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This study compared step test, lactate minimum (LM) test and reverse lactate threshold (RLT) test protocols with maximal lactate steady state (MLSS) in free-swimming. All test protocols used fixed duration increments and high work-rate resolution (≤ 0.03 m·sValidation study.23 swimmers or triathletes (12 male and 11 female) of different ages (19.0 ± 5.9 yrs) and performance levels (400 m personal best 1.38 ± 0.13 m·sThe mean differences (± limits of agreement) to speed at MLSS were +1.0 ± 4.1% (speed at 4 mmol·LTest protocols with a fixed step duration and fine increments allowed high accuracy in estimating MLSS pace. With similar criterion agreement to the LM and RLT tests, incremental step tests appear more practicable due to less prior knowledge required and derivation of individual training zones.

Full documentation for the GROMACS 2023.1 release version.

This paper assesses and reports the experience of ten teams working to port,validate, and benchmark several High Performance Computing applications on a novel GPU-accelerated Arm testbed system. The testbed consists of eight NVIDIA Arm HPC Developer Kit systems built by GIGABYTE, each one equipped with a server-class Arm CPU from Ampere Computing and A100 data center GPU from NVIDIA Corp. The systems are connected together using Infiniband high-bandwidth low-latency interconnect. The selected applications and mini-apps are written using several programming languages and use multiple accelerator-based programming models for GPUs such as CUDA, OpenACC, and OpenMP offloading. Working on application porting requires a robust and easy-to-access programming environment, including a variety of compilers and optimized scientific libraries. The goal of this work is to evaluate platform readiness and assess the effort required from developers to deploy well-established scientific workloads on current and future generation Arm-based GPU-accelerated HPC systems. The reported case studies demonstrate that the current level of maturity and diversity of software and tools is already adequate for large-scale production deployments.

MotivationBloom filters are a popular data structure that allows rapid searches in large sequence datasets. So far, all tools work with nucleotide sequences; however, protein sequences are conserved over longer evolutionary distances, and only mutations on the protein level may have any functional significance.ResultsWe present MetaProFi, a Bloom filter-based tool that, for the first time, offers the functionality to build indexes of amino acid sequences and query them with both amino acid and nucleotide sequences, thus bringing sequence comparison to the biologically relevant protein level. MetaProFi implements additional efficient engineering solutions, such as a shared memory system, chunked data storage and efficient compression. In addition to its conceptual novelty, MetaProFi demonstrates state-of-the-art performance and excellent memory consumption-to-speed ratio when applied to various large datasets.Availability and implementationSource code in Python is available at https://github.com/kalininalab/metaprofi.

Full documentation for the GROMACS 2023 release version.

In this chapter, we present an interview study in which chemistry students complete tasks involving stereochemistry and pericyclic reactions. While one group is supported by an Augmented Reality (AR) learning tool, the other group works on the same tasks without this support. During follow-up interviews, we asked students to describe their reasoning for finding a solution. In this way, we are trying to find out whether the use of the AR tool leads to a higher degree of students incorporating spatial aspects into their explanations. The field of organic chemistry offers itself here as spatial skills, such as mental rotation, are central to developing a conceptual understanding. In previous research, the use of AR has supported learners in learning abstract topic specific concepts, in spatial thinking as well as in dealing with the huge variety of organic chemistry representations. In the study, learners who used our AR app tend to be able to involve spatial aspects in their reasoning more often when compared to learners without AR support.

Purpose This study aimed to investigate: 1. The influence of sex and age on the accuracy of the classical model of endurance performance, including maximal oxygen uptake ($$\dot{V}\mathrm{O}_{2}\mathrm{peak}$$ V ˙ O 2 peak ), its fraction (LT2%), and cost of running (CR), for calculating running speed at lactate threshold 2 (vLT2) in young athletes. 2. The impact of different CR determination methods on the accuracy of the model. 3. The contributions of $$\dot{V}\mathrm{O}_{2}\mathrm{peak}$$ V ˙ O 2 peak , LT2%, and CR to vLT2 in different sexes. Methods 45 male and 55 female young squad athletes from different sports (age: 15.4 ± 1.3 years; $$\dot{V}\mathrm{O}_{2}\mathrm{peak}$$ V ˙ O 2 peak : 51.4 ± 6.8 $$\hbox {mL} \cdot \hbox {kg}^{-1} \cdot \hbox {min}^{-1}$$ mL · kg - 1 · min - 1 ) performed an incremental treadmill test to determine $$\dot{V}\mathrm{O}_{2}\mathrm{peak}$$ V ˙ O 2 peak , LT2%, CR, and vLT2. CR was assessed at a fixed running speed (2.8 $$ \hbox {m} \cdot \hbox {s}^{-1} $$ m · s - 1 ), at lactate threshold 1 (LT1), and at 80% of $$\dot{V}\mathrm{O}_{2}\mathrm{peak}$$ V ˙ O 2 peak , respectively. Results Experimentally determined and modeled vLT2 were highly consistent independent of sex and age (ICC $$\ge$$ ≥ 0.959). The accuracy of vLT2 modeling was improved by reducing random variation using individualized CR at 80% $$\dot{V}\mathrm{O}_{2}\mathrm{peak}$$ V ˙ O 2 peak (± 4%) compared to CR at LT1 (± 7%) and at a fixed speed (± 8%). 97% of the total variance of vLT2 was explained by $$\dot{V}\mathrm{O}_{2}\mathrm{peak}$$ V ˙ O 2 peak , LT2%, and CR. While $$\dot{V}\mathrm{O}_{2}\mathrm{peak}$$ V ˙ O 2 peak and CR showed the highest unique (96.5% and 31.9% of total $$R^2$$ R 2 , respectively) and common (– 31.6%) contributions to the regression model, LT2% made the smallest contribution (7.5%). Conclusion Our findings indicate: 1. High accuracy of the classical model of endurance performance in calculating vLT2 in young athletes independent of age and sex. 2. The importance of work rate selection in determining CR to accurately predict vLT2. 3. The largest contribution of $$\dot{V}\mathrm{O}_{2}\mathrm{peak}$$ V ˙ O 2 peak and CR to vLT2, the latter being more important in female athletes than in males, and the least contribution of LT2%.

