Despite ionizing radiation (IR) is being widely used as a standard treatment for lung cancer, many evidences suggest that IR paradoxically promotes cancer malignancy. However, its molecular ...mechanisms underlying radiation-induced cancer progression remain obscure. Here, we report that exposure to fractionated radiation (2 Gy per day for 3 days) induces the secretion of granulocyte-colony-stimulating factor (G-CSF) that has been commonly used in cancer therapies to ameliorate neutropenia. Intriguingly, radiation-induced G-CSF promoted the migratory and invasive properties by triggering the epithelial-mesenchymal cell transition (EMT) in non-small-cell lung cancer cells (NSCLCs). By irradiation, G-CSF was upregulated transcriptionally by β-catenin/TCF4 complex that binds to the promoter region of G-CSF as a transcription factor. Importantly, irradiation increased the stability of β-catenin through the activation of PI3K/AKT (phosphatidylinositol 3-kinase/AKT), thereby upregulating the expression of G-CSF. Radiation-induced G-CSF is recognized by G-CSFR and transduced its intracellular signaling JAK/STAT3 (Janus kinase/signal transducers and activators of transcription), thereby triggering EMT program in NSCLCs. Taken together, our findings suggest that the application of G-CSF in cancer therapies to ameliorate neutropenia should be reconsidered owing to its effect on cancer progression, and G-CSF could be a novel therapeutic target to mitigate the harmful effect of radiotherapy for the treatment of NSCLC.
We identify the electron diffusion region (EDR) of a guide field dayside reconnection site encountered by the Magnetospheric Multiscale (MMS) mission and estimate the terms in generalized Ohm's law ...that controlled energy conversion near the X‐point. MMS crossed the moderate‐shear (∼130°) magnetopause southward of the exact X‐point. MMS likely entered the magnetopause far from the X‐point, outside the EDR, as the size of the reconnection layer was less than but comparable to the magnetosheath proton gyroradius, and also as anisotropic gyrotropic “outflow” crescent electron distributions were observed. MMS then approached the X‐point, where all four spacecraft simultaneously observed signatures of the EDR, for example, an intense out‐of‐plane electron current, moderate electron agyrotropy, intense electron anisotropy, nonideal electric fields, and nonideal energy conversion. We find that the electric field associated with the nonideal energy conversion is (a) well described by the sum of the electron inertial and pressure divergence terms in generalized Ohms law though (b) the pressure divergence term dominates the inertial term by roughly a factor of 5:1, (c) both the gyrotropic and agyrotropic pressure forces contribute to energy conversion at the X‐point, and (d) both out‐of‐the‐reconnection‐plane gradients (∂/∂M) and in‐plane (∂/∂L,N) in the pressure tensor contribute to energy conversion near the X‐point. This indicates that this EDR had some electron‐scale structure in the out‐of‐plane direction during the time when (and at the location where) the reconnection site was observed.
Key Points
We analyze MMS data measured during a slow crossing of the density‐asymmetric magnetopause
Ion and electron dynamics are consistent with a normal crossing of an inner diffusion region
J→·E→′ appeared to result from in and out‐of‐plane gradients of gyrotropic and agyrotropic electron pressure tensor
We report MMS observations of the ion-scale flux transfer events (FTEs) that may involve two main X lines and tearing instability between the two X lines. The four spacecraft detected multiple ...isolated regions with enhanced magnetic field strength and bipolar B(sub )n signatures normal to the nominal magnetopause, indicating FTEs. The currents within the FTEs flow mostly parallel to B, and the magnetic tension force is balanced by the total pressure gradient force. During these events, the plasma bulk flow velocity was directed southward. Detailed analysis of the magnetic and electric field and plasma moments variations suggests that the FTEs were initially embedded within the exhaust region north of an X line but were later located southward/downstream of a subsequent X line. The cross sections of the individual FTEs are in the range of ~2.5-6.8 ion inertial lengths. The observations suggest the formation of multiple secondary FTEs. The presence of an X line in the exhaust region southward of a second X line results from the southward drift of an old X line and the reformation of a new X line. The current layer between the two X lines is unstable to the tearing instability, generating multiple ion-scale flux-rope-type secondary islands.
