Nonlinear Finite Element Analysis of Nanoindentation of Viral Capsids

Recent Atomic Force Microscope (AFM) nanoindentation experiments measuring mechanical response of the protein shells of viruses have provided a quantitative description of their strength and elasticity. To better understand and interpret these measurements, and to elucidate the underlying mechanisms, this paper adopts a course-grained modeling approach within the framework of three-dimensional nonlinear continuum elasticity. Homogeneous, isotropic, elastic, thick shell models are proposed for two capsids: the spherical Cowpea Chlorotic Mottle Virus (CCMV), and the ellipsocylindrical bacteriophage $\phi 29$. As analyzed by the finite element method, these models enable parametric characterization of the effects of AFM tip geometry, capsid dimensions, and capsid constitutive descriptions. The generally nonlinear force response of capsids to indentation is shown to be insensitive to constitutive details, and greatly influenced by geometry. Nonlinear stiffening and softening of the force response is dependent on the AFM tip dimensions and shell thickness. Fits of the models capture the roughly linear behavior observed in experimental measurements and result in estimates of Young's moduli of $\approx$280--360 MPa for CCMV and $\approx$4.5 GPa for $\phi 29$.Comment: 24 pages, 10 figures, submitted to Biophysical Journa

Planning for waterway renewal: balancing institutional reproduction and institutional change

Modern waterway networks are ageing and need to be renewed, yet the institutional context in the waterway sector is averse to change because of path dependencies. Waterway renewal, therefore, requires actors to navigate between institutional reproduction (exploiting current practices) and change (exploring new practices). Using a case study of institutions in the Dutch national waterways, we mainly find instances of institutional reproduction, which turns waterway renewal into a technical and financial exercise. However, institutional change becomes increasingly evident through a new functional-relational path, suggesting that planning for waterway renewal also entails reconsidering novel waterway configurations and incorporating neighbouring spatial developments

Diverging Ambitions and Instruments for Citizen Participation across Different Stages in Green Infrastructure Projects

Both theory and practice increasingly argue that creating green infrastructure in order to make cities climate-proof requires joint public service delivery across the green infrastructure’s lifecycle. Accordingly, citizen participation in each green infrastructure project stage is required, but the type of participation may differ. So far, limited research has been conducted to detangle how participation in green infrastructure projects is operationalised along the different project stages. This article, therefore, presents a comparative case study of nine European green infrastructure projects, in which we aim to determine: (1) how participatory ambitions may differ across green infrastructure project phases; and (2) which instruments are used to realise the participatory ambitions for each phase and whether these instruments differ across stages. The cases demonstrate different participation ambitions and means in the three project phases distinguished in this article (i.e., design, delivery, and maintenance). The design and maintenance stages resulted in high participation ambitions using organisational instruments (e.g., living labs, partnerships with community groups) and market-based instruments (e.g., open calls). In the delivery phase, participation ambitions decreased significantly in our cases, relying on legal instruments (e.g., statutory consultation) and communicative instruments (e.g., community events). Altogether, our exploratory study helps to define participation across the green infrastructure lifecycle: Early stages focus on creating shared commitment that legitimises the green infrastructure, while later stages are also driven by instrumental motives (lowering management costs). Although theory argues for profound participation in the delivery stage as well, our cases show the contrary. Future research can assess this discrepancy

p-mTOR, p-ERK and PTEN Expression in Tumor Biopsies and Organoids as Predictive Biomarkers for Patients with HPV Negative Head and Neck Cancer