This study investigated biomechanical characteristics of Speed Rope Skipping (RS) and estimated the contribution of the lower and upper limbs to overall performance. Lower (jumping), upper (turning), and whole-body (skipping) performance were examined in 23 rope skippers. All tests were recorded by 2 D video and nine skipping tests were performed in a 3 D motion capture system. Similar movement patterns were observed for the lower limbs in all participants, while handle trajectories differed in shape and symmetry according to performance. In general, turning unlike jumping performance was close to and significantly correlated with skipping performance. Therefore, it appears that lower extremity movement may be adapted to the limiting capacity of the upper extremity to maintain movement stability.

Keller, S, Koob, A, Corak, D, von Schoning, V, and Born, DP. How to improve change-of-direction speed in junior team sport athletes-Horizontal, vertical, maximal, or explosive strength training? J Strength Cond Res 34(2): 473-482, 2020-The purpose of the study was to compare the effects of 4 different training methods on change-of-direction (COD) speed in junior team sport athletes. Specifically, we investigated whether horizontal load training incorporating lateral acceleration and deceleration would induce superior performance adaptations with respect to COD speed, compared with common vertically oriented maximal strength (squats and deadlifts), explosive strength (power clean and high pull), and vertical jumping exercises. Male U15 team sport athletes (n = 45) were assigned to 1 of 4 groups and performed 2 intervention training sessions per week for 4 weeks, in addition to their usual sport-specific training. Before and after the training period, COD speed, countermovement and drop jump heights, 1-legged lateral jump, and standing long jump performance were assessed. All 4 training groups improved COD speed (p ≤ 0.01, effect size [ES] ≥1.35). Countermovement and 1-legged lateral jump performance improved with the horizontal load (p < 0.01, ES = 0.81 and p < 0.01, ES = 1.36), maximal (p = 0.01, ES = 0.56 and p < 0.01, ES = 1.14), and explosive strength training (p < 0.01, ES = 0.95 and p < 0.01, ES = 1.60, respectively). The standing long jump improved with the maximal (p < 0.01, ES = 1.14) and explosive strength training (p < 0.01, ES = 0.60). In conclusion, all 4 training methods improved the COD speed in junior U15 team sport athletes. These findings emphasize the importance of well-developed lower-body strength and power, which contribute to fast COD speed. From a practical perspective, conditioning programs for junior athletes can incorporate horizontally and vertically oriented exercises with similar effectiveness on COD speed.

Background Structural annotation of genetic variants in the context of intermolecular interactions and protein stability can shed light onto mechanisms of disease-related phenotypes. Three-dimensional structures of related proteins in complexes with other proteins, nucleic acids, or ligands enrich such functional interpretation, since intermolecular interactions are well conserved in evolution. Results We present d-StructMAn, a novel computational method that enables structural annotation of local genetic variants, such as single-nucleotide variants and in-frame indels, and implements it in a highly efficient and user-friendly tool provided as a Docker container. Using d-StructMAn, we annotated several very large sets of human genetic variants, including all variants from ClinVar and all amino acid positions in the human proteome. We were able to provide annotation for more than 46% of positions in the human proteome representing over 60% proteins. Conclusions d-StructMAn is the first of its kind and a highly efficient tool for structural annotation of protein-coding genetic variation in the context of observed and potential intermolecular interactions. d-StructMAn is readily applicable to proteome-scale datasets and can be an instrumental building machine-learning tool for predicting genotype-to-phenotype relationships.

Introduction: Reactive oxygen and nitrogen species (RONS) are produced as a response to exercise and play a part in guiding the adaptive response to physical training. Exercise in the heat has been shown to further increase accumulation of RONS in systemic circulation; however, a high anti-oxidative response or heat acclimatization mechanisms could attenuate this response. In a previous study, we found reduced RONS concentrations in trained athletes following strenuous cycling in the heat. Therefore, this secondary analysis assessed whether these reduced RONS serum con-centrations are induced by an increased serum antioxidant capacity. Methods: Twelve male cyclists (V̇O2peak: 60 ± 4 ml ∙ kg-1 ∙ min-1) completed a 60-minute constant workload trial (55% peak power output, ambient temperature 30.4 ± 0.6°C) with and without ice vest in a randomized order. The core body temperature (Tcore) was measured by an ingestible capsule. Blood samples were col-lected before and after each trial to determine superoxide dismutase (SOD) and catalase (CAT) activity, total antioxidant capacity (TAC) and RONS. Due to the absence of between-group dif-ferences, data of both conditions were pooled. Results: Tcore statistically increased (p < 0.001) over the experimental trials (+6.0 ± 1.6%, effect size (ES) = 5.6). Concentrations of RONS (-17.2 ± 15.5%, p < 0.001, ES = 1.0) and TAC (-8.9 ± 22.9%, p = 0.04, ES = 0.7) statistically decreased, while the activity of CAT (+15.5 ± 84.0%, p = 0.90, ES = 0.04) and SOD (+9.2 ± 58.7%, p = 0.98, ES = 0.01) remained un-changed. Conclusions: Reduced serum RONS concentrations after strenuous cycling in the heat were not associated with upregulation of serum antioxidant capacity in trained athletes. The prooxidant-antioxidant balance may rather be regulated at a myocellular level and should be further assessed in future studies.

