ICONGETM v1.0 – flexible NUOPC-driven two-way coupling via ESMF exchange grids between the unstructured-grid atmosphere model ICON and the structured-grid coastal ocean model GETM

Two-way model coupling is important for representing the mutual interactions and feedbacks between atmosphere and ocean dynamics. This work presents the development of the two-way coupled model system ICONGETM, consisting of the atmosphere model ICON and the ocean model GETM. ICONGETM is built on the latest NUOPC coupling software with flexible data exchange and conservative interpolation via ESMF exchange grids. With ICON providing a state-of-the-art kernel for numerical weather prediction on an unstructured mesh and GETM being an established coastal ocean model, ICONGETM is especially suited for high-resolution studies. For demonstration purposes the newly developed model system has been applied to a coastal upwelling scenario in the central Baltic Sea

Interactive impacts of meteorological and hydrological conditions on the physical and biogeochemical structure of a coastal system

The German Bight was exposed to record high riverine discharges in June 2013, as a result of flooding of the Elbe and Weser rivers. Several anomalous observations suggested that the hydrodynamical and biogeochemical states of the system were impacted by this event. In this study, we developed a biogeochemical model and coupled it with a previously introduced high-resolution hydrodynamical model of the southern North Sea in order to better characterize these impacts and gain insight into the underlying processes. Performance of the model was assessed using an extensive set of in situ measurements for the period 2011–2014. We first improved the realism of the hydrodynamic model with regard to the representation of cross-shore gradients, mainly through inclusion of flow-dependent horizontal mixing. Among other characteristic features of the system, the coupled model system can reproduce the low salinities, high nutrient concentrations and low oxygen concentrations in the bottom layers observed within the German Bight following the flood event. Through a scenario analysis, we examined the sensitivity of the patterns observed during July 2013 to the hydrological and meteorological forcing in isolation. Within the region of freshwater influence (ROFI) of the Elbe–Weser rivers, the flood event clearly dominated the changes in salinity and nutrient concentrations, as expected. However, our findings point to the relevance of the peculiarities in the meteorological conditions in 2013 as well: a combination of low wind speeds, warm air temperatures and cold bottom-water temperatures resulted in a strong thermal stratification in the outer regions and limited vertical nutrient transport to the surface layers. Within the central region, the thermal and haline dynamics interactively resulted in an intense density stratification. This intense stratification, in turn, led to enhanced primary production within the central region enriched by nutrients due to the flood but led to reduction within the nutrient-limited outer region, and it caused a widespread oxygen depletion in bottom waters. Our results further point to the enhancement of the current velocities at the surface as a result of haline stratification and to intensification of the thermohaline estuarine-like circulation in the Wadden Sea, both driven by the flood event

The human Origin Recognition Complex is essential for pre-RC assembly, mitosis and maintenance of nuclear structure

The Origin Recognition Complex (ORC) cooperates with CDC6, MCM2-7, and CDT1 to form pre- RC complexes at origins of DNA replication. Here we report tiling-sgRNA CRISPR screens that show that each subunit of ORC and CDC6 are essential in human cells. Using an auxin-inducible degradation system, stable cell lines were created that ablate ORC2 rapidly, revealing multiple cell division cycle phenotypes. The primary defect in the absence of ORC2 was cells encountering difficulty in initiating DNA replication or progressing through the cell division cycle due to reduced MCM2-7 loading onto chromatin in G1 phase. The nuclei of ORC2 deficient cells were also large, with decompacted heterochromatin. Some ORC2 deficient cells that completed DNA replication entered into, but never exited mitosis. ORC1 knockout cells also demonstrated extremely slow cell proliferation and abnormal cell and nuclear morphology. Thus, ORC proteins and CDC6 are indispensable for normal cellular proliferation and contribute to nuclear organization

Single-dot Spectroscopy of GaAs Quantum Dots Fabricated by Filling of Self-assembled Nanoholes

We study the optical emission of single GaAs quantum dots (QDs). The QDs are fabricated by filling of nanoholes in AlGaAs and AlAs which are generated in a self-assembled fashion by local droplet etching with Al droplets. Using suitable process parameters, we create either uniform QDs in partially filled deep holes or QDs with very broad size distribution in completely filled shallow holes. Micro photoluminescence measurements of single QDs of both types establish sharp excitonic peaks. We measure a fine-structure splitting in the range of 22–40μeV and no dependence on QD size. Furthermore, we find a decrease in exciton–biexciton splitting with increasing QD size

Correlation of pulse wave velocity with left ventricular mass in patients with hypertension once blood pressure has been normalized

Vascular stiffness has been proposed as a simple method to assess arterial loading conditions of the heart which induce left ventricular hypertrophy (LVH). There is some controversy as to whether the relationship of vascular stiffness to LVH is independent of blood pressure, and which measurement of arterial stiffness, augmentation index (AI) or pulse wave velocity (PWV) is best. Carotid pulse wave contor and pulse wave velocity of patients (n=20) with hypertension whose blood pressure (BP) was under control (<140/90 mmHg) with antihypertensive drug treatment medications, and without valvular heart disease, were measured. Left ventricular mass, calculated from 2D echocardiogram, was adjusted for body size using two different methods: body surface area and height. There was a significant (P<0.05) linear correlation between LV mass index and pulse wave velocity. This was not explained by BP level or lower LV mass in women, as there was no significant difference in PWV according to gender (1140.1+67.8 vs 1110.6+57.7 cm/s). In contrast to PWV, there was no significant correlation between LV mass and AI. In summary, these data suggest that aortic vascular stiffness is an indicator of LV mass even when blood pressure is controlled to less than 140/90 mmHg in hypertensive patients. The data further suggest that PWV is a better proxy or surrogate marker for LV mass than AI and the measurement of PWV may be useful as a rapid and less expensive assessment of the presence of LVH in this patient population

