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Channel mismatch calibration techniques of time-interleaved analog-to-digital converters (TI-ADCs) are reviewed. The research on sampling technology of TI-ADCs is introduced, and the influence mechanism of channel mismatch has been analyzed briefly. Subsequently, the latest research progress of the domestic and foreign error calibration techniques of TI-ADCs is elaborated. The implementation methods, advantages and disadvantages of each calibration technique have been summarized, existing problems are analyzed. Finally, future development trends are prospected. These works could provide a reference for advancing the research field. [ABSTRACT FROM AUTHOR]

Flower busd formation is an important plant growth process. It has been reported that dwarfing rootstocks can significantly affect the flower bud formation of scions. In this study, we found the dwarfing rootstock 'Yunnan' quince could significantly increase the flowering rate of 'Abbé Fetel' pear scions. The RNA-sequencing data revealed significant changes in the expression of genes related to hormone pathways. Furthermore, hormone analyses indicated that 'Yunnan' quince significantly decreased the GA 3 content and increased the cytokinin/auxin ratio in 'Abbé Fetel' pear apical buds. The hormone contents were consistent with the RNA-sequencing data. Moreover, we found the flower development-related genes PbAGL9 and PbCAL-A1 were significantly upregulated and PbTFL1 was significantly downregulated in 'Abbé Fetel'/'Yunnan' quince apical buds. To further clarify the relationship between hormones and flowering-related genes, a hormone response assay was carried out. We found the expression levels of PbCAl-A1 , PbTFL1 and PbAGL9 were regulated by hormones including GA 3 , CPPU and NAA. Y1H and dual-luciferase assays indicated that PbAGL9 significantly decreased the promoter activity of PbTFL1. In summary, 'Yunnan' quince upregulated PbCAL-A1 and PbAGL9 , and downregulated PbTFL1 expression by decreasing the GA 3 content and increasing the cytokinin/auxin ratio in 'Abbé Fetel' pear apical buds. Additionally, 'Yunnan' quince down-regulate PbTFL1 by upregulating the expression of PbAGL9 , and eventually promoted floral induction in 'Abbé Fetel' pear. [ABSTRACT FROM AUTHOR]

Background:Temperature-sensitive liposomes (TSL) in combination with hyperthermia (HT) exposure have emerged as a potentially attractive option to achieve therapeutic drug concentration at targeted tumour site while reducing adverse side effects associated with systemic administration of anticancer drugs. The aim of this study is to elucidate the interplay among different kinetic steps by means of computational modelling. Methods:A multi-compartment model for TSL-mediated delivery of doxorubicin (DOX) is developed, which incorporates descriptions of the pharmacokinetics of TSL and DOX, and their accumulation in tumour tissue following intravascular triggered release. By examining dynamic interactions among TSL properties, tumour physiological properties and treatment regimen, peak intracellular DOX concentration is predicted for continuous and pulse HT exposures. Results:Drug release rate from TSL has a saturable effect on peak intracellular drug concentration, and no further gain could be achieved for release rates greater than 0.1018â€...sâ'1. A similar effect has also been found for heating duration, such that for a given bolus injection, peak intracellular drug concentration reaches its maximum and then levels off after HT duration of 2h. These results suggest that both TSL release rate and HT duration can be optimised in accordance with other parameters, e.g. clearance rate of TSL and administration mode, in order to achieve a desirable level of intracellular drug concentration. However, prolonged heating is not effective for resistant tumour cells with overexpression of ABC (ATP-binding cassette) transporter proteins. Conclusions: The results obtained in this study can be used to guide the design and optimisation of TSL parameters and treatment regimens. [ABSTRACT FROM AUTHOR]

