Transcript fusions as a result of chromosomal rearrangements have been a focus of attention in cancer as they provide attractive therapeutic targets. To identify novel fusion transcripts with the ...potential to be exploited therapeutically, we analyzed RNA sequencing, DNA copy number and gene mutation data from 4366 primary tumor samples. To avoid false positives, we implemented stringent quality criteria that included filtering of fusions detected in RNAseq data from 364 normal tissue samples. Our analysis identified 7887 high confidence fusion transcripts across 13 tumor types. Our fusion prediction was validated by evidence of a genomic rearrangement for 78 of 79 fusions in 48 glioma samples where whole-genome sequencing data were available. Cancers with higher levels of genomic instability showed a corresponding increase in fusion transcript frequency, whereas tumor samples harboring fusions contained statistically significantly fewer driver gene mutations, suggesting an important role for tumorigenesis. We identified at least one in-frame protein kinase fusion in 324 of 4366 samples (7.4%). Potentially druggable kinase fusions involving ALK, ROS, RET, NTRK and FGFR gene families were detected in bladder carcinoma (3.3%), glioblastoma (4.4%), head and neck cancer (1.0%), low-grade glioma (1.5%), lung adenocarcinoma (1.6%), lung squamous cell carcinoma (2.3%) and thyroid carcinoma (8.7%), suggesting a potential for application of kinase inhibitors across tumor types. In-frame fusion transcripts involving histone methyltransferase or histone demethylase genes were detected in 111 samples (2.5%) and may additionally be considered as therapeutic targets. In summary, we described the landscape of transcript fusions detected across a large number of tumor samples and revealed fusion events with clinical relevance that have not been previously recognized. Our results support the concept of basket clinical trials where patients are matched with experimental therapies based on their genomic profile rather than the tissue where the tumor originated.
Summary
We evaluated the efficacy and safety of telbivudine (LdT, 600 mg/day) vs control patients (no treatment) in decreasing vertical transmission of HBV, in HBeAg‐positive mothers (HBVDNA ...>6log10 copies/mL). HBeAg‐positive pregnant women either in the second or third trimester were recruited in a prospective, case–control, open‐label study, at the Second Affiliated Hospital of the Southeast University, China (February 2008‐December 2010). Efficacy (month 7: HBVDNA (+), HBsAg (+) infants) in either the overall group or the treated group and control group was analysed using student's t‐test. Infants were followed for at least 1 year. 362 women received LdT (second trimester n = 257; third trimester n = 105) and 92 were untreated. Before delivery, the mean maternal HBVDNA was 2.73, 2.47, 3.34 and 7.94 log10 copies/mL in the overall, second and third trimester treated and control groups, respectively (P < 0.001). At birth, 11.8% of babies overall (43/365), 13.5% (35/259) of those treated in the second trimester, 7.5% of those treated in the third trimester (8/106) and 20.7% (19/92) of untreated infants were HBsAg positive. At month 7, none of the LdT‐treated infant had detectable HBVDNA, while eight infants from control mothers were HBsAg positive. Vertical transmission was 0% in LdT treated and 9.3% (8/86) in the control groups (P < 0.001). No difference in the vertical transmission rate was found in mothers treated in the second or third trimester. LdT treatment was safe for mothers and infants, and no congenital deformities were reported.
Turbulence is commonly viewed as a type of macroflow, where the Reynolds number (Re) has to be sufficiently high. In microfluidics, when Re is below or on the order of 1 and fast mixing is required, ...so far only chaotic flow has been reported to enhance mixing based on previous publications since turbulence is believed not to be possible to generate in such a low Re microflow. There is even a lack of velocimeter that can measure turbulence in microchannels. In this work, we report a direct observation of the existence of turbulence in microfluidics with Re on the order of 1 in a pressure driven flow under electrokinetic forcing using a novel velocimeter having ultrahigh spatiotemporal resolution. The work could provide a new method to control flow and transport phenomena in lab-on-a-chip and a new perspective on turbulence.
The emergence of the H7N9 influenza virus in humans in Eastern China has raised concerns that a new influenza pandemic could occur. Here, we used a ferret model to evaluate the infectivity and ...transmissibility of A/Shanghai/2/2013 (SH2), a human H7N9 virus isolate. This virus replicated in the upper and lower respiratory tracts of the ferrets and was shed at high titers for 6 to 7 days, with ferrets showing relatively mild clinical signs. SH2 was efficiently transmitted between ferrets via direct contact, but less efficiently by airborne exposure. Pigs were productively infected by SH2 and shed virus for 6 days but were unable to transmit the virus to naïve pigs or ferrets. Under appropriate conditions, human-to-human transmission of the H7N9 virus may be possible.
Solid sorption refrigeration is a type of environmental benign and energy saving technology and the sorbents utilized can be divided into physical, chemical and composite sorbents, according to the ...nature of the forces involved in the adsorption process. The types, characteristics, advantages and disadvantages of different adsorbents, refrigerants and working pairs are summarized in this paper, together with the models that describe the adsorption equilibrium. Moreover, some of the procedures to prepare composite adsorbents are presented. The application of different working pairs for different situations is related with the adsorption heat, the adaptability to the driving temperature and to the desired working pressure. The methods to measure the adsorption quantity of different working pairs are compared, and future research directions of adsorption working pairs are also analyzed.
