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Transient increases in blood eosinophil counts have been observed in dupilumab clinical trials.To assess eosinophil counts and eosinophilia-related treatment-emergent adverse events (TEAEs) across 11 dupilumab clinical trials, comparing adult and adolescent patients with asthma and adult patients with chronic rhinosinusitis with nasal polyps (CRSwNP), atopic dermatitis, and eosinophilic esophagitis.Eosinophil counts, rates of eosinophilia-related TEAEs or treatment-emergent eosinophilia (1,500 cells/μL), discontinuations, clinical symptoms, and efficacy in patients with asthma or CRSwNP with treatment-emergent eosinophilia are presented.Transient increases in mean eosinophil counts were observed in dupilumab-treated patients with asthma (mean range across studies at baseline: 349-370 cells/μL; week 4: 515-578 cells/μL), CRSwNP (baseline: 440-448 cells/μL; week 16: 595 cells/μL), and atopic dermatitis (baseline: 434-600 cells/μL; week 4: 410-710 cells/μL), followed by a decline starting by week 24 to baseline or lower. No increases were seen in patients with eosinophilic esophagitis (baseline: 310 cells/μL; week 4: 230 cells/μL). In dupilumab-treated patients across all studies, rates of eosinophilia TEAEs were 0% to 13.6%. Clinical symptoms associated with increased eosinophils were rare (seven of 4,666 dupilumab-treated patients, including six cases of eosinophilic granulomatosis with polyangiitis) and occurred only in patients with asthma or CRSwNP. Eosinophilia was not associated with reduced dupilumab efficacy.Transient increases in eosinophil counts with dupilumab treatment did not affect efficacy and were rarely of clinical consequence. It remains important for physicians to base judgment on individual patient history and baseline eosinophil counts and to be alert to hypereosinophilic symptoms.

BACKGROUND: Patients with asthma and/or chronic rhinosinusitis with nasal polyps (CRSwNP) experience recurrent respiratory tract infections. Dupilumab targets type 2 inflammation, a common underlying pathophysiology of both conditions, with proven efficacy. OBJECTIVE: To examine investigator-reported respiratory infection adverse events and anti-infective medication use with dupilumab versus placebo in patients with moderate-to-severe asthma or severe CRSwNP. METHODS: We performed a post hoc analysis of the pivotal phase 3 trials LIBERTY ASTHMA QUEST (NCT02414854) and LIBERTY NP SINUS-52 (NCT02898454) in moderate-to-severe asthma and severe CRSwNP, respectively. RESULTS: Investigator-reported respiratory infection events occurred at a significantly lower incidence in patients treated with dupilumab versus placebo, in both asthma (22% lower; P < .0001; 95% CI 0.71-0.85) and CRSwNP (38% lower; P

Fractional exhaled nitric oxide (FeNO) may have a role both as a prognostic and predictive biomarker, in combination with eosinophils, for assessing responsiveness to some biological therapies.We evaluated the value of baseline FeNO, adjusted for baseline blood eosinophil levels and other clinical characteristics, as an independent predictor of treatment response to dupilumab in patients with uncontrolled, moderate-to-severe asthma.We performed a post-hoc analysis of LIBERTY ASTHMA QUEST (NCT02414854), a phase 3, double-blind study in patients aged ≥ 12 years with uncontrolled moderate-to-severe asthma who received dupilumab 200/300 mg, or placebo every 2 weeks up to 52 weeks. Annualized event rate (AER) of severe exacerbations and least squares mean change from baseline in pre-bronchodilator forced expiratory volume in 1 s (FEVAER increased with increasing baseline FeNO in placebo, and decreased in dupilumab groups. The relative risk of severe exacerbations was 22·7%, 58·3%, and 69·3% lower for dupilumab vs placebo for the FeNO25, 25 to50, and ≥ 50 ppb subgroups. The magnitude of FEVIncreased baseline FeNO was associated with greater clinical effects in dupilumab vs placebo, independent of eosinophil levels and other clinical characteristics.

Dupilumab blocks the shared receptor component for interleukin (IL)-4/IL-13, key and central drivers of type 2 inflammation in multiple diseases. In phase 3 QUEST (NCT02414854), add-on dupilumab 200 and 300 mg every 2 weeks reduced severe exacerbations, improved pre-bronchodilator forced expiratory volume in 1 s (FEVAdjusted annualized severe exacerbation rates over the treatment period, least squares (LS) mean change from baseline at Week 12 in pre-bronchodilator FEVDupilumab vs placebo reduced exacerbations and improved pre-bronchodilator FEVDupilumab reduced severe exacerbations and improved lung function and asthma control in subgroups of patients with type 2 asthma and high-dose ICS at baseline.NCT02414854.

