599 research outputs found

    A centering correction method for GNSS antenna diversity theory and implementation using a software receiver

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    GPS is performing well in open sky situation. However, severe attenuation or blockage of signals by high buildings may leads to an insufficient number of received satellites. Antenna diversity scheme is viewed as a method to alleviate signal attenuation and enhance the performance of GNSS positioning in the harsh environments. This paper introduces an antenna diversity system, composed of two spatially separated antennas. If relative geometry of two antennas is known, the carrier phase measurement outputs from these two antennas can be combined with Centering Correction Method (CCM). Even each antenna may not able to acquire more than four satellites this antenna diversity system can still precisely estimate each antenna’s location with centimeter-level accuracy, as long as the sum of the captured satellites by two separate antennas is no less than four

    Low Serum Magnesium Level Is Associated with Microalbuminuria in Chinese Diabetic Patients

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    Whether serum magnesium deficiency is independently associated with the prevalence of microalbuminuria is still unclear. The objective of the present study was to elucidate the association between serum magnesium and microalbuminuria in diabetic patients. A cross-sectional study was conducted in 1829 diabetic subjects (aged ≥ 40 years) from Shanghai, China. Subjects were divided into three groups according to serum magnesium tertiles. A first-voided early-morning spot urine sample was obtained for urinary albumin-creatinine ratio (UACR) measurement. Microalbuminuria was defined as 30 mg/g ≤ UACR < 300 mg/g. Overall, 208 (11.37%) of the study population had microalbuminuria, with similar proportions in both genders (). The prevalence of microalbuminuria in tertile 1 of serum magnesium was higher than the prevalence in tertile 2 and tertile 3 (15.98%, 9.72%, and 8.46%, resp.; for trend <0.0001). After adjustment for age, sex, BMI, blood pressure, lipidaemic profile, HbA1c, eGFR, history of cardiovascular disease, HOMA-IR, antihypertensive and antidiabetic medication, and diabetes duration, we found that, compared with the subjects in tertile 3 of serum magnesium, those in tertile 1 had 1.85 times more likeliness to have microalbuminuria. We concluded that low serum magnesium level was significantly associated with the prevalence of microalbuminuria in middle-aged and elderly Chinese

    Scale effect of circularly polarized luminescent signal of matter

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    Circularly polarized luminescence (CPL) is an important part in the research of modern luminescent materials and photoelectric devices. Usually, chiral molecules or chiral structures are the key factors to induce CPL spontaneous emission. In this study, a scale-effect model based on scalar theory was proposed to better understand the CPL signal of luminescent materials. Besides chiral structures being able to induce CPL, achiral ordered structures can also have a significant influence on CPL signals. These achiral structures are mainly reflected in the particle scale in micro-order or macro-order, i.e. the CPL signal measured under most conditions depends on the scale of the ordered medium, and does not reflect the inherent chirality of the excited state of the luminescent molecule. This kind of influence is difficult to be eliminated by simple and universal strategies in macro-measurement. At the same time, it is found that the measurement entropy of CPL detection may be the key factor to determine the isotropy and anisotropy of the CPL signal. This discovery would bring new opportunities to the research of chiral luminescent materials. This strategy can also greatly reduce the development difficulty of CPL materials and show high application potential in biomedical, photoelectric information and other fields.</p

    Kava Components Down-Regulate Expression of AR and AR Splice Variants and Reduce Growth in Patient-Derived Prostate Cancer Xenografts in Mice

