Ion Analysis at the Highest Stage - The Metrological Approach by National Metrological Institutes

Abstract.: National Metrological Institutes (NMI's) from fifteen different countries participated in interlaboratory comparisons where concentrations of about 1 g kg−1 in solutions of aluminium, copper, iron, magnesium, chloride and phosphate were measured. A very high comparability of the results irrespective of the analyte and the applied measurement technique was observed. The relative in-between laboratory standard deviations of the results as reported by the participating laboratories were between 0.13% for copper and chloride up to 0.33% for aluminium, and all of the 81 results were found in the range of ±1% with respect to the reference value. Due to the gravimetric preparation of the samples, a conventional true reference value was calculated, and no significant deviations of the reference values and the means of all results reported by the institutes were foun

Prosocial effects of coordination - What, how and why?

A wealth of research in recent decades has investigated the effects of various forms of coordination upon prosocial attitudes and behavior. To structure and constrain this research, we provide a framework within which to distinguish and interrelate different hypotheses about the psychological mechanisms underpinning various prosocial effects of various forms of coordination. To this end, we introduce a set of definitions and distinctions that can be used to tease apart various forms of prosociality and coordination. We then identify a range of psychological mechanisms that may underpin the effects of coordination upon prosociality. We show that different hypotheses about the underlying psychological mechanisms motivate different predictions about the effects of various forms of coordination in different circumstances

Bifunctional Ligand Systems for the Radiolabeling of Nanoparticles and Biomolecules with the fac-[99mTc(CO)3]+-Core

The application of nanoparticles (NPs) in the medical field is increasingly growing in importance. NPs such as mesoporous silica NPs, polymeric NPs, magnetic NPs, gold NPs (AuNPs), and quantum dots (QDs) are promising candidates for the design of novel imaging, drug delivery or theranostic agents. A major challenge after administration of NPs to living organisms is the exact localization. Among the various techniques to assess the biodistribution of functional nanostructures, radiolabeling and subsequent detection of the emitted γ-photons allows for noninvasive imaging by single photon emission computed tomography (SPECT) or positron emission tomography (PET). Moreover, radiolabeling provides an accurate quantification of nanostructure localization in different organs or tissues by performing an ex vivo biodistribution. For the 99mTc labeling of AuNPs and QDs a novel coating ligand was synthesized, containing a thiol group as an anchor for the NP surface, a spacer (e.g. polyethylene glycol PEG) and the 2,3-diaminopropionic acid (DAP) chelator for the [99mTc(CO)3]+ fragment. This ligand is multi-functional; it combines the metal chelate with conjugating functions to biological vectors in one single molecule. The concept allows coupling of any targeting function to the chelator. An example with a small molecule target for the prostate specific membrane antigen (PSMA) is given. Derivatized AuNPs and QDs can directly be labeled in one step with [99mTc(OH2)3(CO)3]+. The AuNPs in particular are highly stable in buffer and serum, a prerequisite for in vivo studies excluding misinterpretation of the biodistribution data. AuNPs with differing sizes (7 nm and 14 nm core diameter) were administered intravenously into nude NMRI mice bearing LNCaP xenografts. MicroSPECT images show for both probes rapid clearance from the blood pool via the hepatobiliary pathway. The 7 nm AuNPs revealed a significantly higher bone uptake than the 14 nm AuNPs. The high affinity towards bone mineral is further confirmed in vitro with hydroxyapatite. In case NPs have an intrinsic property for contrast, radiolabeling automatically leads to multi-modal imaging agents. Particularly the development of NP-based dual-modality probes for magnetic resonance imaging (MRI)/PET or MRI/SPECT is intensively investigated. One of the most commonly used radionuclide for clinical SPECT imaging is 99m Tc and the labeling of Fe3O4 NPs with 99mTc was shown to be a successful strategy to obtain dual-modality imaging agents. The focus in this thesis is on the 99mTc labeling of gold containing magnetic nanomaterials (Fe3O4-Au core-shell and heterostructured Fe3O4-Au Dumbbell-like NPs). The key elements for the labeling are novel coating ligands, consisting of mono- or dithiol anchors for the gold surface, a PEG linker and various chelators for the [99mTc(CO)3]+ fragment. In a variety of labeling experiments, favorable coatings were examined and their stability tested. The findings presented herein can form the basis for the development of potential, NP-based SPECT/MRI dual- modality imaging agents. The versatility of the established ligand system was further shown with an intermediate along the synthethic pathway. The terminal hydroxyl group of the triethylene glycol linker conjugated to DAP was combined with L-tyrosine via a Mitsunobu reaction to the para-hydroxy of L-tyrosine. The 99mTc-L-tyrosine derivative was evaluated in healthy and nude NMRI mice bearing a C6 tumor xenograft. Radiolabeled amino acid derivatives in general are highly interesting for tumor imaging due to enhanced amino acid metabolism and protein synthesis in tumors compared to normal peripheral tissue. However, uptake in the tumor and pancreas at 1 h post injection (p.i.) was low, indicating that the tracer was not recognized as an amino acid analogue. Although the 99mTc-L-tyrosine derivative was not suitable for tumor imaging, it may be useful to image and to assess the functionality of the gallbladder. At 1 h p.i., the uptake in the gallbladder was unexpectedly high and the microSPECT images showed a high uptake after already 15 min p.i. In addition, the bifunctional ligand system HS-PEG-DAP is not only well suitable for NP coating, but also for the labeling of biomolecules with a free thiol group. The basis for this novel labeling approach is the well known thiol-disufide exchange reaction. Therefore, the complex HS-PEG-DAP-99mTc(CO)3 was activated with 2,2’- dithiodipyridine to form the pyridyl disulfide derivative. This compound allows the radiolabeling of biomolecues bearing a thiol functionality, exemplified with thioglucose, cysteine and glutathione. The scope of this labeling strategy can be extended to small peptides or even proteins containing a free thiol group

