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| 3. |
- Klionsky, Daniel J., et al.
(author)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Research review (peer-reviewed)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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- Pfaller, M.A., et al.
(author)
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Twelve years of fluconazole in clinical practice : Global-trends in species distribution and fluconazole susceptibility of bloodstream isolates of Candida
- 2004
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In: Clinical Microbiology and Infection. - : Elsevier BV. - 1198-743X .- 1469-0691. ; 10:SUPPL. 1, s. 11-23
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Journal article (peer-reviewed)abstract
- We determined the species distribution and in-vitro susceptibility of 6082 bloodstream infection (BSI) isolates of Candida spp. collected from 250 medical centres in 32 nations over a 10-year period from 1992 through 2001. The species included 3401 C. albicans, 984 C. glabrata, 796 C. parapsilosis, 585 C. tropicalis, 153 C. krusei, 67 C. lusitaniae, 48 C. guilliermondii, 10 C. famata, 10 C. kefyr, six C. pelliculosa, five C. rugosa, four C. lipolytica, three C. dubliniensis, three C. inconspicua, two C. sake and one isolate each of C. lambica, C. norvegensis and C. zeylanoides. Minimum inhibitory concentration determinations were made using the National Committee for Clinical Laboratory Standards reference broth microdilution method. Variation in the rank order and frequency of the different species of Candida was observed over time and by geographic area. The proportion of BSI due to C. albicans and C. glabrata increased and C. parapsilosis decreased over time in Canada, the USA and Europe. C. glabrata was an infrequent cause of BSI in Latin America and the Asia-Pacific region. Very little variation in fluconazole susceptibility was observed among isolates of C. albicans, C. tropicalis and C. parapsilosis. These species accounted for 78% of all BSI and remained highly susceptible (91-100% susceptible) to fluconazole from 1992 to 2001 irrespective of geographic origin. The prevalence of fluconazole resistance among C. glabrata isolates was variable both over time and among the various countries and regions. Resistance to fluconazole among C. glabrata isolates was greatest in the USA and varied by US census region (range 0-23%). These observations are generally encouraging relative to the sustained usefulness of fluconazole as a systemically active antifungal agent for the treatment of candida BSI. © 2004 Copyright by the European Society of Clinical Microbiology and Infectious Diseases.
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- Fischer, U., et al.
(author)
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Early versus Later Anticoagulation for Stroke with Atrial Fibrillation
- 2023
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In: New England Journal of Medicine. - 0028-4793. ; 388:26, s. 2411-2421
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Journal article (peer-reviewed)abstract
- BackgroundThe effect of early as compared with later initiation of direct oral anticoagulants (DOACs) in persons with atrial fibrillation who have had an acute ischemic stroke is unclear.MethodsWe performed an investigator-initiated, open-label trial at 103 sites in 15 countries. Participants were randomly assigned in a 1:1 ratio to early anticoagulation (within 48 hours after a minor or moderate stroke or on day 6 or 7 after a major stroke) or later anticoagulation (day 3 or 4 after a minor stroke, day 6 or 7 after a moderate stroke, or day 12, 13, or 14 after a major stroke). Assessors were unaware of the trial-group assignments. The primary outcome was a composite of recurrent ischemic stroke, systemic embolism, major extracranial bleeding, symptomatic intracranial hemorrhage, or vascular death within 30 days after randomization. Secondary outcomes included the components of the composite primary outcome at 30 and 90 days.ResultsOf 2013 participants (37% with minor stroke, 40% with moderate stroke, and 23% with major stroke), 1006 were assigned to early anticoagulation and 1007 to later anticoagulation. A primary-outcome event occurred in 29 participants (2.9%) in the early-treatment group and 41 participants (4.1%) in the later-treatment group (risk difference, -1.18 percentage points; 95% confidence interval [CI], -2.84 to 0.47) by 30 days. Recurrent ischemic stroke occurred in 14 participants (1.4%) in the early-treatment group and 25 participants (2.5%) in the later-treatment group (odds ratio, 0.57; 95% CI, 0.29 to 1.07) by 30 days and in 18 participants (1.9%) and 30 participants (3.1%), respectively, by 90 days (odds ratio, 0.60; 95% CI, 0.33 to 1.06). Symptomatic intracranial hemorrhage occurred in 2 participants (0.2%) in both groups by 30 days.ConclusionsIn this trial, the incidence of recurrent ischemic stroke, systemic embolism, major extracranial bleeding, symptomatic intracranial hemorrhage, or vascular death at 30 days was estimated to range from 2.8 percentage points lower to 0.5 percentage points higher (based on the 95% confidence interval) with early than with later use of DOACs. (Funded by the Swiss National Science Foundation and others; ELAN ClinicalTrials.gov number, .)
