| 1. |
- Folkersen, Lasse, et al.
(författare)
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Genomic and drug target evaluation of 90 cardiovascular proteins in 30,931 individuals.
- 2020
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Ingår i: Nature metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 2:10, s. 1135-1148
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Tidskriftsartikel (refereegranskat)abstract
- Circulating proteins are vital in human health and disease and are frequently used as biomarkers for clinical decision-making or as targets for pharmacological intervention. Here, we map and replicate protein quantitative trait loci (pQTL) for 90 cardiovascular proteins in over 30,000 individuals, resulting in 451 pQTLs for 85 proteins. For each protein, we further perform pathway mapping to obtain trans-pQTL gene and regulatory designations. We substantiate these regulatory findings with orthogonal evidence for trans-pQTLs using mouse knockdown experiments (ABCA1 and TRIB1) and clinical trial results (chemokine receptors CCR2 and CCR5), with consistent regulation. Finally, we evaluate known drug targets, and suggest new target candidates or repositioning opportunities using Mendelian randomization. This identifies 11 proteins with causal evidence of involvement in human disease that have not previously been targeted, including EGF, IL-16, PAPPA, SPON1, F3, ADM, CASP-8, CHI3L1, CXCL16, GDF15 and MMP-12. Taken together, these findings demonstrate the utility of large-scale mapping of the genetics of the proteome and provide a resource for future precision studies of circulating proteins in human health.
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| 2. |
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| 3. |
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| 4. |
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| 5. |
- Raffan, Eleanor, et al.
(författare)
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A Deletion in the Canine POMC Gene Is Associated with Weight and Appetite in Obesity-Prone Labrador Retriever Dogs
- 2016
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Ingår i: Cell Metabolism. - : Elsevier BV. - 1550-4131 .- 1932-7420. ; 23:5, s. 893-900
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Tidskriftsartikel (refereegranskat)abstract
- Sequencing of candidate genes for obesity in Labrador retriever dogs identified a 14 bp deletion in pro-opiomelanocortin (POMC) with an allele frequency of 12%. The deletion disrupts the b-MSH and beta-endorphin coding sequences and is associated with body weight (per allele effect of 0.33 SD), adiposity, and greater food motivation. Among other dog breeds, the deletion was only found in the closely related flat-coat retriever (FCR), where it is similarly associated with body weight and food motivation. The mutation is significantly more common in Labrador retrievers selected to become assistance dogs than pets. In conclusion, the deletion in POMC is a significant modifier of weight and appetite in Labrador retrievers and FCRs and may influence other behavioral traits.
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| 6. |
- Wang, C. H., et al.
(författare)
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InAs hole inversion and bandgap interface state density of 2 x 10(11) cm(-2) eV(-1) at HfO2/InAs interfaces
- 2013
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Ingår i: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 103:14
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Tidskriftsartikel (refereegranskat)abstract
- High-k/InAs interfaces have been manufactured using InAs surface oxygen termination and low temperature atomic layer deposition of HfO2. Capacitance-voltage (C-V) curves revert to essentially classical shape revealing mobile carrier response in accumulation and depletion, hole inversion is observed, and predicted minority carrier response frequency in the hundred kHz range is experimentally confirmed; reference samples using conventional techniques show a trap dominated capacitance response. C-V curves have been fitted using advanced models including nonparabolicity and Fermi-Dirac distribution. For an equivalent oxide thickness of 1.3 nm, an interface state density D-it = 2.2 x 10(11) cm(-2) eV(-1) has been obtained throughout the InAs bandgap. (C) 2013 AIP Publishing LLC.
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| 7. |
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| 8. |
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| 9. |
- Babadi, Aein S., et al.
