391 research outputs found

    Spin-Orbit Effects on the Shapes of Cross Sections in the 90-Zr(p,p') Reaction at 160 MeV

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    This work was supported by National Science Foundation Grants PHY 76-84033A01, PHY 78-22774, and Indiana Universit

    Differing effects when using phenylephrine and norepinephrine to augment cerebral blood flow after traumatic brain injury in the immature brain

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    Low cerebral blood flow (CBF) states have been demonstrated in children early after traumatic brain injury (TBI), and have been correlated with poorer outcomes. Cerebral perfusion pressure (CPP) support following severe TBI is commonly implemented to correct cerebral hypoperfusion, but the efficacy of various vasopressors has not been determined. Sixteen 4-week-old female swine underwent nonimpact inertial brain injury in the sagittal plane. Intraparenchymal monitors were placed to measure intracranial pressure (ICP), CBF, brain tissue oxygen tension (PbtO(2)), and cerebral microdialysis 30 min to 6 h post-injury. One hour after injury, animals were randomized to receive either phenylephrine (PE) or norepinephrine (NE) infusions titrated to a CPP >70 mm Hg for 5 h. Animals were euthanized 6 h post-TBI, and brains were fixed and stained to assess regions of cell and axonal injury. After initiation of CPP augmentation with NE or PE infusions, there were no differences in ICP between the groups or over time. Animals receiving NE had higher PbtO(2) than those receiving PE (29.6±10.2 vs. 19.6±6.4 torr at 6 h post-injury, p<0.05). CBF increased similarly in both the NE and PE groups. CPP support with PE resulted in a greater reduction in metabolic crisis than with NE (lactate/pyruvate ratio 16.7±2.4 vs. 42.7±10.2 at 6 h post-injury, p<0.05). Augmentation of CPP to 70 mm Hg with PE resulted in significantly smaller cell injury volumes at 6 h post-injury than CPP support with NE (0.4% vs. 1.4%, p<0.05). Despite similar increases in CBF, CPP support with NE resulted in greater brain tissue oxygenation and hypoxic-ischemic injury than CPP support with PE. Future clinical studies comparing the effectiveness of various vasopressors for CPP support are warranted

    Supporting 'design for reuse' with modular design

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    Engineering design reuse refers to the utilization of any knowledge gained from the design activity to support future design. As such, engineering design reuse approaches are concerned with the support, exploration, and enhancement of design knowledge prior, during, and after a design activity. Modular design is a product structuring principle whereby products are developed with distinct modules for rapid product development, efficient upgrades, and possible reuse (of the physical modules). The benefits of modular design center on a greater capacity for structuring component parts to better manage the relation between market requirements and the designed product. This study explores the capabilities of modular design principles to provide improved support for the engineering design reuse concept. The correlations between modular design and 'reuse' are highlighted, with the aim of identifying its potential to aid the little-supported process of design for reuse. In fulfilment of this objective the authors not only identify the requirements of design for reuse, but also propose how modular design principles can be extended to support design for reuse

    Trispecific antibody targeting HIV-1 and T cells activates and eliminates latently-infected cells in HIV/SHIV infections.

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    Agents that can simultaneously activate latent HIV, increase immune activation and enhance the killing of latently-infected cells represent promising approaches for HIV cure. Here, we develop and evaluate a trispecific antibody (Ab), N6/αCD3-αCD28, that targets three independent proteins: (1) the HIV envelope via the broadly reactive CD4-binding site Ab, N6; (2) the T cell antigen CD3; and (3) the co-stimulatory molecule CD28. We find that the trispecific significantly increases antigen-specific T-cell activation and cytokine release in both CD4 &lt;sup&gt;+&lt;/sup&gt; and CD8 &lt;sup&gt;+&lt;/sup&gt; T cells. Co-culturing CD4 &lt;sup&gt;+&lt;/sup&gt; with autologous CD8 &lt;sup&gt;+&lt;/sup&gt; T cells from ART-suppressed HIV &lt;sup&gt;+&lt;/sup&gt; donors with N6/αCD3-αCD28, results in activation of latently-infected cells and their elimination by activated CD8 &lt;sup&gt;+&lt;/sup&gt; T cells. This trispecific antibody mediates CD4 &lt;sup&gt;+&lt;/sup&gt; and CD8 &lt;sup&gt;+&lt;/sup&gt; T-cell activation in non-human primates and is well tolerated in vivo. This HIV-directed antibody therefore merits further development as a potential intervention for the eradication of latent HIV infection

    Talented suppliers? Strategic change and innovation in the UK aerospace industry

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    The 1990s marked the start of extensive re-structuring in the aerospace industry throughout the world. While the ensuing consolidation among prime contractors has been widely researched, the changes affecting the aerospace supply chain have received less attention. This study focuses on the re-structuring taking place within the supply chain of the UK aerospace industry. The findings point to extensive re-structuring. Unlike most earlier studies the lean supply model was found to be a powerful influence, with suppliers moving away from subcontractor status and instead taking on the mantle of ‘talented’ suppliers. While some of the implications of lean supply, in terms of the dynamics of innovation, were not apparent, there were modest signs of increased process innovation on the part of some suppliers

    Quantitative determinations and imaging in different structures of buried human bones from the XVIII-XIXth centuries by energy dispersive X-ray fluorescence - Postmortem evaluation

