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Normal aging is associated with diminished brain perfusion measured as cerebral blood flow (CBF), but previously it is difficult to accurately measure various aspects of perfusion hemodynamics including: bolus arrival times and delays through small arterioles, expressed as arterial-arteriole transit time. To study hemodynamics in greater detail, volumetric arterial spin labeling MRI with variable postlabeling delays was used together with a distributed, dual-compartment tracer model. The main goal was to determine how CBF and other perfusion hemodynamics vary with aging. Twenty cognitive normal female and 15 male subjects (age: 23-84 years old) were studied at 4 T. Arterial spin labeling measurements were performed in the posterior cingulate cortex, precuneus, and whole brain gray matter. CBF declined with advancing age (P < 0.001). Separately from variations in bolus arrival times, arterial-arteriole transit time increased with advancing age (P < 0.01). Finally, women had overall higher CBF values (P < 0.01) and shorter arterial-arteriole transit time (P < 0.01) than men, regardless of age. The findings imply that CBF and blood transit times are compromised in aging, and these changes together with differences between genders should be taken into account when studying brain perfusion. Magn Reson Med 68:912-922,

IntroductionEpidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are associated with favorable response in EGFR mutant lung cancer. Acquired resistance to reversible EGFR TKIs remains a significant barrier, and acquired EGFR T790M-mutation is the major mechanism. Second-generation irreversible EGFR TKI, afatinib, had also been approved for treating EGFR mutant lung cancer patients, but the mechanism of acquired resistance to afatinib has not been well studied.ResultsForty-two patients had tissue specimens taken after acquiring resistance to afatinib. The sensitizing EGFR mutation were all consistent between pre- and post-afatinib tissues. Twenty patients (47.6%) had acquired T790M mutation. T790M rate was not different between first-generation EGFR TKI-naïve patients (50%) and first-generation EGFR TKI-treated patients (46.4%) (p = 0.827). No clinical characteristics or EGFR mutation types were associated with the development of acquired T790M. No other second-site EGFR mutations were detected. There were no small cell or squamous cell lung cancer transformation. Other genetic mutations were not identified in PIK3CA, BRAF, HER2, KRAS, NRAS, MEK1, AKT2, LKB1 and JAK2.MethodsAfatinib-prescription record of our department of pharmacy from January 2007 and December 2014 was retrieved. We investigated patients with tissue specimens available after acquiring resistance to afatinib. Enrolled patients should have partial response or durable stable disease of treatment response to afatinib. Various mechanisms of acquired resistance to first-generation EGFR TKIs were evaluated. Histology and cytology were reviewed. EGFR, PIK3CA, BRAF, HER2, KRAS, NRAS, MEK1, AKT2, LKB1 and JAK2 genetic alterations were evaluated by sequencing. Statistical analysis was performed using Chi-square test and Kaplan-Meier method.ConclusionsT790M was detected in half of the lung adenocarcinoma after acquiring resistance to afatinib. T790M is still the major acquired resistance mechanism. First-generation EGFR TKI exposure did not influence the prevalence of T790M in lung cancer acquired resistance to afatinib.

The experimental manifestation of topological effects in bulk materials under ambient conditions, especially those with practical applications, has attracted enormous research interest. Recent discovery of Weyl semimetal provides an ideal material platform for such endeavors. The Berry curvature in a Weyl semimetal becomes singular at the Weyl node, creating an effective magnetic monopole in the k-space. A pair of Weyl nodes carry quantized effective magnetic charges with opposite signs, and therefore, opposite chirality. Although Weyl-point-related signatures such as chiral anomaly and non-closing surface Fermi arcs have been detected through transport and ARPES measurements, direct experimental evidence of the effective k-space monopole of the Weyl nodes has so far been lacking. In this work, signatures of the singular topology in a type-II Weyl semimetal TaIrTe4 is revealed in the photo responses, which are shown to be directly related to the divergence of Berry curvature. As a result of the divergence of Berry curvature at the Weyl nodes, TaIrTe4 exhibits unusually large photo responsivity of 130.2 mA/W with 4-m excitation in an unbiased field effect transistor at room temperature arising from the third-order nonlinear optical response.The room temperature mid-IR responsivity is approaching the performance of commercial HgCdTe detector operating at low temperature, making Type-II Weyl semimetal TaIrTe4 of practical importance in terms of photo sensing and solar energy harvesting. Furthermore, the circularly polarized galvanic response is also enhanced at 4-m, possibly due to the same Berry curvature singularity enhancement as the shift current. Considering the optical selection rule of Weyl cones with opposite chirality, it may open new experimental possibilities for studying and controlling the chiral polarization of Weyl Fermions through an in-plane DC electric field in addition to the optical helicities.

