Towards a synthetic tutor assistant: The EASEL project and its architecture

Robots are gradually but steadily being introduced in our daily lives. A paramount application is that of education, where robots can assume the role of a tutor, a peer or simply a tool to help learners in a specific knowledge domain. Such endeavor posits specific challenges: affective social behavior, proper modelling of the learner’s progress, discrimination of the learner’s utterances, expressions and mental states, which, in turn, require an integrated architecture combining perception, cognition and action. In this paper we present an attempt to improve the current state of robots in the educational domain by introducing the EASEL EU project. Specifically, we introduce the EASEL’s unified robot architecture, an innovative Synthetic Tutor Assistant (STA) whose goal is to interactively guide learners in a science-based learning paradigm, allowing us to achieve such rich multimodal interactions

Genomic deletions of MSH2 and MLH1 in colorectal cancer families detected by a novel mutation detection approach

Hereditary non-polyposis colorectal cancer is an autosomal dominant condition due to germline mutations in DNA-mismatch-repair genes, in particular MLH1, MSH2 and MSH6. Here we describe the application of a novel technique for the detection of genomic deletions in MLH1 and MSH2. This method, called multiplex ligation-dependent probe amplification, is a quantitative multiplex PCR approach to determine the relative copy number of each MLH1 and MSH2 exon. Mutation screening of genes was performed in 126 colorectal cancer families selected on the basis of clinical criteria and in addition, for a subset of families, the presence of microsatellite instability (MSI-high) in tumours. Thirty-eight germline mutations were detected in 37 (29.4%) of these kindreds, 31 of which have a predicted pathogenic effect. Among families with MSI-high tumours 65.7% harboured germline gene defects. Genomic deletions accounted for 54.8% of the pathogenic mutations. A complete deletion of the MLH1 gene was detected in two families. The multiplex ligation-dependent probe amplification approach is a rapid method for the detection of genomic deletions in MLH1 and MSH2. In addition, it reveals alterations that might escape detection using conventional diagnostic techniques. Multiplex ligation-dependent probe amplification might be considered as an early step in the molecular diagnosis of hereditary non-polyposis colorectal cancer

О параллельной обработке потока данных, адаптированной к области бит произвольной конфигурации

Предлагается модель операции свёртки арифметических многорядных двоичных кодов (МРК), которая учитывает неравномерность распределения бит данных по разрядам. На основе этой модели разрабатываются процедуры и методы свёртки МРК, которые позволяют снизить задержку на обработку.Пропонується модель операції згортки арифметичних багаторядних двійкових кодів (БРК), яка зважає на нерівномірність розподілу біт даних за разрядами. На основі цієї моделі розроблюються процедури і методи згортки БРК, які дозволяють зменшити затримку на обробку.Model of the compressing operation of arithmetic multi-row binary codes (MRC) is offered. In this model irregularity allocation of data bit per digits is considered. Procedures and methods of compressing MRC based on this model allow diminish delay of processing are designed (developed)

Evaluation of a candidate breast cancer associated SNP in ERCC4 as a risk modifier in BRCA1 and BRCA2 mutation carriers. Results from the Consortium of Investigators of Modifiers of BRCA1/BRCA2 (CIMBA)

