Spatial Coherence of a Polariton Condensate

We perform Young's double-slit experiment to study the spatial coherence properties of a two-dimensional dynamic condensate of semiconductor microcavity polaritons. The coherence length of the system is measured as a function of the pump rate, which confirms a spontaneous buildup of macroscopic coherence in the condensed phase. An independent measurement reveals that the position and momentum uncertainty product of the condensate is close to the Heisenberg limit. An experimental realization of such a minimum uncertainty wave packet of the polariton condensate opens a door to coherent matter-wave phenomena such as Josephson oscillation, superfluidity, and solitons in solid state condensate systems

Investigations in vivo of the effects of carbogen breathing on 5-fluorouracil pharmacokinetics and physiology of solid rodent tumours

Purpose: We have shown previously that carbogen (95% 02, 5% CO2) breathing by rodents can increase uptake of anticancer drugs into tumours. The aim of this study was to extend these observations to other rodent models using the anticancer drug 5-fluorouracil (5FU). 5FU pharmacokinetics in tumour and plasma and physiological effects on the tumour by carbogen were investigated to determine the locus of carbogen action on augmenting tumour uptake of 5FU. Methods: Two different tumour models were used, rat GH3 prolactinomas xenografted s.c. into nude mice and rat H9618a hepatomas grown s.c. in syngeneic Buffalo rats. Uptake and metabolism of 5FU in both tumour models with or without host carbogen breathing was studied non-invasively using fluorine-19 magnetic resonance spectroscopy (19F-MRS), while plasma samples from Buffalo rats were used to construct a NONMEM pharmacokinetic model. Physiological effects of carbogen on tumours were studied using 31P-MRS for energy status (NTP/Pi) and pH, and gradient-recalled echo magnetic resonance imaging (GRE-MRI) for blood flow and oxygenation. Results: In both tumour models, carbogan-induced GRE-MRI signal intensity increases of ∼60% consistent with an increase in tumour blood oxygenation and/or flow. In GH3 xenografts, 19F-MRS showed that carbogen had no significant effect on 5FU uptake and metabolism by the tumours, and 31P-MRS showed there was no change in the NTP/Pi ratio. In H9618a hepatomas, 19F-MRS showed that carbogen had no effect on tumour 5FU uptake but significantly (p=0.0003) increased 5FU elimination from the tumour (i.e. decreased the t1/2) and significantly (p=0.029) increased (53%) the rate of metabolism to cytotoxic fluoronucleotides (FNuct). The pharmacokinetic analysis showed that carbogen increased the rate of tumour uptake of 5FU from the plasma but also increased the rate of removal. 31P-MRS showed there were significant (p≤0.02) increases in the hepatoma NTP/Pi ratio of 49% and transmembrane pH gradient of 0.11 units. Conclusions: We suggest that carbogen can transiently increase tumour blood flow, but this effect alone may not increase uptake of anticancer drugs without a secondary mechanism operating. In the case of the hepatoma, the increase in tumour energy status and pH gradient may be sufficient to augment 5FU metabolism to cytotoxic FNuct, while in the GH3 xenografts this was not the case. Thus carbogen breathing does not universally lead to increased uptake of anticancer drug

Hydraulic fracturing tests in anhydrite interbeds in the WIPP, Marker Beds 139 and 140

Hydraulic fracturing tests were integrated with hydrologic tests to estimate the conditions under which gas pressure in the disposal rooms in the Waste Isolation Pilot Plant, Carlsbad, NM (WIPP) will initiate and advance fracturing in nearby anhydrite interbeds. The measurements were made in two marker beds in the Salado formation, MB139 and MB140, to explore the consequences of existing excavations for the extrapolation of results to undisturbed ground. The interpretation of these measurements is based on the pressure-time records in two injection boreholes and several nearby hydrologic observation holes. Data interpretations were aided by post-test borehole video surveys of fracture traces that were made visible by ultraviolet illumination of fluorescent dye in the hydraulic fracturing fluid. The conclusions of this report relate to the upper- and lower-bound gas pressures in the WIPP, the paths of hydraulically and gas-driven fractures in MB139 and MB140, the stress states in MB139 and MB140, and the probable in situ stress states in these interbeds in undisturbed ground far away from the WIPP

