| 1. |
- Aamodt, K., et al.
(författare)
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The ALICE experiment at the CERN LHC
- 2008
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Ingår i: Journal of Instrumentation. - 1748-0221. ; 3:S08002
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Forskningsöversikt (refereegranskat)abstract
- ALICE (A Large Ion Collider Experiment) is a general-purpose, heavy-ion detector at the CERN LHC which focuses on QCD, the strong-interaction sector of the Standard Model. It is designed to address the physics of strongly interacting matter and the quark-gluon plasma at extreme values of energy density and temperature in nucleus-nucleus collisions. Besides running with Pb ions, the physics programme includes collisions with lighter ions, lower energy running and dedicated proton-nucleus runs. ALICE will also take data with proton beams at the top LHC energy to collect reference data for the heavy-ion programme and to address several QCD topics for which ALICE is complementary to the other LHC detectors. The ALICE detector has been built by a collaboration including currently over 1000 physicists and engineers from 105 Institutes in 30 countries, Its overall dimensions are 16 x 16 x 26 m(3) with a total weight of approximately 10 000 t. The experiment consists of 18 different detector systems each with its own specific technology choice and design constraints, driven both by the physics requirements and the experimental conditions expected at LHC. The most stringent design constraint is to cope with the extreme particle multiplicity anticipated in central Pb-Pb collisions. The different subsystems were optimized to provide high-momentum resolution as well as excellent Particle Identification (PID) over a broad range in momentum, up to the highest multiplicities predicted for LHC. This will allow for comprehensive studies of hadrons, electrons, muons, and photons produced in the collision of heavy nuclei. Most detector systems are scheduled to be installed and ready for data taking by mid-2008 when the LHC is scheduled to start operation, with the exception of parts of the Photon Spectrometer (PHOS), Transition Radiation Detector (TRD) and Electro Magnetic Calorimeter (EMCal). These detectors will be completed for the high-luminosity ion run expected in 2010. This paper describes in detail the detector components as installed for the first data taking in the summer of 2008.
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| 2. |
- Dancet, Eline A F, et al.
(författare)
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The Role of Scientists and Clinicians in Raising Public Support for Animal Research in Reproductive Biology and Medicine.
- 2012
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Ingår i: Biology of reproduction. - : Oxford University Press (OUP). - 1529-7268 .- 0006-3363.
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Tidskriftsartikel (refereegranskat)abstract
- It is important that researchers active in reproductive animal research, as a group, clearly and compassionately convey specific information to students, patients, and the general public on the merit and need for biomedical research using various formats and seek active support from patient organizations, universities, politicians, celebrities, the media, and international professional organizations related to human and animal health.
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| 3. |
- Alme, J., et al.
(författare)
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The ALICE TPC, a large 3-dimensional tracking device with fast readout for ultra-high multiplicity events
- 2010
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Ingår i: Nuclear Instruments & Methods in Physics Research. Section A: Accelerators, Spectrometers, Detectors, and Associated Equipment. - : Elsevier BV. - 0167-5087 .- 0168-9002. ; 622:1, s. 316-367
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Tidskriftsartikel (refereegranskat)abstract
- The design, construction, and commissioning of the ALICE Time-Projection Chamber (TPC) is described. It is the main device for pattern recognition, tracking, and identification of charged particles in the ALICE experiment at the CERN LHC. The TPC is cylindrical in shape with a volume close to 90 m(3) and is operated in a 0.5T solenoidal magnetic field parallel to its axis. In this paper we describe in detail the design considerations for this detector for operation in the extreme multiplicity environment of central Pb-Pb collisions at LHC energy. The implementation of the resulting requirements into hardware (field cage, read-out chambers, electronics), infrastructure (gas and cooling system, laser-calibration system), and software led to many technical innovations which are described along with a presentation of all the major components of the detector, as currently realized. We also report on the performance achieved after completion of the first round of stand-alone calibration runs and demonstrate results close to those specified in the TPC Technical Design Report. (C) 2010 CERN for the benefit of the ALICE collaboration. Published by Elsevier B.V. All rights reserved.
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- Oprea, Tudor I, et al.
(författare)
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Unexplored therapeutic opportunities in the human genome
- 2018
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Ingår i: Nature Reviews Drug Discovery. - : Springer Science and Business Media LLC. - 1474-1776 .- 1474-1784. ; 17:5, s. 317-332
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Tidskriftsartikel (refereegranskat)abstract
- A large proportion of biomedical research and the development of therapeutics is focused on a small fraction of the human genome. In a strategic effort to map the knowledge gaps around proteins encoded by the human genome and to promote the exploration of currently understudied, but potentially druggable, proteins, the US National Institutes of Health launched the Illuminating the Druggable Genome (IDG) initiative in 2014. In this article, we discuss how the systematic collection and processing of a wide array of genomic, proteomic, chemical and disease-related resource data by the IDG Knowledge Management Center have enabled the development of evidence-based criteria for tracking the target development level (TDL) of human proteins, which indicates a substantial knowledge deficit for approximately one out of three proteins in the human proteome. We then present spotlights on the TDL categories as well as key drug target classes, including G protein-coupled receptors, protein kinases and ion channels, which illustrate the nature of the unexplored opportunities for biomedical research and therapeutic development.