This paper presents a study about augmented-reality-based chemistry learning in a university lecture. Organic chemistry is often perceived as particularly difficult by students because spatial information must be processed in order to understand subject specific concepts and key ideas. To understand typical chemistry-related representations in books or literature, sophisticated mental rotation- and other spatial abilities are needed. Providing an augmented reality (AR) based learning support in the learning setting together with text and pictures is consistent with the idea of multiple external representations and the cognitive theory of multimedia learning. Using multiple external representations has proven to be beneficial for learning success, because different types of representations are processed separately in working memory. Nevertheless, the integration of a new learning medium involves the risk to hinder learning, in case of being not suitable for the learning topic or learning purpose. Therefore, this study investigates how the AR-use affects students’ cognitive load during learning in three different topics of organic chemistry. For this purpose also the usability of AR learning support is considered and the possible reduction of the influence of the mental rotation on learning success will be investigated.

Technological advances of next-generation sequencing present new computational challenges to develop methods to store and query these data in time- and memory-efficient ways. We present MetaProFi (https://github.com/kalininalab/metaprofi), a Bloom filter-based tool that, in addition to supporting nucleotide sequences, can for the first time directly store and query amino acid sequences and translated nucleotide sequences, thus bringing sequence comparison to a more biologically relevant protein level. Owing to the properties of Bloom filters, it has a zero false-negative rate, allows for exact and inexact searches, and leverages disk storage and Zstandard compression to achieve high time and space efficiency. We demonstrate the utility of MetaProFi by indexing UniProtKB datasets at organism- and at sequence-level in addition to the indexing of Tara Oceans dataset and the 2585 human RNA-seq experiments, showing that MetaProFi consumes far less disk space than state-of-the-art-tools while also improving performance.

Purpose: This study assessed the effects of cooling during endurance cycling (percooling) on changes in core body temperature (Tcore), inflammatory, and metabolic responses. Methods: A total of 12 male cyclists (peak oxygen uptake 60 [4] mL·kg−1·min−1) completed a 60-minute constant workload trial (55% of peak power output and ambient temperature 30.4°C [0.6°C]) in a randomized order both with (ICE) and without (CON) an ice vest. An ingestible capsule was used to measure Tcore. Blood samples were collected immediately before and after each trial to determine concentrations of blood lactate, serum cortisol, interleukin-6, and reactive oxygen and nitrogen species. Results: Tcore increased statistically (P P = .006, ES = 1.4). Concentrations of blood lactate (CON: 163% [63%], ES = 1.3; ICE: 149% [91%], ES = 1.3), cortisol (CON: 138% [123%], ES = 1.7; ICE: 81% [102%], ES = 1.0), and interleukin-6 (CON: 661% [324%], ES = 2.1; ICE: 624% [368%], ES = 1.2) statistically increased in both conditions (P P = .002, ES = 0.9; ICE: −15.1% [16.5%], P = .02, ES = 0.9). No correlations were found between the changes of Tcore and blood parameters across the conditions. Conclusions: Despite attenuated Tcore, similar inflammatory and metabolic responses were observed. Our findings suggest percooling to be a promising strategy to attenuate thermal strain without compromising physiological function.

Identification of biologically relevant motifs in proteins is a long-standing problem in bioinformatics, especially when considering distantly related proteins where sequence analysis alone becomes increasingly difficult. Here we present a novel approach to identify such motifs in protein three-dimensional structures without depending on sequence alignment by representing structures as graphs in the form of residue interaction networks and employing a modified frequent subgraph mining algorithm. These networks represent residues as vertices while contacts between residues are denoted by edges labeled with Euclidean distances. We use frequent subgraph mining to determine all subgraphs that are subgraph isomorphic to, i.e. are contained in, at least a given number of such networks generated from structures in the same protein family. For this we introduce two extensions of the classical frequent subgraph mining: approximate matching of distance-based labels to account for small variations between protein structures and scoring as well as score-based filtering of subgraphs in order to identify structurally conserved motifs and to counteract the expanding size of the search space. This approach was then validated by demonstrating that it can rediscover previously characterized functionally important structural motifs in selected protein families. For further validation we show that it is also able to identify motifs that correspond to patterns in the PROSITE database. We then applied our approach to all superfamilies in the SCOP database and found an enrichment of residues in the ligand binding site in the discovered motifs evidencing their functional importance. Finally we use the approach to discover a novel structural motif in jelly-roll capsid proteins found in members of the picornavirus-like superfamily. This is presented together with an efficient open source implementation of the algorithm called RINminer.Author summaryAs the evolutionary distance between proteins increases, their sequence identity drops rapidly, whereas functionally important sequence motifs and three-dimensional (3D) structural scaffold, in which they are embedded, are more conserved. We developed an approach that automatically identifies such motifs by converting protein 3D structures into a set of graphs and then employing the frequent subgraph mining framework. In these graphs, residues are represented as vertices, and if two residues interact in the corresponding protein 3D structure, they are connected by an edge labeled with the Euclidean distance between the residues. In the classical setting of frequent subgraph mining, all subgraphs from a database of graphs are enumerated and the ones that are exactly found, i.e. are subgraph isomorphic, in more than a certain number of graphs are listed as supported. Our approach introduces two new concepts: approximately isomorphic subgraphs and an efficient scoring scheme that allows to retain only biologically relevant subgraph in the enumeration step. Approximate isomorphism allows edge labels not to match exactly, and thus account for natural deviations between 3D structures of related proteins. With our approach, we were able to automatically rediscover known motifs from PROSITE, as well as in three well-studied extremely diverse protein families. We predicted functionally important residues in SCOP superfamilies and demonstrated that they tend to lie in structurally meaningful regions: ligand-binding sites and protein core. Additionally, we present a previously unreported structural motif in jelly-roll viral capsids.

