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© The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License., Hutchinson-Gilford Progeria Syndrome (HGPS) is a premature aging disease in children that leads to early death. Smooth muscle cells (SMCs) are the most affected cells in HGPS individuals, although the reason for such vulnerability remains poorly understood. In this work, we develop a microfluidic chip formed by HGPS-SMCs generated from induced pluripotent stem cells (iPSCs), to study their vulnerability to flow shear stress. HGPS-iPSC SMCs cultured under arterial flow conditions detach from the chip after a few days of culture; this process is mediated by the upregulation of metalloprotease 13 (MMP13). Importantly, double-mutant LmnaG609G/G609GMmp13-/- mice or LmnaG609G/G609GMmp13+/+ mice treated with a MMP inhibitor show lower SMC loss in the aortic arch than controls. MMP13 upregulation appears to be mediated, at least in part, by the upregulation of glycocalyx. Our HGPS-SMCs chip represents a platform for developing treatments for HGPS individuals that may complement previous pre-clinical and clinical treatments., This work was funded by FEDER through the Program COMPETE and by Portuguese fund through FCT in context of the projects EXPL/BIM-MED/2267/2013 and POCI-01-0145-FEDER-029229, as well as the European project ERAatUC (ref. 669088).PRP wishes to thank FCT for a BD fellowship (SFRH/BD/71042/2010). AR is supported by the Miguel Servet research contract CPII15/00003 from Instituto de Salud Carlos III, Spain. The FLI is a member of the Leibniz Association and is financiallysupported by the Federal Government of Germany and the State of Thuringia. The authors gratefully acknowledge support from the FLI proteomics core facility.

This paper proposes a analysis of a LED driver. The driver consists of a resonant switched capacitor converter designed to operate in CCM and fed from nanogrid. This mode of operation allows the reduction of current peaks and, consequently, reduction of conduction losses. There is ZVS in the turn-off of the switches due to the full charge and discharge of the switched capacitor. Therefore, switching losses are also reduced. The inductor operates at twice the switching frequency, contributing to the reduction of the magnetic elements. In addition, this converter has the advantage of stabilizing the power of the LED by adjusting the switching frequency, without the needing sensors and control circuit, which reduces the cost of the circuit. In order to validate the comparative analysis, a 10W prototype was designed in a laboratory, operating with a switching frequency of approximately 58 KHz, and presenting an overall efficiency of 92.8% in nominal conditions.

This paper proposes a design and analysis of output filter with long lifetime electrolytic capacitor for a single stage resonant converter based on a switched capacitor for LED driver. A study about conventional capacitors and long life capacitors is presented. Furthermore, the parameters that degrade the electrolytic capacitors lifetime and the effect of current ripple and of LED intrinsic series resistance on the output filter capacitor C o are discussed. Experimental results are presented in order to validate the methodology proposed for the output filter sizing.

This paper proposes a low-cost educational tool to trace the curves of PV modules. A MOSFET transistor was used to operate as a variable electronic load, which is driven by a simple RC circuit with a low cost objective. The data were captured with a basic digital oscilloscope, which allowed viewing captured curves and save the results for later analysis. The study of the photovoltaic cell electrical model allowed estimating the level of solar radiation, the maximum power point and the PV module temperature at the time of data capture. The theoretical analysis and experimental results of a KC65T module manufactured by Kyocera validated the proposal.

This paper presents the LED driver with power factor correction (PFC) and low current harmonic distortion. The structure provides low current ripple, low percent flicker and zero voltage switching (ZVS). The converter output power is varied by reducing the switching frequency, and it does not use electrolytic capacitors (E-cap), what increase the LED driver lifetime. A prototype was developed to evaluate the performance of the proposal, while results are properly presented and discussed. The experimental results presented power factor is 0.996, 3.19% current total harmonic distortion, 9.5% low frequency current ripple and a percent flicker in accordance with the IEEE Std 1789-2015.

