2,972 research outputs found
Discovery (theoretical prediction and experimental observation) of a large-gap topological-insulator class with spin-polarized single-Dirac-cone on the surface
Recent theories and experiments have suggested that strong spin-orbit
coupling effects in certain band insulators can give rise to a new phase of
quantum matter, the so-called topological insulator, which can show macroscopic
entanglement effects. Such systems feature two-dimensional surface states whose
electrodynamic properties are described not by the conventional Maxwell
equations but rather by an attached axion field, originally proposed to
describe strongly interacting particles. It has been proposed that a
topological insulator with a single spin-textured Dirac cone interfaced with a
superconductor can form the most elementary unit for performing fault-tolerant
quantum computation. Here we present an angle-resolved photoemission
spectroscopy study and first-principle theoretical calculation-predictions that
reveal the first observation of such a topological state of matter featuring a
single-surface-Dirac-cone realized in the naturally occurring BiSe
class of materials. Our results, supported by our theoretical predictions and
calculations, demonstrate that undoped compound of this class of materials can
serve as the parent matrix compound for the long-sought topological device
where in-plane surface carrier transport would have a purely quantum
topological origin. Our study further suggests that the undoped compound
reached via n-to-p doping should show topological transport phenomena even at
room temperature.Comment: 3 Figures, 18 pages, Submitted to NATURE PHYSICS in December 200
Aharonov-Bohm interference in topological insulator nanoribbons
Topological insulators represent novel phases of quantum matter with an
insulating bulk gap and gapless edges or surface states. The two-dimensional
topological insulator phase was predicted in HgTe quantum wells and confirmed
by transport measurements. Recently, Bi2Se3 and related materials have been
proposed as three-dimensional topological insulators with a single Dirac cone
on the surface and verified by angle-resolved photoemission spectroscopy
experiments. Here, we show unambiguous transport evidence of topological
surface states through periodic quantum interference effects in layered
single-crystalline Bi2Se3 nanoribbons. Pronounced Aharonov-Bohm oscillations in
the magnetoresistance clearly demonstrate the coverage of two-dimensional
electrons on the entire surface, as expected from the topological nature of the
surface states. The dominance of the primary h/e oscillation and its
temperature dependence demonstrate the robustness of these electronic states.
Our results suggest that topological insulator nanoribbons afford novel
promising materials for future spintronic devices at room temperature.Comment: 5 pages, 4 figures, RevTex forma
Detecting and predicting neutralization of alemtuzumab responses in MS
Objective: To test the hypothesis that anti-drug antibodies against alemtuzumab could become relevant after repeated treatments for some individuals, possibly explaining occasional treatment resistance. Methods: Recombinant alemtuzumab single-chain variable fragment antibody with a dual tandem nanoluciferase reporter linker was made and used to detect binding anti-drug antibodies. Alemtuzumab IgG Alexa-Fluor 488 conjugate was used in a competitive-binding cell based assay to detect neutralizing anti-drug antibodies. The assays were used to retrospectively screen, blinded, banked-serum samples from people with multiple sclerosis (n=32) who had received three or more cycles of alemtuzumab. Lymphocyte depletion was measured between baseline and about 1 month post-infusion. Results: The number of individuals showing limited depletion of lymphocytes increased with the number of treatment cycles. Lack of depletion was also a poor prognostic feature for future disease activity. Anti-drug antibody responses were detected in 29/32 (90.6%) individuals. Neutralizing antibodies occurred prior to the development of limited depletion in 6/7 individuals (18.8% of the whole sample). Pre-infusion, anti-drug antibody levels predicted limited, post-infusion lymphocyte depletion. Conclusions: Although anti-drug antibodies to alemtuzumab have been portrayed as being of no clinical significance, alemtuzumab-specific antibodies appear to be clinically relevant for some individuals, although causation remains to be established. Monitoring of, lymphocyte depletion and the anti-drug response may be of practical value in patients requiring additional cycles of alemtuzumab. Anti-drug antibody detection may help to inform on re-treatment or switching to another treatment
Characterization of Shewanella oneidensis MtrC: a cell-surface decaheme cytochrome involved in respiratory electron transport to extracellular electron acceptors
MtrC is a decaheme c-type cytochrome associated with the outer cell membrane of Fe(III)-respiring species of the Shewanella genus. It is proposed to play a role in anaerobic respiration by mediating electron transfer to extracellular mineral oxides that can serve as terminal electron acceptors. The present work presents the first spectropotentiometric and voltammetric characterization of MtrC, using protein purified from Shewanella oneidensis MR-1. Potentiometric titrations, monitored by UVβvis absorption and electron paramagnetic resonance (EPR) spectroscopy, reveal that the hemes within MtrC titrate over a broad potential range spanning between approximately +100 and approximately -500 mV (vs. the standard hydrogen electrode). Across this potential window the UVβvis absorption spectra are characteristic of low-spin c-type hemes and the EPR spectra reveal broad, complex features that suggest the presence of magnetically spin-coupled low-spin c-hemes. Non-catalytic protein film voltammetry of MtrC demonstrates reversible electrochemistry over a potential window similar to that disclosed spectroscopically. The voltammetry also allows definition of kinetic properties of MtrC in direct electron exchange with a solid electrode surface and during reduction of a model Fe(III) substrate. Taken together, the data provide quantitative information on the potential domain in which MtrC can operate