β-Carbolines (BC) are pyridoindoles, which can be found in various exogenous and endogenous sources. Recent studies revealed neurostimulative, neuroprotective, neuroregenerative and anti-inflammatory effects of 9-methyl-BC (9-Me-BC). Additionally, 9-me-BC increased neurite outgrowth of dopaminergic neurons independent of dopamine uptake into these neurons. In this study, the role of astrocytes in neurostimulative, neuroregenerative and neuroprotective properties of 9-me-BC was further explored. 9-Me-BC exerted anti-proliferative effects without toxic properties in dopaminergic midbrain and cortical astrocyte cultures. The organic cation transporter (OCT) but not the dopamine transporter seem to mediate at least part the effect of 9-me-BC on astrocytes. Remarkably, 9-me-BC stimulated the gene expression of several important neurotrophic factors for dopaminergic neurons like Artn, Bdnf, Egln1, Tgfb2 and Ncam1. These factors are well known to stimulate neurite outgrowth and to show neuroprotective and neuroregenerative properties to dopaminergic neurons against various toxins. Further, we show that effect of 9-me-BC is mediated through phosphatidylinositol 3-kinase (PI3K) pathway. Additionally, 9-me-BC showed inhibitory properties to monoamine oxidase (MAO) activity with an IC50 value of 1 µM for MAO-A and of 15.5 µM for MAO-B. The inhibition of MAO by 9-me-BC might contribute to the observed increased dopamine content and anti-apoptotic properties in cell culture after 9-me-BC treatment in recent studies. Thus, 9-me-BC have a plethora of beneficial effects on dopaminergic neurons warranting its exploration as a new multimodal anti-parkinsonian medication. Electronic supplementary material The online version of this article (10.1007/s00702-020-02189-9) contains supplementary material, which is available to authorized users.

We present an implementation of the relativistic quantum-chemical density matrix renormalization group (DMRG) approach based on a matrix-product formalism. Our approach allows us to optimize matrix product state (MPS) wave functions including a variational description of scalar-relativistic effects and spin–orbit coupling from which we can calculate, for example, first-order electric and magnetic properties in a relativistic framework. While complementing our pilot implementation (Knecht, S. J. Chem. Phys. 2014, 140, 041101), this work exploits all features provided by its underlying nonrelativistic DMRG implementation based on an matrix product state and operator formalism. We illustrate the capabilities of our relativistic DMRG approach by studying the ground-state magnetization, as well as current density of a paramagnetic f9 dysprosium complex as a function of the active orbital space employed in the MPS wave function optimization.

Scratch and other block-based programming environments are popular and successful in engaging young learners with basic concepts of programming. It is common, and intentional, that programming with Scratch is done using an explorative "tinkering" approach, where blocks are selected from toolboxes and assembled. However, this type of bottom-up programming behaviour is generally associated with code quality issues, makes it difficult to create more complex programs, and may impede the learning of fundamental concepts. In order to investigate whether a more structured approach is feasible, we adapted the object-oriented design methodology of CRC cards (class-responsibility-collaboration) to Scratch programs, such that learners first plan the central aspects of their programs (i.e., the sprites and their interactions), before writing the code. We applied this methodology in the context of a pilot study with two school classes to investigate how this affects the students and their resulting projects. The results of this initial investigation suggest that students are not deterred by the additional design work, and we observed a slight improvement in the completeness and correctness of the resulting programs.

Structural diversity of natural cobamides (Cbas, B12 vitamers) is limited to the nucleotide loop. The loop is connected to the cobalt-containing corrin ring via an (R)-1-aminopropan-2-ol O-2-phosphate (AP-P) linker moiety. AP-P is produced by the l-threonine O-3-phosphate (l-Thr-P) decarboxylase CobD. Here, the CobD homolog SMUL_1544 of the organohalide-respiring epsilonproteobacterium Sulfurospirillum multivorans was characterized as a decarboxylase that produces ethanolamine O-phosphate (EA-P) from l-serine O-phosphate (l-Ser-P). EA-P is assumed to serve as precursor of the linker moiety of norcobamides that function as cofactors in the respiratory reductive dehalogenase. SMUL_1544 (SmCobD) is a pyridoxal-5���-phosphate (PLP)-containing enzyme. The structural analysis of the SmCobD apoprotein combined with the characterization of truncated mutant proteins uncovered a role of the SmCobD N-terminus in efficient l-Ser-P conversion.

In this article we describe the OpenMolcas environment and invite the computational chemistry community to collaborate. The open-source project already includes a large number of new developments realized during the transition from the commercial MOLCAS product to the open-source platform. The paper initially describes the technical details of the new software development platform. This is followed by brief presentations of many new methods, implementations, and features of the OpenMolcas program suite. These developments include novel wave function methods such as stochastic complete active space self-consistent field, density matrix renormalization group (DMRG) methods, and hybrid multiconfigurational wave function and density functional theory models. Some of these implementations include an array of additional options and functionalities. The paper proceeds and describes developments related to explorations of potential energy surfaces. Here we present methods for the optimization of conical intersections, the simulation of adiabatic and nonadiabatic molecular dynamics and interfaces to tools for semiclassical and quantum mechanical nuclear dynamics. Furthermore, the article describes features unique to simulations of spectroscopic and magnetic phenomena such as the exact semiclassical description of the interaction between light and matter, various X-ray processes, magnetic circular dichroism and properties. Finally, the paper describes a number of built-in and add-on features to support the OpenMolcas platform with post calculation analysis and visualization, and new electronic and muonic basis sets.

