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Background: The gene encoding the extracellular matrix (ECM) protease ADAMTS-7 was associated with coronary artery disease (CAD) in genome-wide association studies. ADAMTS-7 is expressed at all stages in human plaques and mice lacking Adamts-7 displayed reduced atherosclerotic plaque formation. While these findings render ADAMTS-7 a promising therapeutic target, the underlying mechanisms remain unknown. Methods and Results: Here, we sought to identify downstream mechanisms of ADAMTS-7 in atherosclerotic plaque formation. Targets of Adamts-7 were identified by high-resolution mass spectrometry of atherosclerotic plaques in Apoe-/- and Apoe-/-Adamts7-/- mice. ECM proteins were identified using solubility profiling. The endogenous inhibitor of matrix metalloproteinases (MMP) Timp-1 was identified as a novel target of Adamts-7. Adamts-7 and Timp-1 were found to be co-localized in atherosclerotic plaques and co-immunoprecipitation (Co-IP) studies revealed TIMP-1 as the first putative target to bind to the catalytic domain of ADAMTS-7. In vitro degradation assays demonstrated that ADAMTS-7 degrades TIMP-1. Co-IP furthermore revealed less binding of TIMP-1 to its canonical target MMP-9 when ADAMTS-7 was present. In line, scaffolding and degradation of TIMP-1 by ADAMTS-7 impaired TIMP-1-mediated inhibition of MMP-9 in vitro. As a downstream mechanism, we investigated collagen content in atherosclerotic plaques of Apoe-/- and Apoe-/- Adamts7-/- mice after Western diet. Collagen stainings of the aortic root revealed less collagen as a readout of higher MMP-9 activity in Apoe-/- as compared to Apoe-/- Adamts7-/- mice. Since ADAMTS-7 might exert its pro-atherogenic effects through interaction with TIMP-1, we established a TIMP-1-ADAMTS-7-interaction assay based on Förster resonance energy transfer (FRET) to identify inhibitors of this protein-protein interaction. Conclusion and Outlook: TIMP-1 represents a novel downstream target of ADAMTS-7 that can explain the role of this novel risk factor in CAD. Our FRET-based protein-protein interaction assay may be used for high-throughput screening to identifiy inhibitors and prevent the initiation or slow the progression of atherosclerosis.

Studies argue that generalist CEOs are more valued by the market for executive labor and receive higher initial compensation. Challenging this prevailing assumption, we acknowledge the drawbacks of extensive career mobility and predict an inverted U-shape relationship between CEO generalist career experience and CEO initial compensation. Integrating the generalism and specialization views of human capital, we postulate that at an initial level, the acquisition of experience breadth from different firms and industries enables CEOs to broaden their knowledge base, obtain a variety of skills, and thus increase their labor market value and initial compensation. After a threshold, however, the accumulation of extensive levels of career generalism through frequent job hopping across firm and industry contexts gradually causes a lack of experience depth and insufficient career specialization, thereby triggering lower CEO market value and initial pay. Data from 197 CEO appointments in large, publicly traded firms support our predictions. Our results also show that the observed inverted U-shape relationship varies with factors nested at different layers of context, highlighting the contingent nature of this area of research.