Defective monocyte oxidative burst predicts infection in alcoholic hepatitis and is associated with reduced expression of NADPH oxidase
Objective In order to explain the increased susceptibility to serious infection in alcoholic hepatitis, we evaluated monocyte phagocytosis, aberrations of associated signalling pathways and their reversibility, and whether phagocytic defects could predict subsequent infection. Design Monocytes were identified from blood samples of 42 patients with severe alcoholic hepatitis using monoclonal antibody to CD14. Phagocytosis and monocyte oxidative burst (MOB) were measured ex vivo using flow cytometry, luminometry and bacterial killing assays. Defects were related to the subsequent development of infection. Intracellular signalling pathways were investigated using western blotting and PCR. Interferon-Ξ³ (IFN-Ξ³) was evaluated for its therapeutic potential in reversing phagocytic defects. Paired longitudinal samples were used to evaluate the effect of in vivo prednisolone therapy. Results MOB, production of superoxide and bacterial killing in response to Escherichia coli were markedly impaired in patients with alcoholic hepatitis. Pretreatment MOB predicted development of infection within two weeks with sensitivity and specificity that were superior to available clinical markers. Accordingly, defective MOB was associated with death at 28 and 90 days. Expression of the gp91phox subunit of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase was reduced in patients with alcoholic hepatitis demonstrating defective MOB. Monocytes were refractory to IFN-Ξ³ stimulation and showed high levels of a negative regulator of cytokine signalling, suppressor of cytokine signalling-1. MOB was unaffected by 7 days in vivo prednisolone therapy. Conclusions Monocyte oxidative burst and bacterial killing is impaired in alcoholic hepatitis while bacterial uptake by phagocytosis is preserved. Defective MOB is associated with reduced expression of NADPH oxidase in these patients and predicts the development of infection and death
CP violation Beyond the MSSM: Baryogenesis and Electric Dipole Moments
We study electroweak baryogenesis and electric dipole moments in the presence
of the two leading-order, non-renormalizable operators in the Higgs sector of
the MSSM. Significant qualitative and quantitative differences from MSSM
baryogenesis arise due to the presence of new CP-violating phases and to the
relaxation of constraints on the supersymmetric spectrum (in particular, both
stops can be light). We find: (1) spontaneous baryogenesis, driven by a change
in the phase of the Higgs vevs across the bubble wall, becomes possible; (2)
the top and stop CP-violating sources can become effective; (3) baryogenesis is
viable in larger parts of parameter space, alleviating the well-known
fine-tuning associated with MSSM baryogenesis. Nevertheless, electric dipole
moments should be measured if experimental sensitivities are improved by about
one order of magnitude.Comment: 33 pages, 6 figure
Transition of plasmodium sporozoites into liver stage-like forms is regulated by the RNA binding protein pumilio
Many eukaryotic developmental and cell fate decisions that are effected post-transcriptionally involve RNA binding proteins as regulators of translation of key mRNAs. In malaria parasites (Plasmodium spp.), the development of round, non-motile and replicating exo-erythrocytic liver stage forms from slender, motile and cell-cycle arrested sporozoites is believed to depend on environmental changes experienced during the transmission of the parasite from the mosquito vector to the vertebrate host. Here we identify a Plasmodium member of the RNA binding protein family PUF as a key regulator of this transformation. In the absence of Pumilio-2 (Puf2) sporozoites initiate EEF development inside mosquito salivary glands independently of the normal transmission-associated environmental cues. Puf2- sporozoites exhibit genome-wide transcriptional changes that result in loss of gliding motility, cell traversal ability and reduction in infectivity, and, moreover, trigger metamorphosis typical of early Plasmodium intra-hepatic development. These data demonstrate that Puf2 is a key player in regulating sporozoite developmental control, and imply that transformation of salivary gland-resident sporozoites into liver stage-like parasites is regulated by a post-transcriptional mechanism
Risk factors for high anti-HHV-8 antibody titers (β₯1:51,200) in black, HIV-1 negative South African cancer patients: a case control study
Background: Infection with human herpesvirus 8 (HHV-8) is the necessary causal agent in the
development of Kaposi's sarcoma (KS). Infection with HIV-1, male gender and older age all increase
risk for KS. However, the geographic distribution of HHV-8 and KS both prior to the HIV/AIDS
epidemic and with HIV/AIDS suggest the presence of an additional co-factor in the development of
KS.
