Publications by authors named "Hallen M"

Purpose: The aim of this study is to, in the Swedish media debate, explore the discursive constructions of challenges in human rights and freedoms following the national spatial strategy for health and survival during the COVID-19 pandemic.

Methods: The study, inspired by a critical discourse analytic approach, focused particularly on the issues addressed, subject positions, relations and rhetoric. Seventeen opinion articles published in Swedish national newspapers December 2019 - February 2022 were analysed.

View Article and Find Full Text PDF

Quantum bits (qubits) are prone to several types of error as the result of uncontrolled interactions with their environment. Common strategies to correct these errors are based on architectures of qubits involving daunting hardware overheads. One possible solution is to build qubits that are inherently protected against certain types of error, so the overhead required to correct the remaining errors is greatly reduced.

View Article and Find Full Text PDF

News reporting about mental illness lack perspectives of the mentally ill themselves and it is almost exclusively psychiatrists who are accessed when healthcare staff is consulted. The perspective of mental health nurses might contribute to the public understanding of mental illness. The purpose of this study was to describe mental health nurses' experiences of how mental illness is portrayed in media.

View Article and Find Full Text PDF

Protein design algorithms must search an enormous conformational space to identify favorable conformations. As a result, those that perform this search with guarantees of accuracy generally start with a conformational pruning step, such as dead-end elimination (DEE). However, the mathematical assumptions of DEE-based pruning algorithms have up to now severely restricted the biophysical model that can feasibly be used in protein design.

View Article and Find Full Text PDF

We present osprey 3.0, a new and greatly improved release of the osprey protein design software. Osprey 3.

View Article and Find Full Text PDF

Motivation: When proteins mutate or bind to ligands, their backbones often move significantly, especially in loop regions. Computational protein design algorithms must model these motions in order to accurately optimize protein stability and binding affinity. However, methods for backbone conformational search in design have been much more limited than for sidechain conformational search.

View Article and Find Full Text PDF

Most protein design algorithms search over discrete conformations and an energy function that is residue-pairwise, that is, a sum of terms that depend on the sequence and conformation of at most two residues. Although modeling of continuous flexibility and of non-residue-pairwise energies significantly increases the accuracy of protein design, previous methods to model these phenomena add a significant asymptotic cost to design calculations. We now remove this cost by modeling continuous flexibility and non-residue-pairwise energies in a form suitable for direct input to highly efficient, discrete combinatorial optimization algorithms such as DEE/A* or branch-width minimization.

View Article and Find Full Text PDF

Background: The mental health-care system in Sweden, as in many other counties, has its main focus on the reduction of psychiatric symptoms and the prevention of relapses. People diagnosed with schizophrenia often have significant health issues and experience reduced well-being in everyday life. The social imaginary of mental illness as an imbalance of the brain has implications concerning general attitudes in society.

View Article and Find Full Text PDF

Finding the global minimum energy conformation (GMEC) of a huge combinatorial search space is the key challenge in computational protein design (CPD) problems. Traditional algorithms lack a scalable and efficient distributed design scheme, preventing researchers from taking full advantage of current cloud infrastructures. We design cloud OSPREY (cOSPREY), an extension to a widely used protein design software OSPREY, to allow the original design framework to scale to the commercial cloud infrastructures.

View Article and Find Full Text PDF

Purpose: The purpose of the present study was to explore the risk for complications and reoperations following open repairs for sliding groin hernias.

Method: All primary indirect inguinal hernia repairs registered in the Swedish Hernia Register 1998-2011 were identified. Repeated and bilateral procedures were excluded.

View Article and Find Full Text PDF

Practical protein design problems require designing sequences with a combination of affinity, stability, and specificity requirements. Multistate protein design algorithms model multiple structural or binding "states" of a protein to address these requirements. comets provides a new level of versatile, efficient, and provable multistate design.

View Article and Find Full Text PDF

Background: Chronic groin postherniorrhaphy pain (CGPP) is common and sometimes so severe that surgical treatment is necessary. The aim of this study was to identify risk factors for being reoperated due to CGPP.

Methods: All 195,707 repairs registered in the Swedish Hernia Register between 1999 and 2011 were included in the study.

View Article and Find Full Text PDF

Despite significant successes in structure-based computational protein design in recent years, protein design algorithms must be improved to increase the biological accuracy of new designs. Protein design algorithms search through an exponential number of protein conformations, protein ensembles, and amino acid sequences in an attempt to find globally optimal structures with a desired biological function. To improve the biological accuracy of protein designs, it is necessary to increase both the amount of protein flexibility allowed during the search and the overall size of the design, while guaranteeing that the lowest-energy structures and sequences are found.

