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| 2. |
- Pearce, Neil E, et al.
(author)
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IARC Monographs : 40 Years of Evaluating Carcinogenic Hazards to Humans
- 2015
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In: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 123:6, s. 507-514
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Journal article (peer-reviewed)abstract
- BACKGROUND: Recently the International Agency for Research on Cancer (IARC) Programme for the Evaluation of Carcinogenic Risks to Humans has been criticized for several of its evaluations, and also the approach used to perform these evaluations. Some critics have claimed that IARC Working Groups' failures to recognize study weaknesses and biases of Working Group members have led to inappropriate classification of a number of agents as carcinogenic to humans.OBJECTIVES: The authors of this paper are scientists from various disciplines relevant to the identification and hazard evaluation of human carcinogens. We have examined here criticisms of the IARC classification process to determine the validity of these concerns. We review the history of IARC evaluations and describe how the IARC evaluations are performed.DISCUSSION: We conclude that these recent criticisms are unconvincing. The procedures employed by IARC to assemble Working Groups of scientists from the various discipline and the techniques followed to review the literature and perform hazard assessment of various agents provide a balanced evaluation and an appropriate indication of the weight of the evidence. Some disagreement by individual scientists to some evaluations is not evidence of process failure. The review process has been modified over time and will undoubtedly be altered in the future to improve the process. Any process can in theory be improved, and we would support continued review and improvement of the IARC processes. This does not mean, however, that the current procedures are flawed.CONCLUSIONS: The IARC Monographs have made, and continue to make, major contributions to the scientific underpinning for societal actions to improve the public's health.
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| 3. |
- Kristan, M., et al.
(author)
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The Eighth Visual Object Tracking VOT2020 Challenge Results
- 2020
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In: Computer Vision. - Cham : Springer International Publishing. - 9783030682378 ; , s. 547-601
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Conference paper (peer-reviewed)abstract
- The Visual Object Tracking challenge VOT2020 is the eighth annual tracker benchmarking activity organized by the VOT initiative. Results of 58 trackers are presented; many are state-of-the-art trackers published at major computer vision conferences or in journals in the recent years. The VOT2020 challenge was composed of five sub-challenges focusing on different tracking domains: (i) VOT-ST2020 challenge focused on short-term tracking in RGB, (ii) VOT-RT2020 challenge focused on “real-time” short-term tracking in RGB, (iii) VOT-LT2020 focused on long-term tracking namely coping with target disappearance and reappearance, (iv) VOT-RGBT2020 challenge focused on short-term tracking in RGB and thermal imagery and (v) VOT-RGBD2020 challenge focused on long-term tracking in RGB and depth imagery. Only the VOT-ST2020 datasets were refreshed. A significant novelty is introduction of a new VOT short-term tracking evaluation methodology, and introduction of segmentation ground truth in the VOT-ST2020 challenge – bounding boxes will no longer be used in the VOT-ST challenges. A new VOT Python toolkit that implements all these novelites was introduced. Performance of the tested trackers typically by far exceeds standard baselines. The source code for most of the trackers is publicly available from the VOT page. The dataset, the evaluation kit and the results are publicly available at the challenge website (http://votchallenge.net ).
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| 4. |
- Lange, C., et al.
(author)
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Perspectives for personalized therapy for patients with multidrug-resistant tuberculosis
- 2018
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In: Journal of Internal Medicine. - : WILEY. - 0954-6820 .- 1365-2796. ; 284:2, s. 163-188
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Research review (peer-reviewed)abstract
- According to the World Health Organization (WHO), tuberculosis is the leading cause of death attributed to a single microbial pathogen worldwide. In addition to the large number of patients affected by tuberculosis, the emergence of Mycobacterium tuberculosis drug-resistance is complicating tuberculosis control in many high-burden countries. During the past 5years, the global number of patients identified with multidrug-resistant tuberculosis (MDR-TB), defined as bacillary resistance at least against rifampicin and isoniazid, the two most active drugs in a treatment regimen, has increased by more than 20% annually. Today we experience a historical peak in the number of patients affected by MDR-TB. The management of MDR-TB is characterized by delayed diagnosis, uncertainty of the extent of bacillary drug-resistance, imprecise standardized drug regimens and dosages, very long duration of therapy and high frequency of adverse events which all translate into a poor prognosis for many of the affected patients. Major scientific and technological advances in recent years provide new perspectives through treatment regimens tailor-made to individual needs. Where available, such personalized treatment has major implications on the treatment outcomes of patients with MDR-TB. The challenge now is to bring these adances to those patients that need them most.
