| 1. |
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| 2. |
- Henstrom, M., et al.
(författare)
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Functional variants in the sucrase-isomaltase gene associate with increased risk of irritable bowel syndrome
- 2018
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Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 67:2, s. 263-270
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Tidskriftsartikel (refereegranskat)abstract
- Objective IBS is a common gut disorder of uncertain pathogenesis. Among other factors, genetics and certain foods are proposed to contribute. Congenital sucraseisomaltase deficiency (CSID) is a rare genetic form of disaccharide malabsorption characterised by diarrhoea, abdominal pain and bloating, which are features common to IBS. We tested sucrase-isomaltase (SI) gene variants for their potential relevance in IBS. Design We sequenced SI exons in seven familial cases, and screened four CSID mutations (p.Val557Gly, p. Gly1073Asp, p.Arg1124Ter and p.Phe1745Cys) and a common SI coding polymorphism (p.Val15Phe) in a multicentre cohort of 1887 cases and controls. We studied the effect of the 15Val to 15Phe substitution on SI function in vitro. We analysed p.Val15Phe genotype in relation to IBS status, stool frequency and faecal microbiota composition in 250 individuals from the general population. Results CSID mutations were more common in patients than asymptomatic controls (p=0.074; OR=1.84) and Exome Aggregation Consortium reference sequenced individuals (p=0.020; OR=1.57). 15Phe was detected in 6/7 sequenced familial cases, and increased IBS risk in case-control and population-based cohorts, with best evidence for diarrhoea phenotypes (combined p=0.00012; OR=1.36). In the population-based sample, 15Phe allele dosage correlated with stool frequency (p=0.026) and Parabacteroides faecal microbiota abundance (p=0.0024). The SI protein with 15Phe exhibited 35% reduced enzymatic activity in vitro compared with 15Val (p<0.05). Conclusions SI gene variants coding for disaccharidases with defective or reduced enzymatic activity predispose to IBS. This may help the identification of individuals at risk, and contribute to personalising treatment options in a subset of patients.
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| 3. |
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| 4. |
- Magnusson, Gunilla, 1968, et al.
(författare)
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Evaluation of screening procedures for congenital cataracts.
- 2003
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Ingår i: Acta paediatrica (Oslo, Norway : 1992). - : Wiley. - 0803-5253 .- 1651-2227. ; 92:12, s. 1468-73
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To evaluate the efficacy of two different Swedish screening procedures for early detection of congenital cataracts in comparison with no screening. METHODS: Children born between January 1992 and December 1998 in Swedish regions with an established eye-screening routine procedure, diagnosed with congenital cataract, and operated on before 1 y of age, were included in a retrospective study. Age at referral and age at time of the operation were compared between regions using different screening procedures: screening in the maternity wards (Region 1), at the well-baby clinics (Region 2) and one region without any screening (Region 3). RESULTS: Seventy-two children were included in the study. Concerning early diagnosis and surgery, Region 1 differed significantly from Regions 2 and 3, which were more similar and were combined for further analysis. The difference in detected cases was greatest at 21 d of age (55% vs 18%; p < 0.001), but persisted even at 100 d of age (78% vs 64%; p < 0.02). Region 1 screening resulted in more and earlier cases detected than the other two regions (22 vs 15 per 100,000 births). In 72% of all cases, surgery was performed in response to referrals from either the maternity wards (36%), or the well-baby clinics (36%). However, half of the cases from the well-baby clinics were detected too late, i.e. at > 100 d. CONCLUSION: Eye screening in the maternity ward is preferable to well-baby clinic screening and to no screening at all, since it leads to early detection. Screening should also be performed routinely at well-baby clinics within the period when successful treatment is possible.
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| 5. |
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| 6. |
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| 7. |
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| 8. |
- Andreasson, Björn Pererik, 1979-, et al.
(författare)
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Detecting oxygen vacancies in SrTiO3 by 3d transition-metal tracer ions
- 2009
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Ingår i: Physical Review B. Condensed Matter and Materials Physics. - College Park, MD : American Physical Society. - 1098-0121 .- 1550-235X. ; 80:21, s. Article number: 212103-
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Tidskriftsartikel (refereegranskat)abstract
- X-ray absorption experiments on 3d transition-metal tracer ions in SrTiO3 are presented. The absorption spectra of the tracer-ion changed upon reduction in the SrTiO3. This change is due to an oxygen vacancy created at the tracer-ion site. This finding is supported by density-functional theory calculations, which prove that the oxygen vacancies preferentially are created at the tracer-ion sites. Using the chemical sensitivity of x-ray absorption spectroscopy, tracer ions can be used to detect oxygen vacancies in SrTiO3 and possibly in other oxide systems. © 2009 The American Physical Society.
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| 9. |
- Andreasson, Björn Pererik, 1979-, et al.
(författare)
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Origin of oxygen vacancies in resistive switching memory devices
- 2009
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Ingår i: Journal of Physics, Conference Series. - Bristol : Institute of Physics Publishing (IOPP). - 1742-6588 .- 1742-6596. ; 190, s. Article number: 012074-
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Tidskriftsartikel (refereegranskat)abstract
- The resistive switching state in Cr-doped SrTiO3 was induced by applying an electric field. This was done in ambient air and in an atmosphere of H2/Ar. The distribution of the thereby introduced oxygen vacancies was studied by spatially resolved X-ray fluorescence images. It was concluded that the oxygen vacancies were introduced in the interface between the SrTiO3 and the positively biased electrode. © 2009 IOP Publishing Ltd.
