2,374 research outputs found
Stereoselective glycosylations using oxathiane spiroketal glycosyl donors
Novel oxathiane spiroketal donors have been synthesised and activated via an umpolung S-arylation strategy using 1,3,5-trimethoxybenzene and 1,3-dimethoxybenzene. The comparative reactivity of the resulting 2,4,6-trimethoxyphenyl (TMP)- and 2,4-dimethoxyphenyl (DMP)-oxathiane spiroketal sulfonium ions is discussed, and their α-stereoselectivity in glycosylation reactions is compared to the analogous TMP- and DMP-sulfonium ions derived from an oxathiane glycosyl donor bearing a methyl ketal group. The results show that the stereoselectivity of the oxathiane glycosyl donors is dependent on the structure of the ketal group and reactivity can be tuned by varying the substituent on the sulfonium ion
Chemical generation and modification of peptides containing multiple dehydroalanines
Chemical formation of dehydroalanine has been widely used for the post-translational modification of protein and peptides, however methods to incorporate multiple dehydroalanine residues into a single peptide have not been defined. We report the use of methyl 2,5-dibromovalerate which can be used to cleanly carry out this transformation
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Mathematical modelling of nanoparticle delivery to vascular tumours
This paper was presented at the 2nd Micro and Nano Flows Conference (MNF2009), which was held at Brunel University, West London, UK. The conference was organised by Brunel University and supported by the Institution of Mechanical Engineers, IPEM, the Italian Union of Thermofluid dynamics, the Process Intensification Network, HEXAG - the Heat Exchange Action Group and the Institute of Mathematics and its Applications.The goal of any cancer therapy is to achieve efficient, tissue-specific targeting of drugs to cancer cells. However, most anticancer agents act on healthy and malignant tissue alike, potentially resulting in side effects to healthy tissue. This has motivated the development of treatment strategies that are cancer-cell
specific; one approach uses biomimetic polymer vesicles (BPV) to deliver chemotherapeutic drugs into cells before releasing them. BPVs are synthetic membrane enclosed, nanometre-sized structures, and provide ideal drug delivery vectors because specific targeting to cancer cells can be achieved by coating with tumourspecific
molecules. We present several mathematical models covering a wide range of length-scales pertinent to BPV-mediated delivery protocols and focus on capturing the in vivo environment by evaluating the impact of the underlying vascular structure upon the governing transport mechanisms. Firstly, we present models of specific binding of BPVs to cancer cells. Subsequently we examine the implications of these model outputs in the contexts of both discrete capillary architectures and higher level homogenized-models that track blood and BPV transport at the tissue scale (both intra- and extra-tumorally). Numerical solutions are discussed, and recommendations are presented on that optimal integration of the models to generate quantitative predictions associated with BPV treatment efficacy
Compressibility of titanosilicate melts
The effect of composition on the relaxed adiabatic bulk modulus (K0) of a range of alkali- and alkaline earth-titanosilicate [X 2 n/n+ TiSiO5 (X=Li, Na, K, Rb, Cs, Ca, Sr, Ba)] melts has been investigated. The relaxed bulk moduli of these melts have been measured using ultrasonic interferometric methods at frequencies of 3, 5 and 7 MHz in the temperature range of 950 to 1600°C (0.02 Pa s < s < 5 Pa s). The bulk moduli of these melts decrease with increasing cation size from Li to Cs and Ca to Ba, and with increasing temperature. The bulk moduli of the Li-, Na-, Ca- and Ba-bearing metasilicate melts decrease with the addition of both TiO2 and SiO2 whereas those of the K-, Rb- and Cs-bearing melts increase. Linear fits to the bulk modulus versus volume fraction of TiO2 do not converge to a common compressibility of the TiO2 component, indicating that the structural role of TiO2 in these melts is dependent on the identity of the cation. This proposition is supported by a number of other property data for these and related melt compositions including heat capacity and density, as well as structural inferences from X-ray absorption spectroscopy (XANES). The compositional dependence of the compressibility of the TiO2 component in these melts explains the difficulty incurred in previous attempts to incorporate TiO2 in calculation schemes for melt compressibility. The empirical relationship KV-4/3 for isostructural materials has been used to evaluate the compressibility-related structural changes occurring in these melts. The alkali metasilicate and disilicate melts are isostructural, independent of the cation. The addition of Ti to the metasilicate composition (i.e. X2TiSiO5), however, results in a series of melts which are not isostructural. The alkaline-earth metasilicate and disilicate compositions are not isostructural, but the addition of Ti to the metasilicate compositions (i.e. XTiSiO5) would appear, on the basis of modulus-volume systematics, to result in the melts becoming isostructural with respect to compressibility
Double quick, double click reversible peptide “stapling”