In this article we describe the OpenMolcas environment and invite the computational chemistry community to collaborate. The open-source project already includes a large number of new developments realized during the transition from the commercial MOLCAS product to the open-source platform. The paper initially describes the technical details of the new software development platform. This is followed by brief presentations of many new methods, implementations, and features of the OpenMolcas program suite. These developments include novel wave function methods such as stochastic complete active space self-consistent field, density matrix renormalization group (DMRG) methods, and hybrid multiconfigurational wave function and density functional theory models. Some of these implementations include an array of additional options and functionalities. The paper proceeds and describes developments related to explorations of potential energy surfaces. Here we present methods for the optimization of conical intersections, the simulation of adiabatic and nonadiabatic molecular dynamics, and interfaces to tools for semiclassical and quantum mechanical nuclear dynamics. Furthermore, the article describes features unique to simulations of spectroscopic and magnetic phenomena such as the exact semiclassical description of the interaction between light and matter, various X-ray processes, magnetic circular dichroism, and properties. Finally, the paper describes a number of built-in and add-on features to support the OpenMolcas platform with postcalculation analysis and visualization, a multiscale simulation option using frozen-density embedding theory, and new electronic and muonic basis sets.

Reliable quantum chemical methods for the description of molecules with dense-lying frontier orbitals are needed in the context of many chemical compounds and reactions. Here, we review developments that led to our newcomputational toolbo x which implements the quantum chemical density matrix renormalization group in a second-generation algorithm. We present an overview of the different components of this toolbox., Comment: 19 pages, 1 table

The organohalide-respiring bacterium Sulfurospirillum multivorans produces a unique cobamide, namely, norpseudo-B 12 , which serves as cofactor of the tetrachloroethene (PCE) reductive dehalogenase (PceA). As previously reported, a replacement of the adeninyl moiety, the lower base of the cofactor, by exogenously applied 5,6-dimethylbenzimidazole led to inactive PceA. To explore the general effect of benzimidazoles on the PCE metabolism, the susceptibility of the organism for guided biosynthesis of various singly substituted benzimidazolyl-norcobamides was investigated, and their use as cofactor by PceA was analyzed. Exogenously applied 5-methylbenzimidazole (5-MeBza), 5-hydroxybenzimidazole (5-OHBza), and 5-methoxybenzimidazole (5-OMeBza) were found to be efficiently incorporated as lower bases into norcobamides (NCbas). Structural analysis of the NCbas by nuclear magnetic resonance spectroscopy uncovered a regioselectivity in the utilization of these precursors for NCba biosynthesis. When 5-MeBza was added, a mixture of 5-MeBza-norcobamide and 6-MeBza-norcobamide was formed, and the PceA enzyme activity was affected. In the presence of 5-OHBza, almost exclusively 6-OHBza-norcobamide was produced, while in the presence of 5-OMeBza, predominantly 5-OMeBza-norcobamide was detected. Both NCbas were incorporated into PceA, and no negative effect on the PceA activity was observed. In crystal structures of PceA, both NCbas were bound in the base-off mode with the 6-OHBza and 5-OMeBza lower bases accommodated by the same solvent-exposed hydrophilic pocket that harbors the adenine as the lower base of authentic norpseudo-B 12 . In this study, a selective production of different norcobamide isomers containing singly substituted benzimidazoles as lower bases is shown, and unique structural insights into their utilization as cofactors by a cobamide-containing enzyme are provided. IMPORTANCE Guided biosynthesis of norcobamides containing singly substituted benzimidazoles as lower bases by the organohalide-respiring epsilonproteobacterium Sulfurospirillum multivorans is reported. An unprecedented specificity in the formation of norcobamide isomers containing hydroxylated or methoxylated benzimidazoles was observed that implicated a strict regioselectivity of the norcobamide biosynthesis in the organism. In contrast to 5,6-dimethylbenzimidazolyl-norcobamide, the incorporation of singly substituted benzimidazolyl-norcobamides as a cofactor into the tetrachloroethene reductive dehalogenase was not impaired. The enzyme was found to be functional with different isomers and not limited to the use of adeninyl-norcobamide. Structural analysis of the enzyme equipped with either adeninyl- or benzimidazolyl-norcobamide cofactors visualized for the first time structurally different cobamides bound in base-off conformation to the cofactor-binding site of a cobamide-containing enzyme.

Multiconfigurational wavefunction analysis and entanglement measures based on von Neumann entropy shed light on the electronic structure of a Ru nitrosyl complex, in particular on the Ru–NO bond., Complete active space self-consistent field (CASSCF) wavefunctions and an orbital entanglement analysis obtained from a density-matrix renormalisation group (DMRG) calculation are used to understand the electronic structure, and, in particular, the Ru–NO bond of a Ru nitrosyl complex. Based on the configurations and orbital occupation numbers obtained for the CASSCF wavefunction and on the orbital entropy measurements evaluated for the DMRG wavefunction, we unravel electron correlation effects in the Ru coordination sphere of the complex. It is shown that Ru–NO π bonds show static and dynamic correlation, while other Ru–ligand bonds feature predominantly dynamic correlation. The presence of static correlation requires the use of multiconfigurational methods to describe the Ru–NO bond. Subsequently, the CASSCF wavefunction is analysed in terms of configuration state functions based on localised orbitals. The analysis of the wavefunctions in the electronic singlet ground state and the first triplet state provides a picture of the Ru–NO moiety beyond the standard representation based on formal oxidation states. A distinct description of the Ru and NO fragments is advocated. The electron configuration of Ru is an equally weighted superposition of RuII and RuIII configurations, with the RuIII configuration originating from charge donation mostly from Cl ligands. However, and contrary to what is typically assumed, the electronic configuration of the NO ligand is best described as electroneutral.

