Characterizing gas flow from aerosol particle injectors

A novel methodology for measuring gas flow from small orifices or nozzles into vacuum is presented. It utilizes a high-intensity femtosecond laser pulse to create a plasma within the gas plume produced by the nozzle, which is imaged by a microscope. Calibration of the imaging system allows for the extraction of absolute number densities. We show detection down to helium densities of $4\times10^{16}$~cm$^{-3}$ with a spatial resolution of a few micrometer. The technique is used to characterize the gas flow from a convergent-nozzle aerosol injector [Struct.\ Dyn.~2, 041717 (2015)] as used in single-particle diffractive imaging experiments at free-electron laser sources. Based on the measured gas-density profile we estimate the scattering background signal under typical operating conditions of single-particle imaging experiments and estimate that fewer than 50 photons per shot can be expected on the detector

The interaction between the Western flower trhips, Frankliniella occidentalis and pot gerbera, Gerbera jamesonii

Gerbera jamesonii is a plant with a large amount of pollen and various flower colours and a favourite host plant for Frankliniella occidentalis. The best growing temperature for gerbera is approximately 20°C. Frankliniella occidentalis or the Western Flower Thrips is a small insect that has become an important pest in greenhouse cultivation all over the world. The high temperatures in the greenhouse are favourable for F. occidentalis. The damages from this pest can be found in flower buds or in growing points. When thrips are piercing the cells and sucking out their contents, the cells are filled with air, which results in silvery spots on the infected plant parts. The leaves can be deformed as a result of the cells collapsing after the sucking. Later necrotic spots can appear and the injured plant part fades and becomes brown. Moreover on the leaves the insect's excreta can be seen as black spots. The damage on the plant is not visible until the damaged plant part (flower buds and leaves) starts to open, that is why it is important with preventive work. Continuous control of the plants is necessary in order to be able to apply an adequate control strategy before the Thrips population gets too large. Biological control is particularly hard to use because F. occidentalis develops very quickly while the reproduction of the natural enemies cannot keep up. Chemical control is also hard to use because Frankliniella occidentalis quickly can develop resistance. Frankliniella occidentalis and gerbera have the same temperature optimum and that makes temperature hard to use as a control mechanism for this pest. At low temperatures F. occidentalis develops more slowly and gerbera plants become smaller and vegetative. High temperatures up to 30ºC favours the Western Flower Thrips whereas the gerbera plant becomes high and elongated at high temperatures. Very high humidity is harmful to gerbera as well as to F. occidentalis. Gerbera can get fade disease and rots while thrips can get caught in the condense-water. The access to pollen is an important roll for the time of development of a Frankliniella population; increasing access results in a faster growth. A large amount of buds and young leaves is an asset for the pest as well as flowering plants. Preventative work including cleaning and control in the greenhouse with sticky traps and good hygiene is a step towards preventing and reducing infestations. More knowledge about the biological interaction between the host plant and the pest is needed to find new control strategies.Gerbera är ett växtslag med mycket pollen och varierande blomfärger som är omtyckt av Frankliniella occidentalis. Optimal odlingstemperatur för gerbera är 20ºC. Frankliniella occidentalis eller den amerikanska blomtripsen är en liten insekt som har blivit en alltmer viktig skadegörare i växthusodling över hela världen. Ju varmare klimat man har i växthuset desto bättre trivs F. occidentalis och skadorna som den orsakar återfinns ofta i blomknoppar eller tillväxtpunkter. Eftersom trips suger ut växtsaften ur cellerna fylls dessa med luft vilket ger ett silverskimrande utseende. Bladen kan deformeras p.g.a. att cellerna kollapsar efter utsugningen. Därefter kan nekros bildas och den skadade växtdelen vissnar och blir brun. På bladen kan man se djurens exkrementer som svarta prickar. Skadorna syns inte förrän den skadade växtdelen nått sitt slutstadium (efter sträckningstillväxt och öppning av blad och blommor). Förebyggande arbete och noggrann övervakning av odlingen underlättar, så att man på ett tidigt stadium kan sätta in rätt bekämpningsmetod innan insekten har hunnit utveckla en stor population. Speciellt biologisk bekämpning är svår att använda eftersom Frankliniella occidentalis har en snabb utvecklingscykel och uppförökningen av nyttodjuren vanligtvis inte hinner med. Kemisk bekämpning är också svår att använda eftersom F. occidentalis snabbt utvecklar resistens. Frankliniella occidentalis och gerbera har samma temperaturoptimum och det är därför svårt att använda temperaturen ur bekämpningssynvinkel. Vid låga temperaturer utvecklas Frankliniella occidentalis långsammare och gerberaplantorna blir småvuxna och vegetativa Hög temperatur gynnar den amerikanska blomtripsen, medan gerberaplantorna blir storvuxna och lösa. För hög luftfuktighet skadar både gerbera och F. occidentalis. Gerbera kan drabbas av vissnesjuka och börja ruttna, medan tripsen kan fastna i kondensvattnet. Pollentillgången är en viktig faktor för hur snabbt den amerikanska blomtripsen förökar sig, ju mer pollen desto snabbare. Många knoppar och unga blad är positivt för Frankliniella occidentalis, liksom blommande plantor. Förebyggande arbete med sanering, kontroll och framförhållning i växthuset med exempelvis klisterfällor och god hygien, är steg i rätt riktning för att kunna minska angreppen. Det behövs mer kunskap om det biologiska samspelet mellan värdväxten och skadedjuret för att hitta nya bekämpningsåtgärder

