Mutations in the chromatin modifier gene KANSL1 cause the 17q21.31 microdeletion syndrome

We show that haploinsufficiency of KANSL1 is sufficient to cause the 17q21.31 microdeletion syndrome, a multisystem disorder characterized by intellectual disability, hypotonia and distinctive facial features. The KANSL1 protein is an evolutionarily conserved regulator of the chromatin modifier KAT8, which influences gene expression through histone H4 lysine 16 (H4K16) acetylation. RNA sequencing studies in cell lines derived from affected individuals and the presence of learning deficits in Drosophila melanogaster mutants suggest a role for KANSL1 in neuronal processes.     

Electronic spin transport and spin precession in single graphene layers at room temperature

Electronic transport in single or a few layers of graphene is the subject of intense interest at present. The specific band structure of graphene, with its unique valley structure and Dirac neutrality point separating hole states from electron states, has led to the observation of new electronic transport phenomena such as anomalously quantized Hall effects, absence of weak localization and the existence of a minimum conductivity. In addition to dissipative transport, supercurrent transport has also been observed. Graphene might also be a promising material for spintronics and related applications, such as the realization of spin qubits, owing to the low intrinsic spin orbit interaction, as well as the low hyperfine interaction of the electron spins with the carbon nuclei. Here we report the observation of spin transport, as well as Larmor spin precession, over micrometre-scale distances in single graphene layers. The 'non-local' spin valve geometry was used in these experiments, employing four-terminal contact geometries with ferromagnetic cobalt electrodes making contact with the graphene sheet through a thin oxide layer. We observe clear bipolar (changing from positive to negative sign) spin signals that reflect the magnetization direction of all four electrodes, indicating that spin coherence extends underneath all of the contacts. No significant changes in the spin signals occur between 4.2 K, 77 K and room temperature. We extract a spin relaxation length between 1.5 and 2 mum at room temperature, only weakly dependent on charge density. The spin polarization of the ferromagnetic contacts is calculated from the measurements to be around ten per cent.     

A Novel Credit Rating Migration Modeling Approach Using Macroeconomic Indicators

Modeling credit rating migrations conditional on macroeconomic conditions allows financial institutions to assess, analyze, and manage the risk related to a credit portfolio. Existing methodologies to model credit rating migrations conditional on the business cycle suffer from poor accuracy, difficult readability, or model inconsistencies. The modeling methodology proposed in this paper extends ordinal logistic regression to estimate the complete migration matrix including default rates as a function of rating dynamics and macroeconomic indicators. The gradient and Hessian derivations show efficient optimization within the Levenberg–Marquardt algorithm. The proposed modeling methodology is applied to model corporate rating migrations using historical data from 1984 to 2011. It is shown that the resulting model captures the cyclical behavior of credit rating migrations and default rates, and is able to approximate historic migration levels with good precision. The model therefore permits analysis of the impact of economical downturn conditions on a credit portfolio. Copyright © 2013 John Wiley & Sons, Ltd.     

Genome-wide association study identifies three new melanoma susceptibility loci

We report a genome-wide association study for melanoma that was conducted by the GenoMEL Consortium. Our discovery phase included 2,981 individuals with melanoma and 1,982 study-specific control individuals of European ancestry, as well as an additional 6,426 control subjects from French or British populations, all of whom were genotyped for 317,000 or 610,000 single-nucleotide polymorphisms (SNPs). Our analysis replicated previously known melanoma susceptibility loci. Seven new regions with at least one SNP with P < 10(-5) and further local imputed or genotyped support were selected for replication using two other genome-wide studies (from Australia and Texas, USA). Additional replication came from case-control series from the UK and The Netherlands. Variants at three of the seven loci replicated at P < 10(-3): an SNP in ATM (rs1801516, overall P = 3.4 × 10(-9)), an SNP in MX2 (rs45430, P = 2.9 × 10(-9)) and an SNP adjacent to CASP8 (rs13016963, P = 8.6 × 10(-10)). A fourth locus near CCND1 remains of potential interest, showing suggestive but inconclusive evidence of replication (rs1485993, overall P = 4.6 × 10(-7) under a fixed-effects model and P = 1.2 × 10(-3) under a random-effects model). These newly associated variants showed no association with nevus or pigmentation phenotypes in a large British case-control series.     

