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Astrocytes are emerging key players in neurological disorders. However, their role in disease etiology is poorly understood owing to inaccessibility of primary human astrocytes. Pluripotent stem cell-derived cells fail to mimic age and due to their clonal origin do not mimic genetic heterogeneity of patients. In contrast, direct conversion constitutes an attractive approach to generate human astrocytes that capture age and genetic diversity. We describe efficient direct conversion of human fibroblasts to functional induced astrocytes (iAs). Expression of the minimal combination Sox9 and Nfib generates iAs with molecular, phenotypic, and functional properties resembling primary human astrocytes. iAs could be obtained by conversion of fibroblasts covering the entire human lifespan. Importantly, iAs supported function of induced neurons obtained through direct conversion from the same fibroblast population. Fibroblast-derived iAs will become a useful tool to elucidate the biology of astrocytes and complement current in vitro models for studies of late-onset neurological disorders.

Background More than 50% of patients have a major complication after emergency gastrointestinal surgery. Intravenous (i.v.) fluid therapy is a life-saving part of treatment, but evidence to guide what i.v. fluid strategy results in the best outcome is lacking. We hypothesised that goal-directed fluid therapy during surgery (GDT group) reduces the risk of major complications or death in patients undergoing major emergency gastrointestinal surgery compared with standard i.v. fluid therapy (STD group). Methods In a randomised, assessor-blinded, two-arm, multicentre trial, we included 312 adult patients with gastrointestinal obstruction or perforation. Patients in the GDT group received i.v. fluid to near-maximal stroke volume. Patients in the STD group received i.v. fluid following best clinical practice. Postoperative target was 0–2 L fluid balance. The primary outcome was a composite of major complications or death within 90 days. Secondary outcomes were time in intensive care, time on ventilator, time in dialysis, hospital stay, and minor complications. Results In a modified intention-to-treat analysis, we found no difference in the primary outcome between groups: 45 (30%) (GDT group) vs 39 (25%) (STD group) (odds ratio=1.24; 95% confidence interval, 0.75–2.05; P=0.40). Hospital stay was longer in the GDT group: median (inter-quartile range), 7 (4–12) vs 6 days (4–8.5) (P=0.04); no other differences were found. Conclusion Compared with pressure-guided i.v. fluid therapy (STD group), flow-guided fluid therapy to near-maximal stroke volume (GDT group) did not improve the outcome after surgery for bowel obstruction or gastrointestinal perforation but may have prolonged hospital stay. Clinical trial registration EudraCT number 2015-000563-14; the Danish Scientific Ethics Committee and the Danish Data Protection Agency (REG-18-2015).

The complement system represents a powerful part of the innate immune system capable of removing pathogens and damaged host cells. Nevertheless, only a subset of therapeutic antibodies are capable of inducing complement dependent cytotoxicity, which has fuelled the search for new strategies to potentiate complement activation. Properdin (FP) functions as a positive complement regulator by stabilizing the alternative pathway C3 convertase. Here, we explore a novel strategy for direct activation of the alternative pathway of complement using bi-specific single domain antibodies (nanobodies) that recruit endogenous FP to a cell surface. As a proof-of-principle, we generated bi-specific nanobodies with specificity toward FP and the validated cancer antigen epidermal growth factor receptor (EGFR) and tested their ability to activate complement onto cancer cell lines expressing EGFR. Treatment led to recruitment of FP, complement activation and significant deposition of C3 fragments on the cells in a manner sensitive to the geometry of FP recruitment. The bi-specific nanobodies induced complement dependent lysis of baby hamster kidney cells expressing human EGFR but were unable to lyse human tumour cells due to the presence of complement regulators. Our results confirm that FP can function as a surface bound focal point for initiation of complement activation independent of prior C3b deposition. However, recruitment of FP by bi-specific nanobodies appears insufficient for overcoming the inhibitory action of the negative complement regulators overexpressed by many human tumour cell lines. Our data provide general information on the efficacy of properdin as an initiator of complement but suggest that properdin recruitment on its own may have limited utility as a platform for potent complement activation on regulated cell surfaces.

Strain 68-1 rhesus cytomegalovirus expressing simian immunodeficiency virus (SIV) antigens (RhCMV/SIV) primes MHC-E-restricted CD8+ T cells that control SIV replication in 50%-60% of the vaccinated rhesus macaques. Whether this unconventional SIV-specific immunity and protection is unique to rhesus macaques or RhCMV or is intrinsic to CMV remains unknown. Here, using cynomolgus CMV vectors expressing SIV antigens (CyCMV/SIV) and Mauritian cynomolgus macaques, we demonstrate that the induction of MHC-E-restricted CD8+ T cells requires matching CMV to its host species. RhCMV does not elicit MHC-E-restricted CD8+ T cells in cynomolgus macaques. However, cynomolgus macaques vaccinated with species-matched 68-1-like CyCMV/SIV mounted MHC-E-restricted CD8+ T cells, and half of the vaccinees stringently controlled SIV post-challenge. Protected animals manifested a vaccine-induced IL-15 transcriptomic signature that is associated with efficacy in rhesus macaques. These findings demonstrate that the ability of species-matched CMV vectors to elicit MHC-E-restricted CD8+ T cells that are required for anti-SIV efficacy is conserved in nonhuman primates, and these data support the development of HCMV/HIV for a prophylactic HIV vaccine.

