| 1. |
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| 2. |
- Bravo, L, et al.
(author)
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- 2021
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swepub:Mat__t
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| 3. |
- Tabiri, S, et al.
(author)
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- 2021
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swepub:Mat__t
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| 4. |
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| 5. |
- Niemi, MEK, et al.
(author)
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- 2021
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swepub:Mat__t
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| 6. |
- Glasbey, JC, et al.
(author)
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- 2021
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swepub:Mat__t
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| 7. |
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| 8. |
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| 9. |
- Bousquet, J, et al.
(author)
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Nrf2-interacting nutrients and COVID-19: time for research to develop adaptation strategies
- 2020
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In: Clinical and translational allergy. - : Wiley. - 2045-7022. ; 10:1, s. 58-
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Journal article (peer-reviewed)abstract
- There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPARγ:Peroxisome proliferator-activated receptor, NFκB: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2α:Elongation initiation factor 2α). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT1R axis (AT1R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity.
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| 10. |
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| 11. |
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| 12. |
- Schiller, D, et al.
(author)
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The Human Affectome
- 2024
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In: Neuroscience and biobehavioral reviews. - 1873-7528. ; 158, s. 105450-
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Journal article (peer-reviewed)
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| 13. |
- Saccardi, R, et al.
(author)
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Benchmarking of survival outcomes following Haematopoietic Stem Cell Transplantation (HSCT): an update of the ongoing project of the European Society for Blood and Marrow Transplantation (EBMT) and Joint Accreditation Committee of ISCT and EBMT (JACIE)
- 2023
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In: Bone marrow transplantation. - : Springer Science and Business Media LLC. - 1476-5365 .- 0268-3369. ; 58:6, s. 659-666
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Journal article (peer-reviewed)abstract
- From 2016 EBMT and JACIE developed an international risk-adapted benchmarking program of haematopoietic stem cell transplant (HSCT) outcome to provide individual EBMT Centers with a means of quality-assuring the HSCT process and meeting FACT-JACIE accreditation requirements relating to 1-year survival outcomes. Informed by previous experience from Europe, North America and Australasia, the Clinical Outcomes Group (COG) established criteria for patient and Center selection, and a set of key clinical variables within a dedicated statistical model adapted to the capabilities of the EBMT Registry. The first phase of the project was launched in 2019 to test the acceptability of the benchmarking model through assessment of Centers’ performance for 1-year data completeness and survival outcomes of autologous and allogeneic HSCT covering 2013–2016. A second phase was delivered in July 2021 covering 2015–2019 and including survival outcomes. Reports of individual Center performance were shared directly with local principal investigators and their responses were assimilated. The experience thus far has supported the feasibility, acceptability and reliability of the system as well as identifying its limitations. We provide a summary of experience and learning so far in this ‘work in progress’, as well as highlighting future challenges of delivering a modern, robust, data-complete, risk-adapted benchmarking program across new EBMT Registry systems.
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| 14. |
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| 15. |
- Ginolfi, M., et al.
(author)
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Detection of companion galaxies around hot dust-obscured hyper-luminous galaxy W0410-0913
- 2022
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 13:1
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Journal article (peer-reviewed)abstract
- The phase transition between galaxies and quasars is often identified with the rare population of hyper-luminous, hot dust-obscured galaxies. Galaxy formation models predict these systems to grow via mergers, that can deliver large amounts of gas toward their centers, induce intense bursts of star formation and feed their supermassive black holes. Here we report the detection of 24 galaxies emitting Lyman-α emission on projected physical scales of about 400 kpc around the hyper-luminous hot dust-obscured galaxy W0410-0913, at redshift z = 3.631, using Very Large Telescope observations. While this indicates that W0410-0913 evolves in a very dense environment, we do not find clear signs of mergers that could sustain its growth. Data suggest that if mergers occurred, as models expect, these would involve less massive satellites, with only a moderate impact on the internal interstellar medium of W0410-0913, which is sustained by a rotationally-supported fast-rotating molecular disk, as Atacama Large Millimeter Array observations suggest.
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| 16. |
- Heintz, K. E., et al.
