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There is an ongoing debate on the importance of genetic factors in cancer development, where gene-centered cancer predisposition seems to show that only 5 to 10% of the cancer cases are inheritable. By conducting a systematic analysis of germline genomes of 9712 cancer patients representing 22 common cancer types along with 16,670 noncancer individuals, we identified seven cancer-associated germline genomic patterns (CGGPs), which summarized trinucleotide mutational spectra of germline genomes. A few CGGPs were consistently enriched in the germline genomes of patients whose tumors had smoking signatures or correlated with oncogenesis- and genome instability–related mutations. Furthermore, subgroups defined by the CGGPs were significantly associated with distinct oncogenic pathways, tumor histological subtypes, and prognosis in 13 common cancer types, suggesting that germline genomic patterns enable to inform treatment and clinical outcomes. These results provided evidence that cancer risk and clinical outcomes could be encoded in germline genomes. Germline variants when organized as genomic patterns are associated with cancer risk, oncogenic pathways, and clinical outcomes.

Non-orthogonal multiple access (NOMA) has been proposed as a promising technology that is capable of improving the spectral efficiency of fifth-generation wireless networks and beyond. However, in practical communication scenarios, transceiver architectures inevitably suffer from radio frequency (RF) front-end related impairments that cause non-negligible performance degradation. This issue can be addressed by analog and digital signal processing algorithms, but factors such as time-varying hardware characteristics and imperfect compensation schemes result to detrimental residual distortions. In the present contribution we investigate the physical layer security of NOMA-based amplify-and-forward relay systems under such realistically incurred residual hardware impairment (RHI) effects. Exact and asymptotic analytic expressions for the corresponding outage probability (OP) and intercept probability (IP) of the considered set up over multipath fading channels are derived and corroborated by respective simulation results. Based on this, it is shown that RHI affects both the legitimate users and eavesdroppers by increasing the OP and decreasing the IP. For a fixed OP, RHI generally increases the corresponding IP, thereby reducing the secure performance of the system. Further interesting insights are also provided, verifying the importance of the offered results for the effective design and deployment of secure cooperative communication systems. acceptedVersion Peer reviewed

Parkinson's disease (PD) is one of the most prevalent neurodegenerative brain diseases; it is accompanied by extensive loss of dopamine (DA) neurons of the substantia nigra that project to the putamen, leading to impaired motor functions. Several genes have been associated with hereditary forms of the disease and transgenic mice have been developed by a number of groups to produce animal models of PD and to explore the basic functions of these genes. Surprisingly, most of the various mouse lines generated such as Parkin KO, Pink1 KO, DJ-1 KO and LRRK2 transgenic have been reported to lack degeneration of nigral DA neuron, one of the hallmarks of PD. However, modest impairments of motor behavior have been reported, suggesting the possibility that the models recapitulate at least some of the early stages of PD, including early dysfunction of DA axon terminals. To further evaluate this possibility, here we provide for the first time a systematic comparison of DA release in four different mouse lines, examined at a young age range, prior to potential age-dependent compensations. Using fast scan cyclic voltammetry in striatal sections prepared from young, 6-8 weeks old mice, we examined sub-second DA overflow evoked by single pulses and action potential trains. Unexpectedly, none of the models displayed any dysfunction of DA overflow or reuptake. These results, compatible with the lack of DA neuron loss in these models, suggest that molecular dysfunctions caused by the absence or mutation of these individual genes are not sufficient to perturb the function and survival of mouse DA neurons.

