In situ observations on deformation behavior and stretching-induced failure of fine pitch stretchable interconnect

Electronic devices capable of performing in extreme mechanical conditions such as stretching, bending, or twisting will improve biomedical and wearable systems. The required capabilities cannot be achieved with conventional building geometries, because of structural rigidity and lack of mechanical stretchability. In this article, a zigzag-patterned structure representing a stretchable interconnect is presented as a promising type of building block. In situ experimental observations on the deformed interconnect are correlated with numerical analysis, providing an understanding of the deformation and failure mechanisms. The experimental results demonstrate that the zigzag-patterned interconnect enables stretchability up to 60% without rupture. This stretchability is accommodated by in-plane rotation of arms and out-of-plane deformation of crests. Numerical analysis shows that the dominating failure cause is interfacial in-plane shear stress. The plastic strain concentration at the arms close to the crests, obtained by numerical simulation, agrees well with the failure location observed in the experiment

Finite element analysis of thermo-elastical modal damping of mems vibrations

The paper deals with finite element analysis of damped modal vibrations Q-factor values determined by thermal-elastic damping in micro-electrical-mechanical systems (MEMS). Mathematically the problem is formulated as a complex eigenvalue problem. Verification problems have been solved by using several computational environments and different presentations of model equations in order to comprehend and reduce the influence of rounding errors. The analysis of damped modal properties of selected real MEMS resonator revealed the main features of thermal-elastic damping by taking into account 3D geometry of the resonator and anchoring (clamping) structur

Printed circuit board technology inspired stretchable circuits

In the past 15 years, stretchable electronic circuits have emerged as a new technology in the domain of assembly, interconnections, and sensor circuit technologies. In the meantime, a wide variety of processes using many different materials have been explored in this new field. In the current contribution, we present an approach inspired by conventional rigid and flexible printed circuit board (PCB) technology. Similar to PCBs, standard packaged, rigid components are assembled on copper contact pads using lead-free solder reflow processes. Stretchability is obtained by shaping the copper tracks as horseshoe-shaped meanders. Elastic materials, predominantly polydimethylsiloxanes, are used to embed the conductors and the components, thus serving as a circuit carrier. We describe mechanical modeling, aimed at optimizing the build-up toward maximum mechanical reliability of the structures. Details on the production process, reliability assessment, and a number of functional demonstrators are described

Correction: The Endocytic Adaptor Eps15 Controls Marginal Zone B Cell Numbers.

Eps15 is an endocytic adaptor protein involved in clathrin and non-clathrin mediated endocytosis. In Caenorhabditis elegans and Drosophila melanogaster lack of Eps15 leads to defects in synaptic vesicle recycling and synapse formation. We generated Eps15-KO mice to investigate its function in mammals. Eps15-KO mice are born at the expected Mendelian ratio and are fertile. Using a large-scale phenotype screen covering more than 300 parameters correlated to human disease, we found that Eps15-KO mice did not show any sign of disease or neural deficits. Instead, altered blood parameters pointed to an immunological defect. By competitive bone marrow transplantation we demonstrated that Eps15-KO hematopoietic precursor cells were more efficient than the WT counterparts in repopulating B220⁺ bone marrow cells, CD19⁻ thymocytes and splenic marginal zone (MZ) B cells. Eps15-KO mice showed a 2-fold increase in MZ B cell numbers when compared with controls. Using reverse bone marrow transplantation, we found that Eps15 regulates MZ B cell numbers in a cell autonomous manner. FACS analysis showed that although MZ B cells were increased in Eps15-KO mice, transitional and pre-MZ B cell numbers were unaffected. The increase in MZ B cell numbers in Eps15 KO mice was not dependent on altered BCR signaling or Notch activity. In conclusion, in mammals, the endocytic adaptor protein Eps15 is a regulator of B-cell lymphopoiesis

