In vivo imaging reveals sigmoidal growth kinetic of β-amyloid plaques

A major neuropathological hallmark of Alzheimer's disease is the deposition of amyloid plaques in the brains of affected individuals. Amyloid plaques mainly consist of fibrillar β-amyloid, which is a cleavage product of the amyloid precursor protein. The amyloid-cascade-hypothesis postulates Aβ accumulation as the central event in initiating a toxic cascade leading to Alzheimer's disease pathology and, ultimately, loss of cognitive function. We studied the kinetics of β-amyloid deposition in Tg2576 mice, which overexpress human amyloid precursor protein with the Swedish mutation. Utilizing long-term two-photon imaging we were able to observe the entire kinetics of plaque growth in vivo. Essentially, we observed that plaque growth follows a sigmoid-shaped curve comprising a cubic growth phase, followed by saturation. In contrast, plaque density kinetics exhibited an asymptotic progression. Taking into account the fact that a critical concentration of Aβ is required to seed new plaques, we can propose the following kinetic model of β-amyloid deposition in vivo. In the early cubic phase, plaque growth is not limited by Aβ concentration and plaque density increases very fast. During the transition phase, plaque density stabilizes whereas plaque volume increases strongly reflecting a robust growth of the plaques. In the late asymptotic phase, Aβ peptide production becomes rate-limiting for plaque growth. In conclusion, the present study offers a direct link between in vitro and in vivo studies facilitating the translation of Aβ-lowering strategies from laboratory models to patients

Effective brilliance amplification in neutron propagation-based phase contrast imaging

Propagation-based neutron phase-contrast tomography was demonstrated on an insect sample, using the ISIS pulsed spallation source. In our proof-of-concept low-fluence experiment the tomogram with Paganin-type phase-retrieval filter applied exhibited an effective net boost of $23\pm 1$ in the signal-to-noise ratio as compared to an attenuation-based tomogram, implying an effective boost in neutron brilliance of well over two orders of magnitude. The phase-retrieval filter applies to monochromatic as well as poly-energetic neutron beams. Expressions are provided for the optimal phase-contrast geometry as well as conditions for the validity of the method. The underpinning theory is derived under the assumption of the sample being composed of a single material, but this can be generalized. The effective boost in brilliance may be employed to give reduced acquisition time, or may instead be used to keep exposure times fixed while improving contrast and spatial resolution

Electric dipole moment of the ρ meson

At a hadronic scale the effect of CP-violating interactions that typically appear in extensions of the Standard Model may be described by an effective Lagrangian, in which the operators are expressed in terms of lepton and partonic gluon and quark fields and ordered by their mass dimension, k⩾4. Using a global-symmetry-preserving truncation of QCD Dyson-Schwinger equations, we compute the ρ-meson's electric dipole moment (EDM), d_ρ, as generated by the leading dimension-four and dimension-five CP-violating operators and an example of a dimension-six four-quark operator. The two dimension-five operators, i.e., the quark EDM and quark chromo-EDM, produce contributions to d_ρ whose coefficients are of the same sign and within a factor of 2 in magnitude. Moreover, should a suppression mechanism be verified for the θ term in any beyond-Standard-Model theory, the contribution from a four-quark operator can match the quark EDM and quark chromo-EDM in importance. This study serves as a prototype for the more challenging task of computing the neutron's EDM

Impact of glycemic control on the incidence of acute kidney injury in critically ill patients: a comparison of two strategies using the RIFLE criteria

OBJECTIVE: To compare the renal outcome in patients submitted to two different regimens of glycemic control, using the RIFLE criteria to define acute kidney injury. INTRODUCTION: The impact of intensive insulin therapy on renal function outcome is controversial. The lack of a criterion for AKI definition may play a role on that. METHODS: Included as the subjects were 228 randomly selected, critically ill patients engaged in intensive insulin therapyor in a carbohydrate-restrictive strategy. Renal outcome was evaluated through the comparison of the last RIFLE score obtained during the ICU stay and the RIFLE score at admission; the outcome was classified as favorable, stable or unfavorable. RESULTS: The two groups were comparable regarding demographic data. AKI developed in 52% of the patients and was associated with a higher mortality (39.4%) compared with those who did not have AKI (8.2%) (p<0.001). Renal function outcome was comparable between the two groups (p=0.37). We observed a significant correlation between blood glucose levels and the incidence of acute kidney injury (p=0.007). In the multivariate logistic regression analysis, only APACHE III scores higher than 60 were identified as an independent risk factor for unfavorable renal outcome. APACHE III scores>60, acute kidney injury and hypoglycemia were risk factors for mortality. CONCLUSION: Intensive insulin therapy and a carbohydrate-restrictive strategy were comparable regarding the incidence of acute kidney injury evaluated using RIFLE criteria

