Fluctuation-induced dynamics of nematic topological defects

Topological defects are increasingly being identified in various biological systems, where their characteristic flow fields and stress patterns are associated with continuous active stress generation by biological entities. Here, using numerical simulations of continuum fluctuating nematohydrodynamics we show that even in the absence of any specific form of active stresses associated with self-propulsion, mesoscopic fluctuations in either orientational alignment or hydrodynamics can independently result in flow patterns around topological defects that resemble the ones observed in active systems. Our simulations further show the possibility of extensile- and contractile-like motion of fluctuation-induced positive half-integer topological defects. Remarkably, isotropic stress fields also reproduce the experimentally measured stress patterns around topological defects in epithelia. Our findings further reveal that extensile- or contractile-like flow and stress patterns around fluctuation-induced defects are governed by passive elastic stresses and flow-aligning behavior of the nematics

Ontology-based assistance system for control process reconfiguration of Robot-Based Applications

Due to increasing global competition, companies are challenged to make their production flexible and adaptable. This leads to a steadily increasing complexity of production systems and thus their automation and control processes. At the same time, control processes must be quickly configurable in order to be able to react to short product life cycles. Robot-based adhesive application in automotive body assembly represents one such control and automation process. In car body assembly, industrial robots are increasingly being used for gluing side panels, enabling flow operation in assembly. In the event of a functional change in the production process, such as the replacement of the adhesive to be used, all the given process interrelationships must be analysed again and reconfigured if necessary in order to ensure the quality of the bonded joint. Comprehensive data management systems that provide an overview of all the system parameters and control levers are often not available in companies, so that reconfiguration is based on experience. Correct adjustment of the process parameters thus requires the user to have precise knowledge of the complex interrelationships between the process and bonding parameters, which makes the search for solutions in the event of a process change more difficult and time-consuming. In order to master the complexity of process planning and configuration, a large number of user-supporting solutions exist in the area of product lifecycle management (PLM). However, these neither have the functionality to generate solution and optimization proposals, nor do they map the existing expert knowledge with so-called empirical values about the system behaviour. The advantages of semantic technologies including ontologies, such as their graph structure and suitability for the use of optimization algorithms, illustrate their potential as the basis of a knowledge-based assistance solution. Against this background, the aim of this paper is to develop an ontology-based knowledge management system that can consolidate existing product and process information and add expert knowledge to it. The resulting knowledge graph of the process is then examined using selected optimization algorithms (PMS, Parallel Machine Scheduling). From the analysis, configuration suggestions can be derived, which can be presented to the user with a visualisation interface. Finally, the potential of ontologies as the basis of a knowledge-based assistance system is evaluated based on given results

High-speed multiplane structured illumination microscopy of living cells using an image-splitting prism

Descloux A, Mueller M, Navikas V, et al. High-speed multiplane structured illumination microscopy of living cells using an image-splitting prism. Nanophotonics. 2020;9(1):143-148.Super-resolution structured illumination microscopy (SR-SIM) can be conducted at video-rate acquisition speeds when combined with high-speed spatial light modulators and sCMOS cameras, rendering it particularly suitable for live-cell imaging. If, however, three-dimensional (3D) information is desired, the sequential acquisition of vertical image stacks employed by current setups significantly slows down the acquisition process. In this work, we present a multiplane approach to SR-SIM that overcomes this slowdown via the simultaneous acquisition of multiple object planes, employing a recently introduced multiplane image splitting prism combined with highspeed SIM illumination. This strategy requires only the introduction of a single optical element and the addition of a second camera to acquire a laterally highly resolved 3D image stack. We demonstrate the performance of multiplane SIM by applying this instrument to imaging the dynamics of mitochondria in living COS-7 cells

