Systematic quantitative investigation of the unscrewing process with regard to breakaway torque

Threaded connections make up the majority of separable connections used today. Their disassembly behaviour strongly depends on the conditions during the life-phase. With the trend towards circular economy, disassembly particularly for remanufacturing requires automation. For production systems this mandates a certain capability of adaptation towards different product conditions. In the regarded case of dismantling threaded connections, this is the automatic selection of appropriate robot tools. One important criterion for the tool-selection is the breakaway torque, which strongly depends on friction parameters within the threads and the head surface. Those are influenced by e.g. corrosion and head type. In this contribution, the results of a systematic experimental investigation of the breakaway torque of threaded connections is presented. The aim of the contribution is to determine the influence on the breakaway torque of typical factors appearing in automated disassembly systems. Therefore, a total of 90 experiments are conducted which include five factors: Nominal diameter; Screw head type; Corrosion; Plate material; Applied torque during assembly

Stream microbial communities and ecosystem functioning show complex responses to multiple stressors in wastewater

Multiple anthropogenic drivers are changing ecosystems globally, with a disproportionate and intensifying impact on freshwater habitats. A major impact of urbanization are inputs from wastewater treatment plants (WWTPs). Initially designed to reduce eutrophication and improve water quality, WWTPs increasingly release a multitude of micropollutants (MPs; i.e., synthetic chemicals) and microbes (including antibiotic-resistant bacteria) to receiving environments. This pollution may have pervasive impacts on biodiversity and ecosystem services. Viewed through multiple lenses of macroecological and ecotoxicological theory, we combined field, flume, and laboratory experiments to determine the effects of wastewater (WW) on microbial communities and organic-matter processing using a standardized decomposition assay. First, we conducted a mensurative experiment sampling 60 locations above and below WWTP discharges in 20 Swiss streams. Microbial respiration and decomposition rates were positively influenced by WW inputs via warming and nutrient enrichment, but with a notable exception: WW decreased the activation energy of decomposition, indicating a "slowing" of this fundamental ecosystem process in response to temperature. Second, next-generation sequencing indicated that microbial community structure below WWTPs was altered, with significant compositional turnover, reduced richness, and evidence of negative MP influences. Third, a series of flume experiments confirmed that although diluted WW generally has positive influences on microbial-mediated processes, the negative effects of MPs are "masked" by nutrient enrichment. Finally, transplant experiments suggested that WW-borne microbes enhance decomposition rates. Taken together, our results affirm the multiple stressor paradigm by showing that different aspects of WW (warming, nutrients, microbes, and MPs) jointly influence ecosystem functioning in complex ways. Increased respiration rates below WWTPs potentially generate ecosystem "disservices" via greater carbon evasion from streams and rivers. However, toxic MP effects may fundamentally alter ecological scaling relationships, indicating the need for a rapprochement between ecotoxicological and macroecological perspectives

Genetic diversity and transmissibility of imported Plasmodium vivax in Qatar and three countries of origin

Malaria control program in the Arabian Peninsula, backed by adequate logistical support, has interrupted transmission with exception of limited sites in Saudi Arabia and sporadic outbreaks in Oman. However, sustained influx of imported malaria represents a direct threat to the above success. Here we examined the extent of genetic diversity among imported P. vivax in Qatar, and its ability to produce gametocytes, compared to parasites in main sites of imported cases, the Indian subcontinent (india) and East Africa (Sudan and Ethiopia). High diversity was seen among imported P. vivax in Qatar, comparable to parasites in the Indian subcontinent and East Africa. Limited genetic differentiation was seen among imported P. vivax, which overlapped with parasites in India, but differentiated from that in Sudan and Ethiopia. Parasite density among imported cases, ranged widely between 26.25–7985934.1 Pv18S rRNA copies/µl blood, with a high prevalence of infections carried gametocytes detectable by qRT-PCR. Parasitaemia was a stronger predictor for P. vivax gametocytes density (r = 0.211, P = 0.04). The extensive diversity of imported P. vivax and its ability to produce gametocytes represent a major threat for re-introduction of malaria in Qatar. The genetic relatedness between P. vivax reported in Qatar and those in India suggest that elimination strategy should target flow and dispersal of imported malaria into the region

