144 research outputs found

    Advances in the theory of III-V Nanowire Growth Dynamics

    Get PDF
    Nanowire (NW) crystal growth via the vapour_liquid_solid mechanism is a complex dynamic process involving interactions between many atoms of various thermodynamic states. With increasing speed over the last few decades many works have reported on various aspects of the growth mechanisms, both experimentally and theoretically. We will here propose a general continuum formalism for growth kinetics based on thermodynamic parameters and transition state kinetics. We use the formalism together with key elements of recent research to present a more overall treatment of III_V NW growth, which can serve as a basis to model and understand the dynamical mechanisms in terms of the basic control parameters, temperature and pressures/beam fluxes. Self-catalysed GaAs NW growth on Si substrates by molecular beam epitaxy is used as a model system.Comment: 63 pages, 25 figures and 4 tables. Some details are explained more carefully in this version aswell as a new figure is added illustrating various facets of a WZ crysta

    Cardiovascular magnetic resonance of myocardial infarction after blunt chest trauma: a heartbreaking soccer-shot

    Get PDF
    Cardiac injury occasionally occurs as a result of blunt chest trauma. Most cardiac complications in chest trauma are due to myocardial contusion rather than direct damage to the coronary arteries. However, traumatic coronary injury has been reported, and a variety of underlying pathophysiological mechanisms have been proposed. We present a 26 year old patient presenting with an acute coronary syndrome as a consequence of a soccer-shot impact to the chest. CMR showed apical inferior infarction, as well as multiple small septal lesions which were presumed to have resulted from embolization. The culprit lesion was a proximal 75% LAD stenosis with a prominent plaque-rupture and thrombus-formation, and the distal LAD was occluded by thromboembolic material

    Augmented Cystine–Glutamate Exchange by Pituitary Adenylate Cyclase-activating Polypeptide Signaling via the VPAC1 Receptor

    Get PDF
    In the central nervous system, cystine import in exchange for glutamate through system xc- is critical for the production of the antioxidant glutathione by astrocytes, as well as the maintenance of extracellular glutamate. Therefore, regulation of system xc- activity affects multiple aspects of cellular physiology and may contribute to disease states. Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuronally derived peptide that has already been demonstrated to modulate multiple aspects of glutamate signaling suggesting PACAP may also target activity of cystine–glutamate exchange via system xc-. In this study, 24-h treatment of primary cortical cultures containing neurons and glia with PACAP concentration-dependently increased system xc- function as measured by radiolabeled cystine uptake. Furthermore, the increase in cystine uptake was completely abolished by the system xc- inhibitor, (S)-4-carboxyphenylglycine (CPG), attributing increases in cystine uptake specifically to system xc- activity. Time course and quantitative PCR results indicate that PACAP signaling may increase cystine–glutamate exchange by increasing expression of xCT, the catalytic subunit of system xc-. Furthermore, the potentiation of system xc- activity by PACAP occurs via a PKA-dependent pathway that is not mediated by the PAC1R, but rather the shared vasoactive intestinal polypeptide receptor VPAC1R. Finally, assessment of neuronal, astrocytic, and microglial-enriched cultures demonstrated that only astrocyte-enriched cultures exhibit enhanced cystine uptake following both PACAP and VIP treatment. These data introduce a novel mechanism by which both PACAP and VIP regulate system xc- activity

    Cultural sensemaking of corporate social responsibility: A dyadic view of Russian–Finnish business relationships

    Get PDF
    International Management (IM) needs a better understanding of how managers of small and medium-sized enterprises (SMEs) make sense of cultural differences in international business relationships, especially regarding corporate social responsibility (CSR) in relationships between firms from emerging and developed countries. We address this lacuna by uncovering how dyads of Russian and Finnish SME managers, engaged in mutual international business relationships, construct their understanding of CSR. The findings indicate that conceptualizations of CSR are embedded both in SME managers' cultural backgrounds and in the contextual environment. This extends previous research on the role of CSR in IM and respond to calls to study the microfoundations of CSR and internationalization, adding to the sparse knowledge of CSR in cross-cultural SME settings.publishedVersionPeer reviewe