Background: Survival rates of head and neck squamous cell carcinoma (HNSCC) have only marginally improved in the last decades. Hence there is a need for predictive biomarkers for long-time survival that can help to guide treatment decisions and might lead to the development of new therapies. The phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR signaling pathway is the most frequently altered pathway in HNSCC, genes are often mutated, amplificated and overexpressed causing aberrant signaling affecting cell growth and differentiation. Numerous genetic alterations of upstream and downstream factors have currently been clarified. However, their predictive value has yet to be established. Therefore we assess the predictive value of p-mTOR, p-ERK and PTEN expression. Methods: Tissue microarrays (TMA’s) of HPV-negative patients with oropharyngeal (n = 48), hypopharyngeal (n = 16) or laryngeal (n = 13) SCC, treated with primary chemoradiation (cisplatin/carboplatin/cetuximab and radiotherapy), were histologically stained for p-mTOR, PTEN and p-ERK. Expression was correlated to overall survival (OS), disease free survival (DFS) and locoregional control (LRC). Also p-mTOR was histologically stained in a separate cohort of HNSCC organoids (n = 8) and correlated to mTOR-inhibitor everolimus response. Results: High p-mTOR expression correlated significantly with worse OS in multivariate analysis in the whole patient cohort [Hazar Ratio (HR) 1.06, 95%CI 1.01–1.11, p = 0.03] and in the cisplatin/carboplatin group with both worse OS (HR 1.09, 95%CI 1.02–1.16, p = 0.02) and DFS (HR 1.06, 95%CI 1.00–1.12, p = 0,04). p-ERK expression correlated significantly with DFS in univariate analysis in the whole patient cohort (HR 1.03, 95%CI 1.00–1.05, p = 0.04) and cisplatin/carboplatin group (HR 1.03, 95%CI 1.00–1.07, p = 0.04). PTEN-expression did not correlate with OS/DFS/LRC. Better organoid response to everolimus correlated significantly to higher p-mTOR expression (Rs = − 0.731, p = 0.04). Conclusions: High p-mTOR expression predicts and high p-ERK expression tends to predict worse treatment outcome in HPV negative HNSCC patients treated with chemoradiation, providing additional evidence that these markers are candidate prognostic biomarkers for survival in this patient population. Also this study shows that the use of HNSCC organoids for biomarker research has potential. The role of PTEN expression as prognostic biomarker remains unclear, as consistent evidence on its prognostic and predictive value is lacking.</p

Actualisatie Onderbouwing Derogatie 2009

In de nazomer van 2005 heeft de Europese Commissie aan Nederland een derogatie toegekend. Daarmee is een ruimer gebruik van dierlijke mest mogelijk op melkveebedrijven gedurende de periode 2006-2009. Deze toekenning vond plaats op basis van een onderbouwing die, onder meer, stoelde op onderzoek van Schröder et al. (2005) en Aarts et al. (2005). Beide studies deden aannames ten aanzien van, bijvoorbeeld, de mate waarin (1) evenwicht heerst tussen mineralisatie en vastlegging van stikstof (N) in de bodem, (2) proefveldresultaten representatief zijn voor de praktijk, (3) weersomstandigheden representatief zijn voor de lange termijn, (4) relaties tussen bodemoverschot en nitraatconcentraties geldig zijn over een breed traject van overschotniveaus, en (5) jaarlijkse schommelingen van de nitraatconcentratie mogen worden uitgemiddeld in de tijd. Om met ingang van 2010 opnieuw een derogatie te krijgen, zal Nederland in de loop van 2009 een geactualiseerde wetenschappelijke onderbouwing moeten aanleveren. Deze moet behalve ‘Nitraatrichtlijn proof’, ook ‘Kaderrichtlijn Water proof’ zijn. Het ministerie van LNV heeft aan de CDM gevraagd om in kaart te brengen welke aannames een nadere toets behoeven en tijdig aan te geven welke data hiervoor de komende jaren verzameld dienen te worden. De CDM heeft aan de Werkgroep Onderbouwing Gebruiksnormen (WOG) gevraagd om deze inventarisatie uit te voeren

How actors are (dis)integrating policy agendas for multi-functional blue and green infrastructure projects on the ground

