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ctDNA mutations identified by somatic mutation callers and cmDetect in the simulated data set. Scatter plot of the allele frequency in blood (x-axis) and in tumor (y-axis) of the simulated ctDNA mutations. ctDNA mutations identified by Mutect (Varscan2) or cmDetect are shown in green; ctDNA mutations identified only by cmDetect are shown in blue; ctDNA mutations not identified are shown in gray.

Quality metrics for the targeted sequencing of the 46 plasma samples.

Relation between number of ctDNA mutations and total number of somatic mutations.

ctDNA mutations identified by cmDetect in 60 TCGA breast cancer patients.

Performance summary of somatic mutation calling using Mutect, Mutect+cmDetect, Varscan2, Varscan2+cmDetect with different filters on maximum variant allele read count and frequency in the blood

details of DNA concentrations and mutation allele frequencies in plasma analyses of 117 metastatic cases.

ctDNA mutations identified by cmDetect in the 60 pan cancer metastatic samples.

List of mutations inserted in the simulated data set

Summary of normal control sample type in a set of whole exome sequencing data in TCGA

ctDNA mutations identified by cmDetect for the breast cancer metastatic cases.

DNA extracted from cancer patients' whole blood may contain somatic mutations from circulating tumor DNA (ctDNA) fragments. In this study, we introduce cmDetect, a computational method for the systematic identification of ctDNA mutations using whole-exome sequencing of a cohort of tumor and corresponding peripheral whole-blood samples. Through the analysis of simulated data, we demonstrated an increase in sensitivity in calling somatic mutations by combining cmDetect to two widely used mutation callers. In a cohort of 93 breast cancer metastatic patients, cmDetect identified ctDNA mutations in 54% of the patients and recovered somatic mutations in cancer genes EGFR, PIK3CA, and TP53. We further showed that cmDetect detected ctDNA in 89% of patients with confirmed mutated cell–free tumor DNA by plasma analyses (n = 9) within 46 pan-cancer patients. Our results prompt immediate consideration of the use of this method as an additional step in somatic mutation calling using whole-exome sequencing data with blood samples as controls. Cancer Res; 76(20); 5954–61. ©2016 AACR.

COSMIC variants identified in the plasma samples.

Clinical information for the 93 breast cancer and 60 pan cancer metastatic patients.

Number of ctDNA mutations according to previous chemotherapy treatment.

ctDNA mutations identified in the simulated data set by cmDetect

List of somatic mutations identified in the 93 breast cancer metastases

Details of the 1000 Genomes samples used in data simulation

An open jet wind tunnel has low-frequency pressure pulsation in common wind speed range due to its unique structural form, which seriously damages the quality of flow field in the test section. The low-frequency pressure fluctuation performance and control mechanism of Jilin University open jet and return flow wind tunnel are investigated by experiments and numerical simulation. The results show that the low-frequency pressure fluctuation is a narrow pulse phenomenon that only occurs in certain intervals, and several velocity intervals may be found in the same wind tunnel. The reliability of the numerical simulation is verified by comparing the peak frequency and amplitude of pressure fluctuation in numerical simulation and wind tunnel tests. A simplified model similar to and amplifying the phenomenon is established. The flow structure and vortex evolution are analyzed via detached eddy simulation. In the test section, large-scale shedding vortices are formed at the nozzle exit, introducing periodic pulsating instantaneous velocity and acting with the collector to form an edge-feedback. This acoustic feedback forms resonance with the pipeline circuit, resulting in poor flow field quality. In accordance with the mechanism of nozzle jet, two methods of controlling pulsation are proposed: spoiler and flow-follow device. The study shows that the effects of two methods are abrupt, and the frequency of pressure pulsation is changed. The spoiler destroys the complete structure of vortex ring in free jet and develops into a complementary double vortex ring structure, which is highly sensitive to size factors. The flow-follow device supplements the velocity loss of the free jet at the nozzle and develops into a double vortex ring with master–slave structure in the middle of the test section. Its vibration reduction effect is greatly affected by the flow velocity. It takes effect in an appropriate range where the flow velocity is higher than the nozzle velocity. If the follow velocity is extremely low, the flow-follow device cannot change the original jet structure. If the follow velocity is extremely high, the momentum of the fan will be greatly reduced, the flow field will be unstable, and another order of pulsation may be induced. This work lays a solid foundation for further understanding the aerodynamic characteristics and optimization mechanism of open jet wind tunnel.

