Structural "δ Doping" to Control Local Magnetization in Isovalent Oxide Heterostructures.

Modulation and δ-doping strategies, in which atomically thin layers of charged dopants are precisely deposited within a heterostructure, have played enabling roles in the discovery of new physical behavior in electronic materials. Here, we demonstrate a purely structural "δ-doping" strategy in complex oxide heterostructures, in which atomically thin manganite layers are inserted into an isovalent manganite host, thereby modifying the local rotations of corner-connected MnO_{6} octahedra. Combining scanning transmission electron microscopy, polarized neutron reflectometry, and density functional theory, we reveal how local magnetic exchange interactions are enhanced within the spatially confined regions of suppressed octahedral rotations. The combined experimental and theoretical results illustrate the potential to utilize noncharge-based approaches to "doping" in order to enhance or suppress functional properties within spatially confined regions of oxide heterostructures.

Spatial control of functional properties via octahedral modulations in complex oxide superlattices.

Control of atomic structure, namely the topology of the corner-connected metal-oxygen octahedra, has emerged as an important route to tune the functional properties at oxide interfaces. Here we investigate isovalent manganite superlattices (SLs), [(La(0.7)Sr(0.3)MnO(3))n/(Eu(0.7)Sr(0.3)MnO(3))n] × m, as a route to spatial control over electronic bandwidth and ferromagnetism through the creation of octahedral superstructures. Electron energy loss spectroscopy confirms a uniform Mn valence state throughout the SLs. In contrast, the presence of modulations of the MnO(6) octahedral rotations along the growth direction commensurate with the SL period is revealed by scanning transmission electron microscopy and X-ray diffraction. We show that the Curie temperatures of the constituent materials can be systematically engineered via the octahedral superstructures leading to a modulated magnetization in samples where the SL period is larger than the interfacial octahedral coupling length scale, whereas a single magnetic transition is observed in the short-period SLs.

Effect of interfacial octahedral behavior in ultrathin manganite films.

We investigate structural coupling of the MnO6 octahedra across a film/substrate interface and the resultant changes of the physical properties of ultrathin La2/3Sr1/3MnO3 (LSMO) films. In order to isolate the effect of interfacial MnO6 octahedral behavior from that of epitaxial strain, LSMO films are grown on substrates with different symmetry and similar lattice parameters. Ultrathin LSMO films show an increased magnetization and electrical conductivity on cubic (LaAlO3)0.3(Sr2AlTaO6)0.7 (LSAT) compared to those grown on orthorhombic NdGaO3 (NGO) substrates, an effect that subsides as the thickness of the films is increased. This study demonstrates that interfacial structural coupling can play a critical role in the functional properties of oxide heterostructures.

Delta doping of ferromagnetism in antiferromagnetic manganite superlattices.

We demonstrate that delta doping can be used to create a dimensionally confined region of metallic ferromagnetism in an antiferromagnetic (AFM) manganite host, without introducing any explicit disorder due to dopants or frustration of spins. Theoretical consideration of these additional carriers shows that they cause a local enhancement of ferromagnetic double exchange with respect to AFM superexchange, resulting in local canting of the AFM spins. This leads to a highly modulated magnetization, as measured by polarized neutron reflectometry. The spatial modulation of the canting is related to the spreading of charge from the doped layer and establishes a fundamental length scale for charge transfer, transformation of orbital occupancy, and magnetic order in these manganites. Furthermore, we confirm the existence of the canted, AFM state as was predicted by de Gennes [Phys. Rev. 118, 141 (1960)] but had remained elusive.

Enhanced ordering temperatures in antiferromagnetic manganite superlattices.

The disorder inherent to doping by cation substitution in the complex oxides can have profound effects on collective-ordered states. Here, we demonstrate that cation-site ordering achieved through digital-synthesis techniques can dramatically enhance the antiferromagnetic ordering temperatures of manganite films. Cation-ordered (LaMnO3)m/(SrMnO3)2m superlattices show Néel temperatures (TN) that are the highest of any La(1-x)Sr(x)MnO3 compound, approximately 70 K greater than compositionally equivalent randomly doped La(1/3)Sr(2/3)MnO3. The antiferromagnetic order is A-type, consisting of in-plane double-exchange-mediated ferromagnetic sheets coupled antiferromagnetically along the out-of-plane direction. Through synchrotron X-ray scattering, we have discovered an in-plane structural modulation that reduces the charge itinerancy and hence the ordering temperature within the ferromagnetic sheets, thereby limiting TN. This modulation is mitigated and driven to long wavelengths by cation ordering, enabling the higher TN values of the superlattices. These results provide insight into how cation-site ordering can enhance cooperative behaviour in oxides through subtle structural phenomena.

Metal-insulator transition and its relation to magnetic structure in (LaMnO3)2n/(SrMnO3)n superlattices.