This paper presents the evaluation of a single-phase topology and a three-phase topology. Photometric and flicker characteristics were compared. To validate the results, a single-phase charge-pump driver for power LEDs driving a 22 W luminaire, and a three-phase driver with a switched capacitor was used for power LEDs driving a 216 W luminaire. The obtained results were compared with the actual norms. The three-phase driver is operating within the recommended operating region in Std. 1789-2015, while the single-phase driver is operating outside the recommended region.

The availability of CRISPR/Cas9 technology has enabled the rapid establishment of gene knockouts in many cell types and even whole organisms. However, conditional inactivation of essential genes remains a challenge. We devised an approach named DECAI (DEgradation based on Cre-regulated- Artificial Intron). It utilizes a small cassette of just 201 nucleotides that is inserted into the coding exon of a target gene using CRISPR/Cas9 technology and homology-directed repair. As its sequence is derived from an artificial intron, the cassette is removed by the splicing machinery and thus leaves no trace in the “off-state”. Upon activation with Cre recombinase (“on-state”), the intron is crippled and the target gene is disrupted by a series of stop codons. We exemplify the utility of this approach on several non-essential and essential human genes. Clones bearing the conditional knockout cassette are recovered at frequencies above 5% and cassette function can be traced at the genomic DNA and the mRNA level. Importantly, cassette activation leads to loss of gene expression as judged by flow cytometry, Western blot or immunofluorescence. Altogether, this highlights the broad utility of the approach for conditional gene inactivation and suggests that this tool could be used to study the loss-of-function phenotypes of essential genes.

Summary The Nucleosome Remodeling and Deacetylase (NuRD) complex is essential for embryonic development and pluripotent stem cell differentiation. In this study, we investigated whether NuRD is also involved in the reverse biological process of induction of pluripotency in neural stem cells. By knocking out MBD3, an essential scaffold subunit of the NuRD complex, at different time points in reprogramming, we found that efficient formation of reprogramming intermediates and induced pluripotent stem cells from neural stem cells requires NuRD activity. We also show that reprogramming of epiblast-derived stem cells to naive pluripotency requires NuRD complex function and that increased MBD3/NuRD levels can enhance reprogramming efficiency when coexpressed with the reprogramming factor NANOG. Our results therefore show that the MBD3/NuRD complex plays a key role in reprogramming in certain contexts and that a chromatin complex required for cell differentiation can also promote reversion back to a naive pluripotent cell state., Graphical Abstract, Highlights • Mbd3 facilitates the initiation of neural stem cell reprogramming • Mbd3 is also required for efficient iPSC generation from EpiSCs and preiPSCs • Overexpression of Mbd3/NuRD facilitates reprogramming in a context-dependent manner, dos Santos et al. show that Mbd3/NuRD plays a positive role in reprogramming in certain contexts and that overexpression of Mbd3 facilitates Nanog-mediated reprogramming.

Oct4 is considered a master transcription factor for pluripotent cell self-renewal, but its biology remains poorly understood. Here, we investigated the role of Oct4 using the process of induced pluripotency. We found that a defined embryonic stem cell (ESC) level of Oct4 is required for pluripotency entry. However, once pluripotency is established, the Oct4 level can be decreased up to sevenfold without loss of self-renewal. Unexpectedly, cells constitutively expressing Oct4 at an ESC level robustly differentiated into all embryonic lineages and germline. In contrast, cells with low Oct4 levels were deficient in differentiation, exhibiting expression of naive pluripotency genes in the absence of pluripotency culture requisites. The restoration of Oct4 expression to an ESC level rescued the ability of these to restrict naive pluripotent gene expression and to differentiate. In conclusion, a defined Oct4 level controls the establishment of naive pluripotency as well as commitment to all embryonic lineages.

