Search

Supplementary Methods and Results from Enigmol: A Novel Sphingolipid Analogue with Anticancer Activity against Cancer Cell Lines and In vivo Models for Intestinal and Prostate Cancer

Supplementary Figures 1-6 from Enigmol: A Novel Sphingolipid Analogue with Anticancer Activity against Cancer Cell Lines and In vivo Models for Intestinal and Prostate Cancer

Supplementary Material from Enigmol: A Novel Sphingolipid Analogue with Anticancer Activity against Cancer Cell Lines and In vivo Models for Intestinal and Prostate Cancer

Are democratic norms under pressure from social divisions in society? An emerging literature in political science examines if and when citizens condone undemocratic behaviors (Broockman, Kalla, & Westwood, 2022; Graham & Svolik, 2020; Krishnarajan, 2022; McCoy, Simonovits, & Littvay, 2020; Saikkonen & Christensen, 2023). Central to this question is who engages in these undemocratic behaviors. Earlier work has largely focused on democratic norm violations by political elites. Some of these studies find that citizens are willing to accept undemocratic behaviors by their in-group political elites if they or their party gain from it politically (Graham & Svolik, 2020; Kalmoe & Mason, 2022) while other studies remain more skeptical (Broockman et al., 2022). What happens if we focus on other highly salient social divisions in society? We shift our focus to the citizens level and study if, when, and why citizens support undemocratic behaviors by different social groups. We will run our experiment in the Netherlands. Over the past years, highly salient protests have erupted in the Netherlands. Farmers and climate activists, with their respective grievances, have protested against the current Cabinet’s climate policies using identical protest actions (e.g. vandalizing state property, obstructing highways). We leverage these similarities in a conjoint experiment that randomizes protesting social groups (farmers versus climate activists), protest actions, and the use of political violence. This allows us to estimate (i) how citizens respond to similar protest actions by different social groups (climate activists versus farmers) and (ii) if and when citizens are willing to support undemocratic behaviors, including the use of violence.

Over the last half-century, the world’s human population has doubled, impacting almost all ocean and land areas. The threats facing primates in the wild have never been greater or more complex. Primatologists have long been aware of these threats and, since the 1970s, have coordinated efforts to safeguard these threatened species, through the International Union for Conservation of Nature Species Survival Commission (IUCN SSC) Primate Specialist Group (PSG). In an effort to stem the threat of extinction to primates, this group of now 700 experts+ has published 17 conservation action plans since 1977. As we look toward the next half-century, we take stock of the history of primate action planning to better understand the costs and benefits of these plans as a conservation tool. Here, we reviewed all plans published by the IUCN SSC PSG. In total, they described USD 246 million in planned primate conservation programming and were cited 1657 times by others. We found that half of the plans had been assessed in regard to their implementation, although these assessments were not standardized. Those that had been assessed, showed evidence of positive impacts on awareness raising, collaboration, fundraising, project implementation and policy, although the impact varied by plan. For example, three of the plans directly resulted in USD 15.92 million in funds raised; four plans quantified implementation rates, which ranged from 38% to 74% of actions partially or completely achieved 5 years after plan publication; and four plans attributed the gazettement of 19 protected areas across 11 countries as indirect successes following the publication of plans. Considered together, we reflect on the ‘return-on-investment’ for developing these plans and consider a range of ‘lessons learned’ for future primate action planning efforts.

The reviewed Judgment concerns a post-election dispute relating to the Walloon Parliament elections held on 25 May 2014. The European Court of Human Rights sitting as a Grand Chamber held unanimously on 10 July 2020 that the Kingdom of Belgium had violated the right to free elections and the right to an effective remedy at the occasion of the 2014 elections for the Walloon Regional Parliament.