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    In this work, a non-commercial triaxial geometry energy dispersive X-ray Fluorescence (EDXRF) setup and a benchtop mu-XRF system were used to identify postmortem contamination in buried bones. For two of the individuals, unusually high concentrations of Cu and Pb, but also Zn (in one individual) were observed. The pigments of the burial shroud coverings have been identified as the source of contamination.Accurate and precise quantitative results were obtained by nondestructive process using fundamental parameters method taking into account the matrix absorption effects.A total of 30 bones from 13 individuals, buried between the mid-XVlllth to early XIXth centuries, were analyzed to study the elemental composition and elemental distribution. The bones were collected from a church in Almada (Portugal), called Ermida do Espirito Santo, located near the Tagus River and at the sea neighbourhood.The triaxial geometry setup was used to quantify Ca, Fe, Cu, Zn, Br, Sr and Pb of powder pressed bone pellets (n=9 for each bone). Cluster analysis was performed considering the elemental concentrations for the different bones. There was a clear association between some bones regarding Fe, Cu, Zn, Br and Pb content but not a categorization between cortical and trabecular bones. The elemental distribution of Cu, Zn and Pb were assessed by the benchtop p.-analysis, the M4 Tornado, based on a polycapillary system which provides multi-elemental 2D maps. The results showed that contamination was mostly on the surface of the bone confirming that it was related to the burial shroud covering the individuals

    Taking the First Steps towards a Standard for Reporting on Phylogenies: Minimum Information about a Phylogenetic Analysis (MIAPA)

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    In the eight years since phylogenomics was introduced as the intersection of genomics and phylogenetics, the field has provided fundamental insights into gene function, genome history and organismal relationships. The utility of phylogenomics is growing with the increase in the number and diversity of taxa for which whole genome and large transcriptome sequence sets are being generated. We assert that the synergy between genomic and phylogenetic perspectives in comparative biology would be enhanced by the development and refinement of minimal reporting standards for phylogenetic analyses. Encouraged by the development of the Minimum Information About a Microarray Experiment (MIAME) standard, we propose a similar roadmap for the development of a Minimal Information About a Phylogenetic Analysis (MIAPA) standard. Key in the successful development and implementation of such a standard will be broad participation by developers of phylogenetic analysis software, phylogenetic database developers, practitioners of phylogenomics, and journal editors. This paper is part of the special issue of OMICS on data standards.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63208/1/omi.2006.10.231.pd

    Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis

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    SummaryPolycythemia vera (PV), essential thrombocythemia (ET), and myeloid metaplasia with myelofibrosis (MMM) are clonal disorders arising from hematopoietic progenitors. An internet-based protocol was used to collect clinical information and biological specimens from patients with these diseases. High-throughput DNA resequencing identified a recurrent somatic missense mutation JAK2V617F in granulocyte DNA samples of 121 of 164 PV patients, of which 41 had homozygous and 80 had heterozygous mutations. Molecular and cytogenetic analyses demonstrated that homozygous mutations were due to duplication of the mutant allele. JAK2V617F was also identified in granulocyte DNA samples from 37 of 115 ET and 16 of 46 MMM patients, but was not observed in 269 normal individuals. In vitro analysis demonstrated that JAK2V617F is a constitutively active tyrosine kinase

    Report from the fifth international consensus meeting to harmonize core outcome measures for atopic eczema/dermatitis clinical trials (HOME initiative)

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    This is the report from the fifth meeting of the Harmonising Outcome Measures for Eczema initiative (HOME V). The meeting was held on 12–14 June 2017 in Nantes, France, with 81 participants. The main aims of the meeting were (i) to achieve consensus over the definition of the core domain of long-term control and how to measure it and (ii) to prioritize future areas of research for the measurement of the core domain of quality of life (QoL) in children. Moderated whole-group and small-group consensus discussions were informed by presentations of qualitative studies, systematic reviews and validation studies. Small-group allocations were performed a priori to ensure that each group included different stakeholders from a variety of geographical regions. Anonymous whole-group voting was carried out using handheld electronic voting pads according to predefined consensus rules. It was agreed by consensus that the long-term control domain should include signs, symptoms, quality of life and a patient global instrument. The group agreed that itch intensity should be measured when assessing long-term control of eczema in addition to the frequency of itch captured by the symptoms domain. There was no recommendation of an instrument for the core outcome domain of quality of life in children, but existing instruments were assessed for face validity and feasibility, and future work that will facilitate the recommendation of an instrument was agreed upon. The Harmonising Outcome Measures for Eczema (HOME) initiative is an international group working together to develop a core outcome set (COS) for clinical trials in eczema (synonymous with atopic eczema and atopic dermatitis). HOME is coordinated from the Centre of Evidence Based Dermatology, University of Nottingham, U.K. Participation in HOME is open to anyone with an interest in outcomes for eczema. A COS is the agreed upon minimum set of instruments that should be included in all clinical trials for a particular condition. Use of a COS does not preclude using other instruments; other domains and instruments can also be included to meet the specific requirements of individual trials. COS initiatives are active across many fields of medicine and should enable better synthesis of trial data and reduce selective outcome reporting bias. The HOME initiative follows the best current guidance on developing a COS. Four core domains have been identified: clinician-reported signs; patient-reported symptoms; quality of life; and long-term control. The core outcome measurement instruments for clinician-reported signs and patient-reported symptoms have been established: the Eczema Area and Severity Index (EASI) for measuring clinician reported signs was agreed on at the HOME III meeting, and the Patient-Oriented Eczema Measure (POEM) was chosen to measure patient-reported symptoms at the HOME IV meeting. This is a report from the fifth consensus meeting of the HOME initiative (HOME V), which was held on 12–14 June 2017 in Nantes, France. The local organizers were Sebastien Barbarot and Jean-Francois Stalder of Nantes University Hospital, France

    Statistical strategies for avoiding false discoveries in metabolomics and related experiments

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