Single-Step Purification of Monomeric l-Selectin via Aptamer Affinity Chromatography

l-selectin is a transmembrane receptor expressed on the surface of white blood cells and responsible for the tethering of leukocytes to vascular endothelial cells. This initial intercellular contact is the first step of the complex leukocyte adhesion cascade that ultimately permits extravasation of leukocytes into the surrounding tissue in case of inflammation. Here we show the binding of a soluble histidine tagged l-selectin to a recently described shortened variant of an l-selectin specific DNA aptamer with surface plasmon resonance. The high specificity of this aptamer in combination with its high binding affinity of ~12 nM, allows for a single-step protein purification from cell culture supernatants. In comparison to the well-established Ni-NTA based technology, aptamer affinity chromatography (AAC) was easier to establish, resulted in a 3.6-fold higher protein yield, and increased protein purity. Moreover, due to target specificity, the DNA aptamer facilitated binding studies directly from cell culture supernatant, a helpful characteristic to quickly monitor successful expression of biological active l-selectin. View Full-Tex

Examining approaches for modeling individual tree growth response to thinning in Norway spruce

Using periodic measurements from permanent plots in non-thinned and thinned Norway spruce (Picea abies (L.) H. Karst.) stands in Norway, individual-tree growth models were developed to predict annual diameter increment, height increment, and height to crown base increment. Based on long-term data across a range of thinning regimes and stand conditions, alternative approaches for modeling response to treatment were assessed. Dynamic thinning response functions in the form of multiplicative modifiers that predict no effect at the time of thinning, a rapid increase followed by an early maximum before the effect gradually declines to zero could not be fitted to initially derived baseline models without thinning related predictors. However, alternative approaches were used and found to perform well. Specifically, indicator variables representing varying time periods after thinning were statistically significant and behaved in a robust manner as well as consistent with general expectations. In addition, they improved overall prediction accuracy when incorporated as fixed effects into the baseline models for diameter and height to crown base increment. Further, more simply, including exponentially decreasing multiplicative thinning response functions improved prediction accuracy for height increment and height to crown base increment. Irrespective of studied attribute and modelling approach, improvement in performance of these extended models was relatively limited when compared to the corresponding baseline models and more pronounced in trees from thinned stands. We conclude that the largely varying and often multi-year measurement intervals of the periodic data used in this study likely prevented the development of more sophisticated thinning response functions. However, based on the evaluation of the final models’ overall performance such complex response functions may not to be necessary to reliably predict individual tree growth after thinning for certain conditions or species, which should be further considered in future analyses of similar nature.publishedVersio

Temperature Schedules for Self-Supervised Contrastive Methods on Long-Tail Data

Most approaches for self-supervised learning (SSL) are optimised on curated balanced datasets, e.g. ImageNet, despite the fact that natural data usually exhibits long-tail distributions. In this paper, we analyse the behaviour of one of the most popular variants of SSL, i.e. contrastive methods, on long-tail data. In particular, we investigate the role of the temperature parameter $\tau$ in the contrastive loss, by analysing the loss through the lens of average distance maximisation, and find that a large $\tau$ emphasises group-wise discrimination, whereas a small $\tau$ leads to a higher degree of instance discrimination. While $\tau$ has thus far been treated exclusively as a constant hyperparameter, in this work, we propose to employ a dynamic $\tau$ and show that a simple cosine schedule can yield significant improvements in the learnt representations. Such a schedule results in a constant `task switching' between an emphasis on instance discrimination and group-wise discrimination and thereby ensures that the model learns both group-wise features, as well as instance-specific details. Since frequent classes benefit from the former, while infrequent classes require the latter, we find this method to consistently improve separation between the classes in long-tail data without any additional computational cost.Comment: ICLR 202

A stand-level growth and yield model for thinned and unthinned even-aged Scots pine forests in Norway

Management of Scots pine (Pinus sylvestris L.) in Norway requires a forest growth and yield model suitable for describing stand dynamics of even-aged forests under contemporary climatic conditions with and without the effects of silvicultural thinning. A system of equations forming such a stand-level growth and yield model fitted to long-term experimental data is presented here. The growth and yield model consists of component equations for (i) dominant height, (ii) stem density (number of stems per hectare), (iii) total basal area, (iv) and total stem volume fitted simultaneously using seemingly unrelated regression. The component equations for stem density, basal area, and volume include a thinning modifier to forecast stand dynamics in thinned stands. It was shown that thinning significantly increased basal area and volume growth while reducing competition related mortality. No significant effect of thinning was found on dominant height. Model examination by means of various fit statistics indicated no obvious bias and improvement in prediction accuracy in comparison to existing models in general. An application of the developed stand-level model comparing different management scenarios exhibited plausible long-term behavior and we propose this is therefore suitable for national deployment.publishedVersio

Stand-level growth models for long-term projections of the main species groups in Norway

Stand-level growth and yield models are important tools that support forest managers and policymakers. We used recent data from the Norwegian National Forest Inventory to develop stand-level models, with components for dominant height, survival (number of survived trees), ingrowth (number of recruited trees), basal area, and total volume, that can predict long-term stand dynamics (i.e. 150 years) for the main species in Norway, namely Norway spruce (Picea abies (L.) Karst.), Scots pine (Pinus sylvestris L.), and birch (Betula pubescens Ehrh. and Betula pendula Roth). The data used represent the structurally heterogeneous forests found throughout Norway with a wide range of ages, tree size mixtures, and management intensities. This represents an important alternative to the use of dedicated and closely monitored long-term experiments established in single species even-aged forests for the purpose of building these stand-level models. Model examination by means of various fit statistics indicated that the models were unbiased, performed well within the data range and extrapolated to biologically plausible patterns. The proposed models have great potential to form the foundation for more sophisticated models, in which the influence of other factors such as natural disturbances, stand structure including species mixtures, and management practices can be included.publishedVersio