Guinea Pig Model for Cutaneous Herpes Simplex Virus Infection

Previous animal models for cutaneous herpes simplex infections have been unsatisfactory because of atypical zosteriform progression of lesions and high animal mortality rates. By using a vaccination technique we have been able to produce lesions in guinea pigs which closely mimic human herpes simplex infection

SGX Switchless Calls Made Configless

Intel's software guard extensions (SGX) provide hardware enclaves to guarantee confidentiality and integrity for sensitive code and data. However, systems leveraging such security mechanisms must often pay high performance overheads. A major source of this overhead is SGX enclave transitions which induce expensive cross-enclave context switches. The Intel SGX SDK mitigates this with a switchless call mechanism for transitionless cross-enclave calls using worker threads. Intel's SGX switchless call implementation improves performance but provides limited flexibility: developers need to statically fix the system configuration at build time, which is error-prone and misconfigurations lead to performance degradations and waste of CPU resources. ZC-SWITCHLESS is a configless and efficient technique to drive the execution of SGX switchless calls. Its dynamic approach optimises the total switchless worker threads at runtime to minimise CPU waste. The experimental evaluation shows that ZC-SWITCHLESS obviates the performance penalty of misconfigured switchless systems while minimising CPU waste.Comment: 10 pages, 53rd Annual IEEE/IFIP International Conference on Dependable Systems and Networks (DSN

The fruits of our labour: Interpersonal coordination generates commitment by signalling a willingness to adapt

Countless everyday activities require us to coordinate our actions and decisions with others. Coordination not only enables us to achieve instrumental goals, but has also been shown to boost commitment, leading people to persevere with an interaction even when their motivation wavers. So far, little is known about the mechanism by which coordination generates commitment. To investigate this, we conducted two experiments which represented very different coordination problems: coordination of movement timing on a joint drumming task (Experiment 1) and coordination of decision-making on a joint object matching task (Experiment 2). In both experiments, the similarity of the participant and partner was manipulated by varying whether or not they had perceptual access to the participant’s workspace, and the participants’ attribution of (un)willingness to invest effort into the joint action by adapting was manipulated by varying whether or not the participant believed their partner had perceptual access. As a measure of commitment, we registered how much participants’ persisted on a boring and effortful task to earn points for their partners. Participants were significantly less committed to earning points for unadaptive partners than for adaptive partners, but only when they believed that their partner was unwilling to adapt rather than unable to adapt. This demonstrates that coordination can generate commitment insofar as it provides a cue that one’s partner is willing to invest effort to adapt for the good of the interaction. Moreover, we demonstrate that this effect generalises across different kinds of coordination

Analyse der Spontanmotorik im 1. Lebensjahr: Markerlose 3-D-Bewegungserfassung zur Früherkennung von Entwicklungsstörungen