Extra-articular malunions of metacarpals and phalanges may cause palmar pain, finger scissoring, and splaying, and interfere with function. Current treatment involves open osteotomy and fixation with plates and screws. We present a minimally invasive method using cannulated headless screws for correction of malunions and examine the outcomes in a series of patients.Twenty malunions were operated on in 17 patients. In 16 cases, the malunion involved the metacarpal and in 4 it involved the proximal phalanx. All proximal phalanx and 3 metacarpal malunions were malrotation types, while the rest of the metacarpal malunions were dorsal angulations. The operation consisted of an opening wedge osteotomy in 8 patients; closing wedge osteotomy in 5; and a transverse osteotomy and derotation in the rest. Concomitant surgery to release tendon adhesions or contracted joints or to perform adipofascial flaps was performed in 8 cases. Fixation was achieved by means of a cannulated headless screw. Immediate range of motion was permitted in all cases.Correction of the malunion and osteotomy union was achieved in all cases. One patient required manipulation of a digit that was found rotated at the first follow-up visit. Eleven fingers achieved more than 280° of total active motion. In 9 digits, the total active motion was less than 280° after the operation, yet improved 76° (range, 140°-30°) from their preoperative total active motion. The mean single-assessment numeric evaluation score for the whole group was 9.1.The fixation provided by the cannulated headless screw is sufficient to permit immediate range of motion. Due to the minimal tissue disruption, this approach may be a reasonable alternative to the standard approach.Therapeutic IV.

Road weather conditions such as ice, snow, or heavy rain can have a significant impact on driver safety. In this paper, we present an approach to continuously monitor the road conditions in real time by equipping a fleet of vehicles with sensors. Based on the observed conditions, a physical road weather model is used to forecast the conditions for the following hours. This can be used to deliver timely warnings to drivers about potentially dangerous road conditions. To optimally process the large data volumes, we show how artificial intelligence is used to (1) calibrate the sensor measurements and (2) to retrieve relevant weather information from camera images. The output of the road weather model is compared to forecasts at road weather station locations to validate the approach.

The technical simplicity of the Darrach procedure may explain why it has been so popular. Excising the distal ulna, however, may have potentially undesired consequences to the biomechanics in two areas: the distal radioulnar and the ulno-carpal joints. These conjointly define the radio-ulno-carpal joint (RUCJ). The RUCJ is not a small and irrelevant articulation that can be removed without possibly paying a functional penalty. It is an important link of the antebrachial frame that provides stability to the distal forearm and the carpus. This article revisits the mechanisms by which some ligaments and muscles ensure that all forces about and within the RUCJ are dealt with efficiently.

Despite the large body of literature on ape conservation, much of the data needed for evidence‐based conservation decision‐making is still not readily accessible and standardized, rendering cross‐site comparison difficult. To support knowledge synthesis and to complement the IUCN SSC Ape Populations, Environments and Surveys database, we created the A.P.E.S. Wiki (https://apeswiki.eva.mpg.de), an open‐access platform providing site‐level information on ape conservation status and context. The aim of this Wiki is to provide information and data about geographical ape locations, to curate information on individuals and organizations active in ape research and conservation, and to act as a tool to support collaboration between conservation practitioners, scientists, and other stakeholders. To illustrate the process and benefits of knowledge synthesis, we used the momentum of the update of the conservation action plan for western chimpanzees (Pan troglodytes verus) and began with this critically endangered taxon. First, we gathered information on 59 sites in West Africa from scientific publications, reports, and online sources. Information was compiled in a standardized format and can thus be summarized using a web scraping approach. We then asked experts working at those sites to review and complement the information (20 sites have been reviewed to date). We demonstrate the utility of the information available through the Wiki, for example, for studying species distribution. Importantly, as an open‐access platform and based on the well‐known wiki layout, the A.P.E.S. Wiki can contribute to direct and interactive information sharing and promote the efforts invested by the ape research and conservation community. The Section on Great Apes and the Section on Small Apes of the IUCN SSC Primate Specialist Group will guide and support the expansion of the platform to all small and great ape taxa. Similar collaborative efforts can contribute to extending knowledge synthesis to all nonhuman primate species.

