| 1. |
- Huyghe, Jeroen R., et al.
(författare)
-
Discovery of common and rare genetic risk variants for colorectal cancer
- 2019
-
Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:1, s. 76-
-
Tidskriftsartikel (refereegranskat)abstract
- To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 x 10(-8), bringing the number of known independent signals for CRC to similar to 100. New signals implicate lower-frequency variants, Kruppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development.
|
|
| 2. |
|
|
| 3. |
- Einspieler, C, et al.
(författare)
-
Cerebral Palsy: Early Markers of Clinical Phenotype and Functional Outcome
- 2019
-
Ingår i: Journal of clinical medicine. - : MDPI AG. - 2077-0383. ; 8:10
-
Tidskriftsartikel (refereegranskat)abstract
- The Prechtl General Movement Assessment (GMA) has become a cornerstone assessment in early identification of cerebral palsy (CP), particularly during the fidgety movement period at 3–5 months of age. Additionally, assessment of motor repertoire, such as antigravity movements and postural patterns, which form the Motor Optimality Score (MOS), may provide insight into an infant’s later motor function. This study aimed to identify early specific markers for ambulation, gross motor function (using the Gross Motor Function Classification System, GMFCS), topography (unilateral, bilateral), and type (spastic, dyskinetic, ataxic, and hypotonic) of CP in a large worldwide cohort of 468 infants. We found that 95% of children with CP did not have fidgety movements, with 100% having non-optimal MOS. GMFCS level was strongly correlated to MOS. An MOS > 14 was most likely associated with GMFCS outcomes I or II, whereas GMFCS outcomes IV or V were hardly ever associated with an MOS > 8. A number of different movement patterns were associated with more severe functional impairment (GMFCS III–V), including atypical arching and persistent cramped-synchronized movements. Asymmetrical segmental movements were strongly associated with unilateral CP. Circular arm movements were associated with dyskinetic CP. This study demonstrated that use of the MOS contributes to understanding later CP prognosis, including early markers for type and severity.
|
|
| 4. |
- Peyton, L, et al.
(författare)
-
Lipopolysaccharide Increases Cortical Kynurenic Acid and Deficits in Reference Memory in Mice
- 2019
-
Ingår i: International journal of tryptophan research : IJTR. - : SAGE Publications. - 1178-6469. ; 12, s. 1178646919891169-
-
Tidskriftsartikel (refereegranskat)abstract
- Kynurenic acid (KYNA), a glial-derived metabolite of tryptophan metabolism, is an antagonist of the alpha 7 nicotinic acetylcholine receptor and the glycine-binding site of N-methyl-d-aspartate (NMDA) receptors. Kynurenic acid levels are increased in both the brain and cerebrospinal fluid of several psychiatric disorders including bipolar disorder, schizophrenia, and Alzheimer disease. In addition, pro-inflammatory cytokines have been found to be elevated in the blood of schizophrenic patients suggesting inflammation may play a role in psychiatric illness. As both pro-inflammatory cytokines and KYNA can be elevated in the brain by peripheral lipopolysaccharide (LPS) injection, we therefore sought to characterize the role of neuroinflammation on learning and memory using a well-described dual-LPS injection model. Mice were injected with an initial injection (0.25 mg/kg LPS, 0.50 mg/kg, or saline) of LPS and then administrated a second injection 16 hours later. Our results indicate both 0.25 and 0.50 mg/kg dual-LPS treatment increased l-kynurenine and KYNA levels in the medial pre-frontal cortex (mPFC). Mice exhibited impaired acquisition of CS+ (conditioned stimulus) Pavlovian conditioning. Notably, mice showed impairment in reference memory while working memory was normal in an 8-arm maze. Taken together, our findings suggest that neuroinflammation induced by peripheral LPS administration contributes to cognitive dysfunction.
|
|
| 5. |
- Berg, Frenk van den, et al.
(författare)
-
Results of the European collaborative project "Product Uniformity Control" to improve the inline sensing of mechanical properties and microstructure of automotive steels
- 2018
-
Ingår i: e-Journal of Nondestructive Testing (eJNDT). - 1435-4934. ; 23:8
-
Tidskriftsartikel (refereegranskat)abstract
- A European consortium consisting of four major steel manufacturers and ten academic technology institutes has conducted a research and development project, called “Product Uniformity Control“ (PUC) in the period 2013 to 2017. This project aimed to develop and improve non-destructive (inline) measurement techniques to characterise the (uniformity of the) microstructure of steel strip products. In this project, a multitude of strip steel samples from various stages of production have been collected from the four participating steel manufacturers. The samples have been characterised in various ways, namely on their (1) non-destructive measurement parameters using different techniques suited for inline evaluation, (2) fundamental ultrasonic and electromagnetic properties (wave speed, ultrasonic attenuation, magnetisation loops, coercive field), (3) tensile properties (stress-strain curves) and (4) microstructure (by optical micrographs and EBSD images). The correlations between these different characterisations will be addressed. Besides the experimental characterisation, a strong accent has been on modelling activities: during the project, fundamental models have been developed to describe, starting from 2D and 3D microstructures, the ultrasonic and magnetic properties, which are next used as input to sensor models that predict the output of the inline measurement systems. This contribution presents the recent results of experimental work, which underlines the importance of associated modelling studies for the interpretation of the measurement data for the benefit of inline characterisation of the mechanical properties complementary to traditional destructive tensile testing.