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| 10. |
- Andreasson, Björn Pererik, 1979-, et al.
(författare)
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Resistive switching in Cr-doped SrTiO3 : An X-ray absorption spectroscopy study
- 2007
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Ingår i: Materials Science & Engineering. - Amsterdam : Elsevier. - 0921-5107 .- 1873-4944. ; 144:1-3, s. 60-63
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Tidskriftsartikel (refereegranskat)abstract
- X-ray absorption spectroscopy was used to study the microscopic origin of conductance and resistive switching in chromium-doped strontium titanate (Cr:SrTiO3). Differences in the X-ray absorption near edge spectroscopy (XANES) at the Cr K-edge indicate that the valence of Cr changes from 3+ to 4+ underneath the anode of our sample device after the application of an electric field. Spatially resolved X-ray fluorescence microscopy (μ-XRF) maps show that the Cr4+ region retracts from the anode-Cr:SrTiO3 interface after a conducting state has been achieved. This interface region is studied with extended X-ray absorption fine structure (EXAFS) and the results are compared with structural parameters obtained from density functional theory (DFT) calculations. They confirm that oxygen vacancies which are localized at the octahedron with a Cr at its center are introduced at the interface. It is proposed that the switching state is not due to a valence change of chromium but caused by changes of oxygen vacancies at the interface. © 2007 Elsevier B.V. All rights reserved.
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| 11. |
- Andreasson, Björn Pererik, 1979-, et al.
(författare)
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Spatial distribution of oxygen vacancies in Cr-doped SrTiO3 during an electric-field-driven insulator-to-metal transition
- 2009
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Ingår i: Applied Physics Letters. - College Park, MD : American Institute of Physics (AIP). - 0003-6951 .- 1077-3118. ; 94:1, s. Article number: 013513-
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Tidskriftsartikel (refereegranskat)abstract
- Spatially resolved x-ray fluorescence maps are presented that show the introduction and the evolution of oxygen vacancies in chromium-doped strontium titanate during an electric-field-driven insulator-to-metal transition. The vacancies are introduced at the anode and diffuse through the crystal toward the cathode. The spatial distribution of vacancies is explained by a model describing the electrical breakdown as a percolation process. Strong differences in the vacancy distribution were found when the transition took place in air and in a hydrogen-enriched atmosphere. In air, the vacancies disappeared from the surface, whereas in the reducing hydrogen atmosphere, they remained at the surface. © 2009 American Institute of Physics.
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| 12. |
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| 13. |
- Andreasson, Joakim, 1973, et al.
(författare)
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A simplicity-guided approach toward molecular set-reset memories
- 2010
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Ingår i: New Journal of Chemistry. - : Royal Society of Chemistry (RSC). - 1369-9261 .- 1144-0546. ; 34:12, s. 2701-2703
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Tidskriftsartikel (refereegranskat)abstract
- Photochromic switches fulfill the general molecular design criteria for the surprisingly straightforward small-scale integration of seemingly complex set-reset latches. The implications of this re-interpretation are discussed with the example of a dithienylethene photochrome. The concept is shown to be valid for a multitude of well-introduced bistable switches with clearly differentiated output signals, e.g., optical signals for the presented example.
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| 14. |
- Andreasson, Joakim, 1973, et al.
(författare)
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All-Photonic Multifunctional Molecular Logic Device
- 2011
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 1520-5126 .- 0002-7863. ; 133:30, s. 11641-11648
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Tidskriftsartikel (refereegranskat)abstract
- Photochromes are photoswitchable, bistable chromophores which, like transistors, can implement binary logic operations. When several photochromes are combined in one molecule, interactions between them such as energy and electron transfer allow design of simple Boolean logic gates and more complex logic devices with all-photonic inputs and outputs. Selective isomerization of individual photochromes can be achieved using light of different wavelengths, and logic outputs can employ absorption and emission properties at different wavelengths, thus allowing a single molecular species to perform several different functions, even simultaneously. Here, we report a molecule consisting of three linked photochromes that can be configured as AND, XOR, INH, half-adder, half-subtractor, multiplexer, demultiplexer, encoder, decoder, keypad lock, and logically reversible transfer gate logic devices, all with a common initial state. The system demonstrates the advantages of light-responsive molecules as multifunctional, reconfigurable nanoscale logic devices that represent an approach to true molecular information processing units.
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| 15. |
- Andreasson, Joakim, 1973, et al.
(författare)
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Molecules for security measures: From keypad locks to advanced communication protocols
- 2018
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Ingår i: Chemical Society Reviews. - : Royal Society of Chemistry (RSC). - 1460-4744 .- 0306-0012. ; 47:7, s. 2266-2279
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Forskningsöversikt (refereegranskat)abstract
- The idea of using molecules in the context of information security has sparked the interest of researchers from many scientific disciplines. This is clearly manifested in the diversity of the molecular platforms and the analytical techniques used for this purpose, some of which we highlight in this Tutorial Review. Moreover, those molecular systems can be used to emulate a broad spectrum of security measures. For a long time, molecular keypad locks enjoyed a clear preference and the review starts off with a description of how these devices developed. In the last few years, however, the field has evolved into something larger. Examples include more complex authentication protocols (multi-factor authentication and one-time passwords), the recognition of erroneous procedures in data transmission (parity devices), as well as steganographic and cryptographic protection.
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| 16. |
- Andreasson, Joakim, 1973, et al.