This paper develops a new method informed by data and models to recover information about investor beliefs. Our approach uses information embedded in forward-looking asset prices in conjunction with asset pricing models. We step back from presuming rational expectations and entertain potential belief distortions bounded by a statistical measure of discrepancy. Additionally, our method allows for the direct use of sparse survey evidence to make these bounds more informative. Within our framework, market-implied beliefs may differ from those implied by rational expectations due to behavioral/psychological biases of investors, ambiguity aversion, or omitted permanent components to valuation. Formally, we represent evidence about investor beliefs using a novel nonlinear expectation function deduced using model-implied moment conditions and bounds on statistical divergence. We illustrate our method with a prototypical example from macro-finance using asset market data to infer belief restrictions for macroeconomic growth rates. Institutional subscribers to the NBER working paper series, and residents of developing countries may download this paper without additional charge at www.nber.org.

Tuberculosis (TB) is a highly heterogeneous disease that develops in a subset of individuals infected with aerosolized Mycobacterium tuberculosis (Mtb). We sought to develop an improved experimental model by infecting mice with an ultra-low dose (ULD, 1-3 founding Mtb bacteria), which is believed to reflect a physiologic inoculum. ULD-infected mice exhibited bacterial burdens ranging from

Interferon gamma (IFNɣ) produced by CD4 T cells is required for immune containment of Mycobacterium tuberculosis (Mtb) infection. Despite this, IFNɣ plays a minor role in CD4 T cell- mediated immunity within the lung. In this study, we use a recently-developed murine model of physiologic Mtb infection coupled with advanced quantitative imaging to demonstrate that IFNɣ production by Mtb-specific T cells is rapidly extinguished within the granuloma, but not in unaffected areas of the lung. This is mediated via TGFβ signaling, which is observed preferentially within granulomas in mice and Rhesus macaques, and results in cell-intrinsic immunosuppression in effector T helper 1 cells within the granuloma. Blockade of TGFβ signaling in T cells results in improved function and decreased pulmonary bacterial burden. These findings uncover a potent spatially localized immunosuppressive mechanism associated with Mtb infection and provide potential targets for host-directed therapy.

Introduction: IgA nephropathy (IgAN) is characterized by glomerular deposition of galactose-deficient IgA1 and complement proteins and leads to renal impairment. Complement deposition through the alternative and lectin activation pathways is associated with renal injury.Methods: To elucidate the contribution of the lectin pathway to IgAN, we measured the 11 plasma lectin pathway components in a well-characterized cohort of patients with IgAN.Results: M-ficolin, L-ficolin, mannan-binding lectin (MBL)-associated serine protease (MASP)-1 and MBL-associated protein (MAp) 19 were increased, whereas plasma MASP-3 levels were decreased in patients with IgAN compared with healthy controls. Progressive disease was associated with low plasma MASP-3 levels and increased glomerular staining for C3b/iC3b/C3c, C3d, C4d, C5b-9, and factor H-related protein 5 (FHR5). Glomerular FHR5 deposition positively correlated with glomerular C3b/iC3b/C3c, C3d, and C5b-9 deposition, but not with glomerular C4d. These observations, together with the finding that glomerular factor H (fH) deposition was reduced in progressive disease, are consistent with a role for fH deregulation by FHR5 in renal injury in IgAN.Conclusion: Our data indicate that circulating MASP-3 levels could be used as a biomarker of disease severity in IgAN and that glomerular staining for FHR5 could both indicate alternative complement pathway activation and be a tissue marker of disease severity.

Investigations of diving behavior of the Atlantic walrus (Odobenus rosmarus rosmarus) in the high Arctic Greenland and Canada are important for understanding behavioral adaptations and area utilization of this Arctic benthic feeder. Furthermore, such information along with estimations of annual consumption and carrying capacity of walruses are needed in management decisions of this utilized species. Satellite-linked transmitters deployed on 27 walruses from 2010 to 2013 provided data for investigations of diving behavior in three predefined main areas: NW Greenland, Smith Sound and NE Canada. Sub-areas within each main area were also compared. Depth of dives, dive rates, time at depth of dives, haul-out periods and vertical speeds were estimated. Majority of dives targeted depths from 10 to 100m, which corresponds to the distribution of walrus preferred food items. Four dives to depths >500m occurred and are the deepest ever documented for a walrus. Dive rates and time at depth of dives were significantly different between sub-areas (p