Local governments are increasingly considering blue and green infrastructure (BGI) in order to climate-proof cities. Because BGI can have multiple benefits beyond climate adaptation, policy integration is required. Since drainage services have traditionally been within the remit of a single department, this is new territory for water management. This article provides a dynamic perspective on the messy process of policy integration ‘on the ground’ in two BGI projects in Dordrecht, NL and Bradford, UK. Drawing on interviews with key actors involved in the cases, our research question is: How are ambitions to integrate policies resulting in multi-functional BGI projects? While previous research typically defines organisational structures as barriers for policy integration, our findings demonstrate instances of actors who are successfully navigating these structures as a route towards policy integration. Nevertheless, we found that actors who push for BGI lack resources and authority, so they mainly rely on more voluntary forms of policy integration that involve concerted action over a number of years. Overall, our cases demonstrate that space for policy integration exists and powerful agencies are sympathetic to this, but more support is needed to achieve this mandate

Recurrent sudden unexpected death in infancy : a case series of sibling deaths

Objectives: To determine the rate of sudden unexpected death in infancy (SUDI) for infants born after a previous SUDI in the same family, and to establish the causes of death and the frequency of child protection concerns in families with recurrent SUDI. Design: Observational study using clinical case records. Setting: The UK’s Care of Next Infant (CONI) programme, which provides additional care to families who have experienced SUDI with their subsequent children. Patients: Infants registered on CONI between January 2000 and December 2015. Main outcome measures: Cause of death, presence of modifiable risk factors for SUDI and child protection concerns. Results: There were 6608 live-born infants registered in CONI with 29 deaths. 26 families had 2 deaths, and 3 families had 3 deaths. The SUDI rate for infants born after one SUDI is 3.93 (95% CI 2.7 to 5.8) per 1000 live births. Cause of death was unexplained for 19 first and 15 CONI deaths. Accidental asphyxia accounted for 2 first and 6 CONI deaths; medical causes for 3 first and 4 CONI deaths; and homicide for 2 first and 4 CONI deaths. 10 families had child protection concerns. Conclusions: The SUDI rate for siblings is 10 times higher than the current UK SUDI rate. Homicide presenting as recurrent SUDI is very rare. Many parents continued to smoke and exposed infants to hazardous co-sleeping situations, with these directly leading to or contributing to the death of six siblings. SUDI parents need support to improve parenting skills and reduce risk to subsequent infants

Development and validation of a foot-and-mouth disease virus SAT serotype-specific 3ABC assay to differentiate infected from vaccinated animals

The effective control of foot-and-mouth disease (FMD) requires sensitive, specific and rapid diagnostic tools. However, the control and eradication of FMD in Africa is complicated by, among other factors, the existence of five of the seven FMD virus (FMDV) serotypes, including the SAT-serotypes 1, 2 and 3 that are genetically and antigenically the most variable FMDV serotypes. A key diagnostic assay to enable a country to re-gain its FMD-free status and for FMD surveillance, is the 3ABC or the non-structural protein (NSP) enzyme-linked immunosorbent assay (ELISA). Although many kits are available to detect 3ABC antibodies, none has been developed specifically for the variable SAT serotypes. This study designed a SAT-specific NSP ELISA and determined whether this assay could better detect NSP-specific antibodies from FMDV SAT-infected livestock. The assay’s performance was compared to validated NSP assays (PrioCheck®-NSP and IZSLER-NSP), using panels of field and experimental sera, vaccinated and/or infected with FMDV SAT1, SAT2 or SAT3. The sensitivity () of the SAT-NSP was estimated as 76% (70%, 81%) whereas the specificity was 96% (95%, 98%) at a 95% confidence interval. The sensitivity and specificity were comparable to the commercial NSP assays, PrioCheck®-NSP (82% and 99%, respectively) and IZSLER-NSP (78% and 98%, respectively). Good correlations were observed for all three assays.Dr FF Maree received funding from the FAO (MTF/INT/003/EEC) and the IAEA (agreement #16085). The work at CODA-CERVA-VAR was funded by the European Community’s Seventh Framework Programme (FP7/2007-2013) under grant agreement no 226556 (FMD-DISCONVAC) and the Veterinary and Agrochemical Research Centre (CODA-CERVA), Ukkel, Belgium.http://www.elsevier.com/locate/jviromet2019-05-01hj2018Microbiology and Plant Patholog