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| 9. |
- Gabriel, J. P., et al.
(author)
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Locomotor pattern in the adult zebrafish spinal cord in vitro
- 2008
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In: Journal of Neurophysiology. - : American Physiological Society. - 0022-3077 .- 1522-1598. ; 99:1, s. 37-48
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Journal article (peer-reviewed)abstract
- The zebrafish is an attractive model system for studying the function of the spinal locomotor network by combining electrophysiological, imaging, and genetic approaches. Thus far, most studies have been focusing on embryonic and larval stages. In this study we have developed an in vitro preparation of the isolated spinal cord from adult zebrafish in which locomotor activity can be induced while the activity of single neurons can be monitored using whole cell recording techniques. Application of NMDA elicited rhythmic locomotor activity that was monitored by recording from muscles or ventral roots in semi-intact or isolated spinal cord preparations, respectively. This rhythmic activity displayed a left-right alternation and a rostrocaudal delay. Blockade of glycinergic synaptic transmission by strychnine switched the alternating activity into synchronous bursting in the left and right sides as well as along the rostrocaudal axis. Whole cell recordings from motoneurons showed that they receive phasic synaptic inputs that were correlated with the locomotor activity recorded in ventral roots. This newly developed in vitro preparation of the adult zebrafish spinal cord will allow examination of the organization of the spinal locomotor network in an adult system to complement studies in zebrafish larvae and new born rodents.
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| 12. |
- Skowronek, T., et al.
(author)
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Reissscheiben from shipwrecks as an indicator for copper qualities produced in the major middle and North European mining districts during the late medieval and early modern period 15th-17th Century AD
- 2021
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In: Journal of Archaeological Science-Reports. - : Elsevier BV. - 2352-409X. ; 39
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Journal article (peer-reviewed)abstract
- Major advances in maritime archaeology in the last 20 years resulted in the discovery of several shipwrecks carrying copper slab ingots, so-called Reissscheiben. With the interest in early modern metal trade growing, geochemical analysis of these raw copper ingots represents invaluable merit for understanding the various qualities produced in the major mining regions in Europe. Here, we present ICP-MS trace elemental and lead isotope data for 52 Reissscheiben ingots salvaged at three different findspots in northern European waters dating to the 15th and 16th century. Our results reveal the Reissscheiben to originate from two different mining centres, Slovakia and the southern Harz foreland. Copper produced in these regions shows significantly different trace elemental patterns probably affected by both different kinds of copper ores used and smelting processes applied. The analytical results reveal the difficulties that early modern copper smelters may have had to deal with when processing sulfidic copper ores, as it seems that refining processes were not understood sufficiently. On the other hand, the written historical sources suggest that early modern brass makers already had a proper understanding of which regions produced the most suitable copper qualities. This paper underlines the potential of using geochemical characterisation of early modern period metals for solving historical questions.
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| 14. |
- Brautigam, L, et al.
(author)
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Vertebrate-specific glutaredoxin is essential for brain development
- 2011
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 108:51, s. 20532-20537
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Journal article (peer-reviewed)abstract
- Cellular functions and survival are dependent on a tightly controlled redox potential. Currently, an increasing amount of data supports the concept of local changes in the redox environment and specific redox signaling events controlling cell function. Specific protein thiol groups are the major targets of redox signaling and regulation. Thioredoxins and glutaredoxins catalyze reversible thiol-disulfide exchange reactions and are primary regulators of the protein thiol redox state. Here, we demonstrate that embryonic brain development depends on the enzymatic activity of glutaredoxin 2. Zebrafish with silenced expression of glutaredoxin 2 lost virtually all types of neurons by apoptotic cell death and the ability to develop an axonal scaffold. As demonstrated in zebrafish and in a human cellular model for neuronal differentiation, glutaredoxin 2 controls axonal outgrowth via thiol redox regulation of collapsin response mediator protein 2, a central component of the semaphorin pathway. This study provides an example of a specific thiol redox regulation essential for vertebrate embryonic development.
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| 15. |
- Kamber, Umut, et al.
