1/f spectrum and memory function analysis of solvation dynamics in a room-temperature ionic liquid

To understand the non-exponential relaxation associated with solvation dynamics in the ionic liquid 1-ethyl-3-methylimidazolium hexafluorophosphate, we study power spectra of the fluctuating Franck-Condon energy gap of a diatomic probe solute via molecular dynamics simulations. Results show 1/f dependence in a wide frequency range over 2 to 3 decades, indicating distributed relaxation times. We analyze the memory function and solvation time in the framework of the generalized Langevin equation using a simple model description for the power spectrum. It is found that the crossover frequency toward the white noise plateau is directly related to the time scale for the memory function and thus the solvation time. Specifically, the low crossover frequency observed in the ionic liquid leads to a slowly-decaying tail in its memory function and long solvation time. By contrast, acetonitrile characterized by a high crossover frequency and (near) absence of 1/f behavior in its power spectra shows fast relaxation of the memory function and single-exponential decay of solvation dynamics in the long-time regime.Comment: 10 pages, 4 figure

\u3cem\u3eStreptococcus agalactiae \u3c/em\u3eStrains with Chromosomal Deletions Evade Detection with Molecular Methods

Surveillance of circulating microbial populations is critical for monitoring the performance of a molecular diagnostic test. In this study, we characterized 31 isolates of Streptococcus agalactiae (group B Streptococcus [GBS]) from several geographic locations in the United States and Ireland that contain deletions in or adjacent to the region of the chromosome that encodes the hemolysin gene cfb, the region targeted by the Xpert GBS and GBS LB assays. PCR-negative, culture-positive isolates were recognized during verification studies of the Xpert GBS assay in 12 laboratories between 2012 and 2018. Whole-genome sequencing of 15 GBS isolates from 11 laboratories revealed four unique deletions of chromosomal DNA ranging from 181 bp to 49 kb. Prospective surveillance studies demonstrated that the prevalence of GBS isolates containing deletions in the convenience sample wa

Integrin alpha V beta 3 targeted dendrimer‐rapamycin conjugate reduces fibroblast‐mediated prostate tumor progression and metastasis

Therapeutic strategies targeting both cancer cells and associated cells in the tumor microenvironment offer significant promise in cancer therapy. We previously reported that generation 5 (G5) dendrimers conjugated with cyclic‐RGD peptides target cells expressing integrin alpha V beta 3. In this study, we report a novel dendrimer conjugate modified to deliver the mammalian target of rapamycin (mTOR) inhibitor, rapamycin. In vitro analyses demonstrated that this drug conjugate, G5‐FI‐RGD‐rapamycin, binds to prostate cancer (PCa) cells and fibroblasts to inhibit mTOR signaling and VEGF expression. In addition, G5‐FI‐RGD‐rapamycin inhibits mTOR signaling in cancer cells more efficiently under proinflammatory conditions compared to free rapamycin. In vivo studies established that G5‐FI‐RGD‐rapamycin significantly inhibits fibroblast‐mediated PCa progression and metastasis. Thus, our results suggest the potential of new rapamycin‐conjugated multifunctional nanoparticles for PCa therapy.Here, we synthesized and characterized a novel dendrimer conjugate, G5‐FI‐RGD‐rapamycin. Multifunctional G5‐FI‐RGD‐rapamycin binds to PCa and fibroblasts via alpha V beta 3 integrin and significantly inhibits mTOR signaling and VEGF expression. These in vitro data were confirmed by in vivo data that G5‐FI‐RGD‐rapamycin inhibits fibroblast‐mediated PCa progression and metastasis.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146470/1/jcb26727.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146470/2/jcb26727_am.pd

GX 339-4: the distance, state transitions, hysteresis and spectral correlations

We study X-ray and variability and distance of GX 339-4. We derive d>7 kpc, based on recent determination of the binary parameters. We study data from the Ginga/ASM, the CGRO/BATSE, and the RXTE/ASM, PCA and HEXTE. From 1987 to 2004, GX 339-4 underwent 15 outbursts and went through all known states of black-hole binaries. We also present the PCA data from the initial stage of the 2004 outburst. We then study colour-colour and colour-flux correlations. In the hard state, there is a strong anticorrelation between the 1.5-5 and 3-12 keV spectral slopes, which we explain by thermal Comptonization of disc photons. There is also a softening of the spectrum above 3 keV with the increasing flux that becomes stronger with increasing energy up to 200 keV. This indicates an anticorrelation between the electron temperature and luminosity, explained by hot accretion models. In addition, we see a variable broad-band slope with a pivot at 200 keV. We confirm the presence of pronounced hysteresis, with the hard-to-soft state transitions occurring at much higher (and variable) luminosities than the soft-to-hard transitions. We fit the ASM data with a model consisting of an outer accretion disc and a hot inner flow. State transitions are associated then with variations in the disc truncation radius, which we fit as 6GM/c^2 in the soft state and several times that in the hard state. The disappearence of the inner disc takes place at a lower accretion rate than its initial appearance due to the dependence of the transitions on the source history. We provide further evidence against the X-ray emission in the hard state being nonthermal synchrotron, and explain the observed radio-X-ray correlation by the jet power being correlated with the accretion power.Comment: MNRAS, in press (a substantially revised version, including new data from the Feb. 2004 outburst of GX 339-4