The COnstrain Dark Energy with X-ray clusters (CODEX) sample contains the largest flux limited sample of X-ray clusters at $0.35 < z < 0.65$. It was selected from ROSAT data in the 10,000 square degrees of overlap with BOSS, mapping a total number of 2770 high-z galaxy clusters. We present here the full results of the CFHT CODEX program on cluster mass measurement, including a reanalysis of CFHTLS Wide data, with 25 individual lensing-constrained cluster masses. We employ $lensfit$ shape measurement and perform a conservative colour-space selection and weighting of background galaxies. Using the combination of shape noise and an analytic covariance for intrinsic variations of cluster profiles at fixed mass due to large scale structure, miscentring, and variations in concentration and ellipticity, we determine the likelihood of the observed shear signal as a function of true mass for each cluster. We combine 25 individual cluster mass likelihoods in a Bayesian hierarchical scheme with the inclusion of optical and X-ray selection functions to derive constraints on the slope $��$, normalization $��$, and scatter $��_{\ln ��| ��}$ of our richness-mass scaling relation model in log-space: $\left = ����+ ��$, with $��= \ln (M_{200c}/M_{\mathrm{piv}})$, and $M_{\mathrm{piv}} = 10^{14.81} M_{\odot}$. We find a slope $��= 0.49^{+0.20}_{-0.15}$, normalization $ \exp(��) = 84.0^{+9.2}_{-14.8}$ and $��_{\ln ��| ��} = 0.17^{+0.13}_{-0.09}$ using CFHT richness estimates. In comparison to other weak lensing richness-mass relations, we find the normalization of the richness statistically agreeing with the normalization of other scaling relations from a broad redshift range ($0.0 37 pages, 12 figures

Autophagy, a self-defense mechanism, has been found to be associated with drug resistance in hepatocellular carcinoma (HCC). Our study was designed to investigate the role and related mechanisms of autophagy in matrine-induced apoptosis in hepatoma cells of HepG2 and Bel7402. Cell apoptosis was detected by flow cytometry analysis (Annexin V–FITC/PI double-staining assay), the activity and activating cleavages of caspase-3, -8, and -9. MTT assay and colony forming assay were used to assess the effect of matrine on growth and proliferation of HCC cells. Autophagic flux in HCC cells was analyzed using the expression of LC3BI/II and p62/SQSTM1, GFP-LC3 transfection, and transmission electron microscopy. Moreover, regarding to the associated mechanisms, the effects of matrine on the phosphoinositide 3-kinase/AKT/mTOR pathway and beclin-1 were studied. Our results showed that: (1) both autophagy and apoptosis could be induced by treatment with matrine; (2) using the autophagic inhibitor chloroquine and beclin-1 small-interfering RNA, cell apoptosis induced by matrine could be enhanced in a caspase-dependent manner; and (3) autophagy was induced via inhibition of PI3K/AKT/mTOR pathway and up-regulation of beclin-1. In conclusion, inhibition of autophagy could enhance matrine-induced apoptosis in human hepatoma cells.