The Chandra Deep Field South: the 1 Million Second

We present the main results from our 940 ksec observation of the Chandra Deep Field South (CDFS), using the source catalog described in an accompanying paper (Giacconi et al. 2001). We extend the measurement of source number counts to 5.5e-17 erg/cm^2/s in the soft 0.5-2 keV band and 4.5e-16 erg/cm^2/s in the hard 2-10 keV band. The hard band LogN-LogS shows a significant flattening (slope~=0.6) below ~1e-14 erg/cm^2/s, leaving at most 10-15% of the X-ray background (XRB) to be resolved, the main uncertainty lying in the measurement of the total flux of the XRB. On the other hand, the analysis in the very hard 5-10 keV band reveals a relatively steep LogN-LogS (slope ~=1.3) down to 1e-15 erg/cm^2/s. Together with the evidence of a progressive flattening of the average X-ray spectrum near the flux limit, this indicates that there is still a non negligible population of faint hard sources to be discovered at energies not well probed by Chandra, which possibly contribute to the 30 keV bump in the spectrum of the XRB. We use optical redshifts and identifications, obtained with the VLT, for one quarter of the sample to characterize the combined optical and X-ray properties of the CDFS sample. Different source types are well separated in a parameter space which includes X-ray luminosity, hardness ratio and R-K color. Type II objects, while redder on average than the field population, have colors which are consistent with being hosted by a range of galaxy types. Type II AGN are mostly found at z<~1, in contrast with predictions based on AGN population synthesis models, thus suggesting a revision of their evolutionary parameters.Comment: Accepted by The Astrophysical Journal, 24 pages, 8 figures, 1 color jpg plate (fig.1

A novel approach to simulate gene-environment interactions in complex diseases

Background: Complex diseases are multifactorial traits caused by both genetic and environmental factors. They represent the major part of human diseases and include those with largest prevalence and mortality (cancer, heart disease, obesity, etc.). Despite a large amount of information that has been collected about both genetic and environmental risk factors, there are few examples of studies on their interactions in epidemiological literature. One reason can be the incomplete knowledge of the power of statistical methods designed to search for risk factors and their interactions in these data sets. An improvement in this direction would lead to a better understanding and description of gene-environment interactions. To this aim, a possible strategy is to challenge the different statistical methods against data sets where the underlying phenomenon is completely known and fully controllable, for example simulated ones. Results: We present a mathematical approach that models gene-environment interactions. By this method it is possible to generate simulated populations having gene-environment interactions of any form, involving any number of genetic and environmental factors and also allowing non-linear interactions as epistasis. In particular, we implemented a simple version of this model in a Gene-Environment iNteraction Simulator (GENS), a tool designed to simulate case-control data sets where a one gene-one environment interaction influences the disease risk. The main aim has been to allow the input of population characteristics by using standard epidemiological measures and to implement constraints to make the simulator behaviour biologically meaningful. Conclusions: By the multi-logistic model implemented in GENS it is possible to simulate case-control samples of complex disease where gene-environment interactions influence the disease risk. The user has full control of the main characteristics of the simulated population and a Monte Carlo process allows random variability. A knowledge-based approach reduces the complexity of the mathematical model by using reasonable biological constraints and makes the simulation more understandable in biological terms. Simulated data sets can be used for the assessment of novel statistical methods or for the evaluation of the statistical power when designing a study

Electric/magnetic duality for chiral gauge theories with anomaly cancellation

We show that 4D gauge theories with Green-Schwarz anomaly cancellation and possible generalized Chern-Simons terms admit a formulation that is manifestly covariant with respect to electric/magnetic duality transformations. This generalizes previous work on the symplectically covariant formulation of anomaly-free gauge theories as they typically occur in extended supergravity, and now also includes general theories with (pseudo-)anomalous gauge interactions as they may occur in global or local N=1 supersymmetry. This generalization is achieved by relaxing the linear constraint on the embedding tensor so as to allow for a symmetric 3-tensor related to electric and/or magnetic quantum anomalies in these theories. Apart from electric and magnetic gauge fields, the resulting Lagrangians also feature two-form fields and can accommodate various unusual duality frames as they often appear, e.g., in string compactifications with background fluxes.Comment: 37 pages; v2: typos corrected and 1 reference adde

The Farthest Known Supernova: Support for an Accelerating Universe and a Glimpse of the Epoch of Deceleration

We present photometric observations of an apparent Type Ia supernova (SN Ia) at a redshift of ~1.7, the farthest SN observed to date. SN 1997ff, was discovered in a repeat observation by the HST of the HDF-), and serendipitously monitored with NICMOS on HST throughout the GTO campaign. The SN type can be determined from the host galaxy type:an evolved, red elliptical lacking enough recent star formation to provide a significant population of core-collapse SNe. The class- ification is further supported by diagnostics available from the observed colors and temporal behavior of the SN, both of which match a typical SN Ia. The photo- metric record of the SN includes a dozen flux measurements in the I, J, and H bands spanning 35 days in the observed frame. The redshift derived from the SN photometry, z=1.7+/-0.1, is in excellent agreement with the redshift estimate of z=1.65+/-0.15 derived from the U_300,B_450,V_606,I_814,J_110,J_125,H_160, H_165,K_s photometry of the galaxy. Optical and near-infrared spectra of the host provide a very tentative spectroscopic redshift of 1.755. Fits to observations of the SN provide constraints for the redshift-distance relation of SNe~Ia and a powerful test of the current accelerating Universe hypothesis. The apparent SN brightness is consistent with that expected in the decelerating phase of the preferred cosmological model, Omega_M~1/3, Omega_Lambda~2/3. It is inconsistent with grey dust or simple luminosity evolution, candidate astro- physical effects which could mimic past evidence for an accelerating Universe from SNe Ia at z~0.5.We consider several sources of possible systematic error including lensing, SN misclassification, selection bias, and calibration errors. Currently, none of these effects appears likely to challenge our conclusions.Comment: Accepted to the Astrophysical Journal 38 pages, 15 figures, Pretty version available at http://icarus.stsci.edu/~stefano/ariess.tar.g