Visual encounter distance models are important tools for predicting how light and water clarity mediate visual predator-prey interactions that affect the structure and function of aquatic ecosystems at multiple spatial, temporal, and organizational scales. The two main varieties of visual encounter distance models, mechanistic and empirical, are used for similar purposes but take fundamentally different approaches to model development and have different strengths and weaknesses in terms of predictive accuracy, physical and biological interpretability of parameters, ability to incorporate outside information, and utility for knowledge transfer. To overcome weaknesses of existing mechanistic and empirical models and bridge the gap between approaches, we developed a generalized visual reaction distance model that relaxes assumptions of a widely-used mechanistic model that are violated in real predator-prey interactions. We compared the performance of the generalized visual reaction distance model to a widely used mechanistic model and an empirical visual encounter distance model by fitting models to data from four predator-prey experiments. The generalized visual reaction distance model substantially outperformed the other models in all cases based on fit to reaction distance data and presents an attractive alternative to prior models based on comparatively high predictive accuracy, use of interpretable parameters, and ability to incorporate outside information—characteristics that facilitate knowledge transfer.

Employment of physicians by hospitals – typically referred to as vertical integration – has increased significantly. Received theories fail to explain a key fact: The extent of vertical integration in not-for-profit (NFP) hospitals is substantially higher than in for-profit (FP) hospitals. We develop a model in which vertical externalities in the joint provision of complementary health care services by independent hospitals and physicians cause total prices and cost to be higher, and quantity, quality and profits to be lower, relative to a vertically integrated organization. This establishes an incentive for hospitals to integrate. We show that these externalities impact NFP hospitals more than they do FPs, so that NFPs have stronger incentives to integrate. Using data on US hospitals from 2000-2015 and with controls for other covariates including state-level “corporate-practice-of-medicine” regulations, we find support for our predictions. Our model not only explains patterns of vertical integration observed in the US hospital industry, but also has surprising implications for the effects of such integration on hospital and physician prices, and hence, for antitrust policy and empirical studies of pricing.

Tuberculosis (TB) is a heterogeneous disease manifesting in a subset of individuals infected with aerosolized Mycobacterium tuberculosis (Mtb). Unlike human TB, murine infection results in uniformly high lung bacterial burdens and poorly organized granulomas. To develop a TB model that more closely resembles human disease, we infected mice with an ultra-low dose (ULD) of between 1–3 founding bacteria, reflecting a physiologic inoculum. ULD-infected mice exhibited highly heterogeneous bacterial burdens, well-circumscribed granulomas that shared features with human granulomas, and prolonged Mtb containment with unilateral pulmonary infection in some mice. We identified blood RNA signatures in mice infected with an ULD or a conventional Mtb dose (50–100 CFU) that correlated with lung bacterial burdens and predicted Mtb infection outcomes across species, including risk of progression to active TB in humans. Overall, these findings highlight the potential of the murine TB model and show that ULD infection recapitulates key features of human TB.

The circular economy rationale is increasingly promoted as a means to move from a global plastic waste dilemma to a plastics economy that is aligned with the principles of sustainable development. However, any such effort will have to account for the socio-economic settings in low-income and middle-income countries of the global south which are the main entry points of mismanaged plastic wastes into the environment. Since waste management and recycling in these economies are characterized by a great degree of informality, there is an urgent need to find models for partnering with the informal recycling sector in an effective, scalable, and sustainable manner. In this work, we present the case of a for-profit company located in Nairobi, Kenya, that operates on the interface between formal and informal by processing post-consumer plastics sourced from local waste pickers through a fair-trade-like business model. Economic incentives, trust building measures, and a general willingness to learn and adapt were identified as prerequisites for establishing accountable supplier-buyer relationships. The combination of informed material pre-sorting by the individual waste picker and subsequent industrial scale sorting and washing resulted in recyclates that were comparable to commercially available benchmark recyclates from the sophisticated formal recycling system of a high-income country in terms of both composition and selected engineering properties. High-quality mechanical recycling of plastic wastes under informal conditions seems feasible and may even come along with socio-economic benefits for marginalized waste pickers when suitable modes of cooperation are put in place.

The production and consumption of smartphones have been associated with a wide range of sustainability issues throughout the life cycle. While the dominant industry practices and resulting social and ecological problems have been discussed in depth in the extant literature, it has not been investigated so far how sustainability pioneers alleviate unsustainability in the smartphone industry through their business models. Addressing this gap, this exploratory multiple case study analyzes sustainable business models of 16 sustainability pioneers along the entire smartphone life cycle. Based on a variety of business model designs in the sample, the findings reveal seven sustainable business model patterns that are explained in terms of their value proposition, value creation and delivery, and value capture. One key finding is that most patterns extend beyond a single life cycle phase into other phases, which allows them to develop more comprehensive solutions than single-phase sustainable business models. This article furthermore discusses how sustainable business models of pioneers address sustainability issues of the smartphone industry. Comparing empirical insights with the emerging sustainable business model concept shows that the ‘ideal’ sustainable business model suggested in academic literature could not be observed. This article concludes with implications for sustainable business model research and practice. First, solving the industry’s sustainability issues comprehensively requires a combination of pioneering sustainable business models and collaboration of actors. Second, the sustainable business models explored in this study provide design options for pioneer and conventional smartphone companies alike.