(author)
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The Gas and Stellar Content of a Metal-poor Galaxy at z = 8.496 as Revealed by JWST and ALMA
- 2023
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In: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 944:2
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Journal article (peer-reviewed)abstract
- We present a joint analysis of the galaxy S04590 at z = 8.496 based on NIRSpec, NIRCam, and NIRISS observations obtained as part of the Early Release Observations program of the James Webb Space Telescope (JWST) and the far-infrared [C ii] 158 μm emission line detected by dedicated Atacama Large Millimeter/submillimeter Array (ALMA) observations. We determine the physical properties of S04590 from modeling of the spectral energy distribution (SED) and through the redshifted optical nebular emission lines detected with JWST/NIRSpec. The best-fit SED model reveals a low-mass (M ⋆ = 107.2-108 M ⊙) galaxy with a low oxygen abundance of 12 + log ( O / H ) = 7.16 − 0.12 + 0.10 derived from the strong nebular and auroral emission lines. Assuming that [C ii] effectively traces the interstellar medium, we estimate the total gas mass of the galaxy to be M gas = (8.0 ± 4.0) × 108 M ⊙ based on the luminosity and spatial extent of [C ii]. This yields an exceptionally high gas fraction, f gas = M gas/(M gas + M ⋆) ≳ 90%, though one still consistent with the range expected for low metallicity. We further derive the metal mass of the galaxy based on the gas mass and gas-phase metallicity, which we find to be consistent with the expected metal production from Type II supernovae. Finally, we make the first constraints on the dust-to-gas (DTG) and dust-to-metal (DTM) ratios of galaxies in the epoch of reionization at z ≳ 6, showing overall low mass ratios of logDTG < −3.8 and logDTM < −0.5, though they are consistent with established scaling relations and in particular with those of the local metal-poor galaxy I Zwicky 18. Our analysis highlights the synergy between ALMA and JWST in characterizing the gas, metal, and stellar content of the first generation of galaxies.
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| 17. |
- Janko, Matthew R., et al.
(author)
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In situ bypass and extra-anatomic bypass procedures result in similar survival in patients with secondary aortoenteric fistulas
- 2021
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In: Journal of Vascular Surgery. - : Elsevier. - 0741-5214 .- 1097-6809. ; 73:1, s. 210-221.e1
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Journal article (peer-reviewed)abstract
- Objective: The optimal revascularization modality in secondary aortoenteric fistula (SAEF) remains unclear in the literature. The purpose of this investigation was to determine the revascularization approach associated with the lowest morbidity and mortality using real-world data in patients with SAEF. Methods: A retrospective, multi-institutional study of SAEF from 2002 to 2014 was performed using a standardized database. Baseline demographics, comorbidities, and operative and postoperative variables were recorded. The primary outcome was long-term mortality. Descriptive statistics, Kaplan-Meier survival analysis, and univariate and multivariate analyses were performed. Results: During the study period, 182 patients at 34 institutions from 11 countries presented with SAEF (median age, 72 years; 79% male). The initial aortic procedures that resulted in SAEF were 138 surgical grafts (76%) and 42 endografts (23%), with 2 unknown; 102 of the SAEFs (56%) underwent complete excision of infected aortic graft material, followed by in situ (in-line) bypass (ISB), including antibiotic-soaked prosthetic graft (53), autogenous femoral vein (neoaortoiliac surgery; 17), cryopreserved allograft (28), and untreated prosthetic grafts (4). There were 80 patients (44%) who underwent extra-anatomic bypass (EAB) with infected graft excision. Overall median Kaplan-Meier estimated survival was 319 days (interquartile range, 20-2410 days). Stratified by EAB vs ISB, there was no significant difference in Kaplan-Meier estimated survival (P = .82). In comparing EAB vs ISB, EAB patients were older (74 vs 70 years; P = .01), had less operative hemorrhage (1200 mL vs 2000 mL; P = .04), were more likely to initiate dialysis within 30 days postoperatively (15% vs 5%; P = .02), and were less likely to experience aorta-related hemorrhage within 30 days postoperatively (3% aortic stump dehiscence vs 11% anastomotic rupture; P = .03). There were otherwise no significant differences in presentation, comorbidities, and intraoperative or postoperative variables. Multivariable Cox regression showed that the duration of antibiotic use (hazard ratio, 0.92; 95% confidence interval, 0.86-0.98; P = .01) and rifampin use at time of discharge (hazard ratio, 0.20; 95% confidence interval, 0.05-0.86; P = .03) independently decreased mortality. Conclusions: These data suggest that ISB does not offer a survival advantage compared with EAB and does not decrease the risk of postoperative aorta-related hemorrhage. After repair, <50% of SAEF patients survive 10-months. Each week of antibiotic use decreases mortality by 8%. Further study with risk modeling is imperative for this population. (J Vasc Surg 2021;73:210-21.)
