Controlled transport of water molecules through membranes and capillaries is important in areas as diverse as water purification and healthcare technologies
. Previous attempts to control water ...permeation through membranes (mainly polymeric ones) have concentrated on modulating the structure of the membrane and the physicochemical properties of its surface by varying the pH, temperature or ionic strength
. Electrical control over water transport is an attractive alternative; however, theory and simulations
have often yielded conflicting results, from freezing of water molecules to melting of ice
under an applied electric field. Here we report electrically controlled water permeation through micrometre-thick graphene oxide membranes
. Such membranes have previously been shown to exhibit ultrafast permeation of water
and molecular sieving properties
, with the potential for industrial-scale production. To achieve electrical control over water permeation, we create conductive filaments in the graphene oxide membranes via controllable electrical breakdown. The electric field that concentrates around these current-carrying filaments ionizes water molecules inside graphene capillaries within the graphene oxide membranes, which impedes water transport. We thus demonstrate precise control of water permeation, from ultrafast permeation to complete blocking. Our work opens up an avenue for developing smart membrane technologies for artificial biological systems, tissue engineering and filtration.
Manipulating the surface energy, and thereby the wetting properties of solids, has promise for various physical, chemical, biological and industrial processes. Typically, this is achieved by either ...chemical modification or by controlling the hierarchical structures of surfaces. Here we report a phenomenon whereby the wetting properties of vermiculite laminates are controlled by the hydrated cations on the surface and in the interlamellar space. We find that vermiculite laminates can be tuned from superhydrophilic to hydrophobic simply by exchanging the cations; hydrophilicity decreases with increasing cation hydration free energy, except for lithium. The lithium-exchanged vermiculite laminate is found to provide a superhydrophilic surface due to its anomalous hydrated structure at the vermiculite surface. Building on these findings, we demonstrate the potential application of superhydrophilic lithium exchanged vermiculite as a thin coating layer on microfiltration membranes to resist fouling, and thus, we address a major challenge for oil-water separation technology.
Background
The prevalence of drug allergies documented in electronic health records (EHRs) of large patient populations is understudied.
Objective
We aimed to describe the prevalence of common drug ...allergies and patient characteristics documented in EHRs of a large healthcare network over the last two decades.
Methods
Drug allergy data were obtained from EHRs of patients who visited two large tertiary care hospitals in Boston from 1990 to 2013. The prevalence of each drug and drug class was calculated and compared by sex and race/ethnicity. The number of allergies per patient was calculated and the frequency of patients having 1, 2, 3…, or 10+ drug allergies was reported. We also conducted a trend analysis by comparing the proportion of each allergy to the total number of drug allergies over time.
Results
Among 1 766 328 patients, 35.5% of patients had at least one reported drug allergy with an average of 1.95 drug allergies per patient. The most commonly reported drug allergies in this population were to penicillins (12.8%), sulfonamide antibiotics (7.4%), opiates (6.8%), and nonsteroidal anti‐inflammatory drugs (NSAIDs) (3.5%). The relative proportion of allergies to angiotensin‐converting enzyme (ACE) inhibitors and HMG CoA reductase inhibitors (statins) have more than doubled since early 2000s. Drug allergies were most prevalent among females and white patients except for NSAIDs, ACE inhibitors, and thiazide diuretics, which were more prevalent in black patients.
Conclusion
Females and white patients may be more likely to experience a reaction from common medications. An increase in reported allergies to ACE inhibitors and statins is noteworthy.
We report the discovery of TOI 837b and its validation as a transiting planet. We characterize the system using data from the NASA Transiting Exoplanet Survey Satellite mission, the ESA Gaia mission, ...ground-based photometry from El Sauce and ASTEP400, and spectroscopy from CHIRON, FEROS, and Veloce. We find that TOI 837 is a T = 9.9 mag G0/F9 dwarf in the southern open cluster IC 2602. The star and planet are therefore million years old. Combining the transit photometry with a prior on the stellar parameters derived from the cluster color-magnitude diagram, we find that the planet has an orbital period of and is slightly smaller than Jupiter ( ). From radial velocity monitoring, we limit to less than 1.20 MJup (3 ). The transits either graze or nearly graze the stellar limb. Grazing transits are a cause for concern, as they are often indicative of astrophysical false-positive scenarios. Our follow-up data show that such scenarios are unlikely. Our combined multicolor photometry, high-resolution imaging, and radial velocities rule out hierarchical eclipsing binary scenarios. Background eclipsing binary scenarios, though limited by speckle imaging, remain a 0.2% possibility. TOI 837b is therefore a validated adolescent exoplanet. The planetary nature of the system can be confirmed or refuted through observations of the stellar obliquity and the planetary mass. Such observations may also improve our understanding of how the physical and orbital properties of exoplanets change in time.
Abstract
Wide-field surveys for transiting planets are well suited to searching diverse stellar populations, enabling a better understanding of the link between the properties of planets and their ...parent stars. We report the discovery of HAT-P-69 b (TOI 625.01) and HAT-P-70 b (TOI 624.01), two new hot Jupiters around A stars from the Hungarian-made Automated Telescope Network (HATNet) survey that have also been observed by the
Transiting Exoplanet Survey Satellite
. HAT-P-69 b has a mass of
M
Jup
and a radius of
R
Jup
and resides in a prograde 4.79 day orbit. HAT-P-70 b has a radius of
R
Jup
and a mass constraint of
M
Jup
and resides in a retrograde 2.74 day orbit. We use the confirmation of these planets around relatively massive stars as an opportunity to explore the occurrence rate of hot Jupiters as a function of stellar mass. We define a sample of 47,126 main-sequence stars brighter than
T
mag
= 10 that yields 31 giant planet candidates, including 18 confirmed planets, 3 candidates, and 10 false positives. We find a net hot Jupiter occurrence rate of 0.41 ± 0.10% within this sample, consistent with the rate measured by
Kepler
for FGK stars. When divided into stellar mass bins, we find the occurrence rate to be 0.71 ± 0.31% for G stars, 0.43 ± 0.15% for F stars, and 0.26 ± 0.11% for A stars. Thus, at this point, we cannot discern any statistically significant trend in the occurrence of hot Jupiters with stellar mass.
