136 research outputs found
Auditory coding of reaching space
Reaching movements are usually initiated by visual events and controlled visually and kinesthetically. Lately, studies have focused on the possible benefit of auditory information for localization tasks, and also for movement control. This explorative study aimed to investigate if it is possible to code reaching space purely by auditory information. Therefore, the precision of reaching movements to merely acoustically coded target positions was analyzed. We studied the efficacy of acoustically effect-based and of additional acoustically performance-based instruction and feedback and the role of visual movement control. Twenty-four participants executed reaching movements to merely acoustically presented, invisible target positions in three mutually perpendicular planes in front of them. Effector-endpoint trajectories were tracked using inertial sensors. Kinematic data regarding the three spatial dimensions and the movement velocity were sonified. Thus, acoustic instruction and real-time feedback of the movement trajectories and the target position of the hand were provided. The subjects were able to align their reaching movements to the merely acoustically instructed targets. Reaching space can be coded merely acoustically, additional visual movement control does not enhance reaching performance. On the basis of these results, a remarkable benefit of kinematic movement acoustics for the neuromotor rehabilitation of everyday motor skills can be assumed
Synthesis and Characterisation of a Boron-Rich Symmetric Triazine Bearing a Hypoxia-Targeting Nitroimidazole Moiety
Boron Neutron Capture Therapy (BNCT) is a binary therapy that promises to be suitable in treating many non-curable cancers. To that, the discovery of new boron compounds able to accumulate selectively in the tumour tissue is still required. Hypoxia, a deficiency of oxygen in tumor tissue, is a great challenge in the conventional treatment of cancer, because hypoxic areas are resistant to conventional anticancer treatments. 2-Nitroimidazole derivatives are known to be hypoxia markers due to their enrichment by bioreduction in hypoxic cells. In the present work, 2-nitroimidazole was chosen as the starting point for the synthesis of a new boron-containing compound based on a 1,3,5-triazine skeleton. Two o-carborane moieties were inserted to achieve a high ratio of boron on the molecular weight, exploiting a short PEG spacer to enhance the polarity of the compound and outdistance the active part from the core. The compound showed no toxicity on normal human primary fibroblasts, while it showed noteworthy toxicity in multiple myeloma cells together with a consistent intracellular boron accumulation
The role of high-field magnetic resonance imaging in parkinsonian disorders:Pushing the boundaries forward
Historically, magnetic resonance imaging (MRI) has contributed little to the study of Parkinson's disease (PD), but modern MRI approaches have unveiled several complementary markers that are useful for research and clinical applications. Iron- and neuromelanin-sensitive MRI detect qualitative changes in the substantia nigra. Quantitative MRI markers can be derived from diffusion weighted and iron-sensitive imaging or volumetry. Functional brain alterations at rest or during task performance have been captured with functional and arterial spin labeling perfusion MRI. These markers are useful for the diagnosis of PD and atypical parkinsonism, to track disease progression from the premotor stages of these diseases and to better understand the neurobiological basis of clinical deficits. A current research goal using MRI is to generate time-dependent models of the evolution of PD biomarkers that can help understand neurodegeneration and provide reliable markers for therapeutic trials. This article reviews recent advances in MRI biomarker research at high-field (3T) and ultra high field-imaging (7T) in PD and atypical parkinsonism. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society
Visual feedback explains why propointing is better than antipointing in spatial neglect
Kathrin S. Utz held a post-doctoral research fellowship of the Friedrich-AlexanderUniversity Erlangen-Nuremberg (program for the promotion of equal opportunities of women in science) at the time of data collection. Thomas Schenk was supported by grants from the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG, grant no’s: DFG-SCHE 735/2-1 and DFG-SCHE 735/3-1).Peer reviewedPostprin
Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context
Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts
Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas
Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN
Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas
This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing
molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin
Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images
Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images
of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL
maps are derived through computational staining using a convolutional neural network trained to
classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and
correlation with overall survival. TIL map structural patterns were grouped using standard
histopathological parameters. These patterns are enriched in particular T cell subpopulations
derived from molecular measures. TIL densities and spatial structure were differentially enriched
among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial
infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic
patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for
the TCGA image archives with insights into the tumor-immune microenvironment
Earth Virtualization Engines (EVE)
To manage Earth in the Anthropocene, new tools, new institutions, and new forms of international cooperation will be required. Earth Virtualization Engines is proposed as an international federation of centers of excellence to empower all people to respond to the immense and urgent challenges posed by climate change
- …