Theory of Chiral Order in Random Copolymers

Recent experiments have found that polyisocyanates composed of a mixture of opposite enantiomers follow a chiral ``majority rule:'' the chiral order of the copolymer, measured by optical activity, is dominated by whichever enantiomer is in the majority. We explain this majority rule theoretically by mapping the random copolymer onto the random-field Ising model. Using this model, we predict the chiral order as a function of enantiomer concentration, in quantitative agreement with the experiments, and show how the sharpness of the majority-rule curve can be controlled.Comment: 13 pages, including 4 postscript figures, uses REVTeX 3.0 and epsf.st

Theory of Cylindrical Tubules and Helical Ribbons of Chiral Lipid Membranes

We present a general theory for the equilibrium structure of cylindrical tubules and helical ribbons of chiral lipid membranes. This theory is based on a continuum elastic free energy that permits variations in the direction of molecular tilt and in the curvature of the membrane. The theory shows that the formation of tubules and helical ribbons is driven by the chirality of the membrane. Tubules have a first-order transition from a uniform state to a helically modulated state, with periodic stripes in the tilt direction and ripples in the curvature. Helical ribbons can be stable structures, or they can be unstable intermediate states in the formation of tubules.Comment: 43 pages, including 12 postscript figures, uses REVTeX 3.0 and epsf.st

Order and Frustration in Chiral Liquid Crystals

This paper reviews the complex ordered structures induced by chirality in liquid crystals. In general, chirality favors a twist in the orientation of liquid-crystal molecules. In some cases, as in the cholesteric phase, this favored twist can be achieved without any defects. More often, the favored twist competes with applied electric or magnetic fields or with geometric constraints, leading to frustration. In response to this frustration, the system develops ordered structures with periodic arrays of defects. The simplest example of such a structure is the lattice of domains and domain walls in a cholesteric phase under a magnetic field. More complex examples include defect structures formed in two-dimensional films of chiral liquid crystals. The same considerations of chirality and defects apply to three-dimensional structures, such as the twist-grain-boundary and moire phases.Comment: 39 pages, RevTeX, 14 included eps figure

Phase II trial of N-methylformamide in advanced head and neck cancer

Eighteen patients with advanced epidermoid carcinoma of the head and neck were entered into a phase II trial of N-Methylformamide (NMF), 800 mg/M 2 IV daily for 5 days every 4 weeks. Seventeen patients had received prior radiation therapy and 11 were previously treated with chemotherapy. No complete or partial responses were observed. The major toxicity was gastrointestinal. Fifty percent of patients experienced nausea and vomiting or reversible hepatotoxicity with greater than a 3-fold elevation of liver enzymes. Mild reversible myelosuppression occurred in 2 patients. NMF in this dose and schedule was not a useful agent to treat recurrent epidermoid carcinoma of the head and neck.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45297/1/10637_2004_Article_BF00203547.pd

The ICON-A model for direct QBO simulations on GPUs (version icon-cscs:baf28a514)

Classical numerical models for the global atmosphere, as used for numerical weather forecasting or climate research, have been developed for conventional central processing unit (CPU) architectures. This hinders the employment of such models on current top-performing supercomputers, which achieve their computing power with hybrid architectures, mostly using graphics processing units (GPUs). Thus also scientific applications of such models are restricted to the lesser computer power of CPUs. Here we present the development of a GPU-enabled version of the ICON atmosphere model (ICON-A), motivated by a research project on the quasi-biennial oscillation (QBO), a global-scale wind oscillation in the equatorial stratosphere that depends on a broad spectrum of atmospheric waves, which originates from tropical deep convection. Resolving the relevant scales, from a few kilometers to the size of the globe, is a formidable computational problem, which can only be realized now on top-performing supercomputers. This motivated porting ICON-A, in the specific configuration needed for the research project, in a first step to the GPU architecture of the Piz Daint computer at the Swiss National Supercomputing Centre and in a second step to the JUWELS Booster computer at the Forschungszentrum Jülich. On Piz Daint, the ported code achieves a single-node GPU vs. CPU speedup factor of 6.4 and allows for global experiments at a horizontal resolution of 5 km on 1024 computing nodes with 1 GPU per node with a turnover of 48 simulated days per day. On JUWELS Booster, the more modern hardware in combination with an upgraded code base allows for simulations at the same resolution on 128 computing nodes with 4 GPUs per node and a turnover of 133 simulated days per day. Additionally, the code still remains functional on CPUs, as is demonstrated by additional experiments on the Levante compute system at the German Climate Computing Center. While the application shows good weak scaling over the tested 16-fold increase in grid size and node count, making also higher resolved global simulations possible, the strong scaling on GPUs is relatively poor, which limits the options to increase turnover with more nodes. Initial experiments demonstrate that the ICON-A model can simulate downward-propagating QBO jets, which are driven by wave–mean flow interaction