The molecular mechanism underlying gastric cancer (GC) invasion and metastasis is still poorly understood. In this study, we tried to investigate the roles of CXCR4 and CXCR2 signalings in gastric ...cancer metastasis. A highly invasive gastric cancer cell model was established. Chemokines receptors were profiled to search for the accountable ones. Then the underlying molecular mechanism was investigated using both in vitro and in vivo techniques, and the clinical relevance of CXCR4 and CXCR2 expression was studied in gastric cancer samples. CXCR4 and CXCR2 were highly expressed in a high invasive gastric cancer cell model and in gastric cancer tissues. Overexpression of CXCR4 and CXCR2 was associated with more advanced tumor stage and poorer survival for GC patients. CXCR4 and CXCR2 expression strongly correlated with each other in the way that CXCR2 expression changed accordingly with the activity of CXCR4 signaling and CXCR4 expression also changed in agreement with CXCR2 activity. Further studies demonstrated CXCR4 and CXCR2 can both activated NF-κB and STAT3 signaling, while NF-κBp65 can then transcriptionally activate CXCR4 and STAT3 can activate CXCR2 expression. This crosstalk between CXCR4 and CXCR2 contributed to EMT, migration and invasion of gastric cancer. Finally, Co-inhibition of CXCR4 and CXCR2 is more effective in reducing gastric cancer metastasis. Our results demonstrated that CXCR4 and CXCR2 cross-activate each other to promote the metastasis of gastric cancer.
Abstract
We report the joint WASP/KELT discovery of WASP-167b/KELT-13b, a transiting hot Jupiter with a 2.02-d orbit around a V = 10.5, F1V star with Fe/H = 0.1 ± 0.1. The 1.5 R
Jup planet was ...confirmed by Doppler tomography of the stellar line profiles during transit. We place a limit of <8 M
Jup on its mass. The planet is in a retrograde orbit with a sky-projected spin–orbit angle of λ = −165° ± 5°. This is in agreement with the known tendency for orbits around hotter stars to be more likely to be misaligned. WASP-167/KELT-13 is one of the few systems where the stellar rotation period is less than the planetary orbital period. We find evidence of non-radial stellar pulsations in the host star, making it a δ-Scuti or γ-Dor variable. The similarity to WASP-33, a previously known hot-Jupiter host with pulsations, adds to the suggestion that close-in planets might be able to excite stellar pulsations.
An elevated DNA-repair capacity in cancer cells leads to radiation resistance and severely limits the efficacy of radiation therapy. Activation of Akt is tightly associated with resistance to ...radiotherapy, and Mre11 protein has important role during the repair of DNA double-strand breaks (DSBs). In this report, our results showed that inhibition of Akt activity impaired the repair of DSBs in CNE2 cells, whereas activated Akt promoted the repair of DSBs in HeLa cells. Knockdown of Mre11 also impaired the process of DSB repair in both these two cell lines. More importantly, we found that Akt could regulate Mre11 expression. Inhibition of Akt activity by small interfering RNA or LY294002 efficiently downregulated the Mre11 expression in CNE2 cells, and transfection with myr-Akt plasmid in HeLa cells upregulated the Mre11 expression. In addition, luciferase reporter analysis revealed that Mre11 reporter activity increased after transfection with myr-Akt1 plasmids, and this myr-Akt1-induced transcriptional activity was blocked in the presence of LY294002. Further study showed GSK3β/β-catenin/LEF-1 pathway was involved in this regulation. Knockdown of β-catenin or LEF-1 led to the downregulation of Mre11, whereas overexpression of β-catenin led to upregulation of Mre11. The chromatin immunoprecipitation assay assay showed β-catenin/LEF-1 heterodimer could directly bind to the promoter of Mre11 in vivo. And the luciferase activity of the pGL3-Mre11 and pGL3-Lef increased in HeLa cells following β-catenin plasmid co-transfected, but was abolished when the LEF-1-binding conserved sequences of Mre11 promoter were mutated. These results together support Akt can upregulate the expression of Mre11 through GSK3β/ β-catenin/LEF pathway to elevate DSB-repair capacity in cancer cells.
Bortezomib therapy has proven successful for the treatment of relapsed/refractory, relapsed, and newly diagnosed multiple myeloma (MM); however, dose-limiting toxicities and the development of ...resistance limit its long-term utility. Here, we show that P5091 is an inhibitor of deubiquitylating enzyme USP7, which induces apoptosis in MM cells resistant to conventional and bortezomib therapies. Biochemical and genetic studies show that blockade of HDM2 and p21 abrogates P5091-induced cytotoxicity. In animal tumor model studies, P5091 is well tolerated, inhibits tumor growth, and prolongs survival. Combining P5091 with lenalidomide, HDAC inhibitor SAHA, or dexamethasone triggers synergistic anti-MM activity. Our preclinical study therefore supports clinical evaluation of USP7 inhibitor, alone or in combination, as a potential MM therapy.
► P5091 is a potent and selective inhibitor of deubiquitylating enzyme USP7 ► P5091 triggers in vitro and in vivo antimyeloma activity ► P5091 activates HDM2/p53/p21 signaling axis ► Synergistic anti-MM activity of P5091 with SAHA, lenalidomide, or dexamethasone
PDF
