Experimental application of sum rules for electron energy loss magnetic chiral dichroism

We present a derivation of the orbital and spin sum rules for magnetic circular dichroic spectra measured by electron energy loss spectroscopy in a transmission electron microscope. These sum rules are obtained from the differential cross section calculated for symmetric positions in the diffraction pattern. Orbital and spin magnetic moments are expressed explicitly in terms of experimental spectra and dynamical diffraction coefficients. We estimate the ratio of spin to orbital magnetic moments and discuss first experimental results for the Fe L_{2,3} edge.Comment: 11 pages, 2 figure

Breathing Metal–Organic Framework Based on Flexible Inorganic Building Units

Five novel bismuth carboxylate coordination polymers were synthesized from biphenyl-3,4\u2032,5-tricarboxylic acid (H3BPT) and [1,1\u2032:4\u2032,1\u2032\u2032]terphenyl-3,3\u2032\u2032,5,5\u2032\u2032-tetracarboxylic acid (H4TPTC). One of the phases, [Bi(BPT)]\ub72MeOH (denoted SU-100, as synthesized), is the first example, to the best of our knowledge, of a reversibly flexible bismuth-based metal\u2013organic framework. The material exhibits continuous changes to its unit cell parameters and pore shape depending on the solvent it is immersed in and the dryness of the sample. Typically, in breathing carboxylate-based MOFs, flexibility occurs through tilting of the organic linkers without significantly altering the coordination environment around the cation. In contrast to this, the continuous breathing mechanism in SU-100 involves significant changes to bond angles within the Bi2O12 inorganic building unit (IBU). The flexibility of the IBU of SU-100 reflects the nondiscrete coordination geometry of the bismuth cation. A disproportionate increase in the solvent accessible void volume was observed when compared to the expansion of the unit cell volume of SU-100. Additionally, activated SU-100 (SU-100-HT) exhibits a large increase in unit cell volume, yet has the smallest void volume of all the studied samples

Gammaretrovirus-mediated correction of SCID-X1 is associated with skewed vector integration site distribution in vivo

We treated 10 children with X-linked SCID (SCID-X1) using gammaretrovirus-mediated gene transfer. Those with sufficient follow-up were found to have recovered substantial immunity in the absence of any serious adverse events up to 5 years after treatment. To determine the influence of vector integration on lymphoid reconstitution, we compared retroviral integration sites (RISs) from peripheral blood CD3(+) T lymphocytes of 5 patients taken between 9 and 30 months after transplantation with transduced CD34(+) progenitor cells derived from 1 further patient and I healthy donor. Integration occurred preferentially in gene regions on either side of transcription start sites, was clustered, and correlated with the expression level in CD34(+) progenitors during transduction. In contrast to those in CD34(+) cells, RISs recovered from engrafted CD3(+)T cells were significantly overrepresented within or near genes encoding proteins with kinase or transferase activity or involved in phosphorus metabolism. Although gross patterns of gene expression were unchanged in transduced cells, the divergence of RIS target frequency between transduced progenitor cells and post-thymic T lymphocytes indicates that vector integration influences cell survival, engraftment, or proliferation

On the Ground State of Electron Gases at Negative Compressibility

Two- and three-dimensional electron gases with a uniform neutralizing background are studied at negative compressibility. Parametrized expressions for the dielectric function are used to access this strong-coupling regime, where the screened Coulomb potential becomes overall attractive for like charges. Closely examining these expressions reveals that the ground state with a periodic modulation of the charge density, albeit exponentially damped, replaces the homogeneous one at positive compressibility. The wavevector characterizing the new ground state depends on the density and is complex, having a positive imaginary part, as does the homogeneous ground state, and real part, as does the genuine charge density wave.Comment: 6 double-column pages, 2 figures. 2nd version is an extension of the 1st one, giving more detail