The development of constrained peptides for inhibition of protein–protein interactions is an emerging strategy in chemical biology and drug discovery. This manuscript introduces a versatile, rapid and reversible approach to constrain peptides in a bioactive helical conformation using BID and RNase S peptides as models. Dibromomaleimide is used to constrain BID and RNase S peptide sequence variants bearing cysteine (Cys) or homocysteine (hCys) amino acids spaced at i and i + 4 positions by double substitution. The constraint can be readily removed by displacement of the maleimide using excess thiol. This new constraining methodology results in enhanced α-helical conformation (BID and RNase S peptide) as demonstrated by circular dichroism and molecular dynamics simulations, resistance to proteolysis (BID) as demonstrated by trypsin proteolysis experiments and retained or enhanced potency of inhibition for Bcl-2 family protein–protein interactions (BID), or greater capability to restore the hydrolytic activity of the RNAse S protein (RNase S peptide). Finally, use of a dibromomaleimide functionalized with an alkyne permits further divergent functionalization through alkyne–azide cycloaddition chemistry on the constrained peptide with fluorescein, oligoethylene glycol or biotin groups to facilitate biophysical and cellular analyses. Hence this methodology may extend the scope and accessibility of peptide stapling
Atomic transition frequencies, isotope shifts, and sensitivity to variation of the fine structure constant for studies of quasar absorption spectra
Theories unifying gravity with other interactions suggest spatial and
temporal variation of fundamental "constants" in the Universe. A change in the
fine structure constant, alpha, could be detected via shifts in the frequencies
of atomic transitions in quasar absorption systems. Recent studies using 140
absorption systems from the Keck telescope and 153 from the Very Large
Telescope, suggest that alpha varies spatially. That is, in one direction on
the sky alpha seems to have been smaller at the time of absorption, while in
the opposite direction it seems to have been larger.
To continue this study we need accurate laboratory measurements of atomic
transition frequencies. The aim of this paper is to provide a compilation of
transitions of importance to the search for alpha variation. They are E1
transitions to the ground state in several different atoms and ions, with
wavelengths ranging from around 900 - 6000 A, and require an accuracy of better
than 10^{-4} A. We discuss isotope shift measurements that are needed in order
to resolve systematic effects in the study. The coefficients of sensitivity to
alpha-variation (q) are also presented.Comment: Includes updated version of the "alpha line" lis
The nonlinear anomalous lattice elasticity associated with the high-pressure phase transition in spodumene: A high precission static compression study
The high-pressure behavior of the lattice elasticity of spodumene, LiAlSi2O6,
was studied by static compression in a diamond-anvil cell up to 9.3 GPa.
Investigations by means of single-crystal XRD and Raman spectroscopy within the
hydrostatic limits of the pressure medium focus on the pressure ranges around
similar to 3.2 and similar to 7.7 GPa, which have been reported previously to
comprise two independent structural phase transitions. While our measurements
confirm the well-established first-order C2/c-P2(1)/c transformation at 3.19
GPa (with 1.2% volume discontinuity and a hysteresis between 0.02 and 0.06
GPa), both unit-cell dimensions and the spectral changes observed in
high-pressure Raman spectra give no evidence for structural changes related to
a second phase transition. Monoclinic lattice parameters and unit-cell volumes
at in total 59 different pressure points have been used to re-calculate the
lattice-related properties of spontaneous strain, volume strain, and the bulk
moduli as a function of pressure across the transition. A modified Landau free
energy expansion in terms of a one component order parameter has been developed
and tested against these experimentally determined data. The Landau solution
provides a much better reproduction of the observed anomalies than any
equation-of-state fit to data sets truncated below and above P (tr), thus
giving Landau parameters of K (0) = 138.3(2) GPa, K' = 7.46(5), lambda (V) =
33.6(2) GPa, a = 0.486(3), b = -29.4(6) GPa and c = 551(11) GPa
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Risk measures for direct real estate investments with non-normal or unknown return distributions
The volatility of returns is probably the most widely used risk measure for real estate. This is rather surprising since a number of studies have cast doubts on the view that volatility can capture the manifold risks attached to properties and corresponds to the risk attitude of investors. A central issue in this discussion is the statistical properties of real estate returns—in contrast to neoclassical capital market theory they are mostly non-normal and often unknown, which render many statistical measures useless. Based on a literature review and an analysis of data from Germany we provide evidence that volatility alone is inappropriate for measuring the risk of direct real estate.
We use a unique data sample by IPD, which includes the total returns of 939 properties across different usage types (56% office, 20% retail, 8% others and 16% residential properties) from 1996 to 2009, the German IPD Index, and the German Property Index. The analysis of the distributional characteristics shows that German real estate returns in this period were not normally distributed and that a logistic distribution would have been a better fit. This is in line with most of the current literature on this subject and leads to the question which indicators are more appropriate to measure real estate risks. We suggest that a combination of quantitative and qualitative risk measures more adequately captures real estate risks and conforms better with investor attitudes to risk. Furthermore, we present criteria for the purpose of risk classification
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