Truffle-producing fungi (hypogeous sporocarps) are important mycorrhizal symbionts and provide a key food source for many animals, including small mammals. To better understand truffle diversity and associations in the northeastern US, we surveyed for truffles and analyzed spores in eastern chipmunk (Tamias striatus) scat across hardwood (angiosperm-dominated), softwood (gymnosperm-dominated), and mixed forest at Bartlett Experimental Forest, New Hampshire. Truffle biomass ranged from 3.8 kg/ha in hardwood forest to 31.4 kg/ha in softwood forest and was up to 35 times greater than mushroom (epigeous sporocarp) production in softwood forest. Elaphomyces species were the most common truffle taxa in both field surveys and chipmunk scat. Scat analysis indicated that truffle richness increased over the summer and accurately reflected fruiting time, providing greater resolution of richness than field surveys alone. Basal area of eastern hemlock (Tsuga canadensis) was the primary driver of Elaphomyces biomass and was the best explanatory variable of truffle community composition. We discuss implications of hemlock loss, due to the introduced hemlock woolly adelgid (Adelges tsugae), on forest mycorrhizal communities and food webs.

Objects are said to automatically “afford” various actions depending upon the motor repertoire of the actor. Such affordances play a part in how we prepare to handle or manipulate tools and other objects. Evidence obtained through fMRI, EEG and TMS has proven that this is the case but, as yet, the temporal evolution of affordances has not been fully investigated. The aim here was to further explore the timing of evoked motor activity using visual stimuli tailored to drive the motor system. Therefore, we presented three kinds of stimuli in stereoscopic depth; whole hand grasp objects which afforded a power-grip, pinch-grip objects which afforded a thumb and forefinger precision-grip and an empty desk, affording no action. In order to vary functional motor priming while keeping visual stimulation identical, participants adopted one of two postures, with either the dominant or non-dominant hand forward. EEG data from 29 neurologically healthy subjects were analysed for the N1 evoked potential, observed in visual discrimination tasks, and for the N2 ERP component, previously shown to correlate with affordances (Proverbio, A.M., Adorni, R., D’Aniello, G.E., 2011. 250 ms to code for action affordance during observation of manipulable objects. Neuropsychologia 49, 2711–2717). We observed a link between ERPs, previously considered to reflect motor priming, and the positioning of the dominant hand. A significant interaction was detected in the left-hemisphere N2 between the participants’ posture and the object category they viewed. These results indicate strong affordance-related activity around 300ms after stimulus presentation, particularly when the dominant hand can easily reach an object.

A better understanding of practice-induced functional and structural changes in our brains can help us design more effective learning environments that provide better outcomes. Although there is growing evidence from human neuroimaging that experience-dependent brain plasticity is expressed in measurable brain changes that are correlated with behavioural performance, the relationship between behavioural performance and structural or functional brain changes, and particularly the time course of these changes, is not well characterised. To understand the link between neuroplastic changes and behavioural performance, 15 healthy participants in this study followed a systematic eye movement training programme for 30 min daily at home, 5 days a week and for 6 consecutive weeks. Behavioural performance statistics and eye tracking data were captured throughout the training period to evaluate learning outcomes. Imaging data (DTI and fMRI) were collected at baseline, after two and six weeks of continuous training, and four weeks after training ended. Participants showed significant improvements in behavioural performance (faster task completion time, lower fixation number and fixation duration). Spatially overlapping reductions in microstructural diffusivity measures (MD, AD and RD) and functional activation increases (BOLD signal) were observed in two main areas: extrastriate visual cortex (V3d) and the frontal part of the cerebellum/Fastigial Oculomotor Region (FOR), which are both involved in visual processing. An increase of functional activity was also recorded in the right frontal eye field. Behavioural, structural and functional changes were correlated. Microstructural change is a better predictor for long-term behavioural change than functional activation is, whereas the latter is superior in predicting instantaneous performance. Structural and functional measures at week 2 of the training programme also predict performance at week 6 and 10, which suggests that imaging data at an early stage of training may be useful in optimising practice environments or rehabilitative training programmes.

