Development and Investigation of NW(OR)3, NMo(OR)3, and Mo2(OR)6 Complexes for Triple-Bond Metathesis.

The application of alkyne metathesis in the development of polymers, pharmaceuticals, natural products, and many other products has surged. In response, an expansion of current catalysts and methods to synthesize the catalysts is desired. This work focuses on the systematic design and development of tungsten and molybdenum-based alkylidyne and nitride complexes for triple-bond metathesis. Nitrile-alkyne cross metathesis (NACM), a new type of metathesis involving the exchange of alkyne and nitrile moieties was developed. NACM activity was found with three tungsten nitride complexes, [N≡W(OCMe2CF3)3]3 (1), N≡W(OCMe¬(CF3)2)3(DME) (2), and [Li(DME)2][N≡W(OCMe(CF3)2)4] (3). Optimization of the NACM conditions including reaction medium, temperature, concentration, and catalyst loading were completed. NACM resulted in a mixture of symmetrical and unsymmetrical alkyne products with 2 favoring the formation of symmetrical alkynes relative to 1. These product ratio differences were accounted for through variances in catalyst resting state during NACM. The selective formation of symmetrical or unsymmetrical alkynes in high yield can be achieved by altering the reaction conditions. Although 2 exhibits greater NACM activity than 1, broader substrate compatibility is found with 2. Catalyst deactivation was substrate-dependent; conversion to alkylidyne complexes prior to deactivation occurring with some substrates. The utility of NACM was illustrated through the synthesis of large arylene-ethynylene macrocycles. Methods to readily synthesize alkylidyne species from N≡Mo(OR)3 and Mo2(OR)6 were developed. The irreversible formation of benzylidyne complexes from N≡Mo(OCMe(CF3)2)3 and N≡Mo(OC(CF3)3)3(MeCN) was achieved. The first evidence for the formation of RC≡Mo(OR)3 complexes (OR=OCMe3, OCMe2CF3, and OCMe(CF3)2) through the interaction of Mo2(OR)6 complexes with internal alkynes was discovered. The first example of the reversible formation of alkylidyne and Mo2(OR)6 species (OR=OCMe3, OCMe2CF3) was also achieved. Extension of the formation of molybdenum alkylidyne complexes from nitride complexes that contain OCMe¬3 and OCMe2CF3 ligands was achieved in situ in the presence of Lewis acids. Attempted isolation of alkylidyne complexes formed in situ was unsuccessful due to decomposition of the formed alkylidyne species in the presence of the Lewis acid. Several simple Lewis acids were found to increase the rate of alkyne metathesis with N≡Mo(OR)3 and Mo2(OR)6 complexes (OR= OCMe3, OCMe2CF3, and OCMe(CF3)2).Ph.D.ChemistryUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/62253/1/amdawson_2.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/62253/2/amdawson_1.pd

Multicritical Nishimori point in the phase diagram of the +- J Ising model on a square lattice

We investigate the critical behavior of the random-bond +- J Ising model on a square lattice at the multicritical Nishimori point in the T-p phase diagram, where T is the temperature and p is the disorder parameter (p=1 corresponds to the pure Ising model). We perform a finite-size scaling analysis of high-statistics Monte Carlo simulations along the Nishimori line defined by $2p-1={\rm Tanh}(1/T)$, along which the multicritical point lies. The multicritical Nishimori point is located at p^*=0.89081(7), T^*=0.9528(4), and the renormalization-group dimensions of the operators that control the multicritical behavior are y_1=0.655(15) and y_2 = 0.250(2); they correspond to the thermal exponent \nu= 1/y_2=4.00(3) and to the crossover exponent \phi= y_1/y_2=2.62(6).Comment: 23 page

The critical behavior of 3D Ising glass models: universality and scaling corrections

We perform high-statistics Monte Carlo simulations of three three-dimensional Ising spin-glass models: the +-J Ising model for two values of the disorder parameter p, p=1/2 and p=0.7, and the bond-diluted +-J model for bond-occupation probability p_b = 0.45. A finite-size scaling analysis of the quartic cumulants at the critical point shows conclusively that these models belong to the same universality class and allows us to estimate the scaling-correction exponent omega related to the leading irrelevant operator, omega=1.0(1). We also determine the critical exponents nu and eta. Taking into account the scaling corrections, we obtain nu=2.53(8) and eta=-0.384(9).Comment: 9 pages, published versio

