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

The influence of artificially increased hip and trunk stiffness on balance control in man

Lightweight corsets were used to produce mid-body stiffening, rendering the hip and trunk joints practically inflexible. To examine the effect of this artificially increased stiffness on balance control, we perturbed the upright stance of young subjects (20-34years of age) while they wore one of two types of corset or no corset at all. One type, the "half-corset”, only increased hip stiffness, and the other, the "full-corset”, increased stiffness of the hips and trunk. The perturbations consisted of combined roll and pitch rotations of the support surface (7.5deg, 60deg/s) in one of six different directions. Outcome measures were biomechanical responses of the legs, trunk, arms and head, and electromyographic (EMG) responses from leg, trunk, and upper arm muscles. With the full-corset, a decrease in forward stabilising trunk pitch rotation compared to the no-corset condition occurred for backward pitch tilts of the support surface. In contrast, the half-corset condition yielded increased forward trunk motion. Trunk backward pitch motion after forwards support-surface perturbations was the same for all corset conditions. Ankle torques and lower leg angle changes in the pitch direction were decreased for both corset conditions for forward pitch tilts of the support-surface but unaltered for backward tilts. Changes in trunk roll motion with increased stiffness were profound. After onset of a roll support-surface perturbation, the trunk rolled in the opposite direction to the support-surface tilt for the no-corset and half-corset conditions, but in the same direction as the tilt for the full-corset condition. Initial head roll angular accelerations (at 100ms) were larger for the full-corset condition but in the same direction (opposite platform tilt) for all conditions. Arm roll movements were initially in the same direction as trunk movements, and were followed by large compensatory arm movements only for the full-corset condition. Leg muscle (soleus, peroneus longus, but not tibialis anterior) balance-correcting responses were reduced for roll and pitch tilts under both corset conditions. Responses in paraspinals were also reduced. These results indicate that young healthy normals cannot rapidly modify movement strategies sufficiently to account for changes in link flexibility following increases in hip and trunk stiffness. The changes in leg and trunk muscle responses failed to achieve a normal roll or pitch trunk end position at 700ms (except for forward tilt rotations), even though head accelerations and trunk joint proprioception seemed to provide information on changed trunk movement profiles over the first 300ms following the perturbation. The major adaptation to stiffness involved increased use of arm movements to regain stability. The major differences in trunk motion for the no-corset, half-corset and full-corset conditions support the concept of a multi-link pendulum with different control dynamics in the pitch and roll planes as a model of human stance. Stiffening of the hip and trunk increases the likelihood of a loss of balance laterally and/or backwards. Thus, these results may have implications for the elderly and others, with and without disease states, who stiffen for a variety of reason

The effect of voluntary lateral trunk bending on balance recovery following multi-directional stance perturbations

Stabilising shifts of the centre of mass (COM) are observed during balance recovery when subjects simultaneously execute voluntary unilateral knee flexion or unilateral arm raising. Here, we examined whether voluntary lateral trunk bending provided more beneficial stabilising effects, and how motor programs of balance corrections are combined with those of the focal voluntary action. The upright balance of 24 healthy young subjects (19-33years of age) was perturbed using multi-directional rotations of the support-surface. The perturbations consisted of combined pitch and roll rotations (7.5° and 60°/s) presented randomly in six different directions. Three conditions were tested: perturbation of stance only (PO); combined balance perturbation and cued uphill bending of the trunk (CONT); and combined perturbation and cued downhill bending of the trunk (IPS). For comparison, subjects were required to perform trunk bending alone (TO). Outcome measures were biomechanical responses and surface EMG activity of several muscles. Calculated predicted outcomes (PO+TO) were compared with combined measures (CONT or IPS). CONT trunk bending uphill showed two phases of benefit in balance recovery for laterally but, in contrast to voluntary knee bending, not for posterior directed components of the perturbations. IPS trunk bending had negative effects on balance. Early balance correcting muscle responses were marginally greater than PO responses. Prominent secondary balance correcting responses, having a similar timing as voluntary responses observed under TO conditions, were seen under CONT only in trunk muscles. These, and later stabilising, responses had amplitudes as expected from PO+TO conditions being significantly greater than PO responses. The ability with which different muscle synergies for balance corrections and voluntary trunk bending were integrated into one indicates a flexible adjustment of the CNS programs to the demands of both task