Additional co-authors: Fabiano R de MELO, P Fan, Cyril C Grueter, Diana C Guzman-Caro, Eckhard W Heymann, Ilka Herbinger, Minh D Hoang, Robert H Horwich, Tatyana Humle, Rachel A Ikemeh, Inaoyom S Imong, Leandro Jerusalinsky, Steig E Johnson, Peter M Kappeler, Maria Cecilia M Kierulff, Inza Kone, Rebecca Kormos, Khac Q LE, Baoguo Li, Andrew J Marshall, Erik Meijaard, Russel A Mittermeier, Yasuyuki Muroyama, Eleonora Neugebauer, Lisa Orth, Erwin Palacios, Sarah K Papworth, Andrew J Plumptre, Ben M Rawson, Johannes Refisch, Jonah Ratsimbazafy, Christian Roos, Joanna M Setchell, Rebecca K Smith, Tene Sop, Christoph Schwitzer, Kathy Slater, Shirley C Strum, William J Sutherland, Mauricio Talebi, Janette Wallis, Serge Wich, Roman M Wittig, Hjalmar S Kuhl

Despite the large body of literature on ape conservation, much of the data needed for evidence‐based conservation decision‐making is still not readily accessible and standardized, rendering cross‐site comparison difficult. To support knowledge synthesis and to complement the IUCN SSC Ape Populations, Environments and Surveys database, we created the A.P.E.S. Wiki (https://apeswiki.eva.mpg.de), an open‐access platform providing site‐level information on ape conservation status and context. The aim of this Wiki is to provide information and data about geographical ape locations, to curate information on individuals and organizations active in ape research and conservation, and to act as a tool to support collaboration between conservation practitioners, scientists, and other stakeholders. To illustrate the process and benefits of knowledge synthesis, we used the momentum of the update of the conservation action plan for western chimpanzees (Pan troglodytes verus) and began with this critically endangered taxon. First, we gathered information on 59 sites in West Africa from scientific publications, reports, and online sources. Information was compiled in a standardized format and can thus be summarized using a web scraping approach. We then asked experts working at those sites to review and complement the information (20 sites have been reviewed to date). We demonstrate the utility of the information available through the Wiki, for example, for studying species distribution. Importantly, as an open‐access platform and based on the well‐known wiki layout, the A.P.E.S. Wiki can contribute to direct and interactive information sharing and promote the efforts invested by the ape research and conservation community. The Section on Great Apes and the Section on Small Apes of the IUCN SSC Primate Specialist Group will guide and support the expansion of the platform to all small and great ape taxa. Similar collaborative efforts can contribute to extending knowledge synthesis to all nonhuman primate species.

Threats to biodiversity are well documented. However, to effectively conserve species and their habitats, we need to know which conservation interventions do (or do not) work. Evidence-based conservation evaluates interventions within a scientific framework. The Conservation Evidence project has summarized thousands of studies testing conservation interventions and compiled these as synopses for various habitats and taxa. In the present article, we analyzed the interventions assessed in the primate synopsis and compared these with other taxa. We found that despite intensive efforts to study primates and the extensive threats they face, less than 1% of primate studies evaluated conservation effectiveness. The studies often lacked quantitative data, failed to undertake postimplementation monitoring of populations or individuals, or implemented several interventions at once. Furthermore, the studies were biased toward specific taxa, geographic regions, and interventions. We describe barriers for testing primate conservation interventions and propose actions to improve the conservation evidence base to protect this endangered and globally important taxon.

The Tapanuli orangutan survives today in less than 1,200 km of rainforest in northern Sumatra, Indonesia, in an area known as Batang Toru, where it was scientifically discovered in 1997. Teeming with endangered fauna and flora, the Batang Toru forest has been partially felled and fragmented and parts of the remainder allocated to agriculture, mining, hydropower and geothermal-energy production. The Tapanuli orangutan is estimated to number just 767 individuals, divided among three subpopulations. Its total remaining habitat 10 is merely a tenth the size of Sydney, Australia.