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| 8. |
- Antonova, M., et al.
(author)
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Baby MIND : a magnetized segmented neutrino detector for the WAGASCI experiment
- 2017
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In: Journal of Instrumentation. - : IOP PUBLISHING LTD. - 1748-0221. ; 12
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Journal article (peer-reviewed)abstract
- T2K (Tokai-to-Kamioka) is a long-baseline neutrino experiment in Japan designed to study various parameters of neutrino oscillations. Anear detector complex (ND280) is located 280m downstream of the production target and measures neutrino beam parameters before any oscillations occur. ND280's measurements are used to predict the number and spectra of neutrinos in the Super-Kamiokande detector at the distance of 295 km. The difference in the target material between the far (water) and near (scintillator, hydrocarbon) detectors leads to the main non-cancelling systematic uncertainty for the oscillation analysis. In order to reduce this uncertainty a new WAter-Grid-And-SCintillator detector (WAGASCI) has been developed. A magnetized iron neutrino detector (Baby MIND) will be used to measure momentum and charge identification of the outgoing muons from charged current interactions. The Baby MIND modules are composed of magnetized iron plates and long plastic scintillator bars read out at the both ends with wavelength shifting fibers and silicon photomultipliers. The front-end electronics board has been developed to perform the readout and digitization of the signals from the scintillator bars. Detector elements were tested with cosmic rays and in the PS beam at CERN. The obtained results are presented in this paper.
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| 9. |
- Antonova, M., et al.
(author)
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Synchronization of the distributed readout frontend electronics of the Baby MIND detector
- 2017
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In: 2017 XXVI International Scientific Conference Electronics (ET). - : IEEE. - 9781538617533
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Conference paper (peer-reviewed)abstract
- Baby MIND is a new downstream muon range detector for the WGASCI experiment. This article discusses the distributed readout system and its timing requirements. The paper presents the design of the synchronization subsystem and the results of its test.
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| 11. |
- Antonova, M., et al.
(author)
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Baby MIND : a magnetized segmented neutrino detector for the WAGASCI experiment
- 2017
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In: Journal of Instrumentation. - : Institute of Physics (IOP). - 1748-0221. ; 12:07, s. 1-6
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Journal article (peer-reviewed)abstract
- T2K (Tokai-to-Kamioka) is a long-baseline neutrino experiment in Japan designed to study various parameters of neutrino oscillations. A near detector complex (ND280) is located 280 m downstream of the production target and measures neutrino beam parameters before any oscillations occur. ND280’s measurements are used to predict the number and spectra of neutrinos in the Super-Kamiokande detector at the distance of 295 km. The difference in the target material between the far (water) and near (scintillator, hydrocarbon) detectors leads to the main non-cancelling systematic uncertainty for the oscillation analysis. In order to reduce this uncertainty a new WAter-Grid-And-SCintillator detector (WAGASCI) has been developed. A magnetized iron neutrino detector (Baby MIND) will be used to measure momentum and charge identification of the outgoing muons from charged current interactions. The Baby MIND modules are composed of magnetized iron plates and long plastic scintillator bars read out at the both ends with wavelength shifting fibers and silicon photomultipliers. The front-end electronics board has been developed to perform the readout and digitization of the signals from the scintillator bars. Detector elements were tested with cosmic rays and in the PS beam at CERN. The obtained results are presented in this paper.
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| 12. |
- Antonova, M., et al.
(author)
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Proposal for characterization of muon spectrometers for neutrino beam lines with the Baby MIND
- 2015
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Reports (other academic/artistic)abstract
- Neutrino detectors based on state-of-the-art plastic scintillators read out with solid state photo-sensors, as well as new magnetization schemes, have been developed in the framework of AIDA. Meaningful size prototypes are under construction. In the framework of the CERN neutrino platform, we propose to test a Totally Active Scintillator Detector (TASD) and a prototype of a Magnetized Iron Neutrino Detector (MIND), called Baby MIND in the H8 beam line in 2016-2018. The design of the detectors and the purpose and plans for the beam tests are presented. An opportunity to use the Baby MIND detector in a real neutrino beam at JPARC for the measurement of the cross-section ratio between Water and scintillator (WAGASCI experiment) is described.
