| 51. |
- Hedenborg, Mathias, et al.
(författare)
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A Framework for Memory Efficient Context-Sensitive Program Analysis
- 2022
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Ingår i: Theory of Computing Systems. - : Springer. - 1432-4350 .- 1433-0490. ; 66, s. 911-956
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Tidskriftsartikel (refereegranskat)abstract
- Static program analysis is in general more precise if it is sensitive to execution contexts (execution paths). But then it is also more expensive in terms of memory consumption. For languages with conditions and iterations, the number of contexts grows exponentially with the program size. This problem is not just a theoretical issue. Several papers evaluating inter-procedural context-sensitive data-flow analysis report severe memory problems, and the path-explosion problem is a major issue in program verification and model checking.In this paper we propose χ-terms as a means to capture and manipulate context-sensitive program information in a data-flow analysis. χ-terms are implemented as directed acyclic graphs without any redundant subgraphs. We introduce the k-approximation and the l-loop-approximation that limit the size of the context-sensitive information at the cost of analysis precision. We prove that every context-insensitive data-flow analysis has a corresponding k, l-approximated context-sensitive analysis, and that these analyses are sound and guaranteed to reach a fixed point.We also present detailed algorithms outlining a compact, redundancy-free, and DAG-based implementation of χ-terms.
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| 52. |
- Hedenborg, Mathias, et al.
(författare)
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Approximating Context-Sensitive Program Information
- 2015
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Ingår i: Proceedings Kolloquium Programmiersprachen (KPS 2015).
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Static program analysis is in general more precise if it is sensitive to execution contexts (execution paths). In this paper we propose χ-terms as a mean to capture and manipulate context-sensitive program information in a data-flow analysis. We introduce finite k-approximation and loop approximation that limit the size of the context-sensitive information. These approximated χ-terms form a lattice with a finite depth, thus guaranteeing every data-flow analysis to reach a fixed point.
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| 53. |
- Hedenborg, Mathias, et al.
(författare)
-
Memory efficient context-sensitive program analysis
- 2021
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Ingår i: Journal of Systems and Software. - : Elsevier. - 0164-1212 .- 1873-1228. ; 177
-
Tidskriftsartikel (refereegranskat)abstract
- Static program analysis is in general more precise if it is sensitive to execution contexts (execution paths). But then it is also more expensive in terms of memory consumption. For languages with conditions and iterations, the number of contexts grows exponentially with the program size. This problem is not just a theoretical issue. Several papers evaluating inter-procedural context-sensitive data-flow analysis report severe memory problems, and the path-explosion problem is a major issue in program verification and model checking.In this paper we propose χ-terms as a means to capture and manipulate context-sensitive program information in a data-flow analysis. χ-terms are implemented as directed acyclic graphs without any redundant subgraphs.To show the efficiency of our approach we run experiments comparing the memory usage of χ-terms with four alternative data structures. Our experiments show that χ-terms clearly outperform all the alternatives in terms of memory efficiency.
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| 54. |
- Hikmet Noraddin, Feria, 1989-, et al.
(författare)
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A high-resolution spatial map of cilia-associated proteins based on characterization of the human fallopian tube-specific proteome
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Molecular changes in the fallopian tubes (FT) play a crucial role in the development of cancer and reproductive disorders. Here, we aimed to map key FT proteins on the single-cell level utilizing an integrated transcriptomics and proteomics approach. Based on RNA-seq, 310 genes were identified as elevated in FT, out of which a majority were associated with motile cilia function. An in-depth spatial characterization was performed for 133 of these genes in FT and other human tissues with motile cilia, localizing the proteins to different subcellular structures of ciliated cells. The specificity for ciliated cells was validated with single-cell RNA-seq and spatial mass-spectrometry data. Our approach enabled us to identify 44 novel cilia-related proteins lacking previous evidence on the protein level, as well as several other proteins not described in the context of cilia biology. The high-resolution spatial map aids in further disentangling pathways involved in infertility and diseases linked to cilia-specific functions.
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| 55. |
- Hilland, Eva, et al.
(författare)
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Aberrant default mode connectivity in adolescents with early-onset psychosis : A resting state fMRI study
- 2022
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Ingår i: NeuroImage. - : Elsevier. - 2213-1582. ; 33
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Tidskriftsartikel (refereegranskat)abstract
- Abnormal default mode network (DMN) connectivity has been found in schizophrenia and other psychotic disorders. However, there are limited studies on early onset psychosis (EOP), and their results show lack of agreement. Here, we investigated within-network DMN connectivity in EOP compared to healthy controls (HC), and its relationship to clinical characteristics. A sample of 68 adolescent patients with EOP (mean age 16.53 +/- 1.12 [SD] years, females 66%) and 95 HC (mean age 16.24 +/- 1.50 [SD], females 60%) from two Scandinavian cohorts underwent resting state functional magnetic resonance imaging (rsfMRI). A group independent component analysis (ICA) was performed to identify the DMN across all participants. Dual regression was used to estimate spatial maps reflecting each participant's DMN network, which were compared between EOP and HC using voxel-wise general linear models and permutation-based analyses. Subgroup analyses were performed within the patient group, to explore associations between diagnostic subcategories and current use of psychotropic medication in relation to connectivity strength. The analysis revealed significantly reduced DMN connectivity in EOP compared to HC in the posterior cingulate cortex, precuneus, fusiform cortex, putamen, pallidum, amygdala, and insula. The subgroup analysis in the EOP group showed strongest deviations for affective psychosis, followed by other psychotic disorders and schizophrenia. There was no association between DMN connectivity strength and the current use of psychotropic medication. In conclusion, the findings demonstrate weaker DMN connectivity in adolescent patients with EOP compared to healthy peers, and differential effects across diagnostic subcategories, which may inform our understanding of underlying disease mechanisms in EOP.