Achromobacter xylosoxidans is increasingly recognized as a colonizer of cystic fibrosis (CF) patients, but the role that A. xylosoxidans plays in pathology remains unknown. This knowledge gap is largely due to the lack of model systems available to study the toxic potential of this bacterium. Recently, a phospholipase A(2) (PLA(2)) encoded by a majority of A. xylosoxidans genomes, termed AxoU, was identified. Here, we show that AxoU is a type III secretion system (T3SS) substrate that induces cytotoxicity to mammalian cells. A tissue culture model was developed showing that a subset of A. xylosoxidans isolates from CF patients induce cytotoxicity in macrophages, suggestive of a pathogenic or inflammatory role in the CF lung. In a toxic strain, cytotoxicity is correlated with transcriptional activation of axoU and T3SS genes, demonstrating that this model can be used as a tool to identify and track expression of virulence determinants produced by this poorly understood bacterium.

We present a motorized distal scanning endoscope with an outer diameter of 1.35 mm and 52 fps rotation speed for in vivo imaging in the peripheral airways of lungs. Three lung segments of an asthma patient pre and post bronchial thermoplasty (BT) treatment were imaged. Optical coherence tomography (OCT) intensity images, attenuation coefficient (AC) images and polarization sensitive OCT (PS-OCT) images showing both birefringence, optic axis uniformity (OAxU) and optic axis (OA) orientation were extracted from the acquired data. PS-OCT endoscopy visualized airway smooth muscle layer thickness and location pre and post BT treatment as means to predict its effectiveness.

Objectives/Interrogation: To propose a novel surgical technique to treat patients with wrist stiffness due to a soft tissue contracture in flexion-pronation after injuries or cast immobilisation. Methods: Lack of extension and radial deviation, presented as a form of wrist stiffness, is related[for full text, please go to the a.m. URL], 14th Triennial Congress of the International Federation of Societies for Surgery of the Hand (IFSSH), 11th Triennial Congress of the International Federation of Societies for Hand Therapy (IFSHT), 11th Triennial Congress of the International Federation of Societies for Hand Therapy (IFSHT)

We demonstrate the use of a motorized distal scanning endoscope to acquirein vivodata in lungs of severe-asthma patients before and after an asthma treatment procedure called bronchial thermoplasty. Conventional optical coherence tomography (OCT) intensity images and polarisation sensitive OCT images were extracted from the acquired data. PS-OCT endoscopy allowing the visualization and segmentation of airway smooth muscle layer - which plays a key role in bronchoconstriction during asthma attacks - showed its potential as means to evaluate the effectiveness of bronchial thermoplasty.

This paper reviews the results of the archaeological investigations at Ziyaret Tepe, located on the river Tigris 60 km east of Diyarbakir in southeastern Turkey. Known in antiquity as Tušhan, the site was a provincial capital and garrison town of the Assyrian Empire. While the project originally expected to have only a few years to conduct operations, we were in the end able to work at the site for a period of almost two decades. The approaches involved included surface collection, geo-physical prospection, large-scale excavation, targeted soundings and material, epigraphic and environmental analyses pursued through multiple techniques. The architecture uncovered included the remains of a palace, an administrative building, the defensive wall, a city gate and both high and low status housing. Key finds included cremation burials, an archive of cuneiform texts dating to the end of the empire, another tablet hinting at the existence of a previously unknown language, and evidence for the use of clay tokens in administration in the first millennium BC. Together these finds have helped us to document the occupation and utilisation of ancient Tušhan across the whole span of Neo- Assyrian rule, from its (re-)founding by Ashurnasirpal II in 882 BC to its abandonment as the empire collapsed in 611 BC.

Der Aufsatz widmet sich der Frage, wie sich mit der technologischen Entwicklung des Digitalen aus der Sicht der offentlichen Kunst umgehen lasst. Das Initiativprojekt Stadtkuratorin Hamburg, das aktuell ein KunstlerInnen-Programm zur Digitalitat entwickelt, wird kurz vorgestellt und Begriffe des Offentlichen geklart. An die kritische Einschatzung einer Smart City als Mittlerin fur Top-Down-Entscheidungswege schliest sich ein kunstlerisches Beispiel an, das Entscheidungswege und ihre Spielraume zu offnen vermag, ohne vordergrundig zu politisieren.