Superlattices of (LaMnO3){2n}/(SrMnO3){n} (1or=3. Measurements of transport, magnetization, and polarized neutron reflectivity reveal that the ferromagnetism is relatively uniform in the metallic state, and is strongly modulated in the insulating state, being high in LaMnO3 and suppressed in SrMnO3. The modulation is consistent with a Mott transition driven by the proximity between the (LaMnO3)/(SrMnO3) interfaces. The insulating state for n>or=3 obeys variable range hopping at low temperatures. We suggest that this is due to states at the Fermi level that emerge at the (LaMnO3)/(SrMnO3) interfaces and are localized by disorder.

The North American Multiple System Atrophy Study Group.

The North American Multiple System Atrophy Study Group involves investigators in 12 US medical centers funded by a grant from the National Institutes of Health. The objectives are to examine the environmental and genetic risk factors for MSA; elucidate pathogenic mechanisms underlying the disorder; and refine evaluations used for assessment. During its first year, the group enrolled 87 patients, implemented four cores, and initiated four scientific projects. Most patients among the 87 had parkinsonian features, which frequently began asymmetrically and remained asymmetrical; one-third responded to levodopa and many developed levodopa complications; almost two-thirds of the patients had cerebellar dysfunction, of these 90% had ataxia; urinary incontinence occurred commonly, and sleep disorders affected most. The investigators studied the effects of oxidative and nitrative stress upon the formation of alpha-synuclein inclusions; generated transgenic models of alpha-synuclein accumulation that recapitulate several behavioral and neuropathological features of MSA; and compared the severity of the autonomic features of MSA, Parkinson's disease and dementia with Lewy bodies.

Does cardioplegia type affect outcome and survival in patients with advanced left ventricular dysfunction? Results from the CABG Patch Trial.

BACKGROUND: There is controversy regarding which cardioplegic solution, temperature, and route of administration provides superior protection. The CABG Patch Trial enrolled a high-risk group of coronary artery disease patients with an ejection fraction of <36%. Thus, they constitute an ideal group to benefit most from optimal cardioplegic protection. METHODS AND RESULTS: All patients randomized into the trial were compared with respect to the use of blood and crystalloid cardioplegia. In addition, a questionnaire was sent to surgeons requesting blood cardioplegic temperature and route. Patients receiving crystalloid cardioplegia versus those receiving blood cardioplegia were found to have significantly more operative deaths (2% versus 0.3%, P:=0.02), postoperative myocardial infarctions (10% versus 2%, P:<0.001), shock (13% versus 7%, P:=0. 013), and postoperative conduction defects (21.6% versus 12.4%, P:=0. 001). Despite this, early death (6% crystalloid versus 4% blood cardioplegia) and late death (24% crystalloid versus 21% blood cardioplegia) statistics were not significantly different. Patients receiving normothermic blood had less postoperative right ventricular dysfunction (10%) than did patients receiving cold blood (25%) or cold blood with warm reperfusion (30%) (P:=0.004). There was no significant difference in early or late death. Finally, patients who received combined antegrade and retrograde cardioplegia had significantly less inotrope use (71% versus 84%, P:=0.002), right ventricular dysfunction (23% versus 41%, P:=0.001), and postoperative balloon pump use (12% versus 19%, P:=0.02) than did those who received antegrade cardioplegia. There was no difference in survival. CONCLUSIONS: Blood cardioplegia and combined antegrade and retrograde cardioplegia are superior to crystalloid and antegrade cardioplegia alone for postoperative morbidity. Despite this, there is no significant difference in early or late survival.

A novel antithrombin gene mutation: slippage and mispairing as a mechanism of genetic disease.

There is a high degree of genetic heterogeneity underlying antithrombin deficiency indicating that a number of genetic mechanisms are responsible for the disorder. We report the identification of a five nucleotide (CAGAA) deletion in exon 2 of the antithrombin gene that results in a shift in the frame of translation of the mRNA and introduces a premature STOP signal in codon 70. The deleted nucleotides represent one repeat of a duplicated sequence within codons 36-39. The deletion may have arisen by slippage and mispairing of the repeated sequences at the replication fork during DNA synthesis.

Possible misdiagnosis using the Xba I polymorphism for prenatal diagnosis of haemophilia A.

A mother of two haemophilia A sons presented at 7 weeks pregnancy for a prenatal diagnosis. Southern blot analysis of haemophilia DNA at the factor VIII intron 22 Xba I restriction fragment length polymorphism (RFLP) site revealed an Xba I haplotype of A-B+C-. This haplotype has been alluded to but not reported before, and when a 1.6 kb Bst XI fragment of p482.6 is used as a probe the resulting band pattern is similar to that of females heterozygous at site A.

Non-secretion of ABO blood group antigens: a host factor predisposing to recurrent urinary tract infections and renal scarring.

In a study of 718 women referred for specialist investigation for recurrent urinary tract infections, 250 (34.8%, P less than 0.01) were non-secretors. The proportion of non-secretors among the women with renal scars (42.6%) was higher than that found for women with no evidence of renal scars (36.6%). Among 29 patients in whom symptoms began in childhood or adolescence, 51.7% were non-secretors. The proportion of non-secretors among individuals with renal scars in this study (42.6%) and that reported in the accompanying paper for Swedish children (40%) suggests that non-secretion might influence the pathogenic sequelae of these infections. Possible host-parasite interactions underlying the increased proportion of non-secretors among women with recurrent urinary tract infections and those leading to development of renal scars are discussed.