Near-field coded-mask technique and its potential for proton therapy monitoring

Objective. Prompt-gamma imaging encompasses several approaches to the online monitoring of the beam range or deposited dose distribution in proton therapy. We test one of the imaging techniques - a coded mask approach - both experimentally and via simulations. Approach. Two imaging setups have been investigated experimentally. Each of them comprised a structured tungsten collimator in the form of a modified uniformly redundant array mask and a LYSO:Ce scintillation detector of fine granularity. The setups differed in detector dimensions and operation mode (1D or 2D imaging). A series of measurements with radioactive sources have been conducted, testing the performance of the setups for near-field gamma imaging. Additionally, Monte Carlo simulations of a larger setup of the same type were conducted, investigating its performance with a realistic gamma source distribution occurring during proton therapy. Main results. The images of point-like sources reconstructed from two small-scale prototypes' data using the maximum-likelihood expectation maximisation algorithm constitute the experimental proof of principle for the near-field coded-mask imaging modality, both in the 1D and the 2D mode. Their precision allowed us to calibrate out certain systematic offsets appearing due to the limited alignment accuracy of setup elements. The simulation of the full-scale setup yielded a mean distal falloff retrieval precision of 0.72 mm in the studies for beam energy range 89.5–107.9 MeV and with 1 × 10$^{8}$ protons (a typical number for distal spots). The implemented algorithm of image reconstruction is relatively fast—a typical procedure needs several seconds. Significance. Coded-mask imaging appears a valid option for proton therapy monitoring. The results of simulations let us conclude that the proposed full-scale setup is competitive with the knife-edge-shaped and the multi-parallel slit cameras investigated by other groups

Using a motor imagery questionnaire to estimate the performance of a Brain–Computer Interface based on object oriented motor imagery

<p>Objectives: The primary objective was to test whether motor imagery (MI) questionnaires can be used to detect BCI ‘illiterate’. The second objective was to test how different MI paradigms, with and without the physical presence of the goal of an action, influence a BCI classifier.</p> <p>Methods: Kinaesthetic (KI) and visual (VI) motor imagery questionnaires were administered to 30 healthy volunteers. Their EEG was recorded during a cue-based, simple imagery (SI) and goal oriented imagery (GOI).</p> <p>Results: The strongest correlation (Pearson r2 = 0.53, p = 1.6e-5) was found between KI and SI, followed by a moderate correlation between KI and GOI (r2 = 0.33, p = 0.001) and a weak correlation between VI and SI (r2 = 0.21, p = 0.022) and VI and GOI (r2 = 0.17, p = 0.05). Classification accuracy was similar for SI (71.1 ± 7.8%) and GOI (70.5 ± 5.9%) though corresponding classification features differed in 70% participants. Compared to SI, GOI improved the classification accuracy in ‘poor’ imagers while reducing the classification accuracy in ‘very good’ imagers.</p> <p>Conclusion: The KI score could potentially be a useful tool to predict the performance of a MI based BCI. The physical presence of the object of an action facilitates motor imagination in ‘poor’ able-bodied imagers.</p> <p>Significance: Although this study shows results on able-bodied people, its general conclusions should be transferable to BCI based on MI for assisted rehabilitation of the upper extremities in patients.</p&gt

Complement Activation Is Associated With Disease Severity in Multiple Sclerosis.