β Cell dysfunction exists more than 5 years before type 1 diabetes diagnosis

BACKGROUND: The duration and patterns of β cell dysfunction during type 1 diabetes (T1D) development have not been fully defined. METHODS: Metabolic measures derived from oral glucose tolerance tests (OGTTs) were compared between autoantibody-positive (aAb+) individuals followed in the TrialNet Pathway to Prevention study who developed diabetes after 5 or more years or less than 5 years of longitudinal follow-up (Progressors≥5, n = 75; Progressors<5, n = 474) and 144 aAb-negative (aAb-) relatives. RESULTS: Mean age at study entry was 15.0 ± 12.6 years for Progressors≥5; 12.0 ± 9.1 for Progressors<5; and 16.3 ± 10.4 for aAb- relatives. At baseline, Progressors≥5 already exhibited significantly lower fasting C-peptide (P < 0.01), C-peptide AUC (P < 0.001), and early C-peptide responses (30- to 0-minute C-peptide; P < 0.001) compared with aAb- relatives, while 2-hour glucose (P = 0.03), glucose AUC (<0.001), and Index60 (<0.001) were all higher. Despite significant baseline impairment, metabolic measures in Progressors≥5 were relatively stable until 2 years prior to T1D diagnosis, when there was accelerated C-peptide decline and rising glycemia from 2 years until diabetes diagnosis. Remarkably, patterns of progression within 3 years of diagnosis were nearly identical between Progressors≥5 and Progressors<5. CONCLUSION: These data provide insight into the chronicity of β cell dysfunction in T1D and indicate that β cell dysfunction may precede diabetes diagnosis by more than 5 years in a subset of aAb+ individuals. Even among individuals with varying lengths of aAb positivity, our findings indicate that patterns of metabolic decline are uniform within the last 3 years of progression to T1D. TRIAL REGISTRATION: Clinicaltrials.gov NCT00097292. FUNDING: The Type 1 Diabetes TrialNet Study Group is a clinical trials network currently funded by the NIH through the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Allergy and Infectious Diseases, and The Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Juvenile Diabetes Research Foundation

Critical behavior of the random-anisotropy model in the strong-anisotropy limit

We investigate the nature of the critical behavior of the random-anisotropy Heisenberg model (RAM), which describes a magnetic system with random uniaxial single-site anisotropy, such as some amorphous alloys of rare earths and transition metals. In particular, we consider the strong-anisotropy limit (SRAM), in which the Hamiltonian can be rewritten as the one of an Ising spin-glass model with correlated bond disorder. We perform Monte Carlo simulations of the SRAM on simple cubic L^3 lattices, up to L=30, measuring correlation functions of the replica-replica overlap, which is the order parameter at a glass transition. The corresponding results show critical behavior and finite-size scaling. They provide evidence of a finite-temperature continuous transition with critical exponents $\eta_o=-0.24(4)$ and $\nu_o=2.4(6)$. These results are close to the corresponding estimates that have been obtained in the usual Ising spin-glass model with uncorrelated bond disorder, suggesting that the two models belong to the same universality class. We also determine the leading correction-to-scaling exponent finding $\omega = 1.0(4)$.Comment: 24 pages, 13 figs, J. Stat. Mech. in pres

Alteration-related minerals from fluid-rock interactions: implications for new clues assessing volcanic hazards