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| 5. |
- Beaumont, Robin N, et al.
(författare)
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Genome-wide association study of placental weight identifies distinct and shared genetic influences between placental and fetal growth.
- 2023
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Ingår i: Nature genetics. - 1546-1718 .- 1061-4036. ; 55:11, s. 1807-19
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Tidskriftsartikel (refereegranskat)abstract
- A well-functioning placenta is essential for fetal and maternal health throughout pregnancy. Using placental weight as a proxy for placental growth, we report genome-wide association analyses in the fetal (n=65,405), maternal (n=61,228) and paternal (n=52,392) genomes, yielding 40 independent association signals. Twenty-six signals are classified as fetal, four maternal and three fetal and maternal. A maternal parent-of-origin effect is seen near KCNQ1. Genetic correlation and colocalization analyses reveal overlap with birth weight genetics, but 12 loci are classified as predominantly or only affecting placental weight, with connections to placental development and morphology, and transport of antibodies and amino acids. Mendelian randomization analyses indicate that fetal genetically mediated higher placental weight is causally associated with preeclampsia risk and shorter gestational duration. Moreover, these analyses support the role of fetal insulin in regulating placental weight, providing a key link between fetal and placental growth.
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| 11. |
- Asikainen, S, et al.
(författare)
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Antibiotika vid parodontala behandlingar
- 2002
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Ingår i: Tandläkartidningen. ; 94, s. 26-33
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Forskningsöversikt (refereegranskat)abstract
- Inom parodontalvården kan systemisk behandling med lämpligt antibiotikum i vissa situationer vara indicerad som ett tillägg till konventionell behandling, till exempel vid akuta infektioner, snabbt progredierande former av parodontit (inkluderande juvenil parodontit) och hos patienter med komprometterat immunsystem. Denna terapeutiska ansats grundas på uppfattningen att den marginala parodontiten i dess olika former kan anses vara en endogen polymikrobiell opportunistisk infektion där en ekologisk obalans uppstått, varvid vissa så kallade parodontitpatogena bakteriearter kommit att dominera. Eftersom det är näst intill omöjligt att kliniskt diagnostisera en pågående parodontal destruktion kan diagnostiken lämpligen kompletteras med en mikrobiologisk analys. Val av antibiotikum görs på basis av dessa diagnostiska kriterier. Då infektionerna är att betrakta som endogena kan vi inte räkna med att eliminera dessa parodontitpatogener, däremot kan vi med antibiotika hämma deras aktivitet och kontrollera deras tillväxt. För att uppnå en bestående parodontal hälsa krävs att de parodontala vävnaderna efter behandling åter kan anses vara fria från inflammation och uppvisa ett reducerat, men friskt, fäste. Lokal behandling med olika antibiotika finns som behandlingsform men det saknas alltjämt studier som övertygande visar bättre kliniska långtidseffekter när subgingival depuration kombineras med lokal antibiotikabehandling än de resultat som kan uppnås med enbart konserverande parodontal behandling.
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| 16. |
- Graae, Bente J., et al.
(författare)
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Stay or go - how topographic complexity influences alpine plant population and community responses to climate change
- 2018
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Ingår i: Perspectives in plant ecology, evolution and systematics. - : Elsevier BV. - 1433-8319 .- 1618-0437. ; 30, s. 41-50
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Tidskriftsartikel (refereegranskat)abstract
- In the face of climate change, populations have two survival options - they can remain in situ and tolerate the new climatic conditions (stay), or they can move to track their climatic niches (go). For sessile and small-stature organisms like alpine plants, staying requires broad climatic tolerances, realized niche shifts due to changing biotic interactions, acclimation through plasticity, or rapid genetic adaptation. Going, in contrast, requires good dispersal and colonization capacities. Neither the magnitude of climate change experienced locally nor the capacities required for staying/going in response to climate change are constant across landscapes, and both aspects may be strongly affected by local microclimatic variation associated with topographic complexity. We combine ideas from population and community ecology to discuss the effects of topographic complexity in the landscape on the immediate stay or go opportunities of local populations and communities, and on the selective pressures that may have shaped the stay or go capacities of the species occupying contrasting landscapes. We demonstrate, using example landscapes of different topographical complexity, how species' thermal niches could be distributed across these landscapes, and how these, in turn, may affect many population and community ecological processes that are related to adaptation or dispersal. Focusing on treeless alpine or Arctic landscapes, where temperature is expected to be a strong determinant, our theorethical framework leads to the hypothesis that populations and communities of topographically complex (rough and patchy) landscapes should be both more resistant and more resilient to climate change than those of topographically simple (flat and homogeneous) landscapes. Our theorethical framework further points to how meta-community dynamics such as mass effects in topographically complex landscapes and extinction lags in simple landscapes, may mask and delay the long-term outcomes of these landscape differences under rapidly changing climates.
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- Skotte, Line, et al.