Making Sense of the Sustainable Smart PSS Value Proposition

While academia attributes superior value potential to sustainable smart PSS (SSPSS), in practice, they are not widely implemented. To address this gap, we analyze how the notion of SSPSS value is constructed through sensemaking. Adopting a case study approach, we explore differences in organizational sensemaking. Moreover, we analyze how the three functional roles “digital innovation and technology”, “sustainability”, and “market” involved in innovating SSPSS make sense of the value proposition. We conclude that value is subjective and the value proposition of SSPSS is multi-faceted. Each facet is constructed through the interaction of organizational, functional roles’, and individual sensemaking. At the organizational level, commitment, identity, and expectations influence the creation of shared meaning. At the functional role level, actors differ in their sensemaking based on the cognitive frames applied. At the individual level, subjective beliefs impact sensemaking. Hence, sensemaking is a multi-level process that raises the question of alignment

DECISION SUPPORT FOR SELECTING AN APPLICATION LANDSCAPE INTEGRATION STRATEGY IN MERGERS AND ACQUISITIONS

Mergers and Acquisitions (M&A) represent a powerful strategic instrument increasingly applied in today\u27s business environment. Besides juridical, financial, and organizational challenges, it is crucial to rapidly integrate the existing application landscapes in order to capitalize the aspired synergies. Literature documents four commonly agreed strategies: \u27best-of-breed\u27, \u27absorption\u27, \u27co-existence\u27, and \u27new-build\u27. However, no consolidated set of criteria exists to ease the selection of an integration strategy most suitable for the merger or the acquisition. Based on the results of a literature study, this paper proposes four integration profiles enabling a structured decision support for selecting the appropriate application landscape strategy during M&A. Each profile comprises relevant driving factors and resulting consequences as selection criteria. The identified literature statements regarding the criteria are validated by means of 12 confirmatory interviews with M&A experts. Furthermore, collected findings from an additional exploratory interview part with the practitioners complement the devised strategy profiles

«Sister Mary Joseph’s nodule»

Der «Sister Mary Joseph’s nodule» (SMJN) ist ein umbilikaler Knoten, der als Hautmetastase eines intraabdominalen oder pelvinen Karzinoms auftreten kann. Er wurde 1928 erstmalig durch den amerikanischen Chirurgen, Dr. W. J. Mayo (1861–1939), beschrieben. Namensgeberin war seine Operationsassistentin Sister Mary Joseph Dempsey, die ihn auf die umbilikale Veränderung aufmerksam machte [1]. Meist tritt die Metastase im Spätstadium der zugrunde liegenden Tumorerkrankung auf. Sie kann sich allerdings auch als erstes klinisch fassbares Symptom manifestieren

Dealing with negative stereotypes in sports: the role of cognitive anxiety when multiple identities are activated in sensorimotor tasks

Based on research on stereotype threat and multiple identities, this work explores the beneficial effects of activating a positive social identity when a negative identity is salient on women’s performance in sports. Further, in line with research on the effects of anxiety in sports, we investigate whether the activation of a positive social identity buffers performance from cognitive anxiety associated with a negative stereotype. Two experiments tested these predictions in field settings. Experiment 1 (N = 83) shows that the simultaneous activation of a positive (i.e., member of a soccer team) and a negative social identity (i.e., woman) led to better performance than the activation of only a negative social identity for female soccer players. Experiment 2 (N = 46) demonstrates that identity condition moderated the effect of cognitive anxiety on performance for female basketball players. Results are discussed concerning multiple identities’ potential for dealing with stressful situations

Chimeric antigen receptor T cell-based targeting of CD317 as a novel immunotherapeutic strategy against glioblastoma

BACKGROUND: Chimeric antigen receptor (CAR) T cell therapy has proven to be successful against hematological malignancies. However, exploiting CAR T cells to treat solid tumors is more challenging for various reasons including the lack of suitable target antigens. Here, we identify the transmembrane protein CD317 as a novel target antigen for CAR T cell therapy against glioblastoma, one of the most aggressive solid tumors. METHODS: CD317-targeting CAR T cells were generated by lentivirally transducing human T cells from healthy donors. The anti-glioma activity of CD317-CAR T cells toward various glioma cells was assessed in vitro in cell lysis assays. Subsequently, we determined the efficacy of CD317-CAR T cells to control tumor growth in vivo in clinically relevant mouse glioma models. RESULTS: We generated CD317-specific CAR T cells and demonstrate strong anti-tumor activity against several glioma cell lines as well as primary patient-derived cells with varying CD317 expression levels in vitro. A CRISPR/Cas9-mediated knockout of CD317 protected glioma cells from CAR T cell lysis, demonstrating the target specificity of the approach. Silencing of CD317 expression in T cells by RNA interference reduced fratricide of engineered T cells and further improved their effector function. Using orthotopic glioma mouse models, we demonstrate the antigen-specific anti-tumor activity of CD317-CAR T cells, which resulted in prolonged survival and cure of a fraction of CAR T cell-treated animals. CONCLUSIONS: These data reveal a promising role of CD317-CAR T cell therapy against glioblastoma, which warrants further evaluation to translate this immunotherapeutic strategy into clinical neuro-oncology