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- Rivera, Sylvia L., et al.
(författare)
-
Chemically Induced Cell Wall Stapling in Bacteria
- 2021
-
Ingår i: Cell Chemical Biology. - : Cell Press. - 2451-9456 .- 2451-9448. ; 28:2, s. 213-e4
-
Tidskriftsartikel (refereegranskat)abstract
- Transpeptidation reinforces the structure of cell-wall peptidoglycan, an extracellular heteropolymer that protects bacteria from osmotic lysis. The clinical success of transpeptidase-inhibiting beta-lactam antibiotics illustrates the essentiality of these cross-linkages for cell-wall integrity, but the presence of multiple, seemingly redundant transpeptidases in many species makes it challenging to determine cross-link function. Here, we present a technique to link peptide strands by chemical rather than enzymatic reaction. We employ bio-compatible click chemistry to induce triazole formation between azido- and alkynyl-D-alanine residues that are metabolically installed in the peptidoglycan of Gram-positive or Gram-negative bacteria. Synthetic triazole cross-links can be visualized using azidocoumarin-D-alanine, an amino acid derivative that undergoes fluorescent enhancement upon reaction with terminal alkynes. Cell-wall stapling protects Escherichia coli from treatment with the broad-spectrum beta-lactams ampicillin and carbenicillin. Chemical control of cell-wall structure in live bacteria can provide functional insights that are orthogonal to those obtained by genetics.
|
|
| 9. |
- Van Den Berg, F. D., et al.
(författare)
-
Product uniformity control - A research collaboration of european steel industries to non-destructive evaluation of microstructure and mechanical properties
- 2018
-
Ingår i: Stud. Appl. Electromagn. Mech.. - : IOS Press. - 9781614998358 ; 43, s. 120-129
-
Konferensbidrag (refereegranskat)abstract
- In steel manufacturing, the conventional method to determine the mechanical properties and microstructure is by offline, destructive (lab-)characterisation of sample material that is typically taken from the head or the tail of the coil. Since coils can be up to 7 km long, the samples are not always representative for the main coil body. Also, the time delay (typically a few days) between the actual production and the availability of the characterisation results implies that these results cannot be exploited for real-time adaptation of the process settings. Information about the microstructure and material properties can also be obtained from electromagnetic (EM) and ultrasonic (US) parameters, which can be measured in real-time, non-destructively, and over the full length of the steel strip product. With the aim to improve the consistency in product quality by use of inline EM and US measurements, a European project called "Product Uniformity Control" (PUC) has been set up as a broad collaboration between 4 major European Steel Manufacturers and 10 Universities / Research institutes. Using both numerical simulations and experimental characterisations, we study the inline measured EM and US parameters in regard of the microstructural and mechanical properties. In this way, we aim to establish an improved understanding of their mutual relationships, and to apply this knowledge in existing and new nondestructive evaluation techniques. In this paper, the concerted approach of modelling and experimental validation will be addressed, and results of this work will be shown in combination with inline measured data.
|
|
| 10. |
- Vytiniotis, Dimitrios, et al.
(författare)
-
HALO: Haskell to logic through denotational semantics
- 2013
-
Ingår i: Conference Record of the Annual ACM Symposium on Principles of Programming Languages. - New York, NY, USA : ACM. - 0730-8566. - 9781450318327 ; , s. 431-442
-
Konferensbidrag (refereegranskat)abstract
- Even well-typed programs can go wrong in modern functional languages, by encountering a pattern-match failure, or simply returning the wrong answer. An increasingly-popular response is to allow programmers to write contracts that express semantic properties, such as crash-freedom or some useful post-condition. We study the static verification of such contracts. Our main contribution is a novel translation to first-order logic of both Haskell programs, and contracts written in Haskell, all justified by denotational semantics. This translation enables us to prove that functions satisfy their contracts using an off-the-shelf first-order logic theorem prover.
|
|
