Spin-flip effects on the current-in-plane magnetotransport in magnetic multilayers with arbitrary magnetization alignments

An extended Boltzmann equation approach, with nondiagonal components of the electron distribution, function taken into account, is proposed to study spin-flip effects on the magnetoresistance (MR) in magnetic inhomogeneous systems with arbitrary magnetization alignments. The presence of spin-flip scattering is found to reduce the MR and to decrease deviation of the MR from linear dependence on sin 2(θ/2) where θ is the angle between the magnetizations of successive magnetic films.published_or_final_versio

Spin and orbital excitations in undoped manganites

We develop a theory for spin and orbital excitations in undoped manganites to account for the spin and orbital orderings observed experimentally. It is found that the anisotropy of the magnetic structure is closely related to the orbital ordering, and the Jahn-Teller effect stabilizes the orbital ordering. The phase diagram and the low-energy excitation spectra for both spin and orbital orderings are obtained. The calculated critical temperatures can be quantitatively comparable to the experimental data. © 2000 American Institute of Physics.published_or_final_versio

Phase diagram of an extended Kondo lattice model for manganites: The Schwinger-boson mean-field approach

We investigate the phase diagram of an extended Kondo lattice model for doped manganese oxides in the presence of strong but finite Hund's coupling and on-site Coulomb interaction. By means of the Schwinger-boson mean-field approach, it is found that, besides magnetic ordering, there will be nonuniform charge distributions, such as charge ordering and phase separation, if the interaction between electrons prevails over the hybridization. Which of the charge ordering and phase separation appears is determined by a competition between effective repulsive and attractive interactions due to virtual processes of electron hopping. Calculated results show that strong electron correlations caused by the on-site Coulomb interaction as well as the finite Hund's coupling play an important role in the magnetic ordering and charge distribution at low temperatures. ©2000 The American Physical Society.published_or_final_versio

Giant magnetoresistance in magnetic granular systems

Based on a semiclassical model, the transport properties in systems of cylindrical or spherical magnetic granules are investigated analytically. It is shown that the conductivities as well as the magnetoresistance of these systems depend strongly on the size of the granules. In particular, there is always an optimum granular size for the magnetoresistance. ©1996 American Institute of Physics.published_or_final_versio

Macroscopic theory of giant magnetoresistance in magnetic granular metals

A macroscopic theory of giant magnetoresistance in granular magnetic materials is developed to improve on that of Rubinstein [Phys. Rev. B 50, 3830 (1994)]. By using a self-consistent method and introducing a useful parametrization, we show the magnetotransport in granular systems to be between those for currents in the plane of layers and currents perpendicular to the plane of the layers in multilayers. The theoretical result in the local limit is found to be in agreement with the observed singular dependence of the giant magnetoresistance on annealing temperature.published_or_final_versio

Using biomarkers to predict TB treatment duration (Predict TB): a prospective, randomized, noninferiority, treatment shortening clinical trial

Background : By the early 1980s, tuberculosis treatment was shortened from 24 to 6 months, maintaining relapse rates of 1-2%. Subsequent trials attempting shorter durations have failed, with 4-month arms consistently having relapse rates of 15-20%. One trial shortened treatment only among those without baseline cavity on chest x-ray and whose month 2 sputum culture converted to negative. The 4-month arm relapse rate decreased to 7% but was still significantly worse than the 6-month arm (1.6%, P<0.01).  We hypothesize that PET/CT characteristics at baseline, PET/CT changes at one month, and markers of residual bacterial load will identify patients with tuberculosis who can be cured with 4 months (16 weeks) of standard treatment.Methods: This is a prospective, multicenter, randomized, phase 2b, noninferiority clinical trial of pulmonary tuberculosis participants. Those eligible start standard of care treatment. PET/CT scans are done at weeks 0, 4, and 16 or 24. Participants who do not meet early treatment completion criteria (baseline radiologic severity, radiologic response at one month, and GeneXpert-detectable bacilli at four months) are placed in Arm A (24 weeks of standard therapy). Those who meet the early treatment completion criteria are randomized at week 16 to continue treatment to week 24 (Arm B) or complete treatment at week 16 (Arm C). The primary endpoint compares the treatment success rate at 18 months between Arms B and C.Discussion: Multiple biomarkers have been assessed to predict TB treatment outcomes. This study uses PET/CT scans and GeneXpert (Xpert) cycle threshold to risk stratify participants. PET/CT scans are not applicable to global public health but could be used in clinical trials to stratify participants and possibly become a surrogate endpoint. If the Predict TB trial is successful, other immunological biomarkers or transcriptional signatures that correlate with treatment outcome may be identified. TRIAL REGISTRATION: NCT02821832

Stem cell function and stress response are controlled by protein synthesis.

