MethylPurify: tumor purity deconvolution and differential methylation detection from single tumor DNA methylomes

We propose a statistical algorithm MethylPurify that uses regions with bisulfite reads showing discordant methylation levels to infer tumor purity from tumor samples alone. MethylPurify can identify differentially methylated regions (DMRs) from individual tumor methylome samples, without genomic variation information or prior knowledge from other datasets. In simulations with mixed bisulfite reads from cancer and normal cell lines, MethylPurify correctly inferred tumor purity and identified over 96% of the DMRs. From patient data, MethylPurify gave satisfactory DMR calls from tumor methylome samples alone, and revealed potential missed DMRs by tumor to normal comparison due to tumor heterogeneity. Electronic supplementary material The online version of this article (doi:10.1186/s13059-014-0419-x) contains supplementary material, which is available to authorized users

Higgs boson production in photon-photon collision at ILC: a comparative study in different little Higgs models

We study the process \gamma\gamma->h->bb_bar at ILC as a probe of different little Higgs models, including the simplest little Higgs model (SLH), the littlest Higgs model (LH), and two types of littlest Higgs models with T-parity (LHT-I, LHT-II). Compared with the Standard Model (SM) prediction, the production rate is found to be sizably altered in these little Higgs models and, more interestingly, different models give different predictions. We find that the production rate can be possibly enhanced only in the LHT-II for some part of the parameter space, while in all other cases the rate is suppressed. The suppression can be 10% in the LH and as much as 60% in both the SLH and the LHT-I/LHT-II. The severe suppression in the SLH happens for a large \tan\beta and a small m_h, in which the new decay mode h->\eta\eta (\eta is a light pseudo-scalar) is dominant; while for the LHT-I/LHT-II the large suppression occurs when f and m_h are both small so that the new decay mode h->A_H A_H is dominant. Therefore, the precision measurement of such a production process at the ILC will allow for a test of these models and even distinguish between different scenarios.Comment: Version in JHEP (h-g-g & h-gamma-gamma expressions added

Integrative analysis of genomic sequencing data reveals higher prevalence of LRP1B mutations in lung adenocarcinoma patients with COPD

AbstractBoth chronic Obstruction Pulmonary Disease (COPD) and lung cancer are leading causes of death globally. Although COPD and lung cancer coexist frequently, it is unknown whether lung cancer patients with COPD harbor distinct genomic characteristics compared to those without COPD. In this study, we retrospectively analyzed genomic sequencing data from 272 patients with lung adenocarcinoma (LUAD) and compared the genetic alterations in LUAD patients with and without COPD. Integrative analysis of whole-genome and exome sequencing data revealed that COPD and non-COPD groups showed high concordance in mutational burden and spectra. Notably, we also found that EGFR mutations were more prevalent in LUAD patients without COPD, whereas mutated LRP1B was more frequently observed in LUAD patients with COPD. In addition, multi-variable analysis with logistic regression demonstrated that mutation of LRP1B was a predictive marker for the presence of COPD in the patients with LUAD. Our analysis demonstrated for the first time the high concordance in genomic alterations between the tumors from LUAD patients with and without COPD. We also identified higher prevalence of LRP1B among the LUAD patients with COPD, which might help understand the underlying mechanisms which link COPD and lung cancer.</jats:p

Numerical investigation on stress corrosion cracking behavior of dissimilar weld joints in pressurized water reactor plants

There have been incidents recently where stress corrosion cracking (SCC) observed in the dissimilar metal weld (DMW) joints connecting the reactor pressure vessel (RPV) nozzle with the hot leg pipe. Due to the complex microstructure and mechanical heterogeneity in the weld region, dissimilar metal weld joints are more susceptible to SCC than the bulk steels in the simulated high temperature water environment of pressurized water reactor (PWR). Tensile residual stress (RS), in addition to operating loads, has a great contribution to SCC crack growth. Limited experimental conditions, varied influence factors and diverging experimental data make it difficult to accurately predict the SCC behavior of DMW joints with complex geometry, material configuration, operating loads and crack shape. Based on the film slip/dissolution oxidation model and elastic-plastic finite element method (EPFEM), an approach is developed to quantitatively predict the SCC growth rate of a RPV outlet nozzle DMW joint. Moreover, this approach is expected to be a pre-analytical tool for SCC experiment of DMW joints in PWR primary water environment

