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Background: Circulating infliximab (IFX) concentrations correlate with clinical outcomes, forming the basis of the IFX concentration monitoring in patients with Crohn's disease. This study aims to investigate and refine the exposure-response relationship by linking the disease activity markers "Crohn's disease activity index" (CDAI) and C-reactive protein (CRP) to IFX exposure. In addition, we aim to explore the correlations between different disease markers and exposure metrics.
Methods: Data from 47 Crohn's disease patients of a randomized controlled trial were analyzed post hoc. All patients had secondary treatment failure at inclusion and had received intensified IFX of 5 mg/kg every 4 weeks for up to 20 weeks. Graphical analyses were performed to explore exposure-response relationships. Metrics of exposure included area under the concentration-time curve (AUC) and trough concentrations (Cmin). Disease activity was measured by CDAI and CRP values, their change from baseline/last visit, and response/remission outcomes at week 12.
Results: Although trends toward lower Cmin and lower AUC in nonresponders were observed, neither CDAI nor CRP showed consistent trends of lower disease activity with higher IFX exposure across the 30 evaluated relationships. As can be expected, Cmin and AUC were strongly correlated with each other. Contrarily, the disease activity markers were only weakly correlated with each other.
Conclusions: No significant relationship between disease activity, as evaluated by CDAI or CRP, and IFX exposure was identified. AUC did not add benefit compared with Cmin. These findings support the continued use of Cmin and call for stringent objective disease activity (bio-)markers (eg, endoscopy) to form the basis of personalized IFX therapy for Crohn's disease patients with IFX treatment failure.
Accelerating knowledge
(2019)
As knowledge-intensive processes are often carried out in teams and demand for knowledge transfers among various knowledge carriers, any optimization in regard to the acceleration of knowledge transfers obtains a great economic potential. Exemplified with product development projects, knowledge transfers focus on knowledge acquired in former situations and product generations. An adjustment in the manifestation of knowledge transfers in its concrete situation, here called intervention, therefore can directly be connected to the adequate speed optimization of knowledge-intensive process steps. This contribution presents the specification of seven concrete interventions following an intervention template. Further, it describes the design and results of a workshop with experts as a descriptive study. The workshop was used to assess the practical relevance of interventions designed as well as the identification of practical success factors and barriers of their implementation.
The unceasing impact of intense sunlight on earth constitutes a continuous source of energy fueling countless natural processes. On a molecular level, the energy contained in the electromagnetic radiation is transferred through photochemical processes into chemical or thermal energy. In the course of such processes, photo-excitations promote molecules into thermally inaccessible excited states. This induces adaptations of their molecular geometry according to the properties of the excited state. Decay processes towards energetically lower lying states in transient molecular geometries result in the formation of excited state relaxation pathways. The photo-chemical relaxation mechanisms depend on the studied system itself, the interactions with its chemical environment and the character of the involved states. This thesis focuses on systems in which photo-induced deprotonation processes occur at specific atomic sites.
To detect these excited-state proton dynamics at the affected atoms, a local probe of molecular electronic structure is required. Therefore, site-selective and orbital-specific K-edge soft X-ray spectroscopy techniques are used here to detect photo-induced proton dynamics in gaseous and liquid sample environments. The protonation of nitrogen (N) sites in organic molecules and the oxygen (O) atom in the water molecule are probed locally through transitions between 1s orbitals and the p-derived molecular valence electronic structure. The used techniques are X-ray absorption spectroscopy (XAS) and resonant inelastic X-ray scattering (RIXS). Both yield access to the unoccupied local valence electronic structure, whereas the latter additionally probes occupied states.
We apply these probes in optical pump X-ray probe experiments to investigate valence excited-state proton transfer capabilities of aqueous 2-thiopyridone. A characteristic shift of N K-edge X-ray absorption resonances as well as a distinct X-ray emission line are established by us as spectral fingerprints of N deprotonation in the system. We utilize them to identify photo-induced N deprotonation of 2-thiopyridone on femtosecond timescales, in optical pump N K-edge RIXS probe measurements. We further establish excited state proton transfer mechanisms on picosecond and nanosecond timescales along the dominant relaxation pathways of 2-thiopyridone using transient N K-edge XAS.
