Comment on "Nonlinear eigenvalue problems"

The asymptotic behaviour of solutions to $y'(x)=\cos[\pi x y(x)]$ was investigated by Bender, Fring and Komijani (2014). They found, for example, a relation between the initial value $y(0)=a$ and the number of maxima that the solution exhibited. We present an alternative derivation of the asymptotic results that looks at the solutions in the regions $xy$, and confirms the behaviour found previously for larger values of $a$. This method uses the small amplitude and high frequency of the oscillatory behaviour in the region $x<y$

Molecular dynamics simulations and docking of non-nucleoside reverse transcriptase inhibitors (NNRTIs): a possible approach to personalized HIV treatment : from 7th German Conference on Chemoinformatics: 25 CIC-Workshop Goslar, Germany, 6 - 8 November 2011

The human immunodeficiency virus (HIV) is currently ranked sixth in the worldwide causes of death [1]. One treatment approach is to inhibit reverse transcriptase (RT), an enzyme essential for reverse transcription of viral RNA into DNA before integration into the host genome [2]. By using non-nucleoside RT inhibitors (NNRTIs) [3], which target an allosteric binding site, major side effects can be evaded. Unfortunately, high genetic variability of HIV in combination with selection pressure introduced by drug treatment enables the virus to develop resistance against this drug class by developing point mutations. This situation necessitates treatment with alternative NNRTIs that target the particular RT mutants encountered in a patient. Previously, proteochemometric approaches have demonstrated some success in predicting binding of particular NNRTIs to individual mutants; however a structurebased approach may help to further improve the predictive success of such models. Hence, our aim is to rationalize the experimental activity of known NNRTIs against a variety of RT mutants by combining molecular modeling, long-timescale atomistic molecular dynamics (MD) simulation sampling and ensemble docking. Initial control experiments on known inhibitor-RT mutant complexes using this protocol were successful, and the predictivity for further complexes is currently being evaluated. In addition to predictive power, MD simulations of multiple RT mutants are providing fundamental insight into the dynamics of the allosteric NNRTI binding site which is useful for the design of future inhibitors. Overall, work of this type is hoped to contribute to the development of predictive efficacy models for individual patients, and hence towards personalized HIV treatment options

Web-based instruments for strengthening sustainable regional development in the Alps

Web-based information and communication technologies enable the inclusion of all stakeholders in sustainable regional development and raise hopes that these processes will be accomplished from the bottom up and with broad public participation. This article synthesizes, presents, and critically discusses solutions for the Alps that use web 2.0 technologies, in particular: (a) GALPIS and DIAMONT with databases and an interactive webGIS, (b) mountain.TRIP as an efficient communication and information system to link research with practice, and (c) mountain wikis as tools for collaborative regional planning and development. The results indicate that new information and communication instruments enhance the implementation, promotion, assessment, and steering of sustainable regional development in the Alps

Design, synthesis, and biological evaluation of an allosteric inhibitor of HSET that targets cancer cells with supernumerary centrosomes

Centrosomes associate with spindle poles; thus, the presence of two centrosomes promotes bipolar spindle assembly in normal cells. Cancer cells often contain supernumerary centrosomes, and to avoid multipolar mitosis and cell death, these are clustered into two poles by the microtubule motor protein HSET. We report the discovery of an allosteric inhibitor of HSET, CW069, which we designed using a methodology on an interface of chemistry and biology. Using this approach, we explored millions of compounds in silico and utilized convergent syntheses. Only compound CW069 showed marked activity against HSET in vitro. The inhibitor induced multipolar mitoses only in cells containing supernumerary centrosomes. CW069 therefore constitutes a valuable tool for probing HSET function and, by reducing the growth of cells containing supernumerary centrosomes, paves the way for new cancer therapeutics

Molecular dynamics simulations and docking of non-nucleoside reverse transcriptase inhibitors (NNRTIs): a possible approach to personalized HIV treatment

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Expression of a novel versican variant in dorsal root ganglia from spared nerve injury rats

