A microfluidic oligonucleotide synthesizer

De novo gene and genome synthesis enables the design of any sequence without the requirement of a pre-existing template as in traditional genetic engineering methods. The ability to mass produce synthetic genes holds great potential for biological research, but widespread availability of de novo DNA constructs is currently hampered by their high cost. In this work, we describe a microfluidic platform for parallel solid phase synthesis of oligonucleotides that can greatly reduce the cost of gene synthesis by reducing reagent consumption (by 100-fold) while maintaining a 100 pmol synthesis scale so there is no need for amplification before assembly. Sixteen oligonucleotides were synthesized in parallel on this platform and then successfully used in a ligation-mediated assembly method to generate DNA constructs 200 bp in length

Understanding Heisenberg's 'Magical' Paper of July 1925: a New Look at the Calculational Details

In July 1925 Heisenberg published a paper [Z. Phys. 33, 879-893 (1925)] which ended the period of `the Old Quantum Theory' and ushered in the new era of Quantum Mechanics. This epoch-making paper is generally regarded as being difficult to follow, perhaps partly because Heisenberg provided few clues as to how he arrived at the results which he reported. Here we give details of calculations of the type which, we suggest, Heisenberg may have performed. We take as a specific example one of the anharmonic oscillator problems considered by Heisenberg, and use our reconstruction of his approach to solve it up to second order in perturbation theory. We emphasize that the results are precisely those obtained in standard quantum mechanics, and suggest that some discussion of the approach - based on the direct computation of transition amplitudes - could usefully be included in undergraduate courses in quantum mechanics.Comment: 24 pages, no figures, Latex, submitted to Am. J. Phy

On-board demux/demod

To make satellite channels cost competitive with optical cables, the use of small, inexpensive earth stations with reduced antenna size and high powered amplifier (HPA) power will be needed. This will necessitate the use of high e.i.r.p. and gain-to-noise temperature ratio (G/T) multibeam satellites. For a multibeam satellite, onboard switching is required in order to maintain the needed connectivity between beams. This switching function can be realized by either an receive frequency (RF) or a baseband unit. The baseband switching approach has the additional advantage of decoupling the up-link and down-link, thus enabling rate and format conversion as well as improving the link performance. A baseband switching satellite requires the demultiplexing and demodulation of the up-link carriers before they can be switched to their assigned down-link beams. Principles of operation, design and implementation issues of such an onboard demultiplexer/demodulator (bulk demodulator) that was recently built at COMSAT Labs. are discussed

Optimization of the Separation of NDA-Derivatized Methylarginines by Capillary and Microchip Electrophoresis

The methylated arginines (MAs) monomethylarginine (MMA), asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA) have been shown to be independent predictors of cardiovascular disease. This article describes progress regarding the development of an analytical method capable of rapidly analyzing MAs using capillary electrophoresis (CE) and microchip electrophoresis (MCE) with laser-induced fluorescence (LIF) detection. Several parameters including buffer composition and separation voltage were optimized to achieve an ideal separation. The analytes of interest were derivatized with naphthalene-2,3-dicarboxaldehyde (NDA) to produce fluorescent 1-cyanobenz[f]isoindole (CBI) derivatives and then subjected to CE analysis. Baseline resolution of SDMA, ADMA, MMA, and arginine was achieved in less than 8 min. The limits of detection for SDMA, ADMA, MMA, and arginine were determined to be 15, 20, 25, and 5 nM, respectively, which are well below the expected plasma concentrations. The CE separation method was then transferred to a glass MCE device with LIF detection. MAs were baseline resolved in 3 min on-chip using a 14 cm separation channel with detection limits of approximately 10 nM for each species. To the best of the authors’ knowledge, this is the first report of the separation of MAs by MCE

Loss of intranetwork and internetwork resting state functional connections with Alzheimer\u27s disease progression

Alzheimer\u27s disease (AD) is the most common cause of dementia. Much is known concerning AD pathophysiology but our understanding of the disease at the systems level remains incomplete. Previous AD research has used resting-state functional connectivity magnetic resonance imaging (rs-fcMRI) to assess the integrity of functional networks within the brain. Most studies have focused on the default-mode network (DMN), a primary locus of AD pathology. However, other brain regions are inevitably affected with disease progression. We studied rs-fcMRI in five functionally defined brain networks within a large cohort of human participants of either gender (n = 510) that ranged in AD severity from unaffected [clinical dementia rating (CDR) 0] to very mild (CDR 0.5) to mild (CDR 1). We observed loss of correlations within not only the DMN but other networks at CDR 0.5. Within the salience network (SAL), increases were seen between CDR 0 and CDR 0.5. However, at CDR 1, all networks, including SAL, exhibited reduced correlations. Specific networks were preferentially affected at certain CDR stages. In addition, cross-network relations were consistently lost with increasing AD severity. Our results demonstrate that AD is associated with widespread loss of both intranetwork and internetwork correlations. These results provide insight into AD pathophysiology and reinforce an integrative view of the brain\u27s functional organization