UNSTRUCTURED Major depressive episode (MDE) is a common clinical syndrome. It can be found in different pathologies such as mood depressive disorder (MDD), bipolar disorder (BD), post-traumatic stress disorder (PTSD) or even occur in a context of psychotrauma. However, only one syndrome is described in international classifications (DSM 5/ICD 11) which do not take into account the underlying pathology at the origin of the MDE. Clinical interviews are currently the best source of information to obtain the etiological diagnosis of MDE. Nevertheless, it does not allow an early diagnosis and there are no objective measures of extracted clinical information. To remedy this, the use of digital tools and their correlation with clinical symptomatology seems promising. We review the state of the art on the use of digital tools during clinical interviews for etiological diagnosis of MDE. For this purpose, we were interested in four frequently found clinical conditions in which MDE can occur: MDD, BD, PTSD and/or trauma investigated by the means of automated voice analysis, behaviour analysis by video and physiological measures by heart rate variability (HRV) and electrodermal activity (EDA). This paper gives a detailed overview of studies on different digital markers associated with MDE which could be useful for differential diagnosis. A digital phenotype of MDE seem to emerge consisting of modifications in speech features (namely temporal, prosodic, spectral, sources, formants and in speech content), modifications in nonverbal behaviour (Head, hand, body and eyes movement, facial expressivity and gaze) and a decrease in physiological measurements (HRV and EDA). We found similarities but also differences when MDE occur in MDD, BD or PTSD. However, comparative studies were rare in BD or PTSD conditions which do not allow us to identify clear and distinct digital phenotypes. Our search identifies markers from several modalities that hold promise for an objective etiological diagnosis of MDE. To validate their potential, further longitudinal and prospective studies are needed.

Pigments with nanoscale dimensions are added to exterior coatings to achieve desirable color and gloss properties. The present study compared the performance, degradation, and release behavior of an acrylic coating that was pigmented by a nanoform of Cu-phthalocyanine after both natural (i.e., outdoor) and accelerated weathering. Samples were weathered outdoors in three geographically distinct locations across the United States (Arizona, Colorado, Maryland) continuously for 15 months. Identically prepared samples were also artificially weathered under accelerated conditions (increased ultraviolet (UV) light intensity and elevated temperatures) for three months, in one-month increments. After exposure, both sets of samples were characterized with color, gloss, and infrared spectroscopy measurements, and selectively with surface roughness measurements. Results indicated that UV-driven coating oxidation was the principal degradation pathway for both natural and accelerated weathering samples, with accelerated weathering leading to an increased rate of oxidation without altering the fundamental degradation pathway. The inclusion of the nanoform pigment reduced the rate of coating oxidation, via UV absorption by the pigment, leading to improved coating integrity compared to non-pigmented samples. Release measurements collected during natural weathering studies indicated there was never a period of weathering, in any location, that led to copper material release above background copper measurements. Lab-based release experiments performed on samples weathered naturally and under accelerated conditions found that the release of degraded coating material after each type of exposure was diminished by the inclusion of the nanoform pigment. Release measurements also indicated that the nanoform pigment remained embedded within the coating and did not release after weathering.

One of the main uses of nanomaterials (NMs) is as functional fillers embedded in solid matrices, such as plastics, tires and coatings. Such products, named nano-enabled products (NEPs), are widely manufactured and employed. However, the risk assessment of NEPs can be very challenging for industries and regulatory agencies because each NM can display great dissimilarities in their physicochemical properties (e.g. size, surface area, crystalline phase, surface chemistry, impurity content). To comply with the current and future nanosafety requirements, an excessive number of case-by-case studies should be performed for a large number of nanoforms. To achieve a cost-efficient risk assessment approach, it is crucial to define a grouping strategy for NMs. In this work, we evaluated the nanoparticle release, after aging, from two typical automotive coatings (acrylic and melamine coatings), incorporating three widely used (nano)forms of pigments (diketopyrrolopyrrole, Cu-phthalocyanine and iron oxide). The results of this study show how different characteristics of the pigments marginally influence the particle emission and the degradation of the coating, supporting a grouping strategy for NMs sharing the same matrix and intended use.

Are new CEOs with diverse career experience more likely to promote strategic change early after their appointment? We attempt to address this question by integrating seemingly opposing predictions in the managerial cognition literature. We argue that new CEOs with high and low levels of intra-personal experience diversity will promote higher strategic change early after taking charge – compared to those at relatively moderate levels. Analyzing 115 CEO successions, we find support for the theorized U-shaped relationship between intra-personal CEO experience diversity and strategic change. Furthermore, our results suggest that this relationship is influenced by post-CEO-succession TMT turnover. We contribute to the literature on strategic change by adding a more nuanced perspective to the emerging research on new CEO career experience diversity, and its effects on corporate strategy.