(författare)
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Molecules with a sense of logic: a progress report
- 2015
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Ingår i: Chemical Society Reviews. - 1460-4744 .- 0306-0012. ; 44:5, s. 1053-1069
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Forskningsöversikt (refereegranskat)abstract
- In this tutorial review, the most recent developments in the field of molecular logic and information processing are discussed. Special emphasis is given to the report of progress in the concatenation of molecular logic devices and switches, the design of memory systems working according to the principles of sequential logic, the mimicking of transistors, and the research on photochromic platforms with an unprecedented degree of functional integration. Furthermore, a series of achievements that add up to the conceptual diversity of molecular logic is introduced, such as the realization of highly complex and logically reversible Toffoli and Fredkin gates by the action of DNAzymes or the use of a multifluorophoric platform as a viable approach towards keypad lock functions.
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| 17. |
- Andreasson, Joakim, 1973, et al.
(författare)
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Smart molecules at work-mimicking advanced logic operations
- 2010
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Ingår i: Chemical Society Reviews. - : Royal Society of Chemistry (RSC). - 1460-4744 .- 0306-0012. ; 39:1, s. 174-188
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Tidskriftsartikel (refereegranskat)abstract
- Molecular logic is an interdisciplinary research field, which has captured worldwide interest. This tutorial review gives a brief introduction into molecular logic and Boolean algebra. This serves as the basis for a discussion of the state-of-the-art and future challenges in the field. Representative examples from the most recent literature including adders/subtractors, multiplexers/demultiplexers, encoders/decoders, and sequential logic devices (keypad locks) are highlighted. Other horizons, such as the utility of molecular logic in bio-related applications, are discussed as well.
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| 18. |
- Andreasson, Joakim, 1973, et al.
(författare)
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Storage and Processing of Information Using Molecules: The All-Photonic Approach with Simple and Multi-Photochromic Switches
- 2013
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Ingår i: Israel Journal of Chemistry. - : Wiley. - 0021-2148. ; 53:5, s. 236-246
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Forskningsöversikt (refereegranskat)abstract
- The use of photochromes for the implementation of molecular logic operations is a very promising approach toward molecular computing. This statement is based on a) the possibility of operating such molecular devices exclusively with photonic signals and b) spatiotemporally and remotely controlled switching, which is characteristic for photochromes. Herein, a brief overview of the application of simple photochromes and multi-photochromic conjugates for the small-scale functional integration of complicated logic circuits is given. This complements and extends efforts to design molecular photochromic memories for data storage described by many research groups worldwide.
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| 19. |
- Andréasson, Måns, 1994-, et al.
(författare)
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Exploring the dispersion and electrostatic components in arene-arene interactions between ligands and G4 DNA to develop G4-ligands
- 2024
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 67:3, s. 2202-2219
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Tidskriftsartikel (refereegranskat)abstract
- G-Quadruplex (G4) DNA structures are important regulatory elements in central biological processes. Small molecules that selectively bind and stabilize G4 structures have therapeutic potential, and there are currently >1000 known G4 ligands. Despite this, only two G4 ligands ever made it to clinical trials. In this work, we synthesized several heterocyclic G4 ligands and studied their interactions with G4s (e.g., G4s from the c-MYC, c-KIT, and BCL-2 promoters) using biochemical assays. We further studied the effect of selected compounds on cell viability, the effect on the number of G4s in cells, and their pharmacokinetic properties. This identified potent G4 ligands with suitable properties and further revealed that the dispersion component in arene-arene interactions in combination with electron-deficient electrostatics is central for the ligand to bind with the G4 efficiently. The presented design strategy can be applied in the further development of G4-ligands with suitable properties to explore G4s as therapeutic targets.
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| 20. |
- Andreasson, M, et al.
(författare)
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MCEE Mutations in an Adult Patient with Parkinson's Disease, Dementia, Stroke and Elevated Levels of Methylmalonic Acid
- 2019
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Ingår i: International journal of molecular sciences. - : MDPI AG. - 1422-0067. ; 20:11
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Methylmalonic aciduria (MMA-uria) is seen in several inborn errors of metabolism (IEM) affecting intracellular cobalamin pathways. Methylmalonyl-CoA epimerase (MCE) is an enzyme involved in the mitochondrial cobalamin-dependent pathway generating succinyl-CoA. Homozygous mutations in the corresponding MCEE gene have been shown in children to cause MCE deficiency with isolated MMA-uria and a variable clinical phenotype. We describe a 78-year-old man with Parkinson’s disease, dementia and stroke in whom elevated serum levels of methylmalonic acid had been evident for many years. Metabolic work-up revealed intermittent MMA-uria and increased plasma levels of propionyl-carnitine not responsive to treatment with high-dose hydroxycobalamin. Whole genome sequencing was performed, with data analysis targeted towards genes known to cause IEM. Compound heterozygous mutations were identified in the MCEE gene, c.139C>T (p.Arg47X) and c.419delA (p.Lys140fs), of which the latter is novel. To our knowledge, this is the first report of an adult patient with MCEE mutations and MMA-uria, thus adding novel data to the possible phenotypical spectrum of MCE deficiency. Although clinical implications are uncertain, it can be speculated whether intermittent hyperammonemia during episodes of metabolic stress could have precipitated the patient’s ongoing neurodegeneration attributed to Parkinson’s disease.
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| 21. |
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| 22. |
- Andreasson, U., et al.
(författare)
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An enzyme activity as a potential biomarker for Alzheimer's disease.
