Magnetospheric compression due to impact of enhanced solar wind dynamic pressure Pdyn has long been considered as one of the generation mechanisms of electromagnetic ion cyclotron (EMIC) waves. With ...the Van Allen Probe‐A observations, we identify three EMIC wave events that are triggered by Pdyn enhancements under prolonged northward interplanetary magnetic field (IMF) quiet time preconditions. They are in contrast to one another in a few aspects. Event 1 occurs in the middle of continuously increasing Pdyn while Van Allen Probe‐A is located outside the plasmapause at postmidnight and near the equator (magnetic latitude (MLAT) ~ −3°). Event 2 occurs by a sharp Pdyn pulse impact while Van Allen Probe‐A is located inside the plasmapause in the dawn sector and rather away from the equator (MLAT ~ 12°). Event 3 is characterized by amplification of a preexisting EMIC wave by a sharp Pdyn pulse impact while Van Allen Probe‐A is located outside the plasmapause at noon and rather away from the equator (MLAT ~ −15°). These three events represent various situations where EMIC waves can be triggered by Pdyn increases. Several common features are also found among the three events. (i) The strongest wave is found just above the He+ gyrofrequency. (ii) The waves are nearly linearly polarized with a rather oblique propagation direction (~28° to ~39° on average). (iii) The proton fluxes increase in immediate response to the Pdyn impact, most significantly in tens of keV energy, corresponding to the proton resonant energy. (iv) The temperature anisotropy with T⊥ > T|| is seen in the resonant energy for all the events, although its increase by the Pdyn impact is not necessarily always significant. The last two points (iii) and (iv) may imply that in addition to the temperature anisotropy, the increase of the resonant protons must have played a critical role in triggering the EMIC waves by the enhanced Pdyn impact.
Key Points
Three EMIC wave events triggered by various dynamic pressure conditions
Exhibit proton flux increases in expected resonant energy
Exhibit temperature anisotropy with T⊥ > T|| in the resonant energy
We provide detailed mechanisms of Ahnak-mediated potentiation of transforming growth factor β (TGFβ) signaling, which leads to a negative regulation of cell growth. We show that Smad3 interacts with ...Ahnak through MH2 domain and that Ahnak stimulates Smad3 localization into nucleus leading to potentiating TGFβ-induced transcriptional activity of R-Smad. Moreover, overexpression of Ahnak resulted in growth retardation and cell cycle arrest through downregulation of c-Myc and cyclin D1/D2. We describe results from analyses of Ahnak(-/-) mouse model expressing middle T antigen in a mammary gland-specific manner (MMTV(Tg/+)Ahnak(-/-)), which showed significantly progressed hyperplasia of mammary glands compared with MMTV(Tg/+)Ahnak(+/+). Finally, we screened multiple human breast cancer tissues and showed that the expression of Ahnak in cancer tissues is lower than that in control tissues by 50%. Taken together, these data indicate that Ahnak mediates a negative regulation of cell growth and acts as novel tumor suppressor through potentiation of TGFβ signaling.
The effect of displacement and humidity on fretting-induced instability of electrical contact resistance (Rc) was studied. A fretting tester was used to examine Rc in partial and gross slip modes. ...Under the partial slip regime the contact failure was susceptible to the displacement and moisture effectively increased contact stability, which was pronounced at smaller displacements. In the gross slip mode, however, humidity effect was relatively small. The early contact failure at low humidity was attributed to the wear debris agglomeration within the sliding interface, suggesting a high propensity of electrical contact failure at dry conditions.
•The effect of humidity and displacement on fretting induced electrical contact failure was studied.•Humidity effect was pronounced at small displacements due to effective removal of debris.•Premature contact failure was found at low humidity and with large displacements.•Moisture reduced wear debris pileup, producing a smooth contact area with more electrical junctions.•Our results suggested a high propensity of electrical contact failure at dry conditions.
