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After more than twenty years of research, the molecular events of apoptotic cell death can be succinctly stated; different pathways, activated by diverse signals, increase the activity of proteases called caspases that rapidly and irreversibly dismantle condemned cell by cleaving specific substrates. In this time the ideas that apoptosis protects us from tumourigenesis and that cancer chemotherapy works by inducing apoptosis also emerged. Currently, apoptosis research is shifting away from the intracellular events within the dying cell to focus on the effect of apoptotic cells on surrounding tissues. This is producing counterintuitive data showing that our understanding of the role of apoptosis in tumourigenesis and cancer therapy is too simple, with some interesting and provocative implications. Here, we will consider evidence supporting the idea that dying cells signal their presence to the surrounding tissue and, in doing so, elicit repair and regeneration that compensates for any loss of function caused by cell death. We will discuss evidence suggesting that cancer cell proliferation may be driven by inappropriate or corrupted tissue-repair programmes that are initiated by signals from apoptotic cells and show how this may dramatically modify how we view the role of apoptosis in both tumourigenesis and cancer therapy.
Software developers build complex systems using plenty of third-party libraries. Documentation is key to understand and use the functionality provided via the libraries’ APIs. Therefore, functionality is the main focus of contemporary API documentation, while cross-cutting concerns such as security are almost never considered at all, especially when the API itself does not provide security features. Documentations of JavaScript libraries for use in web applications, e.g., do not specify how to add or adapt a Content Security Policy (CSP) to mitigate content injection attacks like Cross-Site Scripting (XSS). This is unfortunate, as security-relevant API documentation might have an influence on secure coding practices and prevailing major vulnerabilities such as XSS. For the first time, we study the effects of integrating security-relevant information in non-security API documentation. For this purpose, we took CSP as an exemplary study object and extended the official Google Maps JavaScript API documentation with security-relevant CSP information in three distinct manners. Then, we evaluated the usage of these variations in a between-group eye-tracking lab study involving N=49 participants. Our observations suggest: (1) Developers are focused on elements with code examples. They mostly skim the documentation while searching for a quick solution to their programming task. This finding gives further evidence to results of related studies. (2) The location where CSP-related code examples are placed in non-security API documentation significantly impacts the time it takes to find this security-relevant information. In particular, the study results showed that the proximity to functional-related code examples in documentation is a decisive factor. (3) Examples significantly help to produce secure CSP solutions. (4) Developers have additional information needs that our approach cannot meet.
Overall, our study contributes to a first understanding of the impact of security-relevant information in non-security API documentation on CSP implementation. Although further research is required, our findings emphasize that API producers should take responsibility for adequately documenting security aspects and thus supporting the sensibility and training of developers to implement secure systems. This responsibility also holds in seemingly non-security relevant contexts.
Das sogenannte „Deutschlandstipendium“ ist 2010 ins Leben gerufen worden. Gemäß den gesetzlichen Vorgaben sollen die Stipendien nach Begabung und Leistung vergeben werden. Darüber hinaus sollen auch gesellschaftliches Engagement oder besondere soziale, familiäre oder persönliche Umstände berücksichtigt werden. Bei der Finanzierung sind die Hochschulen zunächst auf das Einwerben privater Fördermittel angewiesen, die von Bund und Land um denselben Betrag aufgestockt werden. Die privaten Mittelgeber können für die von ihnen anteilig finanzierten Stipendien festlegen, aus welchen Studiengängen ihre Stipendiaten ausgewählt werden sollen. Die Hochschulen haben jedoch darauf zu achten, dass ein Drittel aller zu vergebenden Stipendien ohne eine entsprechende Zweckbindung vergeben werden. Einen direkten Einfluss auf die Auswahl einzelner Kandidaten dürfen die Förderer nicht haben. Vor diesem Hintergrund sind die Hochschulen angehalten, Anreize für private Förderer zu schaffen und parallel Bewerbungs- und Auswahlverfahren zu konzipieren, die die genannten gesetzlichen Vorgaben einhalten. Dadurch entsteht bei den Hochschulen ein erheblicher Verwaltungsaufwand. Zu dessen Reduzierung wird in diesem Artikel ein transparenter, nachvollziehbarer, zeit- und kostensparender Prozess durch einen programmierten Workflow beschrieben.
2-methylacetoacetyl-coenzyme A thiolase (beta-ketothiolase) deficiency: one disease - two pathways
(2020)
Background: 2-methylacetoacetyl-coenzyme A thiolase deficiency (MATD; deficiency of mitochondrial acetoacetyl-coenzyme A thiolase T2/ “beta-ketothiolase”) is an autosomal recessive disorder of ketone body utilization and isoleucine degradation due to mutations in ACAT1.