A comparison of 4 different machine learning algorithms to predict lactoferrin content in bovine milk from mid-infrared spectra

peer-reviewedLactoferrin (LF) is a glycoprotein naturally present in milk. Its content varies throughout lactation, but also with mastitis; therefore it is a potential additional indicator of udder health beyond somatic cell count. Condequently, there is an interest in quantifying this biomolecule routinely. First prediction equations proposed in the literature to predict the content in milk using milk mid-infrared spectrometry were built using partial least square regression (PLSR) due to the limited size of the data set. Thanks to a large data set, the current study aimed to test 4 different machine learning algorithms using a large data set comprising 6,619 records collected across different herds, breeds, and countries. The first algorithm was a PLSR, as used in past investigations. The second and third algorithms used partial least square (PLS) factors combined with a linear and polynomial support vector regression (PLS + SVR). The fourth algorithm also used PLS factors, but included in an artificial neural network with 1 hidden layer (PLS + ANN). The training and validation sets comprised 5,541 and 836 records, respectively. Even if the calibration prediction performances were the best for PLS + polynomial SVR, their validation prediction performances were the worst. The 3 other algorithms had similar validation performances. Indeed, the validation root mean squared error (RMSE) ranged between 162.17 and 166.75 mg/L of milk. However, the lower standard deviation of cross-validation RMSE and the better normality of the residual distribution observed for PLS + ANN suggest that this modeling was more suitable to predict the LF content in milk from milk mid-infrared spectra (R2v = 0.60 and validation RMSE = 162.17 mg/L of milk). This PLS +ANN model was then applied to almost 6 million spectral records. The predicted LF showed the expected relationships with milk yield, somatic cell score, somatic cell count, and stage of lactation. The model tended to underestimate high LF values (higher than 600 mg/L of milk). However, if the prediction threshold was set to 500 mg/L, 82% of samples from the validation having a content of LF higher than 600 mg/L were detected. Future research should aim to increase the number of those extremely high LF records in the calibration set

Generation and characterisation of Friedreich ataxia YG8R mouse fibroblast and neural stem cell models

This article has been made available through the Brunel Open Access Publishing Fund.Background: Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disease caused by GAA repeat expansion in the first intron of the FXN gene, which encodes frataxin, an essential mitochondrial protein. To further characterise the molecular abnormalities associated with FRDA pathogenesis and to hasten drug screening, the development and use of animal and cellular models is considered essential. Studies of lower organisms have already contributed to understanding FRDA disease pathology, but mammalian cells are more related to FRDA patient cells in physiological terms. Methodology/Principal Findings: We have generated fibroblast cells and neural stem cells (NSCs) from control Y47R mice (9 GAA repeats) and GAA repeat expansion YG8R mice (190+120 GAA repeats). We then differentiated the NSCs in to neurons, oligodendrocytes and astrocytes as confirmed by immunocytochemical analysis of cell specific markers. The three YG8R mouse cell types (fibroblasts, NSCs and differentiated NSCs) exhibit GAA repeat stability, together with reduced expression of frataxin and reduced aconitase activity compared to control Y47R cells. Furthermore, YG8R cells also show increased sensitivity to oxidative stress and downregulation of Pgc-1α and antioxidant gene expression levels, especially Sod2. We also analysed various DNA mismatch repair (MMR) gene expression levels and found that YG8R cells displayed significant reduction in expression of several MMR genes, which may contribute to the GAA repeat stability. Conclusions/Significance: We describe the first fibroblast and NSC models from YG8R FRDA mice and we confirm that the NSCs can be differentiated into neurons and glia. These novel FRDA mouse cell models, which exhibit a FRDA-like cellular and molecular phenotype, will be valuable resources to further study FRDA molecular pathogenesis. They will also provide very useful tools for preclinical testing of frataxin-increasing compounds for FRDA drug therapy, for gene therapy, and as a source of cells for cell therapy testing in FRDA mice. © 2014 Sandi et al