Orofacial clefts (OFCs), which include non-syndromic cleft lip with or without cleft palate (CL/P), are among the most common birth defects in humans, affecting approximately 1 in 700 newborns. CL/P is phenotypically heterogeneous and has a complex etiology caused by genetic and environmental factors. Previous genome-wide association studies (GWASs) have identified at least 15 risk loci for CL/P. As these loci do not account for all of the genetic variance of CL/P, we hypothesized the existence of additional risk loci. We conducted a multiethnic GWAS in 6480 participants (823 unrelated cases, 1700 unrelated controls and 1319 case-parent trios) with European, Asian, African and Central and South American ancestry. Our GWAS revealed novel associations on 2p24 near FAM49A, a gene of unknown function (P = 4.22 × 10-8), and 19q13 near RHPN2, a gene involved in organizing the actin cytoskeleton (P = 4.17 × 10-8). Other regions reaching genome-wide significance were 1p36 (PAX7), 1p22 (ARHGAP29), 1q32 (IRF6), 8q24 and 17p13 (NTN1), all reported in previous GWASs. Stratification by ancestry group revealed a novel association with a region on 17q23 (P = 2.92 × 10-8) among individuals with European ancestry. This region included several promising candidates including TANC2, an oncogene required for development, and DCAF7, a scaffolding protein required for craniofacial development. In the Central and South American ancestry group, significant associations with loci previously identified in Asian or European ancestry groups reflected their admixed ancestry. In summary, we have identified novel CL/P risk loci and suggest new genes involved in craniofacial development, confirming the highly heterogeneous etiology of OFCs. Orofacial clefts (OFCs), which include non-syndromic cleft lip with or without cleft palate (CL/P), are among the most common birth defects in humans, affecting approximately 1 in 700 newborns. CL/P is phenotypically heterogeneous and has a complex etiology caused by genetic and environmental factors. Previous genome-wide association studies (GWASs) have identified at least 15 risk loci for CL/P. As these loci do not account for all of the genetic variance of CL/P, we hypothesized the existence of additional risk loci. We conducted a multiethnic GWAS in 6480 participants (823 unrelated cases, 1700 unrelated controls and 1319 case-parent trios) with European, Asian, African and Central and South American ancestry. Our GWAS revealed novel associations on 2p24 near FAM49A, a gene of unknown function (P = 4.22 × 10(-8)), and 19q13 near RHPN2, a gene involved in organizing the actin cytoskeleton (P = 4.17 × 10(-8)). Other regions reaching genome-wide significance were 1p36 (PAX7), 1p22 (ARHGAP29), 1q32 (IRF6), 8q24 and 17p13 (NTN1), all reported in previous GWASs. Stratification by ancestry group revealed a novel association with a region on 17q23 (P = 2.92 × 10(-8)) among individuals with European ancestry. This region included several promising candidates including TANC2, an oncogene required for development, and DCAF7, a scaffolding protein required for craniofacial development. In the Central and South American ancestry group, significant associations with loci previously identified in Asian or European ancestry groups reflected their admixed ancestry. In summary, we have identified novel CL/P risk loci and suggest new genes involved in craniofacial development, confirming the highly heterogeneous etiology of OFCs.

Neutrophils play a critical role in host defense against Pseudomonas aeruginosa infection. Mechanisms underlying the negative regulation of neutrophil function in bacterial clearance remain incompletely defined. Here, we demonstrate that protein tyrosine phosphatase-1B (PTP1B) is a negative regulator of P. aeruginosa clearance by neutrophils. PTP1B-deficient neutrophils display greatly enhanced bacterial phagocytosis and killing, which are accompanied by increased Toll-like receptor 4 (TLR4) signaling activation and nitric oxide (NO) production following P. aeruginosa infection. Interestingly, PTP1B deficiency mainly upregulates the production of IL-6 and IFN-β, leads to enhanced TLR4-dependent STAT1 activation and iNOS expression by neutrophils following P. aeruginosa infection. Further studies reveal that PTP1B and STAT1 are physically associated. These findings demonstrate a negative regulatory mechanism in neutrophil underlying the elimination of P. aeruginosa infection though a PTP1B-STAT1 interaction.

We present the results of structural and magnetic phase comparisons of the iron oxychalcogenides La$_{2}$O$_{2}$Fe$_{2}$O$M$$_{2}$ ($M$ = S, Se). Elastic neutron scattering reveals that $M$ = S and Se have similar nuclear structures at room and low temperatures. We find that both materials obtain antiferromagnetic ordering at a Neel temperature $T_{N}$ 90.1 $\pm$ 0.16 K and 107.2 $\pm$ 0.06 K for $M$= Se and S, respectively. The magnetic arrangements of $M$ = S, Se are obtained through Rietveld refinement. We find the order parameter exponent $\beta$ to be 0.129 $\pm$ 0.006 for $M$ = Se and 0.133 $\pm$ 0.007 for $M$ = S. Each of these values is near the Ising symmetry value of 1/8. This suggests that although lattice and electronic structural modifications result from chalcogen exchange, the nature of the magnetic interactions is similar in these materials.