A Damage Mechanics Approach to Life Prediction for a Salt Structure

Excavated rooms in natural bedded salt formations are being considered for use as repositories for nuclear waste. It is presumed that deformation of the rooms by creep will lead to loss of structural integrity and affect room life history and seal efficiency. At projected repository temperatures, two possible fracture mechanisms in salt are creep-induced microcracking in triaxial compression and cleavage in tension. Thus, an accurate prediction of room life and seal degradation requires a reliable description of the creep and damage processes. While several constitutive models that treat either creep or fracture in salt are available in the literature, very few models have considered creep and damage in a coupled manner. Previously, Munson and Dawson formulated a set of creep equations for salt based on the consideration of dislocation mechanisms in the creep process. This set of creep equations has been generalized to include continuum, isotropic damage as a fully coupled variable in the response equation. The extended model has been referred to as the Multimechanism Deformation Coupled Fracture (MDCF) model. A set of material constants for the creep and damage terms was deduced based on test data for both clean and argillaceous salt. In this paper, the use of the MDCF model for establishing the failure criteria and for analyzing the creep response of a salt structure is demonstrated. The paper is divided into three parts. A summary of the MDCF model is presented first, which is followed by an evaluation of the MDCF model against laboratory data. Finally, finite-element calculations of the creep and damage response of a salt structure are presented and compared against in-situ field measurements

Hydraulic fracturing tests in anhydrite interbeds in the WIPP, Marker Beds 139 and 140

Hydraulic fracturing tests were integrated with hydrologic tests to estimate the conditions under which gas pressure in the disposal rooms in the Waste Isolation Pilot Plant, Carlsbad, NM (WIPP) will initiate and advance fracturing in nearby anhydrite interbeds. The measurements were made in two marker beds in the Salado formation, MB139 and MB140, to explore the consequences of existing excavations for the extrapolation of results to undisturbed ground. The interpretation of these measurements is based on the pressure-time records in two injection boreholes and several nearby hydrologic observation holes. Data interpretations were aided by post-test borehole video surveys of fracture traces that were made visible by ultraviolet illumination of fluorescent dye in the hydraulic fracturing fluid. The conclusions of this report relate to the upper- and lower-bound gas pressures in the WIPP, the paths of hydraulically and gas-driven fractures in MB139 and MB140, the stress states in MB139 and MB140, and the probable in situ stress states in these interbeds in undisturbed ground far away from the WIPP

Feasibility of measuring renal blood flow by phase-contrast magnetic resonance imaging in patients with autosomal dominant polycystic kidney disease

Renal blood flow (RBF) has been shown to predict disease progression in autosomal dominant polycystic kidney disease (ADPKD). We investigated the feasibility and accuracy of phase-contrast RBF by MRI (RBFMRI) in ADPKD patients with a wide range of estimated glomerular filtration rate (eGFR) values. First, we validated RBFMRI measurement using phantoms simulating renal artery hemodynamics. Thereafter, we investigated in a test-set of 21 patients intra- and inter-observer coefficient of variation of RBFMRI. After validation, we measured RBFMRI in a cohort of 91 patients and compared the variability explained by characteristics indicative for disease severity for RBFMRI and RBF measured by continuous hippuran infusion. The correlation in flow measurement using phantoms by phase-contrast MRI was high and fluid collection was high (CCC=0.969). Technical problems that precluded RBFMRI measurement occurred predominantly in patients with a lower eGFR (34% vs. 16%). In subjects with higher eGFRs, variability in RBF explained by disease characteristics was similar for RBFMRI compared to RBFHip, whereas in subjects with lower eGFRs, this was significantly less for RBFMRI. Our study shows that RBF can be measured accurately in ADPKD patients by phase-contrast, but this technique may be less feasible in subjects with a lower eGFR. aEuro cent Renal blood flow (RBF) can be accurately measured by phase-contrast MRI in ADPKD patients. aEuro cent RBF measured by phase-contrast is associated with ADPKD disease severity. aEuro cent RBF measurement by phase-contrast MRI may be less feasible in patients with an impaired eGFR

