| 1. |
- Amann, F., et al.
(författare)
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A search for murarregamma at the level of 10-13
- 1991
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Ingår i: Proceedings of the 25th International Conference on High Energy Physics. - 9810024347 ; , s. 1070-1071
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Konferensbidrag (refereegranskat)abstract
- The MEGA experiment, which is a search for the decay murarregamma with a branching ratio sensitivity of about 10-13, employs highly modular, fast detectors, state-of-the-art electronics, and a staged trigger with on-line filters. The detectors are contained in a 1.5-T solenoidal field produced by a superconducting magnet. Positrons are confined to the central region and are measured by a set of thin MWPCs. Photons are measured by one of four layers of pair spectrometers in the outer region. Most aspects of the design have been validated in engineering runs; data taking will begin in 1990 with much of the electron arm and one pair spectrometer layer installed.
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| 2. |
- Szymanski, J. J., et al.
(författare)
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A study of the decay mu –> e gamma by the MEGA experiment
- 1996
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Ingår i: Proceedings, 9th Meeting, DPF'96, Minneapolis, USA, August 11-15, 1996. Vol. 1, 2.. ; , s. 1450-1452
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Konferensbidrag (refereegranskat)
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| 3. |
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| 4. |
- Ahmed, M., et al.
(författare)
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Search for the lepton-family-number nonconserving decay μ +→e +γ
- 2002
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Ingår i: Physical Review D. - : American Physical Society. - 1550-7998 .- 1550-2368. ; 65:11
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Tidskriftsartikel (refereegranskat)abstract
- The MEGA experiment, which searched for the muon- and electron-number violating decay μ +→e + γ, is described. The spectrometer system, the calibrations, the data taking procedures, the data analysis, and the sensitivity of the experiment are discussed. The most stringent upper limit on the branching ratio, B(μ + →e + γ)<1.2×10 -11 with 90% confidence, is derived from a likelihood analysis.
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| 5. |
- Szymanski, J. J., et al.
(författare)
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MEGA : A search for the decay mu –> e gamma
- 1994
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Ingår i: Intersections between particle and nuclear physics. Proceedings, 5th Conference, St. Petersburg, USA, May 31-June 6, 1994. ; , s. 789-792
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Konferensbidrag (refereegranskat)
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| 6. |
- Kulmala, M., et al.
(författare)
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General overview: European Integrated project on Aerosol Cloud Climate and Air Quality interactions (EUCAARI) - integrating aerosol research from nano to global scales
- 2011
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Ingår i: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 11:24, s. 13061-13143
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Tidskriftsartikel (refereegranskat)abstract
- In this paper we describe and summarize the main achievements of the European Aerosol Cloud Climate and Air Quality Interactions project (EUCAARI). EUCAARI started on 1 January 2007 and ended on 31 December 2010 leaving a rich legacy including: (a) a comprehensive database with a year of observations of the physical, chemical and optical properties of aerosol particles over Europe, (b) comprehensive aerosol measurements in four developing countries, (c) a database of airborne measurements of aerosols and clouds over Europe during May 2008, (d) comprehensive modeling tools to study aerosol processes fron nano to global scale and their effects on climate and air quality. In addition a new Pan-European aerosol emissions inventory was developed and evaluated, a new cluster spectrometer was built and tested in the field and several new aerosol parameterizations and computations modules for chemical transport and global climate models were developed and evaluated. These achievements and related studies have substantially improved our understanding and reduced the uncertainties of aerosol radiative forcing and air quality-climate interactions. The EUCAARI results can be utilized in European and global environmental policy to assess the aerosol impacts and the corresponding abatement strategies.
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| 7. |
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| 8. |
- Ng, M Y M, et al.