- 2010
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5279 .- 1552-5260. ; 6:4, s. 497-498
-
Konferensbidrag (refereegranskat)abstract
- Background: Six different N-terminal amyloid precursor protein (APP) fragments, with molecular weight ∼12 kDa, have previously been identified in human cerebrospinal fluid (CSF). In a pilot study, both the sum of their concentrations, measured by western blot, and the relative abundance pattern, measured by mass spectrometry, were different in Alzheimer's disease (AD) patients compared to healthy controls. To test if these differences were also reflected in protease activities that possibly give rise to the ∼12 kDa fragments an enzymatic assay was developed and the activity in CSF was investigated for its potential as a biomarker for AD. Methods: The substrate in the protease activity assay was a custom made fluorochrome/quencher labeled peptide that covers the cleavage sites in APP (APP118-APP127) corresponding to the C-termini of the six ∼12 kDa APP fragments. The activity was measured in CSF from 55 AD patients and 17 controls. Results: There was a significant increase in the protease activity in CSF from AD patients compared to the controls (p = 0.001). This is in line with previous results which indicate that the sum of the ∼12 kDa fragments are elevated in AD. Results from inhibition studies strongly suggests that the enzyme responsible for the cleavage of the substrate is an aspartic protease since a sub nM IC50 value was recorded for Pepstatin A while no inhibition was observed for the cysteine protease specific inhibitor E64 at concentrations up to100 nM. Conclusions: There exists an enzymatic activity in CSF capable of cleaving a peptide substrate that spans a portion, close to the N-terminal, of APP. In a pilot study the activity is increased in AD patients compared to controls suggesting that it can be used as a biomarker.
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| 23. |
- Barty, A., et al.
(författare)
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Self-terminating diffraction gates femtosecond X-ray nanocrystallography measurements
- 2012
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Ingår i: Nature Photonics. - 1749-4885 .- 1749-4893. ; 6:1, s. 35-40
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Tidskriftsartikel (refereegranskat)abstract
- X-ray free-electron lasers have enabled new approaches to the structural determination of protein crystals that are too small or radiation-sensitive for conventional analysis1. For sufficiently short pulses, diffraction is collected before significant changes occur to the sample, and it has been predicted that pulses as short as 10 fs may be required to acquire atomic-resolution structural information1, 2, 3, 4. Here, we describe a mechanism unique to ultrafast, ultra-intense X-ray experiments that allows structural information to be collected from crystalline samples using high radiation doses without the requirement for the pulse to terminate before the onset of sample damage. Instead, the diffracted X-rays are gated by a rapid loss of crystalline periodicity, producing apparent pulse lengths significantly shorter than the duration of the incident pulse. The shortest apparent pulse lengths occur at the highest resolution, and our measurements indicate that current X-ray free-electron laser technology5 should enable structural determination from submicrometre protein crystals with atomic resolution.
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| 24. |
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| 25. |
- Beijer, U, et al.
(författare)
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Mortality and causes of death among homeless women and men in Stockholm
- 2011
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Ingår i: Scandinavian journal of public health. - : SAGE Publications. - 1651-1905 .- 1403-4948. ; 39:2, s. 121-127
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To study the mortality and causes of death among homeless men and women in relation to the risk indicators, previous treatment for alcohol and drug abuse, previous treatment for mental disorders and non-Swedish citizenship. Methods: The mortality was studied in a cohort comprising 1,757 men and 526 women compared with the general population and persons with inpatient treatment for alcohol- and drug-related disorders. The follow-up period was from 1995 to 1997 until the end of 2005. The causes of death were analyzed. Results: 421 deaths occurred during the follow-up period. The relative risk of death was 3.1, with no difference in mortality between homeless men and homeless women. Previous treatment for alcohol and drug abuse disorders was related to excess mortality and previous treatment for mental disease to lower mortality. Homeless people with inpatient treatment for alcohol or drug use disorders had no higher mortality than the general population in Stockholm with a similar history. There was a dominance of alcohol- and drug-related causes of death. Discussion: Compared with previous studies of homeless people in Stockholm the excess mortality among men found in this study is of the same magnitude. Mortality among women is lower. The mortality rate in homeless people with previous treatment for an alcohol and illicit drug use disorder did not differ from those treated for these disorders in the general population. Conclusions: The most important finding is that excess mortality among homeless men and women in Stockholm is entirely related to alcohol and drug abuse.
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| 26. |
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| 27. |
- Beijer, U, et al.
(författare)
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Physical diseases among homeless people: gender differences and comparisons with the general population
- 2009
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Ingår i: Scandinavian journal of public health. - : SAGE Publications. - 1403-4948 .- 1651-1905. ; 37:1, s. 93-100
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To study morbidity amongst homeless men and women by comparing prevalence of hospital care for somatic diseases and injuries with a control group of men and women from the general population. Methods: A cohort of 1,364 men and 340 women were documented as homeless in 1996. Comparisons are made concerning hospital care for somatic diseases and injuries (1996-2002) among 3,750 men and 1,250 women from the general population. Results: The relative risk (RR) for homeless men and women of being hospitalised was double that of the men and women in the controls (1.93 and 1.96 respectively). Homeless women had a slightly, not significant, increased risk compared to homeless men (RR 1.10). Younger homeless women had a significant higher risk. Among diagnostic categories, the highest prevalence was found among homeless men in the diagnosis group injury/poisoning (22%). The highest risk was found for skin diseases (RR 36.96) and concerned homeless women. There were a number of gender specific diagnoses, where risks were considerably elevated, such as diseases of the genital organs, viral hepatitis, and poisoning for homeless women, and cerebrovascular diseases, diseases of the liver, and concussion for homeless men. Conclusions: Homeless people had twice the risk of being hospitalised for physical diseases compared to the general population. Younger women were particularly at risk compared to homeless men and to women in the controls. There were a number of gender specific diagnoses that are important to take into account when planning services for homeless people.