Despite being an excellent probe mechanism for valence excited-state proton dynamics, the K-edge core-excitation itself also disturbs the electronic structure at specific sites of a molecule. The rapid reaction of protons to 1s photo-excitations can yield directional structural distortions within the femtosecond core-excited state lifetime. These directional proton dynamics can change the energetic separation of eigenstates of the system and alter probabilities for radiative decay between them. Both effects yield spectral signatures of the dynamics in RIXS spectra.
Using these signatures of RIXS transitions into electronically excited states, we investigate proton dynamics induced by N K-edge excitation in the amino-acid histidine. The minor core-excited state dynamics of histidine in basic and neutral chemical environments allow us to establish XAS and RIXS spectral signatures of different N protonation states at its imidazole N sites. Based on these signatures, we identify an excitation-site-independent N-H dissociation for N K-edge excitation under acidic conditions.
Such directional structural deformations, induced by core-excitations, also make proton dynamics in electronic ground states accessible through RIXS transitions into vibrationally excited states. In that context, we interpret high resolution RIXS spectra of the water molecule for three O K-edge resonances based on quantum-chemical wave packet propagation simulations. We show that highly oriented ground state vibrational modes of coupled nuclear motion can be populated through RIXS processes by preparation of core-excited state nuclear wave packets with the same directionality. Based on that, we analytically derive the possibility to extract one-dimensional directional cuts through potential energy surfaces of molecular systems from the corresponding RIXS spectra. We further verify this concept through the extraction of the gas-phase water ground state potential along three coordinates from experimental data in comparison to quantum-chemical simulations of the potential energy surface.
This thesis also contains contributions to instrumentation development for investigations of photo-induced molecular dynamics at high brilliance X-ray light sources. We characterize the setup used for the transient valence-excited state XAS measurements of 2-thiopyridone. Therein, a sub-micrometer thin liquid sample environment is established employing in-vacuum flat-jet technology, which enables a transmission experimental geometry. In combination with a MHz-laser system, we achieve a high detection sensitivity for photo-induced X-ray absorption changes. Additionally, we present conceptual improvements for temporal X-ray optical cross-correlation techniques based on transient changes of multilayer optical properties, which are crucial for the realization of femtosecond time-resolved studies at synchrotrons and free-electron lasers.
Vermetid reefs and rocky shores are hot spots of biodiversity, often referred to as the subtropical equivalent of coral reefs. The development of the ecosystem depends on the activity of several reef builders, including red crustose coralline algae (CCA) such as Neogoniolithon brassica-florida. Despite its importance, little is known about Neogoniolithon sp. acclimation to rapid changes in light intensity and corresponding photosynthetic activity. To overcome the large spatial variability in the light field (due to location and the porous nature of the rocks) we grew Neogoniolithon sp. on glass slides and characterized its photosynthetic performance in response to various light intensities by following O-2 exchange and fluorescence parameters. This was also performed on rock-inhabiting thalli collected from the east Mediterranean basin. Generally, maximal photosynthetic rate was reached when Neogoniolithon sp. thalli grown under low illumination (such as in protected niches where the light intensity can be as low as 1% of surface illumination) were examined. When exposed to light intensities higher than those experienced during growth, Neogoniolithon sp. activates adaptive/protective mechanisms such as state transition and nonphotochemical fluorescence quenching and increases the dark respiration thereafter. We find that the Fv/Fm parameter (variable/maximal fluorescence) is not suitable to assess photosynthetic performance in Neogoniolithon sp. and propose using instead an alternative parameter recently developed. Our findings help to clarify why Neogoniolithon sp. is usually observed in shaded niches along the reef surfaces.