How models can support ecosystem-based management of coral reefs

Despite the importance of coral reef ecosystems to the social and economic welfare of coastal communities, the condition of these marine ecosystems have generally degraded over the past decades. With an increased knowledge of coral reef ecosystem processes and a rise in computer power, dynamic models are useful tools in assessing the synergistic effects of local and global stressors on ecosystem functions. We review representative approaches for dynamically modeling coral reef ecosystems and categorize them as minimal, intermediate and complex models. The categorization was based on the leading principle for model development and their level of realism and process detail. This review aims to improve the knowledge of concurrent approaches in coral reef ecosystem modeling and highlights the importance of choosing an appropriate approach based on the type of question(s) to be answered. We contend that minimal and intermediate models are generally valuable tools to assess the response of key states to main stressors and, hence, contribute to understanding ecological surprises. As has been shown in freshwater resources management, insight into these conceptual relations profoundly influences how natural resource managers perceive their systems and how they manage ecosystem recovery. We argue that adaptive resource management requires integrated thinking and decision support, which demands a diversity of modeling approaches. Integration can be achieved through complimentary use of models or through integrated models that systemically combine all relevant aspects in one model. Such whole-of-system models can be useful tools for quantitatively evaluating scenarios. These models allow an assessment of the interactive effects of multiple stressors on various, potentially conflicting, management objectives. All models simplify reality and, as such, have their weaknesses. While minimal models lack multidimensionality, system models are likely difficult to interpret as they require many efforts to decipher the numerous interactions and feedback loops. Given the breadth of questions to be tackled when dealing with coral reefs, the best practice approach uses multiple model types and thus benefits from the strength of different models types

Herd-level animal management factors associated with the occurrence of bovine neonatal pancytopenia in calves in a multicountry study

Since 2007, mortality associated with a previously unreported haemorrhagic disease has been observed in young calves in several European countries. The syndrome, which has been named ‘bovine neonatal pancytopenia’ (BNP), is characterised by thrombocytopenia, leukocytopenia and a panmyelophthisis. A herd-level case-control study was conducted in four BNP affected countries (Belgium, France, Germany and the Netherlands) to identify herd management risk factors for BNP occurrence. Data were collected using structured face-to-face and telephone interviews of farm managers and their local veterinarians. In total, 363 case farms and 887 control farms were included in a matched multivariable conditional logistic regression analysis. Case-control status was strongly associated with the odds of herd level use of the vaccine PregSure® BVD (PregSure, Pfizer Animal Health) (matched adjusted odds ratio (OR) 107.2; 95% CI: 41.0–280.1). This was also the case for the practices of feeding calves colostrum from the calf’s own dam (OR 2.0; 95% CI: 1.1–3.4) or feeding pooled colostrum (OR 4.1; 95% CI: 1.9–8.8). Given that the study had relatively high statistical power and represented a variety of cattle production and husbandry systems, it can be concluded with some confidence that no other herd level management factors are competent causes for a sufficient cause of BNP occurrence on herd level. It is suggested that genetic characteristics of the dams and BNP calves should be the focus of further investigations aimed at identifying the currently missing component causes that together with PregSure vaccination and colostrum feeding represent a sufficient cause for occurrence of BNP in calves

From a long‑distance threat to the invasion front : a review of the invasive Aedes mosquito species in Belgium between 2007 and 2020

