An ultracold molecular beam for testing fundamental physics

We use two-dimensional transverse laser cooling to produce an ultracold beam of YbF molecules. Through experiments and numerical simulations, we study how the cooling is influenced by the polarization configuration, laser intensity, laser detuning and applied magnetic field. The ultracold part of the beam contains more than $2 \times 10^5$ molecules per shot and has a temperature below 200 $\mu$K, and the cooling yields a 300-fold increase in the brightness of the beam. The method can improve the precision of experiments that use molecules to test fundamental physics. In particular, the beam is suitable for measuring the electron electric dipole moment with a statistical precision better than $10^{-30}$ e cm.Comment: 25 pages, 14 figures. Trajectory simulations added and results compared to experiment; other minor revision

Defining simple and comprehensive assessment units for CO2 storage in saline formations beneath the UK North Sea and continental shelf

In the UK, by far the largest CO2 storage opportunities lie offshore. The North Sea in particular has a long and complex geological history, with potential reservoirs geographically widespread and occurring at multiple stratigraphic levels. Diverse storage estimates have been made, using a range of working methods, and yielding different values, e.g. SCCS (2009); Bentham (2006). Consequently the UK Storage Appraisal Project (UKSAP), commissioned and funded by the Energy Technologies Institute (ETI), is undertaking the most comprehensive assessment to date, using abundant legacy seismic and borehole data. This study has a remit to use best current practice, consistent between locations, to calculate the CO2 storage capacity of the entire UK Continental Shelf (UKCS) within saline aquifers and hydrocarbon fields. The potential storage formations have been subdivided into units for assessment, and filtered to remove units with only a small estimated storage capacity to concentrate resources on more viable units. The size of potential storage units approximate to a power law distribution, similar to that of hydrocarbon fields, with a large number of small units and a small number of large units

RIDME distance measurements using Gd(iii) tags with a narrow central transition

Methods based on pulse electron paramagnetic resonance allow measurement of the electron-electron dipolar coupling between two spin labels. Here we compare the most popular technique, Double Electron-Electron Resonance (DEER or PELDOR), with the dead-time free 5-pulse Relaxation-Induced Dipolar Modulation Enhancement (RIDME) method for Gd(iii)-Gd(iii) distance measurements at W-band (94.9 GHz, ≈3.5 T) using Gd(iii) tags with a small zero field splitting (ZFS). Such tags are important because of their high EPR sensitivity arising from their narrow central transition. Two systems were investigated: (i) a rigid model compound with an inter-spin distance of 2.35 nm, and (ii) two mutants of a homodimeric protein, both labeled with a DOTA-based Gd(iii) chelate and characterized by an inter-spin distance of around 6 nm, one having a narrow distance distribution and the other a broad distribution. Measurements on the model compound show that RIDME is less sensitive to the complications arising from the failure of the weak coupling approximation which affect DEER measurements on systems characterized by short inter-spin distances between Gd(iii) tags having a narrow central transition. Measurements on the protein samples, which are characterized by a long inter-spin distance, emphasize the complications due to the appearance of harmonics of the dipolar interaction frequency in the RIDME traces for S > 1/2 spin systems, as well as enhanced uncertainties in the background subtraction. In both cases the sensitivity of RIDME was found to be significantly better than DEER. The effects of the experimental parameters on the RIDME trace are discussed.This research was supported by the Israeli Science Foundation (grant 334/14) and was made possible in part by the historic generosity of the Harold Perlman Family (D. G.). We also acknowledge the Australian Research Council for a Discovery grant to G. O. and B. G. (DP150100383) and a Future Fellowship to B. G. (FT130100838). D. G. holds the Erich Klieger professorial chair in Chemical Physics