Re-establishment of riparian freshwater wetlands often involves re-meandering of former channelized river sections by narrowing the channel width and depth, which creates frequently inundated floodplains. Inundations are important for floodplains in terms of erosion/accretion of sediment and for deposition of nutrients and organic matter. The links between floodplain hydraulics and deposition of sediment, organic matter and phosphorus were investigated along a 6 km re-meandered channel section of River Odense, Denmark. A 2D dynamic river and floodplain model was set up for the investigated floodplain area. The flow model was validated against in situ measurements of flow velocities and depths during a one-day field campaign in January 2012. Deposition of sediment was measured on 30 artificial grass mats deployed on the floodplain during winter 2011/2012. Total deposition of sediment, organic matter and total phosphorus was estimated by Kriging and amounted to 4.72 kg m −2 , 0.65 kg m −2 and 11.4 g m −2 , respectively. The predicted duration of inundations, distances to inflow, flow velocities, and information on microtopography were compared with sedimentation patterns on the floodplain. Three distinct flow regimes were predicted by the hydraulic model and were classified as small, medium and large inundation events according to spatial extent and inundation depth. The model predicts spatially and temporally changing zones of confluence on the floodplain due to variations in inundation depth. The position of these zones correlates with zones of high sediment deposition. Simple regression models described only up to 76% of the variation in sediment deposition. We conclude that use of dynamic spatial distributed 2D models is necessary if the links between floodplain hydraulics and deposition of sediment, organic matter and phosphorus are to be accurately described.

Since the Brundtland report in 1987 a wide debate has emerged on eco-innovation (e.g. eco-design, cleaner production) and sustainability-oriented innovations (SOIs), that is, the integration of ecological and social aspects into products, processes, and organizational structures. While prior research has often dealt with SOIs in large firms, the last decade has begun to generate broad knowledge on the specificities of SOIs in small and medium sized enterprises (SMEs) as they are increasingly recognized as central contributors to sustainable development. However, this knowledge is scattered across different disciplines, research communities, and journals. Therefore, this paper analyzes the heterogeneous picture research has drawn within the past 20 years with a focus on the innovation practices including different types of SOIs and strategic sustainability behaviors of SMEs through an interdisciplinary, systematic review in a time frame between 1987 and 2010. By consulting major research databases we have analyzed 84 key journal articles bibliographically and thematically. We find that first SME strategic sustainability behavior ranges from resistant, reactive, anticipatory, and innovation-based to sustainability-rooted. Second, we identify innovation practices at the product, process, and organizational level. Third, our results show that research is still strong on eco-innovation rather than on innovation from a triple bottom line perspective (economic, social, and environmental dimension), that is, SOIs of SMEs. Our main theoretical contribution is the development of an integrated framework on SOIs of SMEs where we delineate how distinct strategic sustainability behaviors can explain contingencies in types of innovation practices. Furthermore, for the more proactive SME behaviors we argue that they possess higher capabilities for more radical SOIs with the innovation process itself changing. Therefore, we propose that interaction with external actors (e.g. customers, authorities, research institutes) can ultimately increase the innovative capacity of SMEs for SOIs. Finally, we identify major research gaps with regard to radical SOIs, streamlined innovation methods, the role of SMEs in industry transformation and in sustainable supply chains, as well as a need for a stronger theoretical debate on SOIs of SMEs Since the Brundtland report in 1987 a wide debate has emerged on eco-innovation (e.g. eco-design, cleaner production) and sustainability-oriented innovations (SOIs), that is, the integration of ecological and social aspects into products, processes, and organizational structures. While prior research has often dealt with SOIs in large firms, the last decade has begun to generate broad knowledge on the specificities of SOIs in small and medium sized enterprises (SMEs) as they are increasingly recognized as central contributors to sustainable development. However, this knowledge is scattered across different disciplines, research communities, and journals. Therefore, this paper analyzes the heterogeneous picture research has drawn within the past 20 years with a focus on the innovation practices including different types of SOIs and strategic sustainability behaviors of SMEs through an interdisciplinary, systematic review in a time frame between 1987 and 2010. By consulting major research databases we have analyzed 84 key journal articles bibliographically and thematically. We find that first SME strategic sustainability behavior ranges from resistant, reactive, anticipatory, and innovation-based to sustainability-rooted. Second, we identify innovation practices at the product, process, and organizational level. Third, our results show that research is still strong on eco-innovation rather than on innovation from a triple bottom line perspective (economic, social, and environmental dimension), that is, SOIs of SMEs. Our main theoretical contribution is the development of an integrated framework on SOIs of SMEs where we delineate how distinct strategic sustainability behaviors can explain contingencies in types of innovation practices. Furthermore, for the more proactive SME behaviors we argue that they possess higher capabilities for more radical SOIs with the innovation process itself changing. Therefore, we propose that interaction with external actors (e.g. customers, authorities, research institutes) can ultimately increase the innovative capacity of SMEs for SOIs. Finally, we identify major research gaps with regard to radical SOIs, streamlined innovation methods, the role of SMEs in industry transformation and in sustainable supply chains, as well as a need for a stronger theoretical debate on SOIs of SMEs. © 2013 Elsevier Ltd. All rights reserved.

