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2,020 results on '"Eriksson, Leif A."'

1. An OpenMetBuoy dataset of Marginal Ice Zone dynamics collected around Svalbard in 2022 and 2023

Author

Rabault, Jean, Taelman, Catherine, Idžanović, Martina, Hope, Gaute, Nose, Takehiko, Kristoffersen, Yngve, Jensen, Atle, Breivik, Øyvind, Bryhni, Helge Thomas, Hoppmann, Mario, Demchev, Denis, Korosov, Anton, Johansson, Malin, Eltoft, Torbjørn, Dagestad, Knut-Frode, Röhrs, Johannes, Eriksson, Leif, Moro, Marina Durán, Rikardsen, Edel S. U., Waseda, Takuji, Kodaira, Tsubasa, Lohse, Johannes, Desjonquères, Thibault, Olsen, Sveinung, Gundersen, Olav, de Aguiar, Victor Cesar Martins, Karlsen, Truls, Babanin, Alexander, Voermans, Joey, Park, Jeong-Won, and Müller, Malte

Subjects
Physics - Atmospheric and Oceanic Physics
Abstract

Sea ice is a key element of the global Earth system, with a major impact on global climate and regional weather. Unfortunately, accurate sea ice modeling is challenging due to the diversity and complexity of underlying physics happening there, and a relative lack of ground truth observations. This is especially true for the Marginal Ice Zone (MIZ), which is the area where sea ice is affected by incoming ocean waves. Waves contribute to making the area dynamic, and due to the low survival time of the buoys deployed there, the MIZ is challenging to monitor. In 2022-2023, we released 79 OpenMetBuoys (OMBs) around Svalbard, both in the MIZ and the ocean immediately outside of it. OMBs are affordable enough to be deployed in large number, and gather information about drift (GPS position) and waves (1-dimensional elevation spectrum). This provides data focusing on the area around Svalbard with unprecedented spatial and temporal resolution. We expect that this will allow to perform validation and calibration of ice models and remote sensing algorithms.

Published
2024

2. Solving Quantified Boolean Formulas with Few Existential Variables

Author

Eriksson, Leif, Lagerkvist, Victor, Osipov, George, Ordyniak, Sebastian, Panolan, Fahad, and Rychlicki, Mateusz

Subjects
Computer Science - Computational Complexity, Computer Science - Artificial Intelligence
Abstract

The quantified Boolean formula (QBF) problem is an important decision problem generally viewed as the archetype for PSPACE-completeness. Many problems of central interest in AI are in general not included in NP, e.g., planning, model checking, and non-monotonic reasoning, and for such problems QBF has successfully been used as a modelling tool. However, solvers for QBF are not as advanced as state of the art SAT solvers, which has prevented QBF from becoming a universal modelling language for PSPACE-complete problems. A theoretical explanation is that QBF (as well as many other PSPACE-complete problems) lacks natural parameters} guaranteeing fixed-parameter tractability (FPT). In this paper we tackle this problem and consider a simple but overlooked parameter: the number of existentially quantified variables. This natural parameter is virtually unexplored in the literature which one might find surprising given the general scarcity of FPT algorithms for QBF. Via this parameterization we then develop a novel FPT algorithm applicable to QBF instances in conjunctive normal form (CNF) of bounded clause length. We complement this by a W[1]-hardness result for QBF in CNF of unbounded clause length as well as sharper lower bounds for the bounded arity case under the (strong) exponential-time hypothesis.

Published
2024

3. Improved Algorithms for Allen's Interval Algebra by Dynamic Programming with Sublinear Partitioning

Author

Eriksson, Leif and Lagerkvist, Victor

Subjects
Computer Science - Computational Complexity, Computer Science - Artificial Intelligence
Abstract

Allen's interval algebra is one of the most well-known calculi in qualitative temporal reasoning with numerous applications in artificial intelligence. Recently, there has been a surge of improvements in the fine-grained complexity of NP-hard reasoning tasks, improving the running time from the naive $2^{O(n^2)}$ to $O^*((1.0615n)^{n})$, with even faster algorithms for unit intervals a bounded number of overlapping intervals (the $O^*(\cdot)$ notation suppresses polynomial factors). Despite these improvements the best known lower bound is still only $2^{o(n)}$ (under the exponential-time hypothesis) and major improvements in either direction seemingly require fundamental advances in computational complexity. In this paper we propose a novel framework for solving NP-hard qualitative reasoning problems which we refer to as dynamic programming with sublinear partitioning. Using this technique we obtain a major improvement of $O^*((\frac{cn}{\log{n}})^{n})$ for Allen's interval algebra. To demonstrate that the technique is applicable to more domains we apply it to a problem in qualitative spatial reasoning, the cardinal direction point algebra, and solve it in $O^*((\frac{cn}{\log{n}})^{2n/3})$ time. Hence, not only do we significantly advance the state-of-the-art for NP-hard qualitative reasoning problems, but obtain a novel algorithmic technique that is likely applicable to many problems where $2^{O(n)}$ time algorithms are unlikely.