Slotting allowances are payments manufacturers make to retailers in exchange for product distribution. An important question manufacturers face is whether their salespeople should have the authority to allocate these payments and, if so, what are the implications of doing so. Unfortunately, although slotting allowances have been investigated in the literature, there is little guidance on these issues. Providing such guidance is important because slotting allowances are both costly to manufacturers and frequently demanded by retailers. Therefore, we introduce slotting allowance authority into the literature and suggest that it is positively related to customer loyalty toward the salesperson; however, this relationship largely depends on a customer's relationship motivation. Specifically, we offer a contemporary view of customer motivation by demonstrating that the relationship between slotting allowance authority and customer loyalty is less and more positive with increasing levels of intrinsic relationship motivation and extrinsic relationship motivation , respectively. Moreover, our results indicate a conditional process model whereby slotting allowance authority impacts sales growth through customer loyalty conditioned upon intrinsic- and extrinsic relationship motivations.

Rehabilitating upper limb function after stroke is a key therapeutic goal. In healthy brains, objects, especially tools, are said to cause automatic motoric ‘affordances’; affecting our preparation to handle objects. For example, the N2 event-related potential has been shown to correlate with the functional properties of objects in healthy adults during passive viewing. We posited that such an affordance effect might also be observed in chronic-stage stroke survivors. With either dominant or non-dominant hand forward, we presented three kinds of stimuli in stereoscopic depth; grasp objects affording a power-grip, pinch objects affording a thumb and forefinger precision-grip and an empty desk, affording no action. EEG data from 10 stroke survivors and 15 neurologically healthy subjects were analysed for the N1 and N2 ERP components. Both components revealed differences between the two object stimuli categories and the empty desk for both groups, suggesting the presence of affordance-related motor priming from around 100 to 370 ms after stimulus onset. Hence, we speculate that stroke survivors with loss of upper limb function may benefit from object presentation regimes designed to maximise motor priming when attempting movements with manipulable objects. However, further investigation would be necessary with acute stage patients, especially those diagnosed with apraxia.

Geographic ranges of many taxa have shifted poleward or up-slope under warming. Little is known, however, about the consistency of these dynamics among multiple mountains within a species’ geographic range. We assess climate tracking over the past century for four montane rodents, across the Ruby Mountains and Toiyabe Range within the Great Basin ecoregion of western North America. To do this, we generated species distribution models (SDMs, Maxent) in each mountain range during historical (1923–1940) and modern (2005–2015) time periods. Nineteen bioclimatic variables were derived from 800 m resolution monthly PRISM climate group data. SDMs trained on historic occurrences and climate were projected onto modern climates to estimate expected species distributions along each elevational gradient. Occurrence-based Observed Modern SDMs were compared to these Expected Modern SDMs, with congruence between the two representing the degree of climate tracking. Climate tracking predicted up-slope range expansions and contractions in the Ruby Mountains, while stasis or down-slope contractions were predicted in the Toiyabe Range. Observed Modern SDMs rarely matched climate tracking expectations, and the same species showed variable responses among mountains. Deviations are partially explained by changes in the contribution of temperature vs. precipitation over time. Additionally, optimal niche space in the Ruby Mountains shifted in elevation, but shifted in both elevation and latitude in the Toiyabe Range. Our results indicate that data from one elevational gradient may not be predictive of range dynamics elsewhere, even across similar environmental conditions and habitats, even for the same species. Conservation efforts will be better served by strategies that consider both inter- and intraspecific variation in responses to climate change over space and time.

Chitosan, a soluble polycationic derivative of insoluble chitin, has been widely considered for use in the food, cosmetic and pharmaceutical industries. Commercial (“C”) and in-house laboratory (“L”) prepared chitosan samples extracted from crustaceous shells with different molecular weight and degrees of acetylation (25% and 15%) were compared with regards to (i) weight–average molecular weight (Mw); (ii) sedimentation coefficient (so20,w) distribution, and (iii) intrinsic viscosity ([η]). These parameters were estimated using a combination of analytical ultracentrifugation (AUC), size exclusion chromatography coupled to multi-angle laser light scattering (SEC–MALS) and differential pressure viscometry. Polydisperse distributions were seen from sedimentation coefficient distributions and elution profiles from SEC–MALS. Mw values obtained for each sample by sedimentation equilibrium measurements were in excellent agreement with those obtained from SEC–MALS. Mark–Houwink–Kuhn–Sakurada (MHKS) and Wales van Holde analyses of the data all suggest a semi-flexible conformation. The principle of co-sedimentation was then used to monitor the interactions of the two different molecular weights of L chitosans with two polyanions, DNA and xanthan (another double helical high molecular weight molecule). Interactions were clearly observed and then quantified from the changes in the sedimentation coefficient distribution of the mixture compared to unmixed controls using sedimentation velocity. The interactions appeared to show a strong dependence on molecular weight. The relevance of this for DNA condensation applications is indicated. Turkish Ministry of National Education