Methods: We performed a systematic literature search for all available clinical descriptions of patients with MATD. Two hundred forty-four patients were identified and included in this analysis. Clinical course and biochemical data are presented and discussed.
Results: For 89.6% of patients at least one acute metabolic decompensation was reported. Age at first symptoms ranged from 2 days to 8 years (median 12 months). More than 82% of patients presented in the first 2 years of life, while manifestation in the neonatal period was the exception (3.4%). 77.0% (157 of 204 patients) of patients showed normal psychomotor development without neurologic abnormalities. Conclusion: This comprehensive data analysis provides a systematic overview on all cases with MATD identified in the literature. It demonstrates that MATD is a rather benign disorder with often favourable outcome, when compared with many other organic acidurias.
Nitrile-type inhibitors are known to interact with cysteine proteases in a covalent-reversible manner. The chemotype of 3-cyano-3-aza-β-amino acid derivatives was designed in which the N-cyano group is centrally arranged in the molecule to allow for interactions with the nonprimed and primed binding regions of the target enzymes. These compounds were evaluated as inhibitors of the human cysteine cathepsins K, S, B, and L. They exhibited slow-binding behavior and were found to be exceptionally potent, in particular toward cathepsin K, with second-order rate constants up to 52 900 × 103 M–1 s–1.
Background: 3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency (HMGCLD) is an autosomal recessive disorder of ketogenesis and leucine degradation due to mutations in HMGCL.
Method: We performed a systematic literature search to identify all published cases. Two hundred eleven patients of whom relevant clinical data were available were included in this analysis. Clinical course, biochemical findings and mutation data are highlighted and discussed. An overview on all published HMGCL variants is provided.
Results: More than 95% of patients presented with acute metabolic decompensation. Most patients manifested within the first year of life, 42.4% already neonatally. Very few individuals remained asymptomatic. The neurologic long-term outcome was favorable with 62.6% of patients showing normal development.
Conclusion: This comprehensive data analysis provides a systematic overview on all published cases with HMGCLD including a list of all known HMGCL mutations.
3-Hydroxyisobutyrate Dehydrogenase (HIBADH) deficiency - a novel disorder of valine metabolism
(2021)
3-Hydroxyisobutyric acid (3HiB) is an intermediate in the degradation of the branched-chain amino acid valine. Disorders in valine degradation can lead to 3HiB accumulation and its excretion in the urine. This article describes the first two patients with a new metabolic disorder, 3-hydroxyisobutyrate dehydrogenase (HIBADH) deficiency, its phenotype and its treatment with a low-valine diet. The detected mutation in the HIBADH gene leads to nonsense-mediated mRNA decay of the mutant allele and to a complete loss-of-function of the enzyme. Under strict adherence to a low-valine diet a rapid decrease of 3HiB excretion in the urine was observed. Due to limited patient numbers and intrafamilial differences in phenotype with one affected and one unaffected individual, the clinical phenotype of HIBADH deficiency needs further evaluation.
Animal models are often needed in cancer research but some research questions may be answered with other models, e.g., 3D replicas of patient-specific data, as these mirror the anatomy in more detail. We, therefore, developed a simple eight-step process to fabricate a 3D replica from computer tomography (CT) data using solely open access software and described the method in detail. For evaluation, we performed experiments regarding endoscopic tumor treatment with magnetic nanoparticles by magnetic hyperthermia and local drug release. For this, the magnetic nanoparticles need to be accumulated at the tumor site via a magnetic field trap. Using the developed eight-step process, we printed a replica of a locally advanced pancreatic cancer and used it to find the best position for the magnetic field trap. In addition, we described a method to hold these magnetic field traps stably in place. The results are highly important for the development of endoscopic tumor treatment with magnetic nanoparticles as the handling and the stable positioning of the magnetic field trap at the stomach wall in close proximity to the pancreatic tumor could be defined and practiced. Finally, the detailed description of the workflow and use of open access software allows for a wide range of possible uses.
Background: Cancer heterogeneity poses a serious challenge concerning the toxicity and adverse effects of therapeutic inhibitors, especially when it comes to combinatorial therapies that involve multiple targeted inhibitors. In particular, in non-small cell lung cancer (NSCLC), a number of studies have reported synergistic effects of drug combinations in the preclinical models, while they were only partially successful in the clinical setup, suggesting those alternative clinical strategies (with genetic background and immune response) should be considered. Herein, we investigated the antitumor effect
of cytokine-induced killer (CIK) cells in combination with ALK and PD-1 inhibitors in vitro on genetically variable NSCLC cell lines.
