Tristable nematic liquid-crystal device using micropatterned surface alignment

It has long been appreciated that liquid-crystal (LC) devices in which the LC molecules adopt multiple stable orientations could drastically reduce the power consumption required for high-information-content displays. But for the commonly used nematic LCs, which are intrinsically uniaxial in symmetry, no industrially feasible multi-stable LC device has been realized. Recently we demonstrated how bistability can be robustly engineered into a nematic LC device, by patterning a substrate with an orientational chequerboard pattern that enforces orthogonal LC alignment in neighbouring square domains. As a result of the four-fold symmetry of the pattern, the two diagonal axes of the chequerboard become equally stable macroscopic orientations. Here we extend this symmetry approach to obtain a tristable surface-aligned nematic LC. A microscopic pattern exhibiting six-fold symmetry is inscribed on a polyimide surface using the stylus of an atomic force microscope. The hexagonal symmetry of the microscopic orientational domains in turn gives rise to three stable macroscopic LC orientations, which are mutually switchable by an in-plane electric field. The resulting switching mode is surface driven, and hence should be compatible with demanding flexible display applications.     

Genotype, haplotype and copy-number variation in worldwide human populations

Genome-wide patterns of variation across individuals provide a powerful source of data for uncovering the history of migration, range expansion, and adaptation of the human species. However, high-resolution surveys of variation in genotype, haplotype and copy number have generally focused on a small number of population groups. Here we report the analysis of high-quality genotypes at 525,910 single-nucleotide polymorphisms (SNPs) and 396 copy-number-variable loci in a worldwide sample of 29 populations. Analysis of SNP genotypes yields strongly supported fine-scale inferences about population structure. Increasing linkage disequilibrium is observed with increasing geographic distance from Africa, as expected under a serial founder effect for the out-of-Africa spread of human populations. New approaches for haplotype analysis produce inferences about population structure that complement results based on unphased SNPs. Despite a difference from SNPs in the frequency spectrum of the copy-number variants (CNVs) detected--including a comparatively large number of CNVs in previously unexamined populations from Oceania and the Americas--the global distribution of CNVs largely accords with population structure analyses for SNP data sets of similar size. Our results produce new inferences about inter-population variation, support the utility of CNVs in human population-genetic research, and serve as a genomic resource for human-genetic studies in diverse worldwide populations.     

Structural differences between a ras oncogene protein and the normal protein

One of the most commonly found transforming ras oncogenes in human tumours has a valine codon replacing the glycine codon at position 12 of the normal c-Ha-ras gene. To understand the structural reasons behind cell transformation arising from this single amino acid substitution, we have determined the crystal structure of the GDP-bound form of the mutant protein, p21(Val-12), encoded by this oncogene. We report here the overall structure of p21(Val-12) at 2.2 A resolution and compare it with the structure of the normal c-Ha-ras protein. One of the major differences is that the loop of the transforming ras protein that binds the beta-phosphate of the guanine nucleotide is enlarged. Such a change in the 'catalytic site' conformation could explain the reduced GTPase activity of the mutant, which keeps the protein in the GTP bound 'signal on' state for a prolonged period time, ultimately causing cell transformation.     

Emergent excitations in a geometrically frustrated magnet

Frustrated systems are ubiquitous, and they are interesting because their behaviour is difficult to predict; frustration can lead to macroscopic degeneracies and qualitatively new states of matter. Magnetic systems offer good examples in the form of spin lattices, where all interactions between spins cannot be simultaneously satisfied. Here we report how unusual composite spin degrees of freedom can emerge from frustrated magnetic interactions in the cubic spinel ZnCr(2)O(4). Upon cooling, groups of six spins self-organize into weakly interacting antiferromagnetic loops, whose directors -- the unique direction along which the spins are aligned, parallel or antiparallel -- govern all low-temperature dynamics. The experimental evidence comes from a measurement of the magnetic form factor by inelastic neutron scattering; the data show that neutrons scatter from hexagonal spin clusters rather than individual spins. The hexagon directors are, to a first approximation, decoupled from each other, and hence their reorientations embody the long-sought local zero energy modes for the pyrochlore lattice.     

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140?mm?Hg systolic blood pressure or ≥90?mm?Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.     