Berberine is a pure phenanthren alkaloid isolated from the roots and bark of herbal plants such as
Berberis,
Hydrastis canadensis and
Coptis chinensis. Berberine has been established to inhibit the ...growth of breast cancer cells, but its effects on the drug resistance and anoikis-resistance of breast cancer cells have yet to be elucidated. Anoikis, or detachment-induced apoptosis, may prevent cancer progression and metastasis by blocking signals necessary for survival of localized cancer cells. Resistance to anoikis is regarded as a prerequisite for metastasis; however, little is known about the role of berberine in anoikis-resistance. We established anoikis-resistant cells from the breast cancer cell lines MCF-7 and MDA-MB-231 by culturing them on a Poly-Hema substratum. We then investigated the effects of berberine on the growth of these cells. The anoikis-resistant cells had a reduced growth rate and were more invasive than their respective adherent cell lines. The effect of berberine on growth was compared to that of doxorubicine, which is a drug commonly used to treat breast cancer, in both the adherent and anoikis-resistant cell lines. Berberine promoted the growth inhibition of anoikis-resistant cells to a greater extent than doxorubicine treatment. Treatment with berberine-induced cell cycle arrest at G0/G1 in the anoikis-resistant MCF-7 and MDA-MB-231 cells as compared to untreated control cells. In summary, these results revealed that berberine can efficiently inhibit growth by inducing cell cycle arrest in anoikis-resistant MCF-7 and MDA-MB-231 cells. Further analysis of these phenotypes is essential for understanding the effect of berberine on anoikis-resistant breast cancer cells, which would be relevant for the therapeutic targeting of breast cancer metastasis.
Background: This study was to devise a prognostic model for metastatic gastric cancer patients undergoing first-line chemotherapy. Patients and methods: A retrospective analysis was carried out on ...1455 gastric cancer patients, who received first-line chemotherapy from September 1994 to February 2005. Results: At multivariate level, poor prognostic factors were no previous gastrectomy P = 0.003; relative risk (RR), 1.191; 95% confidence interval (CI) 1.061–1.338, albumin <3.6 g/dl (P = <0.001; RR, 1.245; 95% CI 1.106–1.402), alkaline phosphatase >85 U/l (P = <0.001; RR, 1.224; 95% CI 1.092–1.371), Eastern Cooperative Oncology Group performance status of two or more (P = <0.001; RR, 1.690; 95% CI 1.458–1.959), the presence of bone metastases (P = 0.001; RR, 1.460; 95% CI 1.616–1.836), and the presence of ascites (P = <0.001; RR, 1.452; 95% CI 1.295–1.628). Of 1434 patients, 489 patients (34.1%) were categorized as low-risk group (zero to one factors), 889 patients (62.0%) as intermediate-risk group (two to four factors), and 56 patients (3.9%) as high-risk group (five to six factors). Median survival durations for low, intermediate, and high-risk groups were 12.5 months, 7.0 months, and 2.7 months, respectively. Conclusions: This model should facilitate the individual patient risk stratification and thus, more appropriate therapies for each metastatic gastric cancer patient.
The development of nanocrystals has been intensively pursued, not only for their fundamental scientific interest, but also for many technological applications. The synthesis of monodisperse ...nanocrystals (size variation <5%) is of key importance, because the properties of these nanocrystals depend strongly on their dimensions. For example, the colour sharpness of semiconductor nanocrystal-based optical devices is strongly dependent on the uniformity of the nanocrystals, and monodisperse magnetic nanocrystals are critical for the next-generation multi-terabit magnetic storage media. For these monodisperse nanocrystals to be used, an economical mass-production method needs to be developed. Unfortunately, however, in most syntheses reported so far, only sub-gram quantities of monodisperse nanocrystals were produced. Uniform-sized nanocrystals of CdSe (refs 10,11) and Au (refs 12,13) have been produced using colloidal chemical synthetic procedures. In addition, monodisperse magnetic nanocrystals such as Fe (refs 14,15), Co (refs 16-18), γ-Fe2O3 (refs 19,20), and Fe3O4 (refs 21,22) have been synthesized by using various synthetic methods. Here, we report on the ultra-large-scale synthesis of monodisperse nanocrystals using inexpensive and non-toxic metal salts as reactants. We were able to synthesize as much as 40 g of monodisperse nanocrystals in a single reaction, without a size-sorting process. Moreover, the particle size could be controlled simply by varying the experimental conditions. The current synthetic procedure is very general and nanocrystals of many transition metal oxides were successfully synthesized using a very similar procedure.