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| 13. |
- Magnusson, Joel, 1991, et al.
(author)
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Laser-Particle Collider for Multi-GeV Photon Production
- 2019
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In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 122:25
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Journal article (peer-reviewed)abstract
- As an alternative to Compton backscattering and bremsstrahlung, the process of colliding high-energy electron beams with strong laser fields can more efficiently provide both a cleaner and brighter source of photons in the multi-GeV range for fundamental studies in nuclear and quark-gluon physics. In order to favor the emission of high-energy quanta and minimize their decay into electron-positron pairs, the fields must not only be sufficiently strong, but also well localized. We here examine these aspects and develop the concept of a laser-particle collider tailored for high-energy photon generation. We show that the use of multiple colliding laser pulses with 0.4 PW of total power is capable of converting more than 18% of multi-GeV electrons passing through the high-field region into photons, each of which carries more than half of the electron initial energy. © 2019 authors. Published by the American Physical Society.
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| 15. |
- Richards, Stephen, et al.
(author)
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Genome Sequence of the Pea Aphid Acyrthosiphon pisum
- 2010
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In: PLoS biology. - : Public Library of Science (PLoS). - 1544-9173 .- 1545-7885. ; 8:2, s. e1000313-
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Journal article (peer-reviewed)abstract
- Aphids are important agricultural pests and also biological models for studies of insect-plant interactions, symbiosis, virus vectoring, and the developmental causes of extreme phenotypic plasticity. Here we present the 464 Mb draft genome assembly of the pea aphid Acyrthosiphon pisum. This first published whole genome sequence of a basal hemimetabolous insect provides an outgroup to the multiple published genomes of holometabolous insects. Pea aphids are host-plant specialists, they can reproduce both sexually and asexually, and they have coevolved with an obligate bacterial symbiont. Here we highlight findings from whole genome analysis that may be related to these unusual biological features. These findings include discovery of extensive gene duplication in more than 2000 gene families as well as loss of evolutionarily conserved genes. Gene family expansions relative to other published genomes include genes involved in chromatin modification, miRNA synthesis, and sugar transport. Gene losses include genes central to the IMD immune pathway, selenoprotein utilization, purine salvage, and the entire urea cycle. The pea aphid genome reveals that only a limited number of genes have been acquired from bacteria; thus the reduced gene count of Buchnera does not reflect gene transfer to the host genome. The inventory of metabolic genes in the pea aphid genome suggests that there is extensive metabolite exchange between the aphid and Buchnera, including sharing of amino acid biosynthesis between the aphid and Buchnera. The pea aphid genome provides a foundation for post-genomic studies of fundamental biological questions and applied agricultural problems.
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| 16. |
- Savitz, Sean I., et al.
(author)
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Stem Cell Therapy as an Emerging Paradigm for Stroke (STEPS) II
- 2011
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In: Stroke. - 0039-2499. ; 42:3, s. 825-829
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Research review (peer-reviewed)abstract
- Cell-based therapies represent a new therapeutic approach for stroke. In 2007, investigators from academia, industry leaders, and members of the National Institutes of Health crafted recommendations to facilitate the translational development of cellular therapies as a novel, emerging modality for stroke from animal studies to clinical trials. This meeting was called Stem Cell Therapies as an Emerging Paradigm in Stroke (STEPS) and was modeled on the format of the Stroke Therapy Academic Industry Roundtable (STAIR) meetings. Since publication of the original STEPS guidelines, there has been an explosive growth in the number of cellular products and in the number of new laboratory discoveries that impact the safety and potential efficacy of cell therapies for stroke. Any successful development of a cell product will need to take into consideration several factors, including the preclinical safety and efficacy profile, cell characterization, delivery route, in vivo biodistribution, and mechanism of action. In 2010, a second meeting called STEPS 2 was held to bring together clinical and basic science researchers with industry, regulatory, and National Institutes of Health representatives. At this meeting, participants identified critical gaps in knowledge and research areas that require further studies, updated prior guidelines, and drafted new recommendations to create a framework to guide future investigations in cell-based therapies for stroke.
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| 19. |
- Holland, John, et al.
