Interplay between a Mental Disorder Risk Gene and Developmental Polarity Switch of GABA Action Leads to Excitation-Inhibition Imbalance

Acknowledgments: We thank members of the Ming and Song laboratories for comments and suggestions, D. Johnson for technical support, and J. Schnoll for lab coordination. This work was supported by grants from the National Institutes of Health (NIH) (R01MH105128 and R35NS097370 to G.-L.M. and R37NS047344 to H.S.) and from the National Alliance for Research on Schizophrenia and Depression (NARSAD) to G.-L.M., H.S., and E.K. Author Contributions: E.K. and J.S contributed equally to this work. J.S. performed electrophysiological analysis and E.K. performed morphological analysis. Y.L. and K.-S.H. contributed to electrophysiology data collection, Y.G. and S.G. helped with some of the retrovirus production, and B.B. helped with rabies synaptic tracing. J.P., J.H.L., Q.H., W.L., and K.M.C. contributed to additional data collection. E.K., J.S., H.S., and G-L.M. designed the project and wrote the manuscript.Peer reviewedPublisher PD

Identification of the Crack in Composite Shells

Flaws exist in most machine parts and structures which under critical conditions can rapidly grow and cause the sudden rupture of the component. The catastrophic fracture can be prevented if an early warning, on-line real-time system is devised to trace the crack position and its severity. There are functional relationships between the vibrational frequency and the local compliance. The crack is one of the major elements which gives rise to the local flexibility of the component. Thus, an analysis of the vibrational response of the cracked component, furnishes sufficient information regarding the size and position of the propagating crack. Composite shell-like components are widely used in industry due to their high strength-to-weight ratios. However, these materials are usually susceptible to cracking. Identification of the cracks in composite shells is of great importance and is studied in the present thesis. The vibrational analysis of cracked shells reveals significant changes in the frequency spectrum and the coupling of vibrational modes, which provides promising tools to diagnose the crack and locate its approximate position

Design of experiences to improve empathy, self-knowledge and assertiveness in the adolescent population of Bogotá to reduce and prevent bullying

El flagelo silencioso del acoso escolar está determinando las condiciones de vida y cada vez avasalla, carcome y corroe sin importar la edad. Esto es de suma preocupación debido a los niños, niñas y jóvenes que se ven abocados a asumir un trauma o una experiencia que no les corresponde. Motivo por el cual surge la necesidad de abordar este tema y realizar un análisis para conocer más afondo las causas y casos para así crear un proceso estratégico e innovador mediante el diseño industrial y poder erradicar el problema en su mayoría. Se requieren estrategias y mecanismos de comunicación para facilitar el abordaje del bullying en los colegios y mejorar los resultados para reducir esta problemática. Este acto puede verse directamente relacionado con acoso psicológico/emocional, físico, verbal, sexual, social y tecnológico. El propósito de este trabajo va de la mano con el entendimiento de la situación actual para saber la raíz de este problema, generar soluciones preventivas y reactivas frente a los víctimas y victimarios del bullying en adolescentes de instituciones educativas.The silent scourge of bullying is determining living conditions and each time it overwhelms, eats away and corrodes regardless of age. This is of great concern due to the children and young people who are forced to assume a trauma or an experience that does not correspond to them. Reason why the need arises to address this issue and carry out an analysis to learn more about the causes and cases in order to create a strategic and innovative process through industrial design and to be able to eradicate the problem in its majority. Communication strategies and mechanisms are required to facilitate the approach to bullying in schools and improve results to reduce this problem. This act can be directly related to psychological/emotional, physical, verbal, sexual, social and technological harassment. The purpose of this work goes hand in hand with the understanding of the current situation to know the root of this problem, generate preventive and reactive solutions against the victims and perpetrators of bullying in adolescents from educational institutions.Diseñador (a) IndustrialPregrad

Numerical Assessment of Roll Motion Characteristics and Damping Coefficient of a Ship

Accurate calculation of the roll damping moment at resonance condition is essential for roll motion prediction. Because at the resonance condition, the moment of inertia counteracts restoring moment and only the damping moment resists increase in the roll angle. There are various methods to calculate the roll damping moment which are based on potential flow theory. These methods have limitations to taking into account the viscous effects in estimating the roll motion, while, CFD as a numerical method is capable of considering the viscous effects. In this study, a CFD method based on a harmonic excited roll motion (HERM) technique is used to compute the roll motion and the roll damping moment of a containership’s model in different conditions. The influence of excitation frequency, forward speed and degrees of freedom at beam-sea and oblique-sea realizations are considered in estimating the roll damping coefficients. The results are validated against model tests, where a good agreement is found

Recent advances in genome editing of stem cells for drug discovery and therapeutic application

Genome engineering technologies right from viral vector-mediated to protein-based editing-which include zinc finger nucleases, TALENs, and CRISPR/Cas systems-have been improved significantly. These technologies have facilitated drug discovery and have resulted in the development of potential curative therapies for many intractable diseases. They can efficiently correct genetic errors; however, these technologies have limitations, such as off-target effects and possible safety issues, which need to be considered when employing these techniques in humans. Significant efforts have been made to overcome these limitations and to accelerate the clinical implementation of these technologies. In this review, we focus on the recent technological advancements in genome engineering and their applications in stem cells to enable efficient discovery of drugs and treatment of intractable diseases. (C) 2020 The Authors. Published by Elsevier Inc.

