Search

Introduction A growing number of dominantly inherited Alzheimer's disease (DIAD) cases have become known in Latin American (LatAm) in recent years. However, questions regarding mutation distribution and frequency by country remain open. Methods A literature review was completed aimed to provide estimates for DIAD pathogenic variants in the LatAm population. The search strategies were established using a combination of standardized terms for DIAD and LatAm. Results Twenty-four DIAD pathogenic variants have been reported in LatAm countries. Our combined dataset included 3583 individuals at risk; countries with highest DIAD frequencies were Colombia (n = 1905), Puerto Rico (n = 672), and Mexico (n = 463), usually attributable to founder effects. We found relatively few reports with extensive documentation on biomarker profiles and disease progression. Discussion Future DIAD studies will be required in LatAm, albeit with a more systematic approach to include fluid biomarker and imaging studies. Regional efforts are under way to extend the DIAD observational studies and clinical trials to Latin America.

Introduction: The historical development, frequency, and impact of frontotemporal dementia (FTD) are less clear in Latin America than in high-income countries. Although there is a growing number of dementia studies in Latin America, little is known collectively about FTD prevalence studies by country, clinical heterogeneity, risk factors, and genetics in Latin American countries.Methods: A systematic review was completed, aimed at identifying the frequency, clinical heterogeneity, and genetics studies of FTD in Latin American populations. The search strategies used a combination of standardized terms for FTD and related disorders. In addition, at least one author per Latin American country summarized the available literature. Collaborative or regional studies were reviewed during consensus meetings.Results: The first FTD reports published in Latin America were mostly case reports. The last two decades marked a substantial increase in the number of FTD research in Latin American countries. Brazil (165), Argentina (84), Colombia (26), and Chile (23) are the countries with the larger numbers of FTD published studies. Most of the research has focused on clinical and neuropsychological features (n = 247), including the local adaptation of neuropsychological and behavioral assessment batteries. However, there are little to no large studies on prevalence (n = 4), biomarkers (n = 9), or neuropathology (n = 3) of FTD.Conclusions: Future FTD studies will be required in Latin America, albeit with a greater emphasis on clinical diagnosis, genetics, biomarkers, and neuropathological studies. Regional and country-level efforts should seek better estimations of the prevalence, incidence, and economic impact of FTD syndromes.

In recent years, the demand for gesture recognition has increased enormously due to many applications such as computer games, human-robot interaction, assistance systems, sports, sign language interpreters, and e-commerce. The recognition of hand gestures is one of the most important gesture recognition methods. With simple hand gestures, devices in the smart home area (TV, radio, vacuum cleaner robots, etc.) should be easier to operate. Our method is based on a convolutional neural network, or more precisely on MobileNetV2. With this lean and fast network, we have been able to achieve an accuracy of 99.96 percent in recognition of hand gestures, so that in the future, we will be able to offer an application in the field of Human-Computer Interaction to interact more easily with the ever-increasing number of technologies in everyday life.

In the production of screws, manual methods are often still used to detect defects. This paper aims to use a convolutional neural network-based technique to detect whether defects in screws are caused during production. Our experimental results show that a detection accuracy of 96.67% can be achieved with the proposed technique. Among the defects considered are defects on the objects' surface (e.g., scratches, dents), structural defects like distorted object parts, or defects that manifest themselves by the absence of certain object parts. Our more efficient method can be used in the future for quality control in the manufacture of screws.

Today the postponement of cloud services to data centers at the edge of a network, as well as a further shifting of functionality in the paradigm of fog computing to a multitude of geographically distributed nodes, necessitates a transparent resource evaluation in a heterogeneous environment to expose all available computing capabilities. A lot of monitoring tools to evaluate resource utilization already exist for cloud providers. However, most of them barely fulfill the requirements to monitor services all the way down to the devices of the Internet of Things paradigm.We present an evaluation of existing open source monitoring tools for fog computing scenarios, especially using container virtualization technology. With our results we depict the current state of the art and possible future improvements to handle small, energy-efficient devices without overburdening them.

