Investigating Cellulose Binding of Peptides Derived from Carbohydrate Binding Module 1.

Carbohydrate-binding modules (CBM) have emerged as useful tools for a wide range of tasks, including the use as purification tags or for cellulose fiber modification. For this purpose, the CBM needs to be attached to a target protein leading to large constructs. We investigated if short peptides from the carbohydrate binding site of CBMs can bind in a similar way as native, full-length CBMs to nanocrystalline cellulose (NCC) or cotton linter paper.

Anisotropic Network Analysis of Open/Closed HCN4 Channel Advocates Asymmetric Subunit Cooperativity in cAMP Modulation of Gating.

Hyperpolarization-activated cyclic nucleotide-modulated (HCN) channels are opened in an allosteric manner by membrane hyperpolarization and cyclic nucleotides such as cAMP. Because of conflicting reports from experimental studies on whether cAMP binding to the four available binding sites in the channel tetramer operates cooperatively in gating, we employ here a computational approach as a promising route to examine ligand-induced conformational changes after binding to individual sites. By combining an elastic network model (ENM) with linear response theory (LRT) for modeling the apo-holo transition of the cyclic nucleotide-binding domain (CNBD) in HCN channels, we observe a distinct pattern of cooperativity matching the "positive-negative-positive" cooperativity reported from functional studies.

Impact of a pediatric primary care health-coaching program on change in health-related quality of life in children with mental health problems: results of the PrimA-QuO cohort study.

Mental health problems (MHP) have a considerable negative impact on health-related quality of life (HRQoL) in children and their families. A low threshold Health Coaching (HC) program has been introduced to bring MH services to primary care and strengthen the role of pediatricians. It comprised training concepts as a hands-on approach for pediatricians, standardization of diagnosis and treatment, and extended consultations.

Alkali metal cations modulate the geometry of different binding sites in HCN4 selectivity filter for permeation or block.

Hyperpolarization-activated cyclic-nucleotide gated (HCN) channels are important for timing biological processes like heartbeat and neuronal firing. Their weak cation selectivity is determined by a filter domain with only two binding sites for K+ and one for Na+. The latter acts as a weak blocker, which is released in combination with a dynamic widening of the filter by K+ ions, giving rise to a mixed K+/Na+ current.

Biotite: new tools for a versatile Python bioinformatics library.

Background: Biotite is a program library for sequence and structural bioinformatics written for the Python programming language. It implements widely used computational methods into a consistent and accessible package. This allows for easy combination of various data analysis, modeling and simulation methods.

EasySMPC: a simple but powerful no-code tool for practical secure multiparty computation.

Background: Modern biomedical research is data-driven and relies heavily on the re-use and sharing of data. Biomedical data, however, is subject to strict data protection requirements. Due to the complexity of the data required and the scale of data use, obtaining informed consent is often infeasible.

Record linkage based patient intersection cardinality for rare disease studies using Mainzelliste and secure multi-party computation.

Background: The low number of patients suffering from any given rare diseases poses a difficult problem for medical research: With the exception of some specialized biobanks and disease registries, potential study participants' information are disjoint and distributed over many medical institutions. Whenever some of those facilities are in close proximity, a significant overlap of patients can reasonably be expected, further complicating statistical study feasibility assessments and data gathering. Due to the sensitive nature of medical records and identifying data, data transfer and joint computations are often forbidden by law or associated with prohibitive amounts of effort.

Weak Cation Selectivity in HCN Channels Results From K-Mediated Release of Na From Selectivity Filter Binding Sites.

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels generate the pacemaker current which plays an important role in the timing of various biological processes like the heart beat. We used umbrella sampling to explore the potential of mean force for the conduction of potassium and sodium through the open HCN4 pore. Our data explain distinct functional features like low unitary conductance and weak selectivity as a result of high energetic barriers inside the selectivity filter of this channel.

SPIKE: secure and private investigation of the kidney exchange problem.

Background: The kidney exchange problem (KEP) addresses the matching of patients in need for a replacement organ with compatible living donors. Ideally many medical institutions should participate in a matching program to increase the chance for successful matches. However, to fulfill legal requirements current systems use complicated policy-based data protection mechanisms that effectively exclude smaller medical facilities to participate.

Secure Multi-Party Computation Based Distributed Feasibility Queries - A HiGHmed Use Case.

The integration of routine medical care data into research endeavors promises great value. However, access to this extra-domain data is constrained by numerous technical and legal requirements. The German Medical Informatics Initiative (MII) - initiated by the Federal Ministry of Research and Education (BMBF) - is making progress in setting up Medical Data Integration Centers to consolidate data stored in clinical primary information systems.

Longitudinal changes of mental health problems in children and adolescents treated in a primary care-based health-coaching programme - results of the PrimA-QuO cohort study.

Background: In Germany, 19.1% of boys and 14.5% of girls are affected by mental health problems (MHP).

Consistent Quantification of Complex Dynamics via a Novel Statistical Complexity Measure.

Natural systems often show complex dynamics. The quantification of such complex dynamics is an important step in, e.g.