Signal transduction in bacteria is generally mediated via two-component systems. These systems depend on the transfer of a phosphate molecule from a donor to an acceptor by histidine kinases, thereby activating the acceptor to allow downstream signaling/activation. Several bacterial genomes, including the genome of M. tuberculosis, were shown to encode eukaryotic-like kinases. To better understand the function of these kinases and the regulatory networks within which they operate, identification of downstream targets is essential. We here present a straightforward approach for the identification of bacterial Ser/Thr-kinase substrates. This approach is based on the KESTREL (Kinase Tracking and Substrate Elucidation) procedure combined with reversed-phase chromatography and two-dimensional gel electrophoresis. Using this method, GarA was identified as one potential substrate for the mycobacterial Ser/Thr-protein kinase G (PknG). These results show that the modified KESTREL approach can be successfully employed for the identification of substrates for bacterial Ser/Thr-kinases.

Significance Cancer immunotherapy demonstrates clinical efficacy in selected cancer types. Yet, as the majority of patients do not respond to the most effective immunotherapeutics, novel immunotherapy combinations are extensively investigated. There is increasing clinical interest in combining cancer immunotherapies with antiangiogenic agents, particularly VEGFA pathway inhibitors. Here we show that anti-CD40 immunotherapy increases CD8+ T cell infiltration in the tumor, yet tumor regression is achieved more robustly when anti-CD40 is combined with dual Ang2 and VEGFA blockade, but not VEGFA inhibition alone. Tumor regression was associated with proinflammatory skewing of the tumor microenvironment and intratumoral redistribution of CD8+ T cells. These data emphasize the rationale for blocking Ang2 as a vascular-modulatory strategy in combination with T cell-targeting immunotherapies., Cancer immunotherapies are increasingly combined with targeted therapies to improve therapeutic outcomes. We show that combination of agonistic anti-CD40 with antiangiogenic antibodies targeting 2 proangiogenic factors, vascular endothelial growth factor A (VEGFA) and angiopoietin 2 (Ang2/ANGPT2), induces pleiotropic immune mechanisms that facilitate tumor rejection in several tumor models. On the one hand, VEGFA/Ang2 blockade induced regression of the tumor microvasculature while decreasing the proportion of nonperfused vessels and reducing leakiness of the remaining vessels. On the other hand, both anti-VEGFA/Ang2 and anti-CD40 independently promoted proinflammatory macrophage skewing and increased dendritic cell activation in the tumor microenvironment, which were further amplified upon combination of the 2 treatments. Finally, combined therapy provoked brisk infiltration and intratumoral redistribution of cytotoxic CD8+ T cells in the tumors, which was mainly driven by Ang2 blockade. Overall, these nonredundant synergistic mechanisms endowed T cells with improved effector functions that were conducive to more efficient tumor control, underscoring the therapeutic potential of antiangiogenic immunotherapy in cancer.

In addition of being directly tumoricidal, oncolytic viruses have emerged as potent partners for established and investigational immunotherapies due to their immune-stimulatory effects. The shifting focus on virus-mediated immune modulation calls for a comprehensive analysis of the tumor microenvironment (TME) and the factors orchestrating the antiviral and antitumor immune response. The oncolytic VSV-GP studied in our lab is a safe and potent antitumor agent with a fast replication cycle and killing of a broad range of different cancer types. It induces a robust local inflammatory conversion of the TME and drives a strong adaptive immune response toward the tumor. Here we present our multidisciplinary approach to study VSV-GP treatment effects in tumors by assessing both immune cells (tumor-infiltrating lymphocytes and tumor-associated macrophages) and immune-regulatory factors (cytokines) as well as characterizing immune signatures using an immune-targeted NanoString gene expression system.