(författare)
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Impact of doping and diameter on the electrical properties of GaSb nanowires
- 2017
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Ingår i: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 110:5
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Tidskriftsartikel (refereegranskat)abstract
- The effect of doping and diameter on the electrical properties of vapor-liquid-solid grown GaSb nanowires was characterized using long channel back-gated lateral transistors and top-gated devices. The measurements showed that increasing the doping concentration significantly increases the conductivity while reducing the control over the channel potential and shifting the threshold voltage, as expected. The highest average mobility was 85 cm2/V·s measured for an unintentionally doped GaSb nanowire with a diameter of 45 nm, whereas medium doped nanowires with large diameters (81 nm) showed a value of 153 cm2/V·s. The mobility is found to be independent of nanowire diameter in the range of 36 nm-68 nm, while the resistivity is strongly reduced with increasing diameter attributed to the surface depletion of charge carriers. The data are in good agreement with an analytical calculation of the depletion depth. A high transconductance was achieved by scaling down the channel length to 200 nm, reaching a maximum value of 80 μS/μm for a top-gated GaSb nanowires transistor with an ON-resistance of 26 kΩ corresponding to 3.9 Ω.mm. The lowest contact resistance obtained was 0.35 Ω·mm for transistors with the highest doping concentration.
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| 10. |
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| 11. |
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| 12. |
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| 13. |
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| 14. |
- Girelli, G, et al.
(författare)
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Sequencing Genome Organization
- 2022
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Ingår i: EUROPEAN JOURNAL OF HUMAN GENETICS. - 1018-4813. ; 30:SUPPL 1, s. 16-16
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 15. |
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| 16. |
- Jeppsson, M., et al.
(författare)
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The effect of silver ions and chlorine on the survival of Staphylococcus aureus and Bacillus cereus in dishwater
- 2007
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Ingår i: Environmental Technology. - : Informa UK Limited. - 1479-487X .- 0959-3330. ; 28:12, s. 1419-1427
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Tidskriftsartikel (refereegranskat)abstract
- This paper investigates the effect of chlorine and silver ion solutions on the survival of Bacillus cereus (vegetative phase) and Staphylococcus aureus in batch cultures, representing dishwater. Dishwater contains organic matter and bacteria and bacterial activities are partly reduced by high pH (11-12) and temperature (55-65 degrees C) in professional and domestic dishwashers. in manual dishwashing, temperature and pH are kept lower (45 degrees C and pH 7), which is less sufficient for the reduction of bacteria. In a broth, organic loaded in order to mimic dishwater, solutions of Ag+ or hypochlorite were added at 45 degrees C and pH 7 and samples were withdrawn for a period of 40 minutes. 1 ppm Ag+ was required to obtain a 1 to 2 log unit reduction of B. cereus and S. aureus in 10 minutes. An addition of 160 ppm hypochlorite reduced B. cereus and S. aureus by 4 log units in two minutes, whereas 16 ppm of hypochlorite had no effect on the survival of S. aureus. The level of free residual chlorine varied with the COD value of the cultured solutions. We found that both silver and hypochlorite can be used as antibacterial agents in dishwater. The disadvantage with the use of hypochlorite is that the COD value determines the antibacterial effect. Using Ag+ solutions to reduce bacteria has the drawback that they are toxic to water-living organisms and are considered to develop Ag+ resistant bacteria. To reduce the risk of cross-contamination from dishwater to dishware high temperature and detergent with high pH is to be preferred.
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| 17. |
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| 18. |
- Larsson, D. G. Joakim, 1969, et al.
(författare)
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Critical knowledge gaps and research needs related to the environmental dimensions of antibiotic resistance
- 2018
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 117, s. 132-138
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Forskningsöversikt (refereegranskat)abstract
- There is growing understanding that the environment plays an important role both in the transmission of antibiotic resistant pathogens and in their evolution. Accordingly, researchers and stakeholders world-wide seek to further explore the mechanisms and drivers involved, quantify risks and identify suitable interventions. There is a clear value in establishing research needs and coordinating efforts within and across nations in order to best tackle this global challenge. At an international workshop in late September 2017, scientists from 14 countries with expertise on the environmental dimensions of antibiotic resistance gathered to define critical knowledge gaps. Four key areas were identified where research is urgently needed: 1) the relative contributions of different sources of antibiotics and antibiotic resistant bacteria into the environment; 2) the role of the environment, and particularly anthropogenic inputs, in the evolution of resistance; 3) the overall human and animal health impacts caused by exposure to environmental resistant bacteria; and 4) the efficacy and feasibility of different technological, social, economic and behavioral interventions to mitigate environmental antibiotic resistance.(1)
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| 19. |
- Lee, S. -K, et al.