There is great interest in exploring and exploiting hydrocarbon resources in the Arctic, and one of the main methods of locating and assessing such resources is seismic survey. Marine seismic surveys involve the use of airguns that introduce high-energy noise to the Arctic’s largely pristine underwater acoustic environment. Narwhals may be particularly sensitive to this noise but so far no studies have addressed the question of direct effects of high-energy airgun pulses on these animals. We are concerned about the possibility that three large recent ice entrapments were causally linked to seismic survey activities. On these occasions narwhals remained in coastal summering areas until well into the fall and early winter season, delaying their annual offshore migration and becoming lethally entrapped by rapidly forming fast ice. About 1000 narwhals died in an ice entrapment in Canada in 2008 and about 100 in two entrapments in Northwest Greenland in 2009–10. We conclude that studies of the direct effects of seismic surveys on narwhals are urgently needed and should ideally precede further seismic surveys in narwhal habitats.

A recent paper by Mishchenko et al. compares near-coincident MISR, MODIS, and AERONET aerosol optical depth (AOD) products, and reports much poorer agreement than that obtained by the instrument teams and others. We trace the reasons for the discrepancies primarily to differences in (1) the treatment of outliers, (2) the application of absolute vs. relative criteria for testing agreement, and (3) the ways in which seasonally varying spatial distributions of coincident retrievals are taken into account.

Caveolae are ampullate (flask-shaped) invaginations that are abundant in the plasma membrane of many mammalian cell types. Although caveolae are implicated in a wide range of processes including endothelial transcytosis, lipid homeostasis and cellular signalling, a detailed molecular picture of many aspects of their function has been elusive. Until recently, the only extensively characterised protein components of caveolae were the caveolins. Recently, data from several laboratories have demonstrated that a family of four related proteins, termed cavins 1-4, plays key roles in caveolar biogenesis and function. Salient properties of the cavin family include their propensity to form complexes with each other and their different but overlapping tissue distribution. This review summarises recent data on the cavins, and sets them in the context of open questions on the construction and function of caveolae. The discovery of cavins implies that caveolae might have unexpectedly diverse structural properties, in accord with the wide range of functions attributed to these 'little caves'.

Saturn's icy satellites are among the main scientific objectives of the Cassini-VIMS (Visual and Infrared Mapping Spectrometer) experiment. This paper contains a first systematic and comparative analysis of the full-disk spectral properties of Dione, Enceladus, Epimetheus, Hyperion, Iapetus, Mimas, Phoebe, Rhea and Tethys as observed by VIMS from July 2004 to June 2005. The disk integrated properties (350–5100 nm reflectance spectra and phase curves at 550–2232 nm) and images of satellites are reported and discussed in detail together with the observed geometry. In general, the spectra in the visible spectral range are almost featureless and can be classified according to the spectral slopes: from the bluish Enceladus and Phoebe to the redder Iapetus, Hyperion and Epimetheus. In the 1000–1300 nm range the spectra of Enceladus, Tethys, Mimas and Rhea are characterized by a negative slope, consistent with a surface largely dominated by water ice, while the spectra of Iapetus, Hyperion and Phoebe show a considerable reddening pointing out the relevant role played by darkening materials present on the surface. In between these two classes are Dione and Epimetheus, which have a flat spectrum in this range. The main absorption bands identified in the infrared are the 1520, 2020, 3000 nm H2O/OH bands (for all satellites), although Iapetus dark terrains show mostly a deep 3000 nm band while the 1520 and 2020 nm bands are very faint. In this spectral range, the Iapetus spectrum is characterized by a strong reddening. The CO2 band at 4260 nm and the Fresnel ice peak around 3100 nm are evident only on Hyperion, Phoebe and Iapetus. The phase curves at 550 and at 2232 nm are reported for all the available observations in the 0°–144° range; Rhea shows an opposition surge at visible wavelengths in the 0.5°–1.17° interval. The improvement on the retrieval of the full-disk reflectance spectra can be appreciated by a direct comparison with ground-based telescopic data available from literature. Finally, data processing strategies and recent upgrades introduced in the VIMS-V calibration pipeline (flat-field and destriping–despiking algorithm) are discussed in appendices.