Copy number polymorphism in Fcgr3 predisposes to glomerulonephritis in rats and humans

Identification of the genes underlying complex phenotypes and the definition of the evolutionary forces that have shaped eukaryotic genomes are among the current challenges in molecular genetics. Variation in gene copy number is increasingly recognized as a source of inter-individual differences in genome sequence and has been proposed as a driving force for genome evolution and phenotypic variation. Here we show that copy number variation of the orthologous rat and human Fcgr3 genes is a determinant of susceptibility to immunologically mediated glomerulonephritis. Positional cloning identified loss of the newly described, rat-specific Fcgr3 paralogue, Fcgr3-related sequence (Fcgr3-rs), as a determinant of macrophage overactivity and glomerulonephritis in Wistar Kyoto rats. In humans, low copy number of FCGR3B, an orthologue of rat Fcgr3, was associated with glomerulonephritis in the autoimmune disease systemic lupus erythematosus. The finding that gene copy number polymorphism predisposes to immunologically mediated renal disease in two mammalian species provides direct evidence for the importance of genome plasticity in the evolution of genetically complex phenotypes, including susceptibility to common human disease.     

Construction of protograph LDPC codes with circular generator matrices

The application of protograph low density parity check(LDPC) codes involves the encoding complexity problem.Since the generator matrices are dense,and if the positions of 1 s are irregularity,the encoder needs to store every 1 of the generator matrices by using huge chip area.In order to solve this problem,we need to design the protograph LDPC codes with circular generator matrices.A theorem concerning the circulating property of generator matrices of nonsingular protograph LDPC codes is proposed.The circulating property of generator matrix of nonsingular protograph LDPC codes can be obtained from the corresponding quasi-cyclic parity check matrix.This paper gives a scheme of constructing protograph LDPC codes with circulating generator matrices,and it reveals that the fast encoding algorithm of protograph LDPC codes has lower encoding complexity under the condition of the proposed theorem.Simulation results in additive white Gaussian noise(AWGN) channels show that the bit error rate(BER) performance of the designed codes based on the proposed theorem is much better than that of GB20600 LDPC codes and Tanner LDPC codes.     

Fabrication and characterization of 3D scaffold using 3D plotting system

In this paper, we design and fabricate a 3D scaffold using rapid prototyping (RP) technology for tissue engineering. The scaffold should have a three-dimensional interconnected pore network. We fabricate a polycaprolactone (PCL) scaffold with interconnecting pores and uniform porosity for cell ingrowth using a 3D plotting system. In order to keep the three dimensional shape under mechanical loading while implanted, we design an oscillating nozzle system to increase elastic modulus and yield strength of PCL ...     

ATM phosphorylates p95/nbs1 in an S-phase checkpoint pathway

The rare diseases ataxia-telangiectasia (AT), caused by mutations in the ATM gene, and Nijmegen breakage syndrome (NBS), with mutations in the p95/nbs1 gene, share a variety of phenotypic abnormalities such as chromosomal instability, radiation sensitivity and defects in cell-cycle checkpoints in response to ionizing radiation. The ATM gene encodes a protein kinase that is activated by ionizing radiation or radiomimetic drugs, whereas p95/nbs1 is part of a protein complex that is involved in responses to DNA double-strand breaks. Here, because of the similarities between AT and NBS, we evaluated the functional interactions between ATM and p95/nbs1. Activation of the ATM kinase by ionizing radiation and induction of ATM-dependent responses in NBS cells indicated that p95/nbs1 may not be required for signalling to ATM after ionizing radiation. However, p95/nbs1 was phosphorylated on serine 343 in an ATM-dependent manner in vitro and in vivo after ionizing radiation. A p95/nbs1 construct mutated at the ATM phosphorylation site abrogated an S-phase checkpoint induced by ionizing radiation in normal cells and failed to compensate for this functional deficiency in NBS cells. These observations link ATM and p95/nbs1 in a common signalling pathway and provide an explanation for phenotypic similarities in these two diseases.     

WNT7b mediates macrophage-induced programmed cell death in patterning of the vasculature

Macrophages have a critical role in inflammatory and immune responses through their ability to recognize and engulf apoptotic cells. Here we show that macrophages initiate a cell-death programme in target cells by activating the canonical WNT pathway. We show in mice that macrophage WNT7b is a short-range paracrine signal required for WNT-pathway responses and programmed cell death in the vascular endothelial cells of the temporary hyaloid vessels of the developing eye. These findings indicate that macrophages can use WNT ligands to influence cell-fate decisions--including cell death--in adjacent cells, and raise the possibility that they do so in many different cellular contexts.