The conformation and heterogeneity of lambda-carrageenan, a sulphonated galactan from red seaweed, solubilised in aqueous solvent with the assistance of microwave irradiation, has been assessed by a combination of analytical ultracentrifugation, size-exclusion chromatography, light scattering and capillary viscometry. Preparations appeared generally unimodal on the basis of sedimentation coefficient distributions from sedimentation velocity although at the highest concentrations a shoulder appears with a sedimentation coefficient approximately 1.1 times greater than that of the main component. Even under conditions commensurate with charge suppression simple linear regression was insufficient to represent non-ideal concentration dependence and the extraction of the Gralen concentration dependence parameter ks. A more general fitting algorithm was therefore employed. Mark–Houwink–Kuhn–Sakurada analysis of the change in intrinsic viscosity [η] with molecular weight, together with the Wales–van Holde ratio (combination of ks with [η]) point to an extended flexible conformation for lambda-carrageenan in the (weight average) molecular weight range Mw = 340,000–870,000 g/mol. The origin of the larger sedimentation coefficient component appearing at the higher concentrations is considered.

Tetanus toxoid protein has been characterized with regard oligomeric state and hydrodynamic (low-resolution) shape, important parameters with regard its use in glycoconjugate vaccines. From sedimentation velocity and sedimentation equilibrium analysis in the analytical ultracentrifuge tetanus toxoid protein is shown to be mostly monomeric in solution (~86%) with approximately 14% dimer. The relative proportions do not appear to change significantly with concentration, suggesting the two components are not in reversible equilibrium. Hydrodynamic solution conformation studies based on high precision viscometry, combined with sedimentation data show the protein to be slightly extended conformation in solution with an aspect ratio ~3. The asymmetric structure presents a greater surface area for conjugation with polysaccharide than a more globular structure, underpinning its popular choice as a conjugation protein for glycoconjugate vaccines.

Background & Aims Hepatocyte growth factor/scatter factor (HGF/SF) stimulates hepatocyte DNA synthesis and protects against apoptosis; in vivo it promotes liver regeneration and reduces fibrosis. However, its therapeutic value is limited by its complex domain structure, high cost of production, instability, and poor tissue penetration due to sequestration by heparin sulfate proteoglycans (HSPGs). Methods Using protein engineering techniques, we created a full-length form of HGF/SF (called HP21) and a form of the small, naturally occurring HGF/SF fragment, NK1 (called 1K1), which have reduced affinity for HSPG. We characterized the stability and proliferative and anti-apoptotic effects of these variants in primary human hepatocytes and in rodents. Results Analytical ultracentrifugation showed that 1K1 and NK1 were more stable than the native, full-length protein. All 4 forms of HGF/SF induced similar levels of DNA synthesis in human hepatocytes; 1K1 and NK1 required heparin, an HSPG analogue, for full agonistic activity. All the proteins reduced levels of Fas ligand–mediated apoptosis, reducing the activity of caspase-3/7 and cleavage of poly(adenosine diphosphate–ribose) polymerase. 1K1 was more active than NK1 in rodents; in healthy mice, 1K1 significantly increased hepatocyte DNA synthesis, and in mice receiving carbon tetrachloride, it reduced fibrosis. In rats, after 70% partial hepatectomy, daily administration of 1K1 for 5 days significantly increased liver mass and the bromodeoxyuridine labeling index compared with mice given NK1. Conclusions 1K1, an engineered form of the small, naturally occurring HGF/SF fragment NK1, has reduced affinity for HSPG and exerts proliferative and antiapoptotic effects in cultured hepatocytes. In rodents, 1K1 has antifibrotic effects and promotes liver regeneration. The protein has better stability and is easier to produce than HGF/SF and might be developed as a therapeutic for acute and chronic liver disease.

The production of engineered nanoparticles is growing rapidly as the field of nanotechnology continues to expand. Zinc oxide nanoparticles (ZnO NPs) are used in various applications, including catalysis, electronics, biosensors, medicine, paints, sunscreens and cosmetics, thus it is important to understand the biological effects and risks of ZnO NPs. This study was designed to investigate the apoptosis induction by ZnO NPs via mitogen-activated protein kinase p38 and cell cycle checkpoint protein p53 pathways in human dermal fibroblasts. MTT-based cell viability assay showed a significant decrease in cell survivorship after ZnO NP exposure, and phase contrast images revealed that ZnO NP treated cells had lower density and a rounded morphology. Apoptosis induction was confirmed by the annexin V assay and Western blot analysis showed the up-regulation of p53 and phospho-p38 proteins. Furthermore, in ZnO NP exposed cells, p53 protein was phosphorylated at Ser33 and Ser46 sites known to be phosphorylated by p38. Our results suggest that ZnO NPs have the potential to induce apoptosis in human dermal fibroblasts via p53-p38 pathways.