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| 28. |
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| 29. |
- Budelmann, D., et al.
(författare)
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Antiferromagnetic and superconducting proximity effects in YBa2Cu3O7-delta/PrBa2Cu3O7-delta superlattices
- 2003
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Ingår i: Physical Review B Condensed Matter. - 0163-1829 .- 1095-3795. ; 67, s. 140507-
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Tidskriftsartikel (refereegranskat)abstract
- We investigate the interplay between the antiferromagnetic and superconducting order parameters in YBa2Cu3O7-delta/PrBa2Cu3O7-delta superlattices by inelastic light scattering. The ratio of superconducting to antiferromagnetic order is varied through different modulations 4/6, 4/9, and 4/12 of (Y/Pr)Ba2Cu3O7-delta layers. This allows us to identify the proximity effect of the superconducting order parameter into the antiferromagnetic barrier as signified, e.g., by the sharpening of the two-magnon excitation. This proximity effect as well as gap feature and phonon anomalies reveals the delicate interplay between superconducting and antiferromagnetic order parameters.
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| 30. |
- Bälter, Magnus, 1986, et al.
(författare)
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An All-Photonic Molecule-Based Parity Generator/Checker for Error Detection in Data Transmission
- 2013
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 1520-5126 .- 0002-7863. ; 135:28, s. 10230-10233
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Tidskriftsartikel (refereegranskat)abstract
- The function of a parity generator/checker, which is an essential operation for detecting errors in data transmission, has been realized with multiphotochromic switches by taking advantage of a neuron-like fluorescence response and reversible light-induced transformations between the implicated isomers.
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| 31. |
- Elhai, M, et al.
(författare)
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Outcomes of patients with systemic sclerosis treated with rituximab in contemporary practice: a prospective cohort study
- 2019
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Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 78:7, s. 979-987
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Tidskriftsartikel (refereegranskat)abstract
- To assess the safety and efficacy of rituximab in systemic sclerosis (SSc) in clinical practice.MethodsWe performed a prospective study including patients with SSc from the European Scleroderma Trials and Research (EUSTAR) network treated with rituximab and matched with untreated patients with SSc. The main outcomes measures were adverse events, skin fibrosis improvement, lung fibrosis worsening and steroids use among propensity score-matched patients treated or not with rituximab.Results254 patients were treated with rituximab, in 58% for lung and in 32% for skin involvement. After a median follow-up of 2 years, about 70% of the patients had no side effect. Comparison of treated patients with 9575 propensity-score matched patients showed that patients treated with rituximab were more likely to have skin fibrosis improvement (22.7 vs 14.03 events per 100 person-years; OR: 2.79 [1.47–5.32]; p=0.002). Treated patients did not have significantly different rates of decrease in forced vital capacity (FVC)>10% (OR: 1.03 [0.55–1.94]; p=0.93) nor in carbon monoxide diffusing capacity (DLCO) decrease. Patients having received rituximab were more prone to stop or decrease steroids (OR: 2.34 [1.56–3.53], p<0.0001). Patients treated concomitantly with mycophenolate mofetil had a trend for better outcomes as compared with patients receiving rituximab alone (delta FVC: 5.22 [0.83–9.62]; p=0.019 as compared with controls vs 3 [0.66–5.35]; p=0.012).ConclusionRituximab use was associated with a good safety profile in this large SSc-cohort. Significant change was observed on skin fibrosis, but not on lung. However, the limitation is the observational design. The potential stabilisation of lung fibrosis by rituximab has to be addressed by a randomised trial.
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| 32. |
- Frankel, R., et al.
(författare)
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Autocatalytic amplification of Alzheimer-associated A beta 42 peptide aggregation in human cerebrospinal fluid
- 2019
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease is linked to amyloid beta (A beta) peptide aggregation in the brain, and a detailed understanding of the molecular mechanism of A beta aggregation may lead to improved diagnostics and therapeutics. While previous studies have been performed in pure buffer, we approach the mechanism in vivo using cerebrospinal fluid (CSF). We investigated the aggregation mechanism of A beta 42 in human CSF through kinetic experiments at several A beta 42 monomer concentrations (0.8-10 mu M). The data were subjected to global kinetic analysis and found consistent with an aggregation mechanism involving secondary nucleation of monomers on the fibril surface. A mechanism only including primary nucleation was ruled out. We find that the aggregation process is composed of the same microscopic steps in CSF as in pure buffer, but the rate constant of secondary nucleation is decreased. Most importantly, the autocatalytic amplification of aggregate number through catalysis on the fibril surface is prevalent also in CSF.
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| 33. |
- Gust, D., et al.
(författare)
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Data and signal processing using photochromic molecules
- 2012
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Ingår i: Chemical Communications. - : Royal Society of Chemistry (RSC). - 1364-548X .- 1359-7345. ; 48:14, s. 1947-1957
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Tidskriftsartikel (refereegranskat)abstract
- Photochromes are chromophores that are reversibly isomerized between two metastable forms using light, or light and heat. When photochromes are covalently linked to other chromophores, they can act as molecular photonic analogues of electronic transistors. As bistable switches, they can be incorporated into the design of molecules capable of binary arithmetic and both combinatorial and sequential digital logic operations. Small ensembles of such molecules can perform analogue signal modulation similar to that carried out by transistor amplifiers. Examples of molecules that perform multiple logic functions, act as control elements for fluorescent reporters, and mimic natural photoregulatory functions are presented.