Photodetectors based on Weyl semimetal promise extreme performance in terms of highly sensitive, broadband and self-powered operation owing to its extraordinary material properties. Layered Type-II Weyl semimetal that break Lorentz invariance can be further integrated with other two-dimensional materials to form van der Waals heterostructures and realize multiple functionalities inheriting the advantages of other two-dimensional materials. Herein, we report the realization of a broadband self-powered photodetector based on Type-II Weyl semimetal T -MoTe . The prototype metal-MoTe -metal photodetector exhibits a responsivity of 0.40 mA W and specific directivity of 1.07 × 10 Jones with 43 μs response time at 532 nm. Broadband responses from 532 nm to 10.6 μm are experimentally tested with a potential detection range extendable to far-infrared and terahertz. Furthermore, we identify the response of the detector is polarization angle sensitive due to the anisotropic response of MoTe . The anisotropy is found to be wavelength dependent, and the degree of anisotropy increases as the excitation wavelength gets closer to the Weyl nodes. In addition, with power and temperature dependent photoresponse measurements, the photocurrent generation mechanisms are investigated. Our results suggest this emerging class of materials can be harnessed for broadband angle sensitive, self-powered photodetection with decent responsivities.

The layered ternary compound TaIrTe is an important candidate to host the recently predicted type-II Weyl Fermions that break Lorentz invariance. Photodetectors based on Weyl semimetal promise extreme performance in terms of highly sensitive, broadband, and self-powered operation owing to its topologically protected band structures. In this work, we report the realization of a broadband self-powered photodetector based on TaIrTe. The photocurrent generation mechanisms are investigated with power- and temperature-dependent photoresponse measurements. The prototype metal-TaIrTe-metal photodetector exhibits a responsivity of 20 μA W or a specific detectivity of 1.8 × 10 Jones with 27 μs response time at 10.6 μm. Broadband responses from 532 nm to 10.6 μm are experimentally tested with potential detection range extendable to far-infrared and terahertz. Furthermore, anisotropic response of the TaIrTe photodetector is identified using polarization-angle-dependent measurement with linearly polarized light. The anisotropy is found to be wavelength dependent, and the degree of anisotropy increases as the excitation wavelength gets closer to the Weyl nodes. Our results suggest this emerging class of materials can be harnessed for broadband, polarization angle-sensitive, self-powered photodetection with reasonable responsivities.

Observational studies suggest an association between dietary fiber intake and risk of type 2 diabetes, but the results are inconclusive. We conducted a meta-analysis of prospective studies evaluating the associations of dietary fiber intake and risk of type 2 diabetes. Relevant studies were identified by searching EMBASE (from 1974 to April 2013) and PubMed (from 1966 to April 2013). The fixed or random-effect model was selected based on the homogeneity test among studies. In addition, a 2-stage random-effects dose-response meta-analysis was performed. We identified 17 prospective cohort studies of dietary fiber intake and risk of type 2 diabetes involving 19,033 cases and 488,293 participants. The combined RR (95 % CI) of type 2 diabetes for intake of total dietary fiber, cereal fiber, fruit fiber and insoluble fiber was 0.81 (0.73-0.90), 0.77 (0.69-0.85), 0.94 (0.88-0.99) and 0.75 (0.63-0.89), respectively. A nonlinear relationship was found of total dietary fiber intake with risk of type 2 diabetes (P for nonlinearity < 0.01), and the RRs (95 % CI) of type 2 diabetes were 0.98 (0.90-1.06), 0.97 (0.87-1.07), 0.89 (0.80-0.99), 0.76 (0.65-0.88), and 0.66 (0.53-0.82) for 15, 20, 25, 30, and 35 g/day. The departure from nonlinear relationship was not significant (P for nonlinearity = 0.72), and the risk of type 2 diabetes decreased by 6 % (RR 0.94, 95 % CI 0.93-0.96) for 2 g/day increment in cereal fiber intake. Findings from this meta-analysis indicate that the intakes of dietary fiber may be inversely associated with risk of type 2 diabetes.

Emerging two-dimensional (2D) semiconducting materials serve as promising alternatives for next-generation digital electronics and optoelectronics. However, large-scale 2D semiconductor films synthesized so far are typically polycrystalline with defective grain boundaries that could degrade their performance. Here, for the first time, wafer-size growth of a single-crystal Bi 2 O 2 Se film, which is a novel air-stable 2D semiconductor with high mobility, was achieved on insulating perovskite oxide substrates [SrTiO 3 , LaAlO 3 , (La, Sr)(Al, Ta)O 3 ]. The layered Bi 2 O 2 Se epilayer exhibits perfect lattice matching and strong interaction with perovskite oxide substrates, which enable unidirectional alignment and seamless mergence of multiple seeds into single-crystal continuous films free of detrimental grain boundaries. The single-crystal Bi 2 O 2 Se thin films show excellent spatial homogeneity over the entire wafer and allow for the batch fabrication of high-performance field-effect devices with high mobilities of ∼150 cm 2 V −1 s −1 at room temperature, excellent switching behavior with large on/off ratio of >10 5 , and high drive current of ∼45 μA μm −1 at a channel length of ∼5 μm. Our work makes a step toward the practical applications of high-mobility semiconducting 2D layered materials and provides an alternative platform of oxide heterostructure to investigate novel physical phenomena.