(författare)
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Meta-analysis of 32 genome-wide linkage studies of schizophrenia
- 2009
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 14:8, s. 774-785
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Tidskriftsartikel (refereegranskat)abstract
- A genome scan meta-analysis (GSMA) was carried out on 32 independent genome-wide linkage scan analyses that included 3255 pedigrees with 7413 genotyped cases affected with schizophrenia (SCZ) or related disorders. The primary GSMA divided the autosomes into 120 bins, rank-ordered the bins within each study according to the most positive linkage result in each bin, summed these ranks (weighted for study size) for each bin across studies and determined the empirical probability of a given summed rank (P(SR)) by simulation. Suggestive evidence for linkage was observed in two single bins, on chromosomes 5q (142-168 Mb) and 2q (103-134 Mb). Genome-wide evidence for linkage was detected on chromosome 2q (119-152 Mb) when bin boundaries were shifted to the middle of the previous bins. The primary analysis met empirical criteria for 'aggregate' genome-wide significance, indicating that some or all of 10 bins are likely to contain loci linked to SCZ, including regions of chromosomes 1, 2q, 3q, 4q, 5q, 8p and 10q. In a secondary analysis of 22 studies of European-ancestry samples, suggestive evidence for linkage was observed on chromosome 8p (16-33 Mb). Although the newer genome-wide association methodology has greater power to detect weak associations to single common DNA sequence variants, linkage analysis can detect diverse genetic effects that segregate in families, including multiple rare variants within one locus or several weakly associated loci in the same region. Therefore, the regions supported by this meta-analysis deserve close attention in future studies.
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| 9. |
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| 10. |
- Muller, J., et al.
(författare)
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Choroid Plexus Volume in Multiple Sclerosis vs Neuromyelitis Optica Spectrum Disorder A Retrospective, Cross-sectional Analysis
- 2022
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Ingår i: Neurology-Neuroimmunology & Neuroinflammation. - : Ovid Technologies (Wolters Kluwer Health). - 2332-7812. ; 9:3
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objectives The choroid plexus has been shown to play a crucial role in CNS inflammation. Previous studies found larger choroid plexus in multiple sclerosis (MS) compared with healthy controls. However, it is not clear whether the choroid plexus is similarly involved in MS and in neuromyelitis optica spectrum disorder (NMOSD). Thus, the aim of this study was to compare the choroid plexus volume in MS and NMOSD. Methods In this retrospective, cross-sectional study, patients were included by convenience sampling from 4 international MS centers. The choroid plexus of the lateral ventricles was segmented fully automatically on T1-weighted MRI sequences using a deep learning algorithm (Multi-Dimensional Gated Recurrent Units). Uni- and multivariable linear models were applied to investigate associations between the choroid plexus volume, clinically meaningful disease characteristics, and MRI parameters. Results We studied 180 patients with MS and 98 patients with NMOSD. In total, 94 healthy individuals and 47 patients with migraine served as controls. The choroid plexus volume was larger in MS (median 1,690 mu L, interquartile range [IQR] 648 mu L) than in NMOSD (median 1,403 mu L, IQR 510 mu L), healthy individuals (median 1,533 mu L, IQR 570 mu L), and patients with migraine (median 1,404 mu L, IQR 524 mu L; all p < 0.001), whereas there was no difference between NMOSD, migraine, and healthy controls. This was also true when adjusted for age, sex, and the intracranial volume. In contrast to NMOSD, the choroid plexus volume in MS was associated with the number of T2-weighted lesions in a linear model adjusted for age, sex, total intracranial volume, disease duration, relapses in the year before MRI, disease course, Expanded Disability Status Scale score, disease-modifying treatment, and treatment duration (beta 4.4; 95% CI 0.78-8.1; p = 0.018). Discussion This study supports an involvement of the choroid plexus in MS in contrast to NMOSD and provides clues to better understand the respective pathogenesis.
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| 11. |
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| 12. |
- Horvath, I., et al.
(författare)
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A European Respiratory Society technical standard: exhaled biomarkers in lung disease
- 2017
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 49:4
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Tidskriftsartikel (refereegranskat)abstract
- Breath tests cover the fraction of nitric oxide in expired gas (FeNO), volatile organic compounds (VOCs), variables in exhaled breath condensate (EBC) and other measurements. For EBC and for FeNO, official recommendations for standardised procedures are more than 10 years old and there is none for exhaled VOCs and particles. The aim of this document is to provide technical standards and recommendations for sample collection and analytic approaches and to highlight future research priorities in the field. For EBC and FeNO, new developments and advances in technology have been evaluated in the current document. This report is not intended to provide clinical guidance on disease diagnosis and management. Clinicians and researchers with expertise in exhaled biomarkers were invited to participate. Published studies regarding methodology of breath tests were selected, discussed and evaluated in a consensus-based manner by the Task Force members. Recommendations for standardisation of sampling, analysing and reporting of data and suggestions for research to cover gaps in the evidence have been created and summarised. Application of breath biomarker measurement in a standardised manner will provide comparable results, thereby facilitating the potential use of these biomarkers in clinical practice.