Methods: Between January 1994 and October 1997, we interviewed 2576 black in-patients with
cancer in Johannesburg and Soweto, South Africa. Blood was tested for antibodies against HIV-1
and HHV-8 and the study was restricted to 2191 HIV-1 negative patients. Antibodies against the
latent nuclear antigen of HHV-8 encoded by orf73 were detected with an indirect
immunofluorescence assay. We examined the relationship between high anti-HHV-8 antibody
titers (β₯1:51,200) and sociodemographic and behavioral factors using unconditional logistic
regression models. Variables that were significant at p = 0.10 were included in multivariate analysis.
Results: Of the 2191 HIV-1 negative patients who did not have Kaposi's sarcoma, 854 (39.0%)
were positive for antibodies against HHV-8 according to the immunofluorescent assay. Among
those seropositive for HHV-8, 530 (62.1%) had low titers (1:200), 227 (26.6%) had medium titers
(1:51,200) and 97 (11.4%) had highest titers (1:204,800). Among the 2191 HIV-1 negative patients,
the prevalence of high anti-HHV-8 antibody titers (β₯1:51,200) was independently associated with
increasing age (ptrend = 0.04), having a marital status of separated or divorced (p = 0.003), using
wood, coal or charcoal as fuel for cooking 20 years ago instead of electricity (p = 0.02) and
consuming traditional maize beer more than one time a week (p = 0.02; p-trend for increasing
consumption = 0.05) although this may be due to chance given the large number of predictors
considered in this analysis.
Conclusions: Among HIV-negative subjects, patients with high anti-HHV-8 antibody titers are
characterized by older age. Other associations that may be factors in the development of high anti-
HHV-8 titers include exposure to poverty or a low socioeconomic status environment and
consumption of traditional maize beer. The relationship between these variables and high anti-
HHV-8 titers requires further, prospective study
Multi-level evidence of an allelic hierarchy of USH2A variants in hearing, auditory processing and speech/language outcomes.
Language development builds upon a complex network of interacting subservient systems. It therefore follows that variations in, and subclinical disruptions of, these systems may have secondary effects on emergent language. In this paper, we consider the relationship between genetic variants, hearing, auditory processing and language development. We employ whole genome sequencing in a discovery family to target association and gene x environment interaction analyses in two large population cohorts; the Avon Longitudinal Study of Parents and Children (ALSPAC) and UK10K. These investigations indicate that USH2A variants are associated with altered low-frequency sound perception which, in turn, increases the risk of developmental language disorder. We further show that Ush2a heterozygote mice have low-level hearing impairments, persistent higher-order acoustic processing deficits and altered vocalizations. These findings provide new insights into the complexity of genetic mechanisms serving language development and disorders and the relationships between developmental auditory and neural systems
A study of 54 cases of left displacement of the abomasum: February to July 2005
Fifty-four cows with left displacement of the abomasum (LDA) submitted to the hospital facility at Riverview Veterinary Clinic from February to July 2005 were treated by right flank laparotomy and omentopexy. Five cows died (a survival rate 90.7%) and one cow (1.8%) was culled due to recurrence of the LDA post-operatively. Forty-one cows (76%) returned to good production post-operatively. Thirty-nine cows (72%) were pregnant six months after corrective surgery
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