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    Men living in Fiji and drinking kava have low incidence of prostate cancer (PCa). However, the PCa incidence among Fijian men who had migrated to Australia, increased by 5.1-fold. We therefore examined the potential effects of kava root extracts and its active components (kavalactones and flavokawains) on PCa growth and androgen receptor (AR) expression. PCa cell lines (LNCaP, LAPC-4, 22Rv1, C4-2B, DU145 and PC-3) with different AR expression, and a transformed prostate myofibroblast cell line (WPMY-1), were treated with a commercial kava extract, kavalactones (kawain, 5′6′-dehydrokawain, yangonin, methysticin) and flavokawain B. Expression of AR and its target genes (PSA and TMPRSS2) was examined. Two novel patient-derived PCa xenograft models from high grade PCa specimens were established by implanting the specimens into nude mice and passing tumor pieces through subcutaneous injection in nude mice, and then treated with kava extract and flavokawain B to examine their effects on tumor growth, AR expression and serum PSA levels. The kava extract and flavokawain B effectively down-regulated the expression of both the full-length AR and AR splice variants. The kava extract and kavalactones accelerated AR protein degradation, while flavokawain B inhibited AR mRNA transcription via decreasing Sp1 expression and the binding of Sp1 to the AR promoter. The kava root extract and flavokawain B reduce tumor growth, AR expression in tumor tissues and levels of serum PSA in the patient-derived PCa xenograft models. These results suggest a potential usefulness of a safe kava product or its active components for prevention and treatment of advanced PCa by targeting AR

    Acoustophoresis in Variously Shaped Liquid Droplets

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    The ability to precisely trap, transport and manipulate micrometer-sized objects, including biological cells, DNA-coated microspheres and microorganisms, is very important in life science studies and biomedical applications. In this study, acoustic radiation force in an ultrasonic standing wave field is used for micro-objects manipulation, a technique termed as acoustophoresis. Free surfaces of liquid droplets are used as sound reflectors to confine sound waves inside the droplets. Two techniques were developed for precise control of droplet shapes: edge pinning and hydrophilic/hydrophobic interface pinning. For all tested droplet shapes, including circular, annular and rectangular, our experiments show that polymer micro particles can be manipulated by ultrasound and form into a variety of patterns, for example, concentric rings and radial lines in an annular droplet. The complexity of the pattern increases with increasing frequency, and the observations are in line with simulation results. The acoustic manipulation technique developed here has the potential to be integrated into a more complex on-chip microfluidic circuit. Especially because our method is well compatible with electrowetting technology, which is a powerful tool for manipulating droplets with free surfaces, the combination of the two methods can provide more versatile manipulation abilities and may bring a wealth of novel applications. In the end, we demonstrate for the first time that acoustophoresis can be used for manipulating Caenorhabditis elegans

    Mendelian randomization and clinical trial evidence supports TYK2 inhibition as a therapeutic target for autoimmune diseases

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    Background: To explore the associations of genetically proxied TYK2 inhibition with a wide range of disease outcomes and biomarkers to identify therapeutic repurposing opportunities, adverse effects, and biomarkers of efficacy. Methods: The loss-of-function missense variant rs34536443 in TYK2 gene was used as a genetic instrument to proxy the effect of TYK2 inhibition. A phenome-wide Mendelian randomization (MR) study was conducted to explore the associations of genetically-proxied TYK2 inhibition with 1473 disease outcomes in UK Biobank (N = 339,197). Identified associations were examined for replication in FinnGen (N = 260,405). We further performed tissue -specific gene expression MR, colocalization analyses, and MR with 247 blood biomarkers. A systematic review of randomized controlled trials (RCTs) on TYK2 inhibitor was performed to complement the genetic evidence. Findings: PheWAS-MR found that genetically-proxied TYK2 inhibition was associated with lower risk of a wide range of autoimmune diseases. The associations with hypothyroidism and psoriasis were confirmed in MR analysis of tissue-specific TYK2 gene expression and the associations with systemic lupus erythematosus, psoriasis, and rheumatoid arthritis were observed in colocalization analysis. There were nominal associations of genetically-proxied TYK2 inhibition with increased risk of prostate and breast cancer but not in tissue-specific expression MR or colocalization analyses. Thirty-seven blood biomarkers were associated with the TYK2 loss-of-function mutation. Evidence from RCTs confirmed the effectiveness of TYK2 inhibitors on plaque psoriasis and reported several adverse effects. Interpretation: This study supports TYK2 inhibitor as a potential treatment for psoriasis and several other autoim-mune diseases. Increased pharmacovigilance is warranted in relation to the potential adverse effects.De två första författarna delar förstaförfattarskapet.De tre sista författarna delar sistaförfattarskapet.</p