Measurement, modelling, and closed-loop control of crystal shape distribution: Literature review and future perspectives

Crystal morphology is known to be of great importance to the end-use properties of crystal products, and to affect down-stream processing such as filtration and drying. However, it has been previously regarded as too challenging to achieve automatic closed-loop control. Previous work has focused on controlling the crystal size distribution, where the size of a crystal is often defined as the diameter of a sphere that has the same volume as the crystal. This paper reviews the new advances in morphological population balance models for modelling and simulating the crystal shape distribution (CShD), measuring and estimating crystal facet growth kinetics, and two- and three-dimensional imaging for on-line characterisation of the crystal morphology and CShD. A framework is presented that integrates the various components to achieve the ultimate objective of model-based closed-loop control of the CShD. The knowledge gaps and challenges that require further research are also identified

The trispecific DARPin ensovibep inhibits diverse SARS-CoV-2 variants

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with potential resistance to existing drugs emphasizes the need for new therapeutic modalities with broad variant activity. Here we show that ensovibep, a trispecific DARPin (designed ankyrin repeat protein) clinical candidate, can engage the three units of the spike protein trimer of SARS-CoV-2 and inhibit ACE2 binding with high potency, as revealed by cryo-electron microscopy analysis. The cooperative binding together with the complementarity of the three DARPin modules enable ensovibep to inhibit frequent SARS-CoV-2 variants, including Omicron sublineages BA.1 and BA.2. In Roborovski dwarf hamsters infected with SARS-CoV-2, ensovibep reduced fatality similarly to a standard-of-care monoclonal antibody (mAb) cocktail. When used as a single agent in viral passaging experiments in vitro, ensovibep reduced the emergence of escape mutations in a similar fashion to the same mAb cocktail. These results support further clinical evaluation of ensovibep as a broad variant alternative to existing targeted therapies for Coronavirus Disease 2019 (COVID-19)

The expression of ErbB4 in the human hippocampus and in murine primary astrocyte culture

Morbus Alzheimer is characterized by Aβ plaques, neurofibrillary tangles and different inflammatory conditions that finally lead to neuronal death and neuro- logical symptoms of dementia. Monocausal therapeutic approaches that target amyloid or NFT could not improve clinical symptoms nor the overall outcome and progression of the disease. Accumulation of protein is common for ageing and is not regarded to be necessarily linked to symptoms of dementia. Furthermore, glial response mechanisms to proteopathic load are suspected to have a higher correlation to final clinical stages than load of NFT or Amyloid-β. Therefore, it is crucial to characterize changes of receptor protein expression in glial cells which are able to interact between different pathways of inflammation, cell death and brain circuitry. Specifically, the ErbB4 receptor, a member of the epider- mal growth factor receptor family, is suspected to be involved in AD associated pathways. For the characterization of ErbB4 expression in astrocytes, brain tissue from hu- man (hippocampus, Glioblastoma) and murine samples (whole brain) in control and disease were investigated. Additionally, cultures from murine astrocytes (pri- mary, C8D1A immortalized) and human astrocytes (iPSC derived) were treated with receptor ligands and inflammatory molecule TNFα for 24 h. Subsequently, immunohistochemistry on coverslips, Western Blot and qPCR were performed to detect changes of expression. Immunofluorescent analysis of ErbB4, GFAP, Cleaved-Caspase 3, COX2, C1q and interneuronal markers was performed on postmortem PFA-fixed human samples of hippocampus in AD (n=17) and con- trols (n=14). The spatial distribution and morphological characteristics of ErbB4 was then analyzed and quantified. In addition a digital segmentation and mea- surement of fluorescence of ErbB4 and GFAP was performed with ImageJ. Im- munofluorescence analysis of astrocytes in the CA1 sector of the human hip- pocampi indicated that the ErbB4 expression correlated with GFAP throughout all samples. Higher intensities for ErbB4/GFAP in AD condition compared to controls were measured on qualitative and quantitative analyses. Astrocytes in resting state showed ErbB4 expression limited to the nucleus with no expression 88 Summary in the somatic cytoplasm or processes, in contrast to ErbB4 expression found in astroglial processes in AD samples. Different pathological conditions (Glioblas- toma, dementia with Lewy bodies) showed similar ErbB4 expression patterns in somata and proximal astroglial processes. In addition, analysis of whole human hippocampal sections showed ErbB4 expression in the dentate gyrus and CA4 sector with triangular shaped cell bodies for ErbB4 and Phospho-ErbB4 in the nuclei and somata of neurons and interneurons. The observation of neuronal ErbB4 expression could be reproduced by NeuN/ErbB4 double positive stain- ings from controls (rat and mouse). Immunofluorescence on primary and immor- talized astrocyte cultures showed higher intensities for ErbB4 and GFAP after TNFα treatment. The previously reported selective expression of ErbB4 limited to interneurons [57] could not be confirmed, as pyramidal neurons also expressed ErbB4. Likewise, in contrast to previous studies, microglia was immunonegative for ErbB4. Preliminary results from total RNA extraction/RT/qPCR of primary astrocyte cultures after TNFα administration (24 h) demonstrated upregulation of the ErbB4 ligand NRG1. Unexpectedly, the Western Blot showed bands for ErbB4 at 50 kDa and 230 kDa, reproducible with Phospho- and C-terminal ErbB4 antibodies, not reported in previous studies. Accordingly, these bands were ex- cluded from further quantification. The current thesis also documents a codistribution of ErbB4 with inflammatory markers C1q, Cleaved-Caspase 3 and COX2, indicating a possible induction of inflammatory pathways. This putative neuroinflammatory response may lead to the release of cell growth and neuroprotective molecules suggestive for an anti- inflammatory response. For future experiments, analyses at RNA and protein levels of different anti-/proinflammatory molecules after treatments would help to further understand the effects of ErbB4 activation. Additional stainings with different neuronal markers would allow a deeper understanding on cell specific upregulation of ErbB4. Finally, more comprehensive image analysis including multiple scans from all hippocampal areas could provide a more detailed pattern of ErbB4 expression. Taken together, the increased ErbB4 expression revealed in the current thesis is in agreement with previous studies, highlighting the potential relevance of ErbB4 signalling pathway as a potential therapeutic target in A