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| 13. |
- Monks, P. S., et al.
(författare)
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Atmospheric composition change : global and regional air quality
- 2009
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Ingår i: Atmospheric Environment. - : Elsevier BV. - 1352-2310 .- 1873-2844. ; 43:33, s. 5268-5350
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Forskningsöversikt (refereegranskat)abstract
- Air quality transcends all scales with in the atmosphere from the local to the global with handovers and feedbacks at each scale interaction. Air quality has manifold effects on health, ecosystems heritage and, climate. In this review the state of scientific understanding in relation to global and regional air quality is outlined. The review discusses air quality, in terms of emissions, processing and transport of trace gases and aerosols. New insights into the characterization of both natural and anthropogenic emissions are reviewed looking at both natural (e.g. dust and lightning) as well as plant emissions. Trends in anthropogenic emissions both by region and globally are discussed as well as biomass burning emissions. In terms of chemical processing the major air quality elements of ozone, non-methane hydrocarbons, nitrogen oxides and aerosols are covered. A number of topics are presented as a way of integrating the process view into the atmospheric context; these include the atmospheric oxidation efficiency, halogen and HOx chemistry, nighttime chemistry, tropical chemistry, heat waves, megacities, biomass burning and the regional hot spot of the Mediterranean. New findings with respect to the transport of pollutants across the scales are discussed, in particular the move to quantify the impact of long-range transport on regional air quality. Gaps and research questions that remain intractable are identified. The review concludes with a focus of research and policy questions for the coming decade. In particular, the policy challenges for concerted air quality and climate change policy (co-benefit) are discussed.
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| 14. |
- Schlueter, C., et al.
(författare)
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New HAXPES Applications at PETRA III
- 2018
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Ingår i: Synchrotron Radiation News. - : Informa UK Limited. - 0894-0886 .- 1931-7344. ; 31:4, s. 29-35
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Tidskriftsartikel (refereegranskat)
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| 15. |
- Schlueter, C., et al.
(författare)
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The new dedicated HAXPES beamline P22 at PETRAIII
- 2019
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Ingår i: 13th International Conference on Synchrotron Radiation Instrumentation (SRI2018). - : American Institute of Physics (AIP). - 9780735417823
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Konferensbidrag (refereegranskat)abstract
- A new undulator beamline (P22) for hard X-ray photoelectron spectroscopy (HAXPES) was built at PETRA III (DESY, Hamburg) to meet the increasing demand for HAXPES-based techniques. It provides four special instruments for high-resolution studies of the electronic and chemical structure of functional nano-materials and catalytic interfaces, with a focus on measurements under operando and/or ambient conditions: (i) a versatile solid-state spectroscopy setup with optional wide-angle lens and in-situ electrical characterization, (ii) a HAXPEEM instrument for sub-µm spectro-microscopy applications, (iii) an ambient pressure system (> 1 bar) for operando studies of catalytic reactions and (iv) a time-of-flight spectrometer as a full-field k-microscope for measurements of the 4D spectral function ρ(EB,k). The X-ray optics were designed to deliver high brightness photon flux within the HAXPES energy range 2.4 – 15 keV. An LN2-cooled double-crystal monochromator with interchangeable pairs of Si(111) and (311) crystals is optionally combined with a double channel-cut post-monochromator to generate X-rays with variable energy bandpass adapted to the needs of the experiment. Additionally, the beam polarization can be varied using a diamond phase plate integrated into the beamline. Adaptive beam focusing is realized by Be compound refractive lenses and/or horizontally deflecting mirrors down to a spot size of ∼20x17 µm2 with a flux of up to 1.1x1013 ph/s (for Si(111) at 6 keV).
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| 16. |
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| 17. |
- Arafin, S., et al.