Characteristics of electric field strengthening between coal-mineral particles under microwave irradiation

Both thermal and non-thermal effects induced by microwave radiation can produce a series of effects on coal and rock, and microwave induced discharge is one of the phenomena of microwave non-thermal effects. Coal has a porous and ore-rich skeleton structure with strong heterogeneity. Its internal pores and minerals can affect the electric field. The microwave discharge phenomenon and electric field strengthening characteristics between different component particles are quite different. At present, the relevant researches mainly focus on the coal matrix in the coal body, ignoring the influence of the minerals in the coal body and the irregular shape of the minerals themselves. As a result, the discharge mechanism between real mineral particles and the factors affecting its discharge intensity are still unclear. Therefore, the shape of real coal and rock particles scanned by electronic X-ray tomography (XCT) was described by drawing software, and COMSOL Multiphysics software was used by in this work to discuss the electric field strengthening characteristics of real coal and rock particles under a microwave field and the causes. The results show that the propagation mode and polarization characteristics of microwave have a significant effect on the enhancement of the intergranular electric field, and the intensity of the intergranlar electric field is the largest in x propagation and y polarization. Compared with the other five particle combinations, the particle size and spacing have the most obvious effect on the electric field strengthening of the pyrite-pyrite combination, and the best effect of the electric field strengthening of the coal-rock particle combination appears in the case of large particle size and no spacing. The change of the Angle between particles has a certain influence on the effect of electric field strengthening, and the maximum value of electric field strengthening corresponding to each particle shape appears when the Angle is 0°. The electric field strengthening effect of regular ore particles (round, square, pentagon, etc.) is directly related to the roundness coefficient of the particles. The maximum electric field strength between particles occurs when the Angle of particle tip is about 60° and the roundness coefficient is 0.71. However, the electric field intensity of irregular ore particles has no relation with roundness coefficient and fractal dimension, but gradually increases with the increase of curvature. In addition, the degree of graphitization of carbonaceous materials has a great influence on the electric field strengthening effect, and the electric field intensity increases with the increase of graphitization degree

Seismogenic structures and spatiotemporal seismicity patterns of the 2022 Ms6.0 Maerkang earthquake sequence, Sichuan, China

The 2022 Ms6.0 Maerkang earthquake sequence, Sichuan, China, occurred in an unexpected area with historically rare seismicity in the Bayan Har block. Here we relocated the earthquake sequence, inverted for the focal mechanisms of the larger events, and calculated the rupture directivity of the earthquake sequence to reveal the seismogenic structures and mechanisms of this sequence. The high-precision relocations indicate that the seismogenic structures consist of several clusters that are generally parallel to the nearby NW-trending Songgang fault, and relatively small-scale conjugate faults are also identified. The seismicity migrated from cluster one in the south to cluster two in the north during the sequence. Furthermore, the hypocenters were largely located at 5–10 km depth, thereby highlighting that the seismogenic structures are buried. The vertical fault planes of the seismogenic structures are consistent with the high-dip focal mechanism solutions from seven events. A stress field inversion based on the focal mechanisms indicates that the sequence occurred in a strike-slip environment that was controlled by a NNW–SSE-striking principal compressive stress. The different rupture directivities of the Ms5.8 (southwestward) and Ms6.0 (southeastward) events prove the existence of conjugate faults. The Ms5.8 event induced a coseismic Coulomb stress change of 1.6 MPa where the Ms6.0 event subsequently occurred, thereby highlighting that the Ms5.8 event triggered the Ms6.0 event and produced the spatiotemporal seismicity pattern of the sequence. We therefore conclude that the seismogenic structures of the 2022 Ms6.0 Maerkang earthquake sequence are previously unknown concealed conjugate structures associated with the main Songgang fault. The complex seismogenic structures and their potential to generate large earthquakes warrant the need to better understand the seismogenesis of this area and the seismic risks that may be present

Impacts of the Tropical Pacific/Indian Oceans on the Seasonal Cycle of the West African Monsoon