Methods: We co-cultured the three genetically different NSCLC cell lines NCI-H2228 (EML4-ALK), A549 (KRAS mutation), and HCC-78 (ROS1 rearrangement) with and without nivolumab (PD-1 inhibitor) and crizotinib (ALK inhibitor). Additionally, we profiled the variability of surface expression multiple immune checkpoints, the concentration of absolute dead cells, intracellular granzyme B on CIK cells using flow cytometry as well as RT-qPCR. ELISA and Western blot were performed to verify the activation of CIK cells.
Results: Our analysis showed that (a) nivolumab significantly weakened PD-1 surface expression on CIK cells without impacting other immune checkpoints or PD-1 mRNA expression, (b) this combination strategy showed an effective response on cell viability, IFN-g production, and intracellular release of granzyme B in CD3+ CD56+ CIK cells, but solely in NCI-H2228, (c) the intrinsic expression of Fas ligand (FasL) as a T-cell activation marker in CIK cells was upregulated by this additive effect, and (d) nivolumab induced Foxp3 expression in CD4+CD25+ subpopulation of CIK cells significantly increased. Taken together, we could show that CIK cells in combination with crizotinib and nivolumab can enhance the anti-tumor immune response through FasL activation, leading to increased IFN-g and granzyme B, but only in NCI-H2228 cells with EML4-ALK rearrangement. Therefore, we hypothesize that CIK therapy may be a potential alternative in NSCLC patients harboring EML4-ALK rearrangement, in addition, we support the idea that combination therapies offer significant potential when they are optimized on a patient-by-patient basis.
The simultaneous operation of multiple different semiconducting metal oxide (MOX) gas sensors is demanding for the readout circuitry. The challenge results from the strongly varying signal intensities of the various sensor types to the target gas. While some sensors change their resistance only slightly, other types can react with a resistive change over a range of several decades. Therefore, a suitable readout circuit has to be able to capture all these resistive variations, requiring it to have a very large dynamic range. This work presents a compact embedded system that provides a full, high range input interface (readout and heater management) for MOX sensor operation. The system is modular and consists of a central mainboard that holds up to eight sensor-modules, each capable of supporting up to two MOX sensors, therefore supporting a total maximum of 16 different sensors. Its wide input range is archived using the resistance-to-time measurement method. The system is solely built with commercial off-the-shelf components and tested over a range spanning from 100Ω to 5 GΩ (9.7 decades) with an average measurement error of 0.27% and a maximum error of 2.11%. The heater management uses a well-tested power-circuit and supports multiple modes of operation, hence enabling the system to be used in highly automated measurement applications. The experimental part of this work presents the results of an exemplary screening of 16 sensors, which was performed to evaluate the system’s performance.
The choice of suitable semiconducting metal oxide (MOX) gas sensors for the detection of a specific gas or gas mixture is time-consuming since the sensor’s sensitivity needs to be characterized at multiple temperatures to find its optimal operating conditions. To obtain reliable measurement results, it is very important that the power for the sensor’s integrated heater is stable, regulated and error-free (or error-tolerant). Especially the error-free requirement can be only be achieved if the power supply implements failure-avoiding and failure-detection methods. The biggest challenge is deriving multiple different voltages from a common supply in an efficient way while keeping the system as small and lightweight as possible. This work presents a reliable, compact, embedded system that addresses the power supply requirements for fully automated simultaneous sensor characterization for up to 16 sensors at multiple temperatures. The system implements efficient (avg. 83.3% efficiency) voltage conversion with low ripple output (<32 mV) and supports static or temperature-cycled heating modes. Voltage and current of each channel are constantly monitored and regulated to guarantee reliable operation. To evaluate the proposed design, 16 sensors were screened. The results are shown in the experimental part of this work.
Electrical signal transmission in power electronic devices takes place through high-purity aluminum bonding wires. Cyclic mechanical and thermal stresses during operation lead to fatigue loads, resulting in premature failure of the wires, which cannot be reliably predicted. The following work presents two fatigue lifetime models calibrated and validated based on experimental fatigue results of an aluminum bonding wire and subsequently transferred and applied to other wire types. The lifetime modeling of Wöhler curves for different load ratios shows good but limited applicability for the linear model. The model can only be applied above 10,000 cycles and within the investigated load range of R = 0.1 to R = 0.7. The nonlinear model shows very good agreement between model prediction and experimental results over the entire investigated cycle range. Furthermore, the predicted Smith diagram is not only consistent in the investigated load range but also in the extrapolated load range from R = −1.0 to R = 0.8. A transfer of both model approaches to other wire types by using their tensile strengths can be implemented as well, although the nonlinear model is more suitable since it covers the entire load and cycle range.