(författare)
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Genome-wide association study of febrile seizures implicates fever response and neuronal excitability genes
- 2022
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Ingår i: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 145:2, s. 555-568
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Tidskriftsartikel (refereegranskat)abstract
- Febrile seizures represent the most common type of pathological brain activity in young children and are influenced by genetic, environmental and developmental factors. In a minority of cases, febrile seizures precede later development of epilepsy. We conducted a genome-wide association study of febrile seizures in 7635 cases and 83 966 controls identifying and replicating seven new loci, all with P < 5 × 10-10. Variants at two loci were functionally related to altered expression of the fever response genes PTGER3 and IL10, and four other loci harboured genes (BSN, ERC2, GABRG2, HERC1) influencing neuronal excitability by regulating neurotransmitter release and binding, vesicular transport or membrane trafficking at the synapse. Four previously reported loci (SCN1A, SCN2A, ANO3 and 12q21.33) were all confirmed. Collectively, the seven novel and four previously reported loci explained 2.8% of the variance in liability to febrile seizures, and the single nucleotide polymorphism heritability based on all common autosomal single nucleotide polymorphisms was 10.8%. GABRG2, SCN1A and SCN2A are well-established epilepsy genes and, overall, we found positive genetic correlations with epilepsies (rg = 0.39, P = 1.68 × 10-4). Further, we found that higher polygenic risk scores for febrile seizures were associated with epilepsy and with history of hospital admission for febrile seizures. Finally, we found that polygenic risk of febrile seizures was lower in febrile seizure patients with neuropsychiatric disease compared to febrile seizure patients in a general population sample. In conclusion, this largest genetic investigation of febrile seizures to date implicates central fever response genes as well as genes affecting neuronal excitability, including several known epilepsy genes. Further functional and genetic studies based on these findings will provide important insights into the complex pathophysiological processes of seizures with and without fever.
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| 21. |
- Solé Navais, Pol, et al.
(författare)
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Genetic effects on the timing of parturition and links to fetal birth weight.
- 2023
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Ingår i: Nature genetics. - 1546-1718. ; 55:4, s. 559-567
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Tidskriftsartikel (refereegranskat)abstract
- The timing of parturition is crucial for neonatal survival and infant health. Yet, its genetic basis remains largely unresolved. We present a maternal genome-wide meta-analysis of gestational duration (n=195,555), identifying 22 associated loci (24 independent variants) and an enrichment in genes differentially expressed during labor. A meta-analysis of preterm delivery (18,797 cases, 260,246 controls) revealed six associated loci and large genetic similarities with gestational duration. Analysis of the parental transmitted and nontransmitted alleles (n=136,833) shows that 15 of the gestational duration genetic variants act through the maternal genome, whereas 7 act both through the maternal and fetal genomes and 2 act only via the fetal genome. Finally, the maternal effects on gestational duration show signs of antagonistic pleiotropy with the fetal effects on birth weight: maternal alleles that increase gestational duration have negative fetal effects on birth weight. The present study provides insights into the genetic effects on the timing of parturition and the complex maternal-fetal relationship between gestational duration and birth weight.
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| 22. |
- Westergaard, H.B., et al.
(författare)
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A critical appraisal of the use of umbilical artery Doppler ultrasound in high-risk pregnancies: use of meta-analyses in evidence-based obstetrics
- 2001
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Ingår i: Ultrasound in Obstetrics & Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 17:6, s. 466-476
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To reanalyze randomized controlled trials on the use of umbilical artery Doppler velocimetry in high-risk pregnancies and determine which high-risk pregnancies benefit from the use of Doppler velocimetry, Methods Searching Medline, the Cochrane Library and Embase we found 13 randomized controlled trials on the use of Doppler velocimetry in high-risk pregnancies. Of these, six included pregnancies with strictly defined suspected intrauterine growth restriction and/or hypertensive disease of pregnancy ('well-defined studies;); the rest included a great variety of high-risk pregnancies (general risk studies'). The studies were analyzed with particular regard 50 the heterogeneity and to outcome. Audits of the perinatal deaths reported in the randomized controlled trials were performed by a panel of 32 international experts. Results The 'well-defined studies ' had a more uniform study design as compared to the 'general risk studies' and they showed a significant reduction in antenatal admissions (odds ratio, 0.56; 95% confidence interval, 0.43 - 0. 72), inductions of labor (0. 78; 0.63 -0. 96), elective deliveries (inductions of labor and elective Cesarean sections) (0. 73; 0.61-0.88) and Cesarean sections (0. 78; 0, 65 - 0. 94). By perinatal audit it was found that more perinatal deaths in the 'well-defined studies' were potentially avoidable by use of Doppler velocimetry (P < 0.0005) and the rate of avoidable perinatal deaths was higher among controls (50%) than cases (20%) in this group. Conclusion The randomized controlled trials on umbilical artery Doppler velocimetry show major differences regarding study design and technical and clinical issues and, therefore, they should not be pooled in a simple meta-analysis. By stratification it was found that only in pregnancies with suspected intrauterine growth restriction and/or hypertensive disease of pregnancy will the use of umbilical artery Doppler velocimetry reduce the number of perinatal deaths and unnecessary obstetric interventions.
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