Lewis a blood group antigen of non-secretors: a receptor for candida blastospores.

This study tested the hypothesis that the Lewis a blood group antigen found predominantly on the cells of non-secretors might be one of the receptors for Candida species. Binding of strain 3118C to epithelial cells from either secretor or non-secretor donors was not inhibited by treating the cells with anti-Lewis a or anti-Lewis b antisera. Binding of strain 3091 to non-secretor cells was inhibited by pretreating the cells with anti-Lewis a, but this was not observed for secretor cells. The results suggest that Lewis a might be one of the receptors for some yeast strains.

Characterization of Escherichia coli strains isolated from urine of secretors and non-secretors.

Strains of Escherichia coli isolated from urine of secretors (242) and non-secretors (121) were compared for their serotype and their ability to express mannose-sensitive (MS) haemagglutinins and mannose-resistant (MR) haemagglutinins and to produce haemolysin. The results of the survey refuted our hypothesis that strains with characteristics associated with virulence, those with MR haemagglutinins and/or haemolysins, would be isolated more frequently from non-secretors. MR haemagglutinins were detected among 36.4% of isolates from secretors and 27.3% of isolates from non-secretors. Haemolysin production was detected among 19.8% of isolates from secretors and 12.5% of isolates from non-secretors. Both MR haemagglutinins and haemolysin were detected only on 12.4% of strains from secretors and 6.7% of strains from non-secretors.

Secretor state and immunoglobulin levels among women with recurrent urinary tract infections.

In this study we tested the hypothesis that the increased susceptibility of non-secretors of blood group antigens to recurrent urinary tract infections might be due, in part, to lower levels of IgA reported for non-secretor Caucasian women. Total serum IgA and IgG levels of 200 women in a retrospective study group monitored by the local pyelonephritis unit for 20 yr was compared with those of 100 women from a prospective group recently referred to the clinic. Immunoglobulin levels of the retrospective group were analyzed with reference to the secretor state of the patient, improvement over the 20 yr and presence or absence of renal scars. Total IgA and IgG levels were significantly higher in the sera of non-secretors with or without renal scars and also among patients who had clinically improved over the 20-yr period. Most women appeared to improve regardless of age of onset of infections or treatment prescribed. It was suggested that improvement might be associated with a self-immunization phenomenon. The significantly higher levels of IgA and IgG found among the women in the retrospective study compared with the levels found in the sera of age-matched women in the prospective study is evidence for this hypothesis. The implications of these findings for further investigations of the pathogenesis of urinary tract infections are discussed.

Human T lymphocytes expressing a defined T-cell antigen receptor family specifically kill the hybridoma that makes the anti-receptor monoclonal antibody.

Human T lymphocytes expressing a family of T-cell antigen receptors defined by a particular monoclonal antibody can be induced to grow with the Mab and recombinant IL-2. The resulting population consists largely of cells that have the phenotype T3+, T8+, T4-, and that react with the inducing anti-TcR Mab. The ability of such T cells to kill the hybridoma which produces the inducing Mab has been investigated. Specific killing is demonstrated which is inhibited by Mab to T3, TcR, and LFA-1. Further, lytic activity is rapidly lost when cultures are deprived of lymphokines. Cytolytic activity is restored by incubating cells in recombinant IL-2.

The myelodysplastic syndrome: analysis of laboratory characteristics in relation to the FAB classification.

A detailed study of 43 newly diagnosed cases of myelodysplastic syndrome (MDS) shows that many of the morphological features of blood and bone marrow are common to the different FAB groups. In addition, there is no clear distinction between the groups with regard to CFU-E, BFU-E or CFU-GM colony growth in vitro or ferrokinetic assessment of erythropoiesis in vivo. The interrelationships between all the parameters we have studied have been examined and there is little correlation between erythroid colony formation in vitro, the percentage erythroblasts in the bone marrow, erythroid output measured by ferrokinetics and the peripheral blood reticulocyte count, all of which appear to measure different aspects of erythropoiesis. Reduced erythroid colony growth and a high degree of ineffective erythropoiesis in vivo are common in all groups and appear to be an early manifestation of abnormal function. Decreasing marrow iron turnover is more closely related to increasing numbers of marrow blast cells than any other index of erythropoiesis.

ABO blood group and susceptibility to urinary tract infection: no evidence for involvement of isohaemagglutinins.

Investigations of the possible mechanisms underlying the increased susceptibility of women who are blood group B and non-secretors of water-soluble blood group antigen to recurrent urinary tract infection (UTI) revealed that isohaemagglutinins are not involved in bactericidal killing or agglutination of 8 serotypes (1,2) of Escherichia coli frequently associated with UTI. The implications of these results and possible areas for future studies are discussed.