Children with motor development disorders benefit greatly from early interventions. An early diagnosis in pediatric preventive care (U2–U5) can be improved by automated screening. Current approaches to automated motion analysis, however, are expensive, require lots of technical support, and cannot be used in broad clinical application. Here we present an inexpensive, marker-free video analysis tool (KineMAT) for infants, which digitizes 3‑D movements of the entire body over time allowing automated analysis in the future. Three-minute video sequences of spontaneously moving infants were recorded with a commercially available depth-imaging camera and aligned with a virtual infant body model (SMIL model). The virtual image generated allows any measurements to be carried out in 3‑D with high precision. We demonstrate seven infants with different diagnoses. A selection of possible movement parameters was quantified and aligned with diagnosis-specific movement characteristics. KineMAT and the SMIL model allow reliable, three-dimensional measurements of spontaneous activity in infants with a very low error rate. Based on machine-learning algorithms, KineMAT can be trained to automatically recognize pathological spontaneous motor skills. It is inexpensive and easy to use and can be developed into a screening tool for preventive care for children.Kinder mit motorischer Entwicklungsstörung profitieren von einer frühen Entwicklungsförderung. Eine frühe Diagnosestellung in der kinderärztlichen Vorsorge (U2–U5) kann durch ein automatisiertes Screening verbessert werden. Bisherige Ansätze einer automatisierten Bewegungsanalyse sind jedoch teuer und aufwendig und nicht in der Breite anwendbar. In diesem Beitrag soll ein neues System zur Videoanalyse, das Kinematic Motion Analysis Tool (KineMAT) vorgestellt werden. Es kann bei Säuglingen angewendet werden und kommt ohne Körpermarker aus. Die Methode wird anhand von 7 Patienten mit unterschiedlichen Diagnosen demonstriert. Mit einer kommerziell erhältlichen Tiefenbildkamera (RGB-D[Red-Green-Blue-Depth]-Kamera) werden 3‑minütige Videosequenzen von sich spontan bewegenden Säuglingen aufgenommen und mit einem virtuellen Säuglingskörpermodell (SMIL[Skinned Multi-infant Linear]-Modell) in Übereinstimmung gebracht. Das so erzeugte virtuelle Abbild erlaubt es, beliebige Messungen in 3‑D mit hoher Präzision durchzuführen. Eine Auswahl möglicher Bewegungsparameter wird mit diagnosespezifischen Bewegungsauffälligkeiten zusammengeführt. Der KineMAT und das SMIL-Modell erlauben eine zuverlässige, dreidimensionale Messung der Spontanaktivität bei Säuglingen mit einer sehr niedrigen Fehlerrate. Basierend auf maschinellen Lernalgorithmen kann der KineMAT trainiert werden, pathologische Spontanmotorik automatisiert zu erkennen. Er ist kostengünstig und einfach anzuwenden und soll als Screeninginstrument für die kinderärztliche Vorsorge weiterentwickelt werden

SIVmac239 MVA vaccine with and without a DNA prime, similar prevention of infection by a repeated dose SIVsmE660 challenge despite different immune responses

Vaccine regimens using different agents for priming and boosting have become popular for enhancing T cell and Ab responses elicited by candidate HIV/AIDS vaccines. Here we use a simian model to evaluate immunogenicity and protective efficacy of a recombinant modified vaccinia Ankara (MVA) vaccine in the presence and absence of a recombinant DNA prime. The simian vaccines and regimens represent prototypes for candidate HIV vaccines currently undergoing clinical testing

Genetic landscape of congenital insensitivity to pain and hereditary sensory and autonomic neuropathies

Congenital insensitivity to pain (CIP) and hereditary sensory and autonomic neuropathies (HSAN) are clinically and genetically heterogeneous disorders exclusively or predominantly affecting the sensory and autonomic neurons. Due to the rarity of the diseases and findings based mainly on single case reports or small case series, knowledge about these disorders is limited. Here, we describe the molecular workup of a large international cohort of CIP/HSAN patients including patients from normally under-represented countries. We identify 80 previously unreported pathogenic or likely pathogenic variants in a total of 73 families in the >20 known CIP/HSAN-associated genes. The data expand the spectrum of disease-relevant alterations in CIP/HSAN, including novel variants in previously rarely recognized entities such as ATL3-, FLVCR1- and NGF-associated neuropathies and previously under-recognized mutation types such as larger deletions. In silico predictions, heterologous expression studies, segregation analyses and metabolic tests helped to overcome limitations of current variant classification schemes that often fail to categorize a variant as disease-related or benign. The study sheds light on the genetic causes and disease-relevant changes within individual genes in CIP/HSAN. This is becoming increasingly important with emerging clinical trials investigating subtype or gene-specific treatment strategies