Background: In this study we aimed to evaluate the role of a SNP in intron 1 of the ERCC4 gene (rs744154), previously reported to be associated with a reduced risk of breast cancer in the general population, as a breast cancer risk modifier in BRCA1 and BRCA2 mutation carriers. Methods: We have genotyped rs744154 in 9408 BRCA1 and 5632 BRCA2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and assessed its association with breast cancer risk using a retrospective weighted cohort approach. Results: We found no evidence of association with breast cancer risk for BRCA1 (per-allele HR: 0.98, 95% CI: 0.93–1.04, P=0.5) or BRCA2 (per-allele HR: 0.97, 95% CI: 0.89–1.06, P=0.5) mutation carriers. Conclusion: This SNP is not a significant modifier of breast cancer risk for mutation carriers, though weak associations cannot be ruled out. A Osorio1, R L Milne2, G Pita3, P Peterlongo4,5, T Heikkinen6, J Simard7, G Chenevix-Trench8, A B Spurdle8, J Beesley8, X Chen8, S Healey8, KConFab9, S L Neuhausen10, Y C Ding10, F J Couch11,12, X Wang11, N Lindor13, S Manoukian4, M Barile14, A Viel15, L Tizzoni5,16, C I Szabo17, L Foretova18, M Zikan19, K Claes20, M H Greene21, P Mai21, G Rennert22, F Lejbkowicz22, O Barnett-Griness22, I L Andrulis23,24, H Ozcelik24, N Weerasooriya23, OCGN23, A-M Gerdes25, M Thomassen25, D G Cruger26, M A Caligo27, E Friedman28,29, B Kaufman28,29, Y Laitman28, S Cohen28, T Kontorovich28, R Gershoni-Baruch30, E Dagan31,32, H Jernström33, M S Askmalm34, B Arver35, B Malmer36, SWE-BRCA37, S M Domchek38, K L Nathanson38, J Brunet39, T Ramón y Cajal40, D Yannoukakos41, U Hamann42, HEBON37, F B L Hogervorst43, S Verhoef43, EB Gómez García44,45, J T Wijnen46,47, A van den Ouweland48, EMBRACE37, D F Easton49, S Peock49, M Cook49, C T Oliver49, D Frost49, C Luccarini50, D G Evans51, F Lalloo51, R Eeles52, G Pichert53, J Cook54, S Hodgson55, P J Morrison56, F Douglas57, A K Godwin58, GEMO59,60,61, O M Sinilnikova59,60, L Barjhoux59,60, D Stoppa-Lyonnet61, V Moncoutier61, S Giraud59, C Cassini62,63, L Olivier-Faivre62,63, F Révillion64, J-P Peyrat64, D Muller65, J-P Fricker65, H T Lynch66, E M John67, S Buys68, M Daly69, J L Hopper70, M B Terry71, A Miron72, Y Yassin72, D Goldgar73, Breast Cancer Family Registry37, C F Singer74, D Gschwantler-Kaulich74, G Pfeiler74, A-C Spiess74, Thomas v O Hansen75, O T Johannsson76, T Kirchhoff77, K Offit77, K Kosarin77, M Piedmonte78, G C Rodriguez79, K Wakeley80, J F Boggess81, J Basil82, P E Schwartz83, S V Blank84, A E Toland85, M Montagna86, C Casella87, E N Imyanitov88, A Allavena89, R K Schmutzler90, B Versmold90, C Engel91, A Meindl92, N Ditsch93, N Arnold94, D Niederacher95, H Deißler96, B Fiebig97, R Varon-Mateeva98, D Schaefer99, U G Froster100, T Caldes101, M de la Hoya101, L McGuffog49, A C Antoniou49, H Nevanlinna6, P Radice4,5 and J Benítez1,3 on behalf of CIMB

Using three-dimensional ultrasound in predicting complex gastroschisis:A longitudinal, prospective, multicenter cohort study

Objective: To determine whether complex gastroschisis (ie, intestinal atresia, perforation, necrosis, or volvulus) can prenatally be distinguished from simple gastroschisis by fetal stomach volume and stomach-bladder distance, using three-dimensional (3D) ultrasound. Methods: This multicenter prospective cohort study was conducted in the Netherlands between 2010 and 2015. Of seven university medical centers, we included the four centers that performed longitudinal 3D ultrasound measurements at a regular basis. We calculated stomach volumes (n = 223) using Sonography-based Automated Volume Count. The shortest stomach-bladder distance (n = 241) was determined using multiplanar visualization of the volume datasets. We used linear mixed modelling to evaluate the effect of gestational age and type of gastroschisis (simple or complex) on fetal stomach volume and stomach-bladder distance. Results: We included 79 affected fetuses. Sixty-six (84%) had been assessed with 3D ultrasound at least once; 64 of these 66 were liveborn, nine (14%) had complex gastroschisis. With advancing gestational age, stomach volume significantly increased, and stomach-bladder distance decreased (both P <.001). The developmental changes did not differ significantly between fetuses with simple and complex gastroschisis, neither for fetal stomach volume (P =.85), nor for stomach bladder distance (P =.78). Conclusion: Fetal stomach volume and stomach-bladder distance, measured during pregnancy using 3D ultrasonography, do not predict complex gastroschisis