Aβ42 oligomers play key roles in the pathogenesis of Alzheimer disease, but their structures remain elusive partly due to their transient nature. Here, we show that A42 in a fusion construct can be trapped in a stable oligomer state, which recapitulates characteristics of prefibrillar Aβ42 oligomers and enables us to establish their detailed structures. Site-directed spin labeling and electron paramagnetic resonance studies provide structural restraints in terms of side chain mobility and intermolecular distances at all 42 residue positions. Using these restraints and other biophysical data, we present a novel atomic-level oligomer model. In our model, each Aβ42 protein forms single-sheet with three-strands in an antiparallel arrangement. Each-sheet consists of four Aβ42 molecules in a head-to-tail arrangement. Four-sheets are packed together in a face-to-back fashion. The stacking of identical segments between different-sheets within an oligomer suggests that prefibrillar oligomers may interconvert with fibrils via strand rotation, wherein-strands undergo ~90° rotation along the strand direction. This work provides insights into rational design of therapeutics targeting the process of interconversion between toxic oligomers and non-toxic fibrils. [ABSTRACT FROM AUTHOR]

Corn cob (CC) and waste cooking oil (WCO) were co-pyrolyzed in a fixed bed. The effects of various temperatures of 500 °C, 550 °C, 600 °C and CC/WCO mass ratios of 1:0, 1:0.1, 1:0.5, 1:1 and 0:1 were investigated, respectively. Results show that co-pyrolysis of CC/WCO produce more liquid and less bio-char than pyrolysis of CC individually. Bio-oil and bio-char yields were found to be largely dependent on temperature and CC/WCO ratios. GC/MS of bio-oil show it consists of different classes and amounts of organic compounds other than that from CC pyrolysis. Temperature of 550 °C and CC/WCO ratio of 1:1 seem to be the optimum considering high bio-oil yields (68.6 wt.%) and good bio-oil properties (HHV of 32.78 MJ/kg). In this case, bio-char of 24.96 MJ/kg appears attractive as a renewable source, while gas with LHV of 16.06 MJ/Nm³ can be directly used in boilers as fuel. [ABSTRACT FROM AUTHOR]

The miR-451 was found to be frequently down-regulated in tumors, indicating that miR-451 could play an important role in carcinogenesis. This study uncovered the mechanism by which the miR-451 functions as a tumor suppressor. The target genes of miR-451 were determined using target gene prediction softwares. Then the miR-451 mimics were introduced into RKO and Hela cells respectively. The proliferation and invasion of cells were monitored by MTT, cell cycle and in vitro extracellular matrix invasion assays. Also the angiogenesis of HUVEC cells transfected with miR-451 mimics was examined. Subsequently, IL6R, a predicted target gene of miR-451, was studied by real time PCR, Western blotting, and siRNA technologies. The mRNA and protein levels of IL6R gene were found to be down-regulated in the RKO and Hela cells transfected with miR-451 mimics. Consequently, the cell proliferation was inhibited. Also, the invasion of RKO cells was suppressed. Furthermore, the angiogenesis of HUVEC cells transfected with miR-451 mimics was assayed and the decreased angiogenic ability was detected compared to the controls. All these results were validated by IL6R siRNA experiments. The IL6R gene is a target gene of miR-451. The miR-451 behaves as a tumor suppressor, probably by targeting the IL6R pathway. [ABSTRACT FROM AUTHOR]

Oligomerization of the 42-residue peptide Aβ42 plays a key role in the pathogenesis of Alzheimer disease. Despite great academic and medical interest, the structures of these oligomers have not been well characterized. Site-directed spin labeling combined with electron paramagnetic resonance spectroscopy is a powerful approach for studying structurally ill-defined systems, but its application in amyloid oligomer structure study has not been systematically explored. Here we report a comprehensive structural study on a toxic Aβ42 oligomer, called globulomer, using site-directed spin labeling complemented by other techniques. Transmission electron microscopy shows that these oligomers are globular structures with diameters of ∼7-8 nm. Circular dichroism shows primarilyβ-structures. X-ray powder diffraction suggests a highly ordered intrasheet hydrogenbonding network and a heterogeneous intersheet packing. Residue- level mobility analysis on spin labels introduced at 14 different positions shows a structured state and a disordered state at all labeling sites. Side chain mobility analysis suggests that structural order increases from N- to C-terminal regions. Intermolecular distance measurements at 14 residue positions suggest that C-terminal residues Gly-29-Val-40 form a tightly packed core with intermolecular distances in a narrow range of 11.5-12.5 Å. These intermolecular distances rule out the existence of fibril-like parallel in-register β-structures and strongly suggest an antiparallel β-sheet arrangement in Aβ42 globulomers. [ABSTRACT FROM AUTHOR]