Quantum dynamics in strong fluctuating fields

A large number of multifaceted quantum transport processes in molecular systems and physical nanosystems can be treated in terms of quantum relaxation processes which couple to one or several fluctuating environments. A thermal equilibrium environment can conveniently be modelled by a thermal bath of harmonic oscillators. An archetype situation provides a two-state dissipative quantum dynamics, commonly known under the label of a spin-boson dynamics. An interesting and nontrivial physical situation emerges, however, when the quantum dynamics evolves far away from thermal equilibrium. This occurs, for example, when a charge transferring medium possesses nonequilibrium degrees of freedom, or when a strong time-dependent control field is applied externally. Accordingly, certain parameters of underlying quantum subsystem acquire stochastic character. Herein, we review the general theoretical framework which is based on the method of projector operators, yielding the quantum master equations for systems that are exposed to strong external fields. This allows one to investigate on a common basis the influence of nonequilibrium fluctuations and periodic electrical fields on quantum transport processes. Most importantly, such strong fluctuating fields induce a whole variety of nonlinear and nonequilibrium phenomena. A characteristic feature of such dynamics is the absence of thermal (quantum) detailed balance.Comment: review article, Advances in Physics (2005), in pres

Translation of myelin basic protein mRNA in oligodendrocytes is regulated by integrin activation and hnRNP-K

α6β1-integrin interacts with hnRNP-K, an mRNA-binding protein, during oligodendrocyte differentiation to promote translation of MBP mRNA and myelin synthesis

Comparison of microfluidic digital PCR and conventional quantitative PCR for measuring copy number variation

One of the benefits of Digital PCR (dPCR) is the potential for unparalleled precision enabling smaller fold change measurements. An example of an assessment that could benefit from such improved precision is the measurement of tumour-associated copy number variation (CNV) in the cell free DNA (cfDNA) fraction of patient blood plasma. To investigate the potential precision of dPCR and compare it with the established technique of quantitative PCR (qPCR), we used breast cancer cell lines to investigate HER2 gene amplification and modelled a range of different CNVs. We showed that, with equal experimental replication, dPCR could measure a smaller CNV than qPCR. As dPCR precision is directly dependent upon both the number of replicate measurements and the template concentration, we also developed a method to assist the design of dPCR experiments for measuring CNV. Using an existing model (based on Poisson and binomial distributions) to derive an expression for the variance inherent in dPCR, we produced a power calculation to define the experimental size required to reliably detect a given fold change at a given template concentration. This work will facilitate any future translation of dPCR to key diagnostic applications, such as cancer diagnostics and analysis of cfDNA

Low-fouling, mixed-charge poly-L-lysine polymers with anionic oligopeptide side-chains

Biosensors and biomedical devices require antifouling surfaces to prevent the non-specific adhesion of proteins or cells, for example, when aiming to detect circulating cancer biomarkers in complex natural media (e.g., in blood plasma or serum). A mixed-charge polymer was prepared by the coupling of a cationic polyelectrolyte and an anionic oligopeptide through a modified 'grafting-to' method. The poly-L-lysine (PLL) backbone was modified with different percentages (y%) of maleimide-NHS ester chains (PLL-mal(y%), from 13% to 26%), to produce cationic polymers with specific grafting densities, obtaining a mixed-charge polymer. The anionic oligopeptide structure (CEEEEE) included one cysteine (C) and five glutamic acid (E) units, which were attached to the PLL-mal(y%) polymers, preadsorbed on gold substrates, through the thiol-maleimide Michael-type addition. Contact angle and PM-IRRAS data confirmed monolayer formation of the modified PLLs. Antifouling properties of peptide-PLL surfaces were assessed in adsorption studies using quartz crystal microbalance with dissipation (QCM-D) and surface plasmon resonance imaging (SPRI) techniques. PLL-mal(26%)-CEEEEE showed the best antifouling performance in single-protein solutions, and the nonspecific adsorption of proteins was 46 ng cm−2 using diluted human plasma samples. The new PLL-mal(26%)-CEEEEE polymer offers a prominent low-fouling activity in complex media, with rapid and simple procedures for the synthesis and functionalization of the surface compared to conventional non-fouling materials

SIRT1 Promotes N-Myc Oncogenesis through a Positive Feedback Loop Involving the Effects of MKP3 and ERK on N-Myc Protein Stability

The N-Myc oncoprotein is a critical factor in neuroblastoma tumorigenesis which requires additional mechanisms converting a low-level to a high-level N-Myc expression. N-Myc protein is stabilized when phosphorylated at Serine 62 by phosphorylated ERK protein. Here we describe a novel positive feedback loop whereby N-Myc directly induced the transcription of the class III histone deacetylase SIRT1, which in turn increased N-Myc protein stability. SIRT1 binds to Myc Box I domain of N-Myc protein to form a novel transcriptional repressor complex at gene promoter of mitogen-activated protein kinase phosphatase 3 (MKP3), leading to transcriptional repression of MKP3, ERK protein phosphorylation, N-Myc protein phosphorylation at Serine 62, and N-Myc protein stabilization. Importantly, SIRT1 was up-regulated, MKP3 down-regulated, in pre-cancerous cells, and preventative treatment with the SIRT1 inhibitor Cambinol reduced tumorigenesis in TH-MYCN transgenic mice. Our data demonstrate the important roles of SIRT1 in N-Myc oncogenesis and SIRT1 inhibitors in the prevention and therapy of N-Myc–induced neuroblastoma