Particulate matter from both heavy fuel oil and diesel fuel shipping emissions show strong biological effects on human lung cells at realistic and comparable in vitro exposure conditions

Background: Ship engine emissions are important with regard to lung and cardiovascular diseases especially in coastal regions worldwide. Known cellular responses to combustion particles include oxidative stress and inflammatory signalling. Objectives: To provide a molecular link between the chemical and physical characteristics of ship emission particles and the cellular responses they elicit and to identify potentially harmful fractions in shipping emission aerosols. Methods: Through an air-liquid interface exposure system, we exposed human lung cells under realistic in vitro conditions to exhaust fumes from a ship engine running on either common heavy fuel oil (HFO) or cleaner-burning diesel fuel (DF). Advanced chemical analyses of the exhaust aerosols were combined with transcriptional, proteomic and metabolomic profiling including isotope labelling methods to characterise the lung cell responses. Results: The HFO emissions contained high concentrations of toxic compounds such as metals and polycyclic aromatic hydrocarbon, and were higher in particle mass. These compounds were lower in DF emissions, which in turn had higher concentrations of elemental carbon (“soot”). Common cellular reactions included cellular stress responses and endocytosis. Reactions to HFO emissions were dominated by oxidative stress and inflammatory responses, whereas DF emissions induced generally a broader biological response than HFO emissions and affected essential cellular pathways such as energy metabolism, protein synthesis, and chromatin modification. Conclusions: Despite a lower content of known toxic compounds, combustion particles from the clean shipping fuel DF influenced several essential pathways of lung cell metabolism more strongly than particles from the unrefined fuel HFO. This might be attributable to a higher soot content in DF. Thus the role of diesel soot, which is a known carcinogen in acute air pollution-induced health effects should be further investigated. For the use of HFO and DF we recommend a reduction of carbonaceous soot in the ship emissions by implementation of filtration devices

Identification of a Bacterial-Like HslVU Protease in the Mitochondria of Trypanosoma brucei and Its Role in Mitochondrial DNA Replication

ATP-dependent protease complexes are present in all living organisms, including the 26S proteasome in eukaryotes, Archaea, and Actinomycetales, and the HslVU protease in eubacteria. The structure of HslVU protease resembles that of the 26S proteasome, and the simultaneous presence of both proteases in one organism was deemed unlikely. However, HslVU homologs have been identified recently in some primordial eukaryotes, though their potential function remains elusive. We characterized the HslVU homolog from Trypanosoma brucei, a eukaryotic protozoan parasite and the causative agent of human sleeping sickness. TbHslVU has ATP-dependent peptidase activity and, like its bacterial counterpart, has essential lysine and N-terminal threonines in the catalytic subunit. By epitope tagging, TbHslVU localizes to mitochondria and is associated with the mitochondrial genome, kinetoplast DNA (kDNA). RNAi of TbHslVU dramatically affects the kDNA by causing over-replication of the minicircle DNA. This leads to defects in kDNA segregation and, subsequently, to continuous network growth to an enormous size. Multiple discrete foci of nicked/gapped minicircles are formed on the periphery of kDNA disc, suggesting a failure in repairing the gaps in the minicircles for kDNA segregation. TbHslVU is a eubacterial protease identified in the mitochondria of a eukaryote. It has a novel function in regulating mitochondrial DNA replication that has never been observed in other organisms

Anti-Tumor Effect against Human Cancer Xenografts by a Fully Human Monoclonal Antibody to a Variant 8-Epitope of CD44R1 Expressed on Cancer Stem Cells

BACKGROUND: CD44 is a major cellular receptor for hyaluronic acids. The stem structure of CD44 encoded by ten normal exons can be enlarged by ten variant exons (v1-v10) by alternative splicing. We have succeeded in preparing MV5 fully human IgM and its class-switched GV5 IgG monoclonal antibody (mAb) recognizing the extracellular domain of a CD44R1 isoform that contains the inserted region coded by variant (v8, v9 and v10) exons and is expressed on the surface of various human epithelial cancer cells. METHODS AND PRINCIPAL FINDINGS: We demonstrated the growth inhibition of human cancer xenografts by a GV5 IgG mAb reshaped from an MV5 IgM. The epitope recognized by MV5 and GV5 was identified to a v8-coding region by the analysis of mAb binding to various recombinant CD44 proteins by enzyme-linked immunosorbent assay. GV5 showed preferential reactivity against various malignant human cells versus normal human cells assessed by flow cytometry and immunohistological analysis. When ME180 human uterine cervix carcinoma cells were subcutaneously inoculated to athymic mice with GV5, significant inhibition of tumor formation was observed. Furthermore, intraperitoneal injections of GV5markedly inhibited the growth of visible established tumors from HSC-3 human larynx carcinoma cells that had been subcutaneously transplanted one week before the first treatment with GV5. From in vitro experiments, antibody-dependent cellular cytotoxicity and internalization of CD44R1 seemed to be possible mechanisms for in vivo anti-tumor activity by GV5. CONCLUSIONS: CD44R1 is an excellent molecular target for mAb therapy of cancer, possibly superior to molecules targeted by existing therapeutic mAb, such as Trastuzumab and Cetuximab recognizing human epidermal growth factor receptor family