Simulation of Congenital Heart Defect Corrective Surgeries Using Thin Shell Elements

International audienceCongenital heart defect (CHD) corrective interventions in infants are extremely challenging due to commonly complex and heterogeneous disease pat-terns. At present, cardiac surgeons can only rely on non-invasive imaging prior to surgery. Critical decisions regarding the surgical procedure of choice and its exe-cution must be made during the actual surgery and are strongly dependent on ex-perience. We want to improve surgery planning by providing a simulation system that is able to accurately predict patient-specific results for different surgical pro-cedures preoperatively. Therefore we use a sophisticated simulation model based on thin shell elements. We present a novel joining approach that allows for im-plementing all necessary surgical low-level procedures, e.g. incising and suturing, independent from the simulation model. No modifications are necessary for al-ready approved thin shell implementations and our simulation system can instan-taneously benefit from further improved simulation models in the future. By re-ducing computationally expensive simulations to a minimum during a virtual surgery we can achieve a fluent workflow for surgeons. However, a specialized mesh resampling algorithm is required to fully utilize our simulation system

Updated yield tables and site index curves for Norway spruce and Scots pine growing in Norway

Denne rapporten presenterer oppdaterte bonitetskurver og produksjonstabeller for jevnaldrende renbestand av gran og furu, og gjelder for innlandsstrøk i Norge inkludert Nordland og Troms og Finnmark for furu. Vekstforholdene over hele Norge har endret seg vesentlig de siste 50 årene, og de oppdaterte bonitetskurvene og produksjonstabellene har blitt utviklet for å reflektere det. De oppdaterte bonitetskurvene er basert på totalalder, med en basisalder på 40 år. I forhold til de bonitetskurvene som er i bruk i dag, viser de oppdaterte bonitetskurvene en forlenget økt overhøydevekst, slik at de dermed når større overhøyder ved høye bestandsalder for begge studerte treslag. Oppdaterte produksjonstabeller har blitt utledet for forskjellige boniteter, utgangstettheter og tynningsscenarioer. Tabellene representerer både vanlige forvaltningsalternativer og ulike andre alternativer som kan være av interesse. Sammenligning av de oppdaterte produksjonstabellene med de som er i bruk i dag avslører til dels betydelige forskjeller, inkludert høyere netto volumproduksjon i de nye tabellene for utynnede bestand av begge treslag og nesten alle bonitetsklasser.Oppdaterte produksjonstabeller og bonitetskurver for gran og furu i NorgepublishedVersionpublishedVersio

Size Dependence of Steric Shielding and Multivalency Effects for Globular Binding Inhibitors

Competitive binding inhibitors based on multivalent nanoparticles have shown great potential for preventing virus infections. However, general design principles of highly efficient inhibitors are lacking as the quantitative impact of factors such as virus concentration, inhibitor size, steric shielding, or multivalency effects in the inhibition process is not known. Based on two complementary experimental inhibition assays we determined size- dependent steric shielding and multivalency effects. This allowed us to adapt the Cheng–Prusoff equation for its application to multivalent systems. Our results show that the particle and volume normalized IC50 value of an inhibitor at very low virus concentration predominantly depends on its multivalent association constant, which itself exponentially increases with the inhibitor/virus contact area and ligand density. Compared to multivalency effects, the contribution of steric shielding to the IC50 values is only minor, and its impact is only noticeable if the multivalent dissociation constant is far below the virus concentration, which means if all inhibitors are bound to the virus. The dependence of the predominant effect, either steric shielding or multivalency, on the virus concentration has significant implications on the in vitro testing of competitive binding inhibitors and determines optimal inhibitor diameters for the efficient inhibition of viruses

Direct comparison of steroid and non-steroid eluting small surface pacing leads: Randomized, multicenter clinical trial

Background: The aim of the study was to evaluate the effi cacy and safety of small surfacesteroid-eluting atrial and ventricular pacing leads in comparison to non-steroid leads usingremote monitoring system (Biotronik Home Monitoring®).Methods: In this randomized multicenter prospective trial, SIELLO T steroid-eluting ventricularleads (n = 42) were compared to BPPU T non-steroid leads (n = 46) and SIELLOJT steroid-eluting atrial leads (n = 24) to BPPU JT non-steroid leads (n = 27) (Biotronik,Berlin, Germany) in pacemaker devices with remote monitoring capabilities. Lead parameterswere evaluated during implantation, at 1-week and 1, 3, 6-month outpatient follow-up. Remotemonitoring data were collected weekly.Results: Atrial and ventricular steroid-eluting leads had stable sensing and impedance ascompared to non-steroid leads at implantation and during follow-up. Patients with non-steroidatrial leads had signifi cantly higher threshold compared to steroid leads at 1-week and at1, 3, 6-month follow-up with a peak at 1-month (1-month 1.4 ± 0.6 vs. 0.7 ± 0.3 V at 0.4 ms,p < 0.001; 6-month 0.3 ± 0.5 vs. 0.2 ± 0.3 V at 0.4 ms, p = 0.002). Patients with non-steroidventricular leads had signifi cantly higher threshold compared to steroid leads at 1, 3, 6-month(6-month 1.0 ± 0.3 vs. 0.6 ± 0.2 V at 0.4 ms, p < 0.001). Remote monitoring confi rmed consistentresults. During the study, 3 patients died of non-lead-related death. Lead repositioningwas necessary in 2 atrial, 2 ventricular steroid leads and in 1 ventricular non-steroid lead.Conclusions: Atrial and ventricular pacemaker leads with steroid showed signifi cantly lowerpacing threshold compared to non-steroid leads, confi rmed by remote monitoring