Gelsemium elegans (G. elegans) Benth., recognized as a toxic plant, has been used as traditional Chinese medicine for the treatment of neuropathic pain and cancer for many years. In the present study, we aim to obtain the anti-tumor effects of alkaloids of G. elegans and their active components in hepatocellular carcinoma (HCC) and the potential mechanism was also further investigated. We demonstrated that sempervirine induced HCC cells apoptosis and the apoptosis was associated with cell cycle arrest during the G1 phase, up-regulation of p53 and down-regulation of cyclin D1, cyclin B1 and CDK2. Furthermore, sempervirine inhibited HCC tumor growth and enhances the anti-tumor effect of sorafenib in vivo. In addition, inactivation of Wnt/β-catenin pathway was found to be involved in sempervirine-induced HCC proliferation. The present study demonstrated that alkaloids of G. elegans were a valuable source of active compounds with anti-tumor activity. Our findings justified that the active compound sempervirine inhibited proliferation and induced apoptosis in HCC by regulating Wnt/β-catenin pathway.

Translocator protein 18 kDa (TSPO) is an evolutionarily conserved 5-transmembrane domain protein, and has been considered as an important therapeutic target for the treatment of pain. We have recently reported the in vitro and in vivo pharmacological characterization of koumine as a TSPO positive allosteric modulator (PAM), more precisely ago-PAM. However, the probe dependence in the allostery of koumine is an important question to resolve, and the possible analgesic mechanism of koumine remains to be clarified. Here, we report the in vivo evaluation of the allostery of koumine when orthosteric ligand PK11195 was used and preliminarily explore the possible analgesic mechanism of koumine associated with neurosteroids. We find that koumine is an ago-PAM of the PK11195-mediated analgesic effect at TSPO, and the analgesic mechanism of this TSPO ago-PAM may be associated with neurosteroids as the analgesic effects of koumine in the formalin-induced inflammatory pain model and chronic constriction injury-induced neuropathic pain model can be antagonized by neurosteroid synthesis inhibitor aminoglutethimide. Although our results cannot fully clarify the allosteric modulatory effect of koumine, it further prove the allostery in TSPO and provide a solid foundation for koumine to be used as a new clinical candidate drug to treat pain.

Translocator protein 18 kDa (TSPO) is an evolutionarily conserved 5-transmembrane domain protein, and has been considered as an important therapeutic target for the treatment of pain. We have recently reported the in vitro and in vivo pharmacological characterization of koumine as a TSPO positive allosteric modulator (PAM), more precisely ago-PAM. However, the probe dependence in the allostery of koumine is an important question to resolve, and the possible analgesic mechanism of koumine remains to be clarified. Here, we report the in vivo evaluation of the allostery of koumine when orthosteric ligand PK11195 was used and preliminarily explore the possible analgesic mechanism of koumine associated with neurosteroids. We find that koumine is an ago-PAM of the PK11195-mediated analgesic effect at TSPO, and the analgesic mechanism of this TSPO ago-PAM may be associated with neurosteroids as the analgesic effects of koumine in the formalin-induced inflammatory pain model and chronic constriction injury-induced neuropathic pain model can be antagonized by neurosteroid synthesis inhibitor aminoglutethimide. Although our results cannot fully clarify the allosteric modulatory effect of koumine, it further prove the allostery in TSPO and provide a solid foundation for koumine to be used as a new clinical candidate drug to treat pain.

NF-κB mediates acquired resistance in acute myeloid leukemia (AML) cells treated with DNA-damaging agents. Because DNA repair is the major molecular shift that alters sensitivity to DNA-damaging agents, we explored whether activation of the NF-κB pathway promotes AML cell survival by regulating DNA repair after chemotherapy. Our results showed that RELA, an important subunit of NF-κB, regulated DNA repair by binding to the promoter region of the PARP1 gene and affecting PARP1 gene transcription. Conversely, PARP1 knockdown reduced NF-κB activity, indicating that NF-κB and PARP1 create a positive feedback loop in DNA repair. Simultaneous treatment with the NF-κB inhibitor BMS-345541 and the PARP1 inhibitor olaparib resulted in robust killing of AML cells. This dual inhibition significantly suppressed tumor growth and extended survival times in xenograft tumor models. Implications: RELA and PARP1 form a positive feedback loop to regulate DNA damage repair, simultaneous inhibition of NF-κB and PARP1 increases the antileukemic efficacy of daunorubicin in vitro and in vivo, broadening the use of PARP1 inhibitors.