(author)
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Use of IC information in Japanese financial firms
- 2012
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In: Journal of Intellectual Capital. - : Emerald Group Publishing Limited. - 1469-1930 .- 1758-7468. ; 13:4, s. 562-581
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Journal article (peer-reviewed)abstract
- Purpose - The purpose of this paper is to explore how Japanese Financial Institutions (JFI) acquire and use company intellectual capital (IC) information and other associated intangibles information in their common structured and routine equity investment decisions and how this activity contributed to knowledge creation in the JFIs concerning knowledge of companies, markets and emotions.Design/methodogy/approach – The research employed a multi-case design, using four JFI cases. The JFIs and their IC use were discussed in terms of Nonaka and Toyama’s ’theory of the knowledge creating firm’ (2005). The associated concepts of ‘Ba’, ‘SECI’ and ‘Kata’ were conceptually located within the internal and external order emerging in the cases and were used to analyze JFI knowledge creating behavior. Despite the limits to SECI or Kata processes noted in the cases, these concepts were valuable in analyzing the case data.Findings – Company IC information contributed to earnings estimates and company valuation. Impressionistic and emotional information about intangibles contributed to JFI feelings and confidence in their valuation and information use. Both led to investment decisions. JFI knowledge was an important component of the key interacting and informed contexts used by JFIs to make collective sense of these different but complementary types of information in investment decision making. This created opportunities for improved disclosure and accountability between JFIs and their investee companies. Common patterns of behaviour across the JFIs were counterbalanced by variety and differences noted in JFI behaviour. These included differences in JFI investment philosophy and ‘landscape’.Practical implication – The findings provide important insights in how JFI knowledge creating patterns could limit or progress a common language of communication between companies and markets on the subject of intellectual capital. This could impact on the quality of corporate disclosure and accountability processes. The results will be used in the context of a further development of the Disclosure of Intellectual Assets Based Management in Japan.Originality – The paper combines ideas from the ‘knowledge creating firm’ with conventional ideas of finance, and of disclosure and accountability. This combined theoretical analysis demonstrated a novel and robust theoretical context to interpret the unique Japanese case data, and the distinctive empirical patterns emerging from it.
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| 20. |
- Johanson, Ulf, 1944-, et al.
(author)
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Japanese Financial Institutions and their use of company intangibles informationin company investment decisions – Ba, SECI, Kata and JFIs as knowledge creatingfirms.
- 2010
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Other publication (peer-reviewed)abstract
- The purpose of this paper is to explore how Japanese Financial Institutions (JFI)acquire and use company intellectual capital (IC) information and other associated intangiblesinformation in their common structured and routine equity investment decisions and how thisactivity contributed to knowledge creation in the JFIs concerning knowledge of companies,markets and emotions. Company IC information contributed to earnings estimates and companyvaluation. Impressionistic and emotional information about intangibles contributed to JFIfeelings and confidence in their valuation and information use. Both led to investmentdecisions. JFI knowledge was an important component of the key interacting and informedcontexts used by JFIs to make collective sense of these different but complementary types ofinformation in investment decision making. This created opportunities for improveddisclosure and accountability between JFIs and their investee companies. Common patterns ofbehaviour across the JFIs were counterbalanced by variety and differences noted in JFIbehaviour. These included differences in JFI investment philosophy and ‘landscape’.
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| 28. |
- Zeichner, Sarah S., et al.
(author)
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Polycyclic aromatic hydrocarbons in samples of Ryugu formed in the interstellar medium
- 2023
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In: Science. - : AMER ASSOC ADVANCEMENT SCIENCE. - 0036-8075 .- 1095-9203. ; 382:6677, s. 1411-1415
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Journal article (peer-reviewed)abstract
- Polycyclic aromatic hydrocarbons (PAHs) contain less than or similar to 20% of the carbon in the interstellar medium. They are potentially produced in circumstellar environments (at temperatures greater than or similar to 1000 kelvin), by (similar to 10 kelvin) interstellar clouds, or by processing of carbon-rich dust grains. We report isotopic properties of PAHs extracted from samples of the asteroid Ryugu and the meteorite Murchison. The doubly-C-13 substituted compositions (Delta 2x(13)C values) of the PAHs naphthalene, fluoranthene, and pyrene are 9 to 51 parts per thousand higher than values expected for a stochastic distribution of isotopes. The Delta 2x(13)C values are higher than expected if the PAHs formed in a circumstellar environment, but consistent with formation in the interstellar medium. By contrast, the PAHs phenanthrene and anthracene in Ryugu samples have Delta 2x(13)C values consistent with formation by higher-temperature reactions.
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