Silver and titanium dioxide nanoparticles are known to induce oxidative stress in vitro and in vivo. Here we test if they impact development, mating success, and survivorship in Drosophila melanogaster, and if so, if these effects are reversible by antioxidants. Ingestion of nanotitanium dioxide during the larval stage of the life cycle showed no effects on development or survivorship, up to doses of 200 μg mL−1. Conversely, ingestion of nanosilver had major dose, size, and coating-dependent effects on each of these aspects of life history. Each of these effects was partially or fully reversible by vitamin C. Larvae growing on nanosilver supplemented with vitamin C showed a greater than twofold increase in survivorship compared to flies reared on nanosilver alone, and a threefold increase in mating success. Vitamin C also rescued cuticular and pigmentation defects in nanosilver fed flies. Biochemical assays of superoxide dismutase and glutathione show these markers respond to nanotitanium dioxide and nanosilver induced oxidative stress, and this response is reduced by vitamin C. These results indicate that life history effects of nanosilver ingestion result from oxidative stress, and suggest antioxidants as a potential remediation for nanosilver toxicity. Conversely, the lack of nanotitanium dioxide life history toxicity shows that oxidative stress does not necessarily result in whole organism effects, and argues that nanoparticle toxicity needs to be examined at different levels of biological organization.

Ultra-weak interactions (K(d)>100μM) between proteins have in the last decade become an increasing focus of attention in cell biology, especially in relation to cell-cell interactions and signalling processes. Methods for their quantitative definition are reviewed. NMR spectroscopy plays a major role in this area, as it not only can define interactions as weak or weaker than 3mM, but in favourable cases structural information concerning the complex can be yielded. Free solution technologies mostly fail when addressed to such systems. The AUC has the highest practical capability, but evaluation of the data to yield K(a) values is complicated by the presence of thermodynamic/hydrodynamic effects of a comparable order of magnitude. These effects can however be computationally removed by means of suitable algorithms, and K(d) values of up to 50mM can be characterised. The relative merits of velocity and equilibrium approaches are discussed, and both are shown to have particular advantages.

The first eight and the last two of 20 complement control protein (CCP) modules within complement factor H (fH) encompass binding sites for C3b and polyanionic carbohydrates. These binding sites cooperate self-surface selectively to prevent C3b amplification, thus minimising complement-mediated damage to host. Intervening fH CCPs, apparently devoid of such recognition sites, are proposed to play a structural role. One suggestion is that the generally small CCPs 10–15, connected by longer-than-average linkers, act as a flexible tether between the two functional ends of fH; another is that the long linkers induce a 180° bend in the middle of fH. To test these hypotheses, we determined the NMR-derived structure of fH12–13 consisting of module 12, shown here to have an archetypal CCP structure, and module 13, which is uniquely short and features a laterally protruding helix-like insertion that contributes to a prominent electropositive patch. The unusually long fH12–13 linker is not flexible. It packs between the two CCPs that are not folded back on each other but form a shallow vee shape; analytical ultracentrifugation and X-ray scattering supported this finding. These two techniques additionally indicate that flanking modules (within fH11–14 and fH10–15) are at least as rigid and tilted relative to neighbours as are CCPs 12 and 13 with respect to one another. Tilts between successive modules are not unidirectional; their principal axes trace a zigzag path. In one of two arrangements for CCPs 10–15 that fit well with scattering data, CCP 14 is folded back onto CCP 13. In conclusion, fH10–15 forms neither a flexible tether nor a smooth bend. Rather, it is compact and has embedded within it a CCP module (CCP 13) that appears to be highly specialised given both its deviant structure and its striking surface charge distribution. A passive, purely structural role for this central portion of fH is unlikely.

Deep brain stimulators (DBS) are increasingly used to treat chronic conditions, most commonly movement disorders but also pain and psychiatric disturbances. Given the chronic nature of these conditions, while relatively few anaesthetists will have direct experience of the implantation procedures, many more may encounter patients with implanted devices. Importantly, the presence of the DBS devices may have further implications for the investigation and management of these patients, including the use of MRI and the use of diathermy in surgical procedures. This article reviews the background and implications of DBS implants with this in mind.