Cystic fibrosis (CF), a common lethal pulmonary disorder in Caucasians, is caused by mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR) that disturbs fluid homeostasis and host defense in target organs. The effects of CFTR and Δ508-CFTR were assessed in transgenic mice that 1) lack CFTR expression (Cftr-/-); 2) express the human Δ508 CFTR (CFTRΔ508); 3) overexpress the normal human CFTR (CFTRtg) in respiratory epithelial cells. Genes were selected from Affymetrix Murine Gene-Chips analysis and subjected to functional classification, k-means clustering, promoter cis-elements/modules searching, literature mining, and pathway exploring. Genomic responses to Cftr-/- were not corrected by expression of CFTRΔ508. Genes regulating host defense, inflammation, fluid and electrolyte transport were similarly altered in Cftr-/- and CFTRΔ508 mice. CFTRΔ508 induced a primary disturbance in expression of genes regulating redox and antioxidant systems. Genomic responses to CFTRtg were modest and were not associated with lung pathology. CFTRtg and CFTRΔ508 induced genes encoding heat shock proteins and other chaperones but did not activate the endoplasmic reticulum-associated degradation pathway. RNAs encoding proteins that directly interact with CFTR were identified in each of the CFTR mouse models, supporting the hypothesis that CFTR functions within a multiprotein complex whose members interact at the level of protein-protein interactions and gene expression. Promoters of genes influenced by CFTR shared common regulatory elements, suggesting that their co-expression may be mediated by shared regulatory mechanisms. Genes and pathways involved in the response to CFTR may be of interest as modifiers of CF. [ABSTRACT FROM AUTHOR]

The ring focus antenna has special electromagnetic characteristics and application fields. The phase error of ring focus antenna is analyzed theoretically and simulatedly. The phase error caused by the position deviation of the feed and the subreflector, the compensation relationship between the main reflector and subreflector, and the optical path difference caused by the operation of the antenna in holographic measurement are derived. The results will provide theoretical basis and reference for accurate surface measurement and compensation of the ring focus antenna. [ABSTRACT FROM AUTHOR]

Hypoxia-inducible factor-1 (HIF-1) is a critical transcription factor that regulates the expression of genes involved in cellular adaptation to low oxygen levels. Aberrant regulation of the HIF-1 signaling pathway is linked to various human diseases. Previous studies have established that HIF-1a is rapidly degraded in a von Hippel-Lindau protein (pVHL)-dependent manner under normoxic conditions. In this study, we find that pVHL binding protein 1 (VBP1) is a negative regulator of HIF-1a but not HIF-2a using zebrafish as an in vivo model and in vitro cell culture models. Deletion of vbp1 in zebrafish caused Hif-1a accumulation and upregulation of Hif target genes. Moreover, vbp1 was involved in the induction of hematopoietic stem cells (HSCs) under hypoxic conditions. However, VBP1 interacted with and promoted the degradation of HIF-1a in a pVHL-independent manner. Mechanistically, we identify the ubiquitin ligase CHIP and HSP70 as new VBP1 binding partners and demonstrate that VBP1 negatively regulated CHIP and facilitated CHIP-mediated degradation of HIF-1a. In patients with clear cell renal cell carcinoma (ccRCC), lower VBP1 expression was associated with worse survival outcomes. In conclusion, our results link VBP1 with CHIP stability and provide insights into underlying molecular mechanisms of HIF-1a-driven pathological processes. [ABSTRACT FROM AUTHOR]