Pig islets are an alternative source for islet transplantation to treat type 1 diabetes (T1D), but reproducible curative potential in the pig‐to‐nonhuman primate (NHP) model has not been ...demonstrated. Here, we report that pig islet grafts survived and maintained normoglycemia for >6 months in four of five consecutive immunosuppressed NHPs. Pig islets were isolated from designated pathogen‐free (DPF) miniature pigs and infused intraportally into streptozotocin‐induced diabetic rhesus monkeys under pretreatment with cobra venom factor (CVF), anti‐thymocyte globulin (ATG) induction and maintenance with anti‐CD154 monoclonal antibody and low‐dose sirolimus. Ex vivo expanded autologous regulatory T cells were adoptively transferred in three recipients. Blood glucose levels were promptly normalized in all five monkeys and normoglycemia (90–110 mg/dL) was maintained for >6 months in four cases, the longest currently up to 603 days. Intravenous glucose tolerance tests during the follow‐up period showed excellent glucose disposal capacity and porcine C‐peptide responses. Adoptive transfer of autologous regulatory T cells was likely to be associated with more stable and durable normoglycemia. Importantly, the recipients showed no serious adverse effects. Taken together, our results confirm the clinical feasibility of pig islet transplantation to treat T1D patients without the need for excessive immunosuppressive therapy.
The authors report control of diabetes for longer than six months in four consecutive nonhuman primates by the transplantation of adult pig islets using a modest immunosuppressive regimen with an acceptable adverse effect profile.
On 5 May 2017, MMS observed a crater‐type flux rope on the dawnside tailward magnetopause with fluctuations. The boundary‐normal analysis shows that the fluctuations can be attributed to nonlinear ...Kelvin‐Helmholtz (KH) waves. Reconnection signatures such as flow reversals and Joule dissipation were identified at the leading and trailing edges of the flux rope. In particular, strong northward electron jets observed at the trailing edge indicated midlatitude reconnection associated with the 3‐D structure of the KH vortex. The scale size of the flux rope, together with reconnection signatures, strongly supports the interpretation that the flux rope was generated locally by KH vortex‐induced reconnection. The center of the flux rope also displayed signatures of guide‐field reconnection (out‐of‐plane electron jets, parallel electron heating, and Joule dissipation). These signatures indicate that an interface between two interlinked flux tubes was undergoing interaction, causing a local magnetic depression, resulting in an M‐shaped crater flux rope, as supported by reconstruction.
Plain Language Summary
Magnetic reconnection and Kelvin‐Helmholtz instability (KHI), two of the most fundamental physical processes occurring within the heliosphere and throughout the Universe, often occur simultaneously on the Earth's magnetopause. Previous studies indicate the importance of nonlinearly developed KH waves, which produce multiple kinetic layers facilitating reconnection both in and out of the velocity shear plane and resulting in the magnetic flux rope. However, these studies significantly lacked detailed in situ observations in quantity as well as appropriate 3‐D analyses of the structure of the KH vortex‐induced flux rope. In this paper, we use detailed observations by the MMS spacecraft to investigate both 2‐D and 3‐D structures of the flux rope developed along the KH waves. We found that two flux tubes interact through reconnection to form a single combined structure, which can explain the occurrence of M‐shaped crater flux rope.
Key Points
MMS observed a magnetic flux rope formed on the boundary of a nonlinear Kelvin‐Helmholtz (KH) wave
Both in‐plane and midlatitude reconnection associated with the 3‐D structure of the KH vortex‐inducedflux rope were identified
A current sheet at the flux rope center supported by reconstruction indicates two flux tubes interlinked to form a crater‐type flux rope
We report the analysis of the microlensing event OGLE-2018-BLG-0677. A small feature in the light curve of the event leads to the discovery that the lens is a star-planet system. Although there are ...two degenerate solutions that could not be distinguished for this event, both lead to a similar planet-host mass ratio. We perform a Bayesian analysis based on a Galactic model to obtain the properties of the system and find that the planet corresponds to a super-Earth/sub-Neptune with a mass of . The host star has a mass of . The projected separation for the inner and outer solutions are au and au respectively. At , this is by far the lowest Δχ2 for any securely detected microlensing planet to date, a feature that is closely connected to the fact that it is detected primarily via a "dip" rather than a "bump."
Although magnesium alloys, as the lightest structural alloys, offer significant potential for automotive applications, their applications remain limited due to their poor formability at room ...temperature. Since the strategies used for improving formability usually result in a degradation of strength, there are no high strength magnesium alloys showing good formability. Here we report an alloy design concept that can simultaneously provide high strength and good formability. Such designed alloy when subjected to an appropriate processing technique shows a combination of strength and formability that surpasses those of the existing magnesium alloys reported so far. The alloy design concept used in the present study is based on the utilization of alloying elements that can induce precipitation, as well as maximize the segregation of other texture-controlling alloying elements. Such developed alloy is expected to broaden the application of Mg alloy sheets, which are now starting to gain acceptance by automotive industries.
