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The mechanistic/mammalian target of rapamycin complex 1 (mTORC1) integrates multiple signals to regulate critical cellular processes such as mRNA translation, lipid biogenesis, and autophagy. Germline and somatic mutations in mTOR and genes upstream of mTORC1, such as PTEN, TSC1/2, AKT3, PIK3CA, and components of GATOR1 and KICSTOR complexes, are associated with various epileptic disorders. Increased mTORC1 activity is linked to the pathophysiology of epilepsy in both humans and animal models, and mTORC1 inhibition suppresses epileptogenesis in humans with tuberous sclerosis and animal models with elevated mTORC1 activity. However, the role of mTORC1-dependent translation and the neuronal cell types mediating the effect of enhanced mTORC1 activity in seizures remain unknown. The eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) and 2 (4E-BP2) are translational repressors downstream of mTORC1. Here we show that the ablation of 4E-BP2, but not 4E-BP1, in mice increases the sensitivity to pentylenetetrazole (PTZ)- and kainic acid (KA)–induced seizures. We demonstrate that the deletion of 4E-BP2 in inhibitory, but not excitatory neurons, causes an increase in the susceptibility to PTZ-induced seizures. Moreover, mice lacking 4E-BP2 in parvalbumin, but not somatostatin or VIP inhibitory neurons exhibit a lowered threshold for seizure induction and reduced number of parvalbumin neurons. A mouse model harboring a human PIK3CA mutation that enhances the activity of the PI3K-AKT pathway (Pik3ca(H1047R-Pvalb)) selectively in parvalbumin neurons shows susceptibility to PTZ-induced seizures. Our data identify 4E-BP2 as a regulator of epileptogenesis and highlight the central role of increased mTORC1-dependent translation in parvalbumin neurons in the pathophysiology of epilepsy.

To investigate whether the rate of euploidy and pregnancy outcomes are affected by smooth endoplasmic reticulum clusters (SERc) and other metaphase II human oocyte dysmorphisms.Retrospective analysis of the morphologies of metaphase II (MII) human oocytes, which had developed into 590 biopsied blastocysts derived from 109 patients that received preimplantation genetic testing for aneuploidies (PGT-A) cycles between March 2013 and December 2017. The euploid rate of blastocysts that originated from morphologically abnormal or normal oocytes were analyzed. The chromosome status of the blastocysts was determined and analyzed by array comparative genomic hybridization (aCGH) or next generation sequencing (NGS) following trophectoderm biopsy.According to the odds ratios obtained for each oocyte morphotype, no statistically significant relationship was found between oocyte dysmorphisms and euploid rate. Specifically, although SERc-positive oocytes had a higher rate of arrest at two pronuclei, or 2 PN (26.7% vs. 19.4%, p 0.05), the blastocyst formation rate was not affected as compared with SERc-negative oocytes (40.0% vs. 38.6%, p 0.05). Among nine euploid embryos derived from oocytes with SERc, three single euploid embryo transfers were performed, of which one resulted in blighted ovum, and two resulted in the births of two healthy, singleton term babies.The results presented here suggest that oocyte dysmorphisms do not affect the euploidy rate of the blastocyst. The occurrence of SERc in the oocyte does not seem to impair the developing blastocyst nor does it interfere with good embryo formation rate and euploid rate. Thus, the embryos derived from SERc-positive oocytes could still be considered for embryo transfer if there are no other embryos available.

Objective: It is known that embryos with faster growing potential, especially in blastocyst development, correlate with the increased euploid rate. Our study investigated the preimplantation genetic screening cycle to analyze the correlation between early blastulation (EB) on day 4 embryo and the euploid rate. Materials and methods: This is a retrospective study examining 273 biopsied blastocysts after preimplantation genetic screening obtained from 54 patients from March 2013 to March 2017. Of the 273 biopsied embryos, 81 had early blastulation on day 4 and were classified as the EB (+) group, while the other 192 had no early blastulation and were classified as the EB (−) group. Euploid rates were compared between the two groups. A total of 34 single euploid embryos were transferred, with 14 from the EB (+) group and 20 from the EB (−) group. Clinical pregnancy was compared between the groups. Results: There is a statistically significant increase in the euploid rate in the EB (+) group (49.4% vs. 34.4%, p = 0.02). The clinical pregnancy rate was also increased in the single euploid embryo transfer group with early blastulation, but did not reach statistical significance (71.4% vs. 50.0%, p = 0.211). Conclusions: Early blastulation of day 4 embryo correlates significantly with the euploid rate. Early blastulation of day 4 embryo may serve as a potential aid for embryo selection for transfer in preimplantation genetic screening cycles. Keywords: Blastocyst, Embryonic development, Preimplantation genetic screening, Pregnancy rate, Single embryo transfer

