On Unitary Time Evolution in Gowdy T3T^3 Cosmologies

A non-perturbative canonical quantization of Gowdy $T^3$ polarized models carried out recently is considered. This approach profits from the equivalence between the symmetry reduced model and 2+1 gravity coupled to a massless real scalar field. The system is partially gauge fixed and a choice of internal time is performed, for which the true degrees of freedom of the model reduce to a massless free scalar field propagating on a 2-dimensional expanding torus. It is shown that the symplectic transformation that determines the classical dynamics cannot be unitarily implemented on the corresponding Hilbert space of quantum states. The implications of this result for both quantization of fields on curved manifolds and physically relevant questions regarding the initial singularity are discussed.Comment: 16 pages, no figures, latex file; references added, a proof included. Final version to appear in IJMP

Cellular-Resolution Population Imaging Reveals Robust Sparse Coding in the Drosophila Mushroom Body

Sensory stimuli are represented in the brain by the activity of populations of neurons. In most biological systems, studying population coding is challenging since only a tiny proportion of cells can be recorded simultaneously. Here we used two-photon imaging to record neural activity in the relatively simple Drosophila mushroom body (MB), an area involved in olfactory learning and memory. Using the highly sensitive calcium indicator GCaMP3, we simultaneously monitored the activity of >100 MB neurons in vivo (similar to 5% of the total population). The MB is thought to encode odors in sparse patterns of activity, but the code has yet to be explored either on a population level or with a wide variety of stimuli. We therefore imaged responses to odors chosen to evaluate the robustness of sparse representations. Different odors activated distinct patterns of MB neurons; however, we found no evidence for spatial organization of neurons by either response probability or odor tuning within the cell body layer. The degree of sparseness was consistent across a wide range of stimuli, from monomolecular odors to artificial blends and even complex natural smells. Sparseness was mainly invariant across concentrations, largely because of the influence of recent odor experience. Finally, in contrast to sensory processing in other systems, no response features distinguished natural stimuli from monomolecular odors. Our results indicate that the fundamental feature of odor processing in the MB is to create sparse stimulus representations in a format that facilitates arbitrary associations between odor and punishment or reward

Monitoring activated clotting time for combined heparin and aprotinin application: in vivo evaluation of a new aprotinin-insensitive test using Sonoclot

Objective: Kaolin-based activated clotting time assessed by HEMOCHRON (HkACT) is a clinical standard for heparin monitoring alone and combined with aprotinin during cardiopulmonary bypass (CPB). However, aprotinin is known to prolong not only celite-based but also kaolin-based activated clotting time. Overestimation of activated clotting times implies a potential hazardous risk of subtherapeutic heparin anticoagulation. Recently, a novel ‘aprotinin-insensitive' activated clotting time test has been developed for the SONOCLOT analyzer (SaiACT). The aim of our study was to evaluate SaiACT in patients undergoing CPB in presence of heparin and aprotinin. Methods: Blood samples were taken from 44 elective cardiac surgery patients at the following measurement time points: baseline (T0); before CPB after heparinization (T1 and T2); on CPB, before administration of aprotinin (T3); 15, 30, and 60min on CPB after administration of aprotinin (T4, T5, and T6); after protamine infusion (T7). On each measurement time point, activated clotting time was assessed with HkACT and SaiACT, both in duplicate. Furthermore, the rate of factor Xa inhibition and antithrombin concentration were measured. Statistical analysis was done using Bland and Altman analysis, Pearson's correlation, and ANOVA with post hoc Bonferroni-Dunn correction. Results: Monitoring anticoagulation with SaiACT showed reliable readings. Compared to the established HkACT, SaiACT values were lower at all measurement time points. On CPB but before administration of aprotinin (T3), SaiACT values (mean±SD) were 44±118s lower compared to HkACT. However, the difference between the two measurement techniques increased significantly on CPB after aprotinin administration (T4-T6; 89±152s, P=0.032). Correlation of ACT measurements with anti-Xa activity was unchanged for SaiACT before and after aprotinin administration (r2=0.473 and 0.487, respectively; P=0.794), but was lower for HkACT after aprotinin administration (r2=0.481 and 0.361, respectively; P=0.041). On CPB after administration of aprotinin, 96% of all ACT values were classified as therapeutic by HkACT, but only 86% of all values were classified therapeutic if ACT was determined by SaiACT. Test variability was comparable for SaiACT and HkACT. Conclusions: The use of SaiACT may result in more consistent heparin management that is less affected by aprotinin and a corresponding increase in heparin administration for patients receiving aprotini

Trunk Sway Measures of Postural Stability During Clinical Balance Tests: Effects of Age