(författare)
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Comprehensive analysis of electrically-pumped GaSb-based VCSELs
- 2011
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Ingår i: Optics Express. - 1094-4087 .- 1094-4087. ; 19:18, s. 17267-17282
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Tidskriftsartikel (refereegranskat)abstract
- This paper discusses several performance-related aspects of electrically-pumped GaSb-based buried tunnel junction VCSELs with an emission wavelength of 2.6 mu m based on theoretical and experimental results. These results allow a deeper insight into the internal device physics, such as radial diffusion of carriers, maximum continuous-wave operating temperature, diffraction loss, internal temperature, gain and loss parameters, internal quantum efficiency of the active region etc. These parameters can be taken into account while designing mid-infrared lasers which leads to an improved device performance. A simple thermal model of the devices based on the two-dimensional (2-D) finite element method using the material data from the literature is also presented. In addition, an application-based result utilizing these lasers for the measurement of absolute water vapor concentration by wavelength modulation spectroscopy (WMS) method are also described, hinting that devices are well-suited for the targeted sensing applications.
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| 18. |
- Arafin, S., et al.
(författare)
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Large-Area Single-Mode GaSb-based VCSELs using an Inverted Surface Relief
- 2010
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Ingår i: 23rd Annual Meeting of the IEEE Photonics Society, PHOTINICS 2010. - 9781424453689 ; , s. 61-62
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Konferensbidrag (refereegranskat)abstract
- Large-area GaSb-based BTJ VCSELs at ∼2.35 μm were fabricated using an inverted surface relief technique to support the single transverse mode operation. The devices operate in continuous-wave and are (electro-)thermally tunable over 6 nm.
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| 19. |
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| 20. |
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| 21. |
- Elmer, Steven, et al.
(författare)
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Effects of Locomotor Muscle Fatigue on Joint-specific Power Production During Cycling
- 2012
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Ingår i: Medicine & Science in Sports & Exercise. - 0195-9131 .- 1530-0315. ; 44:8, s. 1504-1511
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: Previous authors have reported reductions in maximum power after high-intensity cycling exercise. Exercise-induced changes in power produced by ankle, knee, and hip joint actions (joint-specific powers), however, have not been reported. PURPOSE: To evaluate joint-specific power production during a cycling time trial (TT) and also compare pre- to post-TT changes in maximal cycling (MAXcyc) joint-specific powers. METHODS: Ten cyclists performed MAXcyc trials (90rpm) before and after a 10min TT (28810W, 90rpm). Pedal forces and limb kinematics were determined with a force-sensing pedal and an instrumented spatial linkage, respectively. Joint-specific powers were calculated and averaged over complete pedal cycles and over extension and flexion phases. RESULTS: Pedal and joint-specific powers did not change during the TT. Pedal power produced during post-TT MAXcyc was reduced by 323% (P<0.001) relative to pre-TT. Relative changes in ankle plantar flexion (435%) and knee flexion powers (525%) were similar but were greater than changes in knee extension (124%) and hip extension powers (286%) (both P<0.05). Pedal and joint-specific powers produced during post-TT MAXcyc were greater than those powers produced during the final 3s of the TT (P<0.01). CONCLUSION: Exercise-induced changes in MAXcyc power manifested with differential power loss at each joint action with ankle plantar flexion and knee flexion exhibiting relatively greater fatigue than knee extension and hip extension. However, changes in MAXcyc joint-specific powers were not presaged by changes in TT joint-specific powers. We conclude that fatigue induced via high-intensity cycling does not alter submaximal joint-specific powers but has distinct functional consequences for MAXcyc joint-specific powers
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| 22. |
- Kalucka, J, et al.
(författare)
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Kidney injury is independent of endothelial HIF-1α
- 2015
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Ingår i: Journal of molecular medicine (Berlin, Germany). - : Springer Science and Business Media LLC. - 1432-1440 .- 0946-2716. ; 93:8, s. 891-904
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Tidskriftsartikel (refereegranskat)
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| 23. |
- Kienhöfer, D, et al.
