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- Niessen, Peter, et al.
(author)
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Recent results from the amanda experiment
- 2003
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In: Proceedings of 38th Rencontres de Moriond on Electroweak Interactions and Unified Theories 15-22 Mar 2003. Les Arcs, France.
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Conference paper (peer-reviewed)abstract
- AMANDA (Antarctic Muon And Neutrino Detector Array) is a neutrino telescope built under the southern polar icecap and its scope is to explore the possibility to detect high energy cosmic neutrinos. This should generate insight into the powerful celestial objects where acceleration mechanisms can bring up to 10 20 eV. We describe the achievements and results from the AMANDA-B10 prototype and the preliminary results from the current AMANDA-II detector which show dramatic increase in sensitivity.
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- Compte, A., et al.
(author)
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Temporally Irregular Mnemonic Persistent Activity in Prefrontal Neurons of Monkeys during a Delayed Response Task
- 2003
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In: Journal of Neurophysiology. - : American Physiological Society. - 0022-3077 .- 1522-1598. ; 90:5, s. 3441-3454
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Journal article (peer-reviewed)abstract
- An important question in neuroscience is whether and how temporal patterns and fluctuations in neuronal spike trains contribute to information processing in the cortex. We have addressed this issue in the memory-related circuits of the prefrontal cortex by analyzing spike trains from a database of 229 neurons recorded in the dorsolateral prefrontal cortex of 4 macaque monkeys during the performance of an oculomotor delayed-response task. For each task epoch, we have estimated their power spectrum together with interspike interval histograms and autocorrelograms. We find that 1) the properties of most (about 60%) neurons approximated the characteristics of a Poisson process. For about 25% of cells, with characteristics typical of interneurons, the power spectrum showed a trough at low frequencies (<20 Hz) and the autocorrelogram a dip near zero time lag. About 15% of neurons had a peak at <20 Hz in the power spectrum, associated with the burstiness of the spike train, 2) a small but significant task dependency of spike-train temporal structure: delay responses to preferred locations were characterized not only by elevated firing, but also by suppressed power at low (<20 Hz) frequencies, and 3) the variability of interspike intervals is typically higher during the mnemonic delay period than during the fixation period, regardless of the remembered cue. The high irregularity of neural persistent activity during the delay period is likely to be a characteristic signature of recurrent prefrontal network dynamics underlying working memory.
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- Goldman, RD, et al.
(author)
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Accumulation of mutant lamin A causes progressive changes in nuclear architecture in Hutchinson-Gilford progeria syndrome
- 2004
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 101:24, s. 8963-8968
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Journal article (peer-reviewed)abstract
- Hutchinson–Gilford progeria syndrome (HGPS) is a premature aging disorder, commonly caused by a point mutation in the lamin A gene that results in a protein lacking 50 aa near the C terminus, denoted LAΔ50. Here we show by light and electron microscopy that HGPS is associated with significant changes in nuclear shape, including lobulation of the nuclear envelope, thickening of the nuclear lamina, loss of peripheral heterochromatin, and clustering of nuclear pores. These structural defects worsen as HGPS cells age in culture, and their severity correlates with an apparent increase in LAΔ50. Introduction of LAΔ50 into normal cells by transfection or protein injection induces the same changes. We hypothesize that these alterations in nuclear structure are due to a concentration-dependent dominant-negative effect of LAΔ50, leading to the disruption of lamin-related functions ranging from the maintenance of nuclear shape to regulation of gene expression and DNA replication.
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- Maddison, P, et al.
(author)
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The rate and pattern of organ damage in late onset systemic lupus erythematosus
- 2002
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In: Journal of Rheumatology. - 0315-162X. ; 29:5, s. 913-917
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Journal article (peer-reviewed)abstract
- Objective. To compare the extent and type of damage in patients with late onset and earlier onset Systemic lupus erythematosus (SLE) using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). Methods. A total of 86 SLE patients with disease onset after the age of 54 years were matched for center, sex, and ethnic origin with 155 SLE patients with disease onset before the age of 40 years. SDI scores were obtained at one year and 5 years after the diagnosis of SLE. Analysis was based on conditional logistic regression. Results. SDI scores were higher in the late onset group than in younger patients at both one [mean 0.7 (range 0-3) vs 0.3 (range 0-3). p < 0.001] and 5 years [mean 1.6 (range 0-8) vs 0.9 (range 0-7); p < 0.001] after diagnosis. There was also a difference in the pattern of organ damage. While damage to the skin, kidneys, and central nervous system occurred with similar frequency, late onset disease was characterized by significantly more cardiovascular (OR 14.13, p < 0.001). ocular (OR 9.38, p 0.001), and musculoskeletal (OR 2.68, p = 0.016) damage and malignancy (OR 7.04, 3 = 0.046). Conclusion. The occurrence of organ damage assessed by the SDI is greater in patients with late onset SLE than in younger patients and, by this criterion, lupus cannot be judged to be more benign in this age group. Also, the pattern of damage is different, but whether this reflects age per se or the effect of the disease in the elderly remains to be established.
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- Belogurov, G A, et al.
(author)
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Catalytically important ionizations along the reaction pathway of yeast pyrophosphatase
- 2000
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In: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 39:45, s. 13931-13938
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Journal article (peer-reviewed)abstract
- Five catalytic functions of yeast inorganic pyrophosphatase were measured over wide pH ranges: steady-state PP(i) hydrolysis (pH 4. 8-10) and synthesis (6.3-9.3), phosphate-water oxygen exchange (pH 4. 8-9.3), equilibrium formation of enzyme-bound PP(i) (pH 4.8-9.3), and Mg(2+) binding (pH 5.5-9.3). These data confirmed that enzyme-PP(i) intermediate undergoes isomerization in the reaction cycle and allowed estimation of the microscopic rate constant for chemical bond breakage and the macroscopic rate constant for PP(i) release. The isomerization was found to decrease the pK(a) of the essential group in the enzyme-PP(i) intermediate, presumably nucleophilic water, from >7 to 5.85. Protonation of the isomerized enzyme-PP(i) intermediate decelerates PP(i) hydrolysis but accelerates PP(i) release by affecting the back isomerization. The binding of two Mg(2+) ions to free enzyme requires about five basic groups with a mean pK(a) of 6.3. An acidic group with a pK(a) approximately 9 is modulatory in PP(i) hydrolysis and metal ion binding, suggesting that this group maintains overall enzyme structure rather than being directly involved in catalysis.
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