Accusative Unaccusatives
(2019)
Business process improvement is an endless challenge for many organizations. As long as there is a process, it must he improved. Nowadays, improvement initiatives are driven by professionals. This is no longer practical because people cannot perceive the enormous data of current business environments. Here, we introduce ubiquitous decision-aware business processes. They pervade the physical space, analyze the ever-changing environments, and make decisions accordingly. We explain how they can be built and used for improvement. Our approach can be a valuable improvement option to alleviate the workload of participants by helping focus on the crucial rather than the menial tasks.
Objectives: Although expected, tendon adaptations in adolescent elite athletes have been underreported. Morphologically, adaptations may occur by an increase in collagen fiber density and/or organization. These characteristics can be captured using spatial frequency parameters extracted from ultrasound images. This study aims to compare Achilles tendon (AT) morphology among sports-specific cohorts of elite adolescent athletes and to compare these findings to recreationally active controls by use of spatial frequency analysis. Design: Cross-sectional observational study. Method: In total, 334 healthy adolescent athletes from four sport categories (ball, combat, endurance, explosive strength) and 35 healthy controls were included. Longitudinal ultrasound scans were performed at the AT insertion and midportion. Intra-tendinous-morphology was quantified by performing spatial frequency analysis assessing eight parameters at standardized ROls. Increased values in five parameters suggest a higher structural organization, and in two parameters higher fiber density. One parameter represents a quotient combining both organization and fiber density. Results: Among athletes, only ball sport athletes exhibited an increase in one summative parameter at pre-insertion site compared to athletes from other sport categories. When compared to athletes, controls had significantly higher values of four parameters at pre-insertion and three parameters at midportion site reflecting differences in both, fiber organization and density. Conclusions: Intra-tendinous-morphology was similar in all groups of adolescent athletes. Higher values found in non-athletes might suggest higher AT fiber density and organization. It is yet unclear whether the lesser structural organization in young athletes represents initial AT pathology, or a physiological adaptive response at the fiber cross-linking level. (C) 2019 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.
Recent investigations propose the acid sphingomyelinase (ASM)/ceramide system as a novel target for antidepressant action. ASM catalyzes the breakdown of the abundant membrane lipid sphingomyelin to the lipid messenger ceramide. This ASM‐induced lipid modification induces a local shift in membrane properties, which influences receptor clustering and downstream signaling. Canonical transient receptor potential channels 6 (TRPC6) are non‐selective cation channels located in the cell membrane that play an important role in dendritic growth, synaptic plasticity and cognition in the brain. They can be activated by hyperforin, an ingredient of the herbal remedy St. John’s wort for treatment of depression disorders. Because of their role in the context of major depression, we investigated the crosstalk between the ASM/ceramide system and TRPC6 ion channels in a pheochromocytoma cell line 12 neuronal cell model (PC12 rat pheochromocytoma cell line). Ca2+ imaging experiments indicated that hyperforin‐induced Ca2+ influx through TRPC6 channels is modulated by ASM activity. While antidepressants, known as functional inhibitors of ASM activity, reduced TRPC6‐mediated Ca2+ influx, extracellular application of bacterial sphingomyelinase rebalanced TRPC6 activity in a concentration‐related way. This effect was confirmed in whole‐cell patch clamp electrophysiology recordings. Lipidomic analyses revealed a decrease in very long chain ceramide/sphingomyelin molar ratio after ASM inhibition, which was connected with changes in the abundance of TRPC6 channels in flotillin‐1–positive lipid rafts as visualized by western blotting. Our data provide evidence that the ASM/ceramide system regulates TRPC6 channels likely by controlling their recruitment to specific lipid subdomains and thereby fine‐tuning their physical properties.
