A Novel Satellite PRN Code Assignment Method Based on Improved RLF Algorithm.

Low Earth Orbit (LEO) satellites have stronger received signals and more rapid geometry changes than Global Navigation Satellite System (GNSS) satellites, making them attractive for positioning, navigation, and timing (PNT) applications. Due to the low altitude, the LEO constellation requires more satellites to cover the entire globe and more Pseudo Random Noise (PRN) codes to realize Code Division Multiple Access (CDMA), which means greater receiver storage resources and receiver acquisition time. In this paper, different from the traditional methods that assign a unique PRN code to each satellite, we propose a novel method in which several satellites share the same PRN code, and simply demonstrate the feasibility and benefits of this method. To determine the minimum number of PRN codes needed for a constellation, we build a mathematical model. After the algorithm comparison, we improve the recursive largest first (RLF) algorithm so that it has a higher running speed and a smaller approximate optimal solution within a certain time period. By studying polar-orbiting and walker constellations, we find that if other satellite parameters remain the same, the higher the orbital altitude is, the more PRN codes are needed, and no matter what the orbital inclination is, the minimum number of PRN codes remains the same. Overall, it is feasible and meaningful for several satellites sharing the same PRN code to save storage resources and reduce the satellite acquisition time of the receiver. If this new technology is applied, the storage resources and the average satellite acquisition time of the receiver will be, at most, one-third of previous ones.

Anticipated pharmacological role of Aviptadil on COVID-19.

Vasoactive intestinal peptide (VIP) is a neuropeptide that is produced by the lymphoid cells and plays a major role in immunological functions for controlling the homeostasis of the immune system. VIP has been identified as a potent anti-inflammatory factor, in boosting both innate and adaptive immunity. Since December 2019, SARS-Cov-2 was found responsible for the disease COVID-19 which has spread worldwide. No specific therapies or 100% effective vaccines are yet available for the treatment of COVID-19. Drug repositioning may offer a strategy and several drugs have been repurposed, including lopinavir/ritonavir, remdesivir, favipiravir, and tocilizumab. This paper describes the main pharmacological properties of synthetic VIP drug (Aviptadil) which is now under clinical trials. A patented formulation of vasoactive intestinal polypeptide (VIP), named RLF-100 (Aviptadil), was developed and finally got approved for human trials by FDA in 2001 and in European medicines agency in 2005. It was awarded Orphan Drug Designation in 2001 by the US FDA for the treatment of acute respiratory distress syndrome and for the treatment of pulmonary arterial hypertension in 2005. Investigational new drug (IND) licenses for human trials of Aviptadil was guaranteed by both the US FDA and EMEA. Preliminary clinical trials seem to support Aviptadil's benefit. However, such drugs like Aviptadil in COVID-19 patients have peculiar safety profiles. Thus, adequate clinical trials are necessary for these compounds.

Características do padrão de refluxo na posição ortostática versus posição supina em pacientes com refluxo laringofaríngeo

Resumo Introdução: Muitos problemas relacionados à laringe têm sido atribuídos ao refluxo laringofaríngeo, inclusive disfonia, pigarro frequente, tosse crônica e sensação de "globus" faríngeo. No entanto, ainda há controvérsias quanto ao diagnóstico e à apresentação clínica dessa condição clínica. Objetivo: Descrever as características do refluxo laringofaríngeo de diferentes posições, em pacientes diagnosticados por meio de pHmetria orofaríngea. Método: Foi feita uma revisão retrospectiva de prontuários de 161 pacientes com refluxo laringofaríngeo diagnosticado por pHmetria orofaríngea de 24 horas. Os indivíduos do estudo foram categorizados em grupos com refluxo laringofaríngeo na posição ortostática e refluxo laringofaríngeo na posição supina com base nos resultados do pH. Os dois grupos foram comparados quanto à apresentação clínica e às características do pH. Resultados: Foram encontradas taxas significativamente mais altas de refluxo laringofaríngeo na posição ortostática em comparação à posição supina (p < 0,0001). Os resultados do índice de sintomas de refluxo foram significativamente maiores no grupo com refluxo laringofaríngeo na posição ortostática em comparação com o grupo com refluxo laringofaríngeo na posição supina. O uso do escore de Ryan composto (composite Ryan score) para a pHmetria orofaríngea de 24 horas foi significantemente maior no grupo com refluxo laringofaríngeo ortostático em relação ao grupo supino (p < 0,0001). Nenhuma diferença significante foi encontrada entre os grupos refluxo laringofaríngeo na posição ortostática e posição supina em relação à frequência da apresentação clínica ou classificações do índice de desvantagem vocal. Conclusão: O refluxo laringofaríngeo foi mais prevalente na posição ortostática entre os grupos de estudo. As características relacionadas ao refluxo, inclusive parâmetros de pH, foram mais evidentes no refluxo laringofaríngeo na posição ortostática.

miR-375 down-regulation of the rearranged L-myc fusion and hypoxia-induced gene domain protein 1A genes and effects on Sertoli cell proliferation.