Climate change is increasingly affecting vulnerable groups and resulting in dire social and economic consequences, especially for those in the Global South. Managing current and emerging climate-related risks will require increasing individual’s and communities’ resilience, including enhancing absorptive, adaptive, and transformative capacities. Policymakers are now considering the role that social protection policies and programmes can play in building climate resilience by contributing to these capacities. However, there is a limited understanding of the extent to which social protection instruments can influence these three resilience-related capacities. Lack of assessment tools or frameworks might contribute to limited evidence of social protection’s ability to increase climate resilience. In particular, there appear to be no frameworks or tools that help assess the role of social cash transfers (SCT) in building adaptive capacity. Based on a multi-staged literature review, we develop an adaptive capacity outcomes framework (ACOF) that can help assess SCT’s contribution to building adaptive capacity, and, consequently, resilience. The framework is then tested using impact evaluation and assessment reports from SCT programmes in Indonesia, Zambia, Ethiopia, Bangladesh, and Tanzania. The exercise finds that SCTs alone have a limited contribution to adaptive capacity outcomes, but interventions that combine cash transfers with other components such as nutrition or livelihood training show positive impacts. We find that the ACOF can support assessments of SCT’s contribution towards adaptive capacity. It can help build evidence, evaluate impacts, and through further research, can facilitate learning on SCTs' role in increasing climate resilience.
Failure prognostic builds up on constant data acquisition and processing and fault diagnosis and is an essential part of predictive maintenance of smart manufacturing systems enabling condition based maintenance, optimised use of plant equipment, improved uptime and yield and to prevent safety problems. Given known control inputs into a plant and real sensor outputs or simulated measurements, the model-based part of the proposed hybrid method provides numerical values of unknown parameter degradation functions at sampling time points by the evaluation of equations that have been derived offline from a bicausal diagnostic bond graph. These numerical values are computed concurrently to the constant monitoring of a system and are stored in a buffer of fixed length. The data-driven part of the method provides a sequence of remaining useful life estimates by repeated projection of the parameter degradation into the future based on the use of values in a sliding time window. Existing software can be used to determine the best fitting function and can account for its random parameters. The continuous parameter estimation and their projection into the future can be performed in parallel for multiple isolated simultaneous parametric faults on a multicore, multiprocessor computer.
The proposed hybrid bond graph model-based, data-driven method is verified by an offline simulation case study of a typical power electronic circuit. It can be used to implement embedded systems that enable cooperating machines in smart manufacturing to perform prognostic themselves.
A Method for the Sustainable Documentation of Operations Processes in Parcel Distribution Centers
(2018)
There is often no common understanding on operational processes in logistics companies as they are not properly documented. Hence, people execute the same process differently and training is conducted by experienced operators on an ad-hoc basis. Furthermore, continuous process improvement is hampered as neither the ideal process nor current issues in as-is processes are visible. A major reason for the missing documentation is the complexity of existing business process modelling languages. Modelling experts are required for initially describing the processes and also for updating the models after process changes. Furthermore, operations people are usually not used to read complex process models in EPCs or BPMN diagrams. In order to overcome these limitations, a domain-specific modelling language which facilitates maintaining up-to-date process models has been designed with a large logistics company in Germany. The paper at hand briefly describes this language and illustrates the method on how to apply it in operations environments.
Integrating physical simulation data into data ecosystems challenges the compatibility and interoperability of data management tools. Semantic web technologies and relational databases mostly use other data types, such as measurement or manufacturing design data. Standardizing simulation data storage and harmonizing the data structures with other domains is still a challenge, as current standards such as the ISO standard STEP (ISO 10303 ”Standard for the Exchange of Product model data”) fail to bridge the gap between design and simulation data. This challenge requires new methods, such as ontologies, to rethink simulation results integration. This research describes a new software architecture and application methodology based on the industrial standard ”Virtual Material Modelling in Manufacturing” (VMAP). The architecture integrates large quantities of structured simulation data and their analyses into a semantic data structure. It is capable of providing data permeability from the global digital twin level to the detailed numerical values of data entries and even new key indicators in a three-step approach: It represents a file as an instance in a knowledge graph, queries the file’s metadata, and finds a semantically represented process that enables new metadata to be created and instantiated.