The SO(5) ⊃SO(3) spherical harmonics form a natural basis for expansion of nuclear collective model angular wave functions. They underlie the recently-proposed algebraic method for diagonalization of the nuclear collective model Hamiltonian in an SU(1,1) ×SO(5) basis. We present a computer code for explicit construction of the SO(5) ⊃SO(3) spherical harmonics and use them to compute the Clebsch-Gordan coefficients needed for collective model calculations in an SO(3)-coupled basis. With these Clebsch-Gordan coefficients it becomes possible to compute the matrix elements of collective model observables by purely algebraic methods.

Covalent attachment of poly(ethylene glycol) (PEG) to therapeutic antibody fragments has been found effective in prolonging the half-life of the protein molecule in vivo. In this study analytical ultracentrifugation (AUC) in combination with small angle X-ray scattering (SAXS) has been applied to a number of antibody fragments and to their respective PEGylated conjugates. Despite the large increase in molecular weight due to the attachment of a 20-40 kDa PEG moiety, the PEGylated conjugates have smaller sedimentation coefficients, s, than their parent antibody fragments, due to a significant increase in frictional ratio f/f(o) (from approximately 1.3 to 2.3-2.8): the solution hydrodynamic properties of the conjugates are clearly dominated by the PEG moiety (f/f(o) approximately 3.0). This observation is reinforced by SAXS data at high values of r (separation of scattering centres within a particle) that appear dominated by the PEG part of the complex. By contrast, SAXS data at low values of r suggest that there are no significant conformational changes of the protein moiety itself after PEGylation The location of the PEGylation site within the conjugate was identified, and found to be consistent with expectation from the conjugation chemistry.

We consider the competition between SU ( 3 ) and pair coupling in the 2 s 1 d nuclear shell model. By working within the framework of the LST -coupling shell model with good supermultiplet symmetry, the problem appears as a competition between two dynamical subgroup chains U ( 6 ) ⊃ SU ( 3 ) ⊃ SO ( 3 ) and U ( 6 ) ⊃ O ( 6 ) ⊃ S O ( 3 ) which has also been studied in the context of the interacting boson model.

Unlike trophoblasts obtained from pregnancy termination material, trophoblasts grown from explanted chorionic villus samples (CVS) from 11-14 weeks of gestation potentially enable investigation of pre-eclampsia and other pregnancy disorders as the pregnancy outcome will later be known. CVS surplus to diagnostic needs were cultured as explants on either Matrigel or gelatin and the outgrowing cells characterised. Cell morphology was examined and the cells were stained for cytokeratin-7 and HLA-G. Outgrowing trophoblasts co-stained strongly for HLA-G and cytokeratin-7. While outgrowths on Matrigel grew faster and were 100% positive for cytokeratin-7, they proved to be embedded in the matrix and difficult to passage. Outgrowths on gelatin could be released by trypsinisation and were subcultured and further characterised before and after freezing. These cells should prove a valuable resource for the examination of disorders of pregnancy.

Measurement of arterial blood gases (ABG) is one of the commonest clinical investigations in emergency, perioperative and critical care. Analysis of ABG measurements can provide information about cardiopulmonary function and biochemical homeostasis that may be invaluable for diagnosis and monitoring therapeutic interventions. Interpretation of ABG measurements is often viewed as complicated and confusing. The aim of this contribution is to describe the underlying physiological mechanisms and provide a stepwise approach to interpretation.

Relationships between the IBM-1 and the Bohr collective model are explored in which the states of the IBM in its various dynamical symmetry limits are identified with subsets of Bohr model states of corresponding dynamical symmetries. The maps of interest are ones which give the contractions of the IBM in the limit of large boson number. The known map from the IBM into the Bohr model gives a contraction appropriate for the U(5) dynamical symmetry limit. A new map is given consistent with a contraction of the O(6) dynamical symmetry of the IBM. This map gives an explicit identification of IBM states in an O(6) ⊃ O(5) basis with states of the Wilets–Jean model and makes it possible to benefit from the different but complementary perspectives of the two models. For example, it leads to explicit expressions for the matrix elements of an IBM O(6) irrep in terms of the known matrix elements of the corresponding Wilets–Jean model. The relationship also shows how to obtain the familiar rotor plus beta- and gamma-vibrational bands of the Bohr–Mottelson model, in the IBM, by the addition to an O(6) Hamiltonian of a scalar cubic in the quadrupole moment operators of the type considered recently by Van Isacker. The establishment of close relationships between the two models enables one to benefit from the different and complementary perspectives they afford. For example, recent developments of an algebraic version of the collective model has shown that the Bohr model has an SU ( 1 , 1 ) × O ( 5 ) dynamical group with representations ranging from those of a spherical vibrator to a beta-vibrational soft-gamma rotor of the Wilets–Jean limit and, with the addition of an interaction, to a rotor of the standard Bohr–Mottelson type with beta- and gamma-vibrational bands. A parallel range of results can now be obtained in the IBM, albeit with some differences, within the framework of an SU ( 1 , 1 ) × O ( 5 ) dynamical group.