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| 18. |
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| 19. |
- Snowden, JA, et al.
(author)
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Benchmarking of survival outcomes following haematopoietic stem cell transplantation: A review of existing processes and the introduction of an international system from the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE)
- 2020
-
In: Bone marrow transplantation. - : Springer Science and Business Media LLC. - 1476-5365 .- 0268-3369. ; 55:4, s. 681-694
-
Journal article (peer-reviewed)abstract
- In many healthcare settings, benchmarking for complex procedures has become a mandatory requirement by competent authorities, regulators, payers and patients to assure clinical performance, cost-effectiveness and safe care of patients. In several countries inside and outside Europe, benchmarking systems have been established for haematopoietic stem cell transplantation (HSCT), but access is not universal. As benchmarking is now integrated into the FACT-JACIE standards, the EBMT and JACIE established a Clinical Outcomes Group (COG) to develop and introduce a universal system accessible across EBMT members. Established systems from seven European countries (United Kingdom, Italy, Belgium, France, Germany, Spain, Switzerland), USA and Australia were appraised, revealing similarities in process, but wide variations in selection criteria and statistical methods. In tandem, the COG developed the first phase of a bespoke risk-adapted international benchmarking model for one-year survival following allogeneic and autologous HSCT based on current capabilities within the EBMT registry core dataset. Data completeness, which has a critical impact on validity of centre comparisons, is also assessed. Ongoing development will include further scientific validation of the model, incorporation of further variables (when appropriate) alongside implementation of systems for clinically meaningful interpretation and governance aiming to maximise acceptance to centres, clinicians, payers and patients across EBMT.
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| 20. |
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| 21. |
- Janko, Matthew, et al.
(author)
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Contemporary Outcomes After Partial Resection of Infected Aortic Grafts
- 2021
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In: Annals of Vascular Surgery. - : Elsevier. - 0890-5096 .- 1615-5947. ; 76, s. 202-210
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Journal article (peer-reviewed)abstract
- INTRODUCTION: Aortic graft infection remains a considerable clinical challenge, and it is unclear which variables are associated with adverse outcomes among patients undergoing partial resection.METHODS: A retrospective, multi-institutional study of patients who underwent partial resection of infected aortic grafts from 2002 to 2014 was performed using a standard database. Baseline demographics, comorbidities, operative, and postoperative variables were recorded. The primary outcome was mortality. Descriptive statistics, Kaplan-Meier (KM) survival analysis, and Cox regression analysis were performed.RESULTS: One hundred fourteen patients at 22 medical centers in 6 countries underwent partial resection of an infected aortic graft. Seventy percent were men with median age 70 years. Ninety-seven percent had a history of open aortic bypass graft: 88 (77%) patients had infected aortobifemoral bypass, 18 (16%) had infected aortobiiliac bypass, and 1 (0.8%) had an infected thoracic graft. Infection was diagnosed at a median 4.3 years post-implant. All patients underwent partial resection followed by either extra-anatomic (47%) or in situ (53%) vascular reconstruction. Median follow-up period was 17 months (IQR 1, 50 months). Thirty-day mortality was 17.5%. The KM-estimated median survival from time of partial resection was 3.6 years. There was no significant survival difference between those undergoing in situ reconstruction or extra-anatomic bypass (P = 0.6). During follow up, 72% of repairs remained patent and 11% of patients underwent major amputation. On univariate Cox regression analysis, Candida infection was associated with increased risk of mortality (HR 2.4; P = 0.01) as well as aortoenteric fistula (HR 1.9, P = 0.03). Resection of a single graft limb only to resection of abdominal (graft main body) infection was associated with decreased risk of mortality (HR 0.57, P = 0.04), as well as those with American Society of Anesthesiologists classification less than 3 (HR 0.35, P = 0.04). Multivariate analysis did not reveal any factors significantly associated with mortality. Persistent early infection was noted in 26% of patients within 30 days postoperatively, and 39% of patients were found to have any post-repair infection during the follow-up period. Two patients (1.8%) were found to have a late reinfection without early persistent postoperative infection. Patients with any post-repair infection were older (67 vs. 60 years, P = 0.01) and less likely to have patent repairs during follow up (59% vs. 32%, P = 0.01). Patients with aortoenteric fistula had a higher rate of any post-repair infection (63% vs. 29%, P < 0.01)CONCLUSION: This large multi-center study suggests that patients who have undergone partial resection of infected aortic grafts may be at high risk of death or post-repair infection, especially older patients with abdominal infection not isolated to a single graft limb, or with Candida infection or aortoenteric fistula. Late reinfection correlated strongly with early persistent postoperative infection, raising concern for occult retained infected graft material.
