9,853 research outputs found
Nature of band-gap states in V-doped TiO2 revealed by resonant photoemission
Band-gap states in V-doped TiO2 have been studied by photoemission spectroscopy over a range of photon energies encompassing the Ti 3p and V 3p core thresholds. The states show resonant enhancement at photon energies significantly higher than found for Ti 3d states introduced into TiO2 by oxygen deficiency or alkalimetal adsorbates. This demonstrates that the gap states relate to electrons trapped on dopant V cations rather than host Ti cations
Caspase 8 activation independent of Fas (CD95/APO-1) signaling may mediate killing of B-chronic lymphocytic leukemia cells by cytotoxic drugs or gamma radiation.
Ligation of the cell-surface Fas molecule by its ligand (Fas-L) or agonistic anti-Fas monoclonal antibodies results in the cleavage and activation of the cysteine protease procaspase 8 followed by the activation of procaspase 3 and by apoptosis. In some leukemia cell lines, cytotoxic drugs induce expression of Fas-L, which may contribute to cell killing through the ligation of Fas. The involvement of Fas, Fas-L, and caspase 8 was studied in the killing of B-cell chronic lymphocytic leukemia (B-CLL) cells by chlorambucil, fludarabine, or gamma radiation. Spontaneous apoptosis was observed at 24-hour incubation, with additional apoptosis induced by each of the cytotoxic treatments. Although Fas mRNA expression was elevated after exposure to chlorambucil, fludarabine, or gamma radiation, Fas protein levels only increased after irradiation. Therefore, Fas expression may be regulated by multiple mechanisms that allow the translation of Fas mRNA only in response to restricted cytotoxic stimuli. None of the cytotoxic stimuli studied here induced Fas-L expression. An agonistic anti-Fas monoclonal antibody (CH-11) did not significantly augment apoptosis induction by any of the death stimuli. A Fas-blocking antibody (ZB4) did not inhibit spontaneous, chlorambucil-, fludarabine-, or radiation-induced apoptosis. However, procaspase 8 processing was induced by all cytotoxic stimuli. These data suggest that the Fas/Fas-L signaling system does not play a major role in the induction of apoptosis in B-CLL cells treated with cytotoxic drugs or radiation. However, Fas-independent activation of caspase 8 may play a crucial role in the regulation of apoptosis in these cells
Geldanamycin and herbimycin A induce apoptotic killing of B chronic lymphocytic leukemia cells and augment the cells' sensitivity to cytotoxic drugs.
We studied the actions of geldanamycin (GA) and herbimycin A (HMA), inhibitors of the chaperone proteins Hsp90 and GRP94, on B chronic lymphocytic leukemia (CLL) cells in vitro. Both drugs induced apoptosis of the majority of CLL isolates studied. Whereas exposure to 4-hour pulses of 30 to 100 nM GA killed normal B lymphocytes and CLL cells with similar dose responses, T lymphocytes from healthy donors as well as those present in the CLL isolates were relatively resistant. GA, but not HMA, showed a modest cytoprotective effect toward CD34+ hematopoietic progenitors from normal bone marrow. The ability of bone marrow progenitors to form hematopoietic colonies was unaffected by pulse exposures to GA. Both GA and HMA synergized with chlorambucil and fludarabine in killing a subset of CLL isolates. GA- and HMA-induced apoptosis was preceded by the up-regulation of the stress-responsive chaperones Hsp70 and BiP. Both ansamycins also resulted in down-regulation of Akt protein kinase, a modulator of cell survival. The relative resistance of T lymphocytes and of CD34+ bone marrow progenitors to GA coupled with its ability to induce apoptosis following brief exposures and to synergize with cytotoxic drugs warrant further investigation of ansamycins as potential therapeutic agents in CLL
Modeling Accuracy and Variability of Motor Timing in Treated and Untreated Parkinson’s Disease and Healthy Controls