OBJECTIVE: This study aimed to screen and identify the target genes of miR-375 in pig Sertoli (ST) cells and to elucidate the effect of miR-375 on the proliferation of ST cells. METHODS: In this study, bioinformatics software was used to predict and verify miR-375 target genes. Quantitative polymerase chain reaction (PCR) was used to detect the relationship between miR-375 and its target genes in ST cells. Enzyme-linked immunosorbent assay (ELISA) of rearranged L-myc fusion (RLF) and hypoxia-induced gene domain protein 1A (HIGD1A) was performed on porcine ST cells, which were transfected with a miR-375 mimics and inhibitor to verify the results. Dual luciferase reporter gene assays were performed to assess the interactions among miR-375, RLF, and HIGD1A. The effect of miR-375 on the proliferation of ST cells was analyzed by CellTiter 96 AQueous One Solution Cell Proliferation Assay (MTS). RESULTS: Five possible target genes of miR-375, including RLF, HIGD1A, colorectal cancer associated 2, POU class 3 homeobox 1, and WW domain binding protein 1 like, were found. The results of quantitative PCR suggested that mRNA expression of RLF and HIGD1A had a negative correlation with miR-375, indicating that RLF and HIGD1A are likely the target genes of miR-375. The ELISA results revealed that RLF and HIGD1A were negatively correlated with the miR-375 protein level. The luminescence results for the miR-375 group co-transfected with wild-type RLF and HIGD1A vector were significantly lower than those of the miR-375 group co-transfected with the blank vector or mutant RLF and HIGD1A vectors. The present findings suggest that RLF and HIGD1A are target genes of miR-375 and that miR-375 inhibits ST cell proliferation according to MTS analysis. CONCLUSION: It was speculated that miR-375 affects cell proliferation through its target genes, which play an important role in the development of testicular tissue.

Loss of Rearranged L-Myc Fusion (RLF) results in defects in heart development in the mouse.

Recently we reported that Rearranged L-Myc Fusion, RLF, acts as an epigenetic modifier maintaining low levels of DNA methylation at CpG island shores and enhancers across the genome. Here we focus on the phenotype of Rlf null mutant mice generated via an ENU mutagenesis screen, to identify genes required for epigenetic regulation. RLF is expressed in a range of fetal mouse tissues, including the fetal heart. Comprehensive timed-mating studies are consistent with our previously reported findings that Rlf homozygous mutant mice rarely survive to adulthood, with the majority dying shortly after birth. Histological analysis of two independent Rlf ENU mutant lines at E11.5-E14.5 showed heart defects resembling those present in humans with Left Ventricular Non-Compaction (LVNC). In situ hybridisation analysis localized expression of Rlf to the endocardium and epicardium of embryonic and postnatal hearts, and transiently to cardiomyocytes during heart looping and early chamber formation stages. RNA-seq analysis of Rlf mutant hearts highlighted defective NOTCH pathway signalling, recently describe as one cause of LVNC. This study provides the first evidence that RLF is required for normal heart development in the mouse. The heart morphological defects present at high penetrance in Rlf mutants are consistent with features of LVNC in humans, and molecular analysis identified attenuated JAGGED 1 expression and NOTCH signalling as likely contributors to these defects. Our study highlights the importance of RLF-dependent epigenetic modifications to DNA for maintaining correct gene regulatory network and intercellular signalling interactions during heart chamber and septal development. Further investigations are needed to define the biochemical role of RLF in the developing heart, and whether RLF mutations are a cause of heart defects in humans.

Dynamics of insulin-like factor 3 and its receptor expression in boar testes.