Published
2023

4. A Fast Algorithm for Consistency Checking Partially Ordered Time

Author

Eriksson, Leif and Lagerkvist, Victor

Subjects
Computer Science - Computational Complexity, Computer Science - Artificial Intelligence
Abstract

Partially ordered models of time occur naturally in applications where agents or processes cannot perfectly communicate with each other, and can be traced back to the seminal work of Lamport. In this paper we consider the problem of deciding if a (likely incomplete) description of a system of events is consistent, the network consistency problem for the point algebra of partially ordered time (POT). While the classical complexity of this problem has been fully settled, comparably little is known of the fine-grained complexity of POT except that it can be solved in $O^*((0.368n)^n)$ time by enumerating ordered partitions. We construct a much faster algorithm with a run-time bounded by $O^*((0.26n)^n)$. This is achieved by a sophisticated enumeration of structures similar to total orders, which are then greedily expanded toward a solution. While similar ideas have been explored earlier for related problems it turns out that the analysis for POT is non-trivial and requires significant new ideas.

Published
2023

7. A Multivariate Complexity Analysis of Qualitative Reasoning Problems

Author

Eriksson, Leif and Lagerkvist, Victor

Subjects
Computer Science - Computational Complexity, Computer Science - Artificial Intelligence
Abstract

Qualitative reasoning is an important subfield of artificial intelligence where one describes relationships with qualitative, rather than numerical, relations. Many such reasoning tasks, e.g., Allen's interval algebra, can be solved in $2^{O(n \cdot \log n)}$ time, but single-exponential running times $2^{O(n)}$ are currently far out of reach. In this paper we consider single-exponential algorithms via a multivariate analysis consisting of a fine-grained parameter $n$ (e.g., the number of variables) and a coarse-grained parameter $k$ expected to be relatively small. We introduce the classes FPE and XE of problems solvable in $f(k) \cdot 2^{O(n)}$, respectively $f(k)^n$, time, and prove several fundamental properties of these classes. We proceed by studying temporal reasoning problems and (1) show that the Partially Ordered Time problem of effective width $k$ is solvable in $16^{kn}$ time and is thus included in XE, and (2) that the network consistency problem for Allen's interval algebra with no interval overlapping with more than $k$ others is solvable in $(2nk)^{2k} \cdot 2^{n}$ time and is included in FPE. Our multivariate approach is in no way limited to these to specific problems and may be a generally useful approach for obtaining single-exponential algorithms.

Published
2022

9. A novel DPH5-related diphthamide-deficiency syndrome causing embryonic lethality or profound neurodevelopmental disorder

Author

Shankar, Suma P, Grimsrud, Kristin, Lanoue, Louise, Egense, Alena, Willis, Brandon, Hörberg, Johanna, AlAbdi, Mayer, Klaus, Ütkür, Koray, Monaghan, Kristin G, Krier, Joel, Stoler, Joan, Alnemer, Maha, Shankar, Prabhu R, Schaffrath, Raffael, Alkuraya, Fowzan S, Brinkmann, Ulrich, Eriksson, Leif A, Lloyd, Kent, Rauen, Katherine A, Network, Undiagnosed Diseases, Acosta, Maria T, Adam, Margaret, Adams, David R, Alvey, Justin, Amendola, Laura, Andrews, Ashley, Ashley, Euan A, Azamian, Mahshid S, Bacino, Carlos A, Bademci, Guney, Balasubramanyam, Ashok, Baldridge, Dustin, Bale, Jim, Bamshad, Michael, Barbouth, Deborah, Bayrak-Toydemir, Pinar, Beck, Anita, Beggs, Alan H, Behrens, Edward, Bejerano, Gill, Bennet, Jimmy, Berg-Rood, Beverly, Bernstein, Jonathan A, Berry, Gerard T, Bican, Anna, Bivona, Stephanie, Blue, Elizabeth, Bohnsack, John, Bonner, Devon, Botto, Lorenzo, Boyd, Brenna, Briere, Lauren C, Brokamp, Elly, Brown, Gabrielle, Burke, Elizabeth A, Burrage, Lindsay C, Butte, Manish J, Byers, Peter, Byrd, William E, Carey, John, Carrasquillo, Olveen, Cassini, Thomas, Chang, Ta Chen Peter, Chanprasert, Sirisak, Chao, Hsiao-Tuan, Clark, Gary D, Coakley, Terra R, Cobban, Laurel A, Cogan, Joy D, Coggins, Matthew, Cole, F Sessions, Colley, Heather A, Cooper, Cynthia M, Cope, Heidi, Craigen, William J, Crouse, Andrew B, Cunningham, Michael, D'Souza, Precilla, Dai, Hongzheng, Dasari, Surendra, Davis, Joie, Dayal, Jyoti G, Deardorff, Matthew, Dell'Angelica, Esteban C, Dipple, Katrina, Doherty, Daniel, Dorrani, Naghmeh, Doss, Argenia L, Douine, Emilie D, Duncan, Laura, Earl, Dawn, Eckstein, David J, Emrick, Lisa T, Eng, Christine M, Esteves, Cecilia, Falk, Marni, Fernandez, Liliana, Fieg, Elizabeth L, and Fisher, Paul G