In addition of being directly tumoricidal, oncolytic viruses have emerged as potent partners for established and investigational immunotherapies due to their immune-stimulatory effects. The shifting focus on virus-mediated immune modulation calls for a comprehensive analysis of the tumor microenvironment (TME) and the factors orchestrating the antiviral and antitumor immune response. The oncolytic VSV-GP studied in our lab is a safe and potent antitumor agent with a fast replication cycle and killing of a broad range of different cancer types. It induces a robust local inflammatory conversion of the TME and drives a strong adaptive immune response toward the tumor. Here we present our multidisciplinary approach to study VSV-GP treatment effects in tumors by assessing both immune cells (tumor-infiltrating lymphocytes and tumor-associated macrophages) and immune-regulatory factors (cytokines) as well as characterizing immune signatures using an immune-targeted NanoString gene expression system.

Ground Calcium Carbonate (GCC) has been used for decades in construction to enhance performance-cost ratio of cement-based products such as grout, mortar or concrete. From dry-mortars to structural concrete, engineers associate GCC with cementitious materials (SCM) to optimize the fluidity, viscosity and reduce the carbon footprint of the mixtures. Nevertheless, the contribution of GCC to the flowability and viscosity of the cement-based systems as well as the range of GCC fineness available to optimize the packing density and strength are poorly appreciated. The benefits of specific GCC products are expected to be particularly useful in formulating concrete or mortar for digital fabrication. This paper will provide an overview of the best practice use of GCC products, aiming to stimulate interest for the material not only for use in digital fabrication with concrete.

A series of supported two- and three-dimensional vanadium oxide surface species on β-SiC with various V coverages are prepared via incipient wetness impregnation and characterized by a variety of ex and in situ techniques. The oxidative dehydrogenation of propane (ODHP) is also used as a probe reaction to complementarily distinguish between two- and three-dimensional VOx surface species. Herein, we show that treating pristine β-SiC with oxygen transforms the existing amorphous SiOxCy surface layer into a more SiO2-type layer, though with a negligible formation of Si–OH sites, which initially were expected to be the anchor sites for VOx species. In its place, the C–OH functional groups identified by X-ray photoelectron spectroscopy (XPS) act as anchor sites for the VOx species during the impregnation process, and are consumed as a function of V coverage. Our experimental observations all corroborate the formation of two- and three-dimensional VOx species on the surface of β-SiC.

Boron nitride catalysis Propene is one of the highest-volume organic chemicals produced. Propene has mainly been made from naphtha, but changes in the global supply chain are creating shortages. Direct conversion from propane, a component of natural gas, via reaction with oxygen is an attractive alternative, but existing approaches produce a large fraction of unwanted CO and CO 2 . Grant et al. report that boron nitride, normally an unreactive material, has high selectivity to catalyze the production of propene (77%) and ethene (13%). Science , this issue p. 1570

