The DRIFT Directional Dark Matter Detector and First Studies of the Head-Tail Effect

Measurement of the direction of the elastic nuclear recoil track and ionization charge distribution along it, gives unique possibility for unambiguous detection of the dark matter WIMP particle. Within current radiation detection technologies only Time Projection Chambers filled with low pressure gas are capable of such measurement. Due to the character of the electronic and nuclear stopping powers of low energy nuclear recoils in the gas, an asymmetric ionization charge distribution along their tracks may be expected. Preliminary study of this effect, called Head-Tail, has been carried out here using the SRIM simulation program for Carbon and Sulfur in 40 Torr carbon disulfide, as relevant to the DRIFT detector. Investigations were focused on ion tracks projected onto the axis of the initial direction of motion in the energy range between 10 and 400 keV. Results indicate the likely existence of an asymmetry influenced by two competing effects: the nature of the stopping power and range straggling. The former tends to result in the Tail being greater than the Head and the latter the reverse. It has been found that for projected tracks the mean position of the ionization charge flows from 'head' to 'tail' with the magnitude depending on the ion type and its energy.Comment: To appear in the proceedings of Dark 2007 Sixth International Heidelberg conference on "Dark Matter in Astro & Particle Physics", Sydney, Australia 24th-28th September 200

Measurement of the Scintillation Efficiency of Na Recoils in NaI(Tl) down to 10 keV Nuclear Recoil Energy relevant to Dark Matter Searches

We present preliminary results of measurements of the quenching factor for Na recoils in NaI(Tl) at room temperature, made at a dedicated neutron facility at the University of Sheffield. Measurements have been performed with a 2.45 MeV mono-energetic neutron generator in the energy range from 10 keV to 100 keV nuclear recoil energy. A BC501A liquid scintillator detector was used to tag neutrons. Cuts on pulse-shape discrimination from the BC501A liquid scintillator detector and neutron time-of-flight were performed on pulses recorded by a digitizer with a 2 ns sampling time. Measured quenching factors range from 19% to 26%, in agreement with other experiments. From pulse-shape analysis, a mean time of pulses from electron and nuclear recoils are compared down to 2 keV electron equivalent energy.Comment: to appear in Proc. 6th Int. Workshop on the Identification of Dark Matter, 11-16 September 2006, Rhodes, Greece; 6 pages, 4 figures; corrected preliminary theoretical estimation curve plotted in figure

Grain Size Constraints on Glacial Circulation in the Southwest Atlantic

Knowledge of past deep-ocean current speeds has the potential to inform our understanding of changes in the climate system on glacial-interglacial timescales, because they may be used to help constrain changes in deep-ocean circulation rates and pathways. Of particular interest is the paleo-flow speed of southern-sourced deep water, which may have acted as a carbon store during the last glacial period. A location of importance in the northward transport of southern-sourced bottom water is the Vema Channel, which divides the Argentine and Brazil basins in the South Atlanti c. We revisit previous studies of paleo-flow in Vema Channel using updated techniques in grain size analysis (i.e., mean sortable silt grain size), in Vema Channel cores and cores from the Brazil margin. Furthermore, we update the interpretation of the previous grain size studies in the light of many years further research into the glacial circulation of the deep Atlantic. Our results are broadly consistent with the existing data and suggest that during the last glacial period there was slightly more vigorous intermediate to middepth (shallower than 2,600 m) circulation in the South Atlantic Ocean than during the Holocene, whereas around 3,500 m the circulation was generally more sluggish. Increased glacial flow speed on the eastern side of the Vema Channel was likely related to an increase in northward velocity of AABW in the channel. An increase in Antarctic Bottom Water flow through the Vema Channel may have helped to sustain the large volume of southern-sourced deep water in the Atlantic during the glacial period

The proteasome cap RPT5/Rpt5p subunit prevents aggregation of unfolded ricin A chain

The plant cytotoxin ricin enters mammalian cells by receptor-mediated endocytosis, undergoing retrograde transport to the endoplasmic reticulum (ER) where its catalytic A chain (RTA) is reductively separated from the holotoxin to enter the cytosol and inactivate ribosomes. The currently accepted model is that the bulk of ER-dislocated RTA is degraded by proteasomes. We show here that the proteasome has a more complex role in ricin intoxication than previously recognised, that the previously reported increase in sensitivity of mammalian cells to ricin in the presence of proteasome inhibitors simply reflects toxicity of the inhibitors themselves, and that RTA is a very poor substrate for proteasomal degradation. Denatured RTA and casein compete for a binding site on the regulatory particle of the 26S proteasome, but their fates differ. Casein is degraded, but the mammalian 26S proteasome AAA-ATPase subunit RPT5 acts as a chaperone that prevents aggregation of denatured RTA and stimulates recovery of catalytic RTA activity in vitro. Furthermore, in vivo, the ATPase activity of Rpt5p is required for maximal toxicity of RTA dislocated from the Saccharomyces cerevisiae ER. Our results implicate RPT5/Rpt5p in the triage of substrates in which either activation (folding) or inactivation (degradation) pathways may be initiated