Koumine is an alkaloid that displays notable activity against inflammatory and neuropathic pain, but its therapeutic target and molecular mechanism still need further study. Translocator protein 18 kDa (TSPO) is a vital therapeutic target for pain treatment, and recent research implies that there may be allostery in TSPO. Our previous competitive binding assay hint that koumine may function as a TSPO positive allosteric modulator (PAM). Here, for the first time, we report the pharmacological characterization of koumine as a TSPO PAM. The results imply that koumine might be a high-affinity ligand of TSPO and that it likely acts as a PAM since it could delay the dissociation of 3H-PK11195 from TSPO. Importantly, the allostery was retained in vivo, as koumine augmented Ro5-4864-mediated analgesic and anti-inflammatory effects in several acute and chronic inflammatory and neuropathic pain models. Moreover, the positive allosteric modulatory effect of koumine on TSPO was further demonstrated in cell proliferation assays in T98G human glioblastoma cells. In summary, we have identified and characterized koumine as a TSPO PAM for the treatment of inflammatory and neuropathic pain. Our data lay a solid foundation for the use of the clinical candidate koumine to treat inflammatory and neuropathic pain, further demonstrate the allostery in TSPO, and provide the first proof of principle that TSPO PAM may be a novel avenue for the discovery of analgesics.

Background Infestation by tea green leafhoppers (Empoasca (Matsumurasca) onukii) can cause a series of biochemical changes in tea leaves. As a typical cell-rupture feeder, E. onukii secretes proteases while using its stylet to probe the tender shoots of tea plants (Camellia sinensis). This study identified and analyzed proteases expressed specifically in the salivary gland (SG) and gut of E. onukii through enzymatic activity assays complemented with an integrated analysis of transcriptomic and proteomic data. Results In total, 129 contigs representing seven types of putative proteases were identified. Transcript abundance of digestive proteases and enzymatic activity assays showed that cathepsin B-like protease, cathepsin L-like protease, and serine proteases (trypsin- and chymotrypsin-like protease) were highly abundant in the gut but moderately abundant in the SG. The abundance pattern of digestive proteases in the SG and gut of E. onukii differed from that of other hemipterans, including Nilaparvata lugens, Laodelphax striatellus, Acyrthosiphum pisum, Halyomorpha halys and Nephotettix cincticeps. Phylogenetic analysis showed that aminopeptidase N-like proteins and serine proteases abundant in the SG or gut of hemipterans formed two distinct clusters. Conclusions Altogether, this study provides insightful information on the digestive system of E. onukii. Compared to five other hemipteran species, we observed different patterns of proteases abundant in the SG and gut of E. onukii. These results will be beneficial in understanding the interaction between tea plants and E. onukii.

Koumine (KM), one of the primary constituents of Gelsemium elegans, has been used for the treatment of inflammatory diseases such as rheumatoid arthritis, but whether KM impacts the activation of the NOD-like receptor protein 3 (NLRP3) inflammasome remains unknown. This study aimed to explore the inhibitory effect of KM on NLRP3 inflammasome activation and the underlying mechanisms both in vitro using macrophages stimulated with LPS plus ATP, nigericin or monosodium urate (MSU) crystals and in vivo using an MSU-induced peritonitis model. We found that KM dose-dependently inhibited IL-1β secretion in macrophages after NLRP3 inflammasome activators stimulation. Furthermore, KM treatment efficiently attenuated the infiltration of neutrophils and suppressed IL-1β production in mice with MSU-induced peritonitis. These results indicated that KM inhibited NLRP3 inflammasome activation, and consistent with this finding, KM effectively inhibited caspase-1 activation, mature IL-1β secretion, NLRP3 formation and pro-IL-1β expression in LPS-primed macrophages treated with ATP, nigericin or MSU. The mechanistic study showed that, KM exerted a potent inhibitory effect on the NLRP3 priming step, which decreased the phosphorylation of IκBα and p65, the nuclear localization of p65, and the secretion of TNF-α and IL-6. Moreover, the assembly of NLRP3 was also interrupted by KM. KM blocked apoptosis-associated speck-like protein containing a CARD (ASC) speck formation and its oligomerization and hampered the NLRP3-ASC interaction. This suppression was attributed to the ability of KM to inhibit the production of reactive oxygen species (ROS). In support of this finding, the inhibitory effect of KM on ROS production was completely counteracted by H2O2, an ROS promoter. Our results provide the first indication that KM exerts an inhibitory effect on NLRP3 inflammasome activation associated with blocking the ROS/NF-κB/NLRP3 signal axis. KM might have potential clinical application in the treatment of NLRP3 inflammasome-related diseases.

