Finding the optimal design of a passive microfluidic mixer.

The ability to thoroughly mix two fluids is a fundamental need in microfluidics. While a variety of different microfluidic mixers have been designed by researchers, it remains unknown which (if any) of these mixers are optimal (that is, which designs provide the most thorough mixing with the smallest possible fluidic resistance across the mixer). In this work, we automatically designed and rationally optimized a microfluidic mixer. We accomplished this by first generating a library of thousands of different randomly designed mixers, then using the non-dominated sorting genetic algorithm II (NSGA-II) to optimize the random chips in order to achieve Pareto efficiency. Pareto efficiency is a state of allocation of resources (e.g. driving force) from which it is impossible to reallocate so as to make any one individual criterion better off (e.g. pressure drop) without making at least one individual criterion (e.g. mixing performance) worse off. After 200 generations of evolution, Pareto efficiency was achieved and the Pareto-optimal front was found. We examined designs at the Pareto-optimal front and found several design criteria that enhance the mixing performance of a mixer while minimizing its fluidic resistance; these observations provide new criteria on how to design optimal microfluidic mixers. Additionally, we compared the designs from NSGA-II with some popular microfluidic mixer designs from the literature and found that designs from NSGA-II have lower fluidic resistance with similar mixing performance. As a proof of concept, we fabricated three mixer designs from 200 generations of evolution and one conventional popular mixer design and tested the performance of these four mixers. Using this approach, an optimal design of a passive microfluidic mixer is found and the criteria of designing a passive microfluidic mixer are established

On the Amplitude of Burst Oscillations in 4U 1636-54: Evidence for Nuclear Powered Pulsars

We present a study of 581 Hz oscillations observed during a thermonuclear X-ray burst from the low mass X-ray binary (LMXB) 4U 1636-54 with the Rossi X-ray Timing Explorer (RXTE). We argue that the combination of large pulsed amplitudes near burst onset and the spectral evidence for localized emission during the rise strongly supports rotational modulation as the mechanism for the oscillations. We discuss how theoretical interpretation of spin modulation amplitudes, pulse profiles and pulse phase spectroscopy can provide constraints on the masses and radii of neutron stars. We also discuss the implication of these findings for the beat frequency models of kHz X-ray variability in LMXB.Comment: AASTEX Latex, 13 pages including 5 figures. Accepted for publication in the Astrophysical Journal Letter

The Long Term Stability of Oscillations During Thermonuclear X-ray Bursts: Constraining the Binary X-ray Mass Function

We report on the long term stability of the millisecond oscillations observed with the Rossi X-ray Timing Explorer (RXTE) during thermonuclear X-ray bursts from the low mass X-ray binaries (LMXB) 4U 1728-34 and 4U 1636-53. We show that bursts from 4U 1728-34 spanning more than 1.5 years have observed asymptotic oscillation periods which are within 0.2 microsec. of each other, well within the magnitude which could be produced by the orbital motion of the neutron star in a typical LMXB. This stability implies a timescale to change the oscillation period of > 23,000 years, suggesting a highly stable process such as stellar rotation as the oscillation mechanism. We show that period offsets in three distinct bursts from 4U 1636-53 can be plausibly interpreted as due to orbital motion of the neutron star in this 3.8 hour binary system. We discuss the constraints on the mass function which can in principle be derived using this technique.Comment: 11 pages, 4 figures. AASTeX, to be published in the Astrophysical Journal Letter

Integron prevalence and diversity in manured soil

Integron abundance and diversity were studied in soil amended with pig slurry. Real-time PCR illustrated a significant increase in class 1 integron prevalence post slurry-application with increased prevalence still evident at 10 months post-application. Culture dependent data revealed 10 genera, including putative human pathogens, carrying class 1 and 2 integrons

Quantum scattering via the S‐matrix version of the Kohn variational principle

This is the published version, also available here: http://dx.doi.org/10.1063/1.454462.The S‐matrix version of the Kohn variational principle is used to obtain a very effective method for quantum scattering calculations. The approach is especially useful for the nonlocal (i.e., exchange) interactions that arise in chemically reactive scattering (and also in electron–atom/molecule scattering). The particular version developed in this paper has a more general structure than an earlier one by Miller and Jansen op de Haar [J. Chem. Phys. 8 6, 6213 (1987)], and applications to an elasticscattering problem, and also to three‐dimensional H+H2 reactive scattering, show that it is also more useful in practice

Bone morphogenetic protein 7 sensitizes O6-methylguanine methyltransferase expressing-glioblastoma stem cells to clinically relevant dose of temozolomide.

