Structure solution of metal-oxide Li battery cathodes from simulated annealing and lithium NMR spectroscopy

Discerning the arrangement of transition metal atoms in Li­[Ni_<i>x</i>Mn_<i>y</i>Co_<i>z</i>]­O₂ cathode materials has remained an open problem for many years despite the commercial importance of some stoichiometries and the even more promising characteristics of others. We present a method for structural determination in this class of cathode materials. A simple definition of the total energy, based on the chemical principle of electroneutrality, is used in combination with a simulated annealing algorithm to generate model structures. The method reproduces the well-known structure of Li­[Li_1/3Mn_2/3]­O₂ and produces structures of the disordered Li­[Ni_<i>x</i>Mn_<i>x</i>Co_{1–2<i>x</i>}]­O₂ phases (where <i>x</i> = 0.02, 0.1, 0.33) that are verified by detailed ⁷Li NMR spectra. For each Li­[Ni_<i>x</i>Mn_<i>x</i>Co_{1–2<i>x</i>}]­O₂ phase, the solution is found to be heavily disordered, yet retaining significant ion pairing. Since the underlying notion of favoring charge-neutral regions is generic, we anticipate its utility in a much broader family of materials

Assessment of Spectral Doppler in Preclinical Ultrasound Using a Small-Size Rotating Phantom

Preclinical ultrasound scanners are used to measure blood flow in small animals, but the potential errors in blood velocity measurements have not been quantified. This investigation rectifies this omission through the design and use of phantoms and evaluation of measurement errors for a preclinical ultrasound system (Vevo 770, Visualsonics, Toronto, ON, Canada). A ray model of geometric spectral broadening was used to predict velocity errors. A small-scale rotating phantom, made from tissue-mimicking material, was developed. True and Doppler-measured maximum velocities of the moving targets were compared over a range of angles from 10° to 80°. Results indicate that the maximum velocity was overestimated by up to 158% by spectral Doppler. There was good agreement (50%). The phantom is capable of validating the performance of blood velocity measurement in preclinical ultrasound

Uninterrupted CAG repeat drives striatum-selective transcriptionopathy and nuclear pathogenesis in human Huntingtin BAC mice

In Huntington's disease (HD), the uninterrupted CAG repeat length, but not the polyglutamine length, predicts disease onset. However, the underlying pathobiology remains unclear. Here, we developed bacterial artificial chromosome (BAC) transgenic mice expressing human mutant huntingtin (mHTT) with uninterrupted, and somatically unstable, CAG repeats that exhibit progressive disease-related phenotypes. Unlike prior mHTT transgenic models with stable, CAA-interrupted, polyglutamine-encoding repeats, BAC-CAG mice show robust striatum-selective nuclear inclusions and transcriptional dysregulation resembling those in murine huntingtin knockin models and HD patients. Importantly, the striatal transcriptionopathy in HD models is significantly correlated with their uninterrupted CAG repeat length but not polyglutamine length. Finally, among the pathogenic entities originating from mHTT genomic transgenes and only present or enriched in the uninterrupted CAG repeat model, somatic CAG repeat instability and nuclear mHTT aggregation are best correlated with early-onset striatum-selective molecular pathogenesis and locomotor and sleep deficits, while repeat RNA-associated pathologies and repeat-associated non-AUG (RAN) translation may play less selective or late pathogenic roles, respectively

Nemitin, a Novel Map8/Map1s Interacting Protein with Wd40 Repeats

In neurons, a highly regulated microtubule cytoskeleton is essential for many cellular functions. These include axonal transport, regional specialization and synaptic function. Given the critical roles of microtubule-associated proteins (MAPs) in maintaining and regulating microtubule stability and dynamics, we sought to understand how this regulation is achieved. Here, we identify a novel LisH/WD40 repeat protein, tentatively named nemitin (neuronal enriched MAP interacting protein), as a potential regulator of MAP8-associated microtubule function. Based on expression at both the mRNA and protein levels, nemitin is enriched in the nervous system. Its protein expression is detected as early as embryonic day 11 and continues through adulthood. Interestingly, when expressed in non-neuronal cells, nemitin displays a diffuse pattern with puncta, although at the ultrastructural level it localizes along the microtubule network in vivo in sciatic nerves. These results suggest that the association of nemitin to microtubules may require an intermediary protein. Indeed, co-expression of nemitin with microtubule-associated protein 8 (MAP8) results in nemitin losing its diffuse pattern, instead decorating microtubules uniformly along with MAP8. Together, these results imply that nemitin may play an important role in regulating the neuronal cytoskeleton through an interaction with MAP8