The transition from a spherical-vibrator to a deformed-rotor phase is examined in this and succeeding papers in the interacting boson and Bohr–Mottelson collective models. This paper explores the transition from a U(5) to an O(6) phase in the interacting boson model with variation of a control parameter α. As expected from other studies, it is observed that a low-lying state of the model can be assigned to one of three phases: a U(5) phase, an O(6) phase, or a transition phase. It is also shown that the range of values of the control parameter, for which the low-lying states are in the transition phase, shrinks as the dimension of the IBM Hilbert space increases and that a sharp phase transition develops as the infinite-dimensional limit is approached. A detailed examination of the states of the two phases shows that the U(5) symmetry of the α=0 limit is mixed throughout much of the U(5) phase and the O(6) symmetry of the α=1 limit is even more strongly mixed throughout much of the O(6) phase. Nevertheless, it is found that quasidynamical U(5) and O(6) symmetries continue to characterize the phases and provide an explanation of the apparent persistence of these symmetries in the face of strong symmetry-breaking interactions. Thus, the analysis suggests a useful definition of a phase associated with a dynamical symmetry. It also adds a perspective to Landau's theory of second-order phase transitions and to Iachello's concept of a critical point symmetry with analytical solutions in the transition region.

A model of a second-order shape phase transition is investigated in the Bohr collective model. The model contains two variable parameters, a mass parameter M and a control parameter α , and is such that when α = 0 the Hamiltonian is that of a harmonic spherical vibrator and when α is large it approaches that of an adiabatically decoupled rotor-vibrator. The results obtained by diagonalization of this Hamiltonian show that the range of α , in which the low-energy states of the model are in a transition region between that of a harmonic spherical vibrator phase (for small α ) and that of an adiabatic rotor-vibrator phase (for large α ), shrinks as M increases and as M → ∞ a critical point develops at α = 0.5 . The dynamical symmetries associated with the limiting phases of this model, which appear to persist in the small and large α domains, are interpreted as quasidynamical symmetries. For finite values of M , the results closely parallel those of the corresponding phase transition of an interacting boson model, studied in paper I of this series, when the mass M of the collective model is set equal to twice the boson number N of the IBM. The various solvable submodels of the Bohr model are related to corresponding limits of the IBM by contraction maps. Such contraction maps imply a correspondence between subsets of states in the domains of the two models for which a given contraction map applies. Thus, by considering the contraction limit of an IBM Hamiltonian in the Bohr model, one can interpret and even anticipate what the results of an IBM calculation would be in its macroscopic N → ∞ limit. The asymptotic scaling of the spectrum at the critical point and Iachello's critical point symmetry in the Bohr model and IBM are considered from this perspective.

A recently proposed computationally tractable version of the Bohr collective model is developed to the extent that we are now justified in describing it as an algebraic collective model. The model has an SU ( 1 , 1 ) × SO ( 5 ) algebraic structure and a continuous set of exactly solvable limits. Moreover, it provides bases for mixed symmetry collective model calculations. However, unlike the standard realization of SU ( 1 , 1 ) , used for computing beta wave functions and their matrix elements in a spherical basis, the algebraic collective model makes use of an SU ( 1 , 1 ) algebra that generates wave functions appropriate for deformed nuclei with intrinsic quadrupole moments ranging from zero to any large value. A previous paper focused on the SO ( 5 ) wave functions, as SO ( 5 ) (hyper-)spherical harmonics, and computation of their matrix elements. This paper gives analytical expressions for the beta matrix elements needed in applications of the model and illustrative results to show the remarkable gain in efficiency that is achieved by using such a basis in collective model calculations for deformed nuclei.