Hepatitis C virus (HCV) nonstructural protein 5A (NS5A) is a phosphoprotein with key functions in regulating viral RNA replication and assembly. Two phosphoisoforms are discriminated by their different apparent molecular weights: a basally phosphorylated (p56) and a hyperphosphorylated (p58) variant. The precise mechanisms governing p58 synthesis and specific functions of the isoforms are poorly understood. Our study aimed at a deeper understanding of determinants involved in p58 synthesis. We analyzed two variants of p56 and p58 of isolate JFH-1 separately by mass spectrometry using an expression model and thereby identified a threonine-rich phosphopeptide exclusively found in the hyperphosphorylated variant. Individual exchange of possible phosphoacceptor sites to phosphoablatant or -mimetic residues had little impact on HCV replication or assembly in cell culture. A phosphospecific antibody recognizing pT242 revealed that this position was indeed phosphorylated only in p58 and depended on casein kinase Iα. Importantly, phosphoablative mutations at positions T244 and S247 abrogated pT242 detection without substantial effects on global p58 levels, whereas mutations in the preceding serine-rich cluster dramatically reduced total p58 levels but had minor impact on pT242 levels, suggesting the existence of distinct subspecies of hyperphosphorylated NS5A. Mass spectrometry analyses of different genotypes showed variable phosphorylation patterns across NS5A and suggested that the threonine-rich region is also phosphorylated at T242 in gt4a and at S249 in gt1a, gt1b, and gt4a. Our data therefore indicate that p58 is not a single homogenously phosphorylated protein species but rather a population of various phosphoisoforms, with high variability between genotypes. IMPORTANCE Hepatitis C virus infections affect 71 million people worldwide and cause severe chronic liver disease. Recently, efficient antiviral therapies have been established, with inhibitors of nonstructural protein NS5A as a cornerstone. NS5A is a central regulator of HCV replication and assembly but is still enigmatic in its molecular functions. It exists in two phosphoisoforms, p56 and p58. We identified a phosphopeptide exclusively found in p58 and analyzed the determinants involved in phosphorylation of this region. We found evidence for very different phosphorylation patterns resulting in p58. These results challenge the concept of p58 being a homogenous species of NS5A molecules phosphorylated at the same positions and argues for at least two independently phosphorylated variants showing the same electrophoretic mobility, likely serving different functions.

Background & Aims The lipid-binding protein, SEC14L2, is crucial for the efficient viral replication of clinical hepatitis C virus (HCV) isolates in cell culture. Given the role of SEC14L2 in HCV replication, we aimed to study a large number of HCV positive sera carrying genotypes 1–4, to identify viral factors associated with efficient replication in culture. Additionally, we investigated whether 13 single nucleotide polymorphisms (SNPs) of SEC14L2 have an impact on RNA replication of naturally occurring HCV isolates. Methods We generated Huh-7.5 cell lines overexpressing SEC14L2 or 13 coding SNPs and tested 73 different HCV positive sera for in vitro replication. Furthermore, we genotyped a cohort of 262 patients with chronic HCV for the common SNP (rs757660) and investigated its effect on the clinical phenotype. Results HCV isolates from genotype 1, 2, 3 and 4 replicate in Huh-7.5 cells overexpressing SEC14L2. Interestingly, only subgenomic replicons from genotypes 1 and 3 showed enhanced replication whereas genotypes 2 and 4 remained unaffected. Furthermore, replication was independent of viral load. Importantly, all tested SNPs supported HCV RNA replication in vitro, while 1 SNP was associated with decreased SEC1L2 expression and viral RNA. All SNPs exhibited comparable cellular cholesterol and vitamin E abundance in naive Huh-7.5 cells. Conclusions This large screen of natural HCV isolates of 4 genotypes underscores the relevance of SEC14L2 as an in vitro HCV host factor. Additionally, SEC14L2 variants appear to recapitulate the wild-type enhancement of HCV replication. Variant rs191341134 showed a decreased effect due to lowered stability, whereas variant rs757660, a high prevalence mutant, showed a similar phenotype to the wild-type. Lay summary Until the year 2015, consistent replication of patient-derived isolates of hepatitis C virus (HCV) in an in vitro model remained a limitation in HCV research. In 2015 a group of authors identified a protein named SEC14L2 that enabled the replication of HCV isolates in cell culture. We performed a large screen encompassing 73 isolates of 4 different HCV genotypes. Additionally, we replaced the natural SEC14L2 with 13 different mutants to test if the protein variation significantly altered its HCV replication enhancing functions. We showed that different genotypes of HCV react differently to the presence of this protein and the variants of the protein mimic the behavior of the wild-type.

In this paper we present a generic Port-Hamiltonian (PH) model that includes cable dynamics (in particular elasticity and couplings with the platform and all cables among each other) of a cable-driven parallel robot (CDPR), which is used as a motion simulator. Moreover we consider changes in the cable parameters, i.e. it’s elasticity, mass and length when the cables are wound/unwound from the winches. To the best of our knowledge nobody considered such a detailed and generic model of a CDPR in PH structure before. Since motion simulators are built to mimic systems with different physical properties, PH modeling can pave the way for physics-shaping controllers.