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| 56. |
- Hjelm, Barbara, et al.
(författare)
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Generation of monospecific antibodies based on affinity capture of polyclonal antibodies
- 2011
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Ingår i: Protein Science. - : Wiley. - 0961-8368 .- 1469-896X. ; 20:11, s. 1824-1835
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Tidskriftsartikel (refereegranskat)abstract
- A method is described to generate and validate antibodies based on mapping the linear epitopes of a polyclonal antibody followed by sequential epitope-specific capture using synthetic peptides. Polyclonal antibodies directed towards four proteins RBM3, SATB2, ANLN, and CNDP1, potentially involved in human cancers, were selected and antibodies to several non-overlapping epitopes were generated and subsequently validated by Western blot, immunohistochemistry, and immunofluorescence. For all four proteins, a dramatic difference in functionality could be observed for these monospecific antibodies directed to the different epitopes. In each case, at least one antibody was obtained with full functionality across all applications, while other epitope-specific fractions showed no or little functionality. These results present a path forward to use the mapped binding sites of polyclonal antibodies to generate epitope-specific antibodies, providing an attractive approach for large-scale efforts to characterize the human proteome by antibodies.
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| 57. |
- Häggmark-Månberg, Anna, et al.
(författare)
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Autoantibody targets in vaccine-associated narcolepsy
- 2016
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Ingår i: Autoimmunity. - : Taylor & Francis. - 0891-6934 .- 1607-842X. ; 49:6, s. 421-433
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Tidskriftsartikel (refereegranskat)abstract
- Narcolepsy is a chronic sleep disorder with a yet unknown cause, but the specific loss of hypocretin-producing neurons together with a strong human leukocyte antigen (HLA) association has led to the hypothesis that autoimmune mechanisms might be involved. Here, we describe an extensive effort to profile autoimmunity repertoires in serum with the aim to find disease-related autoantigens. Initially, 57 serum samples from vaccine-associated and sporadic narcolepsy patients and controls were screened for IgG reactivity towards 10 846 fragments of human proteins using planar microarrays. The discovered differential reactivities were verified on suspension bead arrays in the same sample collection followed by further investigation of 14 antigens in 176 independent samples, including 57 narcolepsy patients. Among these 14 antigens, methyltransferase-like 22 (METTL22) and 5'-nucleotidase cytosolic IA (NT5C1A) were recognized at a higher frequency in narcolepsy patients of both sample sets. Upon sequence analysis of the 14 proteins, polymerase family, member 3 (PARP3), acyl-CoA-binding domain containing 7 (ARID4B), glutaminase 2 (GLS2) and cyclin-dependent kinase-like 1 (CDKL1) were found to contain amino acid sequences with homology to proteins found in the H1N1 vaccine. These findings could become useful elements of further clinical assays that aim towards a better phenotypic understanding of narcolepsy and its triggers.
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| 58. |
- Issa, Sally, et al.
(författare)
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Cohesive zone modeling of crack propagation influenced by martensitic phase transformation
- 2018
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Ingår i: Materials Science and Engineering A. - : Elsevier BV. - 0921-5093. ; 712, s. 564-573
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Tidskriftsartikel (refereegranskat)abstract
- A numerical model that can predict the influence of martensitic phase transformation on crack propagation is proposed. The model is comprised of a large strain plasticity model that accounts for martensitic phase transformation and a cohesive zone model to simulate the interface behavior. Different dependencies of the traction-separation law on the local volume fraction of martensite are investigated. Furthermore, as martensitic phase transformation is strongly temperature dependent, different isothermal settings are considered. It is, for example, verified that at lower temperatures, martensitic phase transformation retards crack propagation to a greater extent. It is also shown that the retarding effect depends on how the martensite dependent cohesive zone model is formulated.
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| 59. |
- Jakobsen, Lis, et al.
(författare)
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Novel asymmetrically localizing components of human centrosomes identified by complementary proteomics methods
- 2011
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Ingår i: EMBO Journal. - : Wiley. - 0261-4189 .- 1460-2075. ; 30:8, s. 1520-1535
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Tidskriftsartikel (refereegranskat)abstract
- Centrosomes in animal cells are dynamic organelles with a proteinaceous matrix of pericentriolar material assembled around a pair of centrioles. They organize the microtubule cytoskeleton and the mitotic spindle apparatus. Mature centrioles are essential for biogenesis of primary cilia that mediate key signalling events. Despite recent advances, the molecular basis for the plethora of processes coordinated by centrosomes is not fully understood. We have combined protein identification and localization, using PCP-SILAC mass spectrometry, BAC transgeneOmics, and antibodies to define the constituents of human centrosomes. From a background of non-specific proteins, we distinguished 126 known and 40 candidate centrosomal proteins, of which 22 were confirmed as novel components. An antibody screen covering 4000 genes revealed an additional 113 candidates. We illustrate the power of our methods by identifying a novel set of five proteins preferentially associated with mother or daughter centrioles, comprising genes implicated in cell polarity. Pulsed labelling demonstrates a remarkable variation in the stability of centrosomal protein complexes. These spatiotemporal proteomics data provide leads to the further functional characterization of centrosomal proteins.
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| 60. |
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