The ability of an alpha-emitter conjugated to a chimaeric anti-CD20 monoclonal antibody to kill selectively human B-lymphoma cells in vitro is reported. Two B-lymphoma cell lines RAEL and K422, and ...normal haematopoietic progenitor cells from human bone marrow aspirates were incubated with(211)At-rituximab (Rituxan(R) or MabTheratrade mark) and plated in clonogenic assays for survival analyses. Following 1 h incubation with(211)At-rituximab, in concentrations which gave an initial activity of 50 kBq ml(-1), a high tumour cell to normal bone marrow cell toxicity ratio was obtained; 4.1 to 1.0 log cell kill. Biodistribution studies of(211)At-rituximab in Balb/c mice showed similar stability as that of the iodinated analogue. The data indicate that testing of(211)At-rituximab in human patients is warranted.
It is becoming increasingly clear that mitochondria play an important role in neural function. Recent studies show mitochondrial morphology to be crucial to cellular physiology and synaptic function ...and a link between mitochondrial defects and neuro-degenerative diseases is strongly suspected. Electron microscopy (EM), with its very high resolution in all three directions, is one of the key tools to look more closely into these issues but the huge amounts of data it produces make automated analysis necessary. State-of-the-art computer vision algorithms designed to operate on natural 2-D images tend to perform poorly when applied to EM data for a number of reasons. First, the sheer size of a typical EM volume renders most modern segmentation schemes intractable. Furthermore, most approaches ignore important shape cues, relying only on local statistics that easily become confused when confronted with noise and textures inherent in the data. Finally, the conventional assumption that strong image gradients always correspond to object boundaries is violated by the clutter of distracting membranes. In this work, we propose an automated graph partitioning scheme that addresses these issues. It reduces the computational complexity by operating on supervoxels instead of voxels, incorporates shape features capable of describing the 3-D shape of the target objects, and learns to recognize the distinctive appearance of true boundaries. Our experiments demonstrate that our approach is able to segment mitochondria at a performance level close to that of a human annotator, and outperforms a state-of-the-art 3-D segmentation technique.
Purposes : The α -emitting radionuclide 211 At conjugated to the CD20 targeting chimeric monoclonal antibody rituximab was studied to: (a) Estimate radiation dose components to lymphoma and bone ...marrow (BM) cells exposed in vitro. (b) Calculate the mean absorbed radiation doses in various normal tissues of mice following intravenous injection. Materials and methods : B-lymphoma cells (RAEL) and normal human BM cells were incubated with increasing concentrations of the radioimmunoconjugate. Based on binding kinetics and on measured cellular and nuclear diameters, the radiation doses were calculated using microdosimetric methods. Results : Targeting of 211 At-rituximab to RAEL cells was extensive and stable compared with the binding to BM cells. The absorbed radiation doses from cell-bound activity at an initial activity concentration of 10 kBq ml -1 were 0.645 and 0.021 Gy to RAEL and BM cells, respectively. In comparison, the contribution from unbound conjugate in the medium during 1h exposure was 0.042 and 0.043 Gy. The D 0 value for RAEL cells was 0.55 Gy, but only 0.34 Gy for BM cells, whereas corresponding D 0 values were 0.72 and 1.21 Gy after a single exposure to external 60 Co γ-rays. Mean absorbed doses of 1.31, 0.48 and 0.36 Gy for blood, lungs and heart were calculated in mice injected with 5.4kBq g -1 of 211 At-rituximab. Conclusion : Despite the higher inherent sensitivity of the BM cells to the α -irradiation, there was, related to the radioactivity concentrations of 211 At-rituximab, several logs greater cell kill in RAEL cells, illustrating the tumour-specific nature of the targeting.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
PICO is a concept for a NASA probe-scale mission aiming to detect or constrain the tensor to scalar ratio \(r\), a parameter that quantifies the amplitude of inflationary gravity waves. We carry out ...map-based component separation on simulations with five foreground models and input \(r\) values \(r_{in}=0\) and \(r_{in} = 0.003\). We forecast \(r\) determinations using a Gaussian likelihood assuming either no delensing or a residual lensing factor \(A_{\rm lens}\) = 27%. By implementing the first full-sky, post component-separation, map-domain delensing, we show that PICO should be able to achieve \(A_{\rm lens}\) = 22% - 24%. For four of the five foreground models we find that PICO would be able to set the constraints \(r < 1.3 \times 10^{-4} \,\, \mbox{to} \,\, r <2.7 \times 10^{-4}\, (95\%)\) if \(r_{in}=0\), the strongest constraints of any foreseeable instrument. For these models, \(r=0.003\) is recovered with confidence levels between \(18\sigma\) and \(27\sigma\). We find weaker, and in some cases significantly biased, upper limits when removing few low or high frequency bands. The fifth model gives a \(3\sigma\) detection when \(r_{in}=0\) and a \(3\sigma\) bias with \(r_{in} = 0.003\). However, by correlating \(r\) determinations from many small 2.5% sky areas with the mission's 555 GHz data we identify and mitigate the bias. This analysis underscores the importance of large sky coverage. We show that when only low multipoles \(\ell \leq 12\) are used, the non-Gaussian shape of the true likelihood gives uncertainties that are on average 30% larger than a Gaussian approximation.
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