POLYORGANOSILOXANES: MOLECULAR NANOPARTICLES, NANOCOMPOSITES AND INTERFACES

Five research projects described. First, a reproducible, lab-scale synthesis of MQ silicone copolymers is presented. MQ copolymers are commercially important materials that have been ignored by the academic community. One possible reason for this is the difficulty of controlling and reproducing the preparative copolymerizations that have been reported. A reproducible method for lab-scale preparation was developed that controls molecular weight by splitting the copolymerization into the discrete steps of sol growth from silicate precursor and end-capping by trimethylsiloxy groups. Characterization of MQ products implicates that they are composed of highly condensed, polycyclic structures. The MQ copolymers prepared in the first project were observed to form tenacious emulsions and foams. This was an obvious indication of surface activity and led to further investigation. No open literature reports any measurements of MQ copolymers at interfaces. In this second project, selected MQ structures were studied at three interfaces: the air-water interface, the oil-water interface and the solid-air interface of supported MQ monolayers. The qualitative surface activity of MQ is confirmed and quantified. Residual silanols are found to be responsible for surfactantcy in MQ copolymers. The third and fourth projects encompass research in Silicone-CNT composites. The first part of this work describes the ease with which CNTs can be dispersed into silicone matrices. Changes in silicone chemistry can improve CNT dispersion resulting in improved conductivities and mechanical reinforcement at CNT loadings of only fractions of a weight percent. The second portion of work on nanocomposites involves the discovery and investigation of the dramatic increase in thermal stability of silicone elastomers containing CNTs. Thermogravimetric analysis and pyrolysis gas chromatography-mass spectrometry indicate that the CNT network constrains silicone polymer chains and alters the mechanisms of decomposition. The last project uses the Piers-Rubinsztajn reaction to rapidly and cleanly modify silicon oxide surfaces. This reaction has been studied very little as a method to modify surfaces and there has yet to be any work that measures dynamic contact angles on smooth surfaces. Trialkylsilane and methylsiloxane monolayers were prepared and analyzed. Monolayer densities are low in this reaction and result in anomalously low contact angle hysteresis for alkylsilane monolayers. Wetting properties in precise methylsiloxane polymer monolayers are shown to depend on graft structure. Dynamic contact lines from the liquid-like mobility of these grafts results in low contact angle hysteresis

Distribution and diel vertical movements of mesopelagic scattering layers in the Red Sea

© The Author(s), 2012. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Marine Biology 159 (2012): 1833-1841, doi:10.1007/s00227-012-1973-y.The mesopelagic zone of the Red Sea represents an extreme environment due to low food concentrations, high temperatures and low oxygen waters. Nevertheless, a 38 kHz echosounder identified at least four distinct scattering layers during the daytime, of which the 2 deepest layers resided entirely within the mesopelagic zone. Two of the acoustic layers were found above a mesopelagic oxygen minimum zone (OMZ), one layer overlapped with the OMZ, and one layer was found below the OMZ. Almost all organisms in the deep layers migrated to the near-surface waters during the night. Backscatter from a 300 kHz lowered Acoustic Doppler Current Profiler indicated a layer of zooplankton within the OMZ. They carried out DVM, yet a portion remained at mesopelagic depths during the night. Our acoustic measurements showed that the bulk of the acoustic backscatter was restricted to waters shallower than 800 m, suggesting that most of the biomass in the Red Sea resides above this depth.This research is based in part on work supported by Award Nos. USA 00002, KSA 00011 and KSA 00011/02 made by KAUST to the Woods Hole Oceanographic Institution

Early Release Science of the Exoplanet WASP-39b with JWST NIRSpec G395H

Measuring the abundances of carbon and oxygen in exoplanet atmospheres is considered a crucial avenue for unlocking the formation and evolution of exoplanetary systems. Access to an exoplanet's chemical inventory requires high-precision observations, often inferred from individual molecular detections with low-resolution space-based and high-resolution ground-based facilities. Here we report the medium-resolution (R$\sim$600) transmission spectrum of an exoplanet atmosphere between 3-5 $\mu$m covering multiple absorption features for the Saturn-mass exoplanet WASP-39b, obtained with JWST NIRSpec G395H. Our observations achieve 1.46x photon precision, providing an average transit depth uncertainty of 221 ppm per spectroscopic bin, and present minimal impacts from systematic effects. We detect significant absorption from CO$_2$ (28.5$\sigma$) and H$_2$O (21.5$\sigma$), and identify SO$_2$ as the source of absorption at 4.1 $\mu$m (4.8$\sigma$). Best-fit atmospheric models range between 3 and 10x solar metallicity, with sub-solar to solar C/O ratios. These results, including the detection of SO$_2$, underscore the importance of characterising the chemistry in exoplanet atmospheres, and showcase NIRSpec G395H as an excellent mode for time series observations over this critical wavelength range.Comment: 44 pages, 11 figures, 3 tables. Resubmitted after revision to Natur

A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants.

