| 1. |
- Kehoe, Laura, et al.
(författare)
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Make EU trade with Brazil sustainable
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 2. |
- Breznau, Nate, et al.
(författare)
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Observing many researchers using the same data and hypothesis reveals a hidden universe of uncertainty
- 2022
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 119:44
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Tidskriftsartikel (refereegranskat)abstract
- This study explores how researchers analytical choices affect the reliability of scientific findings. Most discussions of reliability problems in science focus on systematic biases. We broaden the lens to emphasize the idiosyncrasy of conscious and unconscious decisions that researchers make during data analysis. We coordinated 161 researchers in 73 research teams and observed their research decisions as they used the same data to independently test the same prominent social science hypothesis: that greater immigration reduces support for social policies among the public. In this typical case of social science research, research teams reported both widely diverging numerical findings and substantive conclusions despite identical start conditions. Researchers expertise, prior beliefs, and expectations barely predict the wide variation in research outcomes. More than 95% of the total variance in numerical results remains unexplained even after qualitative coding of all identifiable decisions in each teams workflow. This reveals a universe of uncertainty that remains hidden when considering a single study in isolation. The idiosyncratic nature of how researchers results and conclusions varied is a previously underappreciated explanation for why many scientific hypotheses remain contested. These results call for greater epistemic humility and clarity in reporting scientific findings.
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| 3. |
- Werren, John H, et al.
(författare)
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Functional and evolutionary insights from the genomes of three parasitoid Nasonia species.
- 2010
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 327:5963, s. 343-8
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Tidskriftsartikel (refereegranskat)abstract
- We report here genome sequences and comparative analyses of three closely related parasitoid wasps: Nasonia vitripennis, N. giraulti, and N. longicornis. Parasitoids are important regulators of arthropod populations, including major agricultural pests and disease vectors, and Nasonia is an emerging genetic model, particularly for evolutionary and developmental genetics. Key findings include the identification of a functional DNA methylation tool kit; hymenopteran-specific genes including diverse venoms; lateral gene transfers among Pox viruses, Wolbachia, and Nasonia; and the rapid evolution of genes involved in nuclear-mitochondrial interactions that are implicated in speciation. Newly developed genome resources advance Nasonia for genetic research, accelerate mapping and cloning of quantitative trait loci, and will ultimately provide tools and knowledge for further increasing the utility of parasitoids as pest insect-control agents.
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| 4. |
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| 5. |
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| 6. |
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| 7. |
- Bauer, Pavol, et al.
(författare)
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Fast event-based epidemiological simulations on national scales
- 2016
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Ingår i: The international journal of high performance computing applications. - : SAGE Publications. - 1094-3420 .- 1741-2846. ; 30, s. 438-453
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Tidskriftsartikel (refereegranskat)abstract
- We present a computational modeling framework for data-driven simulations and analysis of infectious disease spread in large populations. For the purpose of efficient simulations, we devise a parallel solution algorithm targeting multi-socket shared-memory architectures. The model integrates infectious dynamics as continuous-time Markov chains and available data such as animal movements or aging are incorporated as externally defined events. To bring out parallelism and accelerate the computations, we decompose the spatial domain and optimize cross-boundary communication using dependency-aware task scheduling. Using registered livestock data at a high spatiotemporal resolution, we demonstrate that our approach not only is resilient to varying model configurations but also scales on all physical cores at realistic workloads. Finally, we show that these very features enable the solution of inverse problems on national scales.
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| 8. |
- Dietz, Benedikt, et al.
(författare)
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Detection of diabetes from whole-body MRI using deep learning
- 2021
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Ingår i: JCI Insight. - : American Society for Clinical Investigation. - 2379-3708. ; 6:21
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is one of the main drivers of type 2 diabetes, but it is not uniformly associated with the disease. The location of fat accumulation is critical for metabolic health. Specific patterns of body fat distribution, such as visceral fat, are closely related to insulin resistance. There might be further, hitherto unknown, features of body fat distribution that could additionally contribute to the disease. We used machine learning with dense convolutional neural networks to detect diabetes-related variables from 2371 T1-weighted whole-body MRI data sets. MRI was performed in participants undergoing metabolic screening with oral glucose tolerance tests. Models were trained for sex, age, BMI, insulin sensitivity, HbA1c, and prediabetes or incident diabetes. The results were compared with those of conventional models. The area under the receiver operating characteristic curve was 87% for the type 2 diabetes discrimination and 68% for prediabetes, both superior to conventional models. Mean absolute regression errors were comparable to those of conventional models. Heatmaps showed that lower visceral abdominal regions were critical in diabetes classification. Subphenotyping revealed a group with high future diabetes and microalbuminuria risk. Our results show that diabetes is detectable from whole-body MRI without additional data. Our technique of heatmap visualization identifies plausible anatomical regions and highlights the leading role of fat accumulation in the lower abdomen in diabetes pathogenesis.
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| 9. |
- Scheer, Monika, et al.
(författare)
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Synovial sarcoma disease characteristics and primary tumor sites differ between patient age groups : a report of the Cooperative Weichteilsarkom Studiengruppe (CWS)
- 2020
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Ingår i: Journal of Cancer Research and Clinical Oncology. - : SPRINGER. - 0171-5216 .- 1432-1335. ; 146:4, s. 953-960
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Tidskriftsartikel (refereegranskat)abstract
- Background: Older age is associated with worse outcome in synovial sarcoma (SS) patients. Differences in disease presentation among distinct age groups, however, are currently unknown.Methods: SS patients < 21 years registered in consecutive CWS trials over the period of 1981-2018 were evaluated. Characteristics were analyzed according to age groups using the Fisher's exact test.Results: The study population included 432 SS patients. Disease characteristics differed according to age groups of children (0-12 years, n = 176), adolescents (13-16 years, n = 178), and young adults (17-21 years, n = 78). The proportion of invasive tumors (T2) was significantly higher in older patients: children 33%, adolescents 39% and young adults 54%, p = 0.009805. Similarly, the proportion of tumors > 10 cm was higher (13%, 21%, 31%; p = 0.005657) whereas conversely, the proportion of small tumors < 3 cm was lower in older patients (29%, 24%, 6%; p = 0.000104). The presence of metastases at first diagnosis was also highest in older patients (6%, 10%, 21%, p = 0.000963). Notably, the proportion of thigh tumors was higher in older patients (p = 0.04173), whereas the proportion of head-neck tumors was lower in older patients (p = 0.08896).Conclusions The rates of large, invasive tumors and the presence of metastases are significantly associated with older patient age. Localization to the thigh is more frequent in older patients.Discussion The causes for these variations require further exploration.
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| 10. |
- Whelan, Jeremy, et al.
