High-speed narrow-bore capillary gas chromatography in combination with a fast and double-focusing mass spectrometer

In this work the application of high-speed narrow-bore capillary GC in combination with a fast scanning double focusing magnetic sector mass spectrometer is evaluated. Special emphasis is placed upon detection limits and scan speed in the full scan mode and in the selected ion monitoring mode (SIM). In the full scan mode, up to 20 scans per second could be obtained. The detection limits are in the low picogram range in the full scan mode and improve even to 5 to 50 fg in the SIM mode, depending on the sample complexity and mass resolving power. It will be illustrated that by increasing the resolution in the SIM mode, interferences from ions of the same nominal mass-to-charge ratio as the ions of interest are significantly reduced. Chemical background noise can therefore be largely eliminated, thus enhancing the signal-to-noise ratio

Effect of Coulomb scattering from trapped charges on the mobility in an organic field-effect transistor

We investigate the effect of Coulomb scattering from trapped charges on the mobility in the two-dimensional channel of an organic field-effect transistor. The number of trapped charges can be tuned by applying a prolonged gate bias. Surprisingly, after increasing the number of trapped charges to a level where strong Coulomb scattering is expected, the mobility has decreased only slightly. Simulations show that this can be explained by assuming that the trapped charges are located in the gate dielectric at a significant distance from the channel instead of in or very close to the channel. The effect of Coulomb scattering is then strongly reduced

Novel criticality in a model with absorbing states

We study a one-dimensional model which undergoes a transition between an active and an absorbing phase. Monte Carlo simulations supported by some additional arguments prompted as to predict the exact location of the critical point and critical exponents in this model. The exponents $\delta=0.5$ and $z=2$ follows from random-walk-type arguments. The exponents $\beta = \nu_{\perp}$ are found to be non-universal and encoded in the singular part of reactivation probability, as recently discussed by H. Hinrichsen (cond-mat/0008179). A related model with quenched randomness is also studied.Comment: 5 pages, 5 figures, generalized version with the continuously changing exponent bet

Monocytes from chronic HBV patients react in vitro to HBsAg and TLR by producing cytokines irrespective of stage of disease

Individuals who are chronically infected with the hepatitis B virus (HBV) are highly heterogenous with respect to serum levels of HBV DNA, HBV particles and viral proteins. Since circulating leukocytes, such as monocytes, are constantly exposed to these viral components, it is likely that the functionality of these cells is affected. However, at present, little information is available on the consequences of the interaction between monocytes and viral components. Therefore, we examined the in vitro effects of HBV surface antigen (HBsAg) on monocytes and evaluated whether these effects were reflected in vivo. We observed that in vitro HBsAg exposure of monocytes induced robust production of IL-6 and TNF. However, between chronic HBV patients with distinct levels of serum HBsAg, HBV early antigen (HBeAg), and HBV DNA, TLR-induced monocyte cytokine production did not differ. Importantly, HBsAg-induced cytokine production by monocytes was similar between patients and healthy controls showing that earlier in vivo exposure to HBsAg does not affect the in vitro response. Additionally, we show that IL-10 is able to inhibit cytokine production by HBsAg-induced monocytes. In conclusion, we demonstrate that monocytes can recognize and respond to HBsAg, resulting in vigorous pro-inflammatory cytokine production in vitro. However, phenotype and function of the monocyte compartment in chronic HBV patients are not influenced by differences in levels of serum viral components, suggesting that regulatory mechanisms are active to avoid excessive in vivo monocyte activation

Citrullinated human and murine MOG_35–55 display distinct biophysical and biochemical behavior

The peptide spanning residues 35 to 55 of the protein myelin oligodendrocyte glycoprotein (MOG) has been studied extensively in its role as a key autoantigen in the neuroinflammatory autoimmune disease multiple sclerosis. Rodents and nonhuman primate species immunized with this peptide develop a neuroinflammatory condition called experimental autoimmune encephalomyelitis, often used as a model for multiple sclerosis. Over the last decade, the role of citrullination of this antigen in the disease onset and progression has come under increased scrutiny. We recently reported on the ability of these citrullinated MOG35–55 peptides to aggregate in an amyloid-like fashion, suggesting a new potential pathogenic mechanism underlying this disease. The immunodominant region of MOG is highly conserved between species, with the only difference between the murine and human protein, a polymorphism on position 42, which is serine in mice and proline for humans. Here, we show that the biophysical and biochemical behavior we previously observed for citrullinated murine MOG35–55 is fundamentally different for human and mouse MOG35–55. The citrullinated human peptides do not show amyloid-like behavior under the conditions where the murine peptides do. Moreover, we tested the ability of these peptides to stimulate lymphocytes derived from MOG immunized marmoset monkeys. While the citrullinated murine peptides did not produce a proliferative response, one of the citrullinated human peptides did. We postulate that this unexpected difference is caused by disparate antigen processing. Taken together, our results suggest that further study on the role of citrullination in MOG-induced experimental autoimmune encephalomyelitis is necessary.</p