Nowadays, touch-input devices are widely available. The use of such touch input devices, e.g., large wall-mounted touchscreens in (team) meeting rooms appear appropiate and desirable. Thus, team meetings can change from one-man-presentation-shows towards collaborative and interactive developing of plans and processes via designing and creating its corresponding diagrams. In this paper, we present an approach for interacting with diagrams using uni-stroke touch gestures. We focus on large wall-mounted touchscreens and present an editor design for such environments. In order to validate the usability of our approach we report on the results of a user study with a diagram editor for Business Process Modeling Networks.

Human noroviruses (huNoV) are the most frequent cause of non-bacterial acute gastroenteritis worldwide, particularly genogroup II genotype 4 (GII.4) variants. The viral nonstructural (NS) proteins encoded by the ORF1 polyprotein induce vesical clusters harboring the viral replication sites. Little is known so far about the ultrastructure of these replication organelles or the contribution of individual NS proteins to their biogenesis. We compared the ultrastructural changes induced by expression of norovirus ORF1 polyproteins with those induced upon infection with murine norovirus (MNV). Characteristic membrane alterations induced by ORF1 expression resembled those found in MNV infected cells, consisting of vesicle accumulations likely built from the endoplasmic reticulum (ER) which included single membrane vesicles (SMVs), double membrane vesicles (DMVs) and multi membrane vesicles (MMVs). In-depth analysis using electron tomography suggested that MMVs originate through the enwrapping of SMVs with tubular structures similar to mechanisms reported for picornaviruses. Expression of GII.4 NS1-2, NS3 and NS4 fused to GFP revealed distinct membrane alterations when analyzed by correlative light and electron microscopy. Expression of NS1-2 induced proliferation of smooth ER membranes forming long tubular structures that were affected by mutations in the active center of the putative NS1-2 hydrolase domain. NS3 was associated with ER membranes around lipid droplets (LDs) and induced the formation of convoluted membranes, which were even more pronounced in case of NS4. Interestingly, NS4 was the only GII.4 protein capable of inducing SMV and DMV formation when expressed individually. Our work provides the first ultrastructural analysis of norovirus GII.4 induced vesicle clusters and suggests that their morphology and biogenesis is most similar to picornaviruses. We further identified NS4 as a key factor in the formation of membrane alterations of huNoV and provide models of the putative membrane topologies of NS1-2, NS3 and NS4 to guide future studies., Author summary Positive-strand RNA viruses induce membrane alterations harboring the viral replication complexes. In the case of human noroviruses (huNoV), the major cause of acute viral gastroenteritis, these are induced by the ORF1 polyprotein, which is post-translationally processed into the functional nonstructural (NS) proteins. Partly due to the lack of efficient cell culture models, little is known so far about membrane alterations induced by huNoV belonging to the most clinically relevant genogroup II, genotype 4 (GII.4), nor about the function of individual NS proteins in their formation. We therefore expressed ORF1 proteins of GII.4 and individual NS proteins in cells to study their contribution to viral replication complex formation. Expression of ORF1 proteins of GII.4 induced vesicular membrane alterations comparable to those found in infected cells and similar to picornaviruses and hepatitis C virus (HCV). GII.4 NS1-2, NS3 and NS4 are contributing to viral membrane alterations. Our work provides new insights into their function in huNoV induced replication complex formation while identifying NS4 as the most important single determinant. This knowledge might provide novel attractive targets for future therapies inhibiting the formation of the membranous viral replication complex, as exemplified by the efficacy of HCV NS5A inhibitors.

In this paper we present preliminary, experimental results of an Adaptive Super-Twisting Sliding-Mode Controller with time-varying gains for redundant Cable-Driven Parallel Robots. The sliding-mode controller is paired with a feed-forward action based on dynamics inversion. An exact sliding-mode differentiator is implemented to retrieve the velocity of the end-effector using only encoder measurements with the properties of finite-time convergence, robustness against perturbations and noise filtering. The platform used to validate the controller is a robot with eight cables and six degrees of freedom powered by \(940\,{\text {W}}\) compact servo drives. The proposed experiment demonstrates the performance of the controller, finite-time convergence and robustness in tracking a trajectory while subject to external disturbances up to approximately 400% the mass of the end-effector.