Recessive mutations in the MPV17 gene cause mitochondrial DNA depletion syndrome, a fatal infantile genetic liver disease in humans. Loss of function in mice leads to glomerulosclerosis and sensineural deafness accompanied with mitochondrial DNA depletion. Mutations in the yeast homolog Sym1, and in the zebra fish homolog tra cause interesting, but not obviously related phenotypes, although the human gene can complement the yeast Sym1 mutation. The MPV17 protein is a hydrophobic membrane protein of 176 amino acids and unknown function. Initially localised in murine peroxisomes, it was later reported to be a mitochondrial inner membrane protein in humans and in yeast. To resolve this contradiction we tested two new mouse monoclonal antibodies directed against the human MPV17 protein in Western blots and immunohistochemistry on human U2OS cells. One of these monoclonal antibodies showed specific reactivity to a protein of 20 kD absent in MPV17 negative mouse cells. Immunofluorescence studies revealed colocalisation with peroxisomal, endosomal and lysosomal markers, but not with mitochondria. This data reveal a novel connection between a possible peroxisomal/endosomal/lysosomal function and mitochondrial DNA depletion.
With the increasing demand for ultrapure water in the pharmaceutical and semiconductor industry, the need for precise measuring instruments for those applications is also growing. One critical parameter of water quality is the amount of total organic carbon (TOC). This work presents a system that uses the advantage of the increased oxidation power achieved with UV/O3 advanced oxidation process (AOP) for TOC measurement in combination with a significant miniaturization compared to the state of the art. The miniaturization is achieved by using polymer-electrolyte membrane (PEM) electrolysis cells for ozone generation in combination with UV-LEDs for irradiation of the measuring solution, as both components are significantly smaller than standard equipment. Conductivity measurement after oxidation is the measuring principle and measurements were carried out in the TOC range between 10 and 1000 ppb TOC. The suitability of the system for TOC measurement is demonstrated using the oxidation by ozonation combined with UV irradiation of defined concentrations of isopropyl alcohol (IPA).
This paper presents a novel approach to address noise, vibration, and harshness (NVH) issues in electrically assisted bicycles (e-bikes) caused by the drive unit. By investigating and optimising the structural dynamics during early product development, NVH can decisively be improved and valuable resources can be saved, emphasising its significance for enhancing riding performance. The paper offers a comprehensive analysis of the e-bike drive unit’s mechanical interactions among relevant components, culminating—to the best of our knowledge—in the development of the first high-fidelity model of an entire e-bike drive unit. The proposed model uses the principles of elastic multi body dynamics (eMBD) to elucidate the structural dynamics in dynamic-transient calculations. Comparing power spectra between measured and simulated motion variables validates the chosen model assumptions. The measurements of physical samples utilise accelerometers, contactless laser Doppler vibrometry (LDV) and various test arrangements, which are replicated in simulations and provide accessibility to measure vibrations onto rotating shafts and stationary structures. In summary, this integrated system-level approach can serve as a viable starting point for comprehending and managing the NVH behaviour of e-bikes.
In this paper, a gas-to-power (GtoP) system for power outages is digitally modeled and experimentally developed. The design includes a solid-state hydrogen storage system composed of TiFeMn as a hydride forming alloy (6.7 kg of alloy in five tanks) and an air-cooled fuel cell (maximum power: 1.6 kW). The hydrogen storage system is charged under room temperature and 40 bar of hydrogen pressure, reaching about 110 g of hydrogen capacity. In an emergency use case of the system, hydrogen is supplied to the fuel cell, and the waste heat coming from the exhaust air of the fuel cell is used for the endothermic dehydrogenation reaction of the metal hydride. This GtoP system demonstrates fast, stable, and reliable responses, providing from 149 W to 596 W under different constant as well as dynamic conditions. A comprehensive and novel simulation approach based on a network model is also applied. The developed model is validated under static and dynamic power load scenarios, demonstrating excellent agreement with the experimental results.