(författare)
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No evidence of pathogenic involvement of cathelicidins in patient cohorts and mouse models of lupus and arthritis
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:12, s. 1-19
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Tidskriftsartikel (refereegranskat)abstract
- Apart from their role in the immune defence against pathogens evidence of a role of antimicrobial peptides (AMPs) in autoimmune diseases has accumulated in the past years. The aim of this project was to examine the functional impact of the human cathelicidin LL-37 and the mouse cathelicidin-related AMP (CRAMP) on the pathogenesis of lupus and arthritis. Serum LL-37 and anti-LL-37 levels were measured by ELISA in healthy donors and patients with Systemic Lupus Erythematosus (SLE) and Rheumatoid arthritis (RA). Pristane-induced lupus was induced in female wild type (WT) and cathelicidin-deficient (CRAMP-/-) mice. Serum levels of anti-Sm/RNP, anti-dsDNA, and anti-histone were determined via ELISA, cytokines in sera and peritoneal lavages were measured via Multiplex. Expression of Interferon I stimulated genes (ISG) was determined by real-time PCR. Collagen-induced arthritis (CIA) was induced in male WT and CRAMP-/- mice and arthritis severity was visually scored and analysed histomorphometrically by OsteoMeasure software. Serum levels of anti-LL-37 were higher in SLE-patients compared to healthy donors or patients with RA. However, no correlation to markers of disease activity or organ involvement was observed. No significant differences of autoantibody or cytokine/chemokine levels, or of expression of ISGs were observed between WT and CRAMP-/- mice after pristane-injection. Furthermore, lung and kidney pathology did not differ in the absence of CRAMP. Incidence and severity of CIA and histological parameters (inflammation, cartilage degradation, and bone erosion) were not different in WT and CRAMP-/- mice. Although cathelicidins are upregulated in mouse models of lupus and arthritis, cathelicidin-deficiency did not persistently affect the diseases. Also in patients with SLE, autoantibodies against cathelicidins did not correlate with disease manifestation. Reactivity against cathelicidins in lupus and arthritis could thus be an epiphenomenon caused by extensive overexpression in blood and affected tissues. In addition, other cationic AMPs could functionally compensate for the deficiency of cathelicidins.
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| 24. |
- Kyrpides, Nikos C, et al.
(författare)
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Genomic encyclopedia of bacteria and archaea: sequencing a myriad of type strains.
- 2014
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Ingår i: PLoS biology. - : Public Library of Science (PLoS). - 1545-7885. ; 12:8
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Tidskriftsartikel (refereegranskat)abstract
- Microbes hold the key to life. They hold the secrets to our past (as the descendants of the earliest forms of life) and the prospects for our future (as we mine their genes for solutions to some of the planet's most pressing problems, from global warming to antibiotic resistance). However, the piecemeal approach that has defined efforts to study microbial genetic diversity for over 20 years and in over 30,000 genome projects risks squandering that promise. These efforts have covered less than 20% of the diversity of the cultured archaeal and bacterial species, which represent just 15% of the overall known prokaryotic diversity. Here we call for the funding of a systematic effort to produce a comprehensive genomic catalog of all cultured Bacteria and Archaea by sequencing, where available, the type strain of each species with a validly published name (currently∼11,000). This effort will provide an unprecedented level of coverage of our planet's genetic diversity, allow for the large-scale discovery of novel genes and functions, and lead to an improved understanding of microbial evolution and function in the environment.
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| 25. |
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| 26. |
- Lopez-Posadas, R., et al.
(författare)
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Rho-A prenylation and signaling link epithelial homeostasis to intestinal inflammation
- 2016
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Ingår i: Journal of Clinical Investigation. - : American Society for Clinical Investigation. - 0021-9738 .- 1558-8238. ; 126:2, s. 611-626
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Tidskriftsartikel (refereegranskat)abstract
- Although defects in intestinal barrier function are a key pathogenic factor in patients with inflammatory bowel diseases (IBDs), the molecular pathways driving disease-specific alterations of intestinal epithelial cells (IECs) are largely unknown. Here, we addressed this issue by characterizing the transcriptome of IECs from IBD patients using a genome-wide approach. We observed disease-specific alterations in IECs with markedly impaired Rho-A signaling in active IBD patients. Localization of epithelial Rho-A was shifted to the cytosol in IBDs, and inflammation was associated with suppressed Rho-A activation due to reduced expression of the Rho-A prenylation enzyme geranylgeranyltransferase-I (GGTase-l). Functionally, we found that mice with conditional loss of Rhoa or the gene encoding GGTase-1, Pggtlb, in IECs exhibit spontaneous chronic intestinal inflammation with accumulation of granulocytes and CD4(+) T cells. This phenotype was associated with cytoskeleton rearrangement and aberrant cell shedding, ultimately leading to loss of epithelial integrity and subsequent inflammation. These findings uncover deficient prenylation of Rho-A as a key player in the pathogenesis of IBDs. As therapeutic triggering of Rho-A signaling suppressed intestinal inflammation in mice with GGTase-l-deficient IECs, our findings suggest new avenues for treatment of epithelial injury and mucosal inflammation in IBD patients.