(författare)
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High-dose chemotherapy and blood autologous stem-cell rescue compared with standard chemotherapy in localized high-risk ewing sarcoma : Results of Euro-E.W.I.N.G.99 and Ewing-2008
- 2018
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Ingår i: Journal of Clinical Oncology. - 0732-183X. ; 36:31, s. 3110-3119
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Tidskriftsartikel (refereegranskat)abstract
- Purpose For over 30 years, the place of consolidation high-dose chemotherapy in Ewing sarcoma (ES) has been controversial. A randomized study was conducted to determine whether consolidation high-dose chemotherapy improved survival in patients with localized ES at high risk for relapse. Methods Randomization between busulfan and melphalan (BuMel) or standard chemotherapy (vincristine, dactinomycin, and ifosfamide [VAI], seven courses) was offered to patients if they were younger than 50 years of age with poor histologic response (≥ 10% viable cells) after receiving vincristine, ifosfamide, doxorubicin, and etoposide (six courses); or had a tumor volume at diagnosis >200 mL if unresected, or initially resected, or resected after radiotherapy. A 15% improvement in 3-year eventfree survival (EFS) was sought (hazard ratio [HR], 0.60). Results Between 2000 and 2015, 240 patients classified as high risk (median age, 17.1 years) were randomly assigned to VAI (n = 118) or BuMel (n = 122). Seventy-eight percent entered the trial because of poor histologic response after chemotherapy alone. Median follow-up was 7.8 years. In an intent-to-treat analysis, the risk of event was significantly decreased by BuMel comparedwith VAI: HR, 0.64 (95%CI, 0.43 to 0.95; P = .026); 3- and 8-year EFS were, respectively, 69.0%(95% CI, 60.2%to 76.6%) versus 56.7%(95%CI, 47.6%to 65.4%) and 60.7%(95%CI, 51.1%to 69.6%) versus 47.1%(95%CI, 37.7% to 56.8%). Overall survival (OS) also favored BuMel: HR, 0.63 (95% CI, 0.41 to 0.95; P = .028); 3- and 8-year OS were, respectively, 78.0% (95% CI, 69.6% to 84.5%) versus 72.2% (95% CI, 63.3% to 79.6%) and 64.5%(95%CI, 54.4% to 73.5%) versus 55.6%(95%CI, 45.8%to 65.1%). Results were consistent in the sensitivity analysis. Two patients died as a result of BuMel-related toxicity, one after standard chemotherapy. Significantly more BuMel patients experienced severe acute toxicities from this course of chemotherapy compared with multiple VAI courses. Conclusion BuMel improved EFS and OS when given after vincristine, ifosfamide, doxorubicin, and etoposide induction in localized ES with predefined high-risk factors. For this group of patients, BuMel may be an important addition to the standard of care.
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| 11. |
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| 12. |
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| 13. |
- Allshire, Arthur, et al.
(författare)
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Transferring Dexterous Manipulation from GPU Simulation to a Remote Real-World TriFinger
- 2022
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Ingår i: 2022 IEEE/RS international conference on intelligent robots and systems (IROS). - : Institute of Electrical and Electronics Engineers (IEEE). ; , s. 11802-11809
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Konferensbidrag (refereegranskat)abstract
- In-hand manipulation of objects is an important capability to enable robots to carry-out tasks which demand high levels of dexterity. This work presents a robot systems approach to learning dexterous manipulation tasks involving moving objects to arbitrary 6-DoF poses. We show empirical benefits, both in simulation and sim-to-real transfer, of using keypoint-based representations for object pose in policy observations and reward calculation to train a model-free reinforcement learning agent. By utilizing domain randomization strategies and large-scale training, we achieve a high success rate of 83% on a real TriFinger system, with a single policy able to perform grasping, ungrasping, and finger gaiting in order to achieve arbitrary poses within the workspace. We demonstrate that our policy can generalise to unseen objects, and success rates can be further improved through finetuning. With the aim of assisting further research in learning in-hand manipulation, we provide a detailed exposition of our system and make the codebase of our system available, along with checkpoints trained on billions of steps of experience, at https://s2r2-ig.github.io
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| 14. |
- Amare, Azmeraw, et al.
(författare)
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Association of Polygenic Score and the involvement of Cholinergic and Glutamatergic Pathways with Lithium Treatment Response in Patients with Bipolar Disorder.
- 2023
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Ingår i: Research square. - : Research Square Platform LLC.
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Tidskriftsartikel (refereegranskat)abstract
- Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental disorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N=2,367) and replicated in the combined PsyCourse (N=89) and BipoLife (N=102) studies. The associations of Li+PGS and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P<����������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������.
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| 15. |
- Amare, Azmeraw T, et al.
(författare)
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Association of polygenic score and the involvement of cholinergic and glutamatergic pathways with lithium treatment response in patients with bipolar disorder.
- 2023
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Ingår i: Molecular psychiatry. - 1476-5578. ; 28, s. 5251-5261
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Tidskriftsartikel (refereegranskat)abstract
- Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental healthdisorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N=2367) and replicated in the combined PsyCourse (N=89) and BipoLife (N=102) studies. The associations of Li+PGS and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P<0.05. Li+PGS was positively associated with lithium treatment response in the ConLi+Gen cohort, in both the categorical (P=9.8×10-12, R2=1.9%) and continuous (P=6.4×10-9, R2=2.6%) outcomes. Compared to bipolar patients in the 1st decile of the risk distribution, individuals in the 10th decile had 3.47-fold (95%CI: 2.22-5.47) higher odds of responding favorably to lithium. The results were replicated in the independent cohorts for the categorical treatment outcome (P=3.9×10-4, R2=0.9%), but not for the continuous outcome (P=0.13). Gene-based analyses revealed 36 candidate genes that are enriched in biological pathways controlled by glutamate and acetylcholine. Li+PGS may be useful in the development of pharmacogenomic testing strategies by enabling a classification of bipolar patients according to their response to treatment.
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| 16. |
- Amare, Azmeraw T, et al.
(författare)
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Association of Polygenic Score for Schizophrenia and HLA Antigen and Inflammation Genes With Response to Lithium in Bipolar Affective Disorder: A Genome-Wide Association Study.
