Ground-water Movement in the Upper Glacial Aquifer in the Manorville Area, Town of Brookhaven, Long Island, New York, in November 1983

Water levels in 52 wells near the Manorville scavenger-waste disposal facility in the Town of Brookhaven were measured in November 1983 to determine the direction and gradients of groundwater flow in the upper glacial aquifer. Groundwater moves south-southeastward (S22 degrees E) from the groundwater divide, about 6 miles north of the facility, to discharge points near East Moriches and beneath Moriches Bay. The hydraulic gradient beneath the disposal facility is 6.5 ft/mi (0.0012 foot/foot), and the rate of horizontal flow is 0.9 to 1.7 ft/day. Vertical movement of groundwater since closure of the disposal facility in 1982 is probably negligible because the vertical gradients are small and the upper glacial aquifer is anisotropic. During operation of the facility, however, groundwater mounding may have developed beneath the unlined settling basins, which could have induced downward movement of water in the upper glacial aquifer. (USGS

Information Spreading in Interacting String Field Theory

The commutator of string fields is considered in the context of light cone string field theory. It is shown that the commutator is in general non--vanishing outside the string light cone. This could have profound implications for our understanding of the localization of information in quantum gravity.Comment: 10 pages, 1 figure, harvmac and epsf, UCSBTH-94-07, SU-ITP-94-

Observation of quantum depletion in a nonequilibrium exciton-polariton condensate

The property of superfluidity, first discovered in liquid 4He, is closely related to Bose-Einstein condensation (BEC) of interacting bosons. However, even at zero temperature, when one would expect the whole bosonic quantum liquid to become condensed, a fraction of it is excited into higher momentum states via interparticle interactions and quantum fluctuations -- the phenomenon of quantum depletion. Quantum depletion of weakly interacting atomic BECs in thermal equilibrium is well understood theoretically but is difficult to measure. This is even more challenging in driven-dissipative systems such as exciton-polariton condensates(photons coupled to electron-hole pairs in a semiconductor), since their nonequilibrium nature is predicted to suppress quantum depletion. Here, we observe quantum depletion of an optically trapped high-density exciton-polariton condensate by directly detecting the spectral branch of elementary excitations populated by this process. Analysis of the population of this branch in momentum space shows that quantum depletion of an exciton-polariton condensate can closely follow or strongly deviate from the equilibrium Bogoliubov theory, depending on the fraction of matter (exciton) in an exciton-polariton. Our results reveal the effects of exciton-polariton interactions beyond the mean-field description and call for a deeper understanding of the relationship between equilibrium and nonequilibrium BECs.Comment: 18 pages, 5 figures, with supplementary informatio

c-Abl phosphorylates α-synuclein and regulates its degradation: implication for α-synuclein clearance and contribution to the pathogenesis of Parkinson's disease

Increasing evidence suggests that the c-Abl protein tyrosine kinase could play a role in the pathogenesis of Parkinson's disease (PD) and other neurodegenerative disorders. c-Abl has been shown to regulate the degradation of two proteins implicated in the pathogenesis of PD, parkin and α-synuclein (α-syn). The inhibition of parkin's neuroprotective functions is regulated by c-Abl-mediated phosphorylation of parkin. However, the molecular mechanisms by which c-Abl activity regulates α-syn toxicity and clearance remain unknown. Herein, using NMR spectroscopy, mass spectrometry, in vitro enzymatic assays and cell-based studies, we established that α-syn is a bona fide substrate for c-Abl. In vitro studies demonstrate that c-Abl directly interacts with α-syn and catalyzes its phosphorylation mainly at tyrosine 39 (pY39) and to a lesser extent at tyrosine 125 (pY125). Analysis of human brain tissues showed that pY39 α-syn is detected in the brains of healthy individuals and those with PD. However, only c-Abl protein levels were found to be upregulated in PD brains. Interestingly, nilotinib, a specific inhibitor of c-Abl kinase activity, induces α-syn protein degradation via the autophagy and proteasome pathways, whereas the overexpression of α-syn in the rat midbrains enhances c-Abl expression. Together, these data suggest that changes in c-Abl expression, activation and/or c-Abl-mediated phosphorylation of Y39 play a role in regulating α-syn clearance and contribute to the pathogenesis of P

Detection of circulating tumour DNA is associated with inferior outcomes in Ewing sarcoma and osteosarcoma: a report from the Children's Oncology Group.