We report the observation of solar wind‐magnetosphere‐ionosphere interactions using a series of flux transfer events (FTEs) observed by Magnetospheric MultiScale (MMS) mission located near the ...dayside magnetopause on 18 December 2017. The FTEs were observed to propagate duskward and either southward or slightly northward, as predicted under duskward and southward interplanetary magnetic field (IMF). The Cooling model also predicted a significant dawnward propagation of northward‐moving FTEs. Near the MMS footprint, a series of poleward‐moving auroral forms (PMAFs) occurred almost simultaneously with those FTEs. They propagated poleward and westward, consistent with the modeled FTE propagation. The intervals between FTEs, relatively consistent with those between PMAFs, strongly suggest a one‐to‐one correspondence between the dayside transients and ionospheric responses. The FTEs embedded in continuous reconnection observed by MMS and corresponding PMAFs individually occurred during persistent auroral activity recorded by an all‐sky imager strongly indicate that those FTEs/PMAFs resulted from the temporal modulation of the reconnection rate during continuous reconnection. With the decay of the PMAFs associated with the FTEs, patch‐like plasma density enhancements were detected to form and propagate poleward and then dawnward. Propagation to the dawn was also suggested by the Super Dual Auroral Radar Network (SuperDARN) convection and Global Positioning System (GPS) total electron content data. We relate the temporal variation of the driving solar‐wind and magnetospheric mechanism to that of the high‐latitude and polar ionospheric responses and estimate the response time.
Plain Language Summary
The solar wind‐magnetosphere coupling often occurs in a nonsteady manner. Such disturbances modify the magnetosphere‐ionosphere system. One of the most common/important processes of such nonsteady phenomena is time‐dependent dayside reconnection, as observationally evidenced by flux transfer events (FTEs), which have been, in turn, represented by ionospheric poleward‐moving auroral forms (PMAFs). Decaying PMAFs have, then, been followed by the occurrence of polar cap patches, which are regions of plasma density enhancements observed in the polar cap. This study indicates a sequence of dynamic processes from the driving solar wind, nonsteady reconnection/FTEs, PMAFs, and polar cap patches. Although a portion of this link has been studied and reported, the complete sequence of these connections and full picture of the solar wind‐magnetopause‐ionosphere coupling have rarely been reported and examined. The series of FTEs embedded in continuous reconnection and corresponding PMAFs individually occurred during persistent auroral activity strongly indicate that the FTEs and PMAFs were in response to the temporal modulation of the reconnection rate during continuous reconnection, rather than the repeated, complete turn‐on and turnoff of dayside reconnection. Our study advances the knowledge of Magnetosphere‐Ionosphere‐Coupling near the cusp region and in the open field‐line region that has been less developed than on closed field lines.
Key Points
Multiple flux transfer events (FTEs) were observed to form on the dayside magnetopause under southward and duskward IMF
Ground‐based observations indicate the poleward‐moving plasma streams or auroral forms (PMAFs) associated with the FTEs
Development and transpolar motion of polar cap patches following the PMAFs complete the link of solar wind‐magnetosphere‐ionosphere coupling
Gender disparities in tuberculosis (TB) cases are reported worldwide, and socio-cultural factors have been proposed as possible causes. To date, gender differences in treatment outcomes of TB ...patients remain controversial. In this prospective observational study, newly diagnosed, culture-proven TB patients from six hospitals in Taiwan were enrolled for analysis. Gender differences in demographic characteristics and treatment outcomes, including sputum conversion and on-treatment mortality, were analysed accordingly. From January 2007 through to December 2009, a total of 1059 patients were enrolled, including 819 (77.3%) males and 240 (22.7%) females. The ratio of male gender was around 50~60% in TB patients below 35 years and >80% for those older than 65 years. When compared with the female patients, the male patients were older, more likely to have the habit of smoking, chronic obstructive pulmonary disorder, malignancy and liver cirrhosis, and more likely to present with haemoptysis, body weight loss and pleural effusion. Regarding treatment outcomes, male gender is associated with a lower 2-month sputum culture conversion rate (78.8% vs. 89.3%, p 0.002) and higher on-treatment mortality (21.1% vs. 12.1%, p 0.002). Kaplan-Meier survival analysis demonstrated significantly higher mortality in the men (p 0.005). In multivariate analysis, male gender was an independent risk factor for 2-month sputum culture un-conversion (OR, 1.96; 95% CI, 1.12–3.41). Our findings suggest that male gender is associated with older age, more co-morbidities and worse treatment outcomes. Gender-specific strategies, including active case finding in elderly women and smoking cessation in male patients, are warranted to optimize TB management.
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