International audience

In this paper we study if approximated linear models are accurate enough to predict the vibrations of a cable of a Cable-Driven Parallel Robot (CDPR) for different pretension levels. In two experiments we investigated the damping of a thick steel cable from the Cablerobot simulator [1] and measured the motion of the cable when a sinusoidal force is applied at one end of the cable. Using this setup and power spectral density analysis we measured the natural frequencies of the cable and compared these results to the frequencies predicted by two linear models: i) the linearization of partial differential equations of motion for a distributed cable, and ii) the discretization of the cable using a finite elements model. This comparison provides remarkable insights into the limits of approximated linear models as well as important properties of vibrating cables used in CDPR.

Purpose We aim to derive an internationally applicable data set to improve prescription safety of psychiatric drugs. Methods We performed an in-depth analysis of the concordance of prescribing information of 10 key psychiatric drugs across four major drug markets with regard to indications, warnings and precautions, and contraindications. Results The individual prescribing information covered on average 71.430.3% of all named indications, 59.517.1% of all potential warnings and precautions and 70.124.4% of all applicable contraindications. Conclusion This substantial variation in key prescribing information across countries highlights the need for a better international cooperation and standardization of prescribing information. Copyright © 2012 John Wiley & Sons, Ltd. key words—prescribing information; Summary of Product Characteristics; antidepressive agents; international comparison; serotonin agents; pharmacoepidemiology

Two extremely bulky bis(aryl)amines, HN(Ar*)(Ph) (HLPh) and HN(Ar*)(Mes) (HLMes) (Ar* = C6H2{C(H)Ph2}2Me-2,6,4; Mes = mesityl), have been prepared by palladium-catalyzed cross-coupling reactions and structurally characterized. These have been utilized in the preparation of the amido-germanium(II) chlorides, [LPhGeCl] and [LMesGeCl]. Reactions of these, and the known complex, [L′GeCl] (L′ = −N(Ar*)(SiMe3)), with Na[CpMo(CO)3] have afforded the first examples of structurally characterized two-coordinate molybdenum substituted germylenes, [Cp(CO)3MoGeN(Ar*)(R)] (R = SiMe3 or Ph). The former readily eliminates a molecule of CO when heated or irradiated with UV light to give an unprecedented amino-germylyne complex, [Cp(CO)2Mo≡GeN(Ar*)(SiMe3)]. The spectroscopic and structural data for this complex, in combination with the results of computational studies, show that this compound is best viewed as having a bent Mo–Ge “triple” bond, with little multiple bond character to its Ge–N interaction. Computational stud...

Reactions of the extremely bulky amido alkali metal complexes, [KL'(η(6)-toluene)], or in situ generated [LiL'] or [LiL″] {L'/ L″ = N(Ar*)(SiR(3)), where Ar* = C(6)H(2){C(H)Ph(2)}(2)Me-2,6,4 and R = Me (L') or Ph (L″)} with group 13 metal(I) halides have yielded a series of monomeric metal(I) amide complexes, [ML'] (M = Ga, In, or Tl) and [ML″] (M = Ga or Tl), all but one of which have been crystallographically characterized. The results of the crystallographic studies, in combination with computational analyses, reveal that the metal centers in these compounds are one coordinate and do not exhibit any significant intra- or intermolecular interactions, other than their N-M linkages. One of the complexes, [InL'], represents the first example of a one-coordinate indium(I) amide. Attempts to extend this study to the preparation of the analogous aluminum(I) amide, [AlL'], were not successful. Despite this, a range of novel and potentially synthetically useful aluminum(III) halide and hydride complexes were prepared en route to [AlL'], the majority of which were crystallographically characterized. These include the alkali metal aluminate complexes, [L'AlH(2)(μ-H)Li(OEt(2))(2)(THF)] and [{L'Al(μ-H)(3)K}(2)], the neutral amido-aluminum hydride complex, [{L'AlH(μ-H)}(2)], and the aluminum halide complexes, [L'AlBr(2)(THF)] and [L'AlI(2)]. Reaction of the latter two systems with a variety of reducing agents led only to intractable product mixtures.

This paper introduces the CableRobot simulator, which was developed at the Max Planck Institute for Biological Cybernetics in cooperation with the Fraunhofer Institute for Manufacturing Engineering and Automation IPA. The simulator is a completely novel approach to the design of motion simulation platforms in so far as it uses cables and winches for actuation instead of rigid links known from hexapod simulators. This approach allows to reduce the actuated mass, scale up the workspace significantly, and provides great flexibility to switch between system configurations in which the robot can be operated. The simulator will be used for studies in the field of human perception research and virtual reality applications. The paper dicusses some of the issues arising from the usage of cables and provides a system overview regarding kinematics and system dynamics as well as giving a brief introduction into possible application use cases.