Farber disease is a rare lysosomal storage disorder resulting from acid ceramidase deficiency and subsequent ceramide accumulation. No treatments for Farber disease are clinically available, and affected patients have a severely shortened lifespan. We have recently reported a novel acid ceramidase deficiency model that mirrors the human disease closely. Acid sphingomyelinase is the enzyme that generates ceramide upstream of acid ceramidase in the lysosomes. Using our acid ceramidase deficiency model, we tested if acid sphingomyelinase could be a potential novel therapeutic target for the treatment of Farber disease. A number of functional acid sphingomyelinase inhibitors are clinically available and have been used for decades to treat major depression. Using these as a therapeutic for Farber disease, thus, has the potential to improve central nervous symptoms of the disease as well, something all other treatment options for Farber disease can’t achieve so far. As a proof-of-concept study, we first cross-bred acid ceramidase deficient mice with acid sphingomyelinase deficient mice in order to prevent ceramide accumulation. Double-deficient mice had reduced ceramide accumulation, fewer disease manifestations, and prolonged survival. We next targeted acid sphingomyelinase pharmacologically, to test if these findings would translate to a setting with clinical applicability. Surprisingly, the treatment of acid ceramidase deficient mice with the acid sphingomyelinase inhibitor amitriptyline was toxic to acid ceramidase deficient mice and killed them within a few days of treatment. In conclusion, our study provides the first proof-of-concept that acid sphingomyelinase could be a potential new therapeutic target for Farber disease to reduce disease manifestations and prolong survival. However, we also identified previously unknown toxicity of the functional acid sphingomyelinase inhibitor amitriptyline in the context of Farber disease, strongly cautioning against the use of this substance class for Farber disease patients
Farber disease is a rare lysosomal storage disorder resulting from acid ceramidase deficiency and subsequent ceramide accumulation. No treatments for Farber disease are clinically available, and affected patients have a severely shortened lifespan. We have recently reported a novel acid ceramidase deficiency model that mirrors the human disease closely. Acid sphingomyelinase is the enzyme that generates ceramide upstream of acid ceramidase in the lysosomes. Using our acid ceramidase deficiency model, we tested if acid sphingomyelinase could be a potential novel therapeutic target for the treatment of Farber disease. A number of functional acid sphingomyelinase inhibitors are clinically available and have been used for decades to treat major depression. Using these as a therapeutic for Farber disease, thus, has the potential to improve central nervous symptoms of the disease as well, something all other treatment options for Farber disease can’t achieve so far. As a proof-of-concept study, we first cross-bred acid ceramidase deficient mice with acid sphingomyelinase deficient mice in order to prevent ceramide accumulation. Double-deficient mice had reduced ceramide accumulation, fewer disease manifestations, and prolonged survival. We next targeted acid sphingomyelinase pharmacologically, to test if these findings would translate to a setting with clinical applicability. Surprisingly, the treatment of acid ceramidase deficient mice with the acid sphingomyelinase inhibitor amitriptyline was toxic to acid ceramidase deficient mice and killed them within a few days of treatment. In conclusion, our study provides the first proof-of-concept that acid sphingomyelinase could be a potential new therapeutic target for Farber disease to reduce disease manifestations and prolong survival. However, we also identified previously unknown toxicity of the functional acid sphingomyelinase inhibitor amitriptyline in the context of Farber disease, strongly cautioning against the use of this substance class for Farber disease patients.
The epicardium, the outer mesothelial layer enclosing the myocardium, plays key roles in heart development and regeneration. During embryogenesis, the epicardium arises from the proepicardium (PE), a cell cluster that appears in the dorsal pericardium (DP) close to the venous pole of the heart. Little is known about how the PE emerges from the pericardial mesothelium. Using a zebrafish model and a combination of genetic tools, pharmacological agents and quantitative in vivo imaging, we reveal that a coordinated collective movement of DP cells drives PE formation. We found that Bmp signaling and the actomyosin cytoskeleton promote constriction of the DP, which enables PE cells to extrude apically. We provide evidence that cell extrusion, which has been described in the elimination of unfit cells from epithelia and the emergence of hematopoietic stem cells, is also a mechanism for PE cells to exit an organized mesothelium and fulfil their developmental fate to form a new tissue layer, the epicardium.
