A modern approach to the Heckel Equation: The effect of compaction pressure on the yield pressure of ibuprofen and its sodium salt

Despite being heavily criticised in the literature the most widely used and accepted compaction equation is the Heckel equation proposed by Heckel in 1961. Its presence in literature for 55 years is due to the ease in which it can distinguish between plastic and brittle materials. Achieving the correct balance of plastic and brittle materials in a formulation is critical to ensure adequate tablet strength is achieved therefore classifying materials using the Heckel equation is attractive. Despite the importance of this understanding, especially in the design and manufacture of direct compression formulations, there are no set analytical testing standards or materials classification guidelines. Instead many workers have attempted to develop techniques for the measurement and classification of a materials deformation but there is still confusion and contradiction present in this field. In this study we repot on report the effect of compaction pressure on the yield pressure of ibuprofen and its sodium salt. Ibuprofen and its sodium salt were selected as models for study due to the availability of comparative literature yield pressure values. The reported variation in yield pressure can be significant e.g, ibuprofen which has literature values of 21-1139 MPa. This study proposes an approach to determine yield pressure from the Heckel equation using a linear regression method. The full linear regression methodology utilised is described and is used to report the yield pressure of ibuprofen and its sodium salt dihydrate. This technique reveals the most representative compaction pressure in order to derive yield pressure to be 121 MPa. The yield pressure of ibuprofen and its sodium salt have been shown to increase with increasing compaction pressure. The reported values lie between 52-78 MPa for ibuprofen and 48-75 MPa for ibuprofen sodium dihydrate. The slightly lower reported yield pressure values for ibuprofen sodium suggest increased plasticity which could be attributed to the water contained within the structure acting as a plasticiser

Clean Diesel Engine Component Improvement Program Diesel Truck Thermoelectric Generator

Hi-Z Technology, Inc. (Hi-Z) is currently developing four different auxiliary generator designs that are used to convert a portion (5 to 20%) of the waste heat from vehicle engines exhaust directly to electricity. The four designs range from 200 Watts to 10 kW. The furthest along is the 1 kW Diesel Truck Thermoelectric Generator (DTTEG) for heavy duty Class 8 Diesel trucks, which, under this program, has been subjected to 543,000 equivalent miles of bouncing and jarring on PACCARâs test track. Test experience on an earlier version of the DTTEG on the same track showed the need for design modifications incorporated in DTTEG Mod 2, such as a heavy duty shock mounting system and reinforcement of the electrical leads mounting system, the thermocouple mounting system and the thermoelectric module restraints. The conclusion of the 543,000 mile test also pointed the way for an upgrading to heavy duty hose or flex connections for the internal coolant connections for the TEG, and consideration of a separate lower temperature cooling loop with its own radiator. Fuel savings of up to $750 per year and a three to five year payback are believed to be possible with the 5 % efficiency modules. The economics are expected to improve considerably to approach a two year payback when the 5 kW to 10 kW generators make it to the market in a few years with a higher efficiency (20%) thermoelectric module system called Quantum Wells, which are currently under development by Hi-Z. Ultimately, as automation takes over to reduce material and labor costs in the high volume production of QW modules, a one year payback for the 5 kW to10 kW generator appears possible. This was one of the stated goals at the beginning of the project. At some future point in time, with the DTTEG becoming standard equipment on all trucks and automobiles, fuel savings from the 25% conversion of exhaust heat to useable electricity nationwide equates to a 10% reduction in the 12 to 15 million barrels per day of imported oil, that much less air pollution, and an equivalent reduction in the trade deficit, which is expected to lower the inflation rate

Clean Diesel Engine Component Improvement Program Diesel Truck Thermoelectric Generator

Hi-Z Technology, Inc. (Hi-Z) is currently developing four different auxiliary generator designs that are used to convert a portion (5 to 20%) of the waste heat from vehicle engines exhaust directly to electricity. The four designs range from 200 Watts to 10 kW. The furthest along is the 1 kW Diesel Truck Thermoelectric Generator (DTTEG) for heavy duty Class 8 Diesel trucks, which, under this program, has been subjected to 543,000 equivalent miles of bouncing and jarring on PACCARâs test track. Test experience on an earlier version of the DTTEG on the same track showed the need for design modifications incorporated in DTTEG Mod 2, such as a heavy duty shock mounting system and reinforcement of the electrical leads mounting system, the thermocouple mounting system and the thermoelectric module restraints. The conclusion of the 543,000 mile test also pointed the way for an upgrading to heavy duty hose or flex connections for the internal coolant connections for the TEG, and consideration of a separate lower temperature cooling loop with its own radiator. Fuel savings of up to $750 per year and a three to five year payback are believed to be possible with the 5 % efficiency modules. The economics are expected to improve considerably to approach a two year payback when the 5 kW to 10 kW generators make it to the market in a few years with a higher efficiency (20%) thermoelectric module system called Quantum Wells, which are currently under development by Hi-Z. Ultimately, as automation takes over to reduce material and labor costs in the high volume production of QW modules, a one year payback for the 5 kW to10 kW generator appears possible. This was one of the stated goals at the beginning of the project. At some future point in time, with the DTTEG becoming standard equipment on all trucks and automobiles, fuel savings from the 25% conversion of exhaust heat to useable electricity nationwide equates to a 10% reduction in the 12 to 15 million barrels per day of imported oil, that much less air pollution, and an equivalent reduction in the trade deficit, which is expected to lower the inflation rate