- 2018
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Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 75:1, s. 65-74
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Tidskriftsartikel (refereegranskat)abstract
- Lithium is a first-line mood stabilizer for the treatment of bipolar affective disorder (BPAD). However, the efficacy of lithium varies widely, with a nonresponse rate of up to 30%. Biological response markers are lacking. Genetic factors are thought to mediate treatment response to lithium, and there is a previously reported genetic overlap between BPAD and schizophrenia (SCZ).To test whether a polygenic score for SCZ is associated with treatment response to lithium in BPAD and to explore the potential molecular underpinnings of this association.A total of 2586 patients with BPAD who had undergone lithium treatment were genotyped and assessed for long-term response to treatment between 2008 and 2013. Weighted SCZ polygenic scores were computed at different P value thresholds using summary statistics from an international multicenter genome-wide association study (GWAS) of 36989 individuals with SCZ and genotype data from patients with BPAD from the Consortium on Lithium Genetics. For functional exploration, a cross-trait meta-GWAS and pathway analysis was performed, combining GWAS summary statistics on SCZ and response to treatment with lithium. Data analysis was performed from September 2016 to February 2017.Treatment response to lithium was defined on both the categorical and continuous scales using the Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder score. The effect measures include odds ratios and the proportion of variance explained.Of the 2586 patients in the study (mean [SD] age, 47.2 [13.9] years), 1478 were women and 1108 were men. The polygenic score for SCZ was inversely associated with lithium treatment response in the categorical outcome, at a threshold P<5×10-2. Patients with BPAD who had a low polygenic load for SCZ responded better to lithium, with odds ratios for lithium response ranging from 3.46 (95% CI, 1.42-8.41) at the first decile to 2.03 (95% CI, 0.86-4.81) at the ninth decile, compared with the patients in the 10th decile of SCZ risk. In the cross-trait meta-GWAS, 15 genetic loci that may have overlapping effects on lithium treatment response and susceptibility to SCZ were identified. Functional pathway and network analysis of these loci point to the HLA antigen complex and inflammatory cytokines.This study provides evidence for a negative association between high genetic loading for SCZ and poor response to lithium in patients with BPAD. These results suggest the potential for translational research aimed at personalized prescribing of lithium.
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| 17. |
- Andersson, Alf, et al.
(författare)
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Inline Process Control – a concept study of efficient in-line process control and process adjustment with respect to product geometry
- 2016
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Ingår i: Swedish Production Symposium 2016 SPS 2016. - Lund, Sweden.
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Konferensbidrag (refereegranskat)abstract
- All manufacturing processes have variation which may violate the fulfillment of assembly, functional, geometrical or esthetical requirements and difficulties to reach desired form in all areas. The cost for geometry defects rises downstream in the process chain. Therefore, it is vital to discover these defects as soon as they appear. Then adjustments can be done in the process without losing products or time. In order to find a solution for this, a project with the overall scope “development of an intelligent process control system” has been initiated. This project consists of five different work packages: Inline measurement, Process Evaluation, Corrective actions, Flexible tooling and demonstrator cell. These work packages address different areas which are necessary to fulfill the overall scope of the project. The system shall both be able to detect geometrical defects, propose adjustments and adjust simple process parameters. The results are demonstrated in a demo cell located at Chalmers University of Technology. In the demonstrator all the different areas have been verified in an industrial case study – assembly of GOR Volvo S80. Efficient offline programming for robot based measurement, efficient process evaluation based on case base reasoning (CBR) methodology, flexible fixtures and process adjustments based on corrective actions regarding in going part positioning.
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| 18. |
- Andersson, Joel, 1981-
(författare)
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Structural evolution of two ore-bearing Palaeoproterozoic metasupracrustal belts in the Kiruna area, Northwestern Fennoscandian Shield
- 2019
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In this project, two key study areas in the northwestern Fennoscandian Shield are under investigation. The “Western supracrustal belt” and “Central Kiruna area” are both located along lithotectonically comparable Rhyacian-Orosirian metasupracrustal belts and both areas are characterized by iron oxide-apatite (IOA) and iron oxide-copper-gold (IOCG)-style mineralizations and related hydrothermal alterations. The area is in general well studied but the structural evolution remains unresolved. In order to build a structural framework for the Kiruna area, the number of deformation events, kinematics, geometries, mineralogy and interrelationships of the dominant structures are under focus in this study. The paired structural-alteration configuration is targeted in order to constrain the relative timing of dominant structures and mineral alteration parageneses in order to use these systems as structural vectors of mineralized systems. Furthermore, the Orosirian stratigraphy is re-evaluated in order to constrain the pre-compressional geological history of the study areas. This is important as it controls the character of the structural development during subsequent compression forming the sub-surface architecture as we see today.The Orosirian stratigraphy suggests the development of a syn-extensional basin in Kiruna where iron oxide-apatite deposits were emplaced. This basin was subsequently inverted accompanied by shearing, folding, and faulting during D1 and D2, refolded during D3, and further fractured during D4. The shortening directions inferred during the deformation events suggest a clockwise rotation of the stress field from NE-SW (D1) to E-W (D2) and finally NNW-SSE (D3). Regional scapolite ± albite alteration is interpreted to be coeval with regional amphibole + magnetite alteration during D1. Mineral alteration parageneses linked to D2 is more potassic in character and often structurally controlled by shear zones. As a regional generalization, the potassic dominated D2-alteration is characterized by sericite ± epidote ± biotite ± chlorite ± magnetite ± sulphide ± K-feldspar. Fe- and Cu-sulphides are concentrated into brittle D2-structures suggesting that a IOCG-style of mineralization can be linked to the potassic D2 event. This implies that iron oxide-apatite emplacement can be linked to the basin development phase, whereas epigenetic Fe- and Cu-sulphides are linked to the basin inversion-phase of the geological evolution, and hence, separated in time and probably not directly genetically linked in Kiruna.
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| 19. |
- Annadani, Yashas, et al.
(författare)
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BayesDAG : Gradient-Based Posterior Inference for Causal Discovery
- 2023
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Ingår i: Advances in Neural Information Processing Systems 36 - 37th Conference on Neural Information Processing Systems, NeurIPS 2023. - : Neural Information Processing Systems Foundation.
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Konferensbidrag (refereegranskat)abstract
- Bayesian causal discovery aims to infer the posterior distribution over causal models from observed data, quantifying epistemic uncertainty and benefiting downstream tasks. However, computational challenges arise due to joint inference over combinatorial space of Directed Acyclic Graphs (DAGs) and nonlinear functions. Despite recent progress towards efficient posterior inference over DAGs, existing methods are either limited to variational inference on node permutation matrices for linear causal models, leading to compromised inference accuracy, or continuous relaxation of adjacency matrices constrained by a DAG regularizer, which cannot ensure resulting graphs are DAGs. In this work, we introduce a scalable Bayesian causal discovery framework based on a combination of stochastic gradient Markov Chain Monte Carlo (SG-MCMC) and Variational Inference (VI) that overcomes these limitations. Our approach directly samples DAGs from the posterior without requiring any DAG regularization, simultaneously draws function parameter samples and is applicable to both linear and nonlinear causal models. To enable our approach, we derive a novel equivalence to the permutation-based DAG learning, which opens up possibilities of using any relaxed gradient estimator defined over permutations. To our knowledge, this is the first framework applying gradient-based MCMC sampling for causal discovery. Empirical evaluation on synthetic and real-world datasets demonstrate our approach's effectiveness compared to state-of-the-art baselines.