The density-matrix renormalization group method has become a standard computational approach to the low-energy physics as well as dynamics of low-dimensional quantum systems. In this paper, we present a new set of applications, available as part of the ALPS package, that provide an efficient and flexible implementation of these methods based on a matrix-product state (MPS) representation. Our applications implement, within the same framework, algorithms to variationally find the ground state and low-lying excited states as well as simulate the time evolution of arbitrary one-dimensional and two-dimensional models. Implementing the conservation of quantum numbers for generic Abelian symmetries, we achieve performance competitive with the best codes in the community. Example results are provided for (i) a model of itinerant fermions in one dimension and (ii) a model of quantum magnetism., 11+5 pages, 8 figures, 2 examples

We present a state-interaction approach for matrix product state (MPS) wave functions in a nonorthogonal molecular orbital basis. Our approach allows us to calculate for example transition and spin-orbit coupling matrix elements between arbitrary electronic states provided that they share the same one-electron basis functions and active orbital space, respectively. The key element is the transformation of the MPS wave functions of different states from a nonorthogonal to a biorthonormal molecular orbital basis representation exploiting a sequence of non-unitary transformations following a proposal by Malmqvist (Int. J. Quantum Chem. 30, 479 (1986)). This is well-known for traditional wave-function parametrizations but has not yet been exploited for MPS wave functions., Comment: 34 pages, 1 figure, submitted to J. Chem. Theory Comput

Summary Corrinoid-dependent reductive dehalogenation is mediated by phylogenetically diverse anaerobic bacteria that either synthesize corrinoids de novo or are dependent on corrinoid salvaging from the environment. The tetrachloroethene (PCE) reduc- tive dehalogenase (PceA) of the Gram-negative Epsilonproteobacterium Sulfurospirillum multivorans harbours a norpseudo-B12 as corrinoid cofactor. Norpseudo-B12 differs from coenzyme B12 in the nucleotide loop structure. Adenine instead of 5,6- dimethylbenzimidazole (DMB) serves as lower ligand base of the central cobalt ion, and the nucleotide loop of norpseudo-B12 lacks a methyl group at position 176. In this study, S. multivorans was grown anaerobically with PCE in the presence of DMB. At a DMB concentration of 25 M, the adenine moiety in the nucleotide loop of norpseudo-B12 was quantita- tively replaced by DMB. The formation of the DMB- containing nor-B12 severely affected PCE-dependent growth and the PceA activity. In DMB-treated cells processing of the cytoplasmic PceA precursor was impeded, a result pointing to retarded cofactor incorporation. PceA enriched from cells cultivated with DMB contained nor-B12. Nor-B12 purified from cells grown in the presence of DMB mediated the abiotic reductive dehalogenation of trichloroacetate to dichloroacetate at a 25-fold lower rate in compari

The market demand for Human-Robot-Collaboration (HRC) systems is steadily increasing. More and more robotic equipment/services providers are emerging in the industrial environment. Due to the shortening product life cycle, manufacturing systems have to adapt the new demands. HRC-systems provide advantages over traditional systems, by combining flexibility and productivity requirements to address these problems. However the engineering design process for collaborative robot installations remains very time consuming. This paper presents an approach using a computerized planning assistant to support the engineering systems design process for collaborative robot installations. It is centered on a knowledge-based expert system and was developed in MATLAB©. The aim of the software tool is to reduce the time required by production facility planners during the engineering design phases.

The tetrachloroethene (PCE)-respiring bacterium Sulfurospirillum multivorans produces a unique cobamide, namely, norpseudo-B 12 , which, in comparison to other cobamides, e.g., cobalamin and pseudo-B 12 , lacks the methyl group in the linker moiety of the nucleotide loop. In this study, the protein SMUL_1544 was shown to be responsible for the formation of the unusual linker moiety, which is most probably derived from ethanolamine-phosphate (EA-P) as the precursor. The product of the SMUL_1544 gene successfully complemented a Salmonella enterica Δ cobD mutant. The cobD gene encodes an l -threonine- O -3-phosphate ( l -Thr-P) decarboxylase responsible for the synthesis of ( R )-1-aminopropan-2-ol O -2-phosphate (AP-P), required specifically for cobamide biosynthesis. When SMUL_1544 was produced in the heterologous host lacking CobD, norpseudo-B 12 was formed, which pointed toward the formation of EA-P rather than AP-P. Guided cobamide biosynthesis experiments with minimal medium supplemented with l -Thr-P supported cobamide biosynthesis in S. enterica producing SMUL_1544 or S. multivorans . Under these conditions, both microorganisms synthesized pseudo-B 12 . This observation indicated a flexibility in the SMUL_1544 substrate spectrum. From the formation of catalytically active PCE reductive dehalogenase (PceA) in S. multivorans cells producing pseudo-B 12 , a compatibility of the respiratory enzyme with the cofactor was deduced. This result might indicate a structural flexibility of PceA in cobamide binding. Feeding of l -[3- 13 C]serine to cultures of S. multivorans resulted in isotope labeling of the norpseudo-B 12 linker moiety, which strongly supports the hypothesis of EA-P formation from l -serine- O -phosphate ( l -Ser-P) in this organism. IMPORTANCE The identification of the gene product SMUL_1544 as a putative l -Ser-P decarboxylase involved in norcobamide biosynthesis in S. multivorans adds a novel module to the assembly line of cobamides (complete corrinoids) in prokaryotes. Selected cobamide-containing enzymes (e.g., reductive dehalogenases) showed specificity for their cobamide cofactors. It has recently been proposed that the structure of the linker moiety of norpseudo-B 12 and the mode of binding of the EA-P linker to the PceA enzyme reflect the high specificity of the enzyme for its cofactor. Data reported herein do not support this idea. In fact, norpseudo-B 12 was functional in the cobamide-dependent methionine biosynthesis of S. enterica , raising questions about the role of norcobamides in nature.