Pesticide Risks in Small StreamsHow to Get as Close as Possible to the Stress Imposed on Aquatic Organisms

The risks associated with pesticides in small streams remain poorly characterized. The challenges reside in understanding the complexities of (1) the highly dynamic concentration profiles of (2) several hundred active substances with (3) differing seasonality. The present study addressed these three challenges simultaneously. Five small streams in catchments under intensive agricultural land use were sampled using half-day composite samples from March to August 2015. Of 213 active substances quantified using liquid chromatography–high resolution mass spectrometry, a total of 128 was detected at least at one of the sites. Ecotoxicological acute and/or chronic quality criteria were exceeded for a total of 32 different active substances. The evaluation of risks over time revealed the necessity to evaluate the sequences of different active substances that are imposed on aquatic organisms. In contrast, a substance-specific perspective provides only a very limited assessment. Scenarios for reduction of either temporal resolution, number of substances or seasonal coverage were defined. It could be shown that risks can be underestimated by more than a factor of 10 in vulnerable catchments and that an increased temporal resolution is essential to cover acute risks but that a focused selection of substances is a possibility to reduce expenditures

Pesticide Risks in Small StreamsHow to Get as Close as Possible to the Stress Imposed on Aquatic Organisms

The risks associated with pesticides in small streams remain poorly characterized. The challenges reside in understanding the complexities of (1) the highly dynamic concentration profiles of (2) several hundred active substances with (3) differing seasonality. The present study addressed these three challenges simultaneously. Five small streams in catchments under intensive agricultural land use were sampled using half-day composite samples from March to August 2015. Of 213 active substances quantified using liquid chromatography–high resolution mass spectrometry, a total of 128 was detected at least at one of the sites. Ecotoxicological acute and/or chronic quality criteria were exceeded for a total of 32 different active substances. The evaluation of risks over time revealed the necessity to evaluate the sequences of different active substances that are imposed on aquatic organisms. In contrast, a substance-specific perspective provides only a very limited assessment. Scenarios for reduction of either temporal resolution, number of substances or seasonal coverage were defined. It could be shown that risks can be underestimated by more than a factor of 10 in vulnerable catchments and that an increased temporal resolution is essential to cover acute risks but that a focused selection of substances is a possibility to reduce expenditures