This study aimed to investigate the effect of sulfated polysaccharide from red seaweed Solieria filiformis (Fraction F II) in the inflammatory hypernociception in the temporomandibular joint (TMJ) of rats. Male Wistar rats were pretreated (30min) with a subcutaneous injection (s.c.) of vehicle or FII (0.03, 0.3 or 3.0mg/kg) followed by intra-TMJ injection of 1.5% Formalin or 5-hydroxytryptamine (5-HT, 225μg/TMJ). In other set of experiments rats were pretreated (15min) with an intrathecal injection of the non-selective opioid receptors Naloxone, or μ-opioid receptor antagonist CTOP, or δ-opioid receptor Naltridole hydrochloride, or κ-opioid receptor antagonist Nor-Binaltorphimine (Nor-BNI) followed by injection of FII (s.c.). After 30min, the animals were treated with an intra-TMJ injection of 1.5% formalin. After TMJ treatment, behavioral nociception response was evaluated for a 45-min observation period, animals were terminally anesthetized and periarticular tissue, trigeminal ganglion and subnucleus caudalis (SC) were collected plasma extravasation and ELISA analysis. Pretreatment with F II significantly reduced formalin- and serotonin-induced TMJ nociception, inhibit the plasma extravasation and inflammatory cytokines release induced by 1.5% formalin in the TMJ. Pretreatment with intrathecal injection of Naloxone, CTOP, Naltridole or Nor-BNI blocked the antinociceptive effect of F II in the 1.5% formalin-induced TMJ nociception. In addition, F II was able to significantly increase the β-endorphin release in the subnucleus caudalis. The results suggest that F II has a potential antinociceptive and anti-inflammatory effect in the TMJ mediated by activation of opioid receptors in the subnucleus caudalis and inhibition of the release of inflammatory mediators in the periarticular tissue.

This paper presents a dimmable charge-pump driver to power light-emitting diodes (LEDs) with power factor correction (PFC) and Zero Voltage Switching (ZVS). The proposed LED driver does not utilize electrolytic capacitors, providing a high useful lifetime, and it can stabilize the output current in open loop control without needing current sensors, which reduces the cost. The output power is proportional to the switching frequency, which allows the LEDs dimming. A prototype with 22 W was implemented and experimental results were discussed. The prototype presented a power factor of 0.996 and an efficiency of 89.5 %. The driver output power was reduced by more than 40% through the switching frequency while varying of 53 kHz to 30 kHz and the converter has continues to operate in ZVS.

This paper presents a switched capacitor-based converter to drive high power light emitting diodes (LEDs). Unlike the traditional switched capacitor based one, the proposed converter uses an inductor to avoid the forced charging and discharging operation reducing stress current in circuit. The proposed converter provides inherent power factor correction (PFC) and the switched capacitors are used as isolation capacitors. The proposed converter also uses a LC filter to reduce the output current ripple through LED array instead using a bulk electrolytic capacitor. The basic description of the topology is presented and a laboratory prototype of 48 W has been implemented. The experimental results presented demonstrate the technical feasibility of the proposed converter applied as LED driver.

This paper proposes a resonant switched capacitor-based converter to driver high power light emitting diodes (LEDs). Unlike the traditional switched capacitor based one, the proposed converter uses an inductor to avoid the forced charging and discharging operation reducing stress current in circuit. The proposed converter provides inherent power factor correction (PFC) and the switched capacitors are used as isolation capacitors. The basic description of the topology is presented and a 49 W, 220 V ac grid laboratory prototypes has been implemented. The experimental results presented demonstrate the technical feasibility of the proposed converter applied as LED driver.

This study evaluated the influence of the bimaxillary flask (BMF) and two different investing materials on first molar inclination in dentures processed by microwave irradiation.The BMF may minimise tooth displacement, saving time and improving occlusion.Forty pairs of dentures were randomised into four groups: stone wall in monomaxillary flask; silicone wall in BMF; stone wall in BMF; acrylic resin retentions and silicone in BMF. Dentures were processed by microwave irradiation. Two referential points were established on tooth surface. A microscope and a digital pachymeter were used to measure the distance between these points, and the angles α (right maxillary molar), β (left maxillary molar), α' (right mandibular molar) and β' (left mandibular molar) were calculated by the law of cosines. Data were submitted to Kruskal-Wallis (5% significance).No difference was observed among the groups (p0.05). In the intra-group analysis, α was significantly different for groups I, II and III; α', for groups II and IV; β, for all groups; β', for groups III and IV.First molar inclination was similar for monomaxillary and BMFs. The use of stone or silicone as investing materials presented the same effect on tooth inclination.