View Article and Find Full Text PDF

As the sole viral antigen on the HIV-1-virion surface, trimeric Env is a focus of vaccine efforts. Here we present the structure of the ligand-free HIV-1-Env trimer, fix its conformation and determine its receptor interactions. Epitope analyses revealed trimeric ligand-free Env to be structurally compatible with broadly neutralizing antibodies but not poorly neutralizing ones.

View Article and Find Full Text PDF

In macromolecular design, conformational energies are sensitive to small changes in atom coordinates; thus, modeling the small, continuous motions of atoms around low-energy wells confers a substantial advantage in structural accuracy. However, modeling these motions comes at the cost of a very large number of energy function calls, which form the bottleneck in the design calculations. In this work, we remove this bottleneck by consolidating all conformational energy evaluations into the pre-computation of a local polynomial expansion of the energy about the "ideal" conformation for each low-energy, "rotameric" state of each residue pair.

View Article and Find Full Text PDF

Kinesin motors hydrolyze ATP to produce force and do work in the cell--how the motors do this is not fully understood, but is thought to depend on the coupling of ATP hydrolysis to microtubule binding by the motor. Transmittal of conformational changes from the microtubule- to the nucleotide-binding site has been proposed to involve the central β-sheet, which could undergo large structural changes important for force production. We show here that mutation of an invariant residue in loop L7 of the central β-sheet of the Drosophila kinesin-14 Ncd motor alters both nucleotide and microtubule binding, although the mutated residue is not present in either site.

View Article and Find Full Text PDF

Computational protein and drug design generally require accurate modeling of protein conformations. This modeling typically starts with an experimentally determined protein structure and considers possible conformational changes due to mutations or new ligands. The DEE/A* algorithm provably finds the global minimum-energy conformation (GMEC) of a protein assuming that the backbone does not move and the sidechains take on conformations from a set of discrete, experimentally observed conformations called rotamers.

View Article and Find Full Text PDF

Cellular processes are "noisy". In each cell, concentrations of molecules are subject to random fluctuations due to the small numbers of these molecules and to environmental perturbations. While noise varies with time, it is often measured at steady state, for example by flow cytometry.

View Article and Find Full Text PDF

Background: Previous studies have suggested that the use of mesh in groin hernia repair may be associated with an increased risk for male infertility as a result of inflammatory obliteration of structures in the spermatic cord. In a recent study, we could not find an increased incidence of involuntary childlessness. The aim of this study was to evaluate this issue further.

View Article and Find Full Text PDF

Described here is a mass spectrometry-based covalent labeling protocol that utilizes the amine reactive reagent, s-methyl thioacetimidate (SMTA), to study the chemical denaturant-induced equilibrium unfolding/refolding properties of proteins and protein-ligand complexes in solution. The protocol, which involves evaluating the rate at which globally protected amine groups in a protein are modified with SMTA as a function of chemical denaturant concentration, is developed and applied to the analysis of eight protein samples including six purified protein samples (ubiquitin, BCAII, RNaseA, 4OT, and lysozyme with, and without GlcNAc), a five-protein mixture comprised of ubiquitin, BCAII, RNaseA, Cytochrome C, and lysozyme, and a yeast cell lysate. In ideal cases the folding free energies of proteins and the dissociation constants of protein-ligand complexes can be accurately evaluated using the protocol.

View Article and Find Full Text PDF

The nonprocessive kinesin-14 Ncd motor binds to microtubules and hydrolyzes ATP, undergoing a single displacement before releasing the microtubule. A lever-like rotation of the coiled-coil stalk is thought to drive Ncd displacements or steps along microtubules. Crystal structures and cryoelectron microscopy reconstructions imply that stalk rotation is correlated with ADP release and microtubule binding by the motor.

View Article and Find Full Text PDF

Background: Anastral spindles assemble by a mechanism that involves microtubule nucleation and growth from chromatin. It is still uncertain whether γ-tubulin, a microtubule nucleator essential for mitotic spindle assembly and maintenance, plays a role. Not only is the requirement for γ-tubulin to form anastral Drosophila oocyte meiosis I spindles controversial, but its presence in oocyte meiosis I spindles has not been demonstrated and is uncertain.

View Article and Find Full Text PDF