Quantized charge transport through a static quantum dot using a surface acoustic wave

We present a detailed study of the surface acoustic wave mediated quantized transport of electrons through a split gate device containing an impurity potential defined quantum dot within the split gate channel. A new regime of quantized transport is observed at low RF powers where the surface acoustic wave amplitude is comparable to the quantum dot charging energy. In this regime resonant transport through the single-electron dot state occurs which we interpret as turnstile-like operation in which the traveling wave amplitude modulates the entrance and exit barriers of the quantum dot in a cyclic fashion at GHz frequencies. For high RF powers, where the amplitude of the surface acoustic wave is much larger than the quantum dot energies, the quantized acoustoelectric current transport shows behavior consistent with previously reported results. However, in this regime, the number of quantized current plateaus observed and the plateau widths are determined by the properties of the quantum dot, demonstrating that the microscopic detail of the potential landscape in the split gate channel has a profound influence on the quantized acoustoelectric current transport.Comment: 9 page

Resistivity of a Metal between the Boltzmann Transport Regime and the Anderson Transition

We study the transport properties of a finite three dimensional disordered conductor, for both weak and strong scattering on impurities, employing the real-space Green function technique and related Landauer-type formula. The dirty metal is described by a nearest neighbor tight-binding Hamiltonian with a single s-orbital per site and random on-site potential (Anderson model). We compute exactly the zero-temperature conductance of a finite size sample placed between two semi-infinite disorder-free leads. The resistivity is found from the coefficient of linear scaling of the disorder averaged resistance with sample length. This ``quantum'' resistivity is compared to the semiclassical Boltzmann expression computed in both Born approximation and multiple scattering approximation.Comment: 5 pages, 3 embedded EPS figure

Small-molecule activity-based probe for monitoring ubiquitin C-terminal hydrolase L1 (UCHL1) activity in live cells and zebrafish embryos

Many reagents have emerged to study the function of specific enzymes in vitro. On the other hand, target specific reagents are scarce or need improvement, allowing investigations of the function of individual enzymes in their native cellular context. Here we report the development of a target-selective fluorescent small-molecule activity-based DUB probe that is active in live cells and an in vivo animal model. The probe labels active ubiquitin carboxy-terminal hydrolase L1 (UCHL1), also known as neuron-specific protein PGP9.5 (PGP9.5) and Parkinson disease 5 (PARK5), a DUB active in neurons that constitutes 1 to 2% of the total brain protein. UCHL1 variants have been linked with neurodegenerative disorders Parkinson's and Alzheimer's diseases. In addition, high levels of UCHL1 also correlate often with cancer and especially metastasis. The function of UCHL1 activity or its role in cancer and neurodegenerative disease is poorly understood and few UCHL1-specific activity tools exist. We show that the reagents reported here are specific to UCHL1 over all other DUBs detectable by competitive activity-based protein profiling and by mass spectrometry. Our cell-penetrable probe, which contains a cyanimide reactive moiety, binds to the active-site cysteine residue of UCHL1 in an activity-dependent manner. Its use is demonstrated by the fluorescent labeling of active UCHL1 both in vitro and in live cells. We furthermore show that this probe can selectively and spatiotemporally report UCHL1 activity during the development of zebrafish embryos. Our results indicate that our probe has potential applications as a diagnostic tool for diseases with perturbed UCHL1 activity.Cancer Signaling networks and Molecular Therapeutic

A flexible MHC class I multimer loading system for large-scale detection of antigen-specific T cells

Tumorimmunolog

Tailoring Anderson localization by disorder correlations in 1D speckle potentials

We study Anderson localization of single particles in continuous, correlated, one-dimensional disordered potentials. We show that tailored correlations can completely change the energy-dependence of the localization length. By considering two suitable models of disorder, we explicitly show that disorder correlations can lead to a nonmonotonic behavior of the localization length versus energy. Numerical calculations performed within the transfer-matrix approach and analytical calculations performed within the phase formalism up to order three show excellent agreement and demonstrate the effect. We finally show how the nonmonotonic behavior of the localization length with energy can be observed using expanding ultracold-atom gases