Longitudinal Stability Characteristics of a 42 Degree Sweptback Wing and Tail Combination at a Reynolds Number of 6.8 x 10(exp 6)

Results are given of a wind-tunnel investigation at a Reynolds number of 6.8 x 10(exp 6) to determine the static longitudinal stability characteristics of a 42 degree sweptback wing and fuselage combination with a sweptback horizontal tail. Included are the effects of vertical position of fuselage and tail with respect to wing for several combinations of high-lift and staff-control devices. Also included is the effect of a simulated ground

Cytosolic chaperones influence the fate of a toxin dislocated from the endoplasmic reticulum

The plant cytotoxin ricin enters target mammalian cells by receptor-mediated endocytosis and undergoes retrograde transport to the endoplasmic reticulum (ER). Here, its catalytic A chain (RTA) is reductively separated from the cell-binding B chain, and free RTA enters the cytosol where it inactivates ribosomes. Cytosolic entry requires unfolding of RTA and dislocation across the ER membrane such that it arrives in the cytosol in a vulnerable, nonnative conformation. Clearly, for such a dislocated toxin to become active, it must avoid degradation and fold to a catalytic conformation. Here, we show that, in vitro, Hsc70 prevents aggregation of heat-treated RTA, and that RTA catalytic activity is recovered after chaperone treatment. A combination of pharmacological inhibition and cochaperone expression reveals that, in vivo, cytosolic RTA is scrutinized sequentially by the Hsc70 and Hsp90 cytosolic chaperone machineries, and that its eventual fate is determined by the balance of activities of cochaperones that regulate Hsc70 and Hsp90 functions. Cytotoxic activity follows Hsc70-mediated escape of RTA from an otherwise destructive pathway facilitated by Hsp90. We demonstrate a role for cytosolic chaperones, proteins typically associated with folding nascent proteins, assembling multimolecular protein complexes and degrading cytosolic and stalled, cotranslocational clients, in a toxin triage, in which both toxin folding and degradation are initiated from chaperone-bound states

Developing a Core Outcome Set for Prognostic Research in Palliative Cancer Care: Protocol for a Mixed Methods Study

Background: Studies exploring the impact of receiving end-of-life prognoses in patients with advanced cancer use a variety of different measures to evaluate the outcomes, and thus report often conflicting findings. The standardization of outcomes reported in studies of prognostication in palliative cancer care could enable uniform assessment and reporting, as well as intertrial comparisons. A core outcome set promotes consistency in outcome selection and reporting among studies within a particular population. We aim to develop a set of core outcomes to be used to measure the impact of end-of-life prognostication in palliative cancer care. Objective: This protocol outlines the proposed methodology to develop a core outcome set for measuring the impact of end-of-life prognostication in palliative cancer care. Methods: We will adopt a mixed methods approach consisting of 3 phases using methodology recommended by the Core Outcome Measure in Effectiveness Trials (COMET) initiative. In phase I, we will conduct a systematic review to identify existing outcomes that prognostic studies have previously used, so as to inform the development of items and domains for the proposed core outcome set. Phase II will consist of semistructured interviews with patients with advanced cancer who are receiving palliative care, informal caregivers, and clinicians, to explore their perceptions and experiences of end-of-life prognostication. Outcomes identified in the interviews will be combined with those found in existing literature and taken forward to phase III, a Delphi survey, in which we will ask patients, informal caregivers, clinicians, and relevant researchers to rate these outcomes until consensus is achieved as to which are considered to be the most important for inclusion in the core outcome set. The resulting, prioritized outcomes will be discussed in a consensus meeting to agree and endorse the final core outcome set. Results: Ethical approval was received for this study in September 2022. As of July 2023, we have completed and published the systematic review (phase I) and have started recruitment for phase II. Data analysis for phase II has not yet started. We expect to complete the study by October 2024. Conclusions: This protocol presents the stepwise approach that will be taken to develop a core outcome set for measuring the impact of end-of-life prognostication in palliative cancer care. The final core outcome set has the potential for translation into clinical practice, allowing for consistent evaluation of emerging prognostic algorithms and improving communication of end-of-life prognostication. This study will also potentially facilitate the design of future clinical trials of the impact of end-of-life prognostication in palliative care that are acceptable to key stakeholders