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| 27. |
- Martens, A, et al.
(författare)
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An optimized, robust and reproducible protocol to generate well-differentiated primary nasal epithelial models from extremely premature infants
- 2019
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 20069-
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Tidskriftsartikel (refereegranskat)abstract
- Extremely premature infants are prone to severe respiratory infections, and the mechanisms underlying this exceptional susceptibility are largely unknown. Nasal epithelial cells (NEC) represent the first-line of defense and adult-derived ALI cell culture models show promising results in mimicking in vivo physiology. Therefore, the aim of this study was to develop a robust and reliable protocol for generating well-differentiated cell culture models from NECs of extremely premature infants. Nasal brushing was performed in 13 extremely premature infants at term corrected age and in 11 healthy adult controls to obtain NECs for differentiation at air-liquid interface (ALI). Differentiation was verified using imaging and functional analysis. Successful isolation and differentiation was achieved for 5 (38.5%) preterm and 5 (45.5%) adult samples. Preterm and adult ALI-cultures both showed well-differentiated morphology and ciliary function, however, preterm cultures required significantly longer cultivation times for acquiring full differentiation (44 ± 3.92 vs. 23 ± 1.83 days; p < 0.0001). Moreover, we observed that recent respiratory support may impair successful NECs isolation. Herewithin, we describe a safe, reliable and reproducible method to generate well-differentiated ALI-models from NECs of extremely premature infants. These models provide a valuable foundation for further studies regarding immunological and inflammatory responses and respiratory disorders in extremely premature infants.
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| 28. |
- Martinez-Sanchez, LD, et al.
(författare)
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Epithelial RAC1-dependent cytoskeleton dynamics controls cell mechanics, cell shedding and barrier integrity in intestinal inflammation
- 2023
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Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 72:2, s. 275-294
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Tidskriftsartikel (refereegranskat)abstract
- Increased apoptotic shedding has been linked to intestinal barrier dysfunction and development of inflammatory bowel diseases (IBD). In contrast, physiological cell shedding allows the renewal of the epithelial monolayer without compromising the barrier function. Here, we investigated the role of live cell extrusion in epithelial barrier alterations in IBD.DesignTaking advantage of conditional GGTase and RAC1 knockout mice in intestinal epithelial cells (Pggt1biΔIECandRac1iΔIECmice), intravital microscopy, immunostaining, mechanobiology, organoid techniques and RNA sequencing, we analysed cell shedding alterations within the intestinal epithelium. Moreover, we examined human gut tissue and intestinal organoids from patients with IBD for cell shedding alterations and RAC1 function.ResultsEpithelialPggt1bdeletion led to cytoskeleton rearrangement and tight junction redistribution, causing cell overcrowding due to arresting of cell shedding that finally resulted in epithelial leakage and spontaneous mucosal inflammation in the small and to a lesser extent in the large intestine. Both in vivo and in vitro studies (knockout mice, organoids) identified RAC1 as a GGTase target critically involved in prenylation-dependent cytoskeleton dynamics, cell mechanics and epithelial cell shedding. Moreover, inflamed areas of gut tissue from patients with IBD exhibited funnel-like structures, signs of arrested cell shedding and impaired RAC1 function. RAC1 inhibition in human intestinal organoids caused actin alterations compatible with arresting of cell shedding.ConclusionImpaired epithelial RAC1 function causes cell overcrowding and epithelial leakage thus inducing chronic intestinal inflammation. Epithelial RAC1 emerges as key regulator of cytoskeletal dynamics, cell mechanics and intestinal cell shedding. Modulation of RAC1 might be exploited for restoration of epithelial integrity in the gut of patients with IBD.