We report on direct experimental evidence of the population of the 3/2−3/2− intruder state in 27Ne in the knockout of a single neutron from the ground state of 28Ne. This low-lying negative parity state is consistent with a narrower shell gap for exotic nuclei with Z≪NZ≪N and N≈20N≈20. Monte Carlo shell-model calculations with the modern SDPF-M interaction successfully describe neutron-rich nuclei in the vicinity of N=20N=20 where normal and intruder configurations coexist at low excitation energy. This observation demonstrates the importance of direct reactions for the study of exotic nuclei and the predictive power of these large-scale shell-model calculations ispartof: Physics Letters B vol:640 issue:3 pages:86-90 status: published

Mannan-binding lectin (MBL) is attracting considerable interest due to its role in the immune defense. The high frequency of congenital MBL deficiency makes it feasible to evaluate clinical relevance through epidemiological investigations on fairly limited numbers of patients. MBL deficiency is determined by three mutant allotypes termed B, C and D in the coding region as well as mutations in the promoter region. It has been suggested that individuals, with deficiency-associated allotypes, may present significant amounts of low molecular weight MBL. We have compared the quantification of MBL by four commercially available assays with results obtained by our own in-house assays. Most assays are selectively sensitive for the wild type MBL (allotype A), but special combinations of antibodies also detect mutant forms of MBL. Thus a sandwich-type time-resolved immunoflourometric assay (TRIFMA), with a mouse monoclonal antibody (93C) as the catching and detecting antibody, shows B/B and D/D homozygous individuals to present signals corresponding to up to 500 ng MBL per ml (with plasma from an A/A individual as standard) as compared to less than 50 ng/ml and 200 ng/ml, respectively, when measured in other assays. In GPC at isotonic conditions the MBL in B/B and D/D individuals showed a Mr of 450 kDa. This MBL cannot bind to mannan. We further present a new method for quantifying the amount of MBL polypeptide chain. By applying plasma samples on SDS-PAGE at reducing conditions followed by Western blotting and quantification by chemiluminescense, this approach presents single polypeptide chains to the antibody independent of allotype differences in the collagen-like region. Titrations of recombinant MBL served as standard. In sera from homozygous mutants (O/O) the MBL concentrations estimated on Western blot were in the range of 100 to 500 ng/ml and correlated with that measured in the 93C-based TRIFMA.

Strong and weak cation-exchangers were compared for a number of chromatographic parameters, i.e. pH dependence, efficiency, binding strength, particle size distribution, static and dynamic capacity, and scanning electron microscopy (SEM) pictures. Chromatographic resins investigated were Fractogel EMD SO3- (M), Fractogel EMD SE Hicap (M), Fractogel EMD COO- (M), MacroPrep 25S, MacroPrep High S, MacroPrep CM, CM HyperZ, and Matrex Cellufine C-500. Testing was done with three proteins: Anti-FVII Mab (IgG), aprotinin, and lysozyme. For lysozyme and aprotinin with pI above experimental pH, dependence of pH on retention was generally low, though some pronounced decrease of retention with increasing pH was observed for CM HyperZ. For Anti-FVII Mab with pI

Plasmids carrying the mioC promoter region with its two DnaA boxes are as efficient in titration of DnaA protein as plasmids carrying a replication-inactivated oriC region with its five DnaA boxes. The two DnaA boxes upstream of the mioC promoter were mutated in various ways to study the cooperativity between the DnaA boxes, and to study in vivo the in vitro-defined 9mer DnaA box consensus sequence (TT(A)/(T)TNCACA). The quality and cooperativity of the DnaA boxes were determined in two complementary ways: as titration of DnaA protein leading to derepression of the dnaA promoter, and as repression of the mioC promoter caused by the DnaA protein binding to the DnaA boxes. Titration of DnaA protein correlated with repression of the mioC promoter. The level of titration and repression with the normal promoter-proximal box (TTTTCCACA) depends strongly on the presence and the quality of a DnaA box in the promoter-distal position, whereas a promoter-proximal DnaA box with the sequence TTATCCACA titrated DnaA protein and caused significant repression of the mioC promoter without a promoter-distal DnaA box. The quality of the eight different consensus DnaA boxes located in the promoter-proximal position was determined: TTATCCACA had the highest affinity for DnaA protein. In the third position, A was better than T, and the four possibilities in the fifth position could be ranked as CAor=GT. Parallel in vitro experiments using a purified DNA-binding domain of DnaA protein gave the same ranking of the binding affinities of the eight DnaA boxes.