Many digital file formats, which are used every day for different purposes or in different domains, are serialized as simple text. As plain text is a very simple serialization format, numerous tools, which provide general functionality for text, can thus be used for lots of different file formats. It is one reason why the principle of collaboration can easily be ported from one domain to another one as long as the exchange format is text-based. For binary, and consequently more complex formats, specific tools are usually necessary. In this paper, we present an approach that allows for the creation and textual serialization of videos that are composed of other centrally provided videos. We further introduce a library implementation that enables general-purpose tools to constitute the technical basis for collaborative video editing in an on- and offline setting.

In software development processes, diagram editors play an important role. For instance, editors for creating UML diagrams are often used in early stages of software development. Three input methodologies can be distinguished: traditional mode-based editors, sketching editors, and gesture-based editors. Most of today's diagram editors are mode-based and use the mouse as an input device. (Multi-)touch inputs have not been integrated very well, yet, although a variety of touch input devices, such as (multi-)touch monitors and tablet computers, are quite common today. I present an approach for gesture-based editing of diagrams. The idea is that mode-based diagram editors are extended by off-the-shelf unistroke gesture recognizers. In these diagram editors, users can perform editing tasks, such as creating, modifying, and deleting components, by unistroke gestures.

In software development processes, diagram editors play an important role. For instance, editors for creating UML diagrams are often used in early stages of software development. Three input methodologies can be distinguished: traditional mode-based editing, sketch-based editing, and gesture-based editing. Most of today's diagram editors are mode-based and use the mouse as an input device. (Multi-)touch inputs have not been integrated very well, although a variety of touch input devices, such as (multi-)touch monitors and tablet computers, are quite common today. In this paper, we provide some insights into the integration of an off-the-shelf unistroke gesture recognizer into an existing diagram editor framework, and give some details about three example diagram editors that incorporate a new interaction mode, the so-called gesture mode.

With a single exception, all isolates of hepatitis C virus (HCV) require adaptive mutations to replicate efficiently in cell culture. Here, we show that a major class of adaptive mutations regulates the activity of a cellular lipid kinase, phosphatidylinositol 4-kinase IIIα (PI4KA). HCV needs to stimulate PI4KA to create a permissive phosphatidylinositol 4-phosphate-enriched membrane microenvironment in the liver and in primary human hepatocytes (PHHs). In contrast, in Huh7 hepatoma cells, the virus must acquire loss-of-function mutations that prevent PI4KA overactivation. This adaptive mechanism is necessitated by increased PI4KA levels in Huh7 cells compared with PHHs, and is conserved across HCV genotypes. PI4KA-specific inhibitors promote replication of unadapted viral isolates and allow efficient replication of patient-derived virus in cell culture. In summary, this study has uncovered a long-sought mechanism of HCV cell-culture adaptation and demonstrates how a virus can adapt to changes in a cellular environment associated with tumorigenesis.

A comprehensive study of optical and mechanical properties of quartz glass (fused silica) with regard to application in high temperature solar receivers is presented. The dependence of rupture strength on different surface conditions as well as high temperature is analyzed, focussing particularly on damage by devitrification and sandblasting. The influence of typical types of contamination in combination with thermal cycling on the optical properties of fused silica is determined. Cleaning methods are compared regarding effectiveness on contamination-induced degradation for samples with and without antireflective coating. The FEM-aided design of different types of receiver windows and their support structure is presented. A large-scale production process has been developed for producing fused silica dome shaped windows (pressurized window) up to a diameter of 816 mm. Prototypes were successfully pressure-tested in a test bench and certified according to the European Pressure Vessel Directive.

The reduction of the bulky amido-germanium(II) chloride complex, LGeCl (L = N(SiMe(3))(Ar*); Ar* = C(6)H(2)Me{C(H)Ph(2)}(2)-4,2,6), with the magnesium(I) dimer, [{((Mes)Nacnac)Mg}(2)] ((Mes)Nacnac = [(MesNCMe)(2)CH](-); Mes = mesityl), afforded LGeGeL, which represents the first example of a digermyne with a Ge-Ge single bond. Computational studies of the compound have highlighted significant electronic differences between it and multiply bonded digermynes. LGeGeL was shown to cleanly activate H(2) in solution or the solid state, at temperatures as low as -10 °C, to give the mixed valence compound, LGeGe(H)(2)L.