Additional file 2. Additional figures. This file contains 4 additional figures

Additional file 1. Additional tables. This file contains 2 additional tables

Background: Infestation by tea green leafhoppers, Empoasca (Matsumurasca) onukii , could cause a series of biochemical changes in tea leaves. As a typical cell-rupture feeder, E. onukii secretes proteases while probing with its stylet into the tender shoots of tea plants ( Camellia sinensis ). This study identified and analyzed proteases specifically expressed in the salivary gland (SG) and gut of E. onukii through enzymatic activity assays, complemented with an integrated analysis of transcriptome and proteome data.Results: In total, 129 contigs representing seven types of putative proteases were identified. Transcript abundance of digestive proteases and enzymatic activity assays showed that cathepsin B-like protease, cathepsin L-like protease, and serine proteases (trypsin- and chymotrypsin-like protease) were highly abundant in the gut while moderately abundant in the SG. The abundance pattern of digestive proteases in the SG and gut of E. onukii differed from that of other hemipterans including Nilaparvata lugens , Laodelphax striatellus , Acyrthosiphum pisum , Halyomorpha halys and Nephotettix cincticeps . Phylogenetic analysis showed that aminopeptidase N-like proteins and serine proteases abundant in the SG or gut of hemipterans were distributed to two distinct clusters.Conclusions: Altogether, this study provide insightful information on the digestive system of E. onukii and observed different patterns of proteases abundant in the SG and gut of E. onukii , in comparison with other five hemipteran species. These results will be beneficial in understanding the interaction between tea plants and E. onukii .

Humans homozygous or hemizygous for variants predicted to cause a loss of function of the corresponding protein do not necessarily present with overt clinical phenotypes. However, the set of effectively dispensable genes in the human genome has not yet been fully characterized. We report here 190 autosomal genes with 207 predicted loss-of-function variants, for which the frequency of homozygous individuals exceeds 1% in at least one human population from five major ancestry groups. No such genes were identified on the X and Y chromosomes. Manual curation revealed that 28 variants (15%) had been misannotated as loss-of-function, mainly due to linkage disequilibrium with different compensatory variants. Of the 179 remaining variants in 166 genes (0.82% of 20,232 genes), only 11 alleles in 11 genes had previously been confirmed experimentally to be loss-of-function. The set of 166 dispensable genes was enriched in olfactory receptor genes (41 genes), but depleted of genes expressed in a wide range of organs and in leukocytes. The 125 dispensable non-olfactory receptor genes displayed a relaxation of selective constraints both between species and within humans, consistent with greater redundancy. In total, 62 of these 125 genes were found to be dispensable in at least three human populations, suggesting possible evolution toward pseudogenes. Out of the 179 common loss-of-function variants, 72 could be tested for two neutrality selection statistics, and eight displayed robust signals of positive selection. These variants included the knownFUT2mutant allele conferring resistance to intestinal viruses and anAPOL3variant involved in resistance to parasitic infections. Finally, the 41 dispensable olfactory receptor genes also displayed a strong relaxation of selective constraints similar to that observed for the 341 non-dispensable olfactory receptor genes. Overall, the identification of 166 genes for which a sizeable proportion of humans are homozygous for predicted loss-of-function alleles reveals both redundancies and advantages of such deficiencies for human survival.Significance statementHuman genes homozygous for seemingly loss of function (LoF) variants are increasingly reported in a sizeable proportion of individuals without overt clinical phenotypes. Here, we found 166 genes with 179 predicted LoF variants for which the frequency of homozygous individuals exceeds 1% in at least one of the populations present in databases ExAC and gnomAD. This set of putatively dispensable genes showed relaxation of selective constraints suggesting that a large number of these genes are undergoing pseudogenization. Eight of the common LoF variants displayed robust signals of positive selection including two variants located in genes involved in resistance to infectious diseases. The identification of dispensable genes will allow identifying functions that are, at least nowadays, redundant, or possibly advantageous, for human survival.