A qualitative study of Machine Learning practices and engineering challenges in Earth Observation
(2021)
Machine Learning (ML) is ubiquitously on the advance. Like many domains, Earth Observation (EO) also increasingly relies on ML applications, where ML methods are applied to process vast amounts of heterogeneous and continuous data streams to answer socially and environmentally relevant questions. However, developing such ML- based EO systems remains challenging: Development processes and employed workflows are often barely structured and poorly reported. The application of ML methods and techniques is considered to be opaque and the lack of transparency is contradictory to the responsible development of ML-based EO applications. To improve this situation a better understanding of the current practices and engineering-related challenges in developing ML-based EO applications is required. In this paper, we report observations from an exploratory study where five experts shared their view on ML engineering in semi-structured interviews. We analysed these interviews with coding techniques as often applied in the domain of empirical software engineering. The interviews provide informative insights into the practical development of ML applications and reveal several engineering challenges. In addition, interviewees participated in a novel workflow sketching task, which provided a tangible reflection of implicit processes. Overall, the results confirm a gap between theoretical conceptions and real practices in ML development even though workflows were sketched abstractly as textbook-like. The results pave the way for a large-scale investigation on requirements for ML engineering in EO.
This work presents the analysis of data recorded by an eye tracking device in the course of evaluating a foveated rendering approach for head-mounted displays (HMDs). Foveated rendering methods adapt the image synthesis process to the user’s gaze and exploiting the human visual system’s limitations to increase rendering performance. Especially, foveated rendering has great potential when certain requirements have to be fulfilled, like low-latency rendering to cope with high display refresh rates. This is crucial for virtual reality (VR), as a high level of immersion, which can only be achieved with high rendering performance and also helps to reduce nausea, is an important factor in this field. We put things in context by first providing basic information about our rendering system, followed by a description of the user study and the collected data. This data stems from fixation tasks that subjects had to perform while being shown fly-through sequences of virtual scenes on an HMD. These fixation tasks consisted of a combination of various scenes and fixation modes. Besides static fixation targets, moving tar- gets on randomized paths as well as a free focus mode were tested. Using this data, we estimate the precision of the utilized eye tracker and analyze the participants’ accuracy in focusing the displayed fixation targets. Here, we also take a look at eccentricity-dependent quality ratings. Comparing this information with the users’ quality ratings given for the displayed sequences then reveals an interesting connection between fixation modes, fixation accuracy and quality ratings.
Jet engines of airplanes are designed such that in some components damage occurs and accumulates in service without being critical up to a certain level of damage. Since maintenance, repair, and component exchange are very cost-intensive, it is necessary to predict efficiently the component lifetime with high accuracy. A former developed lifetime model, based on interpolated results of aerodynamic and structural mechanics simulations, uses material parameters estimated from literature values of standard creep experiments. For improved accuracy, an experimental procedure is developed for the characterization of the short-time creep behavior, which is relevant for the operation of turbine blades of jet engines. To consider microstructural influences resulting from the manufacturing of thin-walled single crystal turbine blades, small-scale specimens from used turbine blades are extracted and tested in short- and medium-time creep experiments. Based on experimental results and literature values, a creep model, which describes the fracture behavior for a wide range of creep loads, is calibrated and is now used for the lifetime prediction of turbine blades under real loading conditions.
Pozzolanic properties of Pennisetum purpureum grass ash were tested on Portland cement. Results show that the ash can be blended with cements without compromising binding strength of the cement. It was found that Portland cement could be blended with Pennisetum purpureum up to a ratio of 3:2 compromising compressive strength of mortar.Mortar with lower cement replacement took longer to set as evidenced by lower compressive strength within the 28-day aging time. Mortar with higher cement replacement had lower water absorption capacity, an indication that the test pozzolan was of smaller particulate size. XRF analysis and the FTIR spectrum showed that the ash has a higher content of silica. The XRD pattern of the ash showed that the ash was predominantly amorphous. SEM images showed that the ash produced at 600 o C had residual carbon material.
Host-derived succinate accumulates in the airways during bacterial infection. Here, we show that luminal succinate activates murine tracheal brush (tuft) cells through a signaling cascade involving the succinate receptor 1 (SUCNR1), phospholipase Cβ2, and the cation channel transient receptor potential channel subfamily M member 5 (TRPM5). Stimulated brush cells then trigger a long-range Ca2+ wave spreading radially over the tracheal epithelium through a sequential signaling process. First, brush cells release acetylcholine, which excites nearby cells via muscarinic acetylcholine receptors. From there, the Ca2+ wave propagates through gap junction signaling, reaching also distant ciliated and secretory cells. These effector cells translate activation into enhanced ciliary activity and Cl- secretion, which are synergistic in boosting mucociliary clearance, the major innate defense mechanism of the airways. Our data establish tracheal brush cells as a central hub in triggering a global epithelial defense program in response to a danger-associated metabolite.