401 research outputs found
Reconfiguring global pharmaceutical value networks through targeted technology interventions
Targeting a series of advanced manufacturing technology (AMT) âinterventionsâ provides the potential for significant step changes across the pharmaceutical value chain, from early stage âsystem discoveryâ and clinical trials, through to novel service supply models. This research explores future value network configurations which, when aligned with disruptive shifts in technology (process and digital), may enable alternative routes to medicines production and the delivery of additional value to âend-usersâ, i.e. patients and health care providers. We draw on a categorisation of AMTs that may enable a shift from the traditional âbatchâ and centralised manufacturing paradigm of âmake-to-stockâ, towards more re-distributed âcontinuousâ manufacturing and âmake-to-orderâ models. Despite reported benefits in the academic literature (e.g. reduced footprints, improved quality, enhanced flexibility and inventory savings), current adoption rates of continuous technologies in this sector remain low (c. 5%). This paper presents new data sources, in our study of AMT adoption in a global pharmaceutical context â assessing the barriers to implementation, and the pathways to delivering future continuous manufacturing scenarios. Our findings capture the high level of disparity in viewpoints, highlighting the uncertainties and transformational challenges ahead â in terms of opportunity areas, technological readiness and a future vision for the sector, as a whole
Light and Life: Exotic Photosynthesis in Binary Star Systems
The potential for hosting photosynthetic life on Earth-like planets within
binary/multiple stellar systems was evaluated by modelling the levels of
photosynthetically active radiation (PAR) such planets receive. Combinations of
M and G stars in: (i) close-binary systems; (ii) wide-binary systems and (iii)
three-star systems were investigated and a range of stable radiation
environments found to be possible. These environmental conditions allow for the
possibility of familiar, but also more exotic forms of photosynthetic life,
such as infrared photosynthesisers and organisms specialised for specific
spectral niches.Comment: Accepted for publication in: Astrobiolog
QCD Chiral restoration at finite under the Magnetic field: Studies based on the instanton vacuum model
We investigate the chiral restoration at finite temperature under the
strong external magnetic field of the SU(2) light-flavor
QCD matter. We employ the instanton-liquid QCD vacuum configuration accompanied
with the linear Schwinger method for inducing the magnetic field. The
Harrington-Shepard caloron solution is used to modify the instanton parameters,
i.e. the average instanton size and inter-instanton distance
, as functions of . In addition, we include the meson-loop
corrections (MLC) as the large- corrections because they are critical
for reproducing the universal chiral restoration pattern. We present the
numerical results for the constituent-quark mass as well as chiral condensate
which signal the spontaneous breakdown of chiral-symmetry (SBS), as
functions of and . Besides we find that the changes for the and
due to the magnetic field is relatively small, in comparison to those
caused by the finite effect.Comment: 4 pages, 1 table, 6figs. arXiv admin note: significant text overlap
with arXiv:1103.605
Clinical Correlates and Prognostic Significance of the Ventilatory Response to Exercise in Chronic Heart Failure
AbstractObjectives. This study sought to investigate the clinical characteristics of patients with chronic heart failure and an increased ventilatory response to exercise and to examine the prognostic usefulness of this response.Background. The ventilatory response to exercise is increased in many patients with chronic heart failure and may be characterized by the regression slope relating minute ventilation to carbon dioxide output (VÌeâVÌco2slope) during exercise.Methods. One hundred seventy-three consecutive patients (155 men; mean [±SD] age 59.8 ± 11.5 years; radionuclide left ventricular ejection fraction [LVEF] 28.4 ± 14.6%) underwent cardiopulmonary exercise testing (peak oxygen consumption 18.5 ± 7.3 ml/kg per min; VÌeâVÌco2slope 34.8 ± 10.6) over a 2-year period. Using 1.96 standard deviations above the mean VÌeâVÌco2slope of 68 healthy age-matched subjects (mean slope 26.3 ± 4.1), we defined a high ventilatory response to exercise as a slope >34.Results. Eighty-three patients (48%) had an increased VÌeâVÌco2slope (mean 43.1 ± 8.9). There was a difference in age (62.2 vs. 57.3 years, p = 0.005), New York Heart Association functional class (2.9 vs. 2.1, p < 0.001), LVEF (24.7 vs. 31.9%, p = 0.0016), peak oxygen consumption (14.9 vs. 21.7 ml/kg per min, p < 0.0001) and radiographic cardiothoracic ratio (0.58 vs. 0.55, p = 0.002) between these patients and those with a normal slope. In the univariate Cox proportional hazards model, the VÌeâVÌco2slope was an important prognostic factor (p < 0.0001). In the multivariate Cox analyses using several variables (age, peak oxygen consumption, VÌeâVÌco2slope and LVEF), the VÌeâVÌco2slope gave additional prognostic information (p = 0.018) beyond peak oxygen consumption (p = 0.022). Kaplan-Meier survival curves at 18 months demonstrated a survival rate of 95% in patients with a normal VÌeâVÌco2slope compared with 69% in those with a high slope (p < 0.0001).Conclusions. A high VÌeâVÌco2slope selects patients with more severe heart failure and is an independent prognostic marker. The VÌeâVÌco2slope may be used as a supplementary index in the assessment of patients with chronic heart failure.(J Am Coll Cardiol 1997;29:1585â90
Charge Form Factor and Cluster Structure of Li Nucleus
The charge form factor of Li nucleus is considered on the basis of its
cluster structure. The charge density of Li is presented as a
superposition of two terms. One of them is a folded density and the second one
is a sum of He and the deuteron densities. Using the available
experimental data for He and deuteron charge form factors, a good
agreement of the calculations within the suggested scheme is obtained with the
experimental data for the charge form factor of Li, including those in