(author)
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Self-induced spin glass state in elemental and crystalline neodymium
- 2020
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In: Science. - : American Association for the Advancement of Science. - 0036-8075 .- 1095-9203. ; 368:6494
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Journal article (peer-reviewed)abstract
- Spin glasses are a highly complex magnetic state of matter intricately linked to spin frustration and structural disorder. They exhibit no long-range order and exude aging phenomena, distinguishing them from quantum spin liquids. We report a previously unknown type of spin glass state, the spin-Q glass, observable in bulk-like crystalline metallic neodymium thick films. Using spin-polarized scanning tunneling microscopy combined with ab initio calculations and atomistic spin-dynamics simulations, we visualized the variations in atomic-scale noncolinear order and its response to magnetic field and temperature. We quantified the aging phenomena relating the glassiness to crystalline symmetry and the energy landscape. This result not only resolves the long-standing debate of the magnetism of neodymium, but also suggests that glassiness may arise in other magnetic solids lacking extrinsic disorder.
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| 16. |
- Kok, Marleen, et al.
(author)
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PKA-induced phosphorylation of ER alpha at serine 305 and high PAK1 levels is associated with sensitivity to tamoxifen in ER-positive breast cancer
- 2011
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In: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 1573-7217 .- 0167-6806. ; 125:1, s. 1-12
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Journal article (peer-reviewed)abstract
- Phosphorylation of estrogen receptor alpha at serine 305 (ER alpha S305-P) by protein kinase A (PKA) or p21-activated kinase 1 (PAK1) has experimentally been associated with tamoxifen sensitivity. Here, we investigated the clinical application of this knowledge to predict tamoxifen resistance in ER-positive breast cancer patients. Using immunohistochemistry, a score including PAK1 and co-expression of PKA and ER alpha S305-P (PKA/ER alpha S305-P) was developed on a training set consisting of 103 patients treated with tamoxifen for metastatic disease, and validated on 231 patients randomized between adjuvant tamoxifen or no treatment. In the training set, PAK1 levels were associated with tumor progression after tamoxifen (HR 1.57, 95% CI 0.99-2.48), as was co-expression of PKA and ER alpha S305-P (HR 2.00, 95% CI 1.14-3.52). In the validation set, a significant tamoxifen benefit was found among the 73% patients negative for PAK1 and PKA/ER alpha S305-P (HR 0.54, 95% CI 0.34-0.87), while others (27%) were likely to have no benefit from tamoxifen (HR 0.88, 95% 0.42-1.82). The test for interaction showed a significant difference in recurrence-free survival between groups defined by PAK1 and PKA/ER alpha S305-P (P = 0.037). Elevated PAK1 and PKA/ER alpha S305-P appeared to influence tamoxifen sensitivity. Both PAK1 and PKA/ER alpha S305-P levels were associated with sensitivity to tamoxifen in breast tumors and the combination of these variables should be considered in predicting tamoxifen benefit.
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| 17. |
- Myrstener, Maria, et al.
(author)
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Resolving the Drivers of Algal Nutrient Limitation from Boreal to Arctic Lakes and Streams
- 2022
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In: Ecosystems (New York. Print). - : Springer-Verlag New York. - 1432-9840 .- 1435-0629. ; 25, s. 1682-1699
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Journal article (peer-reviewed)abstract
- Nutrient inputs to northern freshwaters are changing, potentially altering aquatic ecosystem functioning through effects on primary producers. Yet, while primary producer growth is sensitive to nutrient supply, it is also constrained by a suite of other factors, including light and temperature, which may play varying roles across stream and lake habitats. Here, we use bioassay results from 89 lakes and streams spanning northern boreal to Arctic Sweden to test for differences in nutrient limitation status of algal biomass along gradients in colored dissolved organic carbon (DOC), water temperature, and nutrient concentrations, and to ask whether there are distinct patterns and drivers between habitats. Single nitrogen (N) limitation or primary N-limitation with secondary phosphorus (P) limitation of algal biomass was the most common condition for streams and lakes. Average response to N-addition was a doubling in biomass; however, the degree of limitation was modulated by the distinct physical and chemical conditions in lakes versus streams and across boreal to Arctic regions. Overall, algal responses to N-addition were strongest at sites with low background concentrations of dissolved inorganic N. Low temperatures constrained biomass responses to added nutrients in lakes but had weaker effects on responses in streams. Further, DOC mediated the response of algal biomass to nutrient addition differently among lakes and streams. Stream responses were dampened at higher DOC, whereas lake responses to nutrient addition increased from low to moderate DOC but were depressed at high DOC. Our results suggest that future changes in nutrient availability, particularly N, will exert strong effects on the trophic state of northern freshwaters. However, we highlight important differences in the physical and chemical factors that shape algal responses to nutrient availability in different parts of aquatic networks, which will ultimately affect the integrated response of northern aquatic systems to ongoing environmental changes.
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