Molecular chaperones safeguard cellular protein homeostasis and obviate proteotoxicity. In the process of aging, as chaperone networks decline, aberrant protein amyloid aggregation accumulates in a mechanism that underpins neurodegeneration, leading to pathologies such as Alzheimer's disease and Parkinson's disease. Thus, it is important to identify and characterize chaperones for preventing such protein aggregation. In this work, we identified that the NAD+ synthase-nicotinamide mononucleotide adenylyltransferase (NMNAT) 3 from mouse (mN3) exhibits potent chaperone activity to antagonize aggregation of a wide spectrum of pathological amyloid client proteins including α-synuclein, Tau (K19), amyloid β, and islet amyloid polypeptide. By combining NMR spectroscopy, cross-linking mass spectrometry, and computational modeling, we further reveal that mN3 uses different region of its amphiphilic surface near the active site to directly bind different amyloid client proteins. Our work demonstrates a client recognition mechanism of NMNAT via which it chaperones different amyloid client proteins against pathological aggregation and implies a potential protective role for NMNAT in different amyloid-associated diseases. [ABSTRACT FROM AUTHOR]

A recombinant human androgen receptor yeast assay was applied to investigate the occurrence of antiandrogens as well as the mechanism for their removal during gray wastewater and coking wastewater treatment. The membrane reactor (MBR) system for gray wastewater treatment could remove 88.0% of antiandrogenic activity exerted by weakly polar extracts and 97.3% of that by moderately strong polar extracts, but only 32.5% of that contributed by strong polar extracts. Biodegradation by microorganisms in the MBR contributed to 95.9% of the total removal. After the treatment, the concentration of antiandrogenic activity in the effluent was still 1.05 μg flutamide equivalence (FEQ)/L, 36.2% of which was due to strong polar extracts. In the anaerobic reactor, anoxic reactor, and membrane reactor system for coking wastewater treatment, the antiandrogenic activity of raw coking wastewater was 78.6 mg FEQ/L, and the effluent of the treatment system had only 0.34 mg FEQ/L. The antiandrogenic activity mainly existed in the medium strong polar and strong polar extracts. Biodegradation by microorganisms contributed to at least 89.2% of the total antiandrogenic activity removal in the system. Biodegradation was the main removal mechanism of antiandrogenic activity in both the wastewater treatment systems. [ABSTRACT FROM AUTHOR]

Multidrug-resistant (MDR) Escherichia coli are responsible for difficult-to-treat infections. We sought to determine the prevalence and characteristics of MDR E. coli strains isolated from poultry and clinical patients in the same geographical region. Eightyseven E. coli strains were isolated from poultry with perihepatitis lesions at different slaughterhouses, and 356 nonrepetitive E. coli strains were isolated from clinical patients. All samples were continuously collected from October to December 2017 in Tai’an, China. The presence of the mcr-1 gene in the strains was assessed by PCR. The genetic relationships of the polymyxin (POL)- resistant E. coli strains were analyzed by pulsed-field gel electrophoresis and multilocus sequence typing. The results indicate that the POL resistance rate for the E. coli isolates from poultry was 31.03% (27 of 87), whereas the human-origin E. coli isolates were 100% sensitive to POL. The mcr-1 gene and extended-spectrum β-lactamase blaCTX-M-14 genes were identified in all 27 POL-resistant avian-origin E. coli isolates. Our pulsedfield gel electrophoresis analysis suggested that the 27 strains were represented by 14 pulsotypes, among which there were 3 strains each with A, E, I, and K pulsotypes, and 1 to 2 strains represented by the other 10 pulsotypes. Furthermore, multilocus sequence typing molecular typing identified 16 sequence types, including 4 ST156 strains, 3 ST533 strains, and 1 to 2 strains represented by the remaining 14 sequence types. In summary, the E. coli strains isolated in the Tai’an area all showed the MDR phenotype, the rate of which for poultry was higher than that for humans. No POL-resistant humanorigin E. coli strains were identified in the clinical patients. Our study reveals that poultry-derived MDR mcr-1–positive E. coli strains may pose a potential risk to humans, and the surveillance findings presented herein will be conducive to our understanding of the prevalence and characteristics of mcr-1–positive E. coli strains in the Tai’an area. [ABSTRACT FROM AUTHOR]