Cytosolic chaperones influence the fate of a toxin dislocated from the endoplasmic reticulum

The plant cytotoxin ricin enters target mammalian cells by receptor-mediated endocytosis and undergoes retrograde transport to the endoplasmic reticulum (ER). Here, its catalytic A chain (RTA) is reductively separated from the cell-binding B chain, and free RTA enters the cytosol where it inactivates ribosomes. Cytosolic entry requires unfolding of RTA and dislocation across the ER membrane such that it arrives in the cytosol in a vulnerable, nonnative conformation. Clearly, for such a dislocated toxin to become active, it must avoid degradation and fold to a catalytic conformation. Here, we show that, in vitro, Hsc70 prevents aggregation of heat-treated RTA, and that RTA catalytic activity is recovered after chaperone treatment. A combination of pharmacological inhibition and cochaperone expression reveals that, in vivo, cytosolic RTA is scrutinized sequentially by the Hsc70 and Hsp90 cytosolic chaperone machineries, and that its eventual fate is determined by the balance of activities of cochaperones that regulate Hsc70 and Hsp90 functions. Cytotoxic activity follows Hsc70-mediated escape of RTA from an otherwise destructive pathway facilitated by Hsp90. We demonstrate a role for cytosolic chaperones, proteins typically associated with folding nascent proteins, assembling multimolecular protein complexes and degrading cytosolic and stalled, cotranslocational clients, in a toxin triage, in which both toxin folding and degradation are initiated from chaperone-bound states

Origins of the Old South: Revolution, Slavery, and Changes in Southern Society, 1776-1800

The American Revolution and its aftermath posed the greatest challenge to the institution of slavery since the first Africans landed in Jamestown. Revolutionary defenses of the natural equality of man provided ammunition for generations of men and women opposed to racial subordination while the ideological strains of the struggle sounded the death knell for slavery in Northern states and led significant numbers of Southerners to question the morality and safety of slaveholding. Most importantly, the bloody and chaotic war in the South provided an unprecedented opportunity for slaves to challenge their bondage as tens of thousands of black men and women fled to the British, the swamps, or the relative anonymity of the cities. In examining the “reconstruction” of Southern slavery in the post-Revolutionary decades, Merging social, military, and economic history, "Origins of the Old South" examines how, in the attempt to rebuild their society from the ravages of war, black and white Southerners together created the new and historically distinct slave society of the “Old South.” The first two chapters of the dissertation demonstrate how the struggle to contain the disorders of a civil war amongst half a million enslaved African-Americans transformed the Southern states—the scene of the war’s bloodiest fighting after 1778—into a crucible in which men, land, and debt melted into capital. State governments redistributed thousands of slaves and millions of acres of land to purchase supplies and raise troops from within a weary populace; the estates of many of the South’s most important planters, comprising roughly ten percent of the region’s real and personal wealth, were confiscated and sold at auction at a fraction of their value; and wartime prestige coupled with the departure of prominent loyalists allowed a legion of “new men” to come into control of the new state governments. The result was the ascendance of a new class of merchant planters, who pushed the locus of Southern development inland, and major changes in the contours of black life in the region. The remaining three chapters of the dissertation examine these twinned consequences of the Revolution over the following three decades. Chapter three follows the experience of enslaved men and women after the war, tracing their movement throughout the Atlantic World and across the boundary between slavery and freedom during the conflict. Chapter four then looks at the impact of the region's ill-fated antislavery push during and immediately after the war, while chapter five shows how early national state governments drove slavery's expansion and closed the revolutionary moment in the process

Simulations of the Nuclear Recoil Head-Tail Signature in Gases Relevant to Directional Dark Matter Searches

We present the first detailed simulations of the head-tail effect relevant to directional Dark Matter searches. Investigations of the location of the majority of the ionization charge as being either at the beginning half (tail) or at the end half (head) of the nuclear recoil track were performed for carbon and sulphur recoils in 40 Torr negative ion carbon disulfide and for fluorine recoils in 100 Torr carbon tetrafluoride. The SRIM simulation program was used, together with a purpose-written Monte Carlo generator, to model production of ionizing pairs, diffusion and basic readout geometries relevant to potential real detector scenarios, such as under development for the DRIFT experiment. The results clearly indicate the existence of a head-tail track asymmetry but with a magnitude critically influenced by two competing factors: the nature of the stopping power and details of the range straggling. The former tends to result in the tail being greater than the head and the latter the reverse.Comment: 22 pages, 12 figures, submitted to Astroparticle Physic