Matrix product states (MPSs) and matrix product operators (MPOs) allow an alternative formulation of the density matrix renormalization group algorithm introduced by White. Here, we describe how non-abelian spin symmetry can be exploited in MPSs and MPOs by virtue of the Wigner--Eckart theorem at the example of the spin-adapted quantum chemical Hamiltonian operator., Comment: 10 pages, 1 table

We present a matrix-product state (MPS)-based quadratically convergent density-matrix renormalization group self-consistent-field (DMRG-SCF) approach. Following a proposal by Werner and Knowles (JCP 82, 5053, (1985)), our DMRG-SCF algorithm is based on a direct minimization of an energy expression which is correct to second-order with respect to changes in the molecular orbital basis. We exploit a simultaneous optimization of the MPS wave function and molecular orbitals in order to achieve quadratic convergence. In contrast to previously reported (augmented Hessian) Newton-Raphson and super-configuration-interaction algorithms for DMRG-SCF, energy convergence beyond a quadratic scaling is possible in our ansatz. Discarding the set of redundant active-active orbital rotations, the DMRG-SCF energy converges typically within two to four cycles of the self-consistent procedure, Comment: 40 pages, 5 figures, 3 tables

Hubbard ladders are an important stepping stone to the physics of the two-dimensional Hubbard model. While many of their properties are accessible to numerical and analytical techniques, the question of whether weakly hole-doped Hubbard ladders are dominated by superconducting or charge-density-wave correlations has so far eluded a definitive answer. In particular, previous numerical simulations of Hubbard ladders have seen a much faster decay of superconducting correlations than expected based on analytical arguments. We revisit this question using a state-of-the-art implementation of the density matrix renormalization group algorithm that allows us to simulate larger system sizes with higher accuracy than before. Performing careful extrapolations of the results, we obtain improved estimates for the Luttinger liquid parameter and the correlation functions at long distances. Our results confirm that, as suggested by analytical considerations, superconducting correlations become dominant in the limit of very small doping., Comment: 10 pages, 12 figures, data analysis included

We describe how to efficiently construct the quantum chemical Hamiltonian operator in matrix product form. We present its implementation as a density matrix renormalization group (DMRG) algorithm for quantum chemical applications in a purely matrix product based framework. Existing implementations of DMRG for quantum chemistry are based on the traditional formulation of the method, which was developed from a viewpoint of Hilbert space decimation and attained a higher performance compared to straightforward implementations of matrix product based DMRG. The latter variationally optimizes a class of ansatz states known as matrix product states (MPS), where operators are correspondingly represented as matrix product operators (MPO). The MPO construction scheme presented here eliminates the previous performance disadvantages while retaining the additional flexibility provided by a matrix product approach; for example, the specification of expectation values becomes an input parameter. In this way, MPOs for different symmetries - abelian and non-abelian - and different relativistic and non-relativistic models may be solved by an otherwise unmodified program., Comment: 11 pages, 7 figures

The role of the corrinoid cofactor in reductive dehalogenation catalysis by tetrachloroethene reductive dehalogenase (PceA) of Sulfurospirillum multivorans was investigated using isotope analysis of carbon and chlorine. Crude extracts containing PceA--harboring either a native norpseudo-B12 or the alternative nor-B12 cofactor--were applied for dehalogenation of tetrachloroethene (PCE) or trichloroethene (TCE), and compared to abiotic dehalogenation with the respective purified corrinoids (norpseudovitamin B12 and norvitamin B12), as well as several commercially available cobalamins and cobinamide. Dehalogenation of TCE resulted in a similar extent of C and Cl isotope fractionation, and in similar dual-element isotope slopes (εC/εCl) of 5.0-5.3 for PceA enzyme and 3.7-4.5 for the corrinoids. Both observations support an identical reaction mechanism. For PCE, in contrast, observed C and Cl isotope fractionation was smaller in enzymatic dehalogenation, and dual-element isotope slopes (2.2-2.8) were distinctly different compared to dehalogenation mediated by corrinoids (4.6-7.0). Remarkably, εC/εCl of PCE depended in addition on the corrinoid type: εC/εCl values of 4.6 and 5.0 for vitamin B12 and norvitamin B12 were significantly different compared to values of 6.9 and 7.0 for norpseudovitamin B12 and dicyanocobinamide. Our results therefore suggest mechanistic and/or kinetic differences in catalytic PCE dehalogenation by enzymes and different corrinoids, whereas such differences were not observed for TCE.

A team of four students from Swiss high schools, selected in a national competition and accompanied by their mentors, represented their country at the 45th International Chemistry Olympiad (IChO) held in July 2013 in Moscow, Russia. The exceptional performances of Patrik Willi, Boris Stolz and Mario De Capitani in both practical and theoretical chemistry were rewarded by three bronze medals at the international level, reflecting their efforts during the year-long preparation prior to the competition.