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| 20. |
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| 21. |
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| 22. |
- Bauer, Peter, 1992-
(författare)
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När slutar invandrarna vandra? : Integrationsfrågan i statlig, kommunal och skolpolitisk diskurs 1967–2000
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- During the last three decades of the 20th century Swedish immigrant policy went through a profound change. In the late 1960s immigrant policy were based on assimilation but during the 1970’s and 1980’s this policy was exchanged to multicultural guidelines. These multicultural guidelines were however abandoned in the late 1990s when integration became a key word in the debate about immigrants. This thesis investigates how these changes were made possible by a shifting understanding of immigrants in state and local discourse (the last represented by Malmö municipality) by operationalizing Carol Lee Bacchis What’s the problem represented to be analysis. Previous research has shown that the social category of immigrants during the first six decades of the 20th century understood immigrants as a threat towards the Swedish race and later the welfare state. From this perspective immigrant policy can be seen as the result of the creation of a problematized immigrant subject, a tendency that is also the case for later decades. The investigation shows that immigrants in the early 1970’s were mainly understood from a class and welfare perspective. During this period immigrants were seen as a threat towards the social cohesion of the welfare state as well as the social democratic ambitions of a raised standard of living for the working class. This understanding led to the development of a multicultural policy where immigrant culture was supported within state and local politics and by structural changes in the education system, aiming to include the category in civic life and improve their living conditions. In the years between 1976 and 1985 the understanding of immigrants however changed. During this period immigrants became increasingly problematized for their lack of employment and a cultural difference. During the end of this period the multicultural policy changed from an emphasis on culture as a resource for social inclusion to that some parts of of a Swedish identity were not subject of choice. Furthermore, this period also lead to increased efforts at the individual level, were the policy aimed to give individual immigrants increased chances at the labor market. During the last fifteen years the 20th century immigrant policy became increasingly politicized, and immigrants became understood as radically culturally different from swedes. In this period immigrant culture were constructed as oppressive towards women and outdated when compared to the modern Swedish culture. Furthermore, the notion of immigrants as unemployed from previous decades continued to play an important part and immigrants were also conceived as living segregated. This view resulted in the creation of integration policies aiming to not handle immigrants as a from the general population different group. Instead, immigrants should become integrated in Swedish society through the general welfare with an emphasis that not all parts of a Swedish identity were choose able.The result of the investigation show that European culture became increasingly normative in the development of Swedish migrant policy, thus excluding European immigrants from the problematized immigrant subject. Thereby the globalization of migration towards Sweden led to a development were immigrant policy shifted focus from class to cultural perspectives.
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| 23. |
- Bauer, Pavol
(författare)
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Parallelism and efficiency in discrete-event simulation
- 2015
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Discrete-event models depict systems where a discrete state is repeatedly altered by instantaneous changes in time, the events of the model. Such models have gained popularity in fields such as Computational Systems Biology or Computational Epidemiology due to the high modeling flexibility and the possibility to easily combine stochastic and deterministic dynamics. However, the system size of modern discrete-event models is growing and/or they need to be simulated at long time periods. Thus, efficient simulation algorithms are required, as well as the possibility to harness the compute potential of modern multicore computers. Due to the sequential design of simulators, parallelization of discrete event simulations is not trivial. This thesis discusses event-based modeling and sensitivity analysis and also examines ways to increase the efficiency of discrete-event simulations and to scale models involving deterministic and stochastic spatial dynamics on a large number of processor cores.
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| 24. |
- Bauer, Pavol
(författare)
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Parallelism in Event-Based Computations with Applications in Biology
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Event-based models find frequent usage in fields such as computational physics and biology as they may contain both continuous and discrete state variables and may incorporate both deterministic and stochastic state transitions. If the state transitions are stochastic, computer-generated random numbers are used to obtain the model solution. This type of event-based computations is also known as Monte-Carlo simulation.In this thesis, I study different approaches to execute event-based computations on parallel computers. This ultimately allows users to retrieve their simulation results in a fraction of the original computation time. As system sizes grow continuously or models have to be simulated at longer time scales, this is a necessary approach for current computational tasks.More specifically, I propose several ways to asynchronously simulate such models on parallel shared-memory computers, for example using parallel discrete-event simulation or task-based computing. The particular event-based models studied herein find applications in systems biology, computational epidemiology and computational neuroscience.In the presented studies, the proposed methods allow for high efficiency of the parallel simulation, typically scaling well with the number of used computer cores. As the scaling typically depends on individual model properties, the studies also investigate which quantities have the greatest impact on the simulation performance.Finally, the presented studies include other insights into event-based computations, such as methods how to estimate parameter sensitivity in stochastic models and how to simulate models that include both deterministic and stochastic state transitions.
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| 25. |
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| 26. |
- Bauer, Pavol, et al.
(författare)
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The URDME manual Version 1.3
- 2017
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- We have developed URDME, a general software for simulation of stochastic reaction-diffusion processes on unstructured meshes. This allows for a more flexible handling of complicated geometries and curved boundaries compared to simulations on structured, cartesian meshes. The underlying algorithm is the next subvolume method, extended to unstructured meshes by obtaining jump coefficients from a finite element formulation of the corresponding macroscopic equation. This manual describes version 1.3 of the software. URDME 1.3 includes support for Comsol Multiphysics 5.x and PDE Toolbox version 1.5 and above.
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| 27. |
- Bauer, Pavol, et al.
(författare)
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URDME v. 1.2: User's manual
- 2012
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- We have developed URDME, a general software for simulation of stochastic reaction-diffusion processes on unstructured meshes. This allows for a more flexible handling of complicated geometries and curved boundaries compared to simulations on structured, cartesian meshes. The underlying algorithm is the next subvolume method, extended to unstructured meshes by obtaining jump coefficients from a finite element formulation of the corresponding macroscopic equation. This manual describes version 1.2 of the software. URDME 1.2 includes support for Comsol Multiphysics 4.1, 4.2, 4.3 as well as the previous version 3.5a. Additionally, support for basic SBML has been added along with the possibility to compile in stand-alone mode.
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| 28. |
- Bauer, Stefanie Lena, 1990-
(författare)
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Guardians of the genome : Connecting chromatin structure and genome integrity in Saccharomyces cerevisiae
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Branched DNA structures arise during recombination and during other DNA repair processes such as repair of stalled replication forks. One branched structure, the Holliday Junction (HJ), is a four-way junction that can connect sister chromatids or homologous chromosomes. We show a physical interaction between the HJ-cleaving enzyme Yen1 and Uls1. Uls1 shares homology with the SWI/SNF-family of chromatin remodelers and has a SUMO-targeted ubiquitin ligase activity, but its cellular role remains poorly characterized. SUMOylation of Yen1 strengthened the interaction with Uls1 and both yen1 and uls1 displayed negative genetic interactions with mutations in a gene encoding an alternative HJ-cleaving enzyme MUS81. Hence, Uls1, Yen1 and Mus81 appeared to be partially redundant. A uls1 strain, however, showed minimal changes in nucleosome positioning and occupancy, as determined by a genome-wide micrococcal nuclease sequencing (MNase-Seq) analysis. Together, these results suggested a role of Uls1 in Yen1-mediated HJ resolution rather than SWI/SNF-like chromatin remodeling activity.Telomeres protect the ends of the linear chromosomes in eukaryotes from both degradation and mistaken recognition as DNA damage. In Saccharomyces cerevisiae, silent information regulator (Sir) proteins silence transcription from telomeres, by forming a higher-order chromatin structure reminiscent of heterochromatin. An MNase-Seq analysis comparing nucleosome occupancy/positioning in a sir2 mutant with a WT strain showed that the histone deacetylase Sir2 was required for stabilizing a nucleosome in subtelomeric X-elements. The Reb1 transcription factor destabilized the same nucleosome, hence competing with Sir2. Transcription at telomeres results in a species of long noncoding RNA called telomeric repeat containing RNAs (TERRAs). Sir2 and Reb1 limited TERRA steady-state levels, by different mechanisms where Reb1 presumably blocked transcription elongation. The transcriptional start sites of TERRAs mapped just centromere proximal to the Sir2-stabilized nucleosome and the nucleosome occupancy of X-elements was dependent on the position close to the telomeres rather than the DNA sequence of the X-element itself.Further analysis of nucleosome occupancy in the sir2 mutant strain revealed Sir2-stabilized nucleosomes in the intergenic spacer region (IGS) of the ribosomal DNA (rDNA) locus. The lowered nucleosome occupancy in the IGS overlapped with the promoter for a non-coding RNA, which in turn regulates rDNA copy number. The sir2 mutant also displayed indirect effects on nucleosome occupancy at cell-type specific genes.Together, the results reveal important roles for Sir2 in regulating nucleosome occupancy/positioning and begin exploring links between chromatin structure, TERRA transcription and maintenance of genome stability.