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Genetics, Pediatric, Human Genome, 2.1 Biological and endogenous factors, Adenosine Diphosphate, Animals, Histidine, Humans, Methyltransferases, Mice, Mice, Inbred C57BL, Neurodevelopmental Disorders, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Syndrome, Nonverbal neurodevelopment delays, Novel gene discovery, Precision animal modeling, Precision genomics, Translational genetics, Undiagnosed Diseases Network, Clinical Sciences, Genetics & Heredity
Abstract

PurposeDiphthamide is a post-translationally modified histidine essential for messenger RNA translation and ribosomal protein synthesis. We present evidence for DPH5 as a novel cause of embryonic lethality and profound neurodevelopmental delays (NDDs).MethodsMolecular testing was performed using exome or genome sequencing. A targeted Dph5 knockin mouse (C57BL/6Ncrl-Dph5em1Mbp/Mmucd) was created for a DPH5 p.His260Arg homozygous variant identified in 1 family. Adenosine diphosphate-ribosylation assays in DPH5-knockout human and yeast cells and in silico modeling were performed for the identified DPH5 potential pathogenic variants.ResultsDPH5 variants p.His260Arg (homozygous), p.Asn110Ser and p.Arg207Ter (heterozygous), and p.Asn174LysfsTer10 (homozygous) were identified in 3 unrelated families with distinct overlapping craniofacial features, profound NDDs, multisystem abnormalities, and miscarriages. Dph5 p.His260Arg homozygous knockin was embryonically lethal with only 1 subviable mouse exhibiting impaired growth, craniofacial dysmorphology, and multisystem dysfunction recapitulating the human phenotype. Adenosine diphosphate-ribosylation assays showed absent to decreased function in DPH5-knockout human and yeast cells. In silico modeling of the variants showed altered DPH5 structure and disruption of its interaction with eEF2.ConclusionWe provide strong clinical, biochemical, and functional evidence for DPH5 as a novel cause of embryonic lethality or profound NDDs with multisystem involvement and expand diphthamide-deficiency syndromes and ribosomopathies.

Published
2022

20. A longitudinal mixed methods evaluation of a facilitation training intervention to build implementation capacity.

Author

Costea, Veronica-Aurelia, Bäck, Annika, Bergström, Anna, Lundin, Andreas, Hasson, Henna, and Eriksson, Leif

Abstract

Background: There is a demand for facilitators who can ease the collaboration within a team or an organization in the implementation of evidence-based interventions (EBIs) and who are positioned to build the implementation capacity in an organization. This study aimed to evaluate the results the Building implementation capacity for facilitation (BIC-F) intervention had on the participants' perceived knowledge, skills, and self-efficacy to facilitate implementation and the normalization of a systematic implementation model into their work routines, and its use into their respective organizations. Methods: The BIC-F intervention was delivered to 37 facilitators in six workshops, which focused on teaching participants to apply a systematic implementation model and various facilitation tools and strategies. A longitudinal mixed methods design was used to evaluate the intervention. Data was collected pre- and post-intervention using questionnaires and semistructured interviews grounded on the Normalization Process Theory (NPT). Quantitative data were analyzed using descriptive (mean, SD) and inferential (paired t-tests) methods. Qualitative data were analyzed using deductive content analysis according to NPT. Results: An increase in the participants' perceived knowledge, skills, and selfefficacy was observed post-intervention. Normalization of the systematic implementation model in the participants' work routines was in an early phase, facilitated by high coherence, however, other NPT mechanisms were not sufficiently activated yet to contribute to full normalization. In the organizations where participants initiated the normalization process, they were still working towards achieving coherence and cognitive participation among relevant stakeholders. Conclusion: The intervention had positive results on the participants' perceived knowledge, skills, and self-efficacy and these recognized the value of a systematic implementation model for their practice. However, further efforts are needed to apply it consistently as a part of their work routines and in the organization. Future interventions should provide long-term support for facilitators, and include methods to transfer training between organizational levels and to overcome contextual barriers. [ABSTRACT FROM AUTHOR]

Published
2024
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23. Selective Bias Virtual Screening for Discovery of Promising Antimalarial Candidates targeting Plasmodium N-Myristoyltransferase

Author

Andrade, Carolina, primary, Sousa, Bruna Katiele de Paula, additional, Sigurdardóttir, Sunniva, additional, Bourgard, Catarina, additional, Borba, Joyce, additional, Clementino, Leandro, additional, Salazar-Alvarez, Luis Carlos, additional, Groustra, Sophia, additional, Zigweid, Rachael, additional, Khim, Monique, additional, Staker, Bart, additional, Costa, Fabio, additional, Eriksson, Leif, additional, and Sunnerhagen, Per, additional

Published
2024
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29. Exploring women’s interpretations of survey questions on pregnancy and pregnancy outcomes: Cognitive interviews in Iganga Mayuge, Uganda

Author

Kwesiga, Doris, Målqvist, Mats, Garimoi Orach, Christopher, Eriksson, Leif, Blencowe, Hannah, Waiswa, Peter, Kwesiga, Doris, Målqvist, Mats, Garimoi Orach, Christopher, Eriksson, Leif, Blencowe, Hannah, and Waiswa, Peter

Abstract

Background: In 2021, Uganda’s neonatal mortality rate was approximately 19 deaths per 1000 live births, with an estimated stillbirth rate of 15.1 per 1000 total births. Data are critical for indicating areas where deaths occur and why, hence driving improvements. Many countries rely on surveys like Demographic and Health Surveys (DHS), which face challenges with respondents’ misinterpretation of questions. However, little is documented about this in Uganda. Cognitive interviews aim to improve questionnaires and assess participants’ comprehension of items. Through cognitive interviews we explored women’s interpretations of questions on pregnancy and pregnancy outcomes. Methods: In November 2021, we conducted cognitive interviews with 20 women in Iganga Mayuge health and demographic surveillance system site in eastern Uganda. We adapted the reproductive section of the DHS VIII women’s questionnaire, purposively selected questions and used concurrent verbal probing. Participants had secondary school education and were English speaking. Cognition was measured through comparing instructions in the DHS interviewers’ manual to participants’ responses and researcher’s knowledge. A qualitative descriptive approach to analysis was undertaken. Results: We report findings under the cognitive aspect of comprehension. Some questions were correctly understood, especially those with less technical terms or without multiple sections. Most participants struggled with questions asking whether the woman has her living biological children residing with her or not. Indeed, some thought it referred to how many living children they had. There were comprehension difficulties with long questions like 210 that asks about miscarriages, newborn deaths, and stillbirths together. Participants had varying meanings for miscarriages, while many misinterpreted stillbirth, not linking it to gestational age. Furthermore, even amongst educated women some survey questions were misunderstood. Conclusions

Published
2024
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33. An experimental target-based platform in yeast for screening Plasmodium vivax deoxyhypusine synthase inhibitors

Author

Fernandes Silva, Suelen, primary, Klippel, Angelica Hollunder, additional, Sigurdardottir, Sunniva, additional, Mahdizadeh, Sayyed Jalil, additional, Tiukova, Ievgeniia, additional, Bourgard, Catarina, additional, Monteiro do Amaral Prado, Heloisa, additional, de Araujo, Renan Vinicius, additional, Bilsland, Elizabeth, additional, King, Ross, additional, Massirer, Katlin Brauer, additional, Eriksson, Leif, additional, Bengtson, Mario Henrique, additional, Sunnerhagen, Per, additional, and Zanelli, Cleslei Fernando, additional

Published
2023
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46. Predicting Enzyme–Substrate Specificity with QM/MM Methods: A Case Study of the Stereospecificity of d‑Glucarate Dehydratase

Author

Tian, Boxue, Wallrapp, Frank, Kalyanaraman, Chakrapani, Zhao, Suwen, Eriksson, Leif A, and Jacobson, Matthew P

Subjects
Generic health relevance, Adipates, Biocatalysis, Glucaric Acid, Hydro-Lyases, Models, Chemical, Models, Molecular, Molecular Dynamics Simulation, Molecular Structure, Protein Binding, Protein Structure, Tertiary, Quantum Theory, Stereoisomerism, Substrate Specificity, Thermodynamics, Medicinal and Biomolecular Chemistry, Biochemistry and Cell Biology, Medical Biochemistry and Metabolomics, Biochemistry & Molecular Biology
Abstract

The stereospecificity of d-glucarate dehydratase (GlucD) is explored by QM/MM calculations. Both the substrate binding and the chemical steps of GlucD contribute to substrate specificity. Although the identification of transition states remains computationally intensive, we suggest that QM/MM computations on ground states or intermediates can capture aspects of specificity that cannot be obtained using docking or molecular mechanics methods.