Tomonaga-Luttinger parameters for quantum wires

The low-energy properties of a homogeneous one-dimensional electron system are completely specified by two Tomonaga-Luttinger parameters $K_{\rho}$ and $v_{\sigma}$. In this paper we discuss microscopic estimates of the values of these parameters in semiconductor quantum wires that exploit their relationship to thermodynamic properties. Motivated by the recognized similarity between correlations in the ground state of a one-dimensional electron liquid and correlations in a Wigner crystal, we evaluate these thermodynamic quantities in a self-consistent Hartree-Fock approximation. According to our calculations, the Hartree-Fock approximation ground state is a Wigner crystal at all electron densities and has antiferromagnetic order that gradually evolves from spin-density-wave to localized in character as the density is lowered. Our results for $K_{\rho}$ are in good agreement with weak-coupling perturbative estimates $K_{\rho}^{pert}$ at high densities, but deviate strongly at low densities, especially when the electron-electron interaction is screened at long distances. $K_{\rho}^{pert}\sim n^{1/2}$ vanishes at small carrier density $n$ whereas we conjecture that $K_{\rho}\to 1/2$ when $n\to 0$, implying that $K_{\rho}$ should pass through a minimum at an intermediate density. Observation of such a non-monotonic dependence on particle density would allow to measure the range of the microscopic interaction. In the spin sector we find that the spin velocity decreases with increasing interaction strength or decreasing $n$. Strong correlation effects make it difficult to obtain fully consistent estimates of $v_{\sigma}$ from Hartree-Fock calculations. We conjecture that v_{\sigma}/\vf\propto n/V_0 in the limit $n\to 0$ where $V_0$ is the interaction strength.Comment: RevTeX, 23 pages, 8 figures include

Mammalian Frataxin: An Essential Function for Cellular Viability through an Interaction with a Preformed ISCU/NFS1/ISD11 Iron-Sulfur Assembly Complex

Frataxin, the mitochondrial protein deficient in Friedreich ataxia, a rare autosomal recessive neurodegenerative disorder, is thought to be involved in multiple iron-dependent mitochondrial pathways. In particular, frataxin plays an important role in the formation of iron-sulfur (Fe-S) clusters biogenesis.. Fe-S cluster biosynthesis

Calibration of the dolomite clumped isotope thermometer from 25 to 350°C, and implications for a universal calibration for all (Ca, Mg, Fe)CO_3 carbonates