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| 29. |
- Bauer, Stefanie L., et al.
(författare)
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Helicase/SUMO-targeted ubiquitin ligase Uls1 interacts with the Holliday junction resolvase Yen1
- 2019
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 14:3
-
Tidskriftsartikel (refereegranskat)abstract
- Resolution of branched DNA structures is pivotal for repair of stalled replication forks and meiotic recombination intermediates. The Yen1 nuclease cleaves both Holliday junctions and replication forks. We show that Yen1 interacts physically with Uls1, a suggested SUMO-targeted ubiquitin ligase that also contains a SWI/SNF-family ATPase-domain. Yen1 is SUMO-modified in its noncatalytic carboxyl terminus and DNA damage induces SUMOylation. SUMO-modification of Yen1 strengthens the interaction to Uls1, and mutations in SUMO interaction motifs in Uls1 weakens the interaction. However, Uls1 does not regulate the steady-state level of SUMO-modified Yen1 or chromatin-associated Yen1. In addition, SUMO-modification of Yen1 does not affect the catalytic activity in vitro. Consistent with a shared function for Uls1 and Yen1, mutations in both genes display similar phenotypes. Both uls1 and yen1 display negative genetic interactions with the alternative HJ-cleaving nuclease Mus81, manifested both in hypersensitivity to DNA damaging agents and in meiotic defects. Point mutations in ULS1 (uls1K975R and uls1C1330S, C1333S) predicted to inactivate the ATPase and ubiquitin ligase activities, respectively, are as defective as the null allele, indicating that both functions of Uls1 are essential. A micrococcal nuclease sequencing experiment showed that Uls1 had minimal effects on global nucleosome positioning/occupancy. Moreover, increased gene dosage of YEN1 partially alleviates the mus81 uls1 sensitivity to DNA damage. We suggest a preliminary model in which Uls1 acts in the same pathway as Yen1 to resolve branched DNA structures.
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| 30. |
- Bauer, Stefanie L., 1990-, et al.
(författare)
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Sir2 and Reb1 antagonistically regulate nucleosome occupancy in subtelomeric X-elements and repress TERRAs by distinct mechanisms
- 2022
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Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 18:9
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Tidskriftsartikel (refereegranskat)abstract
- Telomere chromatin structure is pivotal for maintaining genome stability by regulating the binding of telomere-associated proteins and inhibiting the DNA damage response. In Saccharomyces cerevisiae, silent information regulator (Sir) proteins bind to terminal repeats and to subtelomeric X-elements, resulting in transcriptional silencing. Herein, we show that sir2 mutant strains display a specific loss of a nucleosome residing in the X-elements and that this deficiency is remarkably consistent between different telomeres. The X-elements contain several binding sites for the transcription factor Reb1 and we found that Sir2 and Reb1 compete for stabilizing/destabilizing this nucleosome, i.e. inactivation of Reb1 in a sir2 background reinstated the lost nucleosome. The telomeric-repeat-containing RNAs (TERRAs) originate from subtelomeric regions and extend into the terminal repeats. Both Sir2 and Reb1 repress TERRAs and in a sir2 reb1 double mutant, TERRA levels increased synergistically, showing that Sir2 and Reb1 act in different pathways for repressing TERRAs. We present evidence that Reb1 restricts TERRAs by terminating transcription. Mapping the 5′-ends of TERRAs from several telomeres revealed that the Sir2-stabilized nucleosome is the first nucleosome downstream from the transcriptional start site for TERRAs. Finally, moving an X-element to a euchromatic locus changed nucleosome occupancy and positioning, demonstrating that X-element nucleosome structure is dependent on the local telomere environment.
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| 31. |
- Bauer, Stefan, et al.
(författare)
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Real Robot Challenge : A Robotics Competition in the Cloud
- 2022
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Ingår i: Proceedings of the NeurIPS 2021 Competitions and Demonstrations Track. - : ML Research Press. ; , s. 190-204
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Konferensbidrag (refereegranskat)abstract
- Dexterous manipulation remains an open problem in robotics. To coordinate efforts of the research community towards tackling this problem, we propose a shared benchmark. We designed and built robotic platforms that are hosted at the MPI-IS1 and can be accessed remotely. Each platform consists of three robotic fingers that are capable of dexterous object manipulation. Users are able to control the platforms remotely by submitting code that is executed automatically, akin to a computational cluster. Using this setup, i) we host robotics competitions, where teams from anywhere in the world access our platforms to tackle challenging tasks ii) we publish the datasets collected during these competitions (consisting of hundreds of robot hours), and iii) we give researchers access to these platforms for their own projects.
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| 32. |
- Bauer, Ulrich Stefan, et al.
(författare)
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Validation of Functional Connectivity of Engineered Neuromuscular Junction With Recombinant Monosynaptic Pseudotyped ΔG-Rabies Virus Tracing
- 2022
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Ingår i: Frontiers in Integrative Neuroscience. - : Frontiers Media S.A.. - 1662-5145. ; 16
-
Tidskriftsartikel (refereegranskat)abstract
- Current preclinical models of neurodegenerative disease, such as amyotrophic lateral sclerosis (ALS), can significantly benefit from in vitro neuroengineering approaches that enable the selective study and manipulation of neurons, networks, and functional units of interest. Custom-designed compartmentalized microfluidic culture systems enable the co-culture of different relevant cell types in interconnected but fluidically isolated microenvironments. Such systems can thus be applied for ALS disease modeling, as they enable the recapitulation and study of neuromuscular junctions (NMJ) through co-culturing of motor neurons and muscle cells in separate, but interconnected compartments. These in vitro systems are particularly relevant for investigations of mechanistic aspects of the ALS pathological cascade in engineered NMJ, as progressive loss of NMJ functionality may constitute one of the hallmarks of disease related pathology at early onset, in line with the dying back hypothesis. In such models, ability to test whether motor neuron degeneration in ALS starts at the nerve terminal or at the NMJ and retrogradely progresses to the motor neuron cell body largely relies on robust methods for verification of engineered NMJ functionality. In this study, we demonstrate the functionality of engineered NMJs within a microfluidic chip with a differentially perturbable microenvironment using a designer pseudotyped ΔG-rabies virus for retrograde monosynaptic tracing.
