Interplay of size and Landau quantizations in the de Haas-van Alphen oscillations of metallic nanowires

We examine the interplay between size quantization and Landau quantization in the De Haas-Van Alphen oscillations of clean, metallic nanowires in a longitudinal magnetic field for `hard' boundary conditions, i.e. those of an infinite round well, as opposed to the `soft' parabolically confined boundary conditions previously treated in Alexandrov and Kabanov (Phys. Rev. Lett. {\bf 95}, 076601 (2005) (AK)). We find that there exist {\em two} fundamental frequencies as opposed to the one found in bulk systems and the three frequencies found by AK with soft boundary counditions. In addition, we find that the additional `magic resonances' of AK may be also observed in the infinite well case, though they are now damped. We also compare the numerically generated energy spectrum of the infinite well potential with that of our analytic approximation, and compare calculations of the oscillatory portions of the thermodynamic quantities for both models.Comment: Title changed, paper streamlined on suggestion of referrees, typos corrected, numerical error in figs 2 and 3 corrected and final result simplified -- two not three frequencies (as in the previous version) are observed. Abstract altered accordingly. Submitted to Physical Review

Kondo temperature of magnetic impurities at surfaces

Based on the experimental observation, that only the close vicinity of a magnetic impurity at metal surfaces determines its Kondo behaviour, we introduce a simple model which explains the Kondo temperatures observed for cobalt adatoms at the (111) and (100) surfaces of Cu, Ag, and Au. Excellent agreement between the model and scanning tunneling spectroscopy (STS) experiments is demonstrated. The Kondo temperature is shown to depend on the occupation of the d-level determined by the hybridization between adatom and substrate with a minimum around single occupancy.Comment: 4 pages, 2 figure

A peptide mimic of the chemotaxis inhibitory protein of Staphylococcus aureus: towards the development of novel anti-inflammatory compounds

Complement factor C5a is one of the most powerful pro-inflammatory agents involved in recruitment of leukocytes, activation of phagocytes and other inflammatory responses. C5a triggers inflammatory responses by binding to its G-protein-coupled C5a-receptor (C5aR). Excessive or erroneous activation of the C5aR has been implicated in numerous inflammatory diseases. The C5aR is therefore a key target in the development of specific anti-inflammatory compounds. A very potent natural inhibitor of the C5aR is the 121-residue chemotaxis inhibitory protein of Staphylococcus aureus (CHIPS). Although CHIPS effectively blocks C5aR activation by binding tightly to its extra-cellular N terminus, it is not suitable as a potential anti-inflammatory drug due to its immunogenic properties. As a first step in the development of an improved CHIPS mimic, we designed and synthesized a substantially shorter 50-residue adapted peptide, designated CHOPS. This peptide included all residues important for receptor binding as based on the recent structure of CHIPS in complex with the C5aR N terminus. Using isothermal titration calorimetry we demonstrate that CHOPS has micromolar affinity for a model peptide comprising residues 7–28 of the C5aR N terminus including two O-sulfated tyrosine residues at positions 11 and 14. CD and NMR spectroscopy showed that CHOPS is unstructured free in solution. Upon addition of the doubly sulfated model peptide, however, the NMR and CD spectra reveal the formation of structural elements in CHOPS reminiscent of native CHIPS

Anti-correlation between the mass of a supermassive black hole and the mass accretion rate in type I ultraluminous infrared galaxies and nearby QSOs

We discovered a significant anti-correlation between the mass of a supermassive black hole (SMBH), $M_{\rm BH}$, and the luminosity ratio of infrared to active galactic nuclei (AGN) Eddington luminosity, $L_{\rm IR}/L_{\rm Edd}$, over four orders of magnitude for ultraluminous infrared galaxies with type I Seyfert nuclei (type I ULIRGs) and nearby QSOs. This anti-correlation ($M_{\rm BH}$ vs. $L_{\rm IR}/L_{\rm Edd}$) can be interpreted as the anti-correlation between the mass of a SMBH and the rate of mass accretion onto a SMBH normalized by the AGN Eddington rate, $\dot{M}_{\rm BH}/\dot{M}_{\rm Edd}$. In other words, the mass accretion rate $\dot{M}_{\rm BH}$ is not proportional to that of the central BH mass. Thus, this anti-correlation indicates that BH growth is determined by the external mass supply process, and not the AGN Eddington-limited mechanism. Moreover, we found an interesting tendency for type I ULIRGs to favor a super-Eddington accretion flow, whereas QSOs tended to show a sub-Eddington flow. On the basis of our findings, we suggest that a central SMBH grows by changing its mass accretion rate from super-Eddington to sub-Eddington. According to a coevolution scenario of ULIRGs and QSOs based on the radiation drag process, it has been predicted that a self-gravitating massive torus, whose mass is larger than a central BH, exists in the early phase of BH growth (type I ULIRG phase) but not in the final phase of BH growth (QSO phase). At the same time, if one considers the mass accretion rate onto a central SMBH via a turbulent viscosity, the anti-correlation ($M_{\rm BH}$ vs. $L_{\rm IR}/L_{\rm Edd}$) is well explained by the positive correlation between the mass accretion rate $\dot{M}_{\rm BH}$ and the mass ratio of a massive torus to a SMBH.Comment: 29 pages, 4 figures, accepted for publication in Ap