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

Control of roll and pitch motion during multi-directional balance perturbations

Does the central nervous system (CNS) independently control roll and pitch movements of the human body during balance corrections? To help provide an answer to this question, we perturbed the balance of 16 young healthy subjects using multi-directional rotations of the support surface. All rotations had pitch and roll components, for which either the roll (DR) or the pitch (DP) component were delayed by 150ms or not at all (ND). The outcome measures were the biomechanical responses of the body and surface EMG activity of several muscles. Across all perturbation directions, DR caused equally delayed shifts (150ms) in peak lateral centre of mass (COM) velocity. Across directions, DP did not cause equally delayed shifts in anterior-posterior COM velocity. After 300ms however, the vector direction of COM velocity was similar to the ND directions. Trunk, arm and knee joint rotations followed this roll compared to pitch pattern, but were different from ND rotation synergies after 300ms, suggesting an intersegmental compensation for the delay effects. Balance correcting responses of muscles demonstrated both roll and pitch directed components regardless of axial alignment. We categorised muscles into three groups: pitch oriented, roll oriented and mixed based on their responses to DR and DP. Lower leg muscles were pitch oriented, trunk muscles were roll oriented, and knee and arm muscles were mixed. The results of this study suggest that roll, but not pitch components, of balance correcting movement strategies and muscle synergies are separately programmed by the CNS. Reliance on differentially activated arm and knee muscles to correct roll perturbations reveals a dependence of the pitch response on that of roll, possibly due to biomechanical constraints, and accounts for the failure of DP to be transmitted equally in time across all limbs segments. Thus it appears the CNS preferentially programs the roll response of the body and then adjusts the pitch response accordingl

Oblique internal hydraulic jumps at a stratified estuary mouth

Author Posting. © American Meteorological Society, 2017. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 47 (2017): 85-100, doi:10.1175/JPO-D-15-0234.1.Observations and analyses of two tidally recurring, oblique, internal hydraulic jumps at a stratified estuary mouth (Columbia River, Oregon/Washington) are presented. These hydraulic features have not previously been studied due to the challenges of both horizontally resolving the sharp gradients and temporally resolving their evolution in numerical models and traditional observation platforms. The jumps, both of which recurred during ebb, formed adjacent to two engineered lateral channel constrictions and were identified in marine radar image time series. Jump occurrence was corroborated by (i) a collocated sharp gradient in the surface currents measured via airborne along-track interferometric synthetic aperture radar and (ii) the transition from supercritical to subcritical flow in the cross-jump direction via shipborne velocity and density measurements. Using a two-layer approximation, observed jump angles at both lateral constrictions are shown to lie within the theoretical bounds given by the critical internal long-wave (Froude) angle and the arrested maximum-amplitude internal bore angle, respectively. Also, intratidal and intertidal variability of the jump angles are shown to be consistent with that expected from the two-layer model, applied to varying stratification and current speed over a range of tidal and river discharge conditions. Intratidal variability of the upchannel jump angle is similar under all observed conditions, whereas the downchannel jump angle shows an additional association with stratification and ebb velocity during the low discharge periods. The observations additionally indicate that the upchannel jump achieves a stable position that is collocated with a similarly oblique bathymetric slope.We acknowledge the financial support of the Office of Naval Research under Awards N00014-10-1-0932 and N00014-13-1-0364.2017-07-0