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| 34. |
- Johansson, Per, et al.
(författare)
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Convergence of chromogranin and amyloid metabolism in the brain.
- 2010
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5279 .- 1552-5260. ; 6:4, s. 511-511
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Konferensbidrag (refereegranskat)abstract
- Background: Much is unknown regarding the regulation of amyloid precursor protein (APP) processing in the human central nervous system. It has been hypothesized that amyloidogenic APP-processing preferentially occurs in the regulated secretory pathway of neurons. To test this hypothesis we looked for correlations of APP-derived molecules in CSF with chromogranin (Cg) derived peptides, representing the regulated secretion. Methods: Patients with Alzheimer's disease (AD, N = 32), multiple sclerosis (MS, N = 50) and healthy controls (N = 70) were enrolled. CSF was analyzed for the amyloid peptides Aβ1-42, Aβx-42, Aβx-40, Aβx-38, α-cleaved soluble APP (α-sAPP), β-cleaved soluble APP (β-sAPP), and peptides derived from CgB and SgII (Secretogranin-II, CgC). We investigated CSF levels of the protease BACE1, which processes APP into Aβ, in relation to Cg-levels. Finally, we measured Cg levels in cell media from untreated and BACE1-inhibited SH-SY5Y human neuroblastoma cells. Results: CSF Cg levels correlated to sAPP and Aβ peptides in AD, MS and controls, and to CSF BACE1. Cell medium from BACE1-inhibited cells had decreased CgB levels. Conclusions: These results suggest that a large part of APP in the human central nervous system is processed in the regulated secretory pathway of neurons.
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| 35. |
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| 36. |
- Kohl, S, et al.
(författare)
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CNGB3 mutations account for 50% of all cases with autosomal recessive achromatopsia
- 2005
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Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1476-5438 .- 1018-4813. ; 13:3, s. 302-308
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Tidskriftsartikel (refereegranskat)abstract
- Achromatopsia is a congenital, autosomal recessively inherited disorder characterized by a lack of color discrimination, low visual acuity (<0.2), photophobia, and nystagmus. Mutations in the genes for CNGA3, CNGB3, and GNAT2 have been associated with this disorder. Here, we analyzed the spectrum and prevalence of CNGB3 gene mutations in a cohort of 341 independent patients with achromatopsia. In 163 patients, CNGB3 mutations could be identified. A total of 105 achromats carried apparent homozygous mutations, 44 were compound (double) heterozygotes, and 14 patients had only a single mutant allele. The derived CNGB3 mutation spectrum comprises 28 different mutations including 12 nonsense mutations, eight insertions and/or deletions, five putative splice site mutations, and three missense mutations. Thus, the majority of mutations in the CNGB3 gene result in significantly altered and/or truncated polypeptides. Several mutations were found recurrently, in particular a 1 bp deletion, c.1148delC, which accounts for over 70% of all CNGB3 mutant alleles. In conclusion, mutations in the CNGB3 gene are responsible for approximately 50% of all patients with achromatopsia. This indicates that the CNGB3/ACHM3 locus on chromosome 8q21 is the major locus for achromatopsia in patients of European origin or descent.
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| 37. |
- Kurilshikov, Alexander, et al.
(författare)
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Large-scale association analyses identify host factors influencing human gut microbiome composition
- 2021
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 53:2, s. 156-165
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Tidskriftsartikel (refereegranskat)abstract
- To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts). Microbial composition showed high variability across cohorts: only 9 of 410 genera were detected in more than 95% of samples. A genome-wide association study of host genetic variation regarding microbial taxa identified 31 loci affecting the microbiome at a genome-wide significant (P < 5 x 10(-8)) threshold. One locus, the lactase (LCT) gene locus, reached study-wide significance (genome-wide association study signal: P = 1.28 x 10(-20)), and it showed an age-dependent association with Bifidobacterium abundance. Other associations were suggestive (1.95 x 10(-10) < P < 5 x 10(-8)) but enriched for taxa showing high heritability and for genes expressed in the intestine and brain. A phenome-wide association study and Mendelian randomization identified enrichment of microbiome trait loci in the metabolic, nutrition and environment domains and suggested the microbiome might have causal effects in ulcerative colitis and rheumatoid arthritis.
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| 38. |
- Mill, O., et al.
(författare)
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Analysis and development of hydro power research : synthesis within Swedish Hydro Power Centre
- 2010
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The market for hydropower re-investments in Sweden is approx 2.5 billion SEK/yr the coming decade. Large investments will also be carried out in Swedish tailing dams. This will result in challenging projects and need of experts. A crucial factor for a successful management of these challenges is the supply of engineers and researchers with hydro power and dam skills and knowledge. Swedish Hydro Power Centre (Svenskt vattenkraftcentrum, SVC) is a competence centre for university education and research environments within hydro power and mining dams. SVC comprises of two knowledge areas: Hydraulic Engineering and Hydro Turbines and Generators, respectively. SVC builds high-quality and long term sustainable knowledge at selected universities...
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| 39. |
- Nadkarni, A, et al.