(författare)
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Reduction of the barrier height and enhancement of tunneling current of titanium contacts using embedded Au nano-particles on 4H and 6H silicon carbide
- 2002
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Ingår i: Materials Science Forum. - : Trans Tech Publications Inc.. - 0255-5476 .- 1662-9752. ; 389-393:2, s. 937-940
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Tidskriftsartikel (refereegranskat)abstract
- We have investigated the electrical characteristics of Ti Schottky contacts with embedded Au nano-particles on various types of epilayers of SiC (4H- and 6H-SiC). From our current-voltage (I-V) and capacitance-voltage (C-V) measurements, we observed that Ti Schottky contacts with embedded Au nano-particles had 0.19 eV (n-4H-SiC) and 0.15 eV (n-6H-SiC) lower barrier height than those of particle free Ti Schottky contacts. In order to understand this reduction of the Schottky barrier height (SBH) for Ti Schottky contacts with embedded Au nano-particles, it has been proposed that SBH lowering is caused by an enhanced electric field due to the small size of the Au nano-particles and the large SBH difference. We have also tested these contacts on highly doped n-and p-type SiC material to study ohmic contacts using linear TLM measurements.
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| 20. |
- Lee, S. K., et al.
(författare)
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Reduction of the Schottky barrier height on silicon carbide using Au nano-particles
- 2002
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Ingår i: Solid-State Electronics. - 0038-1101 .- 1879-2405. ; 46:9, s. 1433-1440
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Tidskriftsartikel (refereegranskat)abstract
- By the incorporation of size-selected Au nano-particles in Ti Schottky contacts on silicon carbide, we could observe considerably lower the barrier height of the contacts. This result could be obtained for both n- and p-type Schottky contacts using current-voltage and capacitance voltage measurements. For n-type Schottky contacts, we observed reductions of 0.19-0.25 eV on 4H-SiC and 0.15-0.17 eV on 6H-SiC as compared with particle-free Ti Schottky contacts. For p-type SiC, the reduction was a little lower with 0.02-0.05 eV on 4H- and 0.10-0.13 eV on 6H-SiC. The reduction of the Schottky barrier height is explained using a model with enhanced electric field at the interface due to the small size of the circular patch and the large difference of the barrier height between Ti and Au.
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| 21. |
- Marais, Andrew, et al.
(författare)
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New insights into the mechanisms behind the strengthening of lignocellulosic fibrous networks with polyamines
- 2014
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Ingår i: Cellulose. - : Springer Science and Business Media LLC. - 0969-0239 .- 1572-882X. ; 21:6, s. 3941-3950
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Tidskriftsartikel (refereegranskat)abstract
- Polyelectrolytes have been used extensively in the papermaking industry for various purposes. Although recent studies have shown that polyamines can be efficient dry-strength additives, the mechanism governing the strength enhancement of paper materials following the adsorption of polyamines onto pulp fibres is still not well understood. In this study, the effect of the adsorption of polyallylamine hydrochloride (PAH) onto the surface of unbleached kraft pulp fibres was investigated on both the fibre and the network scale. Isolated fibre crosses were mechanically tested to evaluate the impact of the chemical additive on the interfibre joint strength on the microscopic scale and the effect was compared with that previously observed on the paper sheet scale. X-ray microtomography was used to understand structural changes in the fibrous network following the adsorption of a polyamine such as PAH. Using image analysis methods, it was possible to determine the number of interfibre contacts (or joints) per unit length of fibre as well as the average interfibre joint contact area. The results showed that the median interfibre joint strength increased by 18 % upon adsorption of PAH. This can be achieved both by a larger molecular contact area in the contact zones and by a stronger molecular adhesion. The addition of the polymer also increased the number of efficient interfibre contacts per sheet volume. This combination of effects is the reason why polyamines such as PAH can increase the dry tensile strength of paper materials.