Effectiveness and Safety of Herbal Medicine for Atopic Dermatitis: An Overview of Systematic Reviews

Objectives. Herbal medicine (HM) is attracting attention for treating atopic dermatitis (AD). This overview was conducted to summarize and critically evaluate the current systematic reviews (SRs) on HM for the treatment of AD. Methods. Through comprehensive searches, all relevant SRs on HM for AD published until May 2020 were included. The quality of included SRs was assessed using the AMSTAR-2 tool. Moreover, original randomized controlled trials (RCTs) included in the SRs were resynthesized to investigate the efficacy and safety of oral HM for AD. The quality of evidence for the main findings was evaluated using the GRADE approach. Results. Nine SRs were included in this overview. HM showed significantly better efficacy in terms of total effective rate (TER), itching and sleep symptom scores, quality of life, and the dose of topical treatment used compared with placebo. HM as a monotherapy and/or an adjunctive therapy to conventional medication (CM) showed significantly better results on the efficacy, symptom relief, and some laboratory parameters related to the inflammatory response. The methodological quality was generally low. When 58 original RCTs were reanalyzed, HM showed significantly lower SCORing Atopic Dermatitis (SCORAD) score and higher TER than the placebo or CM. In terms of the safety profile, HM was not significantly different from the placebo and was better than CM. The quality of evidence ranged from “moderate” to “very low.” Conclusion. The results suggested that HM as a monotherapy or an adjunctive therapy is promising for the treatment of AD. However, due to low methodological quality and low quality of evidence, further rigorous, well-designed, high-quality SRs, and RCTs are needed to make clinical recommendations on HM use

16-Channel High-CMRR Neural-Recording Amplifiers Using Common-Made-Tracking Power Supply Rails

This paper presents a neural recording amplifier that operates in environments where large common-mode signals interfere. The proposed scheme employs two types of LDOs that generate isolated supply voltages and a buffer to sense a common-mode signal. Thanks to the isolated supply rails, both the intrinsic common-mode rejection ratio (ICMRR) and common-mode input impedance of the low-noise amplifier (LNA) are increased, which leads to the total common-mode rejection ratio (TCMRR) above 89.2 dB up to 1 kHz even in 16-channel recording with a shared reference electrode. Compared to the conventional method, the TCMRR is improved by 48.7 dB even for 28% mismatch of the electrode-tissue impedance (ETI) and 1% mismatch of the LNA input capacitances. © 2018 IEEE

Acupuncture Modulates Intracranial Self-Stimulation of the Medial Forebrain Bundle in Rats

Acupuncture affects the central nervous system via the regulation of neurotransmitter transmission. We previously showed that Shemen (HT7) acupoint stimulation decreased cocaine-induced dopamine release in the nucleus accumbens. Here, we used the intracranial self-stimulation (ICSS) paradigm to evaluate whether HT stimulation regulates the brain reward function of rats. We found that HT stimulation triggered a rightward shift of the frequency–rate curve and elevated the ICSS thresholds. However, HT7 stimulation did not affect the threshold-lowering effects produced by cocaine. These results indicate that HT7 points only effectively regulates the ICSS thresholds of the medial forebrain bundle in drug-naïve rats

Base editing in human cells with monomeric DddA-TALE fusion deaminases

AbstractInter-bacterial toxin DddA-derived cytosine base editors (DdCBEs) enable targeted C-to-T conversions in nuclear and organellar DNA. DddAtox, the deaminase catalytic domain derived from Burkholderia cenocepacia, is split into two inactive halves to avoid its cytotoxicity in eukaryotic cells, when fused to transcription activator-like effector (TALE) DNA-binding proteins to make DdCBEs. As a result, DdCBEs function as pairs, which hampers gene delivery via viral vectors with a small cargo size. Here, we present non-toxic, full-length DddAtox variants to make monomeric DdCBEs (mDdCBEs), enabling mitochondrial DNA editing with high efficiencies of up to 50%, when transiently expressed in human cells. We demonstrate that mDdCBEs expressed via AAV in cultured human cells can achieve nearly homoplasmic C-to-T editing in mitochondrial DNA. Interestingly, mDdCBEs often produce mutation patterns different from those obtained with conventional dimeric DdCBEs. Furthermore, mDdCBEs allow base editing at sites for which only one TALE protein can be designed. We also show that transfection of mDdCBE-encoding mRNA, rather than plasmid, can reduce off-target editing in human mitochondrial DNA.11Nsciescopu