A missense mutation in Katnal1 underlies behavioural, neurological and ciliary anomalies

Microtubule severing enzymes implement a diverse range of tissue-specific molecular functions throughout development and into adulthood. Although microtubule severing is fundamental to many dynamic neural processes, little is known regarding the role of the family member Katanin p60 subunit A-like 1, KATNAL1, in central nervous system (CNS) function. Recent studies reporting that microdeletions incorporating the KATNAL1 locus in humans result in intellectual disability and microcephaly suggest that KATNAL1 may play a prominent role in the CNS; however, such associations lack the functional data required to highlight potential mechanisms which link the gene to disease symptoms. Here we identify and characterise a mouse line carrying a loss of function allele in Katnal1. We show that mutants express behavioural deficits including in circadian rhythms, sleep, anxiety and learning/memory. Furthermore, in the brains of Katnal1 mutant mice we reveal numerous morphological abnormalities and defects in neuronal migration and morphology. Furthermore we demonstrate defects in the motile cilia of the ventricular ependymal cells of mutants, suggesting a role for Katnal1 in the development of ciliary function. We believe the data we present here are the first to associate KATNAL1 with such phenotypes, demonstrating that the protein plays keys roles in a number of processes integral to the development of neuronal function and behaviour.Molecular Psychiatry advance online publication, 4 April 2017; doi:10.1038/mp.2017.54

Recurrent somatic mutations in POLR2A define a distinct subset of meningiomas

RNA polymerase II mediates the transcription of all protein-coding genes in eukaryotic cells, a process that is fundamental to life. Genomic mutations altering this enzyme have not previously been linked to any pathology in humans, which is a testament to its indispensable role in cell biology. On the basis of a combination of next-generation genomic analyses of 775 meningiomas, we report that recurrent somatic p.Gln403Lys or p.Leu438_His439del mutations in POLR2A, which encodes the catalytic subunit of RNA polymerase II (ref. 1), hijack this essential enzyme and drive neoplasia. POLR2A mutant tumors show dysregulation of key meningeal identity genes including WNT6 and ZIC1/ZIC4. In addition to mutations in POLR2A, NF2, SMARCB1, TRAF7, KLF4, AKT1, PIK3CA, and SMO4 we also report somatic mutations in AKT3, PIK3R1, PRKAR1A, and SUFU in meningiomas. Our results identify a role for essential transcriptional machinery in driving tumorigenesis and define mutually exclusive meningioma subgroups with distinct clinical and pathological features

Systematic evaluation of immune regulation and modulation

Cancer immunotherapies are showing promising clinical results in a variety of malignancies. Monitoring the immune as well as the tumor response following these therapies has led to significant advancements in the field. Moreover, the identification and assessment of both predictive and prognostic biomarkers has become a key component to advancing these therapies. Thus, it is critical to develop systematic approaches to monitor the immune response and to interpret the data obtained from these assays. In order to address these issues and make recommendations to the field, the Society for Immunotherapy of Cancer reconvened the Immune Biomarkers Task Force. As a part of this Task Force, Working Group 3 (WG3) consisting of multidisciplinary experts from industry, academia, and government focused on the systematic assessment of immune regulation and modulation. In this review, the tumor microenvironment, microbiome, bone marrow, and adoptively transferred T cells will be used as examples to discuss the type and timing of sample collection. In addition, potential types of measurements, assays, and analyses will be discussed for each sample. Specifically, these recommendations will focus on the unique collection and assay requirements for the analysis of various samples as well as the high-throughput assays to evaluate potential biomarkers

Resonance characteristics of capacitively loaded CPW open-loop resonators

WOS: 000184197600013Capacitively loaded coplanar waveguide (CPW) open-loop resonators (OLRs) are proposed for maximum miniaturization in uniplanar microwave applications. It is shown that these resonators can be used to achieve a slow-wave effect without occupying extra surface area. Also, the resonators have a size reduction of about 50% at the same resonance frequency, as compared with the conventional open-loop resonator, as well as a higher performance of about 25-30%. The reduction in size of these types of resonators, and their performance (mainly the Q factor), can be controlled by the fingers within the OLR. (C) 2003 Wiley Periodicals, Inc

Calculation of quasistatic parameters for asymmetric coplanar waveguides using fuzzy logic

This paper proposes an efficient fuzzy modeling approach based on subtractive clustering for accurate calculation of the quasistatic parameters of asymmetric coplanar waveguides (ACPWs). The fuzzy model tracks the steps of clustering, preparation of rule based linear equation system and parameter optimization. A comparison between this paper's results and the previous results obtained by using conformal mapping technique has been made. The results show the effectiveness of the model. Copyright 2014 IEICE

Elastic Networks in Reshaping Human Intentions by Proactive Social Robot Moves

This paper focuses on reshaping a previously detected human intention into a desired one, using contextual motions of mobile robots, which are in our applications, autonomous mobile 2-steps stairs and a chair. Our system first estimates the current intention based on human heading and trajectory depicted as orientation and location. Our previous reshaping applications have shown that the current human intention has to be deviated towards the new desired one in phases. In our novel approach, Elastic network generates way points of trajectories each of which acts as transient trajectories directed towards the desired intention's location. Our methodology aims at generating an "intention trajectory" towards the final goal. The initial way points possess destabilizing effects on the obstinance of the person intention making the "robot gain the curiosity and the trust of the person". Each way point generated by the elastic network is executed by moves of an adequate robot (here mobile 2-steps or chair) in adequate directions (towards coffee table, PC, TV, library). After each robot moves, the resulting human intention is estimated and compared to the desired goal in the intention space. Intention trajectories are searched in two modes: the "confident mode" and the "suspicious mode" which are defining human body-mood detected relying on proxemics. This paper analyzes our novel approach of planning trajectories via elastic networks based on these two modes

Calculation of quasistatic parameters for asymmetric coplanar waveguides using fuzzy logic

This paper proposes an efficient fuzzy modeling approach based on subtractive clustering for accurate calculation of the quasistatic parameters of asymmetric coplanar waveguides (ACPWs). The fuzzy model tracks the steps of clustering, preparation of rule based linear equation system and parameter optimization. A comparison between this paper's results and the previous results obtained by using conformal mapping technique has been made. The results show the effectiveness of the model. Copyright 2014 IEICE