Azomethine derivatives of some metals and metalloids

This thesis describes the preparation of some methyleneamino derivatives of beryllium, zinc, gallium and silicon. The structural, implications of their infra-red spectra and nuclear magnetic resonance spectra are discussed. As a background to the work, the characteristics of such compounds are discussed in the Introduction, and in greater detail in each chapter. Di-t-butylmethyleneaminolithium reacts with beryllium chloride giving dimeric di-t-butylmethyleneaminoberyllium chloride, (Bu(^t)(_2)C:NBeCl)(_2), and the lithium beryllates Li(_n)Be(N:CBu(^t)(_2))(_2+n) (n = 1,2). Bis(di-t-butylmethyl-eneamino)beryllium, [(Bu(^t)(_2)C:N)(_2)Be](_2) was inaccessible by this route but was prepared by reacting di-t-butylmethyleneamine with di-isobutylberyllium (2:1). The crystal structure of this compound shows that the terminal CNBe unit is nearly linear and that the Be-N bond is relatively short, appropriate for N →Be (p → p) π-bonding. The structure determination supports the postulate that a high azomethine stretching frequency, v(C=N) is indicative of a linear CNBe unit and Be-N multiple bonding. Attempts to prepare adducts with trimethylamine and tetramethylethylene-diamine were unsuccessful. Reaction between methyleneamines and dialkylberylliums afford the derivatives (R(^2)C:NBeR’)(_2) (R = Bu(^2), Ph; R' = Bu(^i) and R = Ph; R' = Bu(^t)). A new monomeric compound, di-t-butylmethyleneamino-bis(trimethylsilyl)-aminoberyllium, Bu(^t)(_2)C:NBeN(SiMe(_3))(_2) was prepared and characterised. Reactions of zinc chloride with one or two moles of di-t-butylmethyl-eneaminolithium give dimeric iminozinc compounds, (Bu(^t)(_2)C:NZnCl)(_2) and [(Bu(^t)(_2)C:N)(_2)Zn](_2). A high azomethine stretching frequency in the latter compound is attributed to significant pπpπ interaction between zinc and nitrogen. Dimethylzinc reacts with one or two moles of di-t-butylmethyl-eneamine giving [(Bu(^t)(_2)CN)(_n)ZnMe(_2-n)])_2) (n = 1,2). Reaction between di-t-butylmethyleneaminolithium and gallium trichloride affords the compounds Li(_n)Ga(N: CBu(^t)(_2))(_3+n) (n = 0,1,2). Bis(di-t-butylmethyleneamino)gallium chloride could not be isolated, presumably through disproportionation to the mono- and tris-derivatives. A high azomethine stretching frequency, v(C=N), for (Bu(^t)(_2)C:N)(_3)Ga, is taken as evidence for a linear C=N-Ga skeleton with appreciable N=Ga π-bonding. The phenyl analogue (Ph(_2)C:N)(_3)Ga was prepared by a similar method. Equimolar proportions of diphenylmethyleneaminolithium and chlorosilanes Me(_n)SiCl(_4-n), (n = 0,1,2) afford the diphenylmethy1eneamino-silanes (Ph(_2)C:N)(_2)-SiM(_n)Cl(_3-n), apparently through disproportionation of the mono-substituted compounds Ph(_2)C:NSiMe(_n)Cl(_3-n), which could only be isolated when n = 2. The spectra of these compounds show that these may have bent C:NSi skeletons. Preliminary investigations into transition metal systems (R(_2)C:N)(_3)M (M = Fe; R = Bu(^t),Ph and M = Cr; R = Bu(^t)) are discussed in an appendix

Coupled Macrospins: Mode Dynamics in Symmetric and Asymmetric Vertices

We report the microwave response of symmetric and asymmetric threefold clusters with nearly contacting segments that can serve as the node in a Kagome artificial spin ice lattice. The structures are patterned on a coplanar waveguide and consist of elongated and nearly-contacting ellipses with uniform thickness. Branches of the ferromagnetic resonance spectra display mode softening that correlates well with the calculations, whereas agreement between the measured and simulated static magnetization is more qualitative

U.S. Army Small Space Update

In December 2010, the U.S. Army flew its first satellite in 50 years, the SMDC-ONE CubeSat. Placed in a very low orbit, the first SMDC-ONE mission lasted only 35 days but enjoyed great success in demonstrating the viability of CubeSats to perform exfiltration of unattended ground sensors data and serve as a communications relay between ground stations over 1000 land miles apart. The success of SMDC-ONE helped shape the U.S. Army’s Space and Missile Defense Command’s (SMDC) programmatic goals for finding new and innovative ways to implement space applications and technologies that aid the warfighter. Since 2010, SMDC has flown ten additional CubeSats including the three SMDC Nanosatellite Program-3 (SNaP) CubeSats currently on orbit (launched October 2015). This paper addresses several SMDC satellite-related development efforts including SNaP, Army Resilient Global On-the-move SATCOM (ARGOS) Ka-band communications microsatellites, Kestrel Eye (an imaging microsatellite), Kestrel Eye Ground Station (KEGS), Common Ground Station (CGS) for all future Army small satellites, supporting technologies including Small Business Innovative Research (SBIR) efforts, the Concepts Analysis Laboratory, SMDC Space Laboratory, the ACES RED effort and earlier responsive launch vehicle activities. Several of the lessons learned from previous as well as ongoing satellite activities are also covered