Whether protein synthesis and cellular stress response pathways interact to control stem cell function is currently unknown. Here we show that mouse skin stem cells synthesize less protein than their immediate progenitors in vivo, even when forced to proliferate. Our analyses reveal that activation of stress response pathways drives both a global reduction of protein synthesis and altered translational programmes that together promote stem cell functions and tumorigenesis. Mechanistically, we show that inhibition of post-transcriptional cytosine-5 methylation locks tumour-initiating cells in this distinct translational inhibition programme. Paradoxically, this inhibition renders stem cells hypersensitive to cytotoxic stress, as tumour regeneration after treatment with 5-fluorouracil is blocked. Thus, stem cells must revoke translation inhibition pathways to regenerate a tissue or tumour.This work was funded by Cancer Research UK (CR-UK), Worldwide Cancer Research, the Medical Research Council (MRC), the European Research Council (ERC), and EMBO. Research in Michaela Frye's laboratory is supported by a core support grant from the Wellcome Trust and MRC to the Wellcome Trust-Medical Research Cambridge Stem Cell Institute.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/nature1828

Arabidopsis thaliana encodes a bacterial-type heterodimeric isopropylmalate isomerase involved in both Leu biosynthesis and the Met chain elongation pathway of glucosinolate formation

The last steps of the Leu biosynthetic pathway and the Met chain elongation cycle for glucosinolate formation share identical reaction types suggesting a close evolutionary relationship of these pathways. Both pathways involve the condensation of acetyl-CoA and a 2-oxo acid, isomerization of the resulting 2-malate derivative to form a 3-malate derivative, the oxidation-decarboxylation of the 3-malate derivative to give an elongated 2-oxo acid, and transamination to generate the corresponding amino acid. We have now analyzed the genes encoding the isomerization reaction, the second step of this sequence, in Arabidopsis thaliana. One gene encodes the large subunit and three encode small subunits of this enzyme, referred to as isopropylmalate isomerase (IPMI) with respect to the Leu pathway. Metabolic profiling of large subunit mutants revealed accumulation of intermediates of both Leu biosynthesis and Met chain elongation, and an altered composition of aliphatic glucosinolates demonstrating the function of this gene in both pathways. In contrast, the small subunits appear to be specialized to either Leu biosynthesis or Met chain elongation. Green fluorescent protein tagging experiments confirms the import of one of the IPMI small subunits into the chloroplast, the localization of the Met chain elongation pathway in these organelles. These results suggest the presence of different heterodimeric IPMIs in Arabidopsis chloroplasts with distinct substrate specificities for Leu or glucosinolate metabolism determined by the nature of the different small subunit

Etiologic Diagnosis of Lower Respiratory Tract Bacterial Infections Using Sputum Samples and Quantitative Loop-Mediated Isothermal Amplification

Etiologic diagnoses of lower respiratory tract infections (LRTI) have been relying primarily on bacterial cultures that often fail to return useful results in time. Although DNA-based assays are more sensitive than bacterial cultures in detecting pathogens, the molecular results are often inconsistent and challenged by doubts on false positives, such as those due to system- and environment-derived contaminations. Here we report a nationwide cohort study on 2986 suspected LRTI patients across P. R. China. We compared the performance of a DNA-based assay qLAMP (quantitative Loop-mediated isothermal AMPlification) with that of standard bacterial cultures in detecting a panel of eight common respiratory bacterial pathogens from sputum samples. Our qLAMP assay detects the panel of pathogens in 1047(69.28%) patients from 1533 qualified patients at the end. We found that the bacterial titer quantified based on qLAMP is a predictor of probability that the bacterium in the sample can be detected in culture assay. The relatedness of the two assays fits a logistic regression curve. We used a piecewise linear function to define breakpoints where latent pathogen abruptly change its competitive relationship with others in the panel. These breakpoints, where pathogens start to propagate abnormally, are used as cutoffs to eliminate the influence of contaminations from normal flora. With help of the cutoffs derived from statistical analysis, we are able to identify causative pathogens in 750 (48.92%) patients from qualified patients. In conclusion, qLAMP is a reliable method in quantifying bacterial titer. Despite the fact that there are always latent bacteria contaminated in sputum samples, we can identify causative pathogens based on cutoffs derived from statistical analysis of competitive relationship