Background and purpose
The progression pattern of brain structural changes in patients with isolated cerebrovascular disease (CVD) remains unclear. To investigate the role of isolated CVD in ...cognitive impairment patients, patterns of cortical thinning and hippocampal atrophy in pure subcortical vascular mild cognitive impairment (svMCI) and pure subcortical vascular dementia (SVaD) patients were characterized.
Methods
Forty‐five patients with svMCI and 46 patients with SVaD who were negative on Pittsburgh compound B (PiB) positron emission tomography imaging and 75 individuals with normal cognition (NC) were recruited.
Results
Compared with NC, patients with PiB(−) svMCI exhibited frontal, language and retrieval type memory dysfunctions, which in patients with PiB(−) SVaD were further impaired and accompanied by visuospatial and recognition memory dysfunctions. Compared with NC, patients with PiB(−) svMCI exhibited cortical thinning in the frontal, perisylvian, basal temporal and posterior cingulate regions. This atrophy was more prominent and extended further toward the lateral parietal and medial temporal regions in patients with PiB(−) SVaD. Compared with NC subjects, patients with PiB(−) svMCI exhibited hippocampal shape deformities in the lateral body, whilst patients with PiB(−) SVaD exhibited additional deformities within the lateral head and inferior body.
Conclusions
Our findings suggest that patients with CVD in the absence of Alzheimer's disease pathology can be demented, showing cognitive impairment in multiple domains, which is consistent with the topography of cortical thinning and hippocampal shape deformity.
Summary
Several biomarkers of esophageal squamous cell carcinoma (ESCC) have been explored to improve the prognosis of this disease. One of these, the 47‐kDa heat shock protein (HSP47), has been ...screened as a potential biomarker by genomic profiling and is known to be overexpressed in some malignant diseases. In this study, we explored the role and evaluated the prognostic value of HSP47 expression in ESCC. The function of this protein was analyzed by assaying proliferation, wound healing, and colony formation in an HSP47‐knockdown ESCC line. The prognostic implication of HSP47 expression was analyzed by immunohistochemical staining in 157 surgical specimens. HSP47 expression level and other clinical variables were analyzed using multivariate Cox proportional hazards models. Silencing of the HSP47 gene in the ESCC cell line inhibited cell proliferation and colony formation. HSP47 was highly expressed in ESCC tissue samples, compared with normal esophageal tissues. The level of immunohistochemical staining of HSP47 and pathologic stage were significantly correlated with overall and recurrence‐free survival, as shown by multivariate analysis (P = 0.014 and 0.044, respectively). We found that overexpression of HSP47 is associated with poor prognosis in patients with ESCC and that this is consistent with the function of HSP47 in terms of increased cell proliferation and colony formation. These results suggest that HSP47 is a potential prognostic biomarker for ESCC and merits further research for novel diagnostic and therapeutic applications.
Rapid injection of MeV electrons associated with strong substorm dipolarization has been suggested as a potential explanation for some radiation belt enhancement events. However, it has been ...difficult to quantify the contribution of MeV electron injections to radiation belt enhancements. This paper presents two isolated MeV electron injection events for which we quite precisely quantify how the entire outer‐belt immediately changed with the injections. Tracking detailed outer‐belt evolution observed by Van Allen Probes, for both events, we identify large step‐like relativistic electron enhancements (roughly 1 order of magnitude increase for ∼2 MeV electron fluxes) for L ≳ 3.8 and L ≳ 4.6, respectively, that occurred on ∼30‐min time scales nearly instantaneously with the injections. The enhancements occurred almost simultaneously for 10s keV to multi‐MeV electrons, with the lowest L of enhancement region located farther out for higher energy. The outer‐belt stayed at these new levels for ≳several hours without substantial subsequent enhancements.