Small RNA combination therapy for lung cancer

MicroRNAs (miRNAs) and siRNAs have enormous potential as cancer therapeutics, but their effective delivery to most solid tumors has been difficult. Here, we show that a new lung-targeting nanoparticle is capable of delivering miRNA mimics and siRNAs to lung adenocarcinoma cells in vitro and to tumors in a genetically engineered mouse model of lung cancer based on activation of oncogenic Kirsten rat sarcoma viral oncogene homolog (Kras) and loss of p53 function. Therapeutic delivery of miR-34a, a p53-regulated tumor suppressor miRNA, restored miR-34a levels in lung tumors, specifically down-regulated miR-34a target genes, and slowed tumor growth. The delivery of siRNAs targeting Kras reduced Kras gene expression and MAPK signaling, increased apoptosis, and inhibited tumor growth. The combination of miR-34a and siRNA targeting Kras improved therapeutic responses over those observed with either small RNA alone, leading to tumor regression. Furthermore, nanoparticle-mediated small RNA delivery plus conventional, cisplatin-based chemotherapy prolonged survival in this model compared with chemotherapy alone. These findings demonstrate that RNA combination therapy is possible in an autochthonous model of lung cancer and provide preclinical support for the use of small RNA therapies in patients who have cancer.National Cancer Institute (U.S.) (Cancer Center Support (Core) Grant P30-CA14051)National Institutes of Health (U.S.) (Grant 2-PO1-CA42063)National Institutes of Health (U.S.) (Grant RO1-EB000244)National Institutes of Health (U.S.) (Grant RO1-CA115527)National Institutes of Health (U.S.) (Grant RO1-CA132091)National Cancer Institute (U.S.) (1K99CA169512)American Association for Cancer Research (Fellowship)Leukemia & Lymphoma Society of America (Fellowship)National Science Foundation (U.S.). Graduate Research Fellowship ProgramMassachusetts Institute of Technology. Presidential FellowshipUnited States. Dept. of Defense (National Defense Science and Engineering Graduate Fellowship

Near-Infrared Imaging Polarimetry of Inner Region of GG Tau A Disk

By performing non-masked polarization imaging with Subaru/HiCIAO, polarized scattered light from the inner region of the disk around the GG Tau A system was successfully detected in the $H$ band with a spatial resolution of approximately 0.07\arcsec, revealing the complicated inner disk structures around this young binary. This paper reports the observation of an arc-like structure to the north of GG Tau Ab and part of a circumstellar structure that is noticeable around GG Tau Aa extending to a distance of approximately 28 AU from the primary star. The speckle noise around GG Tau Ab constrains its disk radius to <13 AU. Based on the size of the circumbinary ring and the circumstellar disk around GG Tau Aa, the semi-major axis of the binary's orbit is likely to be 62 AU. A comparison of the present observations with previous ALMA and near-infrared (NIR) H$_2$ emission observations suggests that the north arc could be part of a large streamer flowing from the circumbinary ring to sustain the circumstellar disks. According to the previous studies, the circumstellar disk around GG Tau Aa has enough mass and can sustain itself for a duration sufficient for planet formation; thus, our study indicates that planets can form within close (separation $\lesssim$ 100 AU) young binary systems.Comment: Accepted for publication in AJ, 12 pages, 5 figure

Subaru/HiCIAO HKsHK_{\rm s} imaging of LkHα\alpha 330 - multi-band detection of the gap and spiral-like structures

We present $H$- and $K_{\rm s}$-bands observations of the LkH$\alpha$ 330 disk with a multi-band detection of the large gap and spiral-like structures. The morphology of the outer disk ($r\sim$0\farcs3) at PA=0--45$^\circ$ and PA=180--290$^\circ$ are likely density wave-induced spirals and comparison between our observational results and simulations suggests a planet formation. We have also investigated the azimuthal profiles at the ring and the outer-disk regions as well as radial profiles in the directions of the spiral-like structures and semi-major axis. Azimuthal analysis shows a large variety in wavelength and implies that the disk has non-axisymmetric dust distributions. The radial profiles in the major-axis direction (PA=$271^\circ$) suggest that the outer region (r\geq0\farcs25) may be influenced by shadows of the inner region of the disk. The spiral-like directions (PA=10$^\circ$ and 230$^\circ$) show different radial profiles, which suggests that the surfaces of the spiral-like structures are highly flared and/or have different dust properties. Finally, a color-map of the disk shows a lack of an outer eastern region in the $H$-band disk, which may hint the presence of an inner object that casts a directional shadow onto the disk.Comment: 12pages, 16 figures, 2 tables, accepted for publication in A