Published
2013

47. Protein kinase A controls yeast growth in visible light

Author

Molin, Mikael, Logg, Katarina, Bodvard, Kristofer, Peeters, Ken, Forsmark, Annabelle, Roger, Friederike, Jörhov, Anna, Mishra, Neha, Billod, Jean-Marc, Amir, Sabiha, Andersson, Mikael, Eriksson, Leif A., Warringer, Jonas, Käll, Mikael, and Blomberg, Anders

Published
2020
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49. Discovery of novel inhibitors for Pseudomonas aeruginosalipase enzyme from in silicoand in vitrostudies

Author

Gholami, Asma, Minai-Tehrani, Dariush, Farewell, Anne, and Eriksson, Leif A.

Abstract

AbstractPseudomonas aeruginosais an opportunistic pathogen prone to developing drug-resistance and is a major cause of infection for burn patients and patients suffering from cystic fibrosis or are hospitalized in intensive care units. One of the virulence factors of this bacterium is the lipase enzyme that degrades the extracellular matrix of the host tissue and promotes invasion. Bromhexine is a mucolytic drug and has recently been reported to function as a competitive inhibitor of lipase with an IC50value of 49 µM. In the present study, an attempt was made to identify stronger inhibitors from the ChEMBL database of bioactive compounds, as compared to the reference compound Bromhexine. Following docking and MD simulations, four hit compounds (N1-N4) were selected that showed promising binding modes and low RMSD values indicative of stable protein-ligand complexes. From subsequent binding pose metadynamics (BPMD) simulations, two of these (N2 and N4) stood out as more potent than Bromhexine, displaying stable interactions with residues in the catalytic site of the enzyme. Biological investigations were performed for all four compounds. Among them, the same two hit compounds were found to be the most effective binders with IC50values of 22.1 and 27.5 µM, respectively; i.e. roughly twice as efficient as the reference Bromhexine. Taken together, our results show that these hits can be promising new candidates to use as leads for the development of drugs targeting the P. aeruginosalipase enzyme.Communicated by Ramaswamy H. Sarma

Published
2024
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50. Multiscale In SilicoStudy of the Mechanism of Activation of the RtcB Ligase by the PTP1B Phosphatase

Author

Mahdizadeh, Sayyed Jalil, Stier, Michael, Carlesso, Antonio, Lamy, Aurore, Thomas, Melissa, and Eriksson, Leif A.

Abstract

Inositol-requiring enzyme 1 (IRE1) is a transmembrane sensor that is part of a trio of sensors responsible for controlling the unfolded protein response within the endoplasmic reticulum (ER). Upon the accumulation of unfolded or misfolded proteins in the ER, IRE1 becomes activated and initiates the cleavage of a 26-nucleotide intron from human X-box-containing protein 1 (XBP1). The cleavage is mediated by the RtcB ligase enzyme, which splices together two exons, resulting in the formation of the spliced isoform XBP1s. The XBP1s isoform activates the transcription of genes involved in ER-associated degradation to maintain cellular homeostasis. The catalytic activity of RtcB is controlled by the phosphorylation and dephosphorylation of three tyrosine residues (Y306, Y316, and Y475), which are regulated by the ABL1 tyrosine kinase and PTP1B phosphatase, respectively. This study focuses on investigating the mechanism by which the PTP1B phosphatase activates the RtcB ligase using a range of advanced in silico methods. Protein–protein docking identified key interacting residues between RtcB and PTP1B. Notably, the phosphorylated Tyr306 formed hydrogen bonds and salt bridge interactions with the “gatekeeper” residues Arg47 and Lys120 of the inactive PTP1B. Classical molecular dynamics simulation emphasized the crucial role of Asp181 in the activation of PTP1B, driving the conformational change from an open to a closed state of the WPD-loop. Furthermore, QM/MM-MD simulations provided insights into the free energy landscape of the dephosphorylation reaction mechanism of RtcB, which is mediated by the PTP1B phosphatase.

Published
2024
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