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| 22. |
- Janko, Matthew R., et al.
(author)
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In-situ bypass is associated with superior infection-free survival compared with extra-anatomic bypass for the management of secondary aortic graft infections without enteric involvement
- 2022
-
In: Journal of Vascular Surgery. - : Elsevier. - 0741-5214 .- 1097-6809. ; 76:2, s. 546-
-
Journal article (peer-reviewed)abstract
- Objective: The optimal revascularization modality following complete resection of aortic graft infection (AGI) without enteric involvement remains unclear. The purpose of this investigation is to determine the revascularization approach associated with the lowest morbidity and mortality using real-world data in patients undergoing complete excision of AGI. Methods: A retrospective, multi-institutional study of AGI from 2002 to 2014 was performed using a standardized database. Baseline demographics, comorbidities, and perioperative variables were recorded. The primary outcome was infection-free survival. Descriptive statistics, Kaplan-Meier survival analysis, and univariate and multivariable analyses were performed. Results: A total of 241 patients at 34 institutions from seven countries presented with AGI during the study period (median age, 68 years; 75% male). The initial aortic procedures that resulted in AGI were 172 surgical grafts (71%), 66 endografts (27%), and three unknown (2%). Of the patients, 172 (71%) underwent complete excision of infected aortic graft material followed by in situ (in-line) bypass (ISB), including antibiotic-treated prosthetic graft (35%), autogenous femoral vein (neo-aortoiliac surgery) (24%), and cryopreserved allograft (41%). Sixty-nine patients (29%) underwent extra-anatomic bypass (EAB). Overall median Kaplan-Meier estimated survival was 5.8 years. Perioperative mortality was 16%. When stratified by ISB vs EAB, there was a significant difference in Kaplan-Meier estimated infection-free survival (2910 days; interquartile range, 391-3771 days vs 180 days; interquartile range, 27-3750 days; P <.001). There were otherwise no significant differences in presentation, comorbidities, or perioperative variables. Multivariable Cox regression showed lower infection-free survival among patients with EAB (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.6-3.6; P <.001), polymicrobial infection (HR, 2.2; 95% CI, 1.4-3.5; P = .001), methicillin-resistant Staphylococcus aureus infection (HR, 1.7; 95% CI, 1.1-2.7; P = .02), as well as the protective effect of omental/muscle flap coverage (HR, 0.59; 95% CI, 0.37-0.92; P = .02). Conclusions: After complete resection of AGI, perioperative mortality is 16% and median overall survival is 5.8 years. EAB is associated with nearly a two and one-half-fold higher reinfection/mortality compared with ISB. Omental and/or muscle flap coverage of the repair appear protective.
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| 23. |
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| 24. |
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| 25. |
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| 26. |
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| 27. |
- Abercrombie, Daniel, et al.
(author)
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Dark Matter benchmark models for early LHC Run-2 Searches : Report of the ATLAS/CMS Dark Matter Forum
- 2020
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In: Physics of the Dark Universe. - : Elsevier BV. - 2212-6864. ; 27
-
Journal article (peer-reviewed)abstract
- This document is the final report of the ATLAS-CMS Dark Matter Forum, a forum organized by the ATLAS and CMS collaborations with the participation of experts on theories of Dark Matter, to select a minimal basis set of dark matter simplified models that should support the design of the early LHC Run-2 searches. A prioritized, compact set of benchmark models is proposed, accompanied by studies of the parameter space of these models and a repository of generator implementations. This report also addresses how to apply the Effective Field Theory formalism for collider searches and present the results of such interpretations.
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| 28. |
- Abikhodr, A. H., et al.