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| 22. |
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| 23. |
- Muller, L. S. O., et al.
(författare)
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Magnetic resonance imaging of the knee for chronological age estimation-a systematic review
- 2023
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Ingår i: European Radiology. - 0938-7994. ; 33:98, s. 5258-5268
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionRadiographs of the hand and teeth are frequently used for medical age assessment, as skeletal and dental maturation correlates with chronological age. These methods have been criticized for their lack of precision, and magnetic resonance imaging (MRI) of the knee has been proposed as a more accurate method. The aim of this systematic review is to explore the scientific and statistical evidence for medical age estimation based on skeletal maturation as assessed by MRI of the knee.Materials and methodsA systematic review was conducted that included studies published before April 2021 on living individuals between 8 and 30 years old, with presumptively healthy knees for whom the ossification stages had been evaluated using MRI. The correlation between "mature knee" and chronological age and the risk of misclassifying a child as an adult and vice versa was calculated.ResultsWe found a considerable heterogeneity in the published studies -in terms of study population, MRI protocols, and grading systems used. There is a wide variation in the correlation between maturation stage and chronological age.ConclusionData from published literature is deemed too heterogenous to support the use of MRI of the knee for chronological age determination. Further, it is not possible to assess the sensitivity, specificity, negative predictive value, or positive predictive value for the ability of MRI to determine whether a person is over or under 18 years old.
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| 24. |
- Ohki, S, et al.
(författare)
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A study of estimation method for conduction band offset in semiconductor heterostructure by using triple-barrier resonant tunneling diodes
- 2002
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Ingår i: Applied Surface Science. - 1873-5584. ; 190:1-4, s. 288-293
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Tidskriftsartikel (refereegranskat)abstract
- A method for evaluating a band offset of a heterojunction is proposed by measuring temperature dependence of current-voltage (I-V) characteristics in triple-barrier resonant tunneling diodes (TBRTDs). The method was applied for investigating a conduction band offset by using GaAs0.25P0.75/GaAs TBRTDs with thin strain heterobarriers grown by MOCVD and DeltaE(c) was estimated as 200-240 meV. In the strain-barrier TBRTDs, negative differential resistance was observed below 100 K. (C) 2002 Elsevier Science B.V. All rights reserved.
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| 25. |
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| 26. |
- Osbeck, Christina, et al.
(författare)
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Var fjärde elev kränks i skolan
- 2003
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Ingår i: Dagens Nyheter. 2003, februari, 26.
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Tidskriftsartikel (populärvet., debatt m.m.)
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| 27. |
- Schenk, A., et al.
(författare)
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The impact of hetero-junction and oxide-interface traps on the performance of InAs/Si and InAs/GaAsSb nanowire tunnel FETs
- 2017
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Ingår i: 2017 International Conference on Simulation of Semiconductor Processes and Devices, SISPAD 2017. - 9784863486102 ; 2017-September, s. 273-276
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Konferensbidrag (refereegranskat)abstract
- Fabricated InAs/Si and InAs/GaAsSb vertical nanowire tunnel FETs are analyzed by physics-based TCAD with emphasis on the impact of hetero-junction and oxide-interface traps on their performance. After careful fitting of a minimum set of parameters, the effects of diameter scaling and gate alignment are predicted. Trap-assisted tunneling at the oxide interface is suppressed by scaling the diameter into the volume-inversion regime. Gate alignment steepens the slope and increases the ON-current. The 'trap-tolerant' device geometry can result in a small sub-threshold swing despite commonly present trap concentrations.
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| 28. |
- Suhara, M, et al.