PIWI silencing mechanism involving the retrotransposon nimbus orchestrates resistance to infection with Schistosoma mansoni in the snail vector, Biomphalaria glabrata

Copyright: © 2021 Smith et al. Background Schistosomiasis remains widespread in many regions despite efforts at its elimination. By examining changes in the transcriptome at the host-pathogen interface in the snail Biomphalaria glabrata and the blood fluke Schistosoma mansoni, we previously demonstrated that an early stress response in juvenile snails, manifested by induction of heat shock protein 70 (Hsp 70) and Hsp 90 and of the reverse transcriptase (RT) domain of the B. glabrata non-LTR- retrotransposon, nimbus, were critical for B. glabrata susceptibility to S. mansoni. Subsequently, juvenile B. glabrata BS-90 snails, resistant to S. mansoni at 25°C become susceptible by the F2 generation when maintained at 32°C, indicating an epigenetic response. Methodology/Principal findings To better understand this plasticity in susceptibility of the BS-90 snail, mRNA sequences were examined from S. mansoni exposed juvenile BS-90 snails cultured either at 25°C (non-permissive temperature) or 32°C (permissive). Comparative analysis of transcriptomes from snails cultured at the non-permissive and permissive temperatures revealed that whereas stress related transcripts dominated the transcriptome of susceptible BS-90 juvenile snails at 32°C, transcripts encoding proteins with a role in epigenetics, such as PIWI (BgPiwi), chromobox protein homolog 1 (BgCBx1), histone acetyltransferase (BgHAT), histone deacetylase (BgHDAC) and metallotransferase (BgMT) were highly expressed in those cultured at 25°C. To identify robust candidate transcripts that will underscore the anti-schistosome phenotype in B. glabrata, further validation of the differential expression of the above transcripts was performed by using the resistant BS-90 (25°C) and the BBO2 susceptible snail stock whose genome has now been sequenced and represents an invaluable resource for molecular studies in B. glabrata. A role for BgPiwi in B. glabrata susceptibility to S. mansoni, was further examined by using siRNA corresponding to the BgPiwi encoding transcript to suppress expression of BgPiwi, rendering the resistant BS-90 juvenile snail susceptible to infection at 25°C. Given transposon silencing activity of PIWI as a facet of its role as guardian of the integrity of the genome, we examined the expression of the nimbus RT encoding transcript at 120 min after infection of resistant BS90 piwi-siRNA treated snails. We observed that nimbus RT was upregulated, indicating that modulation of the transcription of the nimbus RT was associated with susceptibility to S. mansoni in BgPiwi-siRNA treated BS-90 snails. Furthermore, treatment of susceptible BBO2 snails with the RT inhibitor lamivudine, before exposure to S. mansoni, blocked S. mansoni infection concurrent with downregulation of the nimbus RT transcript and upregulation of the BgPiwi encoding transcript in the lamivudine-treated, schistosome-exposed susceptible snails. Conclusions and significance These findings support a role for the interplay of BgPiwi and nimbus in the epigenetic modulation of plasticity of resistance/susceptibility in the snail-schistosome relationship. Author summary Progress is being made to eliminate schistosomiasis, a tropical disease that remains endemic in the tropics and neotropics. In 2020, WHO proposed controlling the snail population as part of a strategy toward reducing schistosomiasis, a vector borne disease, by 2025. The life cycle of the causative parasite is, however, complex and in the absence of vaccines, new drugs, and access to clean water and sanitation, reduction of schistosomiasis will remain elusive. To break the parasite’s life cycle during the snail stage of its development, a better understanding of the molecular basis of how schistosomes survive, or not, in the snail is required. By examining changes in the transcriptome at the host-pathogen interface in the snail Biomphalaria glabrata and Schistosoma mansoni, we showed that early stress response, manifested by the induction of Heat Shock Proteins (Hsps) and the RT domain of the non-LTR retrotransposon, nimbus, were critical for snail susceptibility. Subsequently, juvenile B. glabrata BS-90 snails, resistant to S. mansoni at 25°C were observed to become susceptible by the F2 generation when maintained at 32°C, indicating an epigenetic response. This study confirms these earlier results and shows an interplay between PIWI and nimbus in the anti-schistosome response in the snail host.National Science Foundation (US) (Grant number Award No. 162281); CBT Knight foundation (US); Brunel University (UK)