Background. The major disadvantage of current clinical tests that screen for balance disorders is a reliance on an examiner's subjective assessment of equilibrium control. To overcome this disadvantage we investigated, using quantified measures of trunk sway, age-related differences of normal subjects for commonly used clinical balance tests. Methods. Three age groups were tested: young (15-25 years; n = 48), middle-aged (45-55 years; n = 50) and elderly (65-75 years; n = 49). Each subject performed a series of fourteen tasks similar to those included in the Tinetti and Clinical Test of Sensory Interaction in Balance protocols. The test battery comprised stance and gait tasks performed under normal, altered visual (eyes closed), and altered proprioceptive (foam support surface) conditions. Quantification of trunk sway was performed using a system that measured trunk angular velocity and position in the roll (lateral) and pitch (fore-aft) planes at the level of the lower back. Ranges of sway amplitude and velocity were examined for age-differences with ANOVA techniques. Results. A comparison between age groups showed several differences. Elderly subjects were distinguished from both middle-aged and young subjects by the range of trunk angular sway and angular velocity because both were greater in roll and pitch planes for stance and stance-related tasks (tandem walking). The most significant age group differences (F = 30, p < .0001) were found for standing on one leg on a normal floor or on a foam support surface with eyes open. Next in significance was walking eight tandem steps on a normal floor (F = 13, p < .0001). For gait tasks, such as walking five steps while rotating or pitching the head or with eyes closed, pitch and roll velocity ranges were influenced by age with middle-aged subjects showing the smallest ranges followed by elderly subjects and then young subjects (F = 12, p < .0001). Walking over a set of low barriers also yielded significant differences between age groups for duration and angular sway. In contrast, task duration was the only variable significantly influenced when walking up and down a set of stairs. An interesting finding for all tasks was the different spread of values for each population. Population distributions were skewed for all ages and broadened with age. Conclusions. Accurate measurement of trunk angular sway during stance and gait tasks provides a simple way of reliably measuring changes in balance stability with age and could prove useful when screening for balance disorders of those prone to fal

Stabilization and humanization of a single-chain Fv antibody fragment specific for human lymphocyte antigen CD19 by designed point mutations and CDR-grafting onto a human framework

A single-chain Fv (scFv) fragment derived from the murine antibody 4G7, specific for human lymphocyte CD19, was engineered for stability and expression in Escherichia coli in view of future use as a therapeutic protein. We compared two orthogonal knowledge-based procedures. In one approach, we designed a mutant with 14 single amino-acid substitutions predicted to correct destabilizing residues in the 4G7-wt sequence to create 4G7-mut. In the second variant, the murine CDRs were grafted to the human acceptor framework huVκ3-huVH3, with 11 additional point mutations introduced to obtain a better match between CDR graft and acceptor framework, to arrive at 4G7-graft. Compared to 4G7-wt, 4G7-mut showed greater thermodynamic stability in guanidinium chloride-induced equilibrium denaturation experiments and somewhat greater stability in human serum. The loop graft maintained the comparatively high stability of the murine loop donor, but did not improve it further. Our analysis indicates that this is due to subtle strain introduced between CDRs and framework, mitigating the otherwise highly favorable properties of the human acceptor framework. This slight strain in the loop graft is also reflected in the binding affinities for CD19 on leukemic cells of 8.4 nM for 4G7-wt, 16.4 nM for 4G7-mut and 30.0 nM for 4G7-graft. This comparison of knowledge-based mutation and loop-grafting-based approaches will be important, when moving molecules forward to therapeutic application

Correlated Strength in Nuclear Spectral Function

We have carried out an (e,e'p) experiment at high momentum transfer and in parallel kinematics to measure the strength of the nuclear spectral function S(k,E) at high nucleon momenta k and large removal energies E. This strength is related to the presence of short-range and tensor correlations, and was known hitherto only indirectly and with considerable uncertainty from the lack of strength in the independent-particle region. This experiment confirms by direct measurement the correlated strength predicted by theory.Comment: 4 pages, 2 figures, accepted by Phys. Rev. Let

Water isotopes in desiccating lichens

The stable isotopic composition of water is routinely used as a tracer to study water exchange processes in vascular plants and ecosystems. To date, no study has focussed on isotope processes in non-vascular, poikilohydric organisms such as lichens and bryophytes. To understand basic isotope exchange processes of non-vascular plants, thallus water isotopic composition was studied in various green-algal lichens exposed to desiccation. The study indicates that lichens equilibrate with the isotopic composition of surrounding water vapour. A model was developed as a proof of concept that accounts for the specific water relations of these poikilohydric organisms. The approach incorporates first their variable thallus water potential and second a compartmentation of the thallus water into two isotopically distinct but connected water pools. Moreover, the results represent first steps towards the development of poikilohydric organisms as a recorder of ambient vapour isotopic composition

Alluvial record of an early Eocene hyperthermal within the Castissent Formation, the Pyrenees, Spain

The late Palaeocene to the middle Eocene (57.5 to 46.5 Ma) recorded a total of 39 hyperthermals – periods of rapid global warming documented by prominent negative carbon isotope excursions (CIEs) as well as peaks in iron content – have been recognized in marine cores. Documenting how the Earth system responded to rapid climatic shifts during hyperthermals provides fundamental information to constrain climatic models. However, while hyperthermals have been well documented in the marine sedimentary record, only a few have been recognized and described in continental deposits, thereby limiting our ability to understand the effect and record of global warming on terrestrial systems. Hyperthermals in the continental record could be a powerful correlation tool to help connect marine and continental deposits, addressing issues of environmental signal propagation from land to sea. In this study, we generate new stable carbon isotope data (δ13C values) across the well-exposed and time-constrained fluvial sedimentary succession of the early Eocene Castissent Formation in the south central Pyrenees (Spain). The δ13C values of pedogenic carbonate reveal – similarly to the global records – stepped CIEs, culminating in a minimum δ13C value that we correlate with the hyperthermal event “U” at ca. 50 Ma. This general trend towards more negative values is most probably linked to higher primary productivity leading to an overall higher respiration of soil organic matter during these climatic events. The relative enrichment in immobile elements (Zr, Ti, Al) and higher estimates of mean annual precipitation together with the occurrence of small iron oxide and iron hydroxide nodules during the CIEs suggest intensification of chemical weathering and/or longer exposure of soils in a highly seasonal climate. The results show that even relatively small-scale hyperthermals compared with their prominent counterparts, such as PETM, ETM2, and ETM3, can leave a recognizable signature in the terrestrial stratigraphic record, providing insights into the dynamics of the carbon cycle in continental environments during these events