The Mars Express spacecraft has a highly inclined orbit around Mars and so has been able to observe the south pole of Mars in illuminated conditions at the end of the southern summer ( L s = 330 ). Spectra from the planetary Fourier spectrometer (PFS) short wavelength (SW) channel were recorded over the permanent ice cap to study its composition in terms of CO 2 ice and H 2 O ice. Models are fitted to the observed data, which include a spatial mixture of soil (not covered by ice) and CO 2 frost (with a specific grain size and a small amount of included dust and H 2 O ice). Two different kinds of spectra were observed: those over the permanent polar cap with almost pure CO 2 ice, negligible water ice, no soil fraction required, and bright; and those over mixed terrain (at the edge of the cap or near troughs) containing a significant soil spatial fraction, more water ice and smaller CO 2 grain size. The amount of water ice given by fits to scaled albedo models is less than 10 ppm by weight. When using multi-stream reflectance models with the appropriate lighting geometry, the water amount must be 2–5 times greater than the albedo fit (less than 50 ppm). At the periphery of the residual polar cap, we found a region almost completely covered by water frost, modeled as a mixture of micron-sized and sub-mm sized grains. Our result using a granular mixture of micron-sized grains of water ice and dust with the CO 2 grains is different from the modeling of OMEGA polar cap observations using molecular mixtures.

Near-infrared spectroscopic imaging of a bright region within the Mars seasonal south polar cap was conducted during southern spring ( L s = 231 ) near the 2003 opposition, using the NASA Infrared Telescope Facility. The measured spectra are well represented by CO2 ice with grain radius of 13 mm and admixed dust and water ice concentrations of 0.005 and 0.002 wt%, respectively. We present a representative spectral (0.2–100 μm) surface albedo for the bright region.

There is a great need to ensure that language tests are accessible to individuals with disabilities. Yet accessibility features can sometimes conflict with the validity of test scores. In some cases the nature of the conflict seems obvious, yet in other cases there is controversy, such as that concerning the use of a “readaloud” accessibility feature on tests of reading. What is needed is a more rigorous approach for reasoning about the validity implications of accessibility features. The approach described in this article seeks to integrate thinking about accessibility, task design, and validity – all in a framework of sharable terminology, concepts, and knowledge representations. We believe that such a framework can allow one to more accurately and quickly identify the validity-related consequences of design changes that are intended to improve accessibility for individuals with disabilities. Such a framework may permit greater inclusion of individuals with disabilities or other sub-populations without invalidating test results.

The measurement of the single proton knock-out reaction from 24F on a 12C target at 46.7 MeV/nucleon yielded a 23O ground state population of (6.6±1.0) mb. The data were compared to calculations based on the many-body shell model and the eikonal theory. The results are consistent with a [ 0 d 5 / 2 6 ] ⊗ 1 s 1 / 2 configuration of 23O.

Two-proton knockout reactions on neutron-rich nuclei [Phys. Rev. Lett. 91 (2003) 012501] have been studied in inverse kinematics at intermediate energy. Strong evidence that the two-proton removal from a neutron-rich system proceeds as a direct reaction is presented, together with a preliminary theoretical discussion of the partial cross sections based on eikonal reaction theory and the many-body shell model. They show that this reaction can be used to characterize the wave functions of the projectiles and holds great promise for the study of neutron-rich nuclei.

L-ficolin and H-ficolin are molecules of the innate immune system. Upon recognition of a suitable target they activate the complement system. The ligand recognition structure of ficolins is contained within a fibrinogen-like domain. We examined the selectivity of the ficolins through inhibiting the binding to bacteria or to beads coupled with N-acetylglucosamine. The binding of L-ficolin to Streptococcus pneumoniae 11F and the beads was inhibited by N-acetylated sugars and not by non-acetylated sugars. However, it was also inhibited by other acetylated compounds. Based on this selectivity L-ficolin is not easily defined as a lectin. The binding of H-ficolin to Aerococcus viridans was not inhibited by any of the sugars or other compounds examined. Based on the selectivity of L-ficolin we developed a new purification procedure involving affinity chromatography on N-acetylcysteine-derivatized Sepharose. The column was loaded in the presence of EDTA and high salt, and L-ficolin was eluted by decreasing the salt concentration. Further purification was achieved by ion exchange chromatography.

With the development of an array of highly-segmented germanium detectors, it now becomes possible to perform in-flight γ-ray spectroscopy experiments on intermediate energy beams with unprecedented γ-ray energy resolution. Presented in this report are examples of two techniques in which SeGA, the most highly-segmented operational germanium array for in-flight spectroscopy with fast beams, was used for the detection of γ rays. SeGA used in conjunction with a high-resolution magnetic spectrograph (S800) to detect the reaction residues in coincidence represents a powerful combination for in-beam γ-ray studies.