An updated radiocarbon-based ice margin chronology for the last deglaciation of the North American Ice Sheet Complex

The North American Ice Sheet Complex (NAISC; consisting of the Laurentide, Cordilleran and Innuitian ice sheets) was the largest ice mass to repeatedly grow and decay in the Northern Hemisphere during the Quaternary. Understanding its pattern of retreat following the Last Glacial Maximum is critical for studying many facets of the Late Quaternary, including ice sheet behaviour, the evolution of Holocene landscapes, sea level, atmospheric circulation, and the peopling of the Americas. Currently, the most up-to-date and authoritative margin chronology for the entire ice sheet complex is featured in two publications (Geological Survey of Canada Open File 1574 [Dyke et al., 2003]; ‘Quaternary Glaciations – Extent and Chronology, Part II’ [Dyke, 2004]). These often-cited datasets track ice margin recession in 36 time slices spanning 18 ka to 1 ka (all ages in uncalibrated radiocarbon years) using a combination of geomorphology, stratigraphy and radiocarbon dating. However, by virtue of being over 15 years old, the ice margin chronology requires updating to reflect new work and important revisions. This paper updates the aforementioned 36 ice margin maps to reflect new data from regional studies. We also update the original radiocarbon dataset from the 2003/2004 papers with 1541 new ages to reflect work up to and including 2018. A major revision is made to the 18 ka ice margin, where Banks and Eglinton islands (once considered to be glacial refugia) are now shown to be fully glaciated. Our updated 18 ka ice sheet increased in areal extent from 17.81 to 18.37 million km2, which is an increase of 3.1% in spatial coverage of the NAISC at that time. Elsewhere, we also summarize, region-by-region, significant changes to the deglaciation sequence. This paper integrates new information provided by regional experts and radiocarbon data into the deglaciation sequence while maintaining consistency with the original ice margin positions of Dyke et al. (2003) and Dyke (2004) where new information is lacking; this is a pragmatic solution to satisfy the needs of a Quaternary research community that requires up-to-date knowledge of the pattern of ice margin recession of what was once the world’s largest ice mass. The 36 updated isochrones are available in PDF and shapefile format, together with a spreadsheet of the expanded radiocarbon dataset (n = 5195 ages) and estimates of uncertainty for each interval

Impacts of seismic activity on long-term repository performance at Yucca Mountain

Several effects of seismic activity on the release of radionuclides from a potential repository at Yucca Mountain are quantified. Future seismic events are predicted using data from the seismic hazard analysis conducted for the Exploratory Studies Facility (ESF). Phenomenological models are developed, including rockfall (thermal-mechanical and seismic) in unbackfilled emplacement drifts, container damage caused by fault displacement within the repository, and flow-path chance caused by changes in strain. Using the composite-porosity flow model (relatively large-scale, regular percolation), seismic events show little effect on total-system releases; using the weeps flow model (episodic pulses of flow in locally saturated fractures), container damage and flow-path changes cause over an order of magnitude increase in releases. In separate calculations using, more realistic representations of faulting, water-table rise caused by seismically induced changes in strain are seen to be higher than previously estimated by others, but not sufficient to reach a potential repository