The purpose of this study was to examine the acute effects of short-term Achilles tendon vibration on plantar flexor torque, twitch contractile properties as well as muscle and cortical activity in young athletes. Eleven female elite soccer players aged 15.6 +/- 0.5 years participated in this study. Three different conditions were applied in randomized order: Achilles tendon vibration (80 Hz) for 30 and 300 s, and a passive control condition (300 s). Tests at baseline and following conditions included the assessment of peak plantar flexor torque during maximum voluntary contraction, electrically evoked muscle twitches (e.g., potentiated twitch peak torque [PT]), and electromyographic (EMG) activity of the plantar flexors. Additionally, electroencephalographic (EEG) activity of the primary motor and somatosensory cortex were assessed during a submaximal dynamic concentric-eccentric plantar flexion exercise using an elastic rubber band. Large-sized main effects of condition were found for EEG absolute alpha-1 and beta-1 band power (p <= 0.011; 1.5 <= d <= 2.6). Post-hoc tests indicated that alpha-1 power was significantly lower at 30 and 300 s (p = 0.009; d = 0.8) and beta-1 power significantly lower at 300 s (p < 0.001; d = 0.2) compared to control condition. No significant effect of condition was found for peak plantar flexor torque, electrical evoked muscle twitches, and EMG activity. In conclusion, short-term local Achilles tendon vibration induced lower brain activity (i.e., alpha-1 and beta-1 band power) but did not affect lower limb peak torque, twitch contractile properties, and muscle activity. Lower brain activity following short-term local Achilles tendon vibration may indicate improved cortical function during a submaximal dynamic exercise in female young soccer players.
The effects of static stretching (StS) on subsequent strength and power activities has been one of the most debated topics in sport science literature over the past decades. The aim of this review is (1) to summarize previous and current findings on the acute effects of StS on muscle strength and power performances; (2) to update readers’ knowledge related to previous caveats; and (3) to discuss the underlying physiological mechanisms of short-duration StS when performed as single-mode treatment or when integrated into a full warm-up routine. Over the last two decades, StS has been considered harmful to subsequent strength and power performances. Accordingly, it has been recommended not to apply StS before strength- and power-related activities. More recent evidence suggests that when performed as a single-mode treatment or when integrated within a full warm-up routine including aerobic activity, dynamic-stretching, and sport-specific activities, short-duration StS (≤60 s per muscle group) trivially impairs subsequent strength and power activities (∆1–2%). Yet, longer StS durations (>60 s per muscle group) appear to induce substantial and practically relevant declines in strength and power performances (∆4.0–7.5%). Moreover, recent evidence suggests that when included in a full warm-up routine, short-duration StS may even contribute to lower the risk of sustaining musculotendinous injuries especially with high-intensity activities (e.g., sprint running and change of direction speed). It seems that during short-duration StS, neuromuscular activation and musculotendinous stiffness appear not to be affected compared with long-duration StS. Among other factors, this could be due to an elevated muscle temperature induced by a dynamic warm-up program. More specifically, elevated muscle temperature leads to increased muscle fiber conduction-velocity and improved binding of contractile proteins (actin, myosin). Therefore, our previous understanding of harmful StS effects on subsequent strength and power activities has to be updated. In fact, short-duration StS should be included as an important warm-up component before the uptake of recreational sports activities due to its potential positive effect on flexibility and musculotendinous injury prevention. However, in high-performance athletes, short-duration StS has to be applied with caution due to its negligible but still prevalent negative effects on subsequent strength and power performances, which could have an impact on performance during competition.