This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.3448Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, with limited therapeutic options. Here we report on a study of >12 million variants, including 163,714 directly genotyped, mostly rare, protein-altering variants. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P < 5 × 10(-8)) distributed across 34 loci. Although wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first genetic association signal specific to wet AMD, near MMP9 (difference P value = 4.1 × 10(-10)). Very rare coding variants (frequency <0.1%) in CFH, CFI and TIMP3 suggest causal roles for these genes, as does a splice variant in SLC16A8. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.We thank all participants of all the studies included for enabling this research by their participation in these studies. Computer resources for this project have been provided by the high-performance computing centers of the University of Michigan and the University of Regensburg. Group-specific acknowledgments can be found in the Supplementary Note. The Center for Inherited Diseases Research (CIDR) Program contract number is HHSN268201200008I. This and the main consortium work were predominantly funded by 1X01HG006934-01 to G.R.A. and R01 EY022310 to J.L.H

Early Release Science of the exoplanet WASP-39b with JWST NIRCam

Measuring the metallicity and carbon-to-oxygen (C/O) ratio in exoplanet atmospheres is a fundamental step towards constraining the dominant chemical processes at work and, if in equilibrium, revealing planet formation histories. Transmission spectroscopy provides the necessary means by constraining the abundances of oxygen- and carbon-bearing species; however, this requires broad wavelength coverage, moderate spectral resolution, and high precision that, together, are not achievable with previous observatories. Now that JWST has commenced science operations, we are able to observe exoplanets at previously uncharted wavelengths and spectral resolutions. Here we report time-series observations of the transiting exoplanet WASP-39b using JWST's Near InfraRed Camera (NIRCam). The long-wavelength spectroscopic and short-wavelength photometric light curves span 2.0 - 4.0 $\mu$m, exhibit minimal systematics, and reveal well-defined molecular absorption features in the planet's spectrum. Specifically, we detect gaseous H$_2$O in the atmosphere and place an upper limit on the abundance of CH$_4$. The otherwise prominent CO$_2$ feature at 2.8 $\mu$m is largely masked by H$_2$O. The best-fit chemical equilibrium models favour an atmospheric metallicity of 1-100$\times$ solar (i.e., an enrichment of elements heavier than helium relative to the Sun) and a sub-stellar carbon-to-oxygen (C/O) ratio. The inferred high metallicity and low C/O ratio may indicate significant accretion of solid materials during planet formation or disequilibrium processes in the upper atmosphere.Comment: 35 pages, 13 figures, 3 tables, Nature, accepte

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Rapid and Clean Covalent Attachment of Methylsiloxane Polymers and Oligomers to Silica Using B(C₆F₅)₃ Catalysis