RIPK3 restricts viral pathogenesis via cell death-independent neuroinflammation

Receptor-interacting protein kinase-3 (RIPK3) is an activator of necroptotic cell death, but recent work has implicated additional roles for RIPK3 in inflammatory signaling independent of cell death. However, while necroptosis has been shown to contribute to antiviral immunity, death-independent roles for RIPK3 in host defense have not been demonstrated. Using a mouse model of West Nile virus (WNV) encephalitis, we show that RIPK3 restricts WNV pathogenesis independently of cell death. Ripk3(-/-) mice exhibited enhanced mortality compared to wild-type (WT) controls, while mice lacking the necroptotic effector MLKL, or both MLKL and caspase-8, were unaffected. The enhanced susceptibility of Ripk3(-/-) mice arose from suppressed neuronal chemokine expression and decreased central nervous system (CNS) recruitment of T lymphocytes and inflammatory myeloid cells, while peripheral immunity remained intact. These data identify pleiotropic functions for RIPK3 in the restriction of viral pathogenesis and implicate RIPK3 as a key coordinator of immune responses within the CNS

Toward understanding I/O behavior in HPC workflows

Scientific discovery increasingly depends on complex workflows consisting of multiple phases and sometimes millions of parallelizable tasks or pipelines. These workflows access storage resources for a variety of purposes, including preprocessing, simulation output, and postprocessing steps. Unfortunately, most workflow models focus on the scheduling and allocation of com- putational resources for tasks while the impact on storage systems remains a secondary objective and an open research question. I/O performance is not usually accounted for in workflow telemetry reported to users. In this paper, we present an approach to augment the I/O efficiency of the individual tasks of workflows by combining workflow description frameworks with system I/O telemetry data. A conceptual architecture and a prototype implementation for HPC data center deployments are introduced. We also identify and discuss challenges that will need to be addressed by workflow management and monitoring systems for HPC in the future. We demonstrate how real-world applications and workflows could benefit from the approach, and we show how the approach helps communicate performance-tuning guidance to users

Cladding mode coupling in highly localized fiber Bragg gratings: modal properties and transmission spectra

The spectral characteristics of a fiber Bragg grating (FBG) with a transversely inhomogeneous refractive index profile, differs con- siderably from that of a transversely uniform one. Transmission spectra of inhomogeneous and asymmetric FBGs that have been inscribed with focused ultrashort pulses with the so-called point-by-point technique are investigated. The cladding mode resonances of such FBGs can span a full octave in the spectrum and are very pronounced (deeper than 20dB). Using a coupled-mode approach, we compute the strength of resonant coupling and find that coupling into cladding modes of higher azimuthal order is very sensitive to the position of the modification in the core. Exploiting these properties allows precise control of such reflections and may lead to many new sensing applications.Comment: Submission to OE, 16 pages, 6 figure

Magnetic anisotropy and phase transitions in single-crystal Tb5(Si2.2Ge1.8)

The Tb5(SixGe4−x) alloy system has many features in common with the Gd5(SixGe4−x)system although it has a more complex magnetic and structural phase diagram. This paper reports on the magnetic anisotropy and magnetic phase transition of single-crystalTb5(Si2.2Ge1.8) which has been investigated by the measurements of M-H and M-T along the a, b, and c axes. The variation of 1/χ vs T indicates that there is a transition from paramagnetic to ferromagnetic at Tc = 110 K. Below this transition temperature M-Hcurves show very strong anisotropy, and it is believed that this is due to the complex spin configuration. M-H measurements at T = 110 K show that the a axis is the easy axis, and that the saturation magnetization is 200 emu/g. The b axis is the hard axis, which needs an external magnetic field much higher than 2 T to saturate the magnetization in that direction, indicating a high magnetocrystalline anisotropy. The c axis is of intermediate hardness. The magnetic properties of this material are therefore very different from those of the related Gd5Si2Ge2 system, in which the b axis was found to be the easy axis and the magnitude of the anisotropy was smaller