Ultrafast precessional magnetization reversal by picosecond magnetic field pulse shaping

Since the invention of the first magnetic memory disk in 1954, much effort has been put into enhancing the speed, bit density and reliability of magnetic memory devices. In the case of magnetic random access memory (MRAM) devices, fast coherent magnetization rotation by precession of the entire memory cell is desired, because reversal by domain-wall motion is much too slow. In principle, the fundamental limit of the switching speed via precession is given by half of the precession period. However, under-critically damped systems exhibit severe ringing and simulations show that, as a consequence, undesired back-switching of magnetic elements of an MRAM can easily be initiated by subsequent write pulses, threatening data integrity. We present a method to reverse the magnetization in under-critically damped systems by coherent rotation of the magnetization while avoiding any ringing. This is achieved by applying specifically shaped magnetic field pulses that match the intrinsic properties of the magnetic elements. We demonstrate, by probing all three magnetization components, that reliable precessional reversal in lithographically structured micrometre-sized elliptical permalloy elements is possible at switching times of about 200 ps, which is ten times faster than the natural damping time constant.     

Functional interactions between receptors in bacterial chemotaxis

Bacterial chemotaxis is a model system for signal transduction, noted for its relative simplicity, high sensitivity, wide dynamic range and robustness. Changes in ligand concentrations are sensed by a protein assembly consisting of transmembrane receptors, a coupling protein (CheW) and a histidine kinase (CheA). In Escherichia coli, these components are organized at the cell poles in tight clusters that contain several thousand copies of each protein. Here we studied the effects of variation in the composition of clusters on the activity of the kinase and its sensitivity to attractant stimuli, monitoring responses in vivo using fluorescence resonance energy transfer. Our results indicate that assemblies of bacterial chemoreceptors work in a highly cooperative manner, mimicking the behaviour of allosteric proteins. Conditions that favour steep responses to attractants in mutants with homogeneous receptor populations also enhance the sensitivity of the response in wild-type cells. This is consistent with a number of models that assume long-range cooperative interactions between receptors as a general mechanism for signal integration and amplification.     

Meta-analysis of genome-wide association studies of asthma in ethnically diverse North American populations

Asthma is a common disease with a complex risk architecture including both genetic and environmental factors. We performed a meta-analysis of North American genome-wide association studies of asthma in 5,416 individuals with asthma (cases) including individuals of European American, African American or African Caribbean, and Latino ancestry, with replication in an additional 12,649 individuals from the same ethnic groups. We identified five susceptibility loci. Four were at previously reported loci on 17q21, near IL1RL1, TSLP and IL33, but we report for the first time, to our knowledge, that these loci are associated with asthma risk in three ethnic groups. In addition, we identified a new asthma susceptibility locus at PYHIN1, with the association being specific to individuals of African descent (P = 3.9 × 10(-9)). These results suggest that some asthma susceptibility loci are robust to differences in ancestry when sufficiently large samples sizes are investigated, and that ancestry-specific associations also contribute to the complex genetic architecture of asthma.     

Dnmt3a is essential for hematopoietic stem cell differentiation

Loss of the de novo DNA methyltransferases Dnmt3a and Dnmt3b in embryonic stem cells obstructs differentiation; however, the role of these enzymes in somatic stem cells is largely unknown. Using conditional ablation, we show that Dnmt3a loss progressively impairs hematopoietic stem cell (HSC) differentiation over serial transplantation, while simultaneously expanding HSC numbers in the bone marrow. Dnmt3a-null HSCs show both increased and decreased methylation at distinct loci, including substantial CpG island hypermethylation. Dnmt3a-null HSCs upregulate HSC multipotency genes and downregulate differentiation factors, and their progeny exhibit global hypomethylation and incomplete repression of HSC-specific genes. These data establish Dnmt3a as a critical participant in the epigenetic silencing of HSC regulatory genes, thereby enabling efficient differentiation.     

A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci

We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10?12) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10?11) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10??) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10?11) and a tag SNP for NAT2 acetylation status (P = 4 × 10?11), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis.     

A CASE FOR SERVICE SYSTEMS ENGINEERING

A case is made for further developing a branch of systems engineering that focuses on problemsand issues which arise in the service sector We promulgate this special focus not only because of thesize and importance of the service sector but also because of the unique opportunities that systemsengineering can exploit in the design and joint production and delivery of services. We begin byconsidering the economic, technological and demographic contexts within which the service sector hasflourished; we then address both services, especially emerging services, and systems engineering,followed by a discussion of how to advance the field of service systems engineering, and concludingwith several remarks. In particular, a number of service systems engineering methods are identified toenhance the design and production/delivery of services, especially taking advantage of the uniquefeatures that characterize services-namely, services, especially emerging services, are information-driven, customer-centric, e-orien