Search for emission of unstable 8^8Be clusters from hot 40^40Ca and 56^56Ni nuclei

The possible occurence of highly deformed configurations is investigated in the $^{40}$Ca and $^{56}$Ni di-nuclear systems as formed in the $^{28}$Si + $^{12}$C and $^{28}$Si + $^{28}$Si reactions, respectively, by using the properties of emitted light charged particles. Inclusive as well as exclusive data of the heavy fragments (A $\geq$ 6) and their associated light charged particles (p, d, t, and $\alpha$-particles) have been collected at the IReS Strasbourg VIVITRON Tandem facility with two bombarding energies $E_{lab}(^{28}$Si) = 112 and 180 MeV by using the ICARE charged particle multidetector array, which consists of nearly 40 telescopes. The measured energy spectra, velocity distributions, in-plane and out-of-plane angular correlations are analysed by Monte Carlo CASCADE statistical-model calculations using a consistent set of parameters with spin-dependent level densities. Although significant deformation effects at high spin are needed, the remaining disagreement observed in the $^{28}$Si + $^{12}$C reaction for the S evaporation residue suggests an unexpected large unstable $^{8}$Be cluster emission of a binary nature.Comment: 13 pages latex, 9 eps figures. Paper presented at the XXXIX International Winter Meeting on Nuclear Physics, Bormio(Italy) January 22-27, 2001 (to be published at Ricerca Scientifica ed Educazione Permanente

The diagnostic accuracy of CT and MRI for the detection of lymph node metastases in gallbladder cancer:A systematic review and meta-analysis

BACKGROUND: Lymph node metastases (LNM) are an ominous prognostic factor in gallbladder cancer (GBC) and, when present, should preclude surgery. However, uncertainty remains regarding the optimal imaging modality for pre-operative detection of LNM and international guidelines vary in their recommendations. The purpose of this study was to systematically review the diagnostic accuracy of computed tomography (CT) versus magnetic resonance imaging (MRI) in the detection of LNM of GBC. METHODS: A literature search of studies published until November 2017 concerning the diagnostic accuracy of CT or MRI regarding the detection of LNM in GBC was performed. Data extraction and risk of bias assessment was performed independently by two reviewers. The sensitivity of CT and MRI in the detection of LNM was reviewed. Additionally, estimated summary sensitivity, specificity and diagnostic accuracy of MRI were calculated in a patient based meta-analysis. RESULTS: Nine studies including 292 patients were included for narrative synthesis and 5 studies including 158 patients were selected for meta-analysis. Sensitivity of CT ranged from 0.25 to 0.93. Estimated summary diagnostic accuracy parameters of MRI were as follows: sensitivity 0.75 (95% CI 0.6 - 0.85), specificity 0.83 (95% CI 0.74 - 0.90), LR + 4.52 (95% CI 2.55-6.48) and LR- 0.3 (95% CI 0.15 - 0.45). Small (<10 mm) LNM were most frequently undetected on pre-operative imaging. Due to a lack of data, no subgroup analysis comparing the diagnostic accuracy of CT versus MRI could be performed. CONCLUSION: The value of current imaging strategies for the pre-operative assessment of nodal status in GBC remains unclear, especially regarding the detection of small LNM. Additional research is warranted in order to establish uniformity in international guidelines, improve pre-operative nodal staging and to prevent futile surgery

Staphylococcus aureus toxin LukSF dissociates from its membrane receptor target to enable renewed ligand sequestration