Plain Language Summary
Since the discovery of the Earth's radiation belts, the populations of energetic particles trapped by the magnetic fields, understanding the origin of radiation belt relativistic electrons has been one of the primary goals in space physics. One proposal for their source is that relativistic electrons are rapidly injected from outside the radiation belts associated with dramatic changes of the background magnetic field. To explore the importance of this process, we conduct a case study of two isolated injection events. With a new analysis technique, we quite precisely determine how the entire radiation belt electron population immediately changed with the injections. For both events, we find large, step‐like relativistic electron enhancements in a significant part of the outer radiation belt. The enhancements occurred promptly with the injections on extremely fast time scales that are comparable to the injection process. Furthermore, they occurred almost simultaneously for a wide energy range, showing an energy‐dependent feature that can be explained by injection process. After the enhancements, the outer‐belt relativistic electron intensities stayed at the enhanced levels for at least several hours without substantial subsequent enhancements, indicating that the enhancements occurred discretely with the injections.
Key Points
Quantitative determination of prompt and global outer‐belt responses for two MeV electron injection events
Large step‐like outer‐belt relativistic electron enhancements on ∼30‐min time scales nearly instantaneously with the injections
The extremely fast step‐like outer‐belt enhancements for the two events are most‐likely injection‐driven
Although many studies have reported an association between serum gamma-glutamyltransferase (GGT) and cardiovascular risk factors, the mechanism of this relationship has not been clarified.
The ...medical records of 29,959 subjects (age, median 48, range 14-90 years; 16,706 men, 13,253 women) who visited the Center for Health Promotion at Samsung Medical Center for a medical check-up between January 2001 and December 2003, were investigated. Subjects with hepatic enzyme/GGT concentrations higher than three times the upper limit of the reference range, a positive test for hepatitis C virus antibody, a positive test for hepatitis B virus surface antigen, currently taking anti-diabetic/anti-hypertensive/anti-lipid medication, or a white blood cell (WBC) count higher than 10,000 cells/ml, were excluded. The subjects of each gender were classified into five groups according to their serum GGT concentrations, into quartiles of the normal range of GGT (groups 1, 2, 3 and 4) and into a group with elevated GGT (group 5).
As the group number increased (group 1 --> 5), the frequencies of all of the following increased: (i) diabetes and impaired fasting glucose (IFG); (ii) hypertension, obesity (body mass index > or = 27 kg/m2), dyslipidaemia (LDL-cholesterol > or = 4.1 mmol/l and/or triglyceride > or = 2.46 mmol/l, or HDL-cholesterol < 1.16 mmol/l); (iii) metabolic syndrome. Moreover, these significant relationships between GGT concentrations within its normal range and the presence of diabetes/IFG, hypertension, obesity, dyslipidaemia, and metabolic syndrome persisted after adjusting for several clinical and biochemical variables and for the presence of fatty liver based on ultrasonographic findings. Odds ratios (95% CI) for group 4 (highest quartile of normal range of GGT) vs. group 1 (lowest quartile of normal range of GGT); the referent group, were 3.16 (2.15-4.65) for diabetes, 2.24 (1.73-2.90) for IFG, 1.93 (1.59-2.33) for obesity, 1.38 (1.23-1.55) for dyslipidaemia and 2.88 (2.28-3.65) for metabolic syndrome in men. In women, the odds ratios were 2.72 (1.34-5.52), 3.67 (2.26-5.97), 2.10 (1.61-2.74), 1.80 (1.58-2.04) and 3.57 (2.52-5.07), respectively.
Our data show that, even within its normal range, serum GGT concentrations are closely associated with the presence of diabetes and cardiovascular risk factors, and that these associations are independent of a fatty liver by ultrasonography.
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