Adding hydrogen atoms to molecular models via fragment superimposition.

Background: Most experimentally determined structures of biomolecules lack annotated hydrogen positions due to their low electron density. However, thorough structure analysis and simulations require knowledge about the positions of hydrogen atoms. Existing methods for their prediction are either limited to a certain range of molecules or only work effectively on small compounds.

Cost Effects of a Health Coaching in Children and Adolescents With Mental Health and Developmental Disorders.

Objective: Health coaching (HC) aims to strengthen the role of primary care pediatricians in the treatment of children and adolescents with mental health and developmental disorders by extending consultation time and using disease-specific manuals. We evaluated the effect of HC on costs of specialized, pediatrician, and overall care.

Methods: In a retrospective cohort study based on German health insurance claims data, we identified children aged up to 17 years with a newly diagnosed mental health and/or developmental disorder between 2013 and 2015.

Erratum: Three-body interactions improve contact prediction within direct-coupling analysis [Phys. Rev. E 96, 052405 (2017)].

This corrects the article DOI: 10.1103/PhysRevE.96.

Mixed-methods evaluation of a structured primary care programme for children and adolescents with mental health problems (PrimA-QuO): a study protocol.

Introduction: More than 17% of German children and adolescents have clinically relevant mental health problems (MHP). Typically, general paediatricians are often the first contact for children with MHP, and referrals to specialised care tend to be the standard approach. A statutory health insurance fund developed a programme for children with MHP (Health Coaching (HC)) aiming to offer targeted but low-threshold services.

Gating movements and ion permeation in HCN4 pacemaker channels.

The HCN1-4 channel family is responsible for the hyperpolarization-activated cation current I/I that controls automaticity in cardiac and neuronal pacemaker cells. We present cryoelectron microscopy (cryo-EM) structures of HCN4 in the presence or absence of bound cAMP, displaying the pore domain in closed and open conformations. Analysis of cAMP-bound and -unbound structures sheds light on how ligand-induced transitions in the channel cytosolic portion mediate the effect of cAMP on channel gating and highlights the regulatory role of a Mg coordination site formed between the C-linker and the S4-S5 linker.

Identification of biophysical interaction patterns in direct coupling analysis.

Direct-coupling analysis is a statistical learning method for protein contact prediction based on sequence information alone. The maximum entropy principle leads to an effective inverse Potts model. Predictions on contacts are based on fitted local fields and couplings from an empirical multiple sequence alignment.

Longitudinal Flow Decorrelations in Xe+Xe Collisions at sqrt[s_{NN}]=5.44 TeV with the ATLAS Detector.

The first measurement of longitudinal decorrelations of harmonic flow amplitudes v_{n} for n=2-4 in Xe+Xe collisions at sqrt[s_{NN}]=5.44  TeV is obtained using 3  μb^{-1} of data with the ATLAS detector at the LHC. The decorrelation signal for v_{3} and v_{4} is found to be nearly independent of collision centrality and transverse momentum (p_{T}) requirements on final-state particles, but for v_{2} a strong centrality and p_{T} dependence is seen.

Inferring functional units in ion channel pores via relative entropy.

Coarse-grained protein models approximate the first-principle physical potentials. Among those modeling approaches, the relative entropy framework yields promising and physically sound results, in which a mapping from the target protein structure and dynamics to a model is defined and subsequently adjusted by an entropy minimization of the model parameters. Minimization of the relative entropy is equivalent to maximization of the likelihood of reproduction of (configurational ensemble) observations by the model.

A threshold-based method to predict thyroid nodules on scintigraphy scans.

Nuclear Medicine imaging is an important modality to follow up abnormalities of thyroid function tests and to uncover and characterize thyroid nodules either de novo or as previously seen on other imaging modalities, namely ultrasound. In general, the hypofunctioning 'cold' nodules pose a higher malignancy potential than hyperfunctioning 'hot' nodules, for which the risk is <1%. Hot nodules are detected by the radiologist as a region of focal increased radiotracer uptake, which appears as a density of pixels that is higher than surrounding normal thyroid parenchyma.

A Spatial and Functional Interaction of a Heterotetramer Survivin-DNA-PKcs Complex in DNA Damage Response.

Substantial evidence has shown that overexpression of the inhibitor of apoptosis protein (IAP) survivin in human tumors correlates significantly with treatment resistance and poor patient prognosis. Survivin serves as a radiation resistance factor that impacts the DNA damage response by interacting with DNA-dependent protein kinase (DNA-PKcs). However, the complexity, molecular determinants, and functional consequences of this interrelationship remain largely unknown.

Mainzelliste SecureEpiLinker (MainSEL): privacy-preserving record linkage using secure multi-party computation.

Motivation: Record Linkage has versatile applications in real-world data analysis contexts, where several datasets need to be linked on the record level in the absence of any exact identifier connecting related records. An example are medical databases of patients, spread across institutions, that have to be linked on personally identifiable entries like name, date of birth or ZIP code. At the same time, privacy laws may prohibit the exchange of this personally identifiable information (PII) across institutional boundaries, ruling out the outsourcing of the record linkage task to a trusted third party.