Suitability of high-pressure xenon as scintillator for gamma ray spectroscopy

In this paper we report the experimental study of high-pressure xenon used as a scintillator, in the context of developing a gamma ray detector. We measure a light yield near 2 photoelectrons per keV for xenon at 40 bar. Together with the light yield, we also measured an energy resolution of ~9% (FWHM) at 662 keV, dominated by the statistical fluctuations in the number of photoelectrons.Comment: 15 pages, 11 figure

Mapping conformational changes of a type IIb Na+/Pi cotransporter by voltage clamp fluorometry.

The fluorescence of a fluorophore depends on its environment, and if attached to a protein it may report on conformational changes. We have combined two-electrode voltage clamp with simultaneous fluorescence measurements to detect conformational changes in a type IIb Na(+)/P(i) cotransporter expressed in Xenopus oocytes. Four novel Cys labelled with a fluorescent probe yielded voltage-and substrate-dependent changes in fluorescence (F). Neither Cys-substitution nor labelling significantly altered the mutants' electrogenic properties. Different F responses to voltage and substrate were recorded at the four sites. S155C, located in an intracellular re-entrant loop in the first half of the protein, and E451C, located in an extracellular re-entrant loop in the second half of the protein both showed Na(+), Li(+)- and P(i)-dependent F signals. S226C and Q319C, located at opposite ends of a large extracellular loop in the middle of the protein, mainly responded to changes in Na(+) and Li(+). Hyperpolarization increased F for S155C and S226C, but decreased F for Q319C and E451C. The labelling and F response of S155C, confirmed that the intracellular loop containing Ser-155 is re-entrant as it is accessible from the extracellular milieu. The behavior of S155C and E451C indicates a strong involvement of the two re-entrant loops in conformational changes during the transport cycle. Moreover, the data for S226C and Q319C suggest that also the large extracellular loop is associated with transport function. Finally, the reciprocal voltage-dependencies of the S155C-E451C and S226C-Q319C pairs suggest reciprocal conformational changes during the transport cycle for their respective local environments

Post-transplant recurrence of steroid resistant nephrotic syndrome in children: the Italian experience

Background: Steroid resistant nephrotic syndrome (SRNS) is a frequent cause of end stage renal disease in children and post-transplant disease recurrence is a major cause of graft loss. Methods: We identified all children with SRNS who underwent renal transplantation in Italy, between 2005 and 2017. Data were retrospectively collected for the presence of a causative gene mutation, sex, histology, duration of pre-transplant dialysis, age at onset and transplant, HLA matching, recurrence, therapy for recurrence, and graft survival. Results: 101 patients underwent a first and 22 a second renal transplant. After a median follow-up of 58.5 months, the disease recurred on the first renal transplant in 53.3% of patients with a non-genetic and none with a genetic SRNS. Age at transplant > 9 years and the presence of at least one HLA-AB match were independent risk factors for recurrence. Duration of dialysis was longer in children with relapse, but did not reach statistical significance. Overall, 24% of patients lost the first graft, with recurrence representing the commonest cause. Among 22 patients who underwent a second transplant, 5 suffered of SRNS recurrence. SRNS relapsed in 5/9 (55%) patients with disease recurrence in their first transplant and 2 of them lost the second graft. Conclusions: Absence of a causative mutation represents the major risk factor for post-transplant recurrence in children with SRNS, while transplant can be curative in genetic SRNS. A prolonged time spent on dialysis before transplantation has no protective effect on the risk of relapse and should not be encouraged. Retransplantation represents a second chance after graft loss for recurrence

Temperature dependence of steady-state and presteady-state kinetics of a type IIb Na+/Pi cotransporter

The temperature dependence of the transport kinetics of flounder Na(+)-coupled inorganic phosphate (P(i)) cotransporters (NaPi-IIb) expressed in Xenopus oocytes was investigated using radiotracer and electrophysiological assays. (32)P(i) uptake was strongly temperature-dependent and decreased by approximately 80% at a temperature change from 25 degrees C to 5 degrees C. The corresponding activation energy (E (a)) was approximately 14 kcal mol(-1) for the cotransport mode. The temperature dependence of the cotransport and leak modes was determined from electrogenic responses to 1 mM P(i) and phosphonoformic acid (PFA), respectively, under voltage clamp. The magnitude of the P(i)- and PFA-induced changes in holding current decreased with temperature. E (a) at -100 mV for the cotransport and leak modes was approximately 16 kcal mol(-1) and approximately 11 kcal mol(-1), respectively, which suggested that the leak is mediated by a carrier, rather than a channel, mechanism. Moreover, E (a) for cotransport was voltage-independent, suggesting that a major conformational change in the transport cycle is electroneutral. To identify partial reactions that confer temperature dependence, we acquired presteady-state currents at different temperatures with 0 mM P(i) over a range of external Na(+). The relaxation time constants increased, and the peak time constant shifted toward more positive potentials with decreasing temperature. Likewise, there was a depolarizing shift of the charge distribution, whereas the total available charge and apparent valency predicted from single Boltzmann fits were temperature-independent. These effects were explained by an increased temperature sensitivity of the Na(+)-debinding rate compared with the other voltage-dependent rate constants

Sodium Transport in Capillaries Isolated from Rat Brain

Brain capillary endothelial cells form a bloodbrain barrier (BBB) that appears to play a role in fluid and ion homeostasis in brain. One important transport system that may be involved in this regulatory function is the Na + ,K + -ATPase that was previously demonstrated to be present in isolated brain capillaries. The goal of the present study was to identify additional Na + transport systems in brain capillaries that might contribute to BBB function. Microvessels were isolated from rat brains and 22 Na + uptake by and efflux from the cells were studied. Total 22 Na + uptake was increased and the rate of 22 Na + efflux was decreased by ouabain, confirming the presence of Na + ,K + -ATPase in capillary cells. After inhibition of Na + ,K + -ATPase activity, another saturable Na + transport mechanism became apparent. Capillary uptake of 22 Na + was stimulated by an elevated concentration of Na + or H + inside the cells and inhibited by extracellular Na + , H + , Li + , and NH 4 + . Amiloride inhibited 22 Na + uptake with a K i between 10 −5 and 10 −6 M but there was no effect of 1 mM furosemide on 22 Na + uptake by the isolated microvessels. These results indicate the presence in brain capillaries of a transport system capable of mediating Na + / Na + and Na + /H + exchange. As a similar transport system does not appear to be present on the luminal membrane of the brain capillary endothelial cell, it is proposed that Na + /H + exchange occurs primarily across the antiluminal membrane.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66187/1/j.1471-4159.1983.tb09065.x.pd

Further phenotypic heterogeneity of CoQ10 deficiency associated with Steroid Resistant Nephrotic Syndrome and novel COQ2 and COQ6 variants.

open16noWe descripe three patients with SRNS associated with pathogentic changes in two CoQ pathway genes: one novel homozygous COQ2 variant was identified in two cousins with adolescent-onset SRNS and mild neurological symptoms (Family 1); and one novel COQ6 variant was found in a child with early onset SRNS without deafness and neurological involvement (Family 2). (A, B) : families (C) : Sanger sequencing showing COQ2 change: NM_015697.7: c.1169G>C; NP_056512.5; p.Gly390Ala (c.1019G>C; p.Gly340Ala, according to KU877220 GenBank sequence) (D) : Sanger sequencing showing COQ6 change: NM_182476.2:c.782C>T; NP_872282.1:p.Pro261Leu. (E, F): Functional complementation in yeast. Serial dilutions of ΔCOQ2 and ΔCOQ6 yeast transformed with wild-type, the empty vector and the mutant alleles; complex II+III (C.II+C.III) and citrate synthase (CS) activities.embargoed_20180801Gigante, M; Diella, S; Santangelo, L; Trevisson, Eva; Acosta, Mj; Amatruda, M; Finzi, G; Caridi, G; Murer, L; Accetturo, M; Ranieri, E; Ghiggeri, Gm; Giordano, M; Grandaliano, G; Salviati, Leonardo; Gesualdo, L.Gigante, M; Diella, S; Santangelo, L; Trevisson, Eva; Acosta, Mj; Amatruda, M; Finzi, G; Caridi, G; Murer, L; Accetturo, M; Ranieri, E; Ghiggeri, Gm; Giordano, M; Grandaliano, G; Salviati, Leonardo; Gesualdo, L

Rituximab in Children with Steroid-Dependent Nephrotic Syndrome: A Multicenter, Open-Label, Noninferiority, Randomized Controlled Trial.

Steroid-dependent nephrotic syndrome (SDNS) carries a high risk of toxicity from steroids or steroid-sparing agents. This open-label, noninferiority, randomized controlled trial at four sites in Italy tested whether rituximab is noninferior to steroids in maintaining remission in juvenile SDNS. We enrolled children age 1-16 years who had developed SDNS in the previous 6-12 months and were maintained in remission with high prednisone doses ( 650.7 mg/kg per day). We randomly assigned participants to continue prednisone alone for 1 month (control) or to add a single intravenous infusion of rituximab (375 mg/m(2); intervention). Prednisone was tapered in both groups after 1 month. For noninferiority, rituximab had to permit steroid withdrawal and maintain 3-month proteinuria (mg/m(2) per day) within a prespecified noninferiority margin of three times the levels among controls (primary outcome). We followed participants for 651 year to compare risk of relapse (secondary outcome). Fifteen children per group (21 boys; mean age, 7 years [range, 2.6-13.5 years]) were enrolled and followed for 6460 months (median, 22 months). Three-month proteinuria was 42% lower in the rituximab group (geometric mean ratio, 0.58; 95% confidence interval, 0.18 to 1.95 [i.e., within the noninferiority margin of three times the levels in controls]). All but one child in the control group relapsed within 6 months; median time to relapse in the rituximab group was 18 months (95% confidence interval, 9 to 32 months). In the rituximab group, nausea and skin rash during infusion were common; transient acute arthritis occurred in one child. In conclusion, rituximab was noninferior to steroids for the treatment of juvenile SDNS

Mapping steam and water flow in petroleum reservoirs

Over the past 5 years, we have applied high-resolution geophysical methods (crosswell seismic and electromagnetics (EM), and passive seismic) to map and characterize petroleum reservoirs in the San Joaquin Valley and to monitor changes during secondary recovery operations. The two techniques provide complementary information. Seismic data reveal the reservoir structure, whereas EM measurements are more sensitive to the pore fluid distribution. Seismic surveys at the south Belridge field were used to map fracture generation and monitor formation changes due to the onset of steam flooding. Early results show possible sensitivity to changes in gas saturation caused by the steam flooding. Crosswell EM surveys were applied at a shallow pilot at Lost Hills for reservoir characterization and steamflood monitoring. Images made from baselines data clearly show the distribution of the target oil sands; repeated surveys during the steam flood allowed us to identify the boundaries of the steam chest and to accurately predict breakthrough. Applications of the EM techniques in steel-cased wells are at an early stage, but preliminary results at Lost Hills show sensitivity to formation resistivity in a water-flood pilot. Finally, passive seismic surveys during hydrofracture operations measured events corelatable in frequency content and magnitude with the size and orientation of induced fractures