Background: Infestation by tea green leafhoppers, Empoasca (Matsumurasca) onukii, could cause a series of biochemical changes in tea leaves. As a typical cell-rupture feeder, E. onukii secretes proteases while probing with its stylet into the tender shoots of tea plants (Camellia sinensis). This study identified and analyzed proteases specifically expressed in the salivary gland (SG) and gut of E. onukii through enzymatic activity assays, complemented with an integrated analysis of transcriptome and proteome data.Results: In total, 129 contigs representing seven types of putative proteases were identified. Transcript abundance of digestive proteases and enzymatic activity assays showed that cathepsin B, cathepsin L, and serine proteases (trypsin and chymotrypsin) were highly abundant in the gut while moderately abundant in the SG. The abundance pattern of digestive proteases in the SG and gut of E. onukii differed from that of other hemipterans including Nilaparvata lugens, Laodelphax striatellus, Nephotettix cincticeps and Acyrthosiphum pisum. Phylogenetic analysis showed that aminopeptidase N-like proteins and serine proteases abundant in the SG or gut of hemipterans were distributed to two distinct clusters. Conclusions: Altogether, this study provide insightful information on the digestive system of E. onukii and observed different patterns of proteases abundant in the SG and gut of E. onukii, in comparison with other five hemipteran species. These results will be beneficial in understanding the interaction between tea plants and E. onukii.

In this paper, we present the unified closed-form expressions of average symbol error probability (ASEP) for both types of system (i.e. coherent and incoherent system) in the presence of pointing error over Malaga ( M ) turbulence channel. With the help of the approximation of exponential-type presentation of Q-function, the unified closed-form expressions are presented, which are generic enough to encompass almost all the modulation techniques of which ASEP involves the integral power of Q-function. Then, we capitalize on the results to provide the asymptotic expressions at high signal-to-noise ratio (SNR). Additionally, the diversity order and coding gain are presented, which reveal that the diversity order is depended on the channel condition and detection scheme, while the coding gain is relevant to the modulation techniques. Moreover, some special cases are presented, such as the results under Gamma–Gamma distribution and K-distribution. Numerical results corroborate the accuracy of the closed-form expressions for different modulation techniques under different turbulence conditions.

Objective: Understanding the heterogeneity and pathophysiology of osteoarthritis (OA) is critical to support the development of tailored disease-modifying treatments. To this aim, transcriptomics tools are highly relevant to delineate dysregulated molecular pathways and identify new therapeutic targets. Methods: We review the methodology and outcomes of transcriptomics studies conducted in OA, based on a comprehensive literature search of the PubMed and Google Scholar databases using the terms “osteoarthritis”, “OA”, “knee OA”, “hip OA”, “genes”, “RNA-seq”, “microarray”, “transcriptomic” and “PCR” as key words. Beyond target-focused RT-qPCR, more comprehensive techniques include microarrays, RNA sequencing (RNA-seq) and single cell RNA-seq analyses. Results: The standardization of those methods to ensure the quality of both RNA extraction and sequencing is critical to get meaningful insights. Transcriptomics studies have been conducted in various tissues involved in the pathogenesis of OA, including articular cartilage, subchondral bone and synovium, as well as in the blood of patients. Molecular pathways dysregulated in OA relate to cartilage degradation, matrix and bone remodeling, neurogenic pain, inflammation, apoptosis and angiogenesis. This knowledge has direct application to patient stratification and further, to the identification of candidate therapeutic targets and biomarkers intended to monitor OA progression. Conclusion: In light of its high-throughput capabilities and ability to provide comprehensive information on major biological processes, transcriptomics represents a powerful method to support the development of new disease-modifying drugs in OA.

