Mutations in the _SC4MOL_ gene encoding a novel methyl sterol oxidase cause autosomal recessive psoriasisiform dermatitis, microcephaly and developmental delay

Disorders of cholesterol biosynthesis have clinical manifestations involving skeleton, eyes, neurologic development, and skin. We describe a patient with congenital cataracts, developmental delay, microcephaly, and low serum cholesterol who developed severe psoriasiform dermatitis and arthralgias beginning at age 3. Her brain MRI indicatedminor gliosis. Quantitative sterol analysis of patient plasma and skin showed marked elevation of 4alpha-methyl- and 4, 4'-dimethylsterols, indicating a deficiency in the first step of sterol C4 demethylation in cholesterol biosynthesis. Molecular studies showed mutations in _SC4MOL_, a gene predicted to encode a sterol C4 methyl oxidase. Thus, our patient has a previously undescribed inborn error of cholesterol biosynthesis. Cellular studies with patient-derived fibroblasts showed higher mitotic rate than control cells in cholesterol-depleted medium, in which _de novo_ cholesterol biosynthesis was increased with the accumulation of methylsterol. Immunologic analyses showed dysregulation of immune-related receptors in the patient and her father. Inhibition of sterol C4 methyl oxidase in human transformed lymphoblasts or in fresh leukocytes induced activation of cell cycle, and immune receptor dysregulation. These findings suggest that methylsterols influence mitotic capacity and immune function. _SC4MOL_ is situated within the psoriasis susceptibility locus _PSORS9_, and is likely a genetic risk factor for common psoriasis

Spin-induced angular momentum switching

When light is transmitted through optically inhomogeneous and anisotropic media the spatial distribution of light can be modified according to its input polarization state. A complete analysis of this process, based on the paraxial approximation, is presented, and we show how it can be exploited to produce a spin-controlled-change in the orbital angular momentum of light beams propagating in patterned space-variant-optical-axis phase plates. We also unveil a new effect. The development of a strong modulation in the angular momentum change upon variation of the optical path through the phase plates.Comment: The original paper of the published version in Opt. Let

Efficient FPGA implementation of high-throughput mixed radix multipath delay commutator FFT processor for MIMO-OFDM

This article presents and evaluates pipelined architecture designs for an improved high-frequency Fast Fourier Transform (FFT) processor implemented on Field Programmable Gate Arrays (FPGA) for Multiple Input Multiple Output Orthogonal Frequency Division Multiplexing (MIMO-OFDM). The architecture presented is a Mixed-Radix Multipath Delay Commutator. The presented parallel architecture utilizes fewer hardware resources compared to Radix-2 architecture, while maintaining simple control and butterfly structures inherent to Radix-2 implementations. The high-frequency design presented allows enhancing system throughput without requiring additional parallel data paths common in other current approaches, the presented design can process two and four independent data streams in parallel and is suitable for scaling to any power of two FFT size N. FPGA implementation of the architecture demonstrated significant resource efficiency and high-throughput in comparison to relevant current approaches within literature. The proposed architecture designs were realized with Xilinx System Generator (XSG) and evaluated on both Virtex-5 and Virtex-7 FPGA devices. Post place and route results demonstrated maximum frequency values over 400 MHz and 470 MHz for Virtex-5 and Virtex-7 FPGA devices respectively

Chemoenzymatic Synthesis of Triazololactams Structurally Related to Pancratistatin

Four tricyclic lactams that structurally resemble alkaloids with the pancratistatin skeleton were synthetized from bromobenzene by a chemoenzymatic strategy. The sequence involved enzymatic dihydroxylation, efficient stereodirected oxidation of double bonds, inter- or intramolecular Huisgen cycloaddition, and a solvent-free cyclization. The complex structures were obtained in high chemical and optical purity and may be good candidates for biological testing.Fil: de la Sovera, Victoria. Universidad de la República. Facultad de Química. Departamento de Química Orgánica; UruguayFil: Suescun, Leopoldo. Universidad de la República. Laboratorio de Cristalografía, Estado Sólido y Materiales; UruguayFil: Bellomo Peraza, Ana Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Bionanociencias ; ArgentinaFil: González, David. Universidad de la República. Facultad de Química. Departamento de Química Orgánica; Urugua

A Chronic Care Model Program Incorporating Group Office Visits for Obesity Treatment in Primary Care

