An important concern in the application of gamma-ray bursts (GRBs) to cosmology is that the calibration of GRB luminosity/energy relations depends on the cosmological model, due to the lack of a sufficient low-redshift GRB sample. In this paper, we present a new method to calibrate GRB relations in a cosmology-independent way. Since objects at the same redshift should have the same luminosity distance, and since the distance moduli of Type Ia supernovae (SNe Ia) obtained directly from observations are completely cosmology independent, we obtain the distance modulus of a GRB at a given redshift by interpolating from the Hubble diagram of SNe Ia. Then we calibrate seven GRB relations without assuming a particular cosmological model and construct a GRB Hubble diagram to constrain cosmological parameters. From the 42 GRBs at 1:4 < z 6:6, we obtain M ¼ 0:25 þ0:04 À0:05 , Ã ¼ 0:75 þ0:05 À0:04for the flat ÃCDM model, and for the dark energy model with a constant equation of state w 0 ¼ À1:05 þ0:27 À0:40 , which is consistent with the concordance model in a 1 confidence region.

The Stroop test was performed before and after ergometer exercise for 15 min at 20, 40, and 60 % of maximum voluntary exercise (EXmax), in order to examine whether dynamic exercise is capable of improving cognitive function and whether the changes in regional cerebral blood flow of the prefrontal cortex are associated with the cognitive improvement. Subjects were asked to answer the displayed color of incongruent color words as quickly as possible. The total time period and the number of errors for the Stroop test were measured as an index of cognitive function. The concentrations of oxygenated-hemoglobin (Oxy-Hb) and deoxygenated-hemoglobin (Deoxy-Hb) in the cerebral prefrontal area were measured with near-infrared spectroscopy to determine the changes in regional cerebral blood flow. Ergometer exercise at 40 % of EXmax, but not 20 and 60 % of EXmax, shortened (P < 0.05) the total time period for the Stroop test by 6.6 ± 1.5 % as compared to the time control. In contrast, the number of errors was not altered by exercise at any intensity. The Oxy-Hb in bilateral prefrontal cortices increased during the Stroop test, while the Deoxy-Hb in those areas was unchanged. Ergometer exercise at 40 % of EXmax, but not at 20 and 60 % of EXmax, significantly augmented the response in the prefrontal Oxy-Hb during the Stroop test. The magnitude of the increased prefrontal Oxy-Hb response tended to correlate with the reduction in total time period for the Stroop test. Thus, it is likely that ergometer exercise at moderate intensity for 15 min may improve cognitive function through the increased neural activity in the prefrontal cortex.

Whether neurogenic vasodilatation contributes to exercise hyperemia is still controversial. Blood flow to noncontracting muscle, however, is chiefly regulated by a neural mechanism. Although vasodilatation in the nonexercising limb was shown at the onset of exercise, it was unclear whether central command or muscle mechanoreflex is responsible for the vasodilatation. To clarify this, using voluntary one-legged cycling with the right leg in humans, we measured the relative changes in concentrations of oxygenated-hemoglobin (Oxy-Hb) of the noncontracting vastus lateralis (VL) muscle with near-infrared spectroscopy as an index of tissue blood flow and femoral blood flow to the nonexercising leg. Oxy-Hb in the noncontracting VL and femoral blood flow increased (P < 0.05) at the start period of voluntary one-legged cycling without accompanying a rise in arterial blood pressure. In contrast, no increases in Oxy-Hb and femoral blood flow were detected at the start period of passive one-legged cycling, suggesting that muscle mechanoreflex cannot explain the initial vasodilatation of the noncontracting muscle during voluntary one-legged cycling. Motor imagery of the voluntary one-legged cycling increased Oxy-Hb of not only the right but also the left VL. Furthermore, an increase in Oxy-Hb of the contracting VL, which was observed at the start period of voluntary one-legged cycling, had the same time course and magnitude as the increase in Oxy-Hb of the noncontracting muscle. Thus it is concluded that the centrally induced vasodilator signal is equally transmitted to the bilateral VL muscles, not only during imagery of exercise but also at the start period of voluntary exercise in humans.

Long noncoding RNAs (lncRNAs) are emerging as key regulators of multiple essential biological processes involved in physiology and pathology. By analyzing the largest compendium of 14,166 samples from normal and tumor tissues, we significantly expand the landscape of human long noncoding RNA with a high-quality atlas: RefLnc (Reference catalog of LncRNA). Powered by comprehensive annotation across multiple sources, RefLnc helps to pinpoint 275 novel intergenic lncRNAs correlated with sex, age or race as well as 369 novel ones associated with patient survival, clinical stage, tumor metastasis or recurrence. Integrated in a user-friendly online portal, the expanded catalog of human lncRNAs provides a valuable resource for investigating lncRNA function in both human biology and cancer development.

The tyrosine phosphorylation barcode encoded in C-terminus of HER2 and its ubiquitination regulate diverse HER2 functions. PTPN18 was reported as a HER2 phosphatase; however, the exact mechanism by which it defines HER2 signaling is not fully understood. Here, we demonstrate that PTPN18 regulates HER2-mediated cellular functions through defining both its phosphorylation and ubiquitination barcodes. Enzymologic characterization and three crystal structures of PTPN18 in complex with HER2 phospho-peptides revealed the molecular basis for the recognition between PTPN18 and specific HER2 phosphorylation sites, which assumes two distinct conformations. Unique structural properties of PTPN18 contribute to the regulation of sub-cellular phosphorylation networks downstream of HER2, which are required for inhibition of HER2-mediated cell growth and migration. Whereas the catalytic domain of PTPN18 blocks lysosomal routing and delays the degradation of HER2 by dephosphorylation of HER2 on pY1112, the PEST domain of PTPN18 promotes K48-linked HER2 ubiquitination and its rapid destruction via the proteasome pathway and an HER2 negative feedback loop. In agreement with the negative regulatory role of PTPN18 in HER2 signaling, the HER2/PTPN18 ratio was correlated with breast cancer stage. Taken together, our study presents a structural basis for selective HER2 dephosphorylation, a previously uncharacterized mechanism for HER2 degradation and a novel function for the PTPN18 PEST domain. The new regulatory role of the PEST domain in the ubiquitination pathway will broaden our understanding of the functions of other important PEST domain-containing phosphatases, such as LYP and PTPN12.