Introduction Oncolytic viruses (OVs), which selectively replicate in and destroy tumor cells, represent a highly promising class of cancer therapeutics with a strong immune stimulatory potential. VSV-GP, a chimeric Vesicular Stomatitis Virus (VSV) pseudotyped with the glycoprotein of the lymphocytic choriomeningitis virus (LCMV) is a potent tumor cell-lysing agent and capable of jump-starting α-tumor immunity. The current study explores the immune promoting properties of VSV-GP and one of its cargo-armed, next generation variants with a T-cell/DC-directed MoA. It further investigates clinically relevant combination therapies with checkpoint inhibition (α-PD-1) as well as a “second mitochondria-derived activator of caspases“ mimetic (SMACm). Experimental Procedures Immune competent mice bearing established LLC1-IFNARKO, B16-F1-OVA or CT26.CL25-IFNARKO tumors were subject to treatments comprising VSV-GP variants, α-PD-1, a SMACm or combinations of the latter. Anti-tumor effects were determined by tumor growth inhibition and/or changes in overall survival. VSV-GP´s tumor cell selective replication, resulting in immune activation as well as cargo mediated immune modulation, were assessed using FFPE based IHC staining as well as NanoString and functional in vitro assays. Data Summary Here we present data on VSV-GP and one of its improved, next generation variants, which display potent α-tumor efficacy and upon systemic delivery increase the local T-cell and dendritic cell infiltration as well as activation within the tumor microenvironment. Building on the observed therapeutic and immune-modulatory potential of VSV-GP and its cargo-armed variant, we further explored therapeutic combinations with a PD-1 blocking antibody, which resulted in a strong improvement of the VSV-GP-mediated α-tumor efficacy. Immunological memory formation in cured animals was demonstrated by a tumor rechallange experiment. We further explored the therapeutic combination of VSV-GP and its cargo-bearing variant with a SMACm, which resulted in a strongly improved therapeutic benefit as well as increased overall survival in case of VSV-GP. The VSV-GP encoded immune-stimulatory cargo further improved this therapeutic synergy. Conclusion In summary VSV-GP induces a pro-inflammatory microenvironment within infected tumors, increases immune cell infiltration, a feature, which is further improved by tumor selective expression of VSV-GP encoded therapeutic cargos, and synergizes with α-PD-1 as well as a SMACm. The strong α-tumor immunity promoting potential of the VSV-GP platform observed in preclinical disease models justifies further testing of VSV-GP variants and the respective therapeutic combinations in clinical trials. Citation Format: Philipp Mueller, Tobias Nolden, Klaus Erb, Monika Petersson, Brigit Stierstorfer, Fabian Heinemann, Valerie Laura Herrmann, Maria Antonietta Impagnatiello, Eric Borges, Knut Elbers, John Park, Guido Wollmann, Patrik Erlmann. Therapeutic potential of cargo-armed next generation variants of VSV-GP and synergy with immune modulators [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4450.

Studies show that generalist CEOs with high levels of career variety receive higher compensation. Challenging this prevailing assumption, we acknowledge the drawbacks of extensive levels of CEO career variety and predict an inverted U-shaped relationship between CEO career variety and CEO initial compensation. Integrating the generalism and specialization views of human capital, we postulate that, at an initial stage, the merits of increasingly varied human capital increase a CEO’s value and hence promote higher levels of compensation. After a threshold, however, the drawbacks associated with extensive levels of career variety offset its merits, gradually diminishing CEO value and pay.

Evaluation in spatial planning aims to raise effectiveness of plans as well as efficiency in planning processes. Given that research regarding evaluation of performance and especially plan implementation is sparse, this study presents a minimal set of indicators for a task-sheet based performance evaluation approach for Swiss cantonal comprehensive plans. Thematic task-sheets are a promising characteristic of cantonal comprehensive plans. They translate the comprehensive planning strategy into concrete evaluable tasks. The presented indicators allow assessing procedural efficiency of coordination and implementation of planning tasks (performance). We argue that if task-sheets comply with certain plan quality characteristics, a task-sheet based performance evaluation approach can support the effectiveness of plans and promote the objectives of the planning strategy. We point out plan content and characteristics necessary for effective execution of our approach. As a result, our findings can serve as a fram...