System Test of the ATLAS Muon Spectrometer in the H8 Beam at the CERN SPS

An extensive system test of the ATLAS muon spectrometer has been performed in the H8 beam line at the CERN SPS during the last four years. This spectrometer will use pressurized Monitored Drift Tube (MDT) chambers and Cathode Strip Chambers (CSC) for precision tracking, Resistive Plate Chambers (RPCs) for triggering in the barrel and Thin Gap Chambers (TGCs) for triggering in the end-cap region. The test set-up emulates one projective tower of the barrel (six MDT chambers and six RPCs) and one end-cap octant (six MDT chambers, A CSC and three TGCs). The barrel and end-cap stands have also been equipped with optical alignment systems, aiming at a relative positioning of the precision chambers in each tower to 30-40 micrometers. In addition to the performance of the detectors and the alignment scheme, many other systems aspects of the ATLAS muon spectrometer have been tested and validated with this setup, such as the mechanical detector integration and installation, the detector control system, the data acquisition, high level trigger software and off-line event reconstruction. Measurements with muon energies ranging from 20 to 300 GeV have allowed measuring the trigger and tracking performance of this set-up, in a configuration very similar to the final spectrometer. A special bunched muon beam with 25 ns bunch spacing, emulating the LHC bunch structure, has been used to study the timing resolution and bunch identification performance of the trigger chambers. The ATLAS first-level trigger chain has been operated with muon trigger signals for the first time

Identification and validation of multiple cell surface markers of clinical-grade adipose-derived mesenchymal stromal cells as novel release criteria for good manufacturing practice-compliant production

Background: Clinical translation of mesenchymal stromal cells (MSCs) necessitates basic characterization of the cell product since variability in biological source and processing of MSCs may impact therapeutic outcomes. Although expression of classical cell surface markers (e.g., CD90, CD73, CD105, and CD44) is used to define MSCs, identification of functionally relevant cell surface markers would provide more robust release criteria and options for quality control. In addition, cell surface expression may distinguish between MSCs from different sources, including bone marrow-derived MSCs and clinical-grade adipose-derived MSCs (AMSCs) grown in human platelet lysate (hPL). Methods: In this work we utilized quantitative PCR, flow cytometry, and RNA-sequencing to characterize AMSCs grown in hPL and validated non-classical markers in 15 clinical-grade donors. Results: We characterized the surface marker transcriptome of AMSCs, validated the expression of classical markers, and identified nine non-classical markers (i.e., CD36, CD163, CD271, CD200, CD273, CD274, CD146, CD248, and CD140B) that may potentially discriminate AMSCs from other cell types. More importantly, these markers exhibit variability in cell surface expression among different cell isolates from a diverse cohort of donors, including freshly prepared, previously frozen, or proliferative state AMSCs and may be informative when manufacturing cells. Conclusions: Our study establishes that clinical-grade AMSCs expanded in hPL represent a homogeneous cell culture population according to classical markers,. Additionally, we validated new biomarkers for further AMSC characterization that may provide novel information guiding the development of new release criteria

Loss of histone methyltransferase Ezh2 stimulates an osteogenic transcriptional program in chondrocytes but does not affectcartilage development

Ezh2 is a histone methyltransferase that suppresses osteoblast maturation and skeletal development. We evaluated the roleof Ezh2 in chondrocyte lineage differentiation and endochondral ossification. Ezh2 was genetically inactivated in the mesenchymal, osteoblastic, and chondrocytic lineages in mice using the Prrx1-Cre,Osx1-Cre, and Col2a1-Cre drivers, respectively. Wild-type and conditional knockout mice were phenotypically assessed by grossmorphology, histology, and micro-CT imaging. Ezh2-deficient chondrocytes in micromass culture models were evaluated usingRNA-sequencing, histologic evaluation, and western blotting. Aged mice with Ezh2 deficiency were also evaluated for prematuredevelopment of osteoarthritis using radiographic analysis. Ezh2 deficiency in murine chondrocytes reduced bone density at 4 weeks of age, although caused no other gross developmentaleffects. Knockdown of Ezh2 in chondrocyte micromass cultures resulted in a global reduction in trimethylation of histone 3lysine 27 (H3K27me3) and altered differentiation in vitro. RNA-seq analysis revealed enrichment of an osteogenic gene expressionprofile in Ezh2 deficient chondrocytes. Joint development proceeded normally in the absence of Ezh2 in chondrocytes withoutinducing excessive hypertrophy or premature osteoarthritis in vivo. In summary, loss of Ezh2 reduced H3K27me3 levels, increased expression of osteogenic genes in chondrocytes, and resulted ina transient post-natal bone phenotype. Remarkably, Ezh2 activity is dispensable for normal chondrocyte maturation and endochondralossification in vivo, even though it appears to have a critical role during early stages of mesenchymal lineage-commitment