Brain structural changes and neuropsychological impairments in male polydipsic schizophrenia

BACKGROUND: Polydipsia frequently occurs in schizophrenia patients. The excessive water loading in polydipsia occasionally induces a hyponatremic state and leads to water intoxication. Whether polydipsia in schizophrenic patients correlates with neuropsychological impairments or structural brain changes is not clear and remains controversial. METHODS: Eight polydipsic schizophrenia patients, eight nonpolydipsic schizophrenia patients, and eight healthy controls were recruited. All subjects underwent magnetic resonance imaging (MRI) and neuropsychological testing. Structural abnormalities were analyzed using a voxel-based morphometry (VBM) approach, and patients’ neuropsychological function was assessed using the Brief Assessment of Cognition in Schizophrenia, Japanese version (BACS-J). RESULTS: No significant differences were found between the two patient groups with respect to the clinical characteristics. Compared with healthy controls, polydipsic patients showed widespread brain volume reduction and neuropsychological impairment. Furthermore, the left insula was significantly reduced in polydipsic patients compared with nonpolydipsic patients. These nonpolydipsic patients performed intermediate to the other two groups in the neuropsychological function test. CONCLUSIONS: It is possible that polydipsia or the secondary hyponatremia might induce left insula volume reduction. Furthermore, this structural brain change may indirectly induce more severe neuropsychological impairments in polydipsic patients. Thus, we suggest that insula abnormalities might contribute to the pathophysiology of polydipsic patients

De novo variants predicting haploinsufficiency for DIP2C are associated with expressive speech delay.

The disconnected (disco)-interacting protein 2 (DIP2) gene was first identified in D. melanogaster and contains a DNA methyltransferase-associated protein 1 (DMAP1) binding domain, Acyl-CoA synthetase domain and AMP-binding sites. DIP2 regulates axonal bifurcation of the mushroom body neurons in D. melanogaster and is required for axonal regeneration in the neurons of C. elegans. The DIP2 homologues in vertebrates, Disco-interacting protein 2 homolog A (DIP2A), Disco-interacting protein 2 homolog B (DIP2B), and Disco-interacting protein 2 homolog C (DIP2C), are highly conserved and expressed widely in the central nervous system. Although there is evidence that DIP2C plays a role in cognition, reports of pathogenic variants in these genes are rare and their significance is uncertain. We present 23 individuals with heterozygous DIP2C variants, all manifesting developmental delays that primarily affect expressive language and speech articulation. Eight patients had de novo variants predicting loss-of-function in the DIP2C gene, two patients had de novo missense variants, three had paternally inherited loss of function variants and six had maternally inherited loss-of-function variants, while inheritance was unknown for four variants. Four patients had cardiac defects (hypertrophic cardiomyopathy, atrial septal defects, and bicuspid aortic valve). Minor facial anomalies were inconsistent but included a high anterior hairline with a long forehead, broad nasal tip, and ear anomalies. Brainspan analysis showed elevated DIP2C expression in the human neocortex at 10-24 weeks after conception. With the cases presented herein, we provide phenotypic and genotypic data supporting the association between loss-of-function variants in DIP2C with a neurocognitive phenotype

