms in patients with schizophrenia. Hallucinations have been related to emotional processing disturbances, altered functional connectivity and effective connectivity deficits. Previously, we observed that, compared to healthy controls, the limbic network responses of patients with auditory hallucinations differed when the subjects were listening to emotionally charged words. We aimed to compare the synchrony patterns and effective connectivity of task-related networks between schizophrenia patients with and without AH and healthy controls. Schizophrenia patients with AH (n = 27) and without AH (n = 14) were compared with healthy participants (n = 31). We examined functional connectivity by analyzing correlations and cross-correlations among previously detected independent component analysis time courses. Granger causality was used to infer the information flow direction in the brain regions. The results demonstrate that the patterns of cortico-cortical functional synchrony differentiated the patients with AH from the patients without AH and from the healthy participants. Additionally, Granger-causal relationships between the networks clearly differentiated the groups. In the patients with AH, the principal causal source was an occipital¿cerebellar component, versus a temporal component in the patients without AH and the healthy controls. These data indicate that an anomalous process of neural connectivity exists when patients with AH process emotional auditory stimuli. Additionally, a central role is suggested for the cerebellum in processing emotional stimuli in patients with persistent AH.Funding for this study was provided by Spanish grants from Ministry of Science and Innovation (ISCIII: FIS P.I.02/0018, P.I.05/2332.), Spanish Mental Health Network: CIBERSAM and Combiomed Network.De La Iglesia-Vaya, M.; Escartí Fabra, MJ.; Molina-Mateo, J.; Marti-Bonmati, L.; Gadea, M.; Castellanos, FX.; Aguilar Garcia-Iturrospe, EJ.... (2014). Abnormal synchrony and effective connectivity in patients with schizophrenia and auditory hallucinations. NeuroImage Clinical. 6:171-179. https://doi.org/10.1016/j.nicl.2014.08.027S171179

Microenvironment‐induced restoration of cohesive growth associated with focal activation of P ‐cadherin expression in lobular breast carcinoma metastatic to the colon

Invasive lobular carcinoma (ILC) is a special breast cancer type characterized by noncohesive growth and E‐cadherin loss. Focal activation of P‐cadherin expression in tumor cells that are deficient for E‐cadherin occurs in a subset of ILCs. Switching from an E‐cadherin deficient to P‐cadherin proficient status (EPS) partially restores cell–cell adhesion leading to the formation of cohesive tubular elements. It is unknown what conditions control EPS. Here, we report on EPS in ILC metastases in the large bowel. We reviewed endoscopic colon biopsies and colectomy specimens from a 52‐year‐old female (index patient) and of 18 additional patients (reference series) diagnosed with metastatic ILC in the colon. EPS was assessed by immunohistochemistry for E‐cadherin and P‐cadherin. CDH1 /E‐cadherin mutations were determined by next‐generation sequencing. The index patient's colectomy showed transmural metastatic ILC harboring a CDH1 /E‐cadherin p.Q610* mutation. ILC cells displayed different growth patterns in different anatomic layers of the colon wall. In the tunica muscularis propria and the tela submucosa, ILC cells featured noncohesive growth and were E‐cadherin‐negative and P‐cadherin‐negative. However, ILC cells invading the mucosa formed cohesive tubular elements in the intercryptal stroma of the lamina propria mucosae. Inter‐cryptal ILC cells switched to a P‐cadherin‐positive phenotype in this microenvironmental niche. In the reference series, colon mucosa infiltration was evident in 13 of 18 patients, one of which showed intercryptal EPS and conversion to cohesive growth as described in the index patient. The large bowel is a common metastatic site in ILC. In endoscopic colon biopsies, the typical noncohesive growth of ILC may be concealed by microenvironment‐induced EPS and conversion to cohesive growth

Interactive and automated application of virtual microscopy

Virtual microscopy can be applied in an interactive and an automated manner. Interactive application is performed in close association to conventional microscopy. It includes image standardization suitable to the performance of an individual pathologist such as image colorization, white color balance, or individual adjusted brightness. The steering commands have to include selection of wanted magnification, easy navigation, notification, and simple measurements (distances, areas). The display of the histological image should be adjusted to the physical limits of the human eye, which are determined by a view angle of approximately 35 seconds. A more sophisticated performance should include acoustic commands that replace the corresponding visual commands. Automated virtual microscopy includes so-called microscopy assistants which can be defined similar to the developed assistants in computer based editing systems (Microsoft Word, etc.). These include an automated image standardization and correction algorithms that excludes images of poor quality (for example uni-colored or out-of-focus images), an automated selection of the most appropriate field of view, an automated selection of the best magnification, and finally proposals of the most probable diagnosis. A quality control of the final diagnosis, and feedback to the laboratory determine the proposed system. The already developed tools of such a system are described in detail, as well as the results of first trials. In order to enhance the speed of such a system, and to allow further user-independent development a distributed implementation probably based upon Grid technology seems to be appropriate. The advantages of such a system as well as the present pathology environment and its expectations will be discussed in detail

Association of latent factors of neuroinflammation with Alzheimer's disease pathology and longitudinal cognitive decline

INTRODUCTION: We investigated the association of inflammatory mechanisms with markers of Alzheimer's disease (AD) pathology and rates of cognitive decline in the AD spectrum.METHODS: We studied 296 cases from the Deutsches Zentrum für Neurodegenerative Erkrankungen Longitudinal Cognitive Impairment and Dementia Study (DELCODE) cohort, and an extension cohort of 276 cases of the Alzheimer's Disease Neuroimaging Initiative study. Using Bayesian confirmatory factor analysis, we constructed latent factors for synaptic integrity, microglia, cerebrovascular endothelial function, cytokine/chemokine, and complement components of the inflammatory response using a set of inflammatory markers in cerebrospinal fluid.RESULTS: We found strong evidence for an association of synaptic integrity, microglia response, and cerebrovascular endothelial function with a latent factor of AD pathology and with rates of cognitive decline. We found evidence against an association of complement and cytokine/chemokine factors with AD pathology and rates of cognitive decline.DISCUSSION: Latent factors provided access to directly unobservable components of the neuroinflammatory response and their association with AD pathology and cognitive decline.</p

Fornix fractional anisotropy mediates the association between Mediterranean diet adherence and memory four years later in older adults without dementia

Here, we investigated whether fractional anisotropy (FA) of hippocampus-relevant white-matter tracts mediates the association between baseline Mediterranean diet adherence (MeDiAd) and verbal episodic memory over four years. Participants were healthy older adults with and without subjective cognitive decline and patients with amnestic mild cognitive impairment from the DELCODE cohort study (n = 376; age: 71.47 ± 6.09 years; 48.7 % female). MeDiAd and diffusion data were obtained at baseline. Verbal episodic memory was assessed at baseline and four yearly follow-ups. The associations between baseline MeDiAd and white matter, and verbal episodic memory's mean and rate of change over four years were tested with latent growth curve modeling. Baseline MeDiAd was associated with verbal episodic memory four years later (95 % confidence interval, CI [0.01, 0.32]) but not with its rate of change over this period. Baseline Fornix FA mediated - and, thus, explained - that association (95 % CI [0.002, 0.09]). Fornix FA may be an appropriate response biomarker of Mediterranean diet interventions on verbal memory in older adults.</p