Background Oncolytic viruses (OV) induce potent antitumor treatment effects not only via direct tumour infection and lysis but also via activation of innate and adaptive immune responses. As such, they show strong synergism in combination with various immunotherapy strategies. Here we address the question to what extend intratumoral viral replication of the vesicular stomatitis virus variant VSV-GP affects the tumour microenvironment of three different syngeneic mouse tumour models B16, TRAMP and LLC. Methods To model tumours with higher permissivity for OVs we generated interferon receptor deficient cells (TRAMP-IFNAR1-/- and LLC1-IFNAR1-/-). Bio-luminescent imaging was used to assess intratumoral virus propagation. Efficacy of VSV-GP was assessed in vivo in syngeneic C57BL/6 mice. The tumour micro environment was studied using flow cytometry, histology, multiplex cytokine ELISA and NanoString® transcriptome analysis. Results Intratumoral viral propagation was enhanced in the IFNAR1-/- tumours compared to B16. In LLC1-IFNAR1-/- tumours, VSV-GP treatment resulted in significant upregulation of over 300 immune-related genes, increase in tumour infiltrating lymphocytes and expression of pro-inflammatory cytokines. In contrast, immune activation markers in virus replication-restricted B16 tumours were only slightly increased. Yet, based on transcriptional analysis, we found a common VSV-GP treatment-associated immune gene signature. Furthermore, we have observed that VSV-GP induces an up-regulation of inflammatory cytokines in all tumour models, such as type-I IFN, IFN-γ and TNF-α, which correlates with an increase of the T-cell infiltration in the tumour. Other cytokines, such as IL-6 or IL-10, were found to be differently regulated depending on the model. Conclusion In conclusion, we present a number of immune-activating consequences of virotherapy treatment in syngeneic tumour models with varying degree of virus propagation. Higher virus activity in the tumour qualitatively and quantitatively shapes the tumour microenvironment differently compared to tumours with restricted virus activity. Legal entity responsible for the study The authors. Funding Christian Doppler Research Association. Disclosure G. Wollmann: Advisory / Consultancy, Research grant / Funding (self): Boehringer Ingelheim. B. Spiesschaert: Full / Part-time employment: Boehringer Ingelheim. P. Erlmann: Full / Part-time employment: Boehringer Ingelheim. B. Stierstorfer: Full / Part-time employment: Boehringer Ingelheim. D. von Laer: Advisory / Consultancy: Boehringer Ingelheim; Shareholder / Stockholder / Stock options, Licensing / Royalties: ViraTherapeutics. P. Mueller: Full / Part-time employment: Boehringer Ingelheim. All other authors have declared no conflicts of interest.

This study develops a multilevel framework examining the relationship between CEO generalist career experience and initial compensation. Drawing on the generalist and specialization views of human ...

Introduction: Oncolytic viruses (OVs), which selectively replicate in and destroy tumor cells, represent a highly promising class of cancer therapeutics. In recent years, the focus in the OV field has significantly shifted from a pure oncolytic mode of action to their strong immune stimulatory potential. Tumor cells lysed by the viruses release pro-inflammatory signals, tumor associated antigens as well as display hallmarks of immunogenic cell death. VSV-GP, a chimeric VSV pseudotyped with the glycoprotein of the lymphocytic choriomeningitis virus (LCMV) is a potent tumor cell-lysing agent and capable of jump-starting α-tumor immunity. The current study explores the immune promoting properties of VSV-GP and investigates clinically relevant combination therapies with checkpoint inhibition (α-PD-1) as well as a “second mitochondria-derived activator of caspases“ mimetic (SMACm). Experimental Procedures: Immune competent mice bearing established LLC1-IFNARKO, B16-F1-OVA or CT26.CL25-IFNARKO tumors were subject to treatments comprising VSV-GP, α-PD-1, a SMACm or combinations of VSV-GP with either of the latter therapies. α-tumor effects were determined by tumor growth inhibition and/or changes in overall survival. VSV-GP's tumor cell selective replication, resulting in immune activation, was assessed using FFPE based IHC staining for the viral N-protein, PD-L1 and different immune cell subsets as well as the NanoString platform (nCounter Pan Cancer Immune Profiling Panel). Data Summary: Here we present data on VSV-GP, which displays potent α-tumor efficacy and upon systemic delivery increases the local T-cell infiltration, expression of chemokines, T-cell and myeloid cell specific activation markers as well as expression of immune checkpoints, such as PD-1 and PD-L1 within the tumor microenvironment. Building on the observed therapeutic potential of VSV-GP as monotherapy, its immune promoting properties and the delineated compensatory mechanisms, such as PD-1/-L1 upregulation, we explored therapeutic combinations with a PD-1 blocking antibody, which resulted in a strong improvement of VSV-GP-mediated α-tumor efficacy as well as overall survival. Cured, tumor free animals were protected from tumor rechallange indicating immunological memory formation. We further explored the therapeutic combination of VSV-GP with a SMACm, which also resulted in a strongly improved therapeutic benefit and increased overall survival. Conclusion: In summary VSV-GP induces a pro-inflammatory microenvironment within infected tumors, increases immune cell infiltration and synergizes with α-PD-1 as well as a SMACm. VSV-GP is a potent OV with a strong α-tumor immunity promoting potential. Preclinical data justify further testing of VSV-GP and the combinations with PD-1 blockade or a SMACm in clinical trials. Citation Format: Philipp Mueller, Patrik Erlmann, Monika Petersson, Tobias Nolden, Carles Urbiola, Liesa-Marie Schreiber, Bart Spiesschaert, Klaus Erb, Birgit Stierstorfer, Maria Antonietta Impagnatiello, Eric Borges, Knut Elbers, Guido Wollmann, John Park. Therapeutic synergy of the chimeric, oncolytic virus VSV-GP with immune modulators [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2267.