A comparative study was performed on heparin resins and strong and weak cation exchangers to investigate the pH dependence, efficiency, binding strength, particle size distribution, static and dynamic capacity, and scanning electron microscopy pictures of chromatographic resins. The resins tested include: Heparin Sepharose FF, SP Sepharose FF, CM Sepharose FF, Heparin Toyopearl 650m, SP Toyopearl 650m, CM Toyopearl 650m, Ceramic Heparin HyperD M, Ceramic S HyperD 20, and Ceramic CM HyperD F. Testing was performed with four different proteins: anti-FVII Mab (IgG), aprotinin, lysozyme, and myoglobin. Dependence of pH on retention was generally very low for proteins with high isoelectric point (pI), though some decrease of retention with increasing pH was observed for CM Ceramic HyperD F and S Ceramic HyperD 20. Binding of anti-FVII Mab with pI

We report unusual and somewhat unexpected observations of the jovian satellite Io, showing strong methane absorption bands. These observations were made by the Cassini VIMS experiment during the Jupiter flyby of December/January 2000/2001. The explanation is straightforward: Entering or exiting from Jupiter's shadow during an eclipse, Io is illuminated by solar light which has transited the atmosphere of Jupiter. This light, therefore becomes imprinted with the spectral signature of Jupiter's upper atmosphere, which includes strong atmospheric methane absorption bands. Intercepting solar light refracted by the jovian atmosphere, Io essentially becomes a "mirror" for solar occultation events of Jupiter. The thickness of the layer where refracted solar light is observed is so large (more than 3000 km at Io's orbit), that we can foresee a nearly continuous multi-year period of similar events at Saturn, utilizing the large and bright ring system. During Cassini's 4-year nominal mission, this probing technique should reveal information of Saturn's atmosphere over a large range of southern latitudes and times.

The PHENIX On-Line system takes signals from the Front End Modules (FEM) on each detector subsystem for the purpose of generating events for physics analysis. Processing of event data begins when the Data Collection Modules (DCM) receive data via fiber-optic links from the FEMs. The DCMs format and zero suppress the data and generate data packets. These packets go to the Event Builders (EvB) that assemble the events in final form. The Level-1 trigger (LVL1) generates a decision for each beam crossing and eliminates uninteresting events. The FEMs carry out all detector processing of the data so that it is delivered to the DCMs using a standard format. The FEMs also provide buffering for LVL1 trigger processing and DCM data collection. This is carried out using an architecture that is pipelined and deadtimeless. All of this is controlled by the Master Timing System (MTS) that distributes the RHIC clocks. A Level-2 trigger (LVL2) gives additional discrimination. A description of the components and operation of the PHENIX On-Line system is given and the solution to a number of electronic infrastructure problems are discussed.

Chlorinated aromatic contaminants are active in carcinogenic processes within the skin and may have the potential to modulate ultraviolet radiation (UV)-induced skin carcinogenesis. Exposure to a complex environmental PCB/PCDD/PCDF mixture (polychlorinated biphenyls/polychlorinated dibenzo-p-dioxins/polychlorinated dibenzofurans) during the irradiation phase of photocarcinogenesis was associated with significant (P < or = 0.001) reductions in papilloma incidence and squamous cell carcinoma multiplicity at irradiated skin sites. This protective effect was associated with significantly (P < 0.0001) reduced chronic epidermal thickening in UV and contaminant-exposed mice compared with mice exposed to UV only. Contaminant exposure was also associated with increased UV absorbance of skin methanol extracts implying a sunscreen-like effect.

The timing, location and particle multiplicity of a PHENIX collision are determined by the Beam–Beam Counters (BBC), the Multiplicity/Vertex Detector (MVD) and the Zero-Degree Calorimeters (ZDC). The BBCs provide both the time of interaction and position of a collision from the flight time of prompt particles. The MVD provides a measure of event particle multiplicity, collision vertex position and fluctuations in charged particle distributions. The ZDCs provide information on the most grazing collisions. A Normalization Trigger Counter (NTC) is used to obtain absolute cross-section measurements for p–p collisions. The BBC, MVD and NTC are described below.

Three capsulated and two non-capsulated isolates of Lactococcus garvieae were investigated in terms of their wall proteins, virulence and interactions with rainbow trout immunoglobulin (Ig). All isolates were similar in integral membrane protein profile, and all were able to bind non-immune rainbow trout Ig, although different proteins appeared to be involved in Ig binding. However, whilst capsulated isolates were highly virulent, non-capsulated isolates were avirulent. This appeared to correlate with susceptibility of the non-capsulated isolates to rainbow trout normal serum. In contrast, the capsulated isolates were resistant to both normal and immune serum killing. In spite of this, passive immunisation of rainbow trout with specific anti-serum to L. garvieae was able to protect against challenge by capsulated isolates of L. garvieae. This suggests the antibody may have some other role in protection against disease caused by this important Gram-positive bacterial fish pathogen.

The present study reports that specific antibody increased the bactericidal activity of rainbow trout head-kidney macrophages against virulent capsulated Lactococcus garvieae in the absence of complement. The observed increased bactericidal activity appeared to result from increased phagocytosis of capsulated L. garvieae in the presence of specific antibody and may in part explain the protective effect of antibody previously reported against this disease.

Thirty-two-fold segmented coaxial high-purity large-volume germanium detectors for use in intermediate-energy radioactive-ion-beam experiments have been developed and tested. This high degree of segmentation will allow a precise localization of the point of photon interaction in the detector, thus allowing accurate doppler reconstruction of the energy of a γ-ray emitted in flight. In this article we report on the design of these detectors and their operational characteristics.