As one of the stimulators on bone formation, osteogenic growth peptide (OGP) improves both proliferation and differentiation of the bone cells in vitro and in vivo. The aim of this work was the preparation of three dimensional porous poly(ε-caprolactone) (PCL) scaffold with high porosity, well interpore connectivity, and then its surface was modified by using chitosan (CS)/OGP coating for application in bone regeneration. In present study, the properties of porous PCL and CS/OGP coated PCL scaffold, including the microstructure, water absorption, porosity, hydrophilicity, mechanical properties, and biocompatibility in vitro were investigated. Results showed that the PCL and CS/OGP-PCL scaffold with an interconnected network structure have a porosity of more than 91.5, 80.8%, respectively. The CS/OGP-PCL scaffold exhibited better hydrophilicity and mechanical properties than that of uncoated PCL scaffold. Moreover, the results of cell culture test showed that CS/OGP coating could stimulate the proliferation and growth of osteoblast cells on CS/OGP-PCL scaffold. These finding suggested that the surface modification could be a effective method on enhancing cell adhesion to synthetic polymer-based scaffolds in tissue engineering application and the developed porous CS/OGP-PCL scaffold should be considered as alternative biomaterials for bone regeneration.

As a core equipment in power system, power transformer plays a vital role in the stability of the power grid. It is necessary to quickly and accurately monitor the fault of the transformer. Frequency response method is an important method for fault diagnosis of transformers. It has many advantages, such as simple and light test equipment, easy measurement and high test sensitivity, intuitive analysis of experimental maps, and comparability of data magnitude analysis. It is considered to be a detection method with good application prospects. In this paper, the monitoring principle of frequency response method and the influencing factors in practical application are analyzed, and the shortcomings of the method and the research direction of the next step are prospected.

State-of-the-art methods assessing pathogenic non-coding variants have mostly been characterized on common disease-associated polymorphisms, yet with modest accuracy and strong positional biases. In this study, we curated 737 high-confidence pathogenic non-coding variants associated with monogenic Mendelian diseases. In addition to interspecies conservation, a comprehensive set of recent and ongoing purifying selection signals in humans is explored, accounting for lineage-specific regulatory elements. Supervised learning using gradient tree boosting on such features achieves a high predictive performance and overcomes positional bias. NCBoost performs consistently across diverse learning and independent testing data sets and outperforms other existing reference methods. Electronic supplementary material The online version of this article (10.1186/s13059-019-1634-2) contains supplementary material, which is available to authorized users.

The study of rare Mendelian diseases through exome sequencing typically yields incomplete diagnostic rates, ~8-70% depending on the disease type. Whole genome sequencing of the unresolved cases allows addressing the hypothesis that causal variants could lay in non-coding regions with damaging regulatory consequences. The large amount of rare and singleton variants found in each individual genome requires computational filtering and scoring strategies to gain power in downstream statistical genetics tests. However, state-of-the-art methods estimating the functional relevance of non-coding genomic regions have been mostly characterized on sets of variants largely composed of trait-associated polymorphisms and associated to common diseases, yet with modest accuracy and strong positional biases. In this work we first curated a collection of n=737 high-confidence pathogenic non-coding single-nucleotide variants in proximalcis-regulatory genomic regions associated to monogenic Mendelian diseases. We then systematically evaluated the ability to predict causal variants of a comprehensive set of natural selection features extracted at three genomic levels: the affected position, the flanking region and the associated gene. In addition to inter-species conservation, a comprehensive set of recent and ongoing purifying selection signals in human was explored, allowing to capture potential constraints associated to recently acquired regulatory elements in the human lineage. A supervised learning approach using gradient tree boosting on such features reached a high predictive performance characterized by an area under the ROC curve = 0.84 and an area under the Precision-Recall curve = 0.47. The figures represent a relative improvement of >10% and >34% respectively upon the performance of current state-of-the-art methods for prioritizing non-coding variants. Performance was consistent under multiple configurations of the sets of variants used for learning and for independent testing. The supervised learning design allowed the assessment of newly seen non-coding variants overcoming gene and positional bias. The scores produced by the approach allow a more consistent weighting and aggregation of candidate pathogenic variants from diverse non-coding regions within and across genes in the context of statistical tests for rare variant association analysis.