the region of large transferred momenta.Comment: 12 pages 5 figure
On the purification of α-cellulose from resinous wood for stable isotope (H, C and O) analysis
α-Cellulose was isolated from four samples of Scots pine (Pinus sylvestris L.). Each sample was divided into two portions. One portion had the resins removed by solvent extraction prior to removal of lignins by treatment with acidic sodium chlorite solution and treatment with sodium hydroxide solution to remove hemicelluloses. The other portion was processed in the same way apart from the solvent extraction step. The isolated wood constituents were characterised by attenuated total reflectance Fourier transform infrared (ATR/FT-IR) spectroscopy. The infrared spectra of the resulting α-cellulose samples were identical indicating that treatment with acidic sodium chlorite and sodium hydroxide was sufficient to remove resins. The values of the stable isotope ratios (carbon, oxygen and hydrogen) for each pair of α-cellulose sub-samples also showed no significant differences within the reproducibility of the methods. The implication of these studies demonstrate that the customary step of resin extraction from pine is unnecessary if sodium chlorite and sodium hydroxide are used for the isolation of α-cellulose following the technique described in this paper. In addition, the study demonstrates that the oxygen isotope ratio of the water used for cellulose extraction does not influence the stable isotope values in the α-cellulose obtained. The importance of isotopic homogeneity within the cellulose sample is also highlighted
Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in âs = 7 TeV pp collisions with the ATLAS detector
A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fbâ1 of protonâproton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results
Jet size dependence of single jet suppression in lead-lead collisions at sqrt(s(NN)) = 2.76 TeV with the ATLAS detector at the LHC
Measurements of inclusive jet suppression in heavy ion collisions at the LHC
provide direct sensitivity to the physics of jet quenching. In a sample of
lead-lead collisions at sqrt(s) = 2.76 TeV corresponding to an integrated
luminosity of approximately 7 inverse microbarns, ATLAS has measured jets with
a calorimeter over the pseudorapidity interval |eta| < 2.1 and over the
transverse momentum range 38 < pT < 210 GeV. Jets were reconstructed using the
anti-kt algorithm with values for the distance parameter that determines the
nominal jet radius of R = 0.2, 0.3, 0.4 and 0.5. The centrality dependence of
the jet yield is characterized by the jet "central-to-peripheral ratio," Rcp.
Jet production is found to be suppressed by approximately a factor of two in
the 10% most central collisions relative to peripheral collisions. Rcp varies
smoothly with centrality as characterized by the number of participating
nucleons. The observed suppression is only weakly dependent on jet radius and
transverse momentum. These results provide the first direct measurement of
inclusive jet suppression in heavy ion collisions and complement previous
measurements of dijet transverse energy imbalance at the LHC.Comment: 15 pages plus author list (30 pages total), 8 figures, 2 tables,
submitted to Physics Letters B. All figures including auxiliary figures are
available at
http://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/HION-2011-02
Liposomes in Biology and Medicine
Drug delivery systems (DDS) have become important tools for the specific delivery of a large number of drug molecules. Since their discovery in the 1960s liposomes were recognized as models to study biological membranes and as versatile DDS of both hydrophilic and lipophilic molecules. Liposomes--nanosized unilamellar phospholipid bilayer vesicles--undoubtedly represent the most extensively studied and advanced drug delivery vehicles. After a long period of research and development efforts, liposome-formulated drugs have now entered the clinics to treat cancer and systemic or local fungal infections, mainly because they are biologically inert and biocompatible and practically do not cause unwanted toxic or antigenic reactions. A novel, up-coming and promising therapy approach for the treatment of solid tumors is the depletion of macrophages, particularly tumor associated macrophages with bisphosphonate-containing liposomes. In the advent of the use of genetic material as therapeutic molecules the development of delivery systems to target such novel drug molecules to cells or to target organs becomes increasingly important. Liposomes, in particular lipid-DNA complexes termed lipoplexes, compete successfully with viral gene transfection systems in this field of application. Future DDS will mostly be based on protein, peptide and DNA therapeutics and their next generation analogs and derivatives. Due to their versatility and vast body of known properties liposome-based formulations will continue to occupy a leading role among the large selection of emerging DDS
PHIP - a novel candidate breast cancer susceptibility locus on 6q14.1
Most non-BRCA1/2 breast cancer families have no identified genetic cause. We used linkage and haplotype analyses in familial and sporadic breast cancer cases to identify a susceptibility locus on chromosome 6q. Two independent genome-wide linkage analysis studies suggested a 3 Mb locus on chromosome 6q and two unrelated Swedish families with a LOD > 2 together seemed to share a haplotype in 6q14.1. We hypothesized that this region harbored a rare high-risk founder allele contributing to breast cancer in these two families. Sequencing of DNA and RNA from the two families did not detect any pathogenic mutations. Finally, 29 SNPs in the region were analyzed in 44,214 cases and 43,532 controls from BCAC, and the original haplotypes in the two families were suggested as low-risk alleles for European and Swedish women specifically. There was also some support for one additional independent moderate-risk allele in Swedish familial samples. The results were consistent with our previous findings in familial breast cancer and supported a breast cancer susceptibility locus at 6q14.1 around the PHIP gene.Peer reviewe
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