Author contributions ID drafted the manuscript and revised it after comments of all co-authors. ID, TVL, KDW and AV carried out the mosquito identifications. ID, KDW, AS, AV, IV, JDW, JD, TVL and WVB collected data in the field and sorted the mosquitoes in the laboratory. WVB, ID and KDW managed the data. NS and JDW performed the DNA barcoding. WD and AV produced the morphological reference collection. WVB, ID, MM and RM coordinated the projects. MK performed the statistical analysis. All authors critically reviewed the manuscript. All authors read and approved the final manuscript.Data supporting the conclusions of this article are included within the article and its additional file. The datasets generated and analysed during the current study are available in the GBIF repository [44–50].ADDITIONAL FILE 1: TABLE S1. Overview of the trapping methods used to monitor invasive mosquito species (IMS) in Belgium during the different years (and projects) and in different risk scenarios, indicating the number of traps or larval sampling visits per site and the frequency of trapping or larval sampling. TABLE S2. Aedes albopictus detections in Belgium between 2007 and 2020 at the ten points of entry (PoEs) per year including the sampling perimeter, collection and detection methods, collection (light grey) and detection (dark grey) period, control measures (X), number of individuals (total, females, males, larvae and eggs) and project. TABLE S3. Aedes japonicus detections in Belgium between 2007 and 2020 at the four points of entry (PoEs) per year including the sampling perimeter, collection and detection methods, collection (light grey) and detection (dark grey) period, the control measures (X), number of individuals (total, females, males, larvae and eggs) and project. TABLE S4. Aedes koreicus detections in Belgium between 2007 and 2020 at the two points of entry (PoEs) per year including the sampling perimeter, collection and detection methods, collection (light grey) and detection (dark grey) period, control measures (X), number of individuals (total, females, males, larvae and eggs) and project.Invasive mosquito species (IMS) and their associated mosquito-borne diseases are emerging in Europe. In Belgium, the first detection of Aedes albopictus (Skuse 1894) occurred in 2000 and of Aedes japonicus japonicus (Theobald 1901) in 2002. Early detection and control of these IMS at points of entry (PoEs) are of paramount importance to slow down any possible establishment. This article reviews the introductions and establishments recorded of three IMS in Belgium based on published (2007–2014) and unpublished (2015–2020) data collected during several surveillance projects. In total, 52 PoEs were monitored at least once for the presence of IMS between 2007 and 2020. These included used tyre and lucky bamboo import companies, airports, ports, parking lots along highways, shelters for imported cutting plants, wholesale markets, industrial areas, recycling areas, cemeteries and an allotment garden at the country border with colonised areas. In general, monitoring was performed between April and November. Mosquitoes were captured with adult and oviposition traps as well as by larval sampling. Aedes albopictus was detected at ten PoEs, Ae. japonicus at three PoEs and Aedes koreicus (Edwards 1917) at two PoEs. The latter two species have established overwintering populations. The percentage of PoEs positive for Ae. albopictus increased significantly over years. Aedes albopictus is currently entering Belgium through lucky bamboo and used tyre trade and passive ground transport, while Ae. japonicus through used tyre trade and probably passive ground transport. In Belgium, the import through passive ground transport was first recorded in 2018 and its importance seems to be growing. Belgium is currently at the invasion front of Ae. albopictus and Ae. japonicus. The surveillance and control management actions at well-known PoEs associated to long-distance introductions are more straightforward than at less-defined PoEs associated with short-distance introductions from colonised areas. These latter PoEs represent a new challenge for IMS management in Belgium in the coming years. Aedes albopictus is expected to become established in Belgium in the coming years, hence increasing the likelihood of local arbovirus transmission. The implementation of a sustainable, structured and long-term IMS management programme, integrating active and passive entomological surveillance, vector control and Public Health surveillance is therefore pivotal.The MODIRISK project (2007–2010) was funded by the Belgian Science Policy Programs; the EXOSURV project (2012) by the Federal, Flemish, Walloon and Brussels Capital region governments, the FASFC project (2013–2016) by the Federal Agency for the Safety of the Food Chain (FASFC), the MEMO and MEMO+2020 projects (2017–2020) by the Flemish, Walloon and Brussels regional governments and the Federal Public Service (FPS) Public Health, Food Chain Safety and Environment in the context of the National Environment and Health Action Plan (NEHAP) (Belgium), and the DiMoc project by the 2018–2019 BiodivERsA3 ERA-Net COFUND programme with the funding organisation FWO. The Barcoding Facility for Organisms and Tissues of Policy Concern is financed by the Belgian Science Policy Office (Belspo) as Belgian federal in-kind contribution to the European Research Infrastructure Consortium “LifeWatch”. The Outbreak Research Team of the Institute of Tropical Medicine is financially supported by the Department of Economy, Science and Innovation of the Flemish government.https://parasitesandvectors.biomedcentral.comam2023Veterinary Tropical Disease

Communication of pharmacogenetic research results to HIV-infected treated patients: standpoints of professionals and patients.