(författare)
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A proposal to estimate homogeneous and inhomogeneous energy level broadening in double barrier resonant tunneling diodes
- 2002
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Ingår i: Compound Semiconductors 2001 (Institute of Physics Conference Series). - 0951-3248. ; :170, s. 363-367
-
Konferensbidrag (refereegranskat)abstract
- In this paper we proposed a method for evaluating a homogeneous broadening (DeltaE(h)) and inhomogeneous broadening (DeltaE(i)) of the resonant energy level width independently by using current-voltage characteristics in double barrier resonant tunneling diodes (DBRTDs). The line shape of the resonant energy broadening is assumed as a convolution of Lorentz function and a Gauss function. Measured transmittance in GaAs0.25P0.75/GaAs DBRTDs grown by MOCVD is well fit to the convolution function. The DeltaE(h), DeltaE(i) were estimated as 4.3[meV] and 1.0 [meV], respectively, where the measured energy-voltage conversion factor 17 is 0.3[eV/V].
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| 29. |
- Troian, Andrea, et al.
(författare)
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InAs-oxide interface composition and stability upon thermal oxidation and high-k atomic layer deposition
- 2018
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Ingår i: AIP Advances. - : AIP Publishing. - 2158-3226. ; 8:12
-
Tidskriftsartikel (refereegranskat)abstract
- Defects at the interface between InAs and a native or high permittivity oxide layer are one of the main challenges for realizing III-V semiconductor based metal oxide semiconductor structures with superior device performance. Here we passivate the InAs(100) substrate by removing the native oxide via annealing in ultra-high vacuum (UHV) under a flux of atomic hydrogen and growing a stoichiometry controlled oxide (thermal oxide) in UHV, prior to atomic layer deposition (ALD) of an Al2O3 high-k layer. The semiconductor-oxide interfacial stoichiometry and surface morphology are investigated by synchrotron based X-ray photoemission spectroscopy, scanning tunneling microscopy, and low energy electron diffraction. After thermal oxide growth, we find a thin non-crystalline layer with a flat surface structure. Importantly, the InAs-oxide interface shows a significantly decreased amount of In3+, As5+, and As0 components, which can be correlated to electrically detrimental defects. Capacitance-voltage measurements confirm a decrease of the interface trap density in gate stacks including the thermal oxide as compared to reference samples. This makes the concept of a thermal oxide layer prior to ALD promising for improving device performance if this thermal oxide layer can be stabilized upon exposure to ambient air.
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| 30. |
- Vasen, T., et al.
(författare)
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InAs nanowire GAA n-MOSFETs with 12-15 nm diameter
- 2016
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Ingår i: 2016 IEEE Symposium on VLSI Technology, VLSI Technology 2016. - 9781509006373 ; 2016-September
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Konferensbidrag (refereegranskat)abstract
- InAs nanowires (NW) grown by MOCVD with diameter d as small as 10 nm and gate-All-Around (GAA) MOSFETs with d = 12-15 nm are demonstrated. Ion = 314 μA/μm, and Ssat =68 mV/dec was achieved at Vdd = 0.5 V (Ioff = 0.1 μA/μm). Highest gm measured is 2693 μS/μm. Device performance is enabled by small diameter and optimized high-k/InAs gate stack process. Device performance tradeoffs between gm, Ron, and Imin are discussed.
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| 31. |
- Wang, C. H., et al.
(författare)
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High-k dielectrics on (100) and (110) n-InAs: Physical and electrical characterizations
- 2014
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Ingår i: AIP Advances. - : AIP Publishing. - 2158-3226. ; 4:4
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Tidskriftsartikel (refereegranskat)abstract
- Two high-k dielectric materials (Al2O3 and HfO2) were deposited on n-type (100) and (110) InAs surface orientations to investigate physical properties of the oxide/semiconductor interfaces and the interface trap density (D-it). X-ray photoelectron spectroscopy analyses (XPS) for native oxides of (100) and (110) as-grown n-InAs epi wafers show an increase in As-oxide on the (100) surface and an increase in InOx on the (110) surface. In addition, XPS analyses of high-k (Al2O3 and HfO2) on n-InAs epi show that the intrinsic native oxide difference between (100) and (110) epi surfaces were eliminated by applying conventional in-situ pre-treatment (TriMethyAluminium (TMA)) before the high-k deposition. The capacitance-voltage (C-V) characterization of HfO2 and Al2O3 MOSCAPs on both types of n-InAs surfaces shows very similar C-V curves. The interface trap density (D-it) profiles show D-it minima of 6.1 x 10(12/)6.5 x 10(12) and 6.6 x 10(12)/7.3 x 10(12) cm(-2) eV(-1) for Al2O3 and HfO2, respectively for (100) and (110) InAs surfaces. The similar interface trap density (D-it) on (100) and (110) surface orientation were observed, which is beneficial to future InAs FinFET device with both (100) and (110) surface channel orientations present. (C) 2014 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 Unported License.
