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Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder of motor neurons. Although most cases of ALS are sporadic (sALS) and of unknown etiology, there are also inherited familial ALS (fALS) cases that share a phenotype similar to sALS pathological and clinical phenotype. In this study, we have identified two new potential genetic ALS biomarkers in human bone marrow mesenchymal stem cells (hMSC) obtained from sALS patients, namely the TDP-43 (TAR DNA-binding protein 43) and SLPI (secretory leukocyte protease inhibitor). Together with the previously discovered ones-CyFIP2 and RbBP9, we investigated whether these four potential ALS biomarkers may be differentially expressed in tissues obtained from mutant SOD1(G93A) transgenic mice, a model that is relevant for at least 20% of the fALS cases. Quantitative real-time PCR analysis of brain, spinal cord and muscle tissues of the mSOD1(G93A) and controls at various time points during the progression of the neurological disease showed differential expression of the four identified biomarkers in correlation with (i) the tissue type, (ii) the stage of the disease and (iii) the gender of the animals, creating thus a novel spatiotemporal molecular signature of ALS. The biomarkers detected in the fALS animal model were homologous to those that were identified in hMSC of our sALS cases. These results support the possibility of a molecular link between sALS and fALS and may indicate common pathogenetic mechanisms involved in both types of ALS. Moreover, these results may pave the path for using the mSOD1(G93A) mouse model and these biomarkers as molecular beacons to evaluate the effects of novel drugs/treatments in ALS.

Abstract Mechanical engineering (ME) departments in research universities face the challenge of educating mechanical engineers who will graduate with a balanced knowledge in engineering science and mechanical design. The source of this challenge is the inherent difference between teaching analytical thinking, which is required for most engineering-science courses, and design thinking, which is required for project-based design courses. The purpose of this paper is first to propose a new approach that can potentially bridge the educational gap between analytical and design thinking, which we refer to as integrated thinking. Second, we show how it can be applied to various ME undergraduate courses, which we refer to as integrated courses. Our approach reforms science engineering courses by (a) stressing the physical interpretation of mathematical derivations; (b) requiring students to analyze, design, and sketch simple mechanical devices based on the learned theoretical material; and (c) modifying project-based design courses to emphasize the importance of analysis as part of the creative design process. A pilot course focusing on dynamics and vibration, which we called Integrated Design and Analysis, was offered in the ME department at the Technion, where it was well-attended by senior ME students. The positive feedback of the students who took the course suggests that integrated thinking might be successfully applied in many areas of ME education, such as fluid mechanics and heat transfer, control, and mechatronics, and that our approach may contribute to changing the current divided pattern in ME education.

This paper describes a novel approach to systematically improve information interactions based solely on its wording. Following an interdisciplinary literature review, we recognized three key attributes of words that drive user engagement: (1) Novelty (2) Familiarity (3) Emotionality. Based on these attributes, we developed a model to systematically improve a given content using computational linguistics, natural language processing (NLP) and text analysis (word frequency, sentiment analysis and lexical substitution). We conducted a pilot study (n=216) in which the model was used to formalize evaluation and optimization of academic titles. A between-group design (A/B testing) was used to compare responses to the original and modified (treatment) titles. Data was collected for selection and evaluation (User Engagement Scale). The pilot results suggest that user engagement with digital information is fostered by, and perhaps dependent upon, the wording being used. They also provide empirical support that engaging content can be systematically evaluated and produced. The preliminary results show that the modified (treatment) titles had significantly higher scores for information use and user engagement (selection and evaluation). We propose that computational linguistics is a useful approach for optimizing information interactions. The empirically based insights can inform the development of digital content strategies, thereby improving the success of information interactions.elop more sophisticated interaction measures. Comment: Dvir, N., & Gafni, R. (2019). Systematic improvement of user engagement with academic titles using computational linguistics. Proceedings of the Informing Science and Information Technology Education Conference, Jerusalem, Israel, pp. 501-512 Santa Rosa, CA: Informing Science Institute. https://doi.org/10.28945/4338

A comprehensive physical model of adiabatic three-wave mixing is developed for the fully nonlinear regime, i.e., without making the undepleted pump approximation. The conditions for adiabatic evolution are rigorously derived, together with an estimate of the bandwidth of the process. Furthermore, these processes are shown to be robust and efficient. Finally, numerical simulations demonstrate adiabatic frequency conversion in a wide variety of physically attainable configurations.

Objective Isotretinoin is among the most notorious human teratogens, documented originally as causing up to 30% of malformations. This systematic review and meta-analysis aimed to evaluate the rates of major malformation (MM) among isotretinoin-exposed pregnant women over the years through a systematic review and meta-analysis.Methods Eligible studies were searched and identified using various databases. Single-arm meta-analysis and meta-analysis of odd ratios among controlled studies were performed using Review Manager version 5.3.Results Ten eligible studies that combined 2,783 isotretinoin-exposed women were included in our study. The rate of MM weighted for the sample size was 15%. Three studies that included an unexposed comparison group were eligible for the meta-analysis. The pooled odds ratio of MM for isotretinoin-exposed women was 3.76. After 2006, the pooled odds ratio of MM for isotretinoin exposure was significantly lower at 1.04.Conclusion The current rate of MM in isotretinoin-exposed women was substantially lower after 2006.

Grid cells in the entorhinal cortex appear to represent spatial location via a triangular coordinate system. Such cells, which have been identified in rats, bats and monkeys, are believed to support a wide range of spatial behaviors. Recording neuronal activity from neurosurgical patients performing a virtual-navigation task, we identified cells exhibiting grid-like spiking patterns in the human brain, suggesting that humans and simpler animals rely on homologous spatial-coding schemes.

A finite discrete graph is turned into a quantum (metric) graph once a finite length is assigned to each edge and the one-dimensional Laplacian is taken to be the operator. We study the dependence of the spectral gap (the first positive Laplacian eigenvalue) on the choice of edge lengths. In particular, starting from a certain discrete graph, we seek the quantum graph for which an optimal (either maximal or minimal) spectral gap is obtained. We fully solve the minimization problem for all graphs. We develop tools for investigating the maximization problem and solve it for some families of graphs.