BACKGROUND AND OBJECTIVES Histopathologic studies have identified immunoglobulin (Ig) deposition and complement activation as contributors of CNS tissue damage in multiple sclerosis (MS). Intrathecal IgM synthesis is associated with higher MS disease activity and severity, and IgM is the strongest complement-activating immunoglobulin. In this study, we investigated whether complement components (CCs) and complement activation products (CAPs) are increased in persons with MS, especially in those with an intrathecal IgM synthesis, and whether they are associated with disease severity and progression. METHODS CC and CAP levels were quantified in plasma and CSF of 112 patients with clinically isolated syndrome (CIS), 127 patients with MS (90 relapsing-remitting, 14 primary progressive, and 23 secondary progressive), 31 inflammatory neurologic disease, and 44 symptomatic controls from the Basel CSF databank study. Patients with CIS/MS were followed in the Swiss MS cohort study (median 6.3 years). Levels of CC/CAP between diagnosis groups were compared; in CIS/MS, associations of CC/CAP levels with intrathecal Ig synthesis, baseline Expanded Disability Status Scale (EDSS) scores, MS Severity Score (MSSS), and neurofilament light chain (NfL) levels were investigated by linear regression, adjusted for age, sex, and albumin quotient. RESULTS CSF (but not plasma) levels of C3a, C4a, Ba, and Bb were increased in patients with CIS/MS, being most pronounced in those with an additional intrathecal IgM production. In CIS, doubling of C3a and C4a in CSF was associated with 0.31 (CI 0.06-0.56; p = 0.016) and 0.32 (0.02-0.62; p = 0.041) increased EDSS scores at lumbar puncture. Similarly, doubling of C3a and Ba in CIS/MS was associated with 0.61 (0.19-1.03; p < 0.01) and 0.74 (0.18-1.31; p = 0.016) increased future MSSS. In CIS/MS, CSF levels of C3a, C4a, Ba, and Bb were associated with increased CSF NfL levels, e.g., doubling of C3a was associated with an increase of 58% (Est. 1.58; CI 1.37-1.81; p < 0.0001). DISCUSSION CNS-compartmentalized activation of the classical and alternative pathways of complement is increased in CIS/MS and associated with the presence of an intrathecal IgM production. Increased complement activation within the CSF correlates with EDSS, future MSSS, and NfL levels, supporting the concept that complement activation contributes to MS pathology and disease progression. Complement inhibition should be explored as therapeutic target to attenuate disease severity and progression in MS

Ectopic callose deposition into woody biomass modulates the nano-architecture of macrofibrils

Plant biomass plays an increasingly important role in the circular bioeconomy, replacing non-renewable fossil resources. Genetic engineering of this lignocellulosic biomass could benefit biorefinery transformation chains by lowering economic and technological barriers to industrial processing. However, previous efforts have mostly targeted the major constituents of woody biomass: cellulose, hemicellulose and lignin. Here we report the engineering of wood structure through the introduction of callose, a polysaccharide novel to most secondary cell walls. Our multiscale analysis of genetically engineered poplar trees shows that callose deposition modulates cell wall porosity, water and lignin contents and increases the lignin-cellulose distance, ultimately resulting in substantially decreased biomass recalcitrance. We provide a model of the wood cell wall nano-architecture engineered to accommodate the hydrated callose inclusions. Ectopic polymer introduction into biomass manifests in new physico-chemical properties and offers new avenues when considering lignocellulose engineering.Bourdon et al. demonstrate the possibility to ectopically synthesize callose, a polymer restricted to primary cell walls, into Arabidopsis and aspen secondary cell walls to manipulate their ultrastructure and ultimately reduce their recalcitrance

Impact of the putative cancer stem cell markers and growth factor receptor expression on the sensitivity of ovarian cancer cells to treatment with various forms of the HER inhibitors and cytotoxic drugs