Carbonate clumped isotope thermometry is based on the temperature-dependent formation of ^(13)C^(18)O^(16)O_2^(2-) ion groups within the lattice of solid carbonate minerals. At low temperatures the bonds between rare, heavy ^(13)C and ^(18)O isotopes are thermodynamically favored, and thus at equilibrium they are present in higher than random abundances. Here we calibrate the use of this temperature proxy in a previously uncalibrated carbonate phase — dolomite [CaMg(CO_3)_2] — over a temperature range that extends to conditions typical of shallow crustal environments, by determining the Δ_(47) values of CO_2 extracted from synthetic or natural (proto)dolomites grown at known temperatures from 25 to 350°C and analyzed in two different laboratories using different procedures for sample analysis, purification and post-measurement data treatment. We found that the Δ_(47) – 1/T^2 dependence for (proto)dolomite is linear between 25 and 350°C, independent of their Mg/Ca compositions or cation order (or the laboratory in which they were analyzed), and offset from, but parallel to, the theoretical predictions of the Δ_(63) dependence to temperature of the abundance of the ^(13)C^(18)O^(16)O_2 isotopologue inside the dolomite and calcite mineral lattices as expected from ab-initio calculations (Schauble et al., 2006). This suggests that neither the equilibrium constant for ^(13)C–^(18)O clumping in (proto)dolomite lattice, nor the experimental fractionation associated with acid digestion to produce CO_2, depend on their formation mechanism, degree of cation order and/or stoichiometry (ie., Mg/Ca ratio) and/or δ^(18)O and δ^(13)C compositions (at least over the range we explored). Thus, we suggest the following single Δ_(47) – 1/T^2 linear regression for describing all dolomite minerals: with T in kelvin and Δ_(47) in the Carbon Dioxide Equilibrium Scale (CDES) of Dennis et al. (2011) and referring to CO_2 extracted by phosphoric acid digestion at 90°C. The listed uncertainties on slope and intercept are 95% confidence intervals. The temperature sensitivity (slope) of this relation is lower than those based on low temperature acid digestion of carbonates, but comparable to most of those based on high temperature acid digestion (with however significantly better constraints on the slope and intercept values, notably due to the large range in temperature investigated and the large number of Δ_(47) measurements performed here, n = 67). We also use this dataset to empirically determine that the acid fractionation factor associated with phosphoric acid digestion of dolomite at 90°C (Δ∗_(dolomite90)) is about + 0.176‰. This is comparable to the Δ∗_(calcite90) experimentally obtained for calcite (Guo et al., 2009), suggesting that the acid fractionation Δ∗ for acid digestion of dolomite and calcite are the same within error of measurement, with apparently no influence of the cation identity. This hypothesis is also supported by the fact that our dolomite calibration data are indistinguishable from published calibration data for calcite, aragonite and siderite generated in similar analytical conditions (ie., carbonate digested at T ⩾ 70°C and directly referenced into CDES), demonstrating excellent consistency among the four (Ca,Mg,Fe)CO_3 mineral phases analyzed in seven different laboratories (this represents a total of 103 mean Δ_(47) values resulting from more than 331 Δ_(47) measurements). These data are used to calculate a composite Δ_(47)–T universal relation for those carbonate minerals of geological interest, for temperatures between -1 and 300°C, that is found to be statistically indistinguishable from the one described by dolomite only: Thus, in order to standardize the temperature estimates out of different laboratories running high temperature digestion of (Ca,Mg,Fe)CO_3 carbonate minerals, we recommend the use of this single Δ_(47)-T calibration to convert Δ_(47CDES) data into accurate and precise temperature estimates. More widely, this study extends the use of the Δ_(47) thermometry to studies of diagenesis and low-grade metamorphism of carbonates with unprecedented precision on temperature estimates based on Δ_(47) measurements — environments where many other thermometers are generally empirical or semi-quantitative

Urinary levels of N-nitroso compounds in relation to risk of gastric cancer: Findings from the Shanghai cohort study

Background: N-Nitroso compounds are thought to play a significant role in the development of gastric cancer. Epidemiological data, however, are sparse in examining the associations between biomarkers of exposure to N-nitroso compounds and the risk of gastric cancer. Methods: A nested case-control study within a prospective cohort of 18,244 middle-aged and older men in Shanghai, China, was conducted to examine the association between urinary level of N-nitroso compounds and risk of gastric cancer. Information on demographics, usual dietary intake, and use of alcohol and tobacco was collected through in-person interviews at enrollment. Urinary levels of nitrate, nitrite, N-nitroso-2-methylthiazolidine-4-carboxylic acid (NMTCA), N-nitrosoproline (NPRO), N-nitrososarcosine (NSAR), N-nitrosothiazolidine-4-carboxylic acid (NTCA), as well as serum H. pylori antibodies were quantified in 191 gastric cancer cases and 569 individually matched controls. Logistic regression method was used to assess the association between urinary levels of N-nitroso compounds and risk of gastric cancer. Results: Compared with controls, gastric cancer patients had overall comparable levels of urinary nitrate, nitrite, and N-nitroso compounds. Among individuals seronegative for antibodies to H. pylori, elevated levels of urinary nitrate were associated with increased risk of gastric cancer. The multivariate-adjusted odds ratios for the second and third tertiles of nitrate were 3.27 (95% confidence interval = 0.76-14.04) and 4.82 (95% confidence interval = 1.05-22.17), respectively, compared with the lowest tertile (P for trend = 0.042). There was no statistically significant association between urinary levels of nitrite or N-nitroso compounds and risk of gastric cancer. Urinary NMTCA level was significantly associated with consumption of alcohol and preserved meat and fish food items. Conclusion: The present study demonstrates that exposure to nitrate, a precursor of N-nitroso compounds, may increase the risk of gastric cancer among individuals without a history of H. pylori infection