The rapid, room-temperature covalent attachment of alkylhydridosilanes (R₃Si–H) to silicon oxide surfaces to form monolayers using tris­(pentafluorophenyl)­borane (B­(C₆F₅)₃, BCF) catalysis has recently been described. This method, unlike alternative routes to monolayers, produces only unreactive H₂ gas as a byproduct and reaches completion within minutes. We report the use of this selective reaction between surface silanols and hydridosilanes to prepare surface-grafted poly­(dimethylsiloxane)­s (PDMSs) with various graft architectures that are controlled by the placement of hydridosilane functionality at one end, both ends, or along the chain of PDMS samples of controlled molecular weight. We also report studies of model methylsiloxane monolayers prepared from pentamethyldisiloxane, heptamethyltrisiloxane (two isomers), heptamethylcyclotetrasiloxane, and tris­(trimethylsiloxy)­silane. These modified silica surfaces with structurally defined methylsiloxane groups are not accessible by conventional silane surface chemistry and proved to be useful in exploring the steric limitations of the reaction. Linear monohydride- and dihydride-terminated PDMS-grafted surfaces exhibit increasing thickness and decreasing contact angle hysteresis with increasing molecular weight up to a particular molecular weight value. Above this value, the hysteresis increases with increasing molecular weight of end-grafted polymers. Poly­(hydridomethyl-<i>co</i>-dimethylsiloxane)­s with varied hydride content (3–100 mol %) exhibit decreasing thickness, decreasing contact angle, and increasing contact angle hysteresis with increasing hydride content. These observations illustrate the importance of molecular mobility in three-phase contact line dynamics on low-hysteresis surfaces. To calibrate our preparative procedure against both monolayers prepared by conventional approaches as well as the recent reports, a series of trialkylsilane (mostly, <i>n</i>-alkyldimethylsilane) monolayers was prepared to determine the reaction time required to achieve the maximum bonding density using dynamic contact angle analysis. Monolayers prepared from hydridosilanes with BCF catalysis have lower bonding densities than those derived from chlorosilanes, and the reactions are more sensitive to alkyl group sterics. This lower bonding density renders greater flexibility to the <i>n</i>-alkyl groups in monolayers and can decrease the contact angle hysteresis

Rediscovering Silicones: MQ Copolymers

Organic solvent-soluble trimethylsiloxysilicate polymers (MQ copolymers) were prepared with controlled molecular weight using kinetically controlled, sulfuric acid-catalyzed, hydrolysis/condensation reactions of tetraethoxysilane (TEOS, tetraethyl orthosilicate) and subsequent (end-capping) reactions with hexamethyl­disiloxane. We have simplified what is a complex, variable-dependent, industrial preparative procedure that involves competitive sol growth and end-capping reactions to one that separates these reactions into discrete steps and can be carried out with control in a common academic lab. These MQ copolymers are model compounds of commercial MQ resins that are important commodity materials with unique impact in a range of applications. Although they are recognized for their broad utility, they are not widely appreciated as (or even considered) unusual molecules with special structures and properties. The number-average molecular weight of the copolymers reported here can be controlled from ∼2000 to ∼15 000 g/mol and their composition is ∼70 mol % silica (Q), yet they are readily soluble in hydrocarbon solvents and liquid silicones. In addition to reporting a synthetic procedure, we make comments and conjectures concerning their polycyclic molecular structures based on their characterization using IR, ¹H, ²⁹Si, and diffusion NMR, dynamic light scattering, gel permeation chromatography, and transmission electron microscopy. Derivatives of these materials that contain vinyl­dimethylsilyl- and hydrido­dimethylsilyl-M units were prepared with the objectives of demonstrating that our synthetic approach is chemically versatile and preparing MQ copolymers that are reactive toward hydrosilylation. We expect that these inorganic/organic hybrid materials, which could be termed “molecular nanoparticles”, could serve as a platform upon which chemical derivatization will permit rational implementation in a wider range of applications and technologies than is currently served by commercial MQ resins

Lanosterol reverses protein aggregation in cataracts

The human lens is comprised largely of crystallin proteins assembled into a highly ordered, interactive macro-structure essential for lens transparency and refractive index. Any disruption of intra- or inter-protein interactions will alter this delicate structure, exposing hydrophobic surfaces, with consequent protein aggregation and cataract formation. Cataracts are the most common cause of blindness worldwide, affecting tens of millions of people1, and currently the only treatment is surgical removal of cataractous lenses. The precise mechanisms by which lens proteins both prevent aggregation and maintain lens transparency are largely unknown. Lanosterol is an amphipathic molecule enriched in the lens. It is synthesized by lanosterol synthase (LSS) in a key cyclization reaction of a cholesterol synthesis pathway. Here we identify two distinct homozygous LSS missense mutations (W581R and G588S) in two families with extensive congenital cataracts. Both of these mutations affect highly conserved amino acid residues and impair key catalytic functions of LSS. Engineered expression of wild-type, but not mutant, LSS prevents intracellular protein aggregation of various cataract-causing mutant crystallins. Treatment by lanosterol, but not cholesterol, significantly decreased preformed protein aggregates both in vitro and in cell-transfection experiments. We further show that lanosterol treatment could reduce cataract severity and increase transparency in dissected rabbit cataractous lenses in vitro and cataract severity in vivo in dogs. Our study identifies lanosterol as a key molecule in the prevention of lens protein aggregation and points to a novel strategy for cataract prevention and treatment