Description: The pre-industrial millennium is among the periods selected by the Paleoclimate Model Intercomparison Project (PMIP) for experiments contributing to the sixth phase of the Coupled Model Intercomparison Project (CMIP6) and the fourth phase of the PMIP (PMIP4). The past1000 transient simulations serve to investigate the response to (mainly) natural forcing under background conditions not too different from today, and to discriminate between forced and internally generated variability on interannual to centennial timescales. This paper describes the motivation and the experimental set-ups for the PMIP4-CMIP6 past1000 simulations, and discusses the forcing agents orbital, solar, volcanic, and land use/land cover changes, and variations in greenhouse gas concentrations. The past1000 simulations covering the pre-industrial millennium from 850 Common Era (CE) to 1849 CE have to be complemented by historical simulations (1850 to 2014 CE) following the CMIP6 protocol. The external forcings for the past1000 experiments have been adapted to provide a seamless transition across these time periods. Protocols for the past1000 simulations have been divided into three tiers. A default forcing data set has been defined for the Tier 1 (the CMIP6 past1000) experiment. However, the PMIP community has maintained the flexibility to conduct coordinated sensitivity experiments to explore uncertainty in forcing reconstructions as well as parameter uncertainty in dedicated Tier 2 simulations. Additional experiments (Tier 3) are defined to foster collaborative model experiments focusing on the early instrumental period and to extend the temporal range and the scope of the simulations. This paper outlines current and future research foci and common analyses for collaborative work between the PMIP and the observational communities (reconstructions, instrumental data).

Description: The Last Glacial Maximum (LGM, 21 000 years ago) is one of the suite of paleoclimate simulations included in the current phase of the Coupled Model Intercomparison Project (CMIP6). It is an interval when insolation was similar to the present, but global ice volume was at a maximum, eustatic sea level was at or close to a minimum, greenhouse gas concentrations were lower, atmospheric aerosol loadings were higher than today, and vegetation and land-surface characteristics were different from today. The LGM has been a focus for the Paleoclimate Modelling Intercomparison Project (PMIP) since its inception, and thus many of the problems that might be associated with simulating such a radically different climate are well documented. The LGM state provides an ideal case study for evaluating climate model performance because the changes in forcing and temperature between the LGM and pre-industrial are of the same order of magnitude as those projected for the end of the 21st century. Thus, the CMIP6 LGM experiment could provide additional information that can be used to constrain estimates of climate sensitivity. The design of the Tier 1 LGM experiment (lgm) includes an assessment of uncertainties in boundary conditions, in particular through the use of different reconstructions of the ice sheets and of the change in dust forcing. Additional (Tier 2) sensitivity experiments have been designed to quantify feedbacks associated with land-surface changes and aerosol loadings, and to isolate the role of individual forcings. Model analysis and evaluation will capitalize on the relative abundance of paleoenvironmental observations and quantitative climate reconstructions already available for the LGM.

Description: Numerical modeling enables a comprehensive understanding not only of the Earth's system today, but also of the past. To date, a significant amount of time and effort has been devoted to paleoclimate modeling and analysis, which involves the latest and most advanced Paleoclimate Modelling Intercomparison Project phase 4 (PMIP4). The definition of seasonality, which is influenced by slow variations in the Earth's orbital parameters, plays a key role in determining the calculated seasonal cycle of the climate. In contrast to the classical calendar used today, where the lengths of the months and seasons are fixed, the angular calendar calculates the lengths of the months and seasons according to a fixed number of degrees along the Earth's orbit. When comparing simulation results for different time intervals, it is essential to account for the angular calendar to ensure that the data for comparison are from the same position along the Earth's orbit. Most models use the classical calendar, which can lead to strong distortions of the monthly and seasonal values, especially for the climate of the past. Here, by analyzing daily outputs from multiple PMIP4 model simulations, we examine calendar effects on surface air temperature and precipitation under mid-Holocene, Last Interglacial, and pre-industrial climate conditions. We came to the following conclusions. (a) The largest cooling bias occurs in boreal autumn when the classical calendar is applied for the mid-Holocene and Last Interglacial, due to the fact that the vernal equinox is fixed on 21 March. (b) The sign of the temperature anomalies between the Last Interglacial and pre-industrial in boreal autumn can be reversed after the switch from the classical to angular calendar, particularly over the Northern Hemisphere continents. (c) Precipitation over West Africa is overestimated in boreal summer and underestimated in boreal autumn when the classical seasonal cycle is applied. (d) Finally, month-length adjusted values for surface air temperature and precipitation are very similar to the day-length adjusted values, and therefore correcting the calendar based on the monthly model results can largely reduce the artificial bias. In addition, we examine the calendar effects in three transient simulations for 6–0 ka by AWI-ESM, MPI-ESM, and IPSL-CM. We find significant discrepancies between adjusted and unadjusted temperature values over continents for both hemispheres in boreal autumn, while for other seasons the deviations are relatively small. A drying bias can be found in the summer monsoon precipitation in Africa (in the classical calendar), whereby the magnitude of bias becomes smaller over time. Overall, our study underlines the importance of the application of calendar transformation in the analysis of climate simulations. Neglecting the calendar effects could lead to a profound artificial distortion of the calculated seasonal cycle of surface air temperature and precipitation.