Amyloid aggregation of pathological proteins is closely associated with a variety of neurodegenerative diseases, and α-synuclein (α-syn) deposition and Tau tangles are considered hallmarks of Parkinson's disease and Alzheimer's disease, respectively. Intriguingly, α-syn and Tau have been found to co-deposit in the brains of individuals with dementia and parkinsonism, suggesting a potential role of cross-talk between these two proteins in neurodegenerative pathologies. Here we show that monomericα-syn and the two variants of Tau, Tau23 and K19, synergistically promote amyloid fibrillation, leading to their co-aggregation in vitro. NMR spectroscopy experiments revealed that α-syn uses its highly negatively charged C terminus to directly interact with Tau23 and K19. Deletion of the C terminus effectively abolished its binding to Tau23 and K19 as well as its synergistic effect on promoting their fibrillation. Moreover, an S129D substitution ofα-syn, mimicking C-terminal phosphorylation of Ser129 in α-syn, which is commonly observed in the brains of Parkinson's disease patients with elevated α-syn phosphorylation levels, significantly enhanced the activity of α-syn in facilitating Tau23 and K19 aggregation. These results reveal the molecular basis underlying the direct interaction between α-syn and Tau. We proposed that this interplay might contribute to pathological aggregation of α-syn and Tau in neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Lysophosphatidic acid receptor 6 (LPAR6) is a G protein-coupled receptor that plays critical roles in cellular morphology and hair growth. Although LPAR6 overexpression is also critical for cancer cell proliferation, its role in liver cancer tumorigenesis and the underlying mechanism are poorly understood. Here, using liver cancer and matched paracancerous tissues, as well as functional assays including cell proliferation, quantitative realtime PCR, RNA-Seq, and ChIP assays, we report that LPAR6 expression is controlled by a mechanism whereby hepatocyte growth factor (HGF) suppresses liver cancer growth. We show that high LPAR6 expression promotes cell proliferation in liver cancer. More importantly, we find that LPAR6 is transcriptionally down-regulated by HGF treatment and that its transcriptional suppression depends on nuclear receptor coactivator 3 (NCOA3). We note that enrichment of NCOA3, which has histone acetyltransferase activity, is associated with histone 3 Lys-27 acetylation (H3K27ac) at the LPAR6 locus in response to HGF treatment, indicating that NCOA3 transcriptionally regulates LPAR6 through the HGF signaling cascade. Moreover, depletion of either LPAR6 or NCOA3 significantly inhibited tumor cell growth in vitro and in vivo (in mouse tumor xenograft assays), similar to the effect of the HGF treatment. Collectively, our findings indicate an epigenetic link between LPAR6 and HGF signaling in liver cancer cells, and suggest that LPAR6 can serve as a biomarker and new strategy for therapeutic interventions for managing liver cancer. [ABSTRACT FROM AUTHOR]

Heat shock protein 104 (HSP104) is a conserved AAA+ protein disaggregase, can disassemble the toxic aggregates formed by different amyloid proteins, and is protective in various animal models associated with amyloid-related diseases. Extensive studies have attempted to elucidate how HSP104 disassembles the aggregated form of clients. Here, we found that HSP104 exhibits a potent holdase activity that does not require energy, prevents the soluble form of amyloid clients from aggregating, and differs from HSP104's disaggregase activity. Using cryo- EM, NMR, and additional biophysical approaches, we found that HSP104 utilizes its small subdomain of nucleotide-binding domain 2 (ssNBD2) to capture the soluble amyloid client (K19 of Tau) independent of its ATP hydrolysis activity. Our results indicate that HSP104 utilizes two fundamental distinct mechanisms to chaperone different forms of amyloid client and highlight the important yet previously unappreciated function of ssNBD2 in chaperoning amyloid client and thereby preventing pathological aggregation. [ABSTRACT FROM AUTHOR]