In this contribution, we compare the optical absorbance behaviour and the structural properties of lead(II)-phthalocyanine (PbPc) and tin(II)-phthalocyanine (SnPc) thin films. To this end, we employ a Ag(1 1 1) substrate terminated with a monolayer of 3,4,9,10-perylene tetracarboxylic dianhydride constituting an internal interface whose main effect is an electronic decoupling of the phthalocyanine adlayer from the metal surface. As deduced from low-energy electron diffraction and scanning tunnelling microscopy (STM) measurements, the epitaxial relations and unit cell compositions of the prevailing PbPc monolayer and multilayer domains are confusingly similar to those of SnPc on PTCDA/Ag(1 1 1). However, SnPc and PbPc can be readily distinguished by their STM-induced switching behaviours: while the former is capable of reversible configurational changes, no effect on the latter could be achieved by us under comparable conditions. This corroborates earlier theoretical predictions and even renders the chemical identification of individual shuttlecock-shaped metal-phthalocyanines feasible.

Background The incidence of allergic rhinitis (AR) has increased constantly over the last decades. The disease can significantly lower quality of life and subsequently might progress to allergic asthma. Allergen-specific immunotherapy is mostly used to cope with the cause of the disease. However, incidence of systemic reactions or limited compliance hampers the widespread use of this therapeutic approach. Therefore, new candidates are examined to improve immunotherapy of allergies. Recently, a new technology was developed with the aim to positively influence the immune system of allergic patients. Virus-like particles (VLPs) represent a potent vaccine platform that has been proven to be immunogenic and clinically effective. To enhance immune cell activation, addition of Toll-like receptor ligands and/or depot-forming adjuvants seems to be helpful. In this context, CpG motifs represent intensive investigated and potent stimulators of T cells. This article focuses on the function of VLPs and CpG motifs and their clinical experience for treatment of AR. Methods A literature review was performed. Results Several published studies showed a beneficial impact of the treatment on allergic symptoms. They tested VLPs filled with or without CpG motifs in combination with or without allergen. Conclusion Results encourage further investigations of VLPs and CpG motifs as adjuncts to or even alternative candidates for immunotherapy of allergic disorders.