Computer codes are developed to calculate Clebsch–Gordan coefficients of SU(3) in both SU(2)- and SO(3)-coupled bases. The efficiency of this code derives from the use of vector coherent state theory to evaluate the required coefficients directly without recursion relations. The approach extends to other compact semi-simple Lie groups. The codes are given in subroutine form so that users can incorporate the codes into other programs. Program summary Title of program: SU3CGVCS Catalogue identifier: ADTN Program summary URL: http://cpc.cs.qub.ac.uk/summaries/ADTN Program obtainable from: CPC Program Library, Queen's University of Belfast, N. Ireland Licensing provisions: Persons requesting the program must sign the standard CPC non-profit use license Computers for which the program is designed and others on which it is operable: SGI Origin 2000, HP Apollo 9000, Sun, IBM SP, Pentium Operating systems under which the program has been tested: IRIX 6.5, HP UX 10.01, SunOS, AIX, Linux Programming language used: FORTRAN 77 Memory required to execute with typical data: On the HP system, it requires about 732 KBytes. Disk space used for output: 2100+2460 bytes No. of bits in a word: 32 bit integer and 64 bit floating point numbers. No. of processors used: 1 Has the code been vectorized: No No. of bytes in distributed program, including test data, etc.: 26 309 No. of lines in distributed program, including test data, etc.: 3969 Distribution format: tar gzip file Nature of physical problem: The group SU(3) and its Lie algebra su (3) have important applications, for example, in elementary particle physics, nuclear physics, and quantum optics [1–3]. The code presented is particularly relevant for the last two fields. Clebsch–Gordan (CG) coefficients are required whenever the symmetries of many-body systems are used for the evaluation of matrix elements of tensor operators. Moreover, the construction of CG coefficients for SU(3) serves as a nontrivial prototype for larger compact semi-simple Lie algebras and even for non semi-simple Lie algebras. It is the simplest Lie algebra to have multiplicity in its outer products and a non-canonical subalgebra, i.e., SO(3). Method of solution: Vector coherent state theory is first used to construct bases for the products of two irreducible representations (irreps) [4]. The bases are SU(2)-coupled so that SU(2)-reduced CG (or isoscalar factors) can be constructed naturally. The CG coefficients in the SO(3) bases are constructed subsequently from the overlaps between the SU(2) and SO(3) bases. Restriction on the complexity of the problem: The programs are limited by computer memory and the maximum size of variable arrays. As dimension overflow conditions are possible, they are flagged and can be fixed by following the directions given as part of the error message. Typical running time: The calculation time for a single SU(3) CG coefficient is very different for SU(2) and SO(3) bases. It varies between 7.3–54.1 ns in SGI Origin 2000, 0.81–5.48 ms in HP Apollo 9000, or 0.055–0.373 ms in Intel Pentium 4 for SU(2) bases while it is between 0.027–0.255 s in Intel Pentium 4 for SO(3) bases. Unusual features of the program: Intrinsic bit functions: and, or, and shift, called iand , ior , and ishft , respectively, in FORTRAN, are used for packing and unpacking the labels for the irreps. Intrinsic logical btest is used to test the bit for the phase factor. References: [1] Y. Ne'eman, Nucl. Phys. 26 (1961) 222; M. Gell-Man, Y. Ne'eman, The Eightfold Way, Benjamin, New York, 1964. [2] J.P. Elliott, Proc. Roy. Soc. A 245 (1958) 128, 562. [3] M. Reck, A. Zeilinger, H.J. Bernstein, P. Bertani, Phys. Rev. Lett. 73 (1994) 58; B.C. Sanders, H. de Guise, D.J. Rowe, A. Mann, J. Phys. A 32 (1999) 7111. [4] D.J. Rowe, C. Bahri, J. Math. Phys. 41 (2000) 6544.

A computationally tractable version of the Bohr-Mottelson collective model is presented which makes it possible to diagonalize realistic collective models and obtain convergent results in relatively small appropriately chosen subspaces of the collective model Hilbert space. Special features of the proposed model is that it makes use of the beta wave functions given analytically by the softened-beta version of the Wilets-Jean model, proposed by Elliott et al., and a simple algorithm for computing SO(5) > SO(3) spherical harmonics. The latter has much in common with the methods of Chacon, Moshinsky, and Sharp but is conceptually and computationally simpler. Results are presented for collective models ranging from the sherical vibrator to the Wilets-Jean and axially symmetric rotor-vibrator models., 16 pages, 9 figures

A novel technique for partial separation of amylose and amylopectin using zonal ultracentrifugation is introduced, supported by analytical ultracentrifuge measurements. Starch was first solubilised in 90% DMSO and 5% sucrose and then layered onto a gradient forming solution of 10–30% sucrose in 90% DMSO, with a cushion made up of 36% caesium chloride and 25% sucrose in water. Solutions were then run in a preparative ultracentrifuge at a rotor speed of 14000 rpm for approximately 25 min. The results for wheat starch showed that this method produced highly purified amylopectin in both soluble and highly aggregated forms, and at least partial purification of the amylose fractions.