TRIM5α is an important host restriction factor that could potently block retrovirus infection. The SPRY domain of TRIM5α mediates post-entry restriction by recognition of and binding to the retroviral capsid. Human TRIM5α also functions as an innate immune sensor to activate AP-1 and NF-kB signaling, which subsequently restrict virus replication. Previous studies have shown that the AP-1 and NF-kB signaling activation relies on the RING motif of TRIM5α. In this study, we have demonstrated that the SPRY domain is essential for rhesus macaque TRIM5α to activate AP-1 but not NF-kB signaling. The AP-1 activation mainly depends on all of theβ-sheet barrel on SPRY structure of TRIM5α. Furthermore, the SPRY-mediated auto-ubiquitination of TRIM5α is required for AP-1 activation. This study reports that rhesus macaque TRIM5α mainly undergoes Lys27-linked and Met1-linked auto-polyubiquitination. Finally, we found that the TRIM5α signaling function was positively correlated with its retroviral restriction activity. This study discovered an important role of the SPRY domain in immune signaling and antiviral activity and further expanded our knowledge of the antiviral mechanism of TRIM5α. [ABSTRACT FROM AUTHOR]

Hydrogen silsesquioxane (HSQ) is an excellent negative-tone resist for electron-beam lithography and sub-5-nm-half-pitch patterns can be achieved using high contrast development processes. However, the quality of HSQ adhesion on different types of substrates varies, thus limiting the function of HSQ in etching masks or metal lift-off process on various substrates. In this study, we proposed several chemical modification methods to improve HSQ adhesion resist onto Si, Cr, Cu, Mo, Au, and indium-tin oxide (ITO) substrates. HSQ adhesion patterns onto Au substrates was significantly improved by utilizing (3-mercaptopropyl) trimethoxysilane (MPTMS) and Poly (diallyldimethylammonium) chloride (PDDA) modifications. The (3-Aminopropyl) triethoxysilane (APTES) enhances the HSQ adhesion on Mo substrates. APTES and PDDA improve HSQ adhesion on Si, Cr, Cu and ITO. The improved adhesive HSQ nanopatterns on these substrates may benefit the fabrication of various nanophotonic and nanoelectronic devices. [ABSTRACT FROM AUTHOR]

The fission yeast HIRA proteins Hip1 and Slm9 are members of an evolutionarily conserved family of histone chaperones that are implicated in nucleosome assembly. Here we have used single-step affinity purification and mass spectrometry to identify factors that interact with both Hip1 and Slm9. This analysis identified Hip3, a previously uncharacterized 187-kDa protein, with similarity to S. cerevisiae Hir3. Consistent with this, cells disrupted for hip3+ exhibit a range of growth defects that are similar to those associated with loss of Hip1 and Slm9. These include temperature sensitivity, a cell cycle delay, and synthetic lethality with cdc25-22. Furthermore, genetic analysis also indicates that disruption of hip3+ is epistatic with mutation of hip1+ and slm9+. Mutation of hip3+ alleviates transcriptional silencing at several heterochromatic loci, including in the outer (otr) centromeric repeats, indicating that Hip3 is required for the integrity of pericentric heterochromatin. As a result, loss of Hip3 function leads to high levels of minichromosome loss and an increased frequency of lagging chromosomes during mitosis. Importantly, the function of Hip1, Slm9, and Hip3 is not restricted to constitutive heterochromatic loci, since these proteins also repress the expression of a number of genes, including the Tf2 retrotransposons. [ABSTRACT FROM AUTHOR]

Studies transcriptional adaptation to cystic fibrosis transmembrane conductance regulator deficiency. RNA influenced by the presence or absence of cyystic fibrosis transmembrane conductance regulator gene (CFTR); Role of CFTR in maintaining pulmonary function.