    Cultural sensemaking of corporate social responsibility: A dyadic view of Russian–Finnish business relationships

    Get PDF
    International Management (IM) needs a better understanding of how managers of small and medium-sized enterprises (SMEs) make sense of cultural differences in international business relationships, especially regarding corporate social responsibility (CSR) in relationships between firms from emerging and developed countries. We address this lacuna by uncovering how dyads of Russian and Finnish SME managers, engaged in mutual international business relationships, construct their understanding of CSR. The findings indicate that conceptualizations of CSR are embedded both in SME managers' cultural backgrounds and in the contextual environment. This extends previous research on the role of CSR in IM and respond to calls to study the microfoundations of CSR and internationalization, adding to the sparse knowledge of CSR in cross-cultural SME settings. </p

    Assessment of a Program for SARS-CoV-2 Screening and Environmental Monitoring in an Urban Public School District

    Get PDF
    Importance: Scalable programs for school-based SARS-CoV-2 testing and surveillance are needed to guide in-person learning practices and inform risk assessments in kindergarten through 12th grade settings. Objectives: To characterize SARS-CoV-2 infections in staff and students in an urban public school setting and evaluate test-based strategies to support ongoing risk assessment and mitigation for kindergarten through 12th grade in-person learning. Design, Setting, and Participants: This pilot quality improvement program engaged 3 schools in Omaha, Nebraska, for weekly saliva polymerase chain reaction testing of staff and students participating in in-person learning over a 5-week period from November 9 to December 11, 2020. Wastewater, air, and surface samples were collected weekly and tested for SARS-CoV-2 RNA to evaluate surrogacy for case detection and interrogate transmission risk of in-building activities. Main Outcomes and Measures: SARS-CoV-2 detection in saliva and environmental samples and risk factors for SARS-CoV-2 infection. Results: A total of 2885 supervised, self-collected saliva samples were tested from 458 asymptomatic staff members (mean [SD] age, 42.9 [12.4] years; 303 women [66.2%]; 25 Black or African American [5.5%], 83 Hispanic [18.1%], 312 White [68.1%], and 35 other or not provided [7.6%]) and 315 students (mean age, 14.2 [0.7] years; 151 female students [48%]; 20 Black or African American [6.3%], 201 Hispanic [63.8%], 75 White [23.8%], and 19 other race or not provided [6.0%]). A total of 46 cases of SARS-CoV-2 (22 students and 24 staff members) were detected, representing an increase in cumulative case detection rates from 1.2% (12 of 1000) to 7.0% (70 of 1000) among students and from 2.1% (21 of 1000) to 5.3% (53 of 1000) among staff compared with conventional reporting mechanisms during the pilot period. SARS-CoV-2 RNA was detected in wastewater samples from all pilot schools as well as in air samples collected from 2 choir rooms. Sequencing of 21 viral genomes in saliva specimens demonstrated minimal clustering associated with 1 school. Geographical analysis of SARS-CoV-2 cases reported district-wide demonstrated higher community risk in zip codes proximal to the pilot schools. Conclusions and Relevance: In this study of staff and students in 3 urban public schools in Omaha, Nebraska, weekly screening of asymptomatic staff and students by saliva polymerase chain reaction testing was associated with increased SARS-CoV-2 case detection, exceeding infection rates reported at the county level. Experiences differed among schools, and virus sequencing and geographical analyses suggested a dynamic interplay of school-based and community-derived transmission risk. Collectively, these findings provide insight into the performance and community value of test-based SARS-CoV-2 screening and surveillance strategies in the kindergarten through 12th grade educational setting

    Compromised Mitochondrial Fatty Acid Synthesis in Transgenic Mice Results in Defective Protein Lipoylation and Energy Disequilibrium