BackgroundNew prognostic markers are needed to identify patients with Ewing sarcoma (EWS) and osteosarcoma unlikely to benefit from standard therapy. We describe the incidence and association with outcome of circulating tumour DNA (ctDNA) using next-generation sequencing (NGS) assays.MethodsA NGS hybrid capture assay and an ultra-low-pass whole-genome sequencing assay were used to detect ctDNA in banked plasma from patients with EWS and osteosarcoma, respectively. Patients were coded as positive or negative for ctDNA and tested for association with clinical features and outcome.ResultsThe analytic cohort included 94 patients with EWS (82% from initial diagnosis) and 72 patients with primary localised osteosarcoma (100% from initial diagnosis). ctDNA was detectable in 53% and 57% of newly diagnosed patients with EWS and osteosarcoma, respectively. Among patients with newly diagnosed localised EWS, detectable ctDNA was associated with inferior 3-year event-free survival (48.6% vs. 82.1%; p = 0.006) and overall survival (79.8% vs. 92.6%; p = 0.01). In both EWS and osteosarcoma, risk of event and death increased with ctDNA levels.ConclusionsNGS assays agnostic of primary tumour sequencing results detect ctDNA in half of the plasma samples from patients with newly diagnosed EWS and osteosarcoma. Detectable ctDNA is associated with inferior outcomes

The Initial Economic Burden of Femur Fractures on Informal Caregivers in Dar es Salaam, Tanzania

BackgroundFemur fracture patients require significant in-hospital care. The burden incurred by caregivers of such patients amplifies the direct costs of these injuries and remains unquantified. Aim Here we aim to establish the in-hospital economic burden faced by informal caregivers of femur fracture patients. Methods 70 unique caregivers for 46 femoral shaft fracture patients were interviewed. Incurred economic burden was determined by the Human Capital Approach, using standardized income data to quantify productivity loss (in $USD). Linear regression assessed the relationship between caregiver burden and patient time-in-hospital.ResultsThe average economic burden incurred was$149, 9% of a caregiver’s annual income and positively correlated with patient time in hospital (p<0.01). Conclusion Caregivers of patients treated operatively for femur fractures lost a large portion of their annual income, and this loss increased with patient time in hospital. These indirect costs of femur fracture treatment constitute an important component of the total injury burden

The novel Parkinson's disease linked mutation G51D attenuates in vitro aggregation and membrane binding of α-synuclein, and enhances its secretion and nuclear localization in cells

A novel mutation in the α-Synuclein (α-Syn) gene "G51D” was recently identified in two familial cases exhibiting features of Parkinson's disease (PD) and multiple system atrophy (MSA). In this study, we explored the impact of this novel mutation on the aggregation, cellular and biophysical properties of α-Syn, in an attempt to unravel how this mutant contributes to PD/MSA. Our results show that the G51D mutation significantly attenuates α-Syn aggregation in vitro. Moreover, it disrupts local helix formation in the presence of SDS, decreases binding to lipid vesicles C-terminal to the site of mutation and severely inhibits helical folding in the presence of acidic vesicles. When expressed in yeast, α-SynG51D behaves similarly to α-SynA30P, as both exhibit impaired membrane association, form few inclusions and are non-toxic. In contrast, enhanced secreted and nuclear levels of the G51D mutant were observed in mammalian cells, as well as in primary neurons, where α-SynG51D was enriched in the nuclear compartment, was hyper-phosphorylated at S129 and exacerbated α-Syn-induced mitochondrial fragmentation. Finally, post-mortem human brain tissues of α-SynG51D cases were examined, and revealed only partial colocalization with nuclear membrane markers, probably due to post-mortem tissue delay and fixation. These findings suggest that the PD-linked mutations may cause neurodegeneration via different mechanisms, some of which may be independent of α-Syn aggregatio