Corrinoid-dependent reductive dehalogenation is mediated by phylogenetically diverse anaerobic bacteria that either synthesize corrinoids de novo or are dependent on corrinoid salvaging from the environment. The tetrachloroethene (PCE) reductive dehalogenase (PceA) of the Gram-negative Epsilonproteobacterium Sulfurospirillum multivorans harbours a norpseudo-B12 as corrinoid cofactor. Norpseudo-B12 differs from coenzyme B12 in the nucleotide loop structure. Adenine instead of 5,6-dimethylbenzimidazole (DMB) serves as lower ligand base of the central cobalt ion, and the nucleotide loop of norpseudo-B12 lacks a methyl group at position 176. In this study, S. multivorans was grown anaerobically with PCE in the presence of DMB. At a DMB concentration of 25 μM, the adenine moiety in the nucleotide loop of norpseudo-B12 was quantitatively replaced by DMB. The formation of the DMB-containing nor-B12 severely affected PCE-dependent growth and the PceA activity. In DMB-treated cells processing of the cytoplasmic PceA precursor was impeded, a result pointing to retarded cofactor incorporation. PceA enriched from cells cultivated with DMB contained nor-B12 . Nor-B12 purified from cells grown in the presence of DMB mediated the abiotic reductive dehalogenation of trichloroacetate to dichloroacetate at a 25-fold lower rate in comparison with norpseudo-B12 , a fact underpinning the relevance of norpseudo-B12 as efficient catalyst for reductive dehalogenation in general.

Background Only very few publications dealing with shoulder arthrodesis after bone resection procedures and no biomechanical studies are available. The presented biomechanical analysis should ascertain the type of arthrodesis with the highest primary stability in different bone loss situations. Methods On 24 fresh cadaveric shoulder specimens three different bone loss situations were investigated under the stress of abduction, adduction, anteversion and retroversion without destruction by the use of a material testing machine. In each of the testings a 16-hole reconstruction plate was used and compared to arthrodesis with an additional dorsal 6-hole plate. Findings The primary stability of shoulder arthrodesis with a 16-hole reconstruction plate after humeral head resection could be increased significantly if an additional dorsal plate was used. However, no significant improvement with the additional plate was detected after resection of the acromion. Of all investigated forms, arthrodesis after humeral head resection with additional plate showed the highest and arthrodesis after humeral head resection without additional plate showed the lowest force values. The mean values for forces achieved in abduction and adduction were considerably higher than those in anteversion and retroversion. Interpretation There are no consistent specifications of arthrodesis techniques after resection situation available, thus the presented biomechanical testings give important information about the most stable form of arthrodesis in different types of bone loss. These findings provide an opportunity to minimize complications such as pseudarthrosis for a satisfying clinical outcome.

The efficient and accurate description of the electronic structure of strongly correlated systems is still a largely unsolved problem. The usual procedures start with a multiconfigurational (usually a Complete Active Space, CAS) wavefunction which accounts for static correlation and add dynamical correlation by perturbation theory, configuration interaction, or coupled cluster expansion. This procedure requires the correct selection of the active space. Intuitive methods are unreliable for complex systems. The inexpensive black-box unrestricted natural orbital (UNO) criterion postulates that the Unrestricted Hartree-Fock (UHF) charge natural orbitals with fractional occupancy (e.g., between 0.02 and 1.98) constitute the active space. UNOs generally approximate the CAS orbitals so well that the orbital optimization in CAS Self-Consistent Field (CASSCF) may be omitted, resulting in the inexpensive UNO-CAS method. A rigorous testing of the UNO criterion requires comparison with approximate full configuration interaction wavefunctions. This became feasible with the advent of Density Matrix Renormalization Group (DMRG) methods which can approximate highly correlated wavefunctions at affordable cost. We have compared active orbital occupancies in UNO-CAS and CASSCF calculations with DMRG in a number of strongly correlated molecules: compounds of electronegative atoms (F2, ozone, and NO2), polyenes, aromatic molecules (naphthalene, azulene, anthracene, and nitrobenzene), radicals (phenoxy and benzyl), diradicals (o-, m-, and p-benzyne), and transition metal compounds (nickel-acetylene and Cr2). The UNO criterion works well in these cases. Other symmetry breaking solutions, with the possible exception of spatial symmetry, do not appear to be essential to generate the correct active space. In the case of multiple UHF solutions, the natural orbitals of the average UHF density should be used. The problems of the UNO criterion and their potential solutions are discussed: finding the UHF solutions, discontinuities on potential energy surfaces, and inclusion of dynamical electron correlation and generalization to excited states.

We present the first implementation of a density matrix renormalization group algorithm embedded in an environment described by density functional theory. The frozen density embedding scheme is used with a freeze-and-thaw strategy for a self-consistent polarization of the orbital-optimized wavefunction and the environmental densities with respect to each other., 4 pages, 3 figures

Complete active space self-consistent field (CASSCF) wavefunctions and an orbital entanglement analysis obtained from a density-matrix renormalisation group (DMRG) calculation are used to understand the electronic structure, and, in particular, the Ru-NO bond of a Ru nitrosyl complex. Based on the configurations and orbital occupation numbers obtained for the CASSCF wavefunction and on the orbital entropy measurements evaluated for the DMRG wavefunction, we unravel electron correlation effects in the Ru coordination sphere of the complex. It is shown that Ru-NO π bonds show static and dynamic correlation, while other Ru-ligand bonds feature predominantly dynamic correlation. The presence of static correlation requires the use of multiconfigurational methods to describe the Ru-NO bond. Subsequently, the CASSCF wavefunction is analysed in terms of configuration state functions based on localised orbitals. The analysis of the wavefunctions in the electronic singlet ground state and the first triplet state provides a picture of the Ru-NO moiety beyond the standard representation based on formal oxidation states. A distinct description of the Ru and NO fragments is advocated. The electron configuration of Ru is an equally weighted superposition of Ru(II) and Ru(III) configurations, with the Ru(III) configuration originating from charge donation mostly from Cl ligands. However, and contrary to what is typically assumed, the electronic configuration of the NO ligand is best described as electroneutral.

A team of four high school students from all over Switzerland represented their country at the 44th International Chemistry Olympiad (IChO) held in July 2012 in Washington D.C., USA. The exceptional performances of Thanh Phong Lê and Nina Gämperli in both practical and theoretical chemistry were rewarded by two bronze medals, reflecting their efforts during the year-long preparation prior to the competition.