    Get PDF
    A mouse model with compromised mitochondrial fatty acid synthesis has been engineered in order to assess the role of this pathway in mitochondrial function and overall health. Reduction in the expression of mitochondrial malonyl CoA-acyl carrier protein transacylase, a key enzyme in the pathway encoded by the nuclear Mcat gene, was achieved to varying extents in all examined tissues employing tamoxifen-inducible Cre-lox technology. Although affected mice consumed more food than control animals, they failed to gain weight, were less physically active, suffered from loss of white adipose tissue, reduced muscle strength, kyphosis, alopecia, hypothermia and shortened lifespan. The Mcat-deficient phenotype is attributed primarily to reduced synthesis, in several tissues, of the octanoyl precursors required for the posttranslational lipoylation of pyruvate and a-ketoglutarate dehydrogenase complexes, resulting in diminished capacity of the citric acid cycle and disruption of energy metabolism. The presence of an alternative lipoylation pathway that utilizes exogenous free lipoate appears restricted to liver and alone is insufficient for preservation of normal energy metabolism. Thus, de novo synthesis of precursors for the protein lipoylation pathway plays a vital role in maintenance of mitochondrial function and overall vigo

    Fatty acid metabolism in aggressive B-cell lymphoma is inhibited by tetraspanin CD37

    Get PDF
    The importance of fatty acid (FA) metabolism in cancer is well-established, yet the mechanisms underlying metabolic reprogramming remain elusive. Here, we identify tetraspanin CD37, a prognostic marker for aggressive B-cell lymphoma, as essential membrane-localized inhibitor of FA metabolism. Deletion of CD37 on lymphoma cells results in increased FA oxidation shown by functional assays and metabolomics. Furthermore, CD37-negative lymphomas selectively deplete palmitate from serum in mouse studies. Mechanistically, CD37 inhibits the FA transporter FATP1 through molecular interaction. Consequently, deletion of CD37 induces uptake and processing of exogenous palmitate into energy and essential building blocks for proliferation, and inhibition of FATP1 reverses this phenotype. Large lipid deposits and intracellular lipid droplets are observed in CD37-negative lymphoma tissues of patients. Moreover, inhibition of carnitine palmitoyl transferase 1 A significantly compromises viability and proliferation of CD37-deficient lymphomas. Collectively, our results identify CD37 as a direct gatekeeper of the FA metabolic switch in aggressive B-cell lymphoma

    Enolase represents a metabolic checkpoint controlling the differential exhaustion programmes of hepatitis virus-specific CD8 + T cells

    Get PDF
    Objective: Exhausted T cells with limited effector function are enriched in chronic hepatitis B and C virus (HBV and HCV) infection. Metabolic regulation contributes to exhaustion, but it remains unclear how metabolism relates to different exhaustion states, is impacted by antiviral therapy, and if metabolic checkpoints regulate dysfunction. Design: Metabolic state, exhaustion and transcriptome of virus-specific CD8+ T cells from chronic HBV-infected (n=31) and HCV-infected patients (n=52) were determined ex vivo and during direct-acting antiviral (DAA) therapy. Metabolic flux and metabolic checkpoints were tested in vitro. Intrahepatic virus-specific CD8+ T cells were analysed by scRNA-Seq in a HBV-replicating murine in vivo model of acute and chronic infection. Results: HBV-specific (core18-27, polymerase455-463) and HCV-specific (NS31073-1081, NS31406-1415, NS5B2594-2602) CD8+ T cell responses exhibit heterogeneous metabolic profiles connected to their exhaustion states. The metabolic state was connected to the exhaustion profile rather than the aetiology of infection. Mitochondrial impairment despite intact glucose uptake was prominent in severely exhausted T cells linked to elevated liver inflammation in chronic HCV infection and in HBV polymerase455-463 -specific CD8+ T cell responses. In contrast, relative metabolic fitness was observed in HBeAg-negative HBV infection in HBV core18-27-specific responses. DAA therapy partially improved mitochondrial programmes in severely exhausted HCV-specific T cells and enriched metabolically fit precursors. We identified enolase as a metabolic checkpoint in exhausted T cells. Metabolic bypassing improved glycolysis and T cell effector function. Similarly, enolase deficiency was observed in intrahepatic HBV-specific CD8+ T cells in a murine model of chronic infection. Conclusion: Metabolism of HBV-specific and HCV-specific T cells is strongly connected to their exhaustion severity. Our results highlight enolase as metabolic regulator of severely exhausted T cells. They connect differential bioenergetic fitness with distinct exhaustion subtypes and varying liver disease, with implications for therapeutic strategies
    • …
    corecore