The human herpesvirus-7 (HHV-7) U21 glycoprotein binds to class I major histocompatibility complex (MHC) molecules in the endoplasmic reticulum (ER) and reroutes them to lysosomes. How this single viral glycoprotein efficiently redirects the U21/class I MHC complex to the lysosomal compartment is poorly understood. To investigate the trafficking of HHV-7 U21, we followed synchronous release of U21 from the ER as it traffics through the secretory system. Sorting of integral membrane proteins from the trans-Golgi network (TGN) has been shown to occur through tubular carriers that emanate from the TGN or through vesicular carriers that recruit GGA (Golgi-localized, γ-ear-containing, ARF-binding protein), clathrin adaptors, and clathrin. Here, we present evidence for the existence of a third type of Golgi-derived carrier that is vesicular, yet clathrin independent. This U21-containing carrier also carries a Golgi membrane protein engineered to form inducible oligomers. We propose that U21 employs the novel mechanism of forming oligomeric complexes with class I MHC molecules that result in sorting of the oligomeric U21/class I MHC complexes to Golgi--derived quality control carriers destined for lysosomes.

Introduction: Immune checkpoint receptor (ICR) blockade has emerged as an effective anti-tumour modality, but only in a subset of cancer patients. Moreover, in Multiple myeloma (MM), single-agent activity has not been observed, highlighting the need to better understand the mechanism of action of this class of drugs. We recently showed that combinatorial ICR blockade using αLAG3 and αPD-1 delays disease progression and improves survival in the transplantable Vκ*MYC model of MM (Croucher et al. ASH 2018). However, despite this being a controlled study with genetically-homogeneous tumours, anti-tumour immune responses were heterogeneous, with only a subset of mice demonstrating a delay in tumour progression (17/29 mice, response rate = 58.6%). Thus, using this model, we set out to define mechanisms underlying variability in response to ICR blockade. Methods: We established a cohort of mice by engrafting 5-week-old C57BL/6 mice with Vκ12598 cells via tail vein injection. Treatment with αLAG3/αPD-1 or Ig-control was initiated 1-week post-engraftment and bone marrow (BM) samples were collected 3 weeks after the start of treatment. Following FACS-enrichment of T cells and plasma cells (PCs), single cell suspensions were subjected to matched single-cell gene expression (5' scRNA-seq) and T cell receptor (TCR)/B cell receptor (BCR) profiling (10x Genomics). Results: Samples were selected for profiling based on response to treatment, with responders (n=4) defined by significantly lower disease burden compared to non-responders (n=3) and control-treated mice (n=5), as measured by serum M-protein and %PCs in BM/spleen at sacrifice. Unsupervised clustering of scRNA-seq data from PCs (n=3,318 cells) identified no gene expression or BCR repertoire differences between control and treated, or between responder and non-responder samples, supporting that variability in response was not related to malignant Vκ12598 cells themselves. Across all samples, a statistically significant difference was not detected between the total number of unique TCR sequences (clonotypes) comparing control-treated (351-2369), non-responders (1185-2327) and responders (1378-1698), with no overlapping TCR sequences between top clonotypes. Evaluation of TCR repertoire diversity revealed that αLAG3/αPD-1 treatment induces clonal T cell expansion in control versus treated mice, but this was not significantly different between responders and non-responders. Analysis of paired scRNA-seq data (n=21,520 cells) revealed that expanded T cells from αLAG3/αPD-1-treated mice occupy a different cell state in responder vs. non-responder mice. We speculate that underlying differences in the TCR repertoire may dictate the downstream phenotype of expanded, anti-tumour T cells in mice treated with combinatorial αLAG3/αPD-1. Tumour control following treatment was associated with clonal expansion of T cells expressing genes related to cytoxicity and activation (Ccl5, Ifng, Fasl, Gzmb), whereas tumour progression was associated with clonal expansion of proliferative T cells (Cdkn3, Birc5, Ccna2, Aurka, Mki67). Although T cell proliferation is typically a phenotype ascribed to effector T cells, recent studies have similarly observed this proliferative cell state in dysfunctional T cells within melanoma tumours. Moreover, emerging evidence supports suppression of T cell proliferation by CDK4/6 inhibitors as a means to augment anti-tumour activity of ICR-based therapy. Thus, studies exploring whether reversal of the observed proliferative T cell state can restore response to αLAG3/αPD-1 treatment in non-responding Vκ12598 mice are ongoing and will be reported. Conclusions: ICR inhibitors demonstrate significant activity in some cancers, however many patients fail to respond and a similarly promising level of efficacy has not been achieved in MM. Studies aimed at unraveling the mechanisms of response and resistance to ICR inhibitors are therefore needed to improve the utility of this class of drugs for all patients. Our approach of using paired single-cell gene expression and TCR repertoire profiling has enabled identification of molecular cell states specifically in expanded T cells of responder vs. non-responder mice. In turn, our work nominates novel mechanisms that may be used as potential biomarkers for anti-tumour immune responses as well as potential targets to augment responses to ICR blockade therapy. Disclosures Chesi: Abcuro: Patents & Royalties: Genetically engineered mouse model of myeloma; Novartis: Consultancy, Patents & Royalties: human CRBN transgenic mouse; Pfizer: Consultancy; Pi Therapeutics: Patents & Royalties: Genetically engineered mouse model of myeloma; Palleon Pharmaceuticals: Patents & Royalties: Genetically engineered mouse model of myeloma. Bergsagel: GSK: Consultancy, Honoraria; Genetech: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Oncopeptides: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Patents & Royalties: human CRBN mouse; Pfizer: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Sebag: Janssen: Research Funding; Bristol Myers-Squibb: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Karyopharm Therapeutics: Consultancy, Honoraria. Trudel: BMS/Celgene: Consultancy, Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; GlaxoSmithKline: Consultancy, Honoraria, Research Funding; Roche: Consultancy; Sanofi: Honoraria; Pfizer: Honoraria, Research Funding; Genentech: Research Funding.