(author)
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Identifying Mixtures of Isomeric Human Milk Oligosaccharides by the Decomposition of IR Spectral Fingerprints
- 2021
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In: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 93:44, s. 14730-14736
-
Journal article (peer-reviewed)abstract
- The analysis of glycans presents a significant challenge that arises from their isomeric heterogeneity. While high-resolution ion mobility spectrometry (IMS) has shown the ability to resolve subtly different glycan isomers, their unambiguous assignment remains difficult. Here, we demonstrate an infrared (IR) spectroscopic approach for identifying isomers in a glycan mixture. To display the feasibility of this approach, we have constructed a small database of cryogenic spectra of five lacto-N-fucopentaose (LNFP) and six disaccharide isomers and demonstrated that in the cases where they cannot be separated by IMS, we can use a cryogenic IR spectrum to identify the isomeric components of a mixture.
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| 29. |
- Artaxo, Paulo, et al.
(author)
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Tropical and Boreal Forest – Atmosphere Interactions : A Review
- 2022
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In: Tellus. Series B, Chemical and physical meteorology. - : Stockholm University Press. - 0280-6509 .- 1600-0889. ; 74:1, s. 24-163
-
Research review (peer-reviewed)abstract
- This review presents how the boreal and the tropical forests affect the atmosphere, its chemical composition, its function, and further how that affects the climate and, in return, the ecosystems through feedback processes. Observations from key tower sites standing out due to their long-term comprehensive observations: The Amazon Tall Tower Observatory in Central Amazonia, the Zotino Tall Tower Observatory in Siberia, and the Station to Measure Ecosystem-Atmosphere Relations at Hyytiäla in Finland. The review is complemented by short-term observations from networks and large experiments.The review discusses atmospheric chemistry observations, aerosol formation and processing, physiochemical aerosol, and cloud condensation nuclei properties and finds surprising similarities and important differences in the two ecosystems. The aerosol concentrations and chemistry are similar, particularly concerning the main chemical components, both dominated by an organic fraction, while the boreal ecosystem has generally higher concentrations of inorganics, due to higher influence of long-range transported air pollution. The emissions of biogenic volatile organic compounds are dominated by isoprene and monoterpene in the tropical and boreal regions, respectively, being the main precursors of the organic aerosol fraction.Observations and modeling studies show that climate change and deforestation affect the ecosystems such that the carbon and hydrological cycles in Amazonia are changing to carbon neutrality and affect precipitation downwind. In Africa, the tropical forests are so far maintaining their carbon sink.It is urgent to better understand the interaction between these major ecosystems, the atmosphere, and climate, which calls for more observation sites, providing long-term data on water, carbon, and other biogeochemical cycles. This is essential in finding a sustainable balance between forest preservation and reforestation versus a potential increase in food production and biofuels, which are critical in maintaining ecosystem services and global climate stability. Reducing global warming and deforestation is vital for tropical forests.
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| 30. |
- Bansal, P., et al.
(author)
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Using SLIM-Based IMS-IMS Together with Cryogenic Infrared Spectroscopy for Glycan Analysis
- 2020
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In: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 92:13, s. 9079-9085
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Journal article (peer-reviewed)abstract
- The isomeric heterogeneity of glycans poses a great challenge for their analysis. While combining ion mobility spectrometry (IMS) with tandem mass spectrometry is a powerful means for identifying and characterizing glycans, it has difficulty distinguishing the subtlest differences between isomers. Cryogenic infrared spectroscopy provides an additional dimension for glycan identification that is extremely sensitive to their structure. Our approach to glycan analysis combines ultrahigh-resolution IMS-IMS using structures for lossless ion manipulation (SLIM) with cryogenic infrared spectroscopy. We present here the design of a SLIM board containing a series of on-board traps in which we perform collision-induced dissociation (CID) at pressures in the millibar range. We characterize the on-board CID process by comparing the fragments generated from a pentapeptide to those obtained on a commercial tandem mass spectrometer. We then apply our new technique to study the mobility and vibrational spectra of CID fragments from two human milk oligosaccharides. Comparison of both the fragment drift times and IR spectra with those of suitable reference compounds allows us to identify their specific isomeric form, including the anomericity of the glycosidic linkage, demonstrating the power of this tool for glycan analysis. Copyright © 2020 American Chemical Society.
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| 31. |
- Béthermin, Matthieu, et al.