Background. Obesity is a chronic disease of epidemic proportions. Primary care providers are on the front line of diagnosing and treating obesity and need better tools to deliver top-notch obesity care. Methods. A pilot randomized trial was conducted to test a chronic care model (CCM) program for obesity compared to usual care. Primary care patients, 18 years and older, with a body mass index (BMI) between 27 and 45 were enrolled. Sixteen weekly 90-minute group office visits were structured with the first 30 minutes encompassing individualized clinical assessments and the final 60 minutes containing the group-based standardized intensive lifestyle training. The primary outcome was weight change at 16 weeks. Secondary outcomes were weight change at 24 weeks, change in diet and physical activity behaviors, self-efficacy for weight control behaviors, and physiologic markers of cardiovascular risk at 16 and 24 weeks. Results. The participants (19 in the active arm and 10 in the control arm) were 49.8 ± 11.5 years old (mean ± SD), 97% women, 55% white, and 41% black. Weight change in the control arm at week 16 was 0.25+ 2.21 kg (mean + SD) and that for the active arm was -5.74 + 4.50 kg (n=16). The difference between the two arms was significant (p = 0.0002). Both the intent-to-treat analysis using the last observation carried forward approach and the analysis including completers only provided similar siginificant results. Conclusions. This study demonstrated that a CCM program incorporating group office visits was feasible and effective for obesity treatment in primary care settings

Effects of misalignments in the optical vortex transformation performed by holograms with embedded phase singularity

Spatial characteristics of diffracted beams produced by a "fork" hologram from an incident circular Laguerre-Gaussian beam whose axis differ from the hologram optical axis are studied theoretically. General analytical representations for the complex amplitude distribution of a diffracted beam are derived in terms of superposition of Kummer beams or hypergeometric-Gaussian beams. The diffracted beam structure is determined by combination of the "proper" topological charge m of the incident vortex beam and the topological charge l of the singularity "imparted" by the hologram. Evolution of the diffracted beam structure is studied in detail for several combinations of m and l and for various incident beam displacements with respect to the optical axis of the hologram. Variations of the intensity and phase distribution due to the incident beam misalignment are investigated and possible applications for the purposeful optical-vortex beam generation and optical measurements are discussed.Comment: 23 pages, 8 figure

Chaotic Interaction of Langmuir Solitons and Long Wavelength Radiation

In this work we analyze the interaction of isolated solitary structures and ion-acoustic radiation. If the radiation amplitude is small solitary structures persists, but when the amplitude grows energy transfer towards small spatial scales occurs. We show that transfer is particularly fast when a fixed point of a low dimensional model is destroyed.Comment: LaTex + 4 eps file

Improvement of image quality of time-domain diffuse optical tomography with lp sparsity regularization

An lp (0 < p ≤ 1) sparsity regularization is applied to time-domain diffuse optical tomography with a gradient-based nonlinear optimization scheme to improve the spatial resolution and the robustness to noise. The expression of the lp sparsity regularization is reformulated as a differentiable function of a parameter to avoid the difficulty in calculating its gradient in the optimization process. The regularization parameter is selected by the L-curve method. Numerical experiments show that the lp sparsity regularization improves the spatial resolution and recovers the difference in the absorption coefficients between two targets, although a target with a small absorption coefficient may disappear due to the strong effect of the lp sparsity regularization when the value of p is too small. The lp sparsity regularization with small p values strongly localizes the target, and the reconstructed region of the target becomes smaller as the value of p decreases. A phantom experiment validates the numerical simulations

Coordination of myeloid differentiation with reduced cell cycle progression by PU.1 Induction of microRNAs targeting cell cycle regulators and lipid anabolism

During macrophage development, myeloid progenitor cells undergo terminal differentiation coordinated with reduced cell cycle progression. Differentiation of macrophages from myeloid progenitors is accompanied by increased expression of the E26 transformation-specific transcription factor PU.1. Reduced PU.1 expression leads to increased proliferation and impaired differentiation of myeloid progenitor cells. It is not understood how PU.1 coordinates macrophage differentiation with reduced cell cycle progression. In this study, we utilized cultured PU.1- inducible myeloid cells to perform genome-wide chromatin immunoprecipitation sequencing (ChIP-seq) analysis coupled with gene expression analysis to determine targets of PU.1 that may be involved in regulating cell cycle progression. We found that genes encoding cell cycle regulators and enzymes involved in lipid anabolism were directly and inducibly bound by PU.1 although their steady-state mRNA transcript levels were reduced. Inhibition of lipid anabolism was sufficient to reduce cell cycle progression in these cells. Induction of PU.1 reduced expression of E2f1, an important activator of genes involved in cell cycle and lipid anabolism, indirectly through microRNA 223. Next-generation sequencing identified microRNAs validated as targeting cell cycle and lipid anabolism for downregulation. These results suggest that PU.1 coordinates cell cycle progression with differentiation through induction of microRNAs targeting cell cycle regulators and lipid anabolism