Parkinson’s disease (PD) is characterized by difficulty with the timing of movements. Data collected using the synchronization–continuation paradigm, an established motor timing paradigm, have produced varying results but with most studies finding impairment. Some of this inconsistency comes from variation in the medication state tested, in the inter-stimulus intervals (ISI) selected, and in changeable focus on either the synchronization (tapping in time with a tone) or continuation (maintaining the rhythm in the absence of the tone) phase. We sought to re-visit the paradigm by testing across four groups of participants: healthy controls, medication naïve de novo PD patients, and treated PD patients both “on” and “off” dopaminergic medication. Four finger tapping intervals (ISI) were used: 250, 500, 1000, and 2000 ms. Categorical predictors (group, ISI, and phase) were used to predict accuracy and variability using a linear mixed model. Accuracy was defined as the relative error of a tap, and variability as the deviation of the participant’s tap from group predicted relative error. Our primary finding is that the treated PD group (PD patients “on” and “off” dopaminergic therapy) showed a significantly different pattern of accuracy compared to the de novo group and the healthy controls at the 250-ms interval. At this interval, the treated PD patients performed “ahead” of the beat whilst the other groups performed “behind” the beat. We speculate that this “hastening” relates to the clinical phenomenon of motor festination. Across all groups, variability was smallest for both phases at the 500-ms interval, suggesting an innate preference for finger tapping within this range. Tapping variability for the two phases became increasingly divergent at the longer intervals, with worse performance in the continuation phase. The data suggest that patients with PD can be best discriminated from healthy controls on measures of motor timing accuracy, rather than variability
Albumin activates the AKT signalling pathway and protects B-chronics lymphocytic leukemia cells from chlorambucil- and radiation-induced apoptosis
Comparison of the Near-Threshold Production of eta- and K-Mesons in Proton-Proton Collisions
The pp -> pp eta and pp -> pLambda K^+ reactions near threshold are dominated
by the first and second S_11 resonance respectively. It is shown that a
one-pion-exchange model exciting these isobars reproduces well the ratio of the
production cross sections. The consequences for this and other channels are
discussed.Comment: 10 pages, LaTeX2e, 1 eps-figur
The Discovery of Gas-Rich, Dusty Starbursts in Luminous Reddened Quasars at with ALMA
We present ALMA observations of cold dust and molecular gas in four high-luminosity, heavily reddened (A mag) Type 1 quasars at with virial MM, to test whether dusty, massive quasars represent the evolutionary link between submillimetre bright galaxies (SMGs) and unobscured quasars. All four quasars are detected in both the dust continuum and in the CO(3-2) line. The mean dust mass is 610M assuming a typical high redshift quasar spectral energy distribution (T=41K, =1.95 or T=47K, =1.6). The implied star formation rates are very high - 1000 M yr in all cases. Gas masses estimated from the CO line luminosities cover 1-5()M and the gas depletion timescales are very short - Myr. A range of gas-to-dust ratios is observed in the sample. We resolve the molecular gas in one quasar - ULASJ23150143 () - which shows a strong velocity gradient over 20 kpc. The velocity field is consistent with a rotationally supported gas disk but other scenarios, e.g. mergers, cannot be ruled out at the current resolution of these data. In another quasar - ULASJ1234+0907 () - we detected molecular line emission from two millimetre bright galaxies within 200 kpc of the quasar, suggesting that this quasar resides in a significant over-density. The high detection rate of both cold dust and molecular gas in these sources, suggests that reddened quasars could correspond to an early phase in massive galaxy formation associated with large gas reservoirs and significant star formation.MB acknowledges funding from the UK Science and Technology Facilities Council (STFC) via an Ernest Rutherford Fellowship. GJ is grateful for support from NRAO through the Grote Reber Doctoral Fellowship Program. RGM and PCH acknowledge funding from STFC via the Institute of Astronomy, Cambridge Consolidated Grant. SA-Z acknowledges support from Peterhouse, Cambridge
True nature of an archetypal self-assembly system: Mobile Au-thiolate species on Au(111)
Alkanethiol self-assembled monolayer (SAM) phases on Au(111) have been assumed to involve direct S head group bonding to the substrate. Using x-ray standing wave experiments, we show the thiolate actually bonds to gold adatoms; self-organization in these archetypal SAM systems must therefore be governed by the movement of these Au-S-R moieties on the surface between two distinct local hollow sites on the surface. The results of recent ab initio total energy calculations provide strong support for this description, and a rationale for the implied significant molecular mobility in these systems
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