    Identifying distinctive tissue and fecal microbial signatures and the tumor-promoting effects of deoxycholic acid on breast cancer

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    IntroductionA growing body of evidence indicates that the dysbiosis of both mammary and intestinal microbiota is associated with the initiation and progression of breast tumors. However, the microbial characteristics of patients with breast tumors vary widely across studies, and replicable biomarkers for early-stage breast tumor diagnosis remain elusive.MethodsWe demonstrate a machine learning-based method for the analysis of breast tissue and gut microbial differences among patients with benign breast disease, patients with breast cancer (BC), and healthy individuals using 16S rRNA sequence data retrieved from eight studies. QIIME 2.0 and R software (version 3.6.1) were used for consistent processing. A naive Bayes classifier was trained on the RDP v16 reference database to assign taxonomy using the Vsearch software.ResultsAfter re-analyzing with a total of 768 breast tissue samples and 1,311 fecal samples, we confirmed that Halomonas and Shewanella were the most representative genera of BC tissue. Bacteroides are frequently and significantly enriched in the intestines of patients with breast tumor. The areas under the curve (AUCs) of random forest models were 74.27% and 68.08% for breast carcinoma tissues and stool samples, respectively. The model was validated for effectiveness via cohort-to-cohort transfer (average AUC =0.65) and leave-one-cohort-out (average AUC = 0.66). The same BC-associated biomarker Clostridium_XlVa exists in the tissues and the gut. The results of the in-vitro experiments showed that the Clostridium-specific-related metabolite deoxycholic acid (DCA) promotes the proliferation of HER2-positive BC cells and stimulates G0/G1 phase cells to enter the S phase, which may be related to the activation of peptide-O-fucosyltransferase activity functions and the neuroactive ligand–receptor interaction pathway.DiscussionThe results of this study will improve our understanding of the microbial profile of breast tumors. Changes in the microbial population may be present in both the tissues and the gut of patients with BC, and specific markers could aid in the early diagnosis of BC. The findings from in-vitro experiments confirmed that Clostridium-specific metabolite DCA promotes the proliferation of BC cells. We propose the use of stool-based biomarkers in clinical application as a non-invasive and convenient diagnostic method

    A novel mRNA vaccine, SYS6006, against SARS-CoV-2

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    The development of vaccines that can efficiently prevent the infection of SARS-CoV-2 is necessary to fight the COVID-19 epidemic. mRNA vaccine has been proven to induce strong humoral and cellular immunity against SARS-CoV-2. Here, we studied the immunogenicity and protection efficacy of a novel mRNA vaccine SYS6006. High expression of mRNA molecules in 293T cells was detected. The initial and boost immunization with a 21-day interval was determined as an optimal strategy for SYS6006. Two rounds of immunization with SYS6006 were able to induce the neutralizing antibodies against the SARS-CoV-2 wild-type (WT) strain, and Delta and Omicron BA.2 variants in mice or non-human primates (NHPs). A3rd round of vaccination could further enhance the titers of neutralization against Delta and Omicron variants. In vitro ELISpot assay showed that SYS6006 could induce memory B cell and T cell immunities specifically against SARS-CoV-2 in mice. FACS analysis indicated that SYS6006 successfully induced SARS-CoV-2-specific activation of T follicular helper cell (Tfh) and Th1 cell, and did not induce CD4+Th2 response in NHPs. SYS6006 vaccine could significantly reduce the viral RNA loads and prevent lung lesions in Delta variant infected hACE2 transgenic mice. Therefore, SYS6006 could provide significant immune protection against SARS-CoV-2
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