Closed-String Tachyons and the Hagedorn Transition in AdS Space

We discuss some aspects of the behaviour of a string gas at the Hagedorn temperature from a Euclidean point of view. Using AdS space as an infrared regulator, the Hagedorn tachyon can be effectively quasi-localized and its dynamics controled by a finite energetic balance. We propose that the off-shell RG flow matches to an Euclidean AdS black hole geometry in a generalization of the string/black-hole correspondence principle. The final stage of the RG flow can be interpreted semiclassically as the growth of a cool black hole in a hotter radiation bath. The end-point of the condensation is the large Euclidean AdS black hole, and the part of spacetime behind the horizon has been removed. In the flat-space limit, holography is manifest by the system creating its own transverse screen at infinity. This leads to an argument, based on the energetics of the system, explaining why the non-supersymmetric type 0A string theory decays into the supersymmetric type IIB vacuum. We also suggest a notion of `boundary entropy', the value of which decreases along the line of flow.Comment: 24 pages, Harvmac. 2 Figures. Typos corrected and reference adde

Alterations in mGluR5 Expression and Signaling in Lewy Body Disease and in Transgenic Models of Alpha- Synucleinopathy – Implications for Excitotoxicity

Dementia with Lewy bodies (DLB) and Parkinson’s Disease (PD) are neurodegenerative disorders of the aging population characterized by the abnormal accumulation of alpha-synuclein (alpha-syn). Previous studies have suggested that excitotoxicity may contribute to neurodegeneration in these disorders, however the underlying mechanisms and their relationship to alpha-syn remain unclear. For this study we proposed that accumulation of alpha-syn might result in alterations in metabotropic glutamate receptors (mGluR), particularly mGluR5 which has been linked to deficits in murine models of PD. In this context, levels of mGluR5 were analyzed in the brains of PD and DLB human cases and alpha-syn transgenic (tg) mice and compared to age-matched, unimpaired controls, we report a 40% increase in the levels of mGluR5 and beta-arrestin immunoreactivity in the frontal cortex, hippocampus and putamen in DLB cases and in the putamen in PD cases. In the hippocampus, mGluR5 was more abundant in the CA3 region and co-localized with alpha-syn aggregates. Similarly, in the hippocampus and basal ganglia of alpha-syn tg mice, levels of mGluR5 were increased and mGluR5 and alpha-syn were co-localized and co-immunoprecipated, suggesting that alpha-syn interferes with mGluR5 trafficking. The increased levels of mGluR5 were accompanied by a concomitant increase in the activation of downstream signaling components including ERK, Elk-1 and CREB. Consistent with the increased accumulation of alpha-syn and alterations in mGluR5 in cognitive- and motor-associated brain regions, these mice displayed impaired performance in the water maze and pole test, these behavioral alterations were reversed with the mGluR5 antagonist, MPEP. Taken together the results from study suggest that mGluR5 may directly interact with alpha-syn resulting in its over activation and that this over activation may contribute to excitotoxic cell death in select neuronal regions. These results highlight the therapeutic importance of mGluR5 antagonists in alpha-synucleinopathies

Bogoliubov excitations of a polariton condensate in dynamical equilibrium with an incoherent reservoir

The classic Bogoliubov theory of weakly interacting Bose gases rests upon the assumption that nearly all the bosons condense into the lowest quantum state at sufficiently low temperatures. Here we develop a generalized version of Bogoliubov theory for the case of a driven-dissipative exciton-polariton condensate with a large incoherent uncondensed component, or excitonic reservoir. We argue that such a reservoir can consist of both excitonic high-momentum polaritons and optically dark superpositions of excitons across different optically active layers, such as multiple quantum wells in a microcavity. In particular, we predict interconversion between the dark and bright (light-coupled) excitonic states that can lead to a dynamical equilibrium between the condensate and reservoir populations. We show that the presence of the reservoir fundamentally modifies both the energy and the amplitudes of the Bogoliubov quasiparticle excitations due to the non-Galilean-invariant nature of polaritons. Our theoretical findings are supported by our experiment, where we directly detect the Bogoliubov excitation branches of an optically trapped polariton condensate in the high-density regime. By analyzing the measured occupations of the excitation branches, we extract the Bogoliubov amplitudes across a range of momenta and show that they agree with our generalized theory.Comment: 16 pages, 7 figure