(författare)
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Brief interventions for alcohol use disorders in low- and middle-income countries: barriers and potential solutions
- 2022
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Ingår i: International journal of mental health systems. - : Springer Science and Business Media LLC. - 1752-4458. ; 16:1, s. 36-
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Tidskriftsartikel (refereegranskat)abstract
- Global alcohol consumption and harmful use of alcohol is projected to increase in the coming decades, and most of the increase will occur in low- and middle-income countries (LMICs); which calls for cost-effective measures to reduce alcohol exposure in these countries. One such evidence based measure is screening and brief intervention (BI) for alcohol problems. Some of the characteristics of BI make them a particularly appealing choice of interventions in low-resource settings. However, despite evidence of effectiveness, implementation of BI in LMICs is rare. In this paper we discuss barriers to implementation of BI in LMICs, with examples from Latin America and India. Key barriers to implementation of BI in LMICs are the lack of financial and structural resources. Specialized services for alcohol use disorders are limited or non-existent. Hence primary care is often the only possible alternative to implement BI. However, health professionals in such settings generally lack training to deal with these disorders. In our review of BI research in these countries, we find some promising results, primarily in countries from Latin America, but so far there is limited research on effectiveness. Appropriate evaluation of efficacy and effectiveness of BI is undermined by lack of generalisability and methodological limitations. No systematic and scientific efforts to explore the implementation and evaluation of BI in primary and community platforms of care have been published in India. Innovative strategies need to be deployed to overcome supply side barriers related to specialist manpower shortages in LMICs. There is a growing evidence on the effectiveness of non-specialist health workers, including lay counsellors, in delivering frontline psychological interventions for a range of disorders including alcohol use disorders in LMICs. This paper is intended to stimulate discussion among researchers, practitioners and policy-makers in LMICs because increasing access to evidence based care for alcohol use disorders in LMICs would need a concerted effort from all these stakeholders.
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| 40. |
- Nilsson, Jesper, 1984, et al.
(författare)
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Switching Properties of a Spiropyran-Cucurbit [7] uril Supramolecular Assembly: Usefulness of the Anchor Approach
- 2012
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Ingår i: ChemPhysChem. - : Wiley. - 1439-7641 .- 1439-4235. ; 13:16, s. 3691-3699
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Tidskriftsartikel (refereegranskat)abstract
- A nitrospiropyran, which was modified with a cadaverine-derived anchor, was investigated with respect to its thermally induced isomerizations, hydrolytic stability of the merocyanine form, and photochromic ring closure. The hostguest complexation of the anchor by the cucurbit[7]uril macrocycle, evidenced by absorption titration, NMR spectroscopy, and electrospray ionization mass spectrometry, produced significant improvements of the switching properties of the photochrome: 1) appearance of the merocyanine form about 70 times faster, 2) practically unlimited hydrolytic stability of the merocyanine (two and a half days without any measureable decay), and 3) fast, clean, and fatigue-resistant photoinduced ring closure back to the spiro form. The importance of an adequate molecular design of the anchor was demonstrated by including control experiments with spiropyrans with a shorter linker or without such structural asset.
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| 41. |
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| 42. |
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| 43. |
- Padayachee, E. R., et al.
(författare)
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Cerebrospinal fluid-induced retardation of amyloid β aggregation correlates with Alzheimer's disease and the APOE ε4 allele
- 2016
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Ingår i: Brain Research. - : Elsevier BV. - 0006-8993. ; 1651, s. 11-16
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Tidskriftsartikel (refereegranskat)abstract
- Misfolding and aggregation of amyloid β (Aβ) are key features of Alzheimer's disease (AD) pathogenesis, but the molecular events controlling this process are not known in detail. In vivo, Aβ aggregation and plaque formation occur in the interstitial fluid of the brain extracellular matrix. This fluid communicates freely with cerebrospinal fluid (CSF). Here, we examined the effect of human CSF on Aβ aggregation kinetics in relation to AD diagnosis and carrier status of the apolipoprotein E (APOE) ε4 allele, the main genetic risk factor for sporadic AD. The aggregation of Aβ was inhibited in the presence of CSF and, surprisingly, the effect was more pronounced in APOE ε4 carriers. However, by fractionation of CSF using size exclusion chromatography, it became evident that it was not the ApoE protein itself that conveyed the inhibition, since the retarding species eluted at lower volume, corresponding to a much higher molecular weight, than ApoE monomers. Cholesterol quantification and immunoblotting identified high-density lipoprotein particles in the retarding fractions, indicating that such particles may be responsible for the inhibition. These results add information to the yet unresolved puzzle on how the risk factor of APOE ε4 functions in AD pathogenesis.
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| 44. |
- Pais, V. F., et al.
(författare)
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OFF-ON-OFF Fluorescence Switch with T-Latch Function
- 2011
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Ingår i: Organic Letters. - : American Chemical Society (ACS). - 1523-7052 .- 1523-7060. ; 13:20, s. 5572-5575
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Tidskriftsartikel (refereegranskat)abstract
- A novel molecular system with characteristics of an OFF-ON-OFF fluorescence switch was designed to integrate the function of a T-latch. In detail, a receptor(1)-fluorophore-receptor(2) architecture was adopted to achieve fluorescence switching upon addition of protons.
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| 45. |
- Pischel, U., et al.
(författare)
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Information Processing with Molecules-Quo Vadis?