An important tenet of learning and memory is the notion of a molecular switch that promotes the formation of long-term memory1–4. The regulation of proteostasis is a critical and rate-limiting step in the consolidation of new memories5–10. One of the most effective and prevalent ways to enhance memory is by regulating the synthesis of proteins controlled by the translation initiation factor eIF211. Phosphorylation of the α-subunit of eIF2 (p-eIF2α), the central component of the integrated stress response (ISR), impairs long-term memory formation in rodents and birds11–13. By contrast, inhibiting the ISR by mutating the eIF2α phosphorylation site, genetically11 and pharmacologically inhibiting the ISR kinases14–17, or mimicking reduced p-eIF2α with the ISR inhibitor ISRIB11, enhances long-term memory in health and disease18. Here we used molecular genetics to dissect the neuronal circuits by which the ISR gates cognitive processing. We found that learning reduces eIF2α phosphorylation in hippocampal excitatory neurons and a subset of hippocampal inhibitory neurons (those that express somatostatin, but not parvalbumin). Moreover, ablation of p-eIF2α in either excitatory or somatostatin-expressing (but not parvalbumin-expressing) inhibitory neurons increased general mRNA translation, bolstered synaptic plasticity and enhanced long-term memory. Thus, eIF2α-dependent mRNA translation controls memory consolidation via autonomous mechanisms in excitatory and somatostatin-expressing inhibitory neurons. Stimulation of de novo protein synthesis in both excitatory and inhibitory, somatostatin-expressing neurons in the mouse hippocampus enhances memory consolidation.

The step-index (SI) and graded-index (GI) plastic optical fibers (POFs) are strong candidates for short-distance transmission, fiber-to-the-home (FTTH) networks, automobile applications and interchip interconnections. The GI POFs which has been proven to reach distances as long as 1 km at 1.25 Gb/s has a relatively low NA. Therefore, the efficient coupling of GI POFs to the light source has become critical to the power budget in the system. Forming a lens-like structure directly on the fiber end is preferred for simplicity of fabrication and packaging, such as polishing and fusion, combing different fibers with the cascaded fiber method and hydroflouride (HF) chemical etching. These approaches are well established, but applicable only to glass. This work proposes a novel structure of a lensed plastic optical fiber (LPOF). The fabrication of the LPOF is demonstrated and the coupling efficiency exceeds 72%.

In this study, CoS coated multi-wall carbon nanotube (CoS/MWCNT) counter electrode (CE) was first incorporated into Pt-free dye-sensitized solar cell (DSSC). This composite film was fabricated using an electrophoresis of MWCNTs onto a fluorinated tin oxide (FTO) substrate and then subjected to CoS electrodeposition. The cyclic voltammetric tests recorded an enhanced electrocatalytic activity when the CoS was deposited onto the surface of the MWCNTs. Additionally, consecutive cyclic voltammetric tests demonstrated that the CE possessed excellent electrochemical stability. Thus, the DSSC assembled with CoS/MWCNT CE showed an enhanced photovoltaic conversion efficiency of 6.96% (compared to 2.91% for DSSCs with MWCNT CE or 5.86% for CoS CE alone) under full sunlight illumination (100 mW cm−2, AM 1.5 G) due to the superior electrocatalytic activity of the out-shell CoS material and highly specific surface of the MWCNTs. Therefore, the CoS/MWCNT composite can be considered as a promising alternative CE for use in low-cost DSSCs. Keywords: CoS, MWCNT, Electrocatalytic activity, Counter electrode, Dye-sensitized solar cell

In this paper, a novel inspection technique for the cascaded fiber fabrication is proposed to improve the coupling performance of such fibers. Instead of using a direct-monitoring method, an indirect technique with the help of the ray tracing and the lens-fiber interference is used. By calculating the optical-path length of the light rays passing through the fiber, the interference fringes and light intensity can be counted. Then, the splicing plane of the cascaded fiber can be determined by observing the difference between the two fiber sections. Simulations and experiments have been performed to find the splicing plane. Finally, the accuracy of fabrication can be improved from 10 to about 1 mum; thus, the coupling loss due to the fabrication process can be reduced

A high-power laser diode (LD) has an elliptical mode field at the endface of its laser diodes. A mode field mismatch between the high-power LD and single-mode fibers (SMFs) results in low coupling efficiency. Accordingly, various methods for coupling between the LD with the higher aspect ratio and SMFs have been employed. Among these approaches, the quadrangular pyramid-shaped fiber endface (QPSFE), which has the capability to control both axial curvatures, can easily match the far field of the high-power LD. However, a QPSFE, which was fabricated by polishing techniques, is hard to employ because of the special shape involved and the need for high precision. This paper presents a novel method for automating QPSFE polishing based on a thorough system analysis and using an online image inspection system. The system successfully supported automatic polishing with an encouraged fiber tip offset that ensures high coupling efficiency. Such an automatic polishing system can also be applied to any other type of fiber endface

This paper presents a high-performance Elliptic Curve Cryptography (ECC) architecture over binary field, based on the Montgomery scalar multiplication algorithm. The word-serial finite field arithmetic unit (AU) is proposed with the optimized operation scheduling and bit-parallel modular reduction. With a dedicated squarer, the 163-bit point scalar multiplication with coordinate conversion can be done in 20.9µs by the design of one AU, and can be further improved to 11.1µs by the one of three AUs, both using 0.13µm CMOS technology. The comparison with other ECC designs justifies the effectiveness of the proposed architecture in terms of performance and area-time efficiency.