International audienceThe aim of pharmacogenetic studies is to adapt therapeutic strategies to individual genetic profiles, thus maximising their efficacy and minimising the likelihood of adverse side effects. Since the advent of personalised medicine, the issue of communicating research results to participants has become increasingly important. We addressed this question in the context of HIV infection, as patients and associations are particularly concerned by research and therapeutic advances. We explored the standpoints of both research professionals and participants involved in a pharmacogenetic study conducted in a cohort of HIV-infected patients. The setting of the research protocol was followed over a 2-year period. Participants' standpoints were collected through a questionnaire and interviews were conducted with research professionals. Of 125 participants, 76% wished to receive individual results and 71% wished to receive collective results; 39% did not know when results might be expected. Communication of global research results is a principle that is generally accepted by professionals. Concerning individual feedback, the professionals felt that it was necessary if it could be of direct benefit to the participant, but they expressed doubts for situations with no recognised benefit. Our results highlight the necessity to consider this issue in greater detail. We suggest the need to anticipate the debates concerning individual feedback, to differentiate between situations and the importance of further investigations on the opportunities and modalities of communication. Finally, our work emphasised the opposite pressures between the pursuit of scientific knowledge and the therapeutic orientation of clinical trials

A prospective randomised, open-labeled, trial comparing sirolimus-containing versus mTOR-inhibitor-free immunosuppression in patients undergoing liver transplantation for hepatocellular carcinoma

<p>Abstract</p> <p>Background</p> <p>The potential anti-cancer effects of mammalian target of rapamycin (mTOR) inhibitors are being intensively studied. To date, however, few randomised clinical trials (RCT) have been performed to demonstrate anti-neoplastic effects in the pure oncology setting, and at present, no oncology endpoint-directed RCT has been reported in the high-malignancy risk population of immunosuppressed transplant recipients. Interestingly, since mTOR inhibitors have both immunosuppressive and anti-cancer effects, they have the potential to simultaneously protect against immunologic graft loss and tumour development. Therefore, we designed a prospective RCT to determine if the mTOR inhibitor sirolimus can improve hepatocellular carcinoma (HCC)-free patient survival in liver transplant (LT) recipients with a pre-transplant diagnosis of HCC.</p> <p>Methods/Design</p> <p>The study is an open-labelled, randomised, RCT comparing sirolimus-containing versus mTOR-inhibitor-free immunosuppression in patients undergoing LT for HCC. Patients with a histologically confirmed HCC diagnosis are randomised into 2 groups within 4-6 weeks after LT; one arm is maintained on a centre-specific mTOR-inhibitor-free immunosuppressive protocol and the second arm is maintained on a centre-specific mTOR-inhibitor-free immunosuppressive protocol for the first 4-6 weeks, at which time sirolimus is initiated. A 2^1/2 -year recruitment phase is planned with a 5-year follow-up, testing HCC-free survival as the primary endpoint. Our hypothesis is that sirolimus use in the second arm of the study will improve HCC-free survival. The study is a non-commercial investigator-initiated trial (IIT) sponsored by the University Hospital Regensburg and is endorsed by the European Liver and Intestine Transplant Association; 13 countries within Europe, Canada and Australia are participating.</p> <p>Discussion</p> <p>If our hypothesis is correct that mTOR inhibition can reduce HCC tumour growth while simultaneously providing immunosuppression to protect the liver allograft from rejection, patients should experience less post-transplant problems with HCC recurrence, and therefore could expect a longer and better quality of life. A positive outcome will likely change the standard of posttransplant immunosuppressive care for LT patients with HCC.</p> <p>Trial Register</p> <p>Trial registered at <url>http://www.clinicaltrials.gov</url>: NCT00355862</p> <p>(EudraCT Number: 2005-005362-36)</p

Diversified actin protrusions promote environmental exploration but are dispensable for locomotion of leukocytes

Most migrating cells extrude their front by the force of actin polymerization. Polymerization requires an initial nucleation step, which is mediated by factors establishing either parallel filaments in the case of filopodia or branched filaments that form the branched lamellipodial network. Branches are considered essential for regular cell motility and are initiated by the Arp2/3 complex, which in turn is activated by nucleation-promoting factors of the WASP and WAVE families. Here we employed rapid amoeboid crawling leukocytes and found that deletion of the WAVE complex eliminated actin branching and thus lamellipodia formation. The cells were left with parallel filaments at the leading edge, which translated, depending on the differentiation status of the cell, into a unipolar pointed cell shape or cells with multiple filopodia. Remarkably, unipolar cells migrated with increased speed and enormous directional persistence, while they were unable to turn towards chemotactic gradients. Cells with multiple filopodia retained chemotactic activity but their migration was progressively impaired with increasing geometrical complexity of the extracellular environment. These findings establish that diversified leading edge protrusions serve as explorative structures while they slow down actual locomotion