Immunodominant Tuberculosis CD8 Antigens Preferentially Restricted by HLA-B

CD8+ T cells are essential for host defense to intracellular bacterial pathogens such as Mycobacterium tuberculosis (Mtb), Salmonella species, and Listeria monocytogenes, yet the repertoire and dominance pattern of human CD8 antigens for these pathogens remains poorly characterized. Tuberculosis (TB), the disease caused by Mtb infection, remains one of the leading causes of infectious morbidity and mortality worldwide and is the most frequent opportunistic infection in individuals with HIV/AIDS. Therefore, we undertook this study to define immunodominant CD8 Mtb antigens. First, using IFN-γ ELISPOT and synthetic peptide arrays as a source of antigen, we measured ex vivo frequencies of CD8+ T cells recognizing known immunodominant CD4+ T cell antigens in persons with latent tuberculosis infection. In addition, limiting dilution was used to generate panels of Mtb-specific T cell clones. Using the peptide arrays, we identified the antigenic specificity of the majority of T cell clones, defining several new epitopes. In all cases, peptide representing the minimal epitope bound to the major histocompatibility complex (MHC)-restricting allele with high affinity, and in all but one case the restricting allele was an HLA-B allele. Furthermore, individuals from whom the T cell clone was isolated harbored high ex vivo frequency CD8+ T cell responses specific for the epitope, and in individuals tested, the epitope represented the single immunodominant response within the CD8 antigen. We conclude that Mtb-specific CD8+ T cells are found in high frequency in infected individuals and are restricted predominantly by HLA-B alleles, and that synthetic peptide arrays can be used to define epitope specificities without prior bias as to MHC binding affinity. These findings provide an improved understanding of immunodominance in humans and may contribute to a development of an effective TB vaccine and improved immunodiagnostics

Geologically constrained evolutionary geomechanical modelling of diapir and basin evolution: a case study from the Tarfaya basin, West African coast

We systematically incorporate burial history, sea floor geometry and tectonic loads from a sequential kinematic restoration model into a 2D evolutionary geomechanical model that simulates the formation of the Sandia salt diapir, Tarfaya basin, NW African Coast. We use a poro-elastoplastic description for the sediment behaviour and a viscoplastic description for the salt. Sedimentation is coupled with salt flow and regional shortening to determine the sediment porosity and strength and to capture the interaction between salt and sediments. We find that temporal and spatial variation in sedimentation rate is a key control on the kinematic evolution of the salt system. Incorporation of sedimentation rates from the kinematic restoration at a location east of Sandia leads to a final geomechanical model geometry very similar to that observed in seismic reflection data. We also find that changes in the variation of shortening rates can significantly affect the present-day stress state above salt. Overall, incorporating kinematic restoration data into evolutionary models provides insights into the key parameters that control the evolution of geologic systems. Furthermore, it enables more realistic evolutionary geomechanical models, which, in turn, provide insights into sediment stress and porosity

Čvrsta disperzija meloksikama: faktorijalno dizajnirani dozirani pripravak za gerijatrijsku populaciju

The objective of the present work was to improve the dissolution properties of the poorly water-soluble drug meloxicam by preparing solid dispersions with hydroxyethylcellulose (HEC), mannitol and polyethylene glycol (PEG) 4000 and to develop a dosage form for geriatric population. Differential scanning calorimetry, X–ray diffractometry, Fourier transform infrared spectroscopy and scanning electron microscopy were used to investigate the solid-state physical structure of the prepared solid dispersions. Higher in vitro dissolution of solid dispersions was recorded compared to their corresponding physical mixtures and the pure drug. PEG 4000 in 1:9 drug to carrier ratio exhibited the highest drug release (100.2%), followed by mannitol (98.2%) and HEC (89.5%) in the same ratio. Meloxicam-PEG 4000 solid dispersion was formulated into suspension and optimization was carried out by 23 factorial design. Formulations containing higher levels of methyl cellulose and higher levels of either sodium citrate or Tween 80 exhibited the highest drug release.Cilj rada bio je poboljšati topljivost meloksikama u vodi pripravom čvrstih disperzija s hidroksietilcelulozom (HEC), manitolom i polietilen glikolom 4000 (PEG 4000) te razviti dozirani pripravaka za gerijatrijsku populaciju. Za ispitivanje fizičke strukture pripravljenih čvrstih disperzija korištene su diferencijalna pretražna kalorimetrija, difraktometrija rentgentskim zrakama, FTIR i pretražna elektronska mikroskopija. Čvrste disperzije su u in vitro uvjetima pokazale bolju topljivost u odnosu na fizičku smjesu i čistu ljekovitu tvar. Najbolje oslobađanje lijeka (100,2%). postignuto je iz disperzija s PEG 4000 (omjer ljekovite tvari i nosača 1:9). Slijede manitol (98,2%) i HEC (89,5%) (isti omjer meloksikama i polimera). Čvrsta disperzija meloksikama s PEG 4000 prevedena je u suspenziju te optimirana 23 faktorijalnim dizajnom. Najbolje oslobađanje ljekovite tvari postignuto je iz pripravaka koji sadrže veći udio etilceluloze i natrijevog citrata, odnosno Tween 80