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| 33. |
- Boen, Rune, et al.
(författare)
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Beyond the global brain differences : intraindividual variability differences in 1q21.1 distal and 15q11.2 bp1-bp2 deletion carriers
- 2024
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Ingår i: Biological Psychiatry. - 0006-3223 .- 1873-2402. ; 95:2, s. 147-160
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Tidskriftsartikel (refereegranskat)abstract
- Background: Carriers of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants exhibit regional and global brain differences compared with noncarriers. However, interpreting regional differences is challenging if a global difference drives the regional brain differences. Intraindividual variability measures can be used to test for regional differences beyond global differences in brain structure.Methods: Magnetic resonance imaging data were used to obtain regional brain values for 1q21.1 distal deletion (n = 30) and duplication (n = 27) and 15q11.2 BP1-BP2 deletion (n = 170) and duplication (n = 243) carriers and matched noncarriers (n = 2350). Regional intra-deviation scores, i.e., the standardized difference between an individual's regional difference and global difference, were used to test for regional differences that diverge from the global difference.Results: For the 1q21.1 distal deletion carriers, cortical surface area for regions in the medial visual cortex, posterior cingulate, and temporal pole differed less and regions in the prefrontal and superior temporal cortex differed more than the global difference in cortical surface area. For the 15q11.2 BP1-BP2 deletion carriers, cortical thickness in regions in the medial visual cortex, auditory cortex, and temporal pole differed less and the prefrontal and somatosensory cortex differed more than the global difference in cortical thickness.Conclusions: We find evidence for regional effects beyond differences in global brain measures in 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants. The results provide new insight into brain profiling of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants, with the potential to increase understanding of the mechanisms involved in altered neurodevelopment.
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| 34. |
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| 35. |
- Caldarelli, Edoardo, et al.
(författare)
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Adaptive Gaussian Process Change Point Detection
- 2022
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Ingår i: International conference on machine learning, vol 162. - : ML Research Press. ; , s. 2542-2571
-
Konferensbidrag (refereegranskat)abstract
- Detecting change points in time series, i.e., points in time at which some observed process suddenly changes, is a fundamental task that arises in many real-world applications, with consequences for safety and reliability. In this work, we propose ADAGA, a novel Gaussian process-based solution to this problem, that leverages a powerful heuristics we developed based on statistical hypothesis testing. In contrast to prior approaches, ADAGA adapts to changes both in mean and covariance structure of the temporal process. In extensive experiments, we show its versatility and applicability to different classes of change points, demonstrating that it is significantly more accurate than current state-of-the-art alternatives.
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| 36. |
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| 37. |
- Chen, Jiang, et al.
(författare)
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The helicase/SUMO-targeted ubiquitin ligase Uls1 interacts both physically and functionally with the Holliday junction resolvase Yen1
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Yen1 is nuclease that can cleave the Holliday junction (HJ), an important DNA intermediate formed during homologous recombination. Here, we show that Yen1 interacts molecularly with Uls1, a SUMO targeted ubiquitin ligase that also belongs to the SWI/SNF-family of DNA-dependent ATPases. We demonstrate that Yen1 is SUMO modified in its carboxyl terminus and that this modification strengthens the interaction between Yen1 and Uls1. Absence of Uls1 increased the steady-state levels of Yen1, but only after extensive DNA damage, suggesting that Uls1 has a role in damage-induced degradation of Yen1. Consistent with a shared role for Uls1 and Yen1, mutations in the two enzymes display similar phenotypes. Both uls1 and yen1 have a negative genetic interaction with the alternative HJ-cleaving nuclease Mus81. This negative genetic interaction is manifested in supersensitivity to DNA damaging agents, but also in a meiotic defect. Neither mus81 uls1 nor mus81 yen1 double mutant diploids can complete meiosis. Moreover, both uls1 and yen1 exacerbates the chromosome mis-segregation phenotype of mus81. However, the mus81 uls1 yen1 triple mutant strain was slightly more sensitive to DNA damage compared to any double mutant combination, indicating that Uls1 and Yen1 also have independent roles in DNA repair. Point mutant alleles of Uls1 (uls1K975R and uls1C1330S/C1333S) that inactivates the ATPase and potential ubiquitin ligase activities are also supersensitive to DNA damage when combined with mus81, indicating that both activities of Uls1 are essential for function. We suggest that Yen1 and Uls1 are involved in an alternative pathway that is responsible for resolving complex DNA repair intermediates in the absence of Mus81.
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| 38. |
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| 39. |
- Conrad, Sarah, et al.
(författare)
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Seasonal Variations of Redox State in Hemiboreal Soils Indicated by Changes of δ56Fe, Sulfate, and Nitrate in Headwater Streams
- 2019
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Ingår i: ACS Earth and Space Chemistry. - : American Chemical Society (ACS). - 2472-3452. ; 3:12, s. 2816-2823
-
Tidskriftsartikel (refereegranskat)abstract
- During recent decades, much focus has been put on the iron (Fe) isotope ratios in soils, rivers, and oceans, while studies on the variation in headwater streams are scarce. Here we assess seasonal water chemical data from 104 hemiboreal headwater streams. Between summer and late autumn, decreasing Fe concentrations and simultaneously increasing sulfate and nitrate concentrations suggest a shift from reduced to oxidized conditions in the soils along the main groundwater flow paths. Fe isotope data, obtained from a subpopulation of 16 streams, show low δ56Fe ratios during summer drought, indicating an important influx of reduced groundwater to the streams with primarily Fe(II) as an important Fe source. In total, the δ56Fe data ranged between −0.8 ± 0.1 and 1.8 ± 0.1‰ with the lowest values in summer and maximum δ56Fe ratios in late autumn or spring, indicating an influx of more oxidized, less Fe(II) rich groundwater during those seasons. Local differences in δ56Fe ratios between the headwater streams, seemed to be driven by the different soil redox status of the catchments. The streams with the lowest δ56Fe ratios during summer are characterized by a small share (4.4 ± 6.6%) of wetlands, indicating discharge of reduced groundwater from mainly anoxic, moist, organic-rich mineral soils during drought. Relatively high total organic carbon (TOC) concentrations (2.4 ± 1.1 mM) and low pH (5.2 ± 0.8) may have restricted efficient Fe(II) oxidation in streamwater especially during the late autumn survey. Our results from hemiboreal headwater streams reveal the importance of climatic, pedogenic, and land cover-derived controls on the provenance of stream Fe loads that is likely broadly applicable to similar streams elsewhere.