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| 29. |
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| 30. |
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| 31. |
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| 32. |
- Orthofer, M, et al.
(författare)
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Identification of ALK in Thinness
- 2020
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Ingår i: Cell. - : Elsevier BV. - 1097-4172 .- 0092-8674. ; 181:6, s. 1246-
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Tidskriftsartikel (refereegranskat)
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| 33. |
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| 34. |
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| 35. |
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| 36. |
- Wang, WZ, et al.
(författare)
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Predicting ROR1/BCL2 combination targeted therapy of small cell carcinoma of the lung
- 2021
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Ingår i: Cell death & disease. - : Springer Science and Business Media LLC. - 2041-4889. ; 12:6, s. 577-
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Tidskriftsartikel (refereegranskat)abstract
- Small cell lung cancer (SCLC) remains a deadly form of cancer, with a 5-year survival rate of less than 10 percent, necessitating novel therapies. Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is an oncofetal protein that is emerging as a therapeutic target and is co-expressed with BCL2 in multiple tumor types due to microRNA coregulation. We hypothesize that ROR1-targeted therapy is effective in small cell lung cancer and synergizes with therapeutic BCL2 inhibition. Tissue microarrays (TMAs) and formalin-fixed paraffin-embedded (FFPE) SCLC patient samples were utilized to determine the prevalence of ROR1 and BCL2 expression in SCLC. Eight SCLC-derived cell lines were used to determine the antitumor activity of a small molecule ROR1 inhibitor (KAN0441571C) alone and in combination with the BCL2 inhibitor venetoclax. The Chou-Talalay method was utilized to determine synergy with the drug combination. ROR1 and BCL2 protein expression was identified in 93% (52/56) and 86% (48/56) of SCLC patient samples, respectively. Similarly, ROR1 and BCL2 were shown by qRT-PCR to have elevated expression in 79% (22/28) and 100% (28/28) of SCLC patient samples, respectively. KAN0441571C displayed efficacy in 8 SCLC cell lines, with an IC50 of 500 nM or less. Synergy as defined by a combination index of <1 via the Chou-Talalay method between KAN0441571C and venetoclax was demonstrated in 8 SCLC cell lines. We have shown that ROR1 inhibition is synergistic with BCL2 inhibition in SCLC models and shows promise as a novel therapeutic target in SCLC.
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| 37. |
- Yarza, P., et al.
(författare)
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Sequencing orphan species initiative (SOS): Filling the gaps in the 16S rRNA gene sequence database for all species with validly published names
- 2013
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Ingår i: Systematic and Applied Microbiology. - : Elsevier BV. - 0723-2020. ; 36:1, s. 69-73
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Tidskriftsartikel (refereegranskat)abstract
- High quality 16S ribosomal RNA (rRNA) gene sequences from the type strains of all species with validly published names, as defined by the International Code of Nomenclature of Bacteria, are a prerequisite for their accurate affiliations within the global genealogical classification and for the recognition of potential new taxa. During the last few years, the Living Tree Project (LTP) has taken care to create a high quality, aligned 16S and 23S rRNA gene sequence database of all type strains. However, the manual curation of the sequence dataset and type strain information revealed that a total of 552 “orphan” species (about 5.7% of the currently classified species) had to be excluded from the reference trees. Among them, 322 type strains were not represented by an SSU entry in the public sequence repositories. The remaining 230 type strains had to be discarded due to bad sequence quality. Since 2010, the LTP team has coordinated a network of researchers and culture collections in order to improve the situation by (re)-sequencing the type strains of these “orphan” species. As a result, we can now report 351 16S rRNA gene sequences of type strains. Nevertheless, 201 species could not be sequenced because cultivable type strains were not available (121), the cultures had either been lost or were never deposited in the first place (66), or it was not possible due to other constraints (14). The International Code of Nomenclature of Bacteria provides a number of mechanisms to deal with the problem of missing type strains and we recommend that due consideration be given to the appropriate mechanisms in order to help solve some of these issues.
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