Rain-induced turbulence and air-sea gas transfer

Author Posting. © American Geophysical Union, 2009. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 114 (2009): C07009, doi:10.1029/2008JC005008.Results from a rain and gas exchange experiment (Bio2 RainX III) at the Biosphere 2 Center demonstrate that turbulence controls the enhancement of the air-sea gas transfer rate (or velocity) k during rainfall, even though profiles of the turbulent dissipation rate ɛ are strongly influenced by near-surface stratification. The gas transfer rate scales with ɛ inline equation for a range of rain rates with broad drop size distributions. The hydrodynamic measurements elucidate the mechanisms responsible for the rain-enhanced k results using SF6 tracer evasion and active controlled flux technique. High-resolution k and turbulence results highlight the causal relationship between rainfall, turbulence, stratification, and air-sea gas exchange. Profiles of ɛ beneath the air-sea interface during rainfall, measured for the first time during a gas exchange experiment, yielded discrete values as high as 10−2 W kg−1. Stratification modifies and traps the turbulence near the surface, affecting the enhancement of the transfer velocity and also diminishing the vertical mixing of mass transported to the air-water interface. Although the kinetic energy flux is an integral measure of the turbulent input to the system during rain events, ɛ is the most robust response to all the modifications and transformations to the turbulent state that follows. The Craig-Banner turbulence model, modified for rain instead of breaking wave turbulence, successfully predicts the near-surface dissipation profile at the onset of the rain event before stratification plays a dominant role. This result is important for predictive modeling of k as it allows inferring the surface value of ɛ fundamental to gas transfer.This work was funded by a generous grant from the David and Lucile Packard Foundation and the Lamont-Doherty Earth Observatory Climate Center. Additional funding was provided by the National Science Foundation (OCE-05-26677) and the Office of Naval Research Young Investigator Program (N00014-04-1-0621)

Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A

The major histocompatibility complex (MHC) on chromosome 6 is associated with susceptibility to more common diseases than any other region of the human genome, including almost all disorders classified as autoimmune. In type 1 diabetes the major genetic susceptibility determinants have been mapped to the MHC class II genes HLA-DQB1 and HLA-DRB1 (refs 1-3), but these genes cannot completely explain the association between type 1 diabetes and the MHC region. Owing to the region's extreme gene density, the multiplicity of disease-associated alleles, strong associations between alleles, limited genotyping capability, and inadequate statistical approaches and sample sizes, which, and how many, loci within the MHC determine susceptibility remains unclear. Here, in several large type 1 diabetes data sets, we analyse a combined total of 1,729 polymorphisms, and apply statistical methods - recursive partitioning and regression - to pinpoint disease susceptibility to the MHC class I genes HLA-B and HLA-A (risk ratios >1.5; Pcombined = 2.01 × 10-19 and 2.35 × 10-13, respectively) in addition to the established associations of the MHC class II genes. Other loci with smaller and/or rarer effects might also be involved, but to find these, future searches must take into account both the HLA class II and class I genes and use even larger samples. Taken together with previous studies, we conclude that MHC-class-I-mediated events, principally involving HLA-B*39, contribute to the aetiology of type 1 diabetes. ©2007 Nature Publishing Group

The genetic architecture of type 2 diabetes

The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of heritability. To test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole genome sequencing in 2,657 Europeans with and without diabetes, and exome sequencing in a total of 12,940 subjects from five ancestral groups. To increase statistical power, we expanded sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support a major role for lower-frequency variants in predisposition to type 2 diabetes

CSF1R inhibitor JNJ-40346527 attenuates microglial proliferation and neurodegeneration in P301S mice

Neuroinflammation and microglial activation are significant processes in Alzheimer’s disease pathology. Recent genome-wide association studies have highlighted multiple immune-related genes in association with Alzheimer’s disease, and experimental data have demonstrated microglial proliferation as a significant component of the neuropathology. In this study, we tested the efficacy of the selective CSF1R inhibitor JNJ-40346527 (JNJ-527) in the P301S mouse tauopathy model. We first demonstrated the anti-proliferative effects of JNJ-527 on microglia in the ME7 prion model, and its impact on the inflammatory profile, and provided potential CNS biomarkers for clinical investigation with the compound, including pharmacokinetic/pharmacodynamics and efficacy assessment by TSPO autoradiography and CSF proteomics. Then, we showed for the first time that blockade of microglial proliferation and modification of microglial phenotype leads to an attenuation of tau-induced neurodegeneration and results in functional improvement in P301S mice. Overall, this work strongly supports the potential for inhibition of CSF1R as a target for the treatment of Alzheimer’s disease and other tau-mediated neurodegenerative diseases