Beam wander effects have been discussed as the main reason for the failure of the first-order Rytov approximation to properly predict the scintillation index of Gaussian beam through the atmospheric turbulent channel of optical wireless communication. This paper investigates the beam wander effects on scintillation theory of Gaussian beam based on the new generalized anisotropic non-Kolmogorov power spectrum, where all the influence of the anisotropy of turbulence, the general spectral power law, and the finite turbulence inner and outer scales are considered simultaneously. For both horizontal path and uplink path, novel expressions of the beam wander, the wander-induced pointing error variance and the beam-wander-induced scintillation index are derived. Numerical simulations are performed to show the significant influence of beam wander on the scintillation index in the propagation of Gaussian beam.

Optical mobile ad-hoc networks suffer from the atmospheric turbulence. A new kind of routing algorithm based on disruption-tolerant network protocols is proposed. The proposed scheme improves the delivery ratio by 40% in severe network environment.

DNA extracted from cancer patients' whole blood may contain somatic mutations from circulating tumor DNA (ctDNA) fragments. In this study, we introduce cmDetect, a computational method for the systematic identification of ctDNA mutations using whole-exome sequencing of a cohort of tumor and corresponding peripheral whole-blood samples. Through the analysis of simulated data, we demonstrated an increase in sensitivity in calling somatic mutations by combining cmDetect to two widely used mutation callers. In a cohort of 93 breast cancer metastatic patients, cmDetect identified ctDNA mutations in 54% of the patients and recovered somatic mutations in cancer genes EGFR, PIK3CA, and TP53. We further showed that cmDetect detected ctDNA in 89% of patients with confirmed mutated cell–free tumor DNA by plasma analyses (n = 9) within 46 pan-cancer patients. Our results prompt immediate consideration of the use of this method as an additional step in somatic mutation calling using whole-exome sequencing data with blood samples as controls. Cancer Res; 76(20); 5954–61. ©2016 AACR.

Leflunomide is an effective drug used in the treatment of rheumatoid arthritis. Here we report the findings of an open-label pilot study, which found that leflunomide is also an effective treatment for myasthenia gravis (MG). This study recruited 15 corticosteroid-dependent MG patients. For 6 months, leflunomide 20 mg was given to these patients daily along with prednisone. The quantitative myasthenia gravis (QMG) scores and MG activities of daily living (MG-ADL) profiles were measured in these MG patients. After 6 months of treatment, 9 of the 15 patients enrolled in this study showed improvements in both QMG and MG-ADL. The mean QMG scores (13.4 to 8.5) and MG-ADL profiles (5.8 to 2.8) were significantly decreased (P = 0.01, 0.006 respectively). Furthermore, we found that the mean corticosteroid doses were reduced after treatment with leflunomide (24.3 to 12.3 mg per day). Leflunomide is a well-tolerated and efficacious treatment for corticosteroid-dependent MG, which may also enable lower doses of corticosteroids to be administered.

Ag-dendrimer nanoclusters were prepared with Ag+ and carboxyl shell (G4.5) poly(amino amine) dendrimers. Self-assembly photosensitive ultrathin films were then fabricated with these Ag-dendrimer nanoclusters as polyanions and diazoresin (DR) as polycation. With UV irradiating the films became stable because of the formation of covalent linkages between the layers. Compared to similar films containing no Ag nanoclusters, the obtained films showed greatly enhanced electric conductivity. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 1515–1519, 2003

Multilayer ultrathin films composed of nitro-containing diazoresin (NDR) as polycation and poly(amidoamine) dendrimers with carboxyl terminal groups (PAMAMC) (G = 1.5, 2.5, 3.5, and 4.5) as polyanion were fabricated on mica by electrostatic layer-by-layer deposition. Subsequent UV irradiation converted the interlayer linkage from ionic to covalent. The films were characterized with UV−vis, FTIR, X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), and X-ray diffraction (XRD). The results show that the uniform multilayer films were formed. All the films with dendrimers of various generations as building blocks have a very smooth surface with a mean roughness of about 0.8−1.1 nm. The thickness of the PAMAMC−NDR bilayer in the films increases with the generation number of the dendrimer, but the average thickness of the dendrimer monolayer is smaller than the diameter of the ideal spherical model of dendrimers with an extended conformation of all branches. They are significantly compressed i...