Real-Time Precise Orbit Determination for LEO between Kinematic and Reduced-Dynamic with Ambiguity Resolution

The real-time integer-ambiguity resolution of the carrier-phase observation is one of the most effective approaches to enhance the accuracy of real-time precise point positioning (PPP), kinematic precise orbit determination (KPOD), and reduced-dynamic precise orbit determination (RPOD) for low earth orbit (LEO) satellites. In this study, the integer phase clock (IPC) and wide-lane satellite bias (WSB) products from CNES (Centre National d’Etudes Spatiales) are used to fix ambiguity in real time. Meanwhile, the three models of real-time PPP, KPOD, and RPOD are applied to validate the contribution of ambiguity resolution. Experimental results show that (1) the average positioning accuracy of IGS stations for ambiguity-fixed solutions is improved from about 7.14 to 5.91 cm, with an improvement of around 17% compared to the real-time float PPP solutions, with enhancement in the east-west direction particularly significant, with an improvement of about 29%; (2) the average accuracy of the estimated LEO orbit with ambiguity-fixed solutions in the real-time KPOD and RPOD mode is improved by about 16% and 10%, respectively, with respect to the corresponding mode with the ambiguity-float solutions; (3) the performance of real-time LEO RPOD is better than that of the corresponding KPOD, regardless of fixed- or float-ambiguity solutions. Moreover, the average ambiguity-fixed ratio can reach more than 90% in real-time PPP, KPOD, and RPOD.

Gonadal Hormone Trigger Traf6-mediated Dynamic Microglial Alterations That Correlate With Depressive Symptomatology

Backgrounds: Gonadal hormone deficiency is associated with the development of depression, but what mediates this association is unclear. To test the possibility that it reflects neuroimmune and neuroinflammatory processes, we analyzed how gonadal hormone deficiency and replacement affect microglial activation and inflammatory response during the development of depressive symptomatology in gonadectomized male mice. Methods: Adult male ICR mice received gonadectomy. Gonadal hormone levels, neuroinflammation, mciroglial activation and depressive behaviors were evaluated 7 days, 14 days, and 30 days later. Furthermore, the neuroprotective mechanism of treatment with testosterone and estradiol on depressive symptomatology were also observed.Results: Testosterone level and the ratio of testosterone to estradiol in the serum and brain tissue of mice exposed to 3-35 days of chronic unpredictable stress were much lower than in control animals. Gonadal hormone sustained deficiency in gonadectomized mice and subsequent led to acute inflammation at day 7 following castration. Activating microglia in mice exposed to 7 days of castration subsequently suppressed the proliferation of microglia, such that their numbers in hippocampus and cortex were lower than the numbers in sham-operated mice after 30 days of castration. Here, we showed that gonadal hormone deficiency induces Traf6-mediated microglia activation, a type of inflammatory mediator. Microglia treated in this way for long time showed down-regulation of activation markers, abnormal morphology and depressive-like behaviors. Restoration and maintenance of a fixed ratio of testosterone to estradiol significantly suppressed microglial activation, neuronal necroptosis, dramatically inducing hippocampal neurogenesis and reducing depressive behaviors via the suppression of Traf6/TAK1 pathway. Conclusions: These findings suggest that activated or immunoreactive microglia contribute to gonadal hormone deficiency-induced depression, as well as testosterone and estradiol exert synergistic anti-depressant effects via suppressing microglial activaton in gonadectomized male mice, possibly through Traf6 signaling.

Direct ink write multi-material printing of PDMS-BTO composites with MWCNT electrodes for flexible force sensors

With recent advances of additive manufacturing (AM) technology, direct ink write (DIW) printing has allowed to incorporate multi-material printing of various materials with freedom of design and complex geometric shapes to complete functional sensors in a one-step fabrication. This paper introduces the use of DIW 3D printing of polydimethylsiloxane (PDMS) with barium titanate (BTO) filler as stretchable composites with tunable piezoelectric properties that can be used for force sensors applications. To improve the bonding between stretchable piezoelectric composites and electrodes, multi-walled carbon nanotubes (MWCNT) was included in the fabrication of electrodes at a fixed ratio of 11 wt. %. The alignment of the BTO dipoles was achieved through corona poling method, which applies an electric charge on the surface layer of the functional material, aligning the dipoles in the desired direction and thus gaining the piezoelectricity. Different BTO mixing ratios (10-50 wt. %) were evaluated in order to obtain tunable piezoelectric properties and compare the sensitivity with respect their elastic properties. Tensile testing and piezoelectric testing were carried out to characterize mechanical and piezoelectric properties. Results showed that fabricated PDMS with 50 wt. % BTO gave the highest piezoelectric coefficient (d33) of 11.5 pC/N and with an output voltage of 385 mV under compression loading of >200 lbF. This demonstrates feasibility of using multi-material DIW printing to fabricate piezoelectric force sensors with integrated electrodes in one-step without compromising the flexibility of the material.

Discovery of Novel Cyclic Ethers with Synergistic Antiplasmodial Activity in Combination with Valinomycin

With drug resistance threatening our first line antimalarial treatments, novel chemotherapeutics need to be developed. Ionophores have garnered interest as novel antimalarials due to their theorized ability to target unique systems found in the Plasmodium-infected erythrocyte. In this study, during the bioassay-guided fractionation of the crude extract of Streptomyces strain PR3, a group of cyclodepsipeptides, including valinomycin, and a novel class of cyclic ethers were identified and elucidated. Further study revealed that the ethers were cyclic polypropylene glycol (cPPG) oligomers that had leached into the bacterial culture from an extraction resin. Molecular dynamics analysis suggests that these ethers are able to bind cations such as K+, NH4+ and Na+. Combination studies using the fixed ratio isobologram method revealed that the cPPGs synergistically improved the antiplasmodial activity of valinomycin and reduced its cytotoxicity in vitro. The IC50 of valinomycin against P. falciparum NF54 improved by 4–5-fold when valinomycin was combined with the cPPGs. Precisely, it was improved from 3.75 ± 0.77 ng/mL to 0.90 ± 0.2 ng/mL and 0.75 ± 0.08 ng/mL when dosed in the fixed ratios of 3:2 and 2:3 of valinomycin to cPPGs, respectively. Each fixed ratio combination displayed cytotoxicity (IC50) against the Chinese Hamster Ovary cell line of 57–65 µg/mL, which was lower than that of valinomycin (12.4 µg/mL). These results indicate that combinations with these novel ethers may be useful in repurposing valinomycin into a suitable and effective antimalarial.