Remote sensing-derived cropland products have depicted the location and extent of agricultural lands with an ever increasing accuracy. However, limited attention has been devoted to distinguishing between actively cropped fields and fallowed fields within agricultural lands, and in particular so in grass fallow systems of semi-arid areas. In the Sahel, one of the largest dryland regions worldwide, crop-fallow rotation practices are widely used for soil fertility regeneration. Yet, little is known about the extent of fallow fields since fallow is not explicitly differentiated within the cropland class in any existing remote sensing-based land use/cover maps, regardless of the spatial scale. With a 10 m spatial resolution and a 5-day revisit frequency, Sentinel-2 satellite imagery made it possible to disentangle agricultural land into cropped and fallow fields, facilitated by Google Earth Engine (GEE) for big data handling. Here we produce the first Sahelian fallow field map at a 10 m resolution for the baseline year 2017, accomplished by designing a remote sensing driven protocol for generating reference data for mapping over large areas. Based on the 2015 Copernicus Dynamic Land Cover map at 100 m resolution, the extent of fallow fields in the cropland class is estimated to be 63% (403,617 km2) for the Sahel in 2017. Similar results are obtained for five contemporary cropland products, with fallow fields occupying 57–62% of the cropland area. Yet, it is noted that the total estimated area coverage depends on the quality of the different cropland products. The share of cropped fields within the Copernicus cropland area is found to be higher in the arid regions (200–300 mm rainfall) as compared to the semi-arid regions (300–600 mm rainfall). The woody cover fraction within cropped and fallow fields is found to have a reversed pattern between arid (higher woody cover in cropped fields) and semi-arid (higher woody cover in fallow fields) regions. The method developed, using cloud-based Earth Observation (EO) data and computation on the GEE platform, is expected to be reproducible for mapping the extent of fallow fields across global croplands. Future applications based on multi-year time series is expected to improve our understanding of crop-fallow rotation dynamics in grass fallow systems being key in teasing apart how cropland intensification and expansion affect environmental variables, such as soil fertility, crop yields and local livelihoods in low-income regions such as the Sahel. The mapping result can be visualized via a web viewer (https://buwuyou.users.earthengine.app/view/fallowinsahel).

This study presents a multiparameter analysis of aerosol trends over the last 2 decades at regional and global scales. Regional time series have been computed for a set of nine optical, chemical-composition and mass aerosol properties by using the observations from several ground-based networks. From these regional time series the aerosol trends have been derived for the different regions of the world. Most of the properties related to aerosol loading exhibit negative trends, both at the surface and in the total atmospheric column. Significant decreases in aerosol optical depth (AOD) are found in Europe, North America, South America, North Africa and Asia, ranging from −1.2 % yr−1 to −3.1 % yr−1. An error and representativity analysis of the spatially and temporally limited observational data has been performed using model data subsets in order to investigate how much the observed trends represent the actual trends happening in the regions over the full study period from 2000 to 2014. This analysis reveals that significant uncertainty is associated with some of the regional trends due to time and space sampling deficiencies. The set of observed regional trends has then been used for the evaluation of 10 models (6 AeroCom phase III models and 4 CMIP6 models) and the CAMS reanalysis dataset and of their skills in reproducing the aerosol trends. Model performance is found to vary depending on the parameters and the regions of the world. The models tend to capture trends in AOD, the column Ångström exponent, sulfate and particulate matter well (except in North Africa), but they show larger discrepancies for coarse-mode AOD. The rather good agreement of the trends, across different aerosol parameters between models and observations, when co-locating them in time and space, implies that global model trends, including those in poorly monitored regions, are likely correct. The models can help to provide a global picture of the aerosol trends by filling the gaps in regions not covered by observations. The calculation of aerosol trends at a global scale reveals a different picture from that depicted by solely relying on ground-based observations. Using a model with complete diagnostics (NorESM2), we find a global increase in AOD of about 0.2 % yr−1 between 2000 and 2014, primarily caused by an increase in the loads of organic aerosols, sulfate and black carbon.