BackgroundTemozolomide (TMZ) is an oral DNA-alkylating agent used for treating patients with glioblastoma. However, therapeutic benefits of TMZ can be compromised by the expression of O6-methylguanine methyltransferase (MGMT) in tumor tissue. Here we used MGMT-expressing glioblastoma stem cells (GSC) lines as a model for investigating the molecular mechanism underlying TMZ resistance, while aiming to explore a new treatment strategy designed to possibly overcome resistance to the clinically relevant dose of TMZ (35 μM).MethodsMGMT-expressing GSC cultures are resistant to TMZ, and IC50 (half maximal inhibitory concentration) is estimated at around 500 μM. Clonogenic GSC surviving 500 μM TMZ (GSC-500 μM TMZ), were isolated. Molecular signatures were identified via comparative analysis of expression microarray against parental GSC (GSC-parental). The recombinant protein of top downregulated signature was used as a single agent or in combination with TMZ, for evaluating therapeutic effects of treatment of GSC.ResultsThe molecular signatures characterized an activation of protective stress responses in GSC-500 μM TMZ, mainly including biotransformation/detoxification of xenobiotics, blocked endoplasmic reticulum stress-mediated apoptosis, epithelial-to-mesenchymal transition (EMT), and inhibited growth/differentiation. Bone morphogenetic protein 7 (BMP7) was identified as the top down-regulated gene in GSC-500 μM TMZ. Although augmenting BMP7 signaling in GSC by exogenous BMP7 treatment did not effectively stop GSC growth, it markedly sensitized both GSC-500 μM TMZ and GSC-parental to 35 μM TMZ treatment, leading to loss of self-renewal and migration capacity. BMP7 treatment induced senescence of GSC cultures and suppressed mRNA expression of CD133, MGMT, and ATP-binding cassette drug efflux transporters (ABCB1, ABCG2), as well as reconfigured transcriptional profiles in GSC by downregulating genes associated with EMT/migration/invasion, stemness, inflammation/immune response, and cell proliferation/tumorigenesis. BMP7 treatment significantly prolonged survival time of animals intracranially inoculated with GSC when compared to those untreated or treated with TMZ alone (p = 0.0017), whereas combination of two agents further extended animal survival compared to BMP7 alone (p = 0.0489).ConclusionsThese data support the view that reduced endogenous BMP7 expression/signaling in GSC may contribute to maintained stemness, EMT, and chemoresistant phenotype, suggesting that BMP7 treatment may provide a novel strategy in combination with TMZ for an effective treatment of glioblastoma exhibiting unmethylated MGMT

Laucysteinamide A, a Hybrid PKS/NRPS Metabolite from a Saipan Cyanobacterium, cf. Caldora penicillata

A bioactivity guided study of a cf. Caldora penicillata species, collected during a 2013 expedition to the Pacific island of Saipan, Northern Mariana Islands (a commonwealth of the USA), led to the isolation of a new thiazoline-containing alkaloid, laucysteinamide A (1). Laucysteinamide A is a new monomeric analogue of the marine cyanobacterial metabolite, somocystinamide A (2), a disulfide-bonded dimeric compound that was isolated previously from a Fijian marine cyanobacterium. The structure and absolute configuration of laucysteinamide A (1) was determined by a detailed analysis of its NMR, MS, and CD spectra. In addition, the highly bioactive lipid, curacin D (3), was also found to be present in this cyanobacterial extract. The latter compound was responsible for the potent cytotoxicity of this extract to H-460 human non-small cell lung cancer cells in vitro