Esterase has been reported to be involved in malathion resistance in the oriental fruit fly, Bactrocera dorsalis (Hendel). However, the underlying molecular mechanism of the esterase‐mediated ...resistance remains largely unknown in this species. Here, with the use of a strain selected for malathion resistance in the laboratory (MR), we found that two overexpressed α‐esterase genes, namely BdCarE4 and BdCarE6, predominant in the adult midgut and fat body, function in conferring malathion resistance in B. dorsalis. Notably, these two genes were found to be mostly close to the esterase E3, which are usually implicated in detoxifying organophosphate insecticides. The transcript levels of BdCarE4 and BdCarE6 were investigated and compared between the MR and a susceptible (MS) strain of B. dorsalis. Both genes were significantly up‐regulated in the MR strain, which was consistent with the enhanced esterase activity in the MR strain. However, no changes in either the coding sequence or gene copy number were observed between the two strains. Subsequently, heterologous expression combined with cytotoxicity assay in Sf9 cells demonstrated that BdCarE4 and BdCarE6 can probably detoxify malathion. Furthermore, RNA interference‐mediated knockdown of each of these two genes significantly increased malathion susceptibility in the MR strain adults. In conclusion, these results expand our molecular understanding of the important role of α‐esterases during the development of resistance to organophosphorous insecticides in B. dorsalis.
Carbon cycling in the coastal zone affects global carbon budgets and is critical for understanding the urgent issues of hypoxia, acidification, and tidal wetland loss. However, there are no regional ...carbon budgets spanning the three main ecosystems in coastal waters: tidal wetlands, estuaries, and shelf waters. Here we construct such a budget for eastern North America using historical data, empirical models, remote sensing algorithms, and process‐based models. Considering the net fluxes of total carbon at the domain boundaries, 59 ± 12% (± 2 standard errors) of the carbon entering is from rivers and 41 ± 12% is from the atmosphere, while 80 ± 9% of the carbon leaving is exported to the open ocean and 20 ± 9% is buried. Net lateral carbon transfers between the three main ecosystem types are comparable to fluxes at the domain boundaries. Each ecosystem type contributes substantially to exchange with the atmosphere, with CO2 uptake split evenly between tidal wetlands and shelf waters, and estuarine CO2 outgassing offsetting half of the uptake. Similarly, burial is about equal in tidal wetlands and shelf waters, while estuaries play a smaller but still substantial role. The importance of tidal wetlands and estuaries in the overall budget is remarkable given that they, respectively, make up only 2.4 and 8.9% of the study domain area. This study shows that coastal carbon budgets should explicitly include tidal wetlands, estuaries, shelf waters, and the linkages between them; ignoring any of them may produce a biased picture of coastal carbon cycling.
Plain Language Summary
A carbon budget for a particular site or region describes the inputs and outputs of carbon to that site or region as well as the processes that change carbon from one form to another. A carbon budget is needed to fully understand many important issues facing coastal waters. We constructed the carbon budget for coastal waters of eastern North America. We found that about 60% of the carbon entering the domain is from rivers and about 40% is from the atmosphere, while about 80% of the carbon leaving the domain goes to the open ocean and about 20% is buried. Transfers of carbon from wetlands to estuaries and from estuaries to the ocean were as important as transfers of carbon at the domain boundaries. Tidal wetlands and estuaries were found to be important to the carbon budget despite making up only 2.4 and 8.9% of the study domain area, respectively. This study shows that coastal carbon budgets should explicitly consider tidal wetlands, estuaries, shelf waters, and the linkages between them; ignoring any of them may produce a biased picture of coastal carbon cycling.
Key Points
Tidal wetlands, estuaries, and shelf waters each contribute substantially to the carbon budget of eastern North American coastal waters
Study region net ecosystem production, atmospheric uptake, and burial are 20.2 ± 4.4, 5.1 ± 2.4, and 2.5 ± 0.7 Tg C yr−1, respectively
Net lateral carbon fluxes between tidal wetlands, estuaries, and shelf waters are large terms in the carbon budget of eastern North American coastal waters
Transiting extrasolar planets constitute only a small fraction of the range of stellar systems found to display periodic, shallow dimmings in wide-field surveys employing small-aperture camera ...arrays. Here we present an efficient selection strategy for follow-up observations, derived from analysis of the light curves of a sample of 67 SuperWASP targets that passed the selection tests we used in earlier papers, but which have subsequently been identified either as planet hosts or as astrophysical false positives. We determine the system parameters using Markov-chain Monte Carlo analysis of the SuperWASP light curves. We use a constrained optimization of χ2 combined with a Bayesian prior based on the main-sequence mass and radius expected from the Two Micron All Sky Survey J−H colour. The Bayesian nature of the analysis allows us to quantify both the departure of the host star from the main-sequence mass–radius relation and the probability that the companion radius is less than 1.5 Jupiter radii. When augmented by direct light-curve analyses that detect binaries with unequal primary and secondary eclipses, and objects with aperture blends that are resolved by SuperWASP, we find that only 13 of the original 67 stars, including the three known planets in the sample, would qualify for follow-up. This suggests that planet discovery ‘hit rates’ better than one-in-five should be achievable. In addition, the stellar binaries that qualify are likely to have astrophysically interesting stellar or substellar secondaries.
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