Radar remote sensing estimates of waves and wave forcing at a tidal inlet

Author Posting. © American Meteorological Society, 2015. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Atmospheric and Oceanic Technology 32 (2015): 842–854, doi:10.1175/JTECH-D-14-00215.1.The time and space variability of wave transformation through a tidal inlet is investigated with radar remote sensing. The frequency of wave breaking and the net wave breaking dissipation at high spatial resolution is estimated using image sequences acquired with a land-based X-band marine radar. Using the radar intensity data, transformed to normalized radar cross section σ0, the temporal and spatial distributions of wave breaking are identified using a threshold developed via the data probability density function. In addition, the inlet bathymetry is determined via depth inversion of the radar-derived frequencies and wavenumbers of the surface waves using a preexisting algorithm (cBathy). Wave height transformation is calculated through the 1D cross-shore energy flux equation incorporating the radar-estimated breaking distribution and bathymetry. The accuracy of the methodology is tested by comparison with in situ wave height observations over a 9-day period, obtaining correlation values R = 0.68 to 0.96, and root-mean-square errors from 0.05 to 0.19 m. Predicted wave forcing, computed as the along-inlet gradient of the cross-shore radiation stress was onshore during high-wave conditions, in good agreement (R = 0.95) with observations.These data were collected as part of a joint field program, Data Assimilation and Remote Sensing for Littoral Applications (DARLA) and Rivers and Inlets (RIVET-1), both funded by the Office of Naval Research. The authors were funded through the Office of Naval Research Grant N00014-10-1-0932 and the Office of the Assistant Secretary of Defense for Research and Engineering.2015-10-0

Long-term results of a multicenter SAKK trial on high-dose ifosfamide and doxorubicin in advanced or metastatic gynecologic sarcomas

Background: Dose intensive chemotherapy has not been tested prospectively for the treatment of gynecologic sarcomas. We investigated the antitumor activity and toxicity of high-dose ifosfamide and doxorubicin, in the context of a multidisciplinary strategy for the treatment of advanced and metastatic, not pretreated, gynecologic sarcomas. Patients and methods: Thirty-nine patients were enrolled onto a phase I-II multicenter trial of ifosfamide, 10 g/m2 as a continuous infusion over 5 days, plus doxorubicin intravenously, 25 mg/m2/day for 3 days with Mesna and granulocyte-colony-stimulating factor every 21 days. Salvage therapy was allowed after chemotherapy. Results: Among the 37 evaluable patients, the tumor was locally advanced (n = 11), with concomitant distant metastases (n = 5) or with distant metastases only (n = 21). After a median of three (range 1-7) chemotherapy cycles, six patients experienced a complete response and 12 a partial response for an overall response rate of 49% (95% CI 32% to 66%). The response rate was higher in poorly differentiated tumors (62%) compared with moderately well differentiated ones (18%), but was not different according to histology subtypes. Eleven patients had salvage therapy, either immediately following chemotherapy (n = 7) or at time of progression (n = 4). With a median follow-up time of 5 years, the median overall survival was 30.5 months. Hematological toxicity was as expected neutropenia, thrombopenia and anemia ≥grade 3 at 50%, 34% and 33% of cycles respectively. No toxic death occurred. Conclusions: High-dose ifosfamide plus doxorubicin is an active regimen for all subtypes of gynecological sarcomas. Its toxicity was manageable in a multicentric setting. The prolonged survival might be due to the multidisciplinary strategy that was possible in one-third of the patient

Receptor-targeted lentiviral vectors are exceptionally sensitive toward the biophysical properties of the displayed single-chain Fv

An increasing number of applications require the expression of single-chain variable fragments (scFv) fusion proteins in mammalian cells at the cell surface membrane. Here we assessed the CD30-specific scFv HRS3, which is used in immunotherapy, for its ability to retarget lentiviral vectors (LVs) to CD30 and to mediate selective gene transfer into CD30-positive cells. Fused to the C-terminus of the type-II transmembrane protein hemagglutinin (H) of measles virus and expressed in LV packaging cells, gene transfer mediated by the released LV particles was inefficient. A series of point mutations in the scFv framework regions addressing its biophysical properties, which substantially improved production and increased the melting temperature without impairing its kinetic binding behavior to CD30, also improved the performance of LV particles. Gene transfer into CD30-positive cells increased ∼100-fold due to improved transport of the H-scFv protein to the plasma membrane. Concomitantly, LV particle aggregation and syncytia formation in packaging cells were substantially reduced. The data suggest that syncytia formation can be triggered by trans-cellular dimerization of H-scFv proteins displayed on adjacent cells. Taken together, we show that the biophysical properties of the targeting ligand have a decisive role for the gene transfer efficiency of receptor-targeted LV