Cosmological Constraints from the Clustering of the Sloan Digital Sky Survey DR7 Luminous Red Galaxies

We present the power spectrum of the reconstructed halo density field derived from a sample of Luminous Red Galaxies (LRGs) from the Sloan Digital Sky Survey Seventh Data Release (DR7). The halo power spectrum has a direct connection to the underlying dark matter power for k <= 0.2 h/Mpc, well into the quasi-linear regime. This enables us to use a factor of ~8 more modes in the cosmological analysis than an analysis with kmax = 0.1 h/Mpc, as was adopted in the SDSS team analysis of the DR4 LRG sample (Tegmark et al. 2006). The observed halo power spectrum for 0.02 < k < 0.2 h/Mpc is well-fit by our model: chi^2 = 39.6 for 40 degrees of freedom for the best fit LCDM model. We find \Omega_m h^2 * (n_s/0.96)^0.13 = 0.141^{+0.009}_{-0.012} for a power law primordial power spectrum with spectral index n_s and \Omega_b h^2 = 0.02265 fixed, consistent with CMB measurements. The halo power spectrum also constrains the ratio of the comoving sound horizon at the baryon-drag epoch to an effective distance to z=0.35: r_s/D_V(0.35) = 0.1097^{+0.0039}_{-0.0042}. Combining the halo power spectrum measurement with the WMAP 5 year results, for the flat LCDM model we find \Omega_m = 0.289 +/- 0.019 and H_0 = 69.4 +/- 1.6 km/s/Mpc. Allowing for massive neutrinos in LCDM, we find \sum m_{\nu} < 0.62 eV at the 95% confidence level. If we instead consider the effective number of relativistic species Neff as a free parameter, we find Neff = 4.8^{+1.8}_{-1.7}. Combining also with the Kowalski et al. (2008) supernova sample, we find \Omega_{tot} = 1.011 +/- 0.009 and w = -0.99 +/- 0.11 for an open cosmology with constant dark energy equation of state w.Comment: 26 pages, 19 figures, submitted to MNRAS. The power spectrum and a module to calculate the likelihoods is publicly available at http://lambda.gsfc.nasa.gov/toolbox/lrgdr/ . v2 fixes abstract formatting issu

Pulmonary Delivery of Proteins Using Nanocomposite Microcarriers.

In this study, Taguchi design was used to determine optimal parameters for the preparation of bovine serum albumin (BSA)-loaded nanoparticles (NPs) using a biodegradable polymer poly(glycerol adipate-co-ω-pentadecalactone) (PGA-co-PDL). NPs were prepared, using BSA as a model protein, by the double emulsion evaporation process followed by spray-drying from leucine to form nanocomposite microparticles (NCMPs). The effect of various parameters on NP size and BSA loading were investigated and dendritic cell (DC) uptake and toxicity. NCMPs were examined for their morphology, yield, aerosolisation, in vitro release behaviour and BSA structure. NP size was mainly affected by the polymer mass used and a small particle size ≤500 nm was achieved. High BSA (43.67 ± 2.3 μg/mg) loading was influenced by BSA concentration. The spray-drying process produced NCMPs (50% yield) with a porous corrugated surface, aerodynamic diameter 1.46 ± 141 μm, fine particle dose 45.0 ± 4.7 μg and fine particle fraction 78.57 ± 0.1%, and a cumulative BSA release of 38.77 ± 3.0% after 48 h. The primary and secondary structures were maintained as shown by sodium dodecyl sulphate poly (acrylamide) gel electrophoresis and circular dichroism. Effective uptake of NPs was seen in DCs with >85% cell viability at 5 mg/mL concentration after 4 h. These results indicate the optimal process parameters for the preparation of protein-loaded PGA-co-PDL NCMPs suitable for inhalation. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci