Isolation of a Housefly Head Protein Fraction that Exhibits High Affinity Binding of Cholinergic Ligands

The purification is described of a protein fraction, isolated from the central nervous system of housefly heads, that exhibits high affinity for cholinergic ligands. The purified material was found tq bind with high affinity acetylcholine, nicotinic ligands such as nicotine and decamethonium as well as atropine, dexetimide a:qg pilocarpine which are of a muscarinic nature. With all the ligands there appeared to be only a single site for binding with measured dissociation constants varying from 6.2 X 10-s M (dexetimide) to 5.4 x 10-6 M (pilocarpine). The concentration of binding sites was in the range of 381 nmol g-1 of protein (atropine) to 560 nmol g-1 of protein (pilocarpine)

Space-Time Clustering and Correlations of Major Earthquakes

Earthquake occurrence in nature is thought to result from correlated elastic stresses, leading to clustering in space and time. We show that occurrence of major earthquakes in California correlates with time intervals when fluctuations in small earthquakes are suppressed relative to the long term average. We estimate a probability of less than 1% that this coincidence is due to random clustering.Comment: 5 pages, 3 figures. Submitted to PR

Isolation of a Housefly Head Protein Fraction that Exhibits High Affinity Binding of Cholinergic Ligands

The purification is described of a protein fraction, isolated from the central nervous system of housefly heads, that exhibits high affinity for cholinergic ligands. The purified material was found tq bind with high affinity acetylcholine, nicotinic ligands such as nicotine and decamethonium as well as atropine, dexetimide a:qg pilocarpine which are of a muscarinic nature. With all the ligands there appeared to be only a single site for binding with measured dissociation constants varying from 6.2 X 10-s M (dexetimide) to 5.4 x 10-6 M (pilocarpine). The concentration of binding sites was in the range of 381 nmol g-1 of protein (atropine) to 560 nmol g-1 of protein (pilocarpine)

Impact of adverse events, treatment modifications, and dose intensity on survival among patients with advanced renal cell carcinoma treated with first‐line sunitinib: a medical chart review across ten centers in five European countries

Angiogenesis inhibitors have become standard of care for advanced and/or metastatic renal cell carcinoma (RCC), but data on the impact of adverse events (AEs) and treatment modifications associated with these agents are limited. Medical records were abstracted at 10 tertiary oncology centers in Europe for 291 patients ≥18 years old treated with sunitinib as first-line treatment for advanced RCC (no prior systemic treatment for advanced disease). Logistic regression models were estimated to compare dose intensity among patients who did and did not experience AEs during the landmark periods (18, 24, and 30 weeks). Cox proportional hazard models were used to explore the possible relationship of low-dose intensity (defined using thresholds of 0.7, 0.8, and 0.9) and treatment modifications during the landmark periods to survival. 64.4% to 67.9% of patients treated with sunitinib reported at least one AE of any grade, and approximately 10% of patients experienced at least one severe (grade 3 or 4) AE. Patients reporting severe AEs were statistically significantly more likely to have dose intensities below either 0.8 or 0.9. Dose intensity below 0.7 and dose discontinuation during all landmark periods were statistically significantly associated with shorter survival time. This study of advanced RCC patients treated with sunitinib in Europe found a significant relationship between AEs and dose intensity. It also found correlations between dose intensity and shorter survival, and between dose discontinuation and shorter survival. These results confirm the importance of tolerable treatment and maintaining dose intensity

Fabrication of a planar micro Penning trap and numerical investigations of versatile ion positioning protocols

We describe a versatile planar Penning trap structure, which allows to dynamically modify the trapping conguration almost arbitrarily. The trap consists of 37 hexagonal electrodes, each with a circumcirle-diameter of 300 m, fabricated in a gold-on-sapphire lithographic technique. Every hexagon can be addressed individually, thus shaping the electric potential. The fabrication of such a device with clean room methods is demonstrated. We illustrate the variability of the device by a detailed numerical simulation of a lateral and a vertical transport and we simulate trapping in racetrack and articial crystal congurations. The trap may be used for ions or electrons, as a versatile container for quantum optics and quantum information experiments.Comment: 10 pages, 7 figures, pdflatex, to be published in New Journal of Physics (NJP) various changes according to the wishes of the NJP referees. Text added and moved around, title changed, abstract changed, references added rev3: one reference had a typo (ref 15), fixed (phys rev a 72, not 71

O(a^2) cutoff effects in lattice Wilson fermion simulations

In this paper we propose to interpret the large discretization artifacts affecting the neutral pion mass in maximally twisted lattice QCD simulations as O(a^2) effects whose magnitude is roughly proportional to the modulus square of the (continuum) matrix element of the pseudoscalar density operator between vacuum and one-pion state. The numerical size of this quantity is determined by the dynamical mechanism of spontaneous chiral symmetry breaking and turns out to be substantially larger than its natural magnitude set by the value of Lambda_QCD.Comment: 38 pages, 1 figure, 2 table

Predictors of progression free survival, overall survival and early cessation of chemotherapy in women with potentially platinum sensitive (PPS) recurrent ovarian cancer (ROC) starting third or subsequent line(> 3) chemotherapy – the GCIG Symptom Benefit Study (SBS)

Background: Potentially platinum sensitive recurrent ovarian cancer (PPS ROC) is defined by a platinum-free interval of >6 months, and usually treated with platinum-based chemotherapy with variable response and benefit in women who have had 3 or more lines of chemotherapy(≥3). We identified baseline characteristics (health-related quality of life[HRQL] and clinicopathological factors), associated with PFS, OS and early progression (within 8 weeks). The goal is to improve patient selection for chemotherapy based on a nomogram predicting PFS. Methods: HRQL was assessed with EORTC QLQ-C30/QLQ-OV28. Associations with PFS and OS were assessed with Cox proportional hazards regression. Variables significant in univariable analysis were included in multivariable analyses using backward elimination to select those significant. Associations with stopping chemotherapy early were assessed with logistic regression. Results: 378 women were enrolled, with median(m)OS and PFS of 16.6 months and 5.3 months, respectively. The majority had ECOGPS 0–1. Chemotherapy was stopped early in 45/378 participants (12%); with mOS 3.4 months (95% CI: 1.7–7.2). Physical function(PF), role function(RF), cognitive function(CF), social function(SF), Global Health Status(GHS) and abdominal/GI symptoms(AGIS) were significant univariable predictors of PFS(p < 0.030). SF remained significant after adjusting for clinicopathological factors; p = 0.03. PF, RF, CF, SF, GHS and AGIS were significant univariable predictors of OS (p < 0.007); PF, RF, SF and GHS remained significant predictors of OS in multivariable models; p < 0.007. Poor baseline PF and GHS were significant univariable predictors of stopping chemotherapy early (p < 0.007) but neither remained significant after adjusting for clinicopathological factors. Conclusion: Baseline HRQL is simple to measure, is predictive of PFS and OS and when used in conjunction with clinicopathological prognostic factors, can assist with clinical decision making and treatment recommendations for women with PPSROC≥3

Pulsed Feedback Defers Cellular Differentiation

Environmental signals induce diverse cellular differentiation programs. In certain systems, cells defer differentiation for extended time periods after the signal appears, proliferating through multiple rounds of cell division before committing to a new fate. How can cells set a deferral time much longer than the cell cycle? Here we study Bacillus subtilis cells that respond to sudden nutrient limitation with multiple rounds of growth and division before differentiating into spores. A well-characterized genetic circuit controls the concentration and phosphorylation of the master regulator Spo0A, which rises to a critical concentration to initiate sporulation. However, it remains unclear how this circuit enables cells to defer sporulation for multiple cell cycles. Using quantitative time-lapse fluorescence microscopy of Spo0A dynamics in individual cells, we observed pulses of Spo0A phosphorylation at a characteristic cell cycle phase. Pulse amplitudes grew systematically and cell-autonomously over multiple cell cycles leading up to sporulation. This pulse growth required a key positive feedback loop involving the sporulation kinases, without which the deferral of sporulation became ultrasensitive to kinase expression. Thus, deferral is controlled by a pulsed positive feedback loop in which kinase expression is activated by pulses of Spo0A phosphorylation. This pulsed positive feedback architecture provides a more robust mechanism for setting deferral times than constitutive kinase expression. Finally, using mathematical modeling, we show how pulsing and time delays together enable “polyphasic” positive feedback, in which different parts of a feedback loop are active at different times. Polyphasic feedback can enable more accurate tuning of long deferral times. Together, these results suggest that Bacillus subtilis uses a pulsed positive feedback loop to implement a “timer” that operates over timescales much longer than a cell cycle

Real‐world conservation planning for evolutionary diversity in the Kimberley, Australia, sidesteps uncertain taxonomy

Targeting phylogenetic diversity (PD) in systematic conservation planning is an efficient way to minimize losses across the Tree of Life. Considering representation of genetic diversity below and above species level, also allows robust analyses within systems where taxonomy is in flux. We use dense sampling of phylogeographic diversity for 11 lizard genera, to demonstrate how PD can be applied to a policy‐ready conservation planning problem. Our analysis bypasses named taxa, using genetic data directly to inform conservation decisions. We highlight areas that should be prioritized for ecological management, and also areas that would provide the greatest benefit if added to the multisector conservation estate. We provide a rigorous and effective approach to represent the spectrum of genetic and species diversity in conservation planning.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/145539/1/conl12438.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145539/2/conl12438-sup-0001-figureS1-S2.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145539/3/conl12438_am.pd