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| 32. |
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| 33. |
- Wernersson, Lars-Erik, et al.
(författare)
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A combined chemical vapor deposition and rapid thermal diffusion process for SiGe Esaki diodes by ultra-shallow junction formation
- 2005
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Ingår i: IEEE Transactions on Nanotechnology. - 1536-125X. ; 4:5, s. 594-598
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Tidskriftsartikel (refereegranskat)abstract
- SiGe Esaki diodes have been realized by rapid thermal diffusion of phosphorous into an SiGe layer grown by ultra-high-vacuum chemical-vapor-deposition on an Si p(+)-substrate for the first time. The phosphorous-doped SiGe forms the n(+)-electrode, while heavily boron-doped Si0.74Ge0.26 and Si substrate is used for the p(+) electrode. The diodes show a peak current density of 0.18 kA/cm(2), a current peak-to-valley ratio of 2.6 at room temperature, and they exhibit only a weak temperature dependence. Cross-sectional transmission microscopy showed a good crystalline quality of the strained Si0.74Ge0.26 layer even after the diffusion step at 900 degrees C.
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| 34. |
- Wernersson, Lars-Erik, et al.
(författare)
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SiGe Esaki tunnel diodes fabricated by UHV-CVD growth and proximity rapid thermal diffusion
- 2004
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Ingår i: Electronics Letters. - : Institution of Engineering and Technology (IET). - 1350-911X .- 0013-5194. ; 40:1, s. 83-85
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Tidskriftsartikel (refereegranskat)abstract
- A process for realisation of SiGe Esaki diodes in layers grown by ultra-high vacuum chemical vapour deposition has been developed and the first Esaki diodes are reported for this growth method. Intrinsic SiGe-layers are grown on highly boron-doped p(+)-Si layers, while post-growth proximity rapid thermal diffusion of phosphorous into the SiGe is employed to form an n(+)-layer. Tunnel diodes with a depletion layer width of about 6 nm have been realised in Si0.74Ge0.26, showing a peak current density of 0.18 kA/cm(2) and a current peak-to-valley ratio of 2.6 at room temperature.
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| 35. |
- Wernersson, Sven, et al.
(författare)
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Backbone H-1, C-13, and N-15 resonance assignments of BoMan26A, a -mannanase of the glycoside hydrolase family 26 from the human gut bacterium Bacteroides ovatus
- 2019
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Ingår i: Biomolecular NMR Assignments. - : Springer Science and Business Media LLC. - 1874-2718 .- 1874-270X. ; 13:1, s. 213-218
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Tidskriftsartikel (refereegranskat)abstract
- Bacteroides ovatus is a member of the human gut microbiota. The importance of this microbial consortium involves the degradation of complex dietary glycans mainly conferred by glycoside hydrolases. In this study we focus on one such catabolic glycoside hydrolase from B. ovatus. The enzyme, termed BoMan26A, is a -mannanase that takes part in the hydrolytic degradation of galactomannans. The crystal structure of BoMan26A has previously been determined to reveal a TIM-barrel like fold, but the relation between the protein structure and the mode of substrate processing has not yet been studied. Here we report residue-specific assignments for 95% of the 344 backbone amides of BoMan26A. The assignments form the basis for future studies of the relationship between substrate interactions and protein dynamics. In particular, the potential role of loops adjacent to glycan binding sites is of interest for such studies.
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| 36. |
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| 37. |
- Xiang, Yang, et al.