Nucleosides with a norbornane fragment as sugar moiety (Figure 1) were found to have antiviral and anticancer activity [1]. [...]

Remodeling of tissue, such as airway smooth muscle (ASM) and extracellular matrix, is considered a key feature of airways disease. No clinically accepted diagnostic method is currently available to assess airway remodeling or the effect of treatment modalities such as bronchial thermoplasty in asthma, other than invasive airway biopsies. Optical coherence tomography (OCT) generates cross-sectional, near-histological images of airway segments and enables identification and quantification of airway wall layers based on light scattering properties only. In this study, we used a custom motorized OCT probe that combines standard and polarization sensitive OCT (PS-OCT) to visualize birefringent tissue in vivo in the airway wall of a patient with severe asthma in a minimally invasive manner. We used optic axis uniformity (OAxU) to highlight the presence of uniformly arranged fiber-like tissue, helping visualizing the abundance of ASM and connective tissue structures. Attenuation coefficient images of the airways are presented for the first time, showing superior architectural contrast compared to standard OCT images. A novel segmentation algorithm was developed to detect the surface of the endoscope sheath and the surface of the tissue. PS-OCT is an innovative imaging technique that holds promise to assess airway remodeling including ASM and connective tissue in a minimally invasive, real-time manner.

Der gerechte Frieden bezeichnet das Leitbild, unter dem der friedensethische Diskurs nach dem Zweiten Weltkrieg in den deutschsprachigen Kirchen um die Jahrtausendwende zu einem weitgehenden Konsens gekommen ist. Es entsteht auf dem Hintergrund der ‒ insbesondere spezifisch deutschen ‒ Weltkriegserfahrungen im 20. Jahrhundert und wird im Rekurs auf die friedensethischen Einsichten der okumenischen Bewegungen – derjenigen im Rahmen des Okumenischen Rates der Kirchen – entwickelt (vgl. Ackermann 2013, S. 75ff.).

My bold suggestions in this paper, as an artisan-anthropologist-therapist, are as follows: (a) human manufacturing of objects brings about individual/collective (deep well-being) experiences of beauty and grace and (b)‘making artifacts’ represents an important ancient continuity in (social-cultural-biological) humanization. Combining these two assertions suggests a universal existence of ‘crafting in the world’. The argument was ignited by the termination of both my mother’s and father’s family blacksmithing workshops in the twentieth century. Being a technical engineer/craftsman in my first career, and being one of six sons, I was deeply puzzled about why and how our transgenerational arts and crafting family tradition would die out when my father closed down his metal construction workshop in 1986. My great-uncles from mother’s side had already closed down their smithy decades earlier.