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| 40. |
- Coombes, Brandon J, et al.
(författare)
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Association of Attention-Deficit/Hyperactivity Disorder and Depression Polygenic Scores with Lithium Response: A Consortium for Lithium Genetics Study.
- 2021
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Ingår i: Complex psychiatry. - : S. Karger AG. - 2673-3005 .- 2673-298X. ; 7:3-4, s. 80-89
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Tidskriftsartikel (refereegranskat)abstract
- Response to lithium varies widely between individuals with bipolar disorder (BD). Polygenic risk scores (PRSs) can uncover pharmacogenomics effects and may help predict drug response. Patients (N = 2,510) with BD were assessed for long-term lithium response in the Consortium on Lithium Genetics using the Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder score. PRSs for attention-deficit/hyperactivity disorder (ADHD), major depressive disorder (MDD), and schizophrenia (SCZ) were computed using lassosum and in a model including all three PRSs and other covariates, and the PRS of ADHD (β = -0.14; 95% confidence interval [CI]: -0.24 to -0.03; p value = 0.010) and MDD (β = -0.16; 95% CI: -0.27 to -0.04; p value = 0.005) predicted worse quantitative lithium response. A higher SCZ PRS was associated with higher rates of medication nonadherence (OR = 1.61; 95% CI: 1.34-1.93; p value = 2e-7). This study indicates that genetic risk for ADHD and depression may influence lithium treatment response. Interestingly, a higher SCZ PRS was associated with poor adherence, which can negatively impact treatment response. Incorporating genetic risk of ADHD, depression, and SCZ in combination with clinical risk may lead to better clinical care for patients with BD.
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| 41. |
- Deleu, T., et al.
(författare)
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Bayesian Structure Learning with Generative Flow Networks
- 2022
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Ingår i: Proceedings of the 38th Conference on Uncertainty in Artificial Intelligence, UAI 2022. - : Association For Uncertainty in Artificial Intelligence (AUAI). ; , s. 518-528
-
Konferensbidrag (refereegranskat)abstract
- In Bayesian structure learning, we are interested in inferring a distribution over the directed acyclic graph (DAG) structure of Bayesian networks, from data. Defining such a distribution is very challenging, due to the combinatorially large sample space, and approximations based on MCMC are often required. Recently, a novel class of probabilistic models, called Generative Flow Networks (GFlowNets), have been introduced as a general framework for generative modeling of discrete and composite objects, such as graphs. In this work, we propose to use a GFlowNet as an alternative to MCMC for approximating the posterior distribution over the structure of Bayesian networks, given a dataset of observations. Generating a sample DAG from this approximate distribution is viewed as a sequential decision problem, where the graph is constructed one edge at a time, based on learned transition probabilities. Through evaluation on both simulated and real data, we show that our approach, called DAG-GFlowNet, provides an accurate approximation of the posterior over DAGs, and it compares favorably against other methods based on MCMC or variational inference.
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| 42. |
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| 43. |
- Dierks, Philipp, et al.
(författare)
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Ground- And Excited-State Properties of Iron(II) Complexes Linked to Organic Chromophores
- 2020
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Ingår i: Inorganic Chemistry. - : American Chemical Society (ACS). - 0020-1669 .- 1520-510X. ; 59:20, s. 14746-14761
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Tidskriftsartikel (refereegranskat)abstract
- Two new bichromophoric complexes, [Fe(bim-ant)2]2+ and [Fe(bim-pyr)2]2+ ([H2-bim]2+ = 1,1′-(pyridine-2,6-diyl)bis(3-methyl-1H-imidazol-3-ium); ant = 9-anthracenyl; pyr = 1-pyrenyl), are investigated to explore the possibility of tuning the excited-state behavior in photoactive iron(II) complexes to design substitutes for noble-metal compounds. The ground-state properties of both complexes are characterized thoroughly by electrochemical methods and optical absorption spectroscopy, complemented by time-dependent density functional theory calculations. The excited states are investigated by static and time-resolved luminescence and femtosecond transient absorption spectroscopy. Both complexes exhibit room temperature luminescence, which originates from singlet states dominated by the chromophore (1Chrom). In the cationic pro-ligands and in the iron(II) complexes, the emission is shifted to red by up to 110 nm (5780 cm-1). This offers the possibility of tuning the organic chromophore emission by metal-ion coordination. The fluorescence lifetimes of the complexes are in the nanosecond range, while triplet metal-to-ligand charge-transfer (3MLCT) lifetimes are around 14 ps. An antenna effect as in ruthenium(II) polypyridine complexes connected to an organic chromophore is found in the form of an internal conversion within 3.4 ns from the 1Chrom to the 1MLCT states. Because no singlet oxygen forms from triplet oxygen in the presence of the iron(II) complexes and light, efficient intersystem crossing to the triplet state of the organic chromophore (3Chrom) is not promoted in the iron(II) complexes.
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| 44. |
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| 45. |
- Ebrahimi-Fakhari, Darius, et al.
(författare)
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Defining the clinical, molecular and imaging spectrum of adaptor protein complex 4-associated hereditary spastic paraplegia
- 2020
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Ingår i: Brain. - OXFORD ENGLAND : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 143:10, s. 2929-2944
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Tidskriftsartikel (refereegranskat)abstract
- Bi-allelic loss-of-function variants in genes that encode subunits of the adaptor protein complex 4 (AP-4) lead to prototypical yet poorly understood forms of childhood-onset and complex hereditary spastic paraplegia: SPG47 (AP4B1), SPG50 (AP4M1), SPG51 (AP4E1) and SPG52 (AP4S1). Here, we report a detailed cross-sectional analysis of clinical, imaging and molecular data of 156 patients from 101 families. Enrolled patients were of diverse ethnic backgrounds and covered a wide age range (1.0-49.3 years). While the mean age at symptom onset was 0.8 +/- 0.6 years [standard deviation (SD), range 0.2-5.0], the mean age at diagnosis was 10.2 +/- 8.5 years (SD, range 0.1-46.3). We define a set of core features: early-onset developmental delay with delayed motor milestones and significant speech delay (50% non-verbal); intellectual disability in the moderate to severe range; mild hypotonia in infancy followed by spastic diplegia (mean age: 8.4 +/- 5.1 years, SD) and later tetraplegia (mean age: 16.1 +/- 9.8 years, SD); postnatal microcephaly (83%); foot deformities (69%); and epilepsy (66%) that is intractable in a subset. At last follow-up, 36% ambulated with assistance (mean age: 8.9 +/- 6.4 years, SD) and 54% were wheelchair-dependent (mean age: 13.4 +/- 9.8 years, SD). Episodes of stereotypic laughing, possibly consistent with a pseudobulbar affect, were found in 56% of patients. Key features on neuroimaging include a thin corpus callosum (90%), ventriculomegaly (65%) often with colpocephaly, and periventricular white-matter signal abnormalities (68%). Iron deposition and polymicrogyria were found in a subset of patients. AP4B1-associated SPG47 and AP4M1-associated SPG50 accounted for the majority of cases. About two-thirds of patients were born to consanguineous parents, and 82% carried homozygous variants. Over 70 unique variants were present, the majority of which are frameshift or nonsense mutations. To track disease progression across the age spectrum, we defined the relationship between disease severity as measured by several rating scales and disease duration. We found that the presence of epilepsy, which manifested before the age of 3 years in the majority of patients, was associated with worse motor outcomes. Exploring genotype-phenotype correlations, we found that disease severity and major phenotypes were equally distributed among the four subtypes, establishing that SPG47, SPG50, SPG51 and SPG52 share a common phenotype, an 'AP-4 deficiency syndrome'. By delineating the core clinical, imaging, and molecular features of AP-4-associated hereditary spastic paraplegia across the age spectrum our results will facilitate early diagnosis, enable counselling and anticipatory guidance of affected families and help define endpoints for future interventional trials.