Staphylococcus aureus Panton-Valentine leukocidin is a pore-forming toxin targeting the human C5a receptor (hC5aR), enabling this pathogen to battle the immune response by destroying phagocytes through targeted lysis. The mechanisms that contribute to rapid cell lysis are largely unexplored. Here, we show that cell lysis may be enabled by a process of toxins targeting receptor clusters and present indirect evidence for receptor recycling that allows multiple toxin pores to be formed close together. With the use of live cell single-molecule super-resolution imaging, Forster resonance energy transfer and nanoscale total internal reflection fluorescence colocalization microscopy, we visualized toxin pore formation in the presence of its natural docking ligand. We demonstrate disassociation of hC5aR from toxin complexes and simultaneous binding of new ligands. This effect may free mobile receptors to amplify hyperinflammatory reactions in early stages of microbial infections and have implications for several other similar bicomponent toxins and the design of new antibiotics.Haapasalo, K., Wollman, A. J. M., de Haas, C. J. C., van Kessel, K. P. M., van Strijp, J. A. G., Leake, M. C. Staphylococcus aureus toxin LukSF dissociates from its membrane receptor target to enable renewed ligand sequestration.Peer reviewe

El Mañana: Año II Número 9 - (09/01/29)

There is no consensus on the treatment of multifocal primary cutaneous anaplastic large cell lymphoma (C-ALCL). Radiotherapy (RT) and methotrexate (MTX) are the current treatment options, but their efficacy is unknown. Recently, targeted therapies showed promising results in C-ALCL, and may therefore be an attractive first choice of treatment. To assess the efficacy of conventional treatment strategies for patients with multifocal C-ALCL, and to define which patients may require novel targeted therapies. In this multicenter study, treatment was evaluated in patients initially presenting (n=24) or relapsing with multifocal C-ALCL (n=17; 23 relapses). Distinction was made between cases with ≤ 5 (n=36) and >5 lesions (n=11). Treatments most commonly used were radiotherapy (n=21), systemic chemotherapy (n=9) and low-dose methotrexate (MTX; n=7) with complete response rates of 100%, 78% and 43%, respectively, and an overall response rate of 100%, 100%, and 57%, respectively. Four patients showed a complete spontaneous regression. Sixteen of 24 patients (67%) first presenting with multifocal C-ALCL relapsed, including all five patients initially treated with CHOP. Compared with patients presenting with 2-5 skin lesions, patients presenting with >5 lesions had a higher chance of developing extracutaneous relapse (56 vs 20%) and more often died of lymphoma (44% vs 7%). Patients with ≤5 lesions should be treated with low-dose RT (2x4 Gy). Maintenance low-dose MTX (20 mg/week) is a suitable option in patients with >5 lesions. Targeted therapies may be considered in rare patients refractory to MTX or patients developing extracutaneous disease. This article is protected by copyright. All rights reserve

Altered MRP is associated with multidrug resistance and reduced drug accumulation in human SW-1573 cells.

We have analysed the contribution of several parameters, e.g. drug accumulation, MDR1 P-glycoprotein (P-gp), multidrug resistance-associated protein (MRP) and topoisomerase (topo) II, to drug resistance in a large set of drug-resistant variants of the human non-small-cell lung cancer cell line SW-1573 derived by selection with low concentrations of doxorubicin or vincristine. Selection with either drug nearly always resulted in MDR clones. The resistance of these clones could be explained by reduced drug accumulation and was associated with a decrease rather than an increase in the low MDR1 mRNA level. To test whether a decrease in MDR1 mRNA indirectly affected resistance in these cells, we introduced a MDR1-specific hammerhead ribozyme into wild-type SW-1573 cells. Although this led to a substantial reduction in MDR1 mRNA, it did not result in resistance. In all resistant clones we found an altered form of the multidrug resistance-associated protein (MRP), migrating slightly slower during SDS-polyacrylamide gel electrophoresis than MRP in parental cells. This altered MRP was also present in non-P-gp MDR somatic cell hybrids of the SW-1573 cells, demonstrating a clear linkage with the MDR phenotype. Treatment of crude cellular membrane fractions with N-glycanase, endoglycosidase H or neuraminidase showed that the altered migration of MRP on SDS-PAGE is due to a post-translational modification. There was no detectable difference in sialic acid content. In most but not all doxorubicin-selected clones, this MDR phenotype was accompanied by a reduction in topo II alpha mRNA level. No reduction was found in the clones selected with vincristine. We conclude from these results that selection of the SW-1573 cell line for low levels of doxorubicin or vincristine resistance, predominantly results in MDR with reduced drug accumulation associated with the presence of an altered MRP protein. This mechanism can be accompanied by other resistance mechanisms, such as reduced topo II alpha mRNA in case of doxorubicin selection