In order to make high-performance liquid chromatography (HPLC) more widely available at home and in small-scale settings, we have simplified two of its most costly modules, namely the pump and the detector. This should make the setup affordable for home or small laboratory use. A manual HPLC pump was constructed so as to fit into a caulk gun from a local hardware store enabling the generation of 100-150 bar of pressure. In order to limit the pressure drop during the running of a chromatogram, a pulse dampener was developed. We further modified the electrochemical detection (ECD) system so as to use a cheap boron-doped diamond electrode with an overlay of thin filter paper, causing an eluent flow over the electrode by wicking and gravity. Both the pump and the detector are at least ten times cheaper than conventional HPLC modules. Using a home-packed JupiterⓇ Proteo reversed phase capillary column we show how this low-cost HPLC system generates well resolving chromatograms after direct injection of fresh urine. The ECD did not lose its sensitivity during regular use over more than half a year. For homovanillic acid (HVA), which is of medical interest, we measured a linear dynamic range of two orders of magnitude, a detection limit of HVA in the injected sample of 3 μM and a coefficient of variation

Review of: "Lincoln and Emancipation", by Edna Greene Medford and of "Lincoln and the Thirteenth Amendment", by Christian Samito.

Active ageing is the process of optimising opportunities for health, participation, and security in order to enhance the quality of life as people age. Provision of adequate mobility services is essential to enable older people, including those with illness or disability, to participate in society. In the past, much effort has been made to make public transport more accessible for older people or to provide specific door-to-door transport services. Transport and mobility services to support ageing society should look into new technologies which can support the elderly in their driving tasks, either using privately owned cars, shared vehicles, or various mobility services to provide door-to-door transport solutions through Mobility as a Service (MaaS), shared mobility, etc. Various driver assistance and vehicle automation technologies which can reduce driver workload and enhance safety will offer viable solutions for the mobility needs of an ageing population. MaaS, which can provide a one-stop solution to access and payment for all types of transport modes, would be an excellent solution for older travellers. This paper aims to provide a forward thinking analysis of transport policy for an ageing population.

This paper, “The results of the thin x-ray mirror module production for the ESA XMM spacecraft," was presented as part of International Conference on Space Optics—ICSO 1997, held in Toulouse, France.

During 2000–2013, 4 genotypes of bluetongue virus (BTV) were detected in Corsica, France. At the end of 2013, a compulsory BTV-1 vaccination campaign was initiated among domestic ruminants; biological samples from goats were tested as part of a corresponding monitoring program. A BTV strain with nucleotide sequences suggestive of a novel serotype was detected.

Phospholipase A2enzymes are ubiquitously distributed throughout the prokaryotic and eukaryotic kingdoms and are utilized in a wide array of cellular processes and physiological and immunological responses. Several patatin-like phospholipase homologs of ExoU fromPseudomonas aeruginosawere selected on the premise that ubiquitin activation of this class of bacterial enzymes was a conserved process. We found that ubiquitin activated all phospholipases tested in bothin vitroandin vivoassays via a conserved serine-aspartate catalytic dyad. Ubiquitin chains versus monomeric ubiquitin were superior in inducing catalysis, and ubiquitin-like proteins failed to activate phospholipase activity. Toxicity studies in a prokaryotic dual-expression system grouped the enzymes into high- and low-toxicity classes. Toxicity measured in eukaryotic cells also suggested a two-tiered classification but was not predictive of the severity of cellular damage, suggesting that each enzyme may correspond to unique properties perhaps based on its specific biological function. Additional studies on lipid binding preference suggest that some enzymes in this family may be differentially sensitive to phosphatidyl-4,5-bisphosphate in terms of catalytic activation enhancement and binding affinity. Further analysis of the function and amino acid sequences of this enzyme family may lead to a useful approach to formulating a unifying model of how these phospholipases behave after delivery into the cytoplasmic compartment.