Increased expression and activation of human epidermal growth factor receptor (EGFR) and HER-2 have been reported in numerous cancers. The aim of this study was to determine the sensitivity of a large panel of human ovarian cancer cell lines (OCCLs) to treatment with various forms of small molecule tyrosine kinase inhibitors (TKIs) and cytotoxic drugs. The aim was to see if there was any association between the protein expression of various biomarkers including three putative ovarian cancer stem cell (CSC) markers (CD24, CD44, CD117/c-Kit), P-glycoprotein (P-gp), and HER family members and response to treatment with these agents. The sensitivity of 10 ovarian tumour cell lines to the treatment with various forms of HER TKIs (gefitinib, erlotinib, lapatinib, sapitinib, afatinib, canertinib, neratinib), as well as other TKIs (dasatinib, imatinib, NVP-AEW541, crizotinib) and cytotoxic agents (paclitaxel, cisplatin and doxorubicin), as single agents or in combination, was determined by SRB assay. The effect on these agents on the cell cycle distribution, and downstream signaling molecules and tumour migration were determined using flow cytometry, western blotting, and the IncuCyte Clear View cell migration assay respectively. Of the HER inhibitors, the irreversible pan-TKIs (canertinib, neratinib and afatinib) were the most effective TKIs for inhibiting the growth of all ovarian cancer cells, and for blocking the phosphorylation of EGFR, HER-2, AKT and MAPK in SKOV3 cells. Interestingly, while the majority of cancer cells were highly sensitive to treatment with dasatinib, they were relatively resistant to treatment with imatinib (i.e., IC50 >10 µM). Of the cytotoxic agents, paclitaxel was the most effective for inhibiting the growth of OCCLs, and of various combinations of these drugs, only treatment with a combination of NVP-AEW541 and paclitaxel produced a synergistic or additive anti-proliferative effect in all three cell lines examined (i.e., SKOV3, Caov3, ES2). Finally, of the TKIs, only treatment with afatinib, neratinib and dasatinib were able to reduce the migration of HER-2 overexpressing SKOV3 cells. We did not find any significant association between the expression of putative ovarian CSC marker, HER family members, c-MET, ALK, and IGF-IR and the response to the irreversible HER TKIs. Our results support the need for further investigations of the therapeutic potential of these irreversible HER family blockers in ovarian cancer, and the therapeutic potential of dasatinib when used in combination with the inhibitors of the HER family members in ovarian cancer

Aggregation tests identify new gene associations with breast cancer in populations with diverse ancestry

Low-frequency variants play an important role in breast cancer (BC) susceptibility. Gene-based methods can increase power by combining multiple variants in the same gene and help identify target genes. We evaluated the potential of gene-based aggregation in the Breast Cancer Association Consortium cohorts including 83,471 cases and 59,199 controls. Low-frequency variants were aggregated for individual genes' coding and regulatory regions. Association results in European ancestry samples were compared to single-marker association results in the same cohort. Gene-based associations were also combined in meta-analysis across individuals with European, Asian, African, and Latin American and Hispanic ancestry. In European ancestry samples, 14 genes were significantly associated (q < 0.05) with BC. Of those, two genes, FMNL3 (P = 6.11 × 10 ) and AC058822.1 (P = 1.47 × 10 ), represent new associations. High FMNL3 expression has previously been linked to poor prognosis in several other cancers. Meta-analysis of samples with diverse ancestry discovered further associations including established candidate genes ESR1 and CBLB. Furthermore, literature review and database query found further support for a biologically plausible link with cancer for genes CBLB, FMNL3, FGFR2, LSP1, MAP3K1, and SRGAP2C. Using extended gene-based aggregation tests including coding and regulatory variation, we report identification of plausible target genes for previously identified single-marker associations with BC as well as the discovery of novel genes implicated in BC development. Including multi ancestral cohorts in this study enabled the identification of otherwise missed disease associations as ESR1 (P = 1.31 × 10 ), demonstrating the importance of diversifying study cohorts. [Abstract copyright: © 2023. The Author(s).

Mapping 123 million neonatal, infant and child deaths between 2000 and 2017

Since 2000, many countries have achieved considerable success in improving child survival, but localized progress remains unclear. To inform efforts towards United Nations Sustainable Development Goal 3.2—to end preventable child deaths by 2030—we need consistently estimated data at the subnational level regarding child mortality rates and trends. Here we quantified, for the period 2000–2017, the subnational variation in mortality rates and number of deaths of neonates, infants and children under 5 years of age within 99 low- and middle-income countries using a geostatistical survival model. We estimated that 32% of children under 5 in these countries lived in districts that had attained rates of 25 or fewer child deaths per 1,000 live births by 2017, and that 58% of child deaths between 2000 and 2017 in these countries could have been averted in the absence of geographical inequality. This study enables the identification of high-mortality clusters, patterns of progress and geographical inequalities to inform appropriate investments and implementations that will help to improve the health of all populations