Maternal Separation Stress Affects Voluntary Ethanol Intake in a Sex Dependent Manner

Maternal separation (MS) stress is a predictive animal model for evaluating the effects of early stress exposure on alcohol use disorders (AUD). The extended amygdala (AMY) is a complex circuit involved in both stress- and ethanol-related responses. We hypothesized that MS stress may increase ethanol consumption in adulthood, as well as augment neuronal activity in extended AMY, in a sex-dependent manner. We aimed to investigate the influence of MS stress on the ethanol consumption of male and female mice, and the involvement of extended amygdala sub-nuclei in this process. The C57BL/6J pups were subjected to 180min of MS, from postnatal day (PND) 1 to 14. The control group was left undisturbed. On PND 45, mice (n=28) in cages were exposed to a bottle containing 20% ethanol (w/v) for 4h during the dark period of the light-dark cycle, for 3weeks. Afterward, mice underwent ethanol self-administration training in operant chambers under fixed ratio (FR) schedule. Then, subjects were tested under 2h sessions of a progressive-ratio (PR) schedule of reinforcement (the last ratio achieved was considered the breaking point), and at the end, a 4h session of FR schedule (binge-intake). An immunohistochemistry assay for Fos protein was performed in Nucleus Accumbens (NAcc), Bed Nucleus of Stria Terminalis (BNST), and AMY. Our results showed that in the third week of training, the female MS group consumed more ethanol than the respective control group. The MS group presented increased breakpoint parameters. Female control group and male MS group were more resistant to bitter quinine taste. Increased Fos-immunoreactive neurons (Fos-IR) were observed in the central nucleus of AMY, but not in NAcc nor BNST in male maternal-separated mice. Maternal separation stress may influence ethanol intake in adulthood, and it is dependent on the sex and reinforcement protocol.

Viral-Mediated Knockdown of Nucleus Accumbens Shell PAC1 Receptor Promotes Excessive Alcohol Drinking in Alcohol-Preferring Rats

Alcohol use disorder (AUD) is a chronic, relapsing disorder whose genetic and environmental susceptibility components are not fully understood. Neuropeptidergic signaling has been repeatedly implicated in modulating excessive alcohol drinking, especially within sub-regions of the striatum. Here, we investigated the potential involvement of the selective receptor for pituitary adenylate cyclase-activating polypeptide (PACAP), PAC1R, in the nucleus accumbens shell (NAcc Shell) in excessive alcohol drinking in alcohol-preferring rats, an established animal model of the genetic propensity for alcoholism. Scr:sP alcohol-preferring rats were trained to operantly self-administer alcohol and then either an AAV virus short-hairpin RNA (shRNA) targeted to knockdown PAC1R, or an AAV control virus were microinfused into the NAcc Shell. NAcc Shell PAC1R shRNA knockdown virus was confirmed to significantly decrease PAC1R levels in the NAcc Shell. The effects of NAcc Shell PAC1R shRNA knockdown on ethanol self-administration were investigated using a Fixed Ratio (FR) 1 and a Progressive Ratio (PR) schedule of reinforcement. The effect of PAC1R knockdown on self-administration of an alternative reinforcer, saccharin, was also assessed. The results showed that the reduction in PAC1R in the NAcc Shell led to excessive ethanol drinking, increased preference for ethanol, and higher motivation to drink. NAcc Shell PAC1R shRNA knockdown did not comparably increase saccharin self-administration, suggesting selectivity of action. These data suggest that NAcc Shell PAC1R may serves as a “brake” on alcohol drinking, and thereby the loss of function of PAC1R leads to excessive alcohol consumption. Therefore, the PACAP/PAC1R system may represent a novel target for the treatment of AUD.

Development of high melt strength polypropylene and its application in thermoplastic elastomeric composition

High melt strength polypropylene (HMS-PP) with a long-chain branched structure is a modified form of polypropylene (PP) which has basic properties of regular PP but with superior melt drawability. This paper reports on the development of gel-free HMS-PP from a linear isotactic PP through the introduction of long-chain branching on its backbone via a reactive extrusion process, using dicetyl-peroxydicarbonate (PODIC) alone or in combination with a coagent. The melt strength and the mechanical properties such as impact and flexural strength of PP showed improvements with the modification with PODIC. 5000 ppm by weight of PODIC was found to provide the best balance of properties. The efficacies of zinc diethyldithiocarbamate (ZDC) and tetramethyl thiuram disulphide (TMTD) as coagents in combination with PODIC to augment properties of HMS-PP further were explored. TMTD offered slightly enhanced performance benefits as compared to ZDC at an optimized concentration of 100 ppm by weight. The application potential of HMS-PP in thermoplastic elastomeric blends of HMS-PP with ethylene-propylene-diene monomer (EPDM) rubber at a fixed ratio of 35/65 by weight was also investigated. Structure-property correlations were established between the extent of long-chain branching in the modified PP and the properties of the resultant thermoplastic elastomeric composition.