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| 46. |
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| 47. |
- Efkarpidis, Nikolaos, et al.
(författare)
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Proactive Scheduling of Mixed Energy Resources at Different Grid Levels
- 2024
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Ingår i: IEEE Transactions on Sustainable Energy. - : Institute of Electrical and Electronics Engineers Inc.. - 1949-3029 .- 1949-3037. ; 15, s. 952-
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Tidskriftsartikel (refereegranskat)abstract
- The optimal utilisation of distribution grids requires the proactive management of volatilities caused by mixed energy resources installed into different grid levels, such as buildings, energy communities (ECs) and substations. In this context, proactive control based on predictions for energy demand and generation is applied. The mitigation of conflicts between the stakeholders' objectives is the main challenge for the control of centralized and distributed energy resources. In this paper, a bi-level approach is proposed for the control of stationary battery energy storage systems (SBES) supporting the local distribution system operator (DSO) at the transformer level, as well as distributed energy resources (DERs) operated by end customers, i.e., EC-members. Model predictive control (MPC)- based and hybrid approaches merging rule- and MPC-based control schemes are evaluated. Simulation studies based on a typical European low voltage (LV) feeder topology yield the performance assessment in terms of technical and economic criteria. The results show an advantage of hybrid approaches with respect to the DSO's cost savings from peak shaving. From the EC's perspective, both hybrid and MPC-based schemes can achieve effective cost savings from proactive energy management.
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| 48. |
- Farnocchia, Davide, et al.
(författare)
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The Second International Asteroid Warning Network Timing Campaign: 2005 LW3
- 2023
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Ingår i: The Planetary Science Journal. - : Institute of Physics (IOP). - 2632-3338. ; 4:11
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Tidskriftsartikel (refereegranskat)abstract
- The Earth close approach of near-Earth asteroid 2005 LW3 on 2022 November 23 represented a good opportunity for a second observing campaign to test the timing accuracy of astrometric observation. With 82 participating stations, the International Asteroid Warning Network collected 1046 observations of 2005 LW3 around the time of the close approach. Compared to the previous timing campaign targeting 2019 XS, some individual observers were able to significantly improve the accuracy of their reported observation times. In particular, U.S. surveys achieved good timing performance. However, no broad, systematic improvement was achieved compared to the previous campaign, with an overall negative bias persisting among the different observers. The calibration of observing times and the mitigation of timing errors should be important future considerations for observers and orbit computers, respectively.
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| 49. |
- Gilligan, Melanie, 1979-
(författare)
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Treating the Abstract of Capital Concretely: Films Against Capitalism
- 2022
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Konstnärligt arbete (övrigt vetenskapligt/konstnärligt)abstract
- This practice-based PhD, Treating the Abstract of Capital Concretely: Films Against Capitalism, looks at how film can oppose the prevailing ideasof capitalist systems.The research asks: What qualities do films have that can be used as strategies against capitalism and what knowledge do these films produce? In an understanding that capitalism projects concepts onto the world, and that mainstream film can frame people’s lives through a reductive capitalist understanding, the research suggests that more politically powerful moving images need to be the focus to create societal change.Treating the Abstract of Capitalism Concretely: Films Against Capitalism, includes six aesthetic, political and conceptual video works, and an accompanying written handbook, that together consider capital as the relation between abstract laws of accumulation and concrete lived situations.Making moving image works against the capitalist system necessarily involves knowledge about capitalism, however, the research charts how the knowledge most central in filmmaking is often associative, affective and combines knowledge with practice. A variety of methodological approaches are pursued through practical and theoretical research about how films can oppose capitalism. This investigation is explored materially, through video projects that interrogate capitalist abstraction from inside social processes,in realities that people live. The video works present a critique of racial and patriarchal capitalism, while the written component presents a contextual discussion about films against capitalism.The PhD submission consists of six video projects: The Common Sense, The Bay Area Protests, Parts-wholes 2, Crowds, Home Together, and Health as Individual vs. Health as Social and a PDF handbook, Treating the Abstractof Capital Concretely: Films Against Capitalism. The written text puts forth theoretical and practical proposals for films against capitalism as well as a 3 script. Connections are here made between different understandings of abstraction, while bringing in ideas from political theory, as well as demonstrating allegory as a technique against capitalism in film.The video works and handbook are accessed via: https://www.films-against-capitalism.com
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| 50. |
- Gispert, Suzana, et al.
(författare)
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The modulation of Amyotrophic Lateral Sclerosis risk by Ataxin-2 intermediate polyglutamine expansions is a specific effect
- 2012
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Ingår i: Neurobiology of Disease. - : Elsevier. - 0969-9961 .- 1095-953X. ; 45:1, s. 356-361
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Tidskriftsartikel (refereegranskat)abstract
- Full expansions of the polyglutamine domain (polyQ >= 34) within the polysome-associated protein ataxin-2 (ATXN2) are the cause of a multi-system neurodegenerative disorder, which usually presents as a Spino-Cerebellar Ataxia and is therefore known as SCA2, but may rarely manifest as Levodopa-responsive Parkinson syndrome or as motor neuron disease. Intermediate expansions (27 <= polyQ <= 33) were reported to modify the risk of Amyotrophic Lateral Sclerosis (ALS). We have now tested the reproducibility and the specificity of this observation. In 559 independent ALS patients from Central Europe, the association of ATXN2 expansions (30 <= polyQ <= 35) with ALS was highly significant. The study of 1490 patients with Parkinson's disease (PD) showed an enrichment of ATXN2 alleles 27/28 in a subgroup with familial cases, but the overall risk of sporadic PD was unchanged. No association was found between polyQ expansions in Ataxin-3 (ATXN3) and ALS risk. These data indicate a specific interaction between ATXN2 expansions and the causes of ALS, possibly through altered RNA-processing as a common pathogenic factor. (C) 2011 Elsevier Inc. All rights reserved.
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