The current consensus is that drought has developed in the Sahel during the second half of the twentieth century as a result of remote effects of oceanic anomalies amplified by local land–atmosphere interactions. This paper focuses on the impacts of oceanic anomalies upon West African climate and specifically aims to identify those from SST anomalies in the Pacific/Indian Oceans during spring and summer seasons, when they were significant. Idealized sensitivity experiments are performed with four atmospheric general circulation models (AGCMs). The prescribed SST patterns used in the AGCMs are based on the leading mode of covariability between SST anomalies over the Pacific/Indian Oceans and summer rainfall over West Africa. The results show that such oceanic anomalies in the Pacific/Indian Ocean lead to a northward shift of an anomalous dry belt from the Gulf of Guinea to the Sahel as the season advances. In the Sahel, the magnitude of rainfall anomalies is comparable to that obtained by other authors using SST anomalies confined to the proximity of the Atlantic Ocean. The mechanism connecting the Pacific/Indian SST anomalies with West African rainfall has a strong seasonal cycle. In spring (May and June), anomalous subsidence develops over both the Maritime Continent and the equatorial Atlantic in response to the enhanced equatorial heating. Precipitation increases over continental West Africa in association with stronger zonal convergence of moisture. In addition, precipitation decreases over the Gulf of Guinea. During the monsoon peak (July and August), the SST anomalies move westward over the equatorial Pacific and the two regions where subsidence occurred earlier in the seasons merge over West Africa. The monsoon weakens and rainfall decreases over the Sahel, especially in August.Peer reviewe

Severe early onset preeclampsia: short and long term clinical, psychosocial and biochemical aspects

Preeclampsia is a pregnancy specific disorder commonly defined as de novo hypertension and proteinuria after 20 weeks gestational age. It occurs in approximately 3-5% of pregnancies and it is still a major cause of both foetal and maternal morbidity and mortality worldwide1. As extensive research has not yet elucidated the aetiology of preeclampsia, there are no rational preventive or therapeutic interventions available. The only rational treatment is delivery, which benefits the mother but is not in the interest of the foetus, if remote from term. Early onset preeclampsia (<32 weeks’ gestational age) occurs in less than 1% of pregnancies. It is, however often associated with maternal morbidity as the risk of progression to severe maternal disease is inversely related with gestational age at onset2. Resulting prematurity is therefore the main cause of neonatal mortality and morbidity in patients with severe preeclampsia3. Although the discussion is ongoing, perinatal survival is suggested to be increased in patients with preterm preeclampsia by expectant, non-interventional management. This temporising treatment option to lengthen pregnancy includes the use of antihypertensive medication to control hypertension, magnesium sulphate to prevent eclampsia and corticosteroids to enhance foetal lung maturity4. With optimal maternal haemodynamic status and reassuring foetal condition this results on average in an extension of 2 weeks. Prolongation of these pregnancies is a great challenge for clinicians to balance between potential maternal risks on one the eve hand and possible foetal benefits on the other. Clinical controversies regarding prolongation of preterm preeclamptic pregnancies still exist – also taking into account that preeclampsia is the leading cause of maternal mortality in the Netherlands5 - a debate which is even more pronounced in very preterm pregnancies with questionable foetal viability6-9. Do maternal risks of prolongation of these very early pregnancies outweigh the chances of neonatal survival? Counselling of women with very early onset preeclampsia not only comprises of knowledge of the outcome of those particular pregnancies, but also knowledge of outcomes of future pregnancies of these women is of major clinical importance. This thesis opens with a review of the literature on identifiable risk factors of preeclampsia

Whole-Brain Mapping of the Inputs and Outputs of the Medial Part of the Olfactory Tubercle

The medial part of the olfactory tubercle (OT) is a brain structure located at the interface of the reward and olfactory system. It is closely related to pheromone-rewards, natural reinforcement, addiction and many other behaviors. However, the structure of the anatomic circuitry of the medial part of the OT is still unclear. In the present study, the medial part of the OT was found to be highly connected with a wide range of brain areas with the help of the pseudorabies virus tracing tool. In order to further investigate the detailed connections for specific neurons, another tracing tool – rabies virus was utilized for D1R-cre and D2R-cre mice. The D1R and D2R neurons in the medial part of the OT were both preferentially innervated by the olfactory areas, especially the piriform cortex, and both had similar direct input patterns. With the help of the adeno-associated virus labeling, it was found that the two subpopulations of neurons primarily innervate with the reward related brain regions, with slightly less axons projecting to the olfactory areas. Thus, the whole-brain input and output circuitry structures for specific types of neurons in the medial part of the OT were systematically investigated, and the results revealed many unique connecting features. This work could provide new insights for further study into the physiological functions of the medial part of the OT