- 2013
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Ingår i: ChemPhysChem. - : Wiley. - 1439-7641 .- 1439-4235. ; 14:1, s. 28-46
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Forskningsöversikt (refereegranskat)abstract
- Information processing at the molecular level is coming of age. Since the first molecular AND gate was proposed about 20 years ago, the molecular interpretation of binary logic has become vastly more sophisticated and complex. However, the field is also at a crossroads. While cleverly designed molecular building blocks are abundant, difficult questions remain. How can molecular components be flexibly assembled into larger circuits, and how can these components communicate with one another. The concept of all-photonic switching with photochromic supermolecules has shown some interesting potential and is discussed in this review. Although the field of molecular logic was originally discussed mainly in terms of a technology that might compete with solid-state computers, potential applications have expanded to include clever molecular systems and materials for drug delivery, sensing, probing, encoding, and diagnostics. These upcoming trends, which are herein illustrated by selected examples, deserve general attention.
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| 46. |
- Remón Ruiz, Patricia, 1982, et al.
(författare)
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An acido- and photochromic molecular device that mimics triode action
- 2016
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Ingår i: Chemical Communications. - : Royal Society of Chemistry (RSC). - 1364-548X .- 1359-7345. ; 52:25, s. 4659-4662
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Tidskriftsartikel (refereegranskat)abstract
- © The Royal Society of Chemistry 2016. The photo-controlled shift of pH titration curves, describing the acidochromic behaviour of a spiropyran switch network, was harnessed for the realisation of a molecular triode. The intricate network can be correctly interpreted with respect to the pH dependence of the main involved species.
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| 47. |
- Remón Ruiz, Patricia, 1982, et al.
(författare)
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An All-Photonic Molecule-Based D Flip-Flop
- 2011
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 1520-5126 .- 0002-7863. ; 133:51, s. 20742-20745
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Tidskriftsartikel (refereegranskat)abstract
- The photochromic fluorescence switching of a fulgimide derivative was used to implement the first molecule-based D (delay) flip-flop device, which works based on the principles of sequential logic. The device operates exclusively with photonic signals and can be conveniently switched in repeated cycles. © 2011 American Chemical Society.
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| 48. |
- Remón Ruiz, Patricia, 1982, et al.
(författare)
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Molecular Implementation of Sequential and Reversible Logic Through Photochromic Energy Transfer Switching
- 2011
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Ingår i: Chemistry - A European Journal. - : Wiley. - 1521-3765 .- 0947-6539. ; 17:23, s. 6492-6500
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Tidskriftsartikel (refereegranskat)abstract
- Photochromic spiropyrans modified with fluorophores were investigated as molecular platforms for the achievement of fluorescence switching through modulation of energy transfer. The dyads were designed in such a way that energy transfer is only observed for the open forms of the photochrome (merocyanine and protonated merocyanine), whereas the closed spiropyran is inactive as an energy acceptor. This was made possible through a deliberate choice of fluorophores (4-amino-1,8-naphthalimide, dansyl, and perylene) that produce zero spectral overlap with the spiro form and considerable overlap for the merocyanine forms. From the Förster theory, energy transfer is predicted to be highly efficient and in some cases of 100 % efficiency. The combined switching by photonic (light of λ>530 nm) and chemical (base) inputs enabled the creation of a sequential logic device, which is the basic element of a keypad lock. Furthermore, in combination with an anthracene-based acidochromic fluorescence switch, a reversible logic device was designed. This enables the unambiguous coding of different input combinations through multicolour fluorescence signalling. All devices can be conveniently reset to their initial states and repeatedly cycled.
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| 49. |
- Teär Fahnehjelm, Kristina, et al.
(författare)
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Most patients with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency develop pathological or subnormal retinal function
- 2016
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Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 105:12, s. 1451-1460
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Tidskriftsartikel (refereegranskat)abstract
- Aim: There have been few studies on long-term electroretinographic findings in patients with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD). This study correlated long-term electroretinographic findings with age, metabolic control and clinical symptoms. Methods: We examined 12 Swedish patients with LCHADD. Visual acuity testing, fundus examinations, optical coherence tomography and electroretinography were performed. The results were correlated to age, the levels of 3-hydroxyacylcarnitine and acylcarnitine and clinical metabolic control. Results: Blindness or moderate visual impairment was found in two patients. Retinal pigmentation, atrophy and fibrosis were present in 11, seven and one of the patients, respectively, and optical coherence tomography showed retinal thinning in three of the six patients examined. Electroretinography was performed on 11 of the 12 patients. It was pathological, with reduced rod and cone responses, in five patients, subnormal in four and was related to poor clinical metabolic control and severe neonatal symptoms. Repeated electroretinographies revealed reduced function with increasing age. Conclusion: More than 80% of the LCHADD patients developed pathological or subnormal retinal function. This was more pronounced in patients with neonatal symptoms, but ameliorated by strict dietary treatment. Annual ophthalmological follow-ups, with electroretinography every second or third year, are recommended.
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| 50. |
- Vinko, S. M., et al.
(författare)
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Electronic Structure of an XUV Photogenerated Solid-Density Aluminum Plasma
- 2010
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 104:22, s. 225001-
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Tidskriftsartikel (refereegranskat)abstract
- By use of high intensity XUV radiation from the FLASH free-electron laser at DESY, we have created highly excited exotic states of matter in solid-density aluminum samples. The XUV intensity is sufficiently high to excite an inner-shell electron from a large fraction of the atoms in the focal region. We show that soft-x-ray emission spectroscopy measurements reveal the electronic temperature and density of this highly excited system immediately after the excitation pulse, with detailed calculations of the electronic structure, based on finite-temperature density functional theory, in good agreement with the experimental results.
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