BACKGROUND: Allergen-specific TH2 responses contribute to the development of allergic asthma. Their increase may be due to a reduced early exposure to environmental pathogens, which induces a TH1 response, and thereby suppresses the allergic TH2 response. QbG10 (bacteriophage Qbeta-derived virus-like particle with CpG-motif G10 inside), a novel Toll-like receptor 9 agonist packaged into virus-like particles, was designed to stimulate the immune system toward a TH1-mediated protective response. OBJECTIVE: We examined clinical efficacy, safety, and tolerability of QbG10 with patient-reported and objective clinical outcome parameters in patients with mild-to-moderate persistent allergic asthma. METHODS: In this proof-of-concept parallel-group, double-blind, randomized trial, 63 asthmatic patients followed conversion to a standardized inhaled steroid and were treated with 7 injections of either QbG10 or placebo. Incorporating a controlled steroid withdrawal, the effects on patient-reported (day- and nighttime asthma symptoms, salbutamol usage, and 7-item-Asthma Control Questionnaire scores) and objective clinical outcome measures (FEV1, fraction of exhaled nitric oxide, and blood eosinophils) were assessed over 12 weeks (ClinicalTrials.gov number, NCT00890734). RESULTS: All patient-reported parameters improved overall between week 0 and 12 in QbG10-treated patients (n = 33) despite steroid withdrawal, compared with deteriorations observed under placebo (n = 30, P < .05). At week 12, two thirds of the QbG10-treated patients had their asthma "well controlled" (Asthma Control Questionnaire score ≤0.75) compared with one third under placebo. FEV1 had worsened to a clinically significant extent in patients on placebo, while it remained stable in QbG10 patients. Adverse events were mostly injection site reactions occurring after QbG10 administration. CONCLUSION: Treatment with QbG10 may contribute to continued asthma control during steroid reduction in patients on moderate or high-dose inhaled steroids.

The quest for advanced designer adsorbents for air filtration and monitoring hazardous trace gases has recently been more and more driven by the need to ensure clean air in indoor, outdoor, and industrial environments. How to increase safety with regard to personal protection in the event of hazardous gas exposure is a critical question for an ever-growing population spending most of their lifetime indoors, but is also crucial for the chemical industry in order to protect future generations of employees from potential hazards. Metal-organic frameworks (MOFs) are already quite advanced and promising in terms of capacity and specific affinity to overcome limitations of current adsorbent materials for trace and toxic gas adsorption. Due to their advantageous features (e.g., high specific surface area, catalytic activity, tailorable pore sizes, structural diversity, and range of chemical and physical properties), MOFs offer a high potential as adsorbents for air filtration and monitoring of hazardous trace gases. Three advanced topics are considered here, in applying MOFs for selective adsorption: (i) toxic gas adsorption toward filtration for respiratory protection as well as indoor and cabin air, (ii) enrichment of hazardous gases using MOFs, and (iii) MOFs as sensors for toxic trace gases and explosives.

This study addresses the debate concerning the performance implications of CEO experience variety. Some scholars take the generalist view of human capital to suggest that high CEO experience variety (i.e., generalism) is beneficial. Yet, others adopt the specialist view to highlight the advantages of human capital specialization. Integrating the opposing views, we argue that the relationship between CEO experience variety and firm performance follows an inverted U-shaped form. Initially, the acquisition of breadth of experience from different firms and industries builds human capital generalism – enabling CEOs to cope with the information processing demands of large firms and realize higher firm performance. After a threshold, however, extensive levels of CEO experience variety come in expense of experience depth and human capital specialization – resulting in declining firm performance. Data from 176 CEOs in large firms support the hypothesized relationship. Our results also show that this relationship varies with the firm’s level of internal and external complexity.

Meeting abstracts Antibody drug conjugates (ADCs) are emerging as powerful treatment strategies with outstanding target specificity and high therapeutic activity in cancer patients. Brentuximab vedotin represents a first-in-class ADC directed against CD30-positive malignancies. We hypothesised that

Correction for ‘Supported two- and three-dimensional vanadium oxide species on the surface of β-SiC’ by Carlos A. Carrero et al., Catal. Sci. Technol., 2017, DOI: 10.1039/c7cy01036b.