Magmatic heat and fluids can interact with a volcanic host rock to form secondary minerals, such as phyllosilicates, zeolites, sulfates, sulfides and oxides. The water-rock reactions, inducing alteration of the primary volcanic material, strongly depend on the magma chemistry and volatile flux, and the nature of the aquatic environment (i.e., sea/ocean and meteoric) and its properties such as temperature, salinity, redox and pH. The newly-grown alteration minerals result from the chemical reaction between the host rock and they can indicate particular physico-chemical conditions. Hence, the mechanisms controlling the formation of secondary mineral associations can be critical, not only for assessing the role of hydrothermally altered host rocks in moderating eruptions styles but also for volcano flank instabilities. In this study, we applied mass balance calculations and thermodynamic modelling to establish the formation and equilibria environments of alteration minerals and hydrothermal fluids at three active volcanic suites: Ruapehu (New Zealand), Mt. Zao (Japan) and Deception Island (Antarctica). Results indicate that the secondary minerals follow different precipitation sequences as a function of the magma composition and the primary mineral assemblage (basalt-andesitic to dacitic for Ruapehu, andesitic for Mt. Zao, and basaltic for Deception Island). Temporal variations in composition and abundances of the hydrothermal paragenesis in Ruapehu and Mt. Zao determinate the evolution of acid¿sulfate alteration zones. We conclude that the combination of the proposed petrologic-geochemical approach, the regional and local tectonic features, and the spatial distribution of the alteration minerals within the volcanic edifices can be used for the assessment of future hydrovolcanic eruptions (including multiple eruption phases) and/or instability flanks episodes. In addition, the biological submarine and global change communities can also benefit from this geochemical procedure in other worldwide submarine volcanoes as the water-rock chemical reaction has direct implication in the oceanic productivity

Correlated Domains in Spin Glasses

We study the 3D Edwards-Anderson spin glasses, by analyzing spin-spin correlation functions in thermalized spin configurations at low T on large lattices. We consider individual disorder samples and analyze connected clusters of very correlated sites: we analyze how the volume and the surface of these clusters increases with the lattice size. We qualify the important excitations of the system by checking how large they are, and we define a correlation length by measuring their gyration radius. We find that the clusters have a very dense interface, compatible with being space filling.Comment: 9 pages, 4 figures. Version accepted for publicatio

Timing of Millisecond Pulsars in NGC 6752. III. On the Presence of Nonluminous Matter in the Cluster’s Core

Millisecond pulsars are subject to accelerations in globular clusters (GCs) that manifest themselves in both the first and second spin period time derivatives, and can be used to explore the mass distribution of the potentials they inhabit. Here we report on over 20 yr of pulsar timing observations of five millisecond radio pulsars in the core of the core-collapse GC NGC 6752 with the Parkes (Murriyang) and MeerKAT radio telescopes, which have allowed us to measure the proper motions, positions, and first and second time derivatives of the pulsars. The pulsar timing parameters indicate that all the pulsars in the core experience accelerations and jerks that can be explained only if an amount of nonluminous mass of at least 2.56x10^3 M_SUN is present in the core of NGC 6752. On the other hand, our studies highly disfavor the presence of an intermediate-mass black hole at the center of the cluster, with a mass equal to or greater than ~3000M_SUN

Predicting for activity of second-line trastuzumab-based therapy in her2-positive advanced breast cancer

<p>Abstract</p> <p>Background</p> <p>In Her2-positive advanced breast cancer, the upfront use of trastuzumab is well established. Upon progression on first-line therapy, patients may be switched to lapatinib. Others however remain candidates for continued antibody treatment (treatment beyond progression). Here, we aimed to identify factors predicting for activity of second-line trastuzumab-based therapy.</p> <p>Methods</p> <p>Ninety-seven patients treated with > 1 line of trastuzumab-containing therapy were available for this analysis. Her2-status was determined by immunohistochemistry and re-analyzed by FISH if a score of 2+ was gained. Time to progression (TTP) on second-line therapy was defined as primary study endpoint. TTP and overall survival (OS) were estimated using the Kaplan-Meier product limit method. Multivariate analyses (Cox proportional hazards model, multinomial logistic regression) were applied in order to identify factors associated with TTP, response, OS, and incidence of brain metastases. <it>p </it>values < 0.05 were considered to indicate statistical significance.</p> <p>Results</p> <p>Median TTP on second-line trastuzumab-based therapy was 7 months (95% CI 5.74-8.26), and 8 months (95% CI 6.25-9.74) on first-line, respectively (n.s.). In the multivariate models, none of the clinical or histopthological features could reliably predict for activity of second-line trastuzumab-based treatment. OS was 43 months suggesting improved survival in patients treated with trastuzumab in multiple-lines. A significant deterioration of cardiac function was observed in three patients; 40.2% developed brain metastases while on second-line trastuzumab or thereafter.</p> <p>Conclusion</p> <p>Trastuzumab beyond progression showed considerable activity. None of the variables investigated correlated with activity of second-line therapy. In order to predict for activity of second-line trastuzumab, it appears necessary to evaluate factors known to confer trastuzumab-resistance.</p