Simulations of neutron background in a time projection chamber relevant to dark matter searches

Presented here are results of simulations of neutron background performed for a time projection chamber acting as a particle dark matter detector in an underground laboratory. The investigated background includes neutrons from rock and detector components, generated via spontaneous fission and (alpha, n) reactions, as well as those due to cosmic-ray muons. Neutrons were propagated to the sensitive volume of the detector and the nuclear recoil spectra were calculated. Methods of neutron background suppression were also examined and limitations to the sensitivity of a gaseous dark matter detector are discussed. Results indicate that neutrons should not limit sensitivity to WIMP-nucleon interactions down to a level of (1 - 3) x 10^{-8} pb in a 10 kg detector.Comment: 27 pages (total, including 3 tables and 11 figures). Accepted for publication in Nuclear Instruments and Methods in Physics Research - Section

Neutron background in large-scale xenon detectors for dark matter searches

Simulations of the neutron background for future large-scale particle dark matter detectors are presented. Neutrons were generated in rock and detector elements via spontaneous fission and (alpha,n) reactions, and by cosmic-ray muons. The simulation techniques and results are discussed in the context of the expected sensitivity of a generic liquid xenon dark matter detector. Methods of neutron background suppression are investigated. A sensitivity of $10^{-9}-10^{-10}$ pb to WIMP-nucleon interactions can be achieved by a tonne-scale detector.Comment: 35 pages, 13 figures, 2 tables, accepted for publication in Astroparticle Physic

First background-free limit from a directional dark matter experiment: results from a fully fiducialised DRIFT detector

The addition of O2 to gas mixtures in time projection chambers containing CS2 has recently been shown to produce multiple negative ions that travel at slightly different velocities. This allows a measurement of the absolute position of ionising events in the z (drift) direction. In this work, we apply the z-fiducialisation technique to a directional dark matter search. In particular, we present results from a 46.3 live-day source-free exposure of the DRIFT-IId detector run in this completely new mode. With full-volume fiducialisation, we have achieved the first background-free operation of a directional detector. The resulting exclusion curve for spin-dependent WIMP-proton interactions reaches 0.9 pb at 100 GeV/c2, a factor of 2 better than our previous work. We describe the automated analysis used here, and argue that detector upgrades, implemented after the acquisition of these data, will bring an additional factor of \u3e3 improvement in the near future

Age at symptom onset and death and disease duration in genetic frontotemporal dementia : an international retrospective cohort study

Background: Frontotemporal dementia is a heterogenous neurodegenerative disorder, with about a third of cases being genetic. Most of this genetic component is accounted for by mutations in GRN, MAPT, and C9orf72. In this study, we aimed to complement previous phenotypic studies by doing an international study of age at symptom onset, age at death, and disease duration in individuals with mutations in GRN, MAPT, and C9orf72. Methods: In this international, retrospective cohort study, we collected data on age at symptom onset, age at death, and disease duration for patients with pathogenic mutations in the GRN and MAPT genes and pathological expansions in the C9orf72 gene through the Frontotemporal Dementia Prevention Initiative and from published papers. We used mixed effects models to explore differences in age at onset, age at death, and disease duration between genetic groups and individual mutations. We also assessed correlations between the age at onset and at death of each individual and the age at onset and at death of their parents and the mean age at onset and at death of their family members. Lastly, we used mixed effects models to investigate the extent to which variability in age at onset and at death could be accounted for by family membership and the specific mutation carried. Findings: Data were available from 3403 individuals from 1492 families: 1433 with C9orf72 expansions (755 families), 1179 with GRN mutations (483 families, 130 different mutations), and 791 with MAPT mutations (254 families, 67 different mutations). Mean age at symptom onset and at death was 49\ub75 years (SD 10\ub70; onset) and 58\ub75 years (11\ub73; death) in the MAPT group, 58\ub72 years (9\ub78; onset) and 65\ub73 years (10\ub79; death) in the C9orf72 group, and 61\ub73 years (8\ub78; onset) and 68\ub78 years (9\ub77; death) in the GRN group. Mean disease duration was 6\ub74 years (SD 4\ub79) in the C9orf72 group, 7\ub71 years (3\ub79) in the GRN group, and 9\ub73 years (6\ub74) in the MAPT group. Individual age at onset and at death was significantly correlated with both parental age at onset and at death and with mean family age at onset and at death in all three groups, with a stronger correlation observed in the MAPT group (r=0\ub745 between individual and parental age at onset, r=0\ub763 between individual and mean family age at onset, r=0\ub758 between individual and parental age at death, and r=0\ub769 between individual and mean family age at death) than in either the C9orf72 group (r=0\ub732 individual and parental age at onset, r=0\ub736 individual and mean family age at onset, r=0\ub738 individual and parental age at death, and r=0\ub740 individual and mean family age at death) or the GRN group (r=0\ub722 individual and parental age at onset, r=0\ub718 individual and mean family age at onset, r=0\ub722 individual and parental age at death, and r=0\ub732 individual and mean family age at death). Modelling showed that the variability in age at onset and at death in the MAPT group was explained partly by the specific mutation (48%, 95% CI 35\u201362, for age at onset; 61%, 47\u201373, for age at death), and even more by family membership (66%, 56\u201375, for age at onset; 74%, 65\u201382, for age at death). In the GRN group, only 2% (0\u201310) of the variability of age at onset and 9% (3\u201321) of that of age of death was explained by the specific mutation, whereas 14% (9\u201322) of the variability of age at onset and 20% (12\u201330) of that of age at death was explained by family membership. In the C9orf72 group, family membership explained 17% (11\u201326) of the variability of age at onset and 19% (12\u201329) of that of age at death. Interpretation: Our study showed that age at symptom onset and at death of people with genetic frontotemporal dementia is influenced by genetic group and, particularly for MAPT mutations, by the specific mutation carried and by family membership. Although estimation of age at onset will be an important factor in future pre-symptomatic therapeutic trials for all three genetic groups, our study suggests that data from other members of the family will be particularly helpful only for individuals with MAPT mutations. Further work in identifying both genetic and environmental factors that modify phenotype in all groups will be important to improve such estimates. Funding: UK Medical Research Council, National Institute for Health Research, and Alzheimer's Society