(författare)
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Trap-aware compact modeling and power-performance assessment of III-V tunnel FET
- 2019
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Ingår i: 2018 IEEE SOI-3D-Subthreshold Microelectronics Technology Unified Conference, S3S 2018. - 9781538676264
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Konferensbidrag (refereegranskat)abstract
- We report, for the first time, on a SPICE simulation study of the circuit-level power-performance impact of device traps in a state-of-the-art III-V heterojunction tunnel FET (TFET). First, the individual parasitic effects of junction bulk traps and oxide interface traps are incorporated in a compact model and validated against measurement-calibrated TCAD data, where we propose an analytical formulation for trap-assisted tunneling at the heterojunction and account for the oxide interface charge with a look-up table. Then, the model is used in SPICE simulations on a ring oscillator test bench to predict the impact of traps on logic circuits. It is found that bulk and oxide traps in TFET together cause up to ∼5x iso-frequency energy penalty in the desired low-supply-voltage domain (0.50 V), of which oxide traps dominate at high switching activity while bulk and oxide traps contribute comparably when switching is less active. This study quantitatively suggests that trap reduction is the key to the enablement of the full benefit of TFET.
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| 38. |
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| 39. |
- Yan, WX, et al.
(författare)
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BLISS is a versatile and quantitative method for genome-wide profiling of DNA double-strand breaks
- 2017
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8, s. 15058-
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Tidskriftsartikel (refereegranskat)abstract
- Precisely measuring the location and frequency of DNA double-strand breaks (DSBs) along the genome is instrumental to understanding genomic fragility, but current methods are limited in versatility, sensitivity or practicality. Here we present Breaks Labeling In Situ and Sequencing (BLISS), featuring the following: (1) direct labelling of DSBs in fixed cells or tissue sections on a solid surface; (2) low-input requirement by linear amplification of tagged DSBs by in vitro transcription; (3) quantification of DSBs through unique molecular identifiers; and (4) easy scalability and multiplexing. We apply BLISS to profile endogenous and exogenous DSBs in low-input samples of cancer cells, embryonic stem cells and liver tissue. We demonstrate the sensitivity of BLISS by assessing the genome-wide off-target activity of two CRISPR-associated RNA-guided endonucleases, Cas9 and Cpf1, observing that Cpf1 has higher specificity than Cas9. Our results establish BLISS as a versatile, sensitive and efficient method for genome-wide DSB mapping in many applications.
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| 40. |
- Ågerstrand, Marlene, et al.
(författare)
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Opportunities to tackle antibiotic resistance development in the aquatic environment through the Water Framework Directive
- 2023
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Ingår i: Ambio. - : Springer Science and Business Media LLC. - 0044-7447 .- 1654-7209. ; 52:5, s. 941-951
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Tidskriftsartikel (refereegranskat)abstract
- Antibiotics are critical components of modern health care. Protecting their efficacy through managing the rise in antibiotic resistance is therefore a global concern. It is not known to what extent environmental pollution from antibiotics contributes to the development of resistance, but encountered concentrations are frequently above concentrations predicted to select for resistance. Hence, measures are needed to manage risks. Here, we analyse if the indirect health risks from antibiotics in the aquatic environment can be considered in the context of the EU Water Framework Directive and the setting of environmental quality standards (EQS). By scrutinising current legislation, we conclude that it is possible to take the indirect health risks from antimicrobial resistance into account when deriving EQS for substances with antibiotic activity. We base this on the following conclusions: (1) human health concerns can be the main driver when setting an EQS, (2) an EQS can be based on data not specified in the guidance document, and (3) there are no restrictions against establishing EQS using data on antimicrobial resistance properties. In addition, since antimicrobial resistance travel across borders, we see strong reasons to prioritise setting these EQS on the EU level over the national level. Even though there is no agreed-upon method for how to develop EQS protective against resistance selection, there are several suggestions available in the literature and a couple of examples of regulatory initiatives. Also, addressing antimicrobial resistance through the Water Framework Directive can act as a driving force for other applicable legislation where such risks are not considered. We end by providing a set of recommendations for the European Commission and the Members States' future work on addressing aquatic pollution and antimicrobial resistance.
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