The ICON Earth System Model Version 1.0

This work documents ICON-ESM 1.0, the first version of a coupled model based 19 on the ICON framework 20 • Performance of ICON-ESM is assessed by means of CMIP6 DECK experiments 21 at standard CMIP-type resolution 22 • ICON-ESM reproduces the observed temperature evolution. Biases in clouds, winds, 23 sea-ice, and ocean properties are larger than in MPI-ESM. Abstract 25 This work documents the ICON-Earth System Model (ICON-ESM V1.0), the first cou-26 pled model based on the ICON (ICOsahedral Non-hydrostatic) framework with its un-27 structured, icosahedral grid concept. The ICON-A atmosphere uses a nonhydrostatic dy-28 namical core and the ocean model ICON-O builds on the same ICON infrastructure, but 29 applies the Boussinesq and hydrostatic approximation and includes a sea-ice model. The 30 ICON-Land module provides a new framework for the modelling of land processes and 31 the terrestrial carbon cycle. The oceanic carbon cycle and biogeochemistry are repre-32 sented by the Hamburg Ocean Carbon Cycle module. We describe the tuning and spin-33 up of a base-line version at a resolution typical for models participating in the Coupled 34 Model Intercomparison Project (CMIP). The performance of ICON-ESM is assessed by 35 means of a set of standard CMIP6 simulations. Achievements are well-balanced top-of-36 atmosphere radiation, stable key climate quantities in the control simulation, and a good 37 representation of the historical surface temperature evolution. The model has overall bi-38 ases, which are comparable to those of other CMIP models, but ICON-ESM performs 39 less well than its predecessor, the Max Planck Institute Earth System Model. Problem-40 atic biases are diagnosed in ICON-ESM in the vertical cloud distribution and the mean 41 zonal wind field. In the ocean, sub-surface temperature and salinity biases are of con-42 cern as is a too strong seasonal cycle of the sea-ice cover in both hemispheres. ICON-43 ESM V1.0 serves as a basis for further developments that will take advantage of ICON-44 specific properties such as spatially varying resolution, and configurations at very high 45 resolution. 46 Plain Language Summary 47 ICON-ESM is a completely new coupled climate and earth system model that ap-48 plies novel design principles and numerical techniques. The atmosphere model applies 49 a non-hydrostatic dynamical core, both atmosphere and ocean models apply unstruc-50 tured meshes, and the model is adapted for high-performance computing systems. This 51 article describes how the component models for atmosphere, land, and ocean are cou-52 pled together and how we achieve a stable climate by setting certain tuning parameters 53 and performing sensitivity experiments. We evaluate the performance of our new model 54 by running a set of experiments under pre-industrial and historical climate conditions 55 as well as a set of idealized greenhouse-gas-increase experiments. These experiments were 56 designed by the Coupled Model Intercomparison Project (CMIP) and allow us to com-57 pare the results to those from other CMIP models and the predecessor of our model, the 58 Max Planck Institute for Meteorology Earth System Model. While we diagnose overall 59 satisfactory performance, we find that ICON-ESM features somewhat larger biases in 60 several quantities compared to its predecessor at comparable grid resolution. We empha-61 size that the present configuration serves as a basis from where future development steps 62 will open up new perspectives in earth system modellin

Quantum Dots for Multiplexed Detection and Characterisation of Prostate Cancer Cells Using a Scanning Near-Field Optical Microscope

In this study scanning near-field optical microscopy (SNOM) has been utilised in conjunction with quantum dot labelling to interrogate the biomolecular composition of cell membranes. The technique overcomes the limits of optical diffraction found in standard fluorescence microscopy and also yields vital topographic information. The technique has been applied to investigate cell-cell adhesion in human epithelial cells. This has been realised through immunofluorescence labelling of the cell-cell adhesion protein E-cadherin. Moreover, a dual labelling protocol has been optimised to facilitate a comparative study of the adhesion mechanisms and the effect of aberrant adhesion protein expression in both healthy and cancerous epithelial cells. This study reports clear differences in the morphology and phenotype of healthy and cancerous cells. In healthy prostate epithelial cells (PNT2), E-cadherin was predominantly located around the cell periphery and within filopodial extensions. The presence of E-cadherin appeared to be enhanced when cell-cell contact was established. In contrast, examination of metastatic prostate adenocarcinoma cells (PC-3) revealed no E-cadherin labelling around the periphery of the cells. This lack of functional E-cadherin in PC-3 cells coincided with a markedly different morphology and PC-3 cells were not found to form close cell-cell associations with their neighbours. We have demonstrated that with a fully optimised sample preparation methodology, multiplexed quantum dot labelling in conjunction with SNOM imaging can be successfully applied to interrogate biomolecular localisation within delicate cellular membranes

Initial stages of water solvation of stepped platinum surfaces

Catalysis and Surface Chemistr