Efficacy and Safety of Three Antiretroviral Regimens for Initial Treatment of HIV-1: A Randomized Clinical Trial in Diverse Multinational Settings

Background:Antiretroviral regimens with simplified dosing and better safety are needed to maximize the efficiency of antiretroviral delivery in resource-limited settings. We investigated the efficacy and safety of antiretroviral regimens with once-daily compared to twice-daily dosing in diverse areas of the world.Methods and Findings:1,571 HIV-1-infected persons (47% women) from nine countries in four continents were assigned with equal probability to open-label antiretroviral therapy with efavirenz plus lamivudine-zidovudine (EFV+3TC-ZDV), atazanavir plus didanosine-EC plus emtricitabine (ATV+DDI+FTC), or efavirenz plus emtricitabine-tenofovir-disoproxil fumarate (DF) (EFV+FTC-TDF). ATV+DDI+FTC and EFV+FTC-TDF were hypothesized to be non-inferior to EFV+3TC-ZDV if the upper one-sided 95% confidence bound for the hazard ratio (HR) was ≤1.35 when 30% of participants had treatment failure.An independent monitoring board recommended stopping study follow-up prior to accumulation of 472 treatment failures. Comparing EFV+FTC-TDF to EFV+3TC-ZDV, during a median 184 wk of follow-up there were 95 treatment failures (18%) among 526 participants versus 98 failures among 519 participants (19%; HR 0.95, 95% CI 0.72-1.27; p = 0.74). Safety endpoints occurred in 243 (46%) participants assigned to EFV+FTC-TDF versus 313 (60%) assigned to EFV+3TC-ZDV (HR 0.64, CI 0.54-0.76; p<0.001) and there was a significant interaction between sex and regimen safety (HR 0.50, CI 0.39-0.64 for women; HR 0.79, CI 0.62-1.00 for men; p = 0.01). Comparing ATV+DDI+FTC to EFV+3TC-ZDV, during a median follow-up of 81 wk there were 108 failures (21%) among 526 participants assigned to ATV+DDI+FTC and 76 (15%) among 519 participants assigned to EFV+3TC-ZDV (HR 1.51, CI 1.12-2.04; p = 0.007).Conclusion: EFV+FTC-TDF had similar high efficacy compared to EFV+3TC-ZDV in this trial population, recruited in diverse multinational settings. Superior safety, especially in HIV-1-infected women, and once-daily dosing of EFV+FTC-TDF are advantageous for use of this regimen for initial treatment of HIV-1 infection in resource-limited countries. ATV+DDI+FTC had inferior efficacy and is not recommended as an initial antiretroviral regimen.Trial Registration:http://www.ClinicalTrials.gov NCT00084136

Highly-parallelized simulation of a pixelated LArTPC on a GPU

The rapid development of general-purpose computing on graphics processing units (GPGPU) is allowing the implementation of highly-parallelized Monte Carlo simulation chains for particle physics experiments. This technique is particularly suitable for the simulation of a pixelated charge readout for time projection chambers, given the large number of channels that this technology employs. Here we present the first implementation of a full microphysical simulator of a liquid argon time projection chamber (LArTPC) equipped with light readout and pixelated charge readout, developed for the DUNE Near Detector. The software is implemented with an end-to-end set of GPU-optimized algorithms. The algorithms have been written in Python and translated into CUDA kernels using Numba, a just-in-time compiler for a subset of Python and NumPy instructions. The GPU implementation achieves a speed up of four orders of magnitude compared with the equivalent CPU version. The simulation of the current induced on 10^3 pixels takes around 1 ms on the GPU, compared with approximately 10 s on the CPU. The results of the simulation are compared against data from a pixel-readout LArTPC prototype