The effects of static stretching (StS) on subsequent strength and power activities has been one of the most debated topics in sport science literature over the past decades. The aim of this review is (1) to summarize previous and current findings on the acute effects of StS on muscle strength and power performances; (2) to update readers’ knowledge related to previous caveats; and (3) to discuss the underlying physiological mechanisms of short-duration StS when performed as single-mode treatment or when integrated into a full warm-up routine. Over the last two decades, StS has been considered harmful to subsequent strength and power performances. Accordingly, it has been recommended not to apply StS before strength- and power-related activities. More recent evidence suggests that when performed as a single-mode treatment or when integrated within a full warm-up routine including aerobic activity, dynamic-stretching, and sport-specific activities, short-duration StS (≤60 s per muscle group) trivially impairs subsequent strength and power activities (∆1–2%). Yet, longer StS durations (>60 s per muscle group) appear to induce substantial and practically relevant declines in strength and power performances (∆4.0–7.5%). Moreover, recent evidence suggests that when included in a full warm-up routine, short-duration StS may even contribute to lower the risk of sustaining musculotendinous injuries especially with high-intensity activities (e.g., sprint running and change of direction speed). It seems that during short-duration StS, neuromuscular activation and musculotendinous stiffness appear not to be affected compared with long-duration StS. Among other factors, this could be due to an elevated muscle temperature induced by a dynamic warm-up program. More specifically, elevated muscle temperature leads to increased muscle fiber conduction-velocity and improved binding of contractile proteins (actin, myosin). Therefore, our previous understanding of harmful StS effects on subsequent strength and power activities has to be updated. In fact, short-duration StS should be included as an important warm-up component before the uptake of recreational sports activities due to its potential positive effect on flexibility and musculotendinous injury prevention. However, in high-performance athletes, short-duration StS has to be applied with caution due to its negligible but still prevalent negative effects on subsequent strength and power performances, which could have an impact on performance during competition.
The importance of cryptic diversity in rotifers is well understood regarding its ecological consequences, but there remains an in depth comprehension of the underlying molecular mechanisms and forces driving speciation. Temperature has been found several times to affect species spatio-temporal distribution and organisms’ performance, but we lack information on the mechanisms that provide thermal tolerance to rotifers. High cryptic diversity was found recently in the freshwater rotifer “Brachionus calyciflorus”, showing that the complex comprises at least four species: B. calyciflorus sensu stricto (s.s.), B. fernandoi, B. dorcas, and B. elevatus. The temporal succession among species which have been observed in sympatry led to the idea that temperature might play a crucial role in species differentiation.
The central aim of this study was to unravel differences in thermal tolerance between species of the former B. calyciflorus species complex by comparing phenotypic and gene expression responses. More specifically, I used the critical maximum temperature as a proxy for inter-species differences in heat-tolerance; this was modeled as a bi-dimensional phenotypic trait taking into consideration the intention and the duration of heat stress. Significant differences on heat-tolerance between species were detected, with B. calyciflorus s.s. being able to tolerate higher temperatures than B. fernandoi.
Based on evidence of within species neutral genetic variation, I further examined adaptive genetic variability within two different mtDNA lineages of the heat tolerant B. calyciflorus s.s. to identify SNPs and genes under selection that might reflect their adaptive history. These analyses did not reveal adaptive genetic variation related to heat, however, they show putatively adaptive genetic variation which may reflect local adaptation. Functional enrichment of putatively positively selected genes revealed signals of adaptation in genes related to “lipid metabolism”, “xenobiotics biodegradation and metabolism” and “sensory system”, comprising candidate genes which can be utilized in studies on local adaptation. An absence of genetically-based differences in thermal adaptation between the two mtDNA lineages, together with our knowledge that B. calyciflorus s.s. can withstand a broad range of temperatures, led to the idea to further investigate shared transcriptomic responses to long-term exposure to high and low temperatures regimes. With this, I identified candidate genes that are involved in the response to temperature imposed stress. Lastly, I used comparative transcriptomics to examine responses to imposed heat-stress in heat-tolerant and heat-sensitive Brachionus species. I found considerably different patterns of gene expression in the two species. Most striking are patterns of expression regarding the heat shock proteins (hsps) between the two species. In the heat-tolerant, B. calyciflorus s.s., significant up-regulation of hsps at low temperatures was indicative of a stress response at the cooler end of the temperature regimes tested here. In contrast, in the heat-sensitive B. fernandoi, hsps generally exhibited up-regulation of these genes along with rising temperatures. Overall, identification of differences in expression of genes suggests suppression of protein biosynthesis to be a mechanism to increase thermal tolerance. Observed patterns in population growth are correlated with the hsp gene expression differences, indicating that this physiological stress response is indeed related to phenotypic life history performance.