Potency assay to predict the anti-inflammatory capacity of a cell therapy product for macrophage-driven diseases: Overcoming the challenges of assay development and validation

Background: Given the high level of product complexity and limited regulatory guidance, designing and implementing appropriate potency assays is often the most challenging part of establishing a quality control testing matrix for a cell-based medicinal product. Among the most elusive tasks are the selection of suitable read-out parameters, the development of assay designs that most closely model the pathophysiological conditions, and the validation of the methods. Here we describe these challenges and how they were addressed in developing an assay that measures the anti-inflammatory potency of mesenchymal stromal cells (MSCs) in an M1 macrophage-dominated inflammatory environment. Methods: An in vitro inflammation model was established by coculturing skin-derived ABCB5+ MSCs with THP-1 monocyte-derived M1-polarized macrophages. Readout was the amount of interleukin 1 receptor antagonist (IL-1RA) secreted by the MSCs in the coculture, measured by an enzyme-linked immunosorbent assay. Results: IL-1RA was quantified with guideline-concordant selectivity, accuracy and precision over a relevant concentration range. Consistent induction of the macrophage markers CD36 and CD80 indicated successful macrophage differentiation and M1 polarization of THP-1 cells, which was functionally confirmed by release of proinflammatory tumor necrosis factor . Testing a wide range of MSC/macrophage ratios revealed the optimal ratio for near-maximal stimulation of MSCs to secrete IL-1RA, providing absolute maximum levels per individual MSC that can be used for future comparison with clinical efficacy. Batch release testing of 71 consecutively manufactured MSC batches showed a low overall failure rate and a high comparability between donors. Conclusions: We describe the systematic development and validation of a therapeutically relevant, straightforward, robust and reproducible potency assay to measure the immunomodulatory capacity of MSCs in M1 macrophage-driven inflammation. The insights into the challenges and how they were addressed may also be helpful to developers of potency assays related to other cellular functions and clinical indications

S100A9 is indispensable for survival of pneumococcal pneumonia in mice

S100A8/A9 has important immunomodulatory roles in antibacterial defense, but its relevance in focal pneumonia caused by Streptococcus pneumoniae (S. pneumoniae) is understudied. We show that S100A9 was significantly increased in BAL fluids of patients with bacterial but not viral pneumonia and correlated with procalcitonin and sequential organ failure assessment scores. Mice deficient in S100A9 exhibited drastically elevated Zn$^{2+}$ levels in lungs, which led to bacterial outgrowth and significantly reduced survival. In addition, reduced survival of S100A9 KO mice was characterized by excessive release of neutrophil elastase, which resulted in degradation of opsonophagocytically important collectins surfactant proteins A and D. All of these features were attenuated in S. pneumoniae-challenged chimeric WT→S100A9 KO mice. Similarly, therapy of S. pneumoniae-infected S100A9 KO mice with a mutant S100A8/A9 protein showing increased half-life significantly decreased lung bacterial loads and lung injury. Collectively, S100A9 controls central antibacterial immune mechanisms of the lung with essential relevance to survival of pneumococcal pneumonia. Moreover, S100A9 appears to be a promising biomarker to distinguish patients with bacterial from those with viral pneumonia. Trial registration: Clinical Trials register (DRKS00000620)

A T-cell antigen atlas for meningioma: novel options for immunotherapy

Meningiomas are the most common primary intracranial tumors. Although most symptomatic cases can be managed by surgery and/or radiotherapy, a relevant number of patients experience an unfavorable clinical course and additional treatment options are needed. As meningiomas are often perfused by dural branches of the external carotid artery, which is located outside the blood-brain barrier, they might be an accessible target for immunotherapy. However, the landscape of naturally presented tumor antigens in meningioma is unknown. We here provide a T-cell antigen atlas for meningioma by in-depth profiling of the naturally presented immunopeptidome using LC-MS/MS. Candidate target antigens were selected based on a comparative approach using an extensive immunopeptidome data set of normal tissues. Meningioma-exclusive antigens for HLA class I and II are described here for the first time. Top-ranking targets were further functionally characterized by showing their immunogenicity through in vitro T-cell priming assays. Thus, we provide an atlas of meningioma T-cell antigens which will be publicly available for further research. In addition, we have identified novel actionable targets that warrant further investigation as an immunotherapy option for meningioma