Relaxin-like factor (RLF), now mainly known as insulin-like factor 3 (INSL3), is essential for testis descent during fetal development; however, its function in the adult testis is still being elucidated. As a major step toward understanding the as-yet-unknown function of INSL3 in boars, this study aimed to develop a time-resolved fluoroimmunoassay for boar INSL3, characterize the dynamics of INSL3 expression during development, and demonstrate the expression of the INSL3 hormone-receptor system in the testis. All samples were collected from Duroc boars. The sensitivity of the assay system established was 8.2 pg/well (164 pg/ml), and no cross-reactivity with other hormones, such as porcine relaxin, was observed. Circulating INSL3 was shown to increase progressively during development. INSL3 secreted from the Leydig cells was released not only into the blood circulation but also into the interstitial and seminiferous compartments in sufficient concentrations. A testicular fractionation study revealed that its receptor RXFP2 transcripts were expressed mainly in testicular germ cells. In addition, INSL3 bound to the germ cell membranes in a hormone-specific and saturable manner. These results reveal that INSL3 secreted into the interstitial compartment from the Leydig cells is transported into the seminiferous compartments, where its receptor RXFP2 is expressed mainly in the germ cells to which INSL3 binds, suggesting that INSL3 functions as a paracrine factor on seminiferous germ cells.

Deletion modification enhances anthrax specific immunity and protective efficacy of a hepatitis B core particle-based anthrax epitope vaccine.

Protective antigen (PA) is one of the major virulence factors of anthrax and is also the major constituent of the current anthrax vaccine. Previously, we found that the 2ß2-2ß3 loop of PA contains a dominant neutralizing epitope, the SFFD. We successfully inserted the 2ß2-2ß3 loop of PA into the major immunodominant region (MIR) of hepatitis B virus core (HBc) protein. The resulting fusion protein, termed HBc-N144-PA-loop2 (HBcL2), can effectively produce anthrax specific protective antibodies in an animal model. However, the protective immunity caused by HBcL2 could still be improved. In this research, we removed amino acids 79-81 from the HBc MIR of the HBcL2. This region was previously reported to be the major B cell epitope of HBc, and in keeping with this finding, we observed that the short deletion in the MIR not only diminished the intrinsic immunogenicity of HBc but also stimulated a higher titer of anthrax specific immunity. Most importantly, this deletion led to the full protection of the immunized mice against a lethal dose anthrax toxin challenge. We supposed that the conformational changes which occurred after the short deletion and foreign insertion in the MIR of HBc were the most likely reasons for the improvement in the immunogenicity of the HBc-based anthrax epitope vaccine.

The guanine nucleotide exchange factor Rlf interacts with SH3 domain-containing proteins via a binding site with a preselected conformation.

Rlf is a guanine nucleotide exchange factor for the small G-proteins RalA and RalB and couples Ras- to Ral-signalling. Here the crystal structure of the catalytic module of Rlf consisting of a REM- and a CDC25-homology domain is determined. The structure is distinguished by an extended three stranded ß-sheet called the flagpole. The flagpole is a conserved element in the RalGDS family of guanine nucleotide exchange factors and stabilises the orientation of the REM-domain relative to the CDC25-homology domain. A proline-rich sequence in the flagpole is unique to Rlf and several proteins that interact with this sequence by SH3 domains are identified. Conformational pre-selection results in a gain of affinity and contributes to the establishment of SH3 domain selectivity.

On the precision of neural computation with interaural level differences in the lateral superior olive.

Interaural level difference (ILD) is one of the basic binaural clues in the spatial localization of a sound source. Due to the acoustic shadow cast by the head, a sound source out of the medial plane results in an increased sound level at the nearer ear and a decreased level at the distant ear. In the mammalian auditory brainstem, the ILD is processed by a neuronal circuit of binaural neurons in the lateral superior olive (LSO). These neurons receive major excitatory projections from the ipsilateral side and major inhibitory projections from the contralateral side. As the sound level is encoded predominantly by the neuronal discharge rate, the principal function of LSO neurons is to estimate and encode the difference between the discharge rates of the excitatory and inhibitory inputs. Two general mechanisms of this operation are biologically plausible: (1) subtraction of firing rates integrated over longer time intervals, and (2) detection of coincidence of individual spikes within shorter time intervals. However, the exact mechanism of ILD evaluation is not known. Furthermore, given the stochastic nature of neuronal activity, it is not clear how the circuit achieves the remarkable precision of ILD assessment observed experimentally. We employ a probabilistic model and complementary computer simulations to investigate whether the two general mechanisms are capable of the desired performance. Introducing the concept of an ideal observer, we determine the theoretical ILD accuracy expressed by means of the just-noticeable difference (JND) in dependence on the statistics of the interacting spike trains, the overall firing rate, detection time, the number of converging fibers, and on the neural mechanism itself. We demonstrate that the JNDs rely on the precision of spike timing; however, with an appropriate parameter setting, the lowest theoretical values are similar or better than the experimental values. Furthermore, a mechanism based on excitatory and inhibitory coincidence detection may give better results than the subtraction of firing rates. This article is part of a Special Issue entitled Neural Coding 2012.