Biological responses to climate change have been widely documented across taxa and regions, but it remains unclear whether species are maintaining a good match between phenotype and environment, i.e. whether observed trait changes are adaptive. Here we reviewed 10,090 abstracts and extracted data from 71 studies reported in 58 relevant publications, to assess quantitatively whether phenotypic trait changes associated with climate change are adaptive in animals. A meta-analysis focussing on birds, the taxon best represented in our dataset, suggests that global warming has not systematically affected morphological traits, but has advanced phenological traits. We demonstrate that these advances are adaptive for some species, but imperfect as evidenced by the observed consistent selection for earlier timing. Application of a theoretical model indicates that the evolutionary load imposed by incomplete adaptive responses to ongoing climate change may already be threatening the persistence of species.
In a previously published article in HIN under the title of “Eduard Dorsch and his unpublished poem on the occasion of Humboldt’s 100th birthday,” I elaborated on Dorsch’s poem that was read in Detroit in front of a German-American audience on Sept. 14, 1869, a day widely celebrated in the US in honor of Humboldt. Although it was not surprising that Dorsch wrote the occasional poem in the first place given his affinities with Humboldt’s world of thought, a discovery of a second occasional poem upon further research in Dorsch’s voluminous papers was indeed unexpected, in this case read on the same date in Monroe, Michigan. Although there are a number of similarities between the Detroit and Monroe versions, there are enough differences that warrant this addendum to my original article.
While Africa’s lacustrine gastropod fauna, in particular of Lake Tanganyika, has received much attention, the continent’s riverine malacofauna has long been neglected. Pseudocleopatra is a relatively poorly known paludomid gastropod genus with species found throughout the lower reaches of the West African Volta and Congo rivers. In the course of ongoing systematic revisions of African paludomids, we present here a morphometric analysis and revision of the recent species assigned to the genus, i.e., P. togoensis, P. voltana, P. dartevellei and P. bennikei, to improve taxonomic acuity for this group. We use available museum material for geometric morphometrics, multivariate ratio analysis and comparisons of radular and opercular characters. Our results demonstrate that the four recent species of Pseudocleopatra are clearly distinguishable on the basis of ratios of shell measurements as well as radular and opercular characters. Pseudocleopatra has generic-level synapomorphies including: concentric opercula with relatively large paucispiral nuclei, and rachidian radular teeth with usually 13–20 cusps. On the basis of this characterisation, the nominal species Cleopatra broecki is transferred to Pseudocleopatra. Additionally, the nominal taxon P. bennikei is synonymized with P. broecki n. comb. The phylogenetic relationships of Pseudocleopatra are currently unknown, but the observed tendency of some fossil taxa assigned to Pseudocleopatra towards thalassoidism, i.e., the resemblance to marine gastropods, has led to the hypothesis that some of the thalassoid endemics in Lake Tanganyika may have originated from or be related to Pseudocleopatra. Should this hypothesis be correct, which is in need of testing by molecular genetic methods when suitable samples become available, Pseudocleopatra may play a crucial role in understanding of the evolution of thalassoidism in African Paludomidae.
Industry 4.0 and the Internet of Things are recent developments that have lead to the creation of new kinds of manufacturing data. Linking this new kind of sensor data to traditional business information is crucial for enterprises to take advantage of the data’s full potential. In this paper, we present a demo which allows experiencing this data integration, both vertically between technical and business contexts and horizontally along the value chain. The tool simulates a manufacturing company, continuously producing both business and sensor data, and supports issuing ad-hoc queries that answer specific questions related to the business. In order to adapt to different environments, users can configure sensor characteristics to their needs.