Melanocortin control of energy balance: evidence from rodent models

Regulation of energy balance is extremely complex, and involves multiple systems of hormones, neurotransmitters, receptors, and intracellular signals. As data have accumulated over the last two decades, the CNS melanocortin system is now identified as a prominent integrative network of energy balance controls in the mammalian brain. Here, we will review findings from rat and mouse models, which have provided an important framework in which to study melanocortin function. Perhaps most importantly, this review attempts for the first time to summarize recent advances in our understanding of the intracellular signaling pathways thought to mediate the action of melanocortin neurons and peptides in control of longterm energy balance. Special attention will be paid to the roles of MC4R/MC3R, as well as downstream neurotransmitters within forebrain and hindbrain structures that illustrate the distributed control of melanocortin signaling in energy balance. In addition, distinctions and controversy between rodent species will be discussed.     

Ternary Diffusion Coefficients of 1-Hexanol-Hexane-Toluene and 1-Propanol-Water-Ethylene Glycol by Taylor Dispersion Method

The Taylor dispersion method was used to measure diffusion coefficients of three-component liquid systems. An improved constrained nonlinear least-square method was used to evaluate the ternary diffusion coefficients directly by fitting the mathematical solutions of the dispersion equation to eluted solute peaks detected using a differential refractometer. Diffusion coefficients of the three-component system of acetone-benzene-CCl4, determined at 25℃, were used to test the procedure. The measured diffusion coefficients were compared with values obtained by optical interferometry and the diaphragm cell method. Ternary diffusion coefficients are also determinated for solutions of 1-hexanol-hexane-toluene and 1-propanol- water-ethylene glycol at 25℃, with an accuracy of approximately 0.05 m^2·s^- 1.     

基于加权递推最小二乘法的微硬盘伺服信号滤波

针对微硬盘伺服信号的滤波问题,采用了一种加权递推最小二乘法.该算法使用最小二乘加权时间平均准则取代通常的最小均方误差准则,并利用该准则导出权向量的自适应迭代公式,算法保证在每步迭代运算中权值都能调整到最佳,同时降低了权值调整量对噪声的敏感程度.实验结果表明:该算法滤波效果好、抗噪能力强、稳态收敛精度高和收敛速度快,适用于诸如微硬盘驱动器之类对收敛速度及消噪要求较高的场合.     

The multidrug-resistant human pathogen Clostridium difficile has a highly mobile, mosaic genome

We determined the complete genome sequence of Clostridium difficile strain 630, a virulent and multidrug-resistant strain. Our analysis indicates that a large proportion (11%) of the genome consists of mobile genetic elements, mainly in the form of conjugative transposons. These mobile elements are putatively responsible for the acquisition by C. difficile of an extensive array of genes involved in antimicrobial resistance, virulence, host interaction and the production of surface structures. The metabolic capabilities encoded in the genome show multiple adaptations for survival and growth within the gut environment. The extreme genome variability was confirmed by whole-genome microarray analysis; it may reflect the organism's niche in the gut and should provide information on the evolution of virulence in this organism.     

The Medicago genome provides insight into the evolution of rhizobial symbioses

Legumes (Fabaceae or Leguminosae) are unique among cultivated plants for their ability to carry out endosymbiotic nitrogen fixation with rhizobial bacteria, a process that takes place in a specialized structure known as the nodule. Legumes belong to one of the two main groups of eurosids, the Fabidae, which includes most species capable of endosymbiotic nitrogen fixation. Legumes comprise several evolutionary lineages derived from a common ancestor 60 million years ago (Myr ago). Papilionoids are the largest clade, dating nearly to the origin of legumes and containing most cultivated species. Medicago truncatula is a long-established model for the study of legume biology. Here we describe the draft sequence of the M. truncatula euchromatin based on a recently completed BAC assembly supplemented with Illumina shotgun sequence, together capturing ～94% of all M. truncatula genes. A whole-genome duplication (WGD) approximately 58 Myr ago had a major role in shaping the M. truncatula genome and thereby contributed to the evolution of endosymbiotic nitrogen fixation. Subsequent to the WGD, the M. truncatula genome experienced higher levels of rearrangement than two other sequenced legumes, Glycine max and Lotus japonicus. M. truncatula is a close relative of alfalfa (Medicago sativa), a widely cultivated crop with limited genomics tools and complex autotetraploid genetics. As such, the M. truncatula genome sequence provides significant opportunities to expand alfalfa's genomic toolbox.