The size and modular structure of versican and its gene suggest the existence of multiple splice variants. We have identified, cloned, and sequenced a previously unknown exon located within the noncoding gene sequence downstream of exon 8. This exon, which we have named exon 8β, specifies two stop-codons. mRNAs of the versican gene with exon 8β are predicted to be constitutively degraded by nonsense-mediated RNA decay. Here, we tested the hypothesis that these transcripts become expressed in a model of neuropathic pain

Insights on physical behavior while working from home:An ecological momentary assessment study

Ever since the COVID-19 pandemic, working from home (WFH) has emerged as a common alternative work environment, but the possible influence on daily physical behavior (PB) (i.e., physical activity (PA), sedentary behavior (SB)) remains unclear. This study aimed to examine daily associations between PB and the work environment (i.e., WFH, working at the office (WAO)), as well as to explore and identify patterns of PB within each work environment. An observational study using a dual-accelerometer system to continuously assess PB for at least 5 days was conducted. The sample consisted of 55 participants providing 276 days of assessment. Additional demographic, contextual, and psychological variables were measured via baseline questionnaire and several smartphone prompts per day. To analyze the effects of the work environment on PB, multilevel analyses were conducted. For the identification of patterns within each work environment, latent class trajectory modelling was applied. Associations between the work environment and various PA parameters were found, indicating that WFH has a negative effect on MVPA time, steps, and physical activity intensity (MET), but a positive effect on short PA bouts (≤5 min). No associations between the work environment and any SB parameter (i.e., SB time, SB breaks, SB bouts) were found. Latent class trajectory modelling revealed three MVPA patterns for days WFH, and two patterns for days WAO. Given the growing prevalence of WFH and the positive health effects associated with MVPA, daily-tailored solutions to enhance MPVA while WFH are urgently needed.</p

Dipolar-coupled moment correlations in clusters of magnetic nanoparticles

Here, we investigate the nature of the moment coupling between 10-nm DMSA-coated magnetic nanoparticles, in both colloidal dispersion and in powder form. The individual iron oxide cores were composed of > 95% maghemite and agglomerated to clusters. At room temperature the ensemble behaved as a superparamagnet according to M\"ossbauer and magnetization measurements, however, with clear signs of dipolar interactions at low temperatures. Analysis of temperature-dependent AC susceptibility data in the superparamagnetic regime indicates a tendency for dipolar coupled anticorrelations of the core moments within the clusters. To resolve the directional correlations between the particle moments we performed polarized small-angle neutron scattering and determined the magnetic spin-flip cross-section of the powder in low magnetic field at 300 K. We extract the underlying pair distance distribution function of the magnetization vector field by an indirect Fourier transform of the cross-section, and which suggests positive as well as negative correlations between nearest neighbor moments, with anticorrelations clearly dominating for next-nearest moments. These tendencies are confirmed by Monte Carlo simulations of such core-clusters.Comment: 11 pages, 6 figure

Insights on physical behavior while working from home: An ecological momentary assessment study

Ever since the COVID-19 pandemic, working from home (WFH) has emerged as a common alternative work environment, but the possible influence on daily physical behavior (PB) (i.e., physical activity (PA), sedentary behavior (SB)) remains unclear. This study aimed to examine daily associations between PB and the work environment (i.e., WFH, working at the office (WAO)), as well as to explore and identify patterns of PB within each work environment. An observational study using a dual-accelerometer system to continuously assess PB for at least 5 days was conducted. The sample consisted of 55 participants providing 276 days of assessment. Additional demographic, contextual, and psychological variables were measured via baseline questionnaire and several smartphone prompts per day. To analyze the effects of the work environment on PB, multilevel analyses were conducted. For the identification of patterns within each work environment, latent class trajectory modelling was applied. Associations between the work environment and various PA parameters were found, indicating that WFH has a negative effect on MVPA time, steps, and physical activity intensity (MET), but a positive effect on short PA bouts (≤5 min). No associations between the work environment and any SB parameter (i.e., SB time, SB breaks, SB bouts) were found. Latent class trajectory modelling revealed three MVPA patterns for days WFH, and two patterns for days WAO. Given the growing prevalence of WFH and the positive health effects associated with MVPA, daily-tailored solutions to enhance MPVA while WFH are urgently needed