Description: Journal of the American Chemical Society DOI: 10.1021/jacs.8b08792

Description: Background: There is a strong need for early assessment of tumor response to chemotherapy in order to avoid the adverse effects of unnecessary chemotherapy and to allow early transition to second-line therapy. The purpose of this study was to determine the feasibility of ultrasonic spectral analysis for the in vivo characterization of changes in tumor microstructure in the evaluation of tumor response to chemotherapy using diagnostic ultrasound. Methods: Experiments were approved by the regional animal care committee. Twenty-four MCF-7 breast cancer bearing nude mice were treated with adriamycin or sterile saline administered by intraperitoneal injection. Ultrasonic radio-frequency (RF) data was collected using a clinically available ultrasound scanner (6-MHz linear transducer). Linear regression parameters (spectral slope and midband-fit) regarding the calibrated power spectra from the RF signals were tested to monitor tumor response to treatment. The section equivalent to the ultrasound imaging plane was stained with hematoxylin and eosin to allow for assessment of the density of tumor cell nuclei. Results: Treatment with adriamycin significantly reduced tumor growth in comparison with the control group (p = 0.003). Significant changes were observed in the ultrasonic parameters of the treated relative to the untreated tumors (p 〈 0.05). The spectral slope increased by 48.5%, from -10.66 +/- 2.96 to -5.49 +/- 2.69; the midband-fit increased by 12.8%, from -57.10 +/- 7.68 to -49.81 +/- 5.40. Treated tumors were associated with a significant decrease in the density of tumor cell nuclei as compared with control tumors (p 〈 0.001). Conclusions: Ultrasonic spectral analysis can detect changes in tumor microstructure after chemotherapy, and this will be helpful in the early evaluation tumor response to chemotherapy.

Description: Analytical Chemistry DOI: 10.1021/ac401496x

Description: Hantavirus is a tripartite negative-sense RNA virus. It can infect humans through contaminated rodent excreta and causes two types of fatal human diseases: hemorrhagic fever with renal syndrome (HFRS) and hant...

Description: Background: The 90-kDa heat shock protein HSP90AA1 is critical for the stability of several proteins that are important for tumor progression and thus, is a promising target for cancer therapy. Selenosemicarbazone metal complexes have been shown to possess anticancer activity through an unknown molecular mechanism. Methods: The MTT assay, fluorescence-activated cell sorting, and fluorescent microscopy were used to analyze the mechanism of the anti-cancer activity of the selenosemicarbazone metal complexes. Additionally, RNA-seq was applied to identify transcriptional gene changes, and in turn, the signaling pathways involved in the process of 2-24a/Cu-induced cell death. Last, the expression of HSP90AA1, HSPA1A, PIM1, and AKT proteins in 2-24a/Cu-treated cells were investigated by western blot analysis. Results: A novel selenosemicarbazone copper complex (2-24a/Cu) efficiently induced G2/M arrest and was cytotoxic in cancer cells. 2-24a/Cu significantly induced oxidative stress in cancer cells. Interestingly, although RNA-seq revealed that the transcription of HSP90AA1 was increased in 2-24a/Cu-treated cells, western blotting showed that the expression of HSP90AA1 protein was significantly decreased in these cells. Furthermore, down-regulation of HSP90AA1 led to the degradation of its client proteins (PIM1 and AKT1), which are also cancer therapy targets. Conclusion: Our results showed that 2-24a/Cu efficiently generates oxidative stress and down-regulates HSP90AA1 and its client proteins (PIM1, AKT1) in U2os and HeLa cells. These results demonstrate the potential application of this novel copper complex in cancer therapy.

Description: Background: Extrarenal nephroblastomatosis is a rare entity which occurs in retroperitoneum and inguinal region predominantly. Here we report two cases of primary extrarenal nephroblastomatosis of Han Chinese in Asian in unusual locations, one is located in testis and paratestis, and the other is paraspinal cord.Case presentationPatient 1 was a 19-month-old boy with a hard and nodular mass adherent to the left testis in inguinal region. Patient 2 was a 9-month-old boy with a 1 x 0.7 x 0.4 cm mass in spinal canal at the midline thoracolumbar region. Histological examinations of the two patients after operations revealed extrarenall nephroblastomatosis with multiple nephrogenic foci, composed of immature glomeruli, tubules and blastemal cells.Then the patients were closely monitored without adjuvant chemotherapy, and has been alive and well without any recurrence for 〉6 months. Conclusions: Most nephrogenic rests remain subclinical, and thus, complete excision of the lesion with conservative treatment is recommended. Otherwise, nephrogenic rests are close associated with Wilms tumor and regular follow-up is required to ensure early detection of malignant transformation.