(author)
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The ALMA-ALPINE [CII] survey: Kennicutt-Schmidt relation in four massive main-sequence galaxies at z ~ 4.5
- 2023
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In: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 680
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Journal article (peer-reviewed)abstract
- Aims. The Kennicutt-Schmidt (KS) relation between the gas and the star formation rate (SFR) surface density (Σgas - ΣSFR) is essential to understand star formation processes in galaxies. To date, it has been measured up to z ~ 2.5 in main-sequence galaxies. In this Letter our aim is to put constraints at z ~ 4.5 using a sample of four massive main-sequence galaxies observed by ALMA at high resolution. Methods. We obtained ~0.3″-resolution [CII] and continuum maps of our objects, which we then converted into gas and obscured SFR surface density maps. In addition, we produced unobscured SFR surface density maps by convolving Hubble ancillary data in the rest-frame UV. We then derived the average ΣSFR in various Σgas bins, and estimated the uncertainties using a Monte Carlo sampling. Results. Our galaxy sample follows the KS relation measured in main-sequence galaxies at lower redshift, and is slightly lower than the predictions from simulations. Our data points probe the high end both in terms of Σgas and ΣSFR, and gas depletion timescales (285-843 Myr) remain similar to z ~ 2 objects. However, three of our objects are clearly morphologically disturbed, and we could have expected shorter gas depletion timescales (≲100 Myr) similar to merger-driven starbursts at lower redshifts. This suggests that the mechanisms triggering starbursts at high redshift may be different than in the low- and intermediate-z Universe.
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| 32. |
- D. V. Godoy, Paulo R., et al.
(author)
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Targeting NRF2, Regulator of Antioxidant System, to Sensitize Glioblastoma Neurosphere Cells to Radiation-Induced Oxidative Stress
- 2020
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In: Oxidative Medicine and Cellular Longevity. - : Hindawi Limited. - 1942-0900 .- 1942-0994. ; 2020
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Journal article (peer-reviewed)abstract
- The presence of glioma stem cells (GSCs), which are enriched in neurospheres, may be connected to the radioresistance of glioblastoma (GBM) due to their enhanced antioxidant defense and elevated DNA repair capacity. The aim was to evaluate the responses to different radiation qualities and to reduce radioresistance of U87MG cells, a GBM cell line. U87MG cells were cultured in a 3D model and irradiated with low (24 mGy/h) and high (0.39 Gy/min) dose rates of low LET gamma and high LET carbon ions (1-2 Gy/min). Thereafter, expression of proteins related to oxidative stress response, extracellular 8-oxo-dG, and neurospheres were determined. LD50 for carbon ions was significantly lower compared to LD50 of high and low dose rate gamma radiation. A significantly higher level of 8-oxo-dG was detected in the media of cells exposed to a low dose rate as compared to a high dose rate of gamma or carbon ions. A downregulation of oxidative stress proteins was also observed (NRF2, hMTH1, and SOD1). The NRF2 gene was knocked down by CRISPR/Cas9 in neurosphere cells, resulting in less self-renewal, more differentiated cells, and less proliferation capacity after irradiation with low and high dose rate gamma rays. Overall, U87MG glioma neurospheres presented differential responses to distinct radiation qualities and NRF2 plays an important role in cellular sensitivity to radiation.
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| 33. |
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| 34. |
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| 35. |
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| 36. |
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| 37. |
- Dyukova, I., et al.
(author)
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A new approach for identifying positional isomers of glycans cleaved from monoclonal antibodies
- 2021
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In: Analyst. - : Royal Society of Chemistry (RSC). - 0003-2654. ; 146:15, s. 4789-4795
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Journal article (peer-reviewed)abstract
- Glycosylation patterns in monoclonal antibodies (mAbs) can vary significantly between different host cell types, and these differences may affect mAbs safety, efficacy, and immunogenicity. Recent studies have demonstrated that glycan isomers with the terminal galactose position on either the Man alpha 1-3 arm or the Man alpha 1-6 arm have an impact on the effector functions and dynamic structure of mAbs. The development of a robust method to distinguish positional isomers of glycans is thus critical to guarantee mAb quality. In this work, we apply high-resolution ion mobility combined with cryogenic infrared spectroscopy to distinguish isomeric glycans with different terminal galactose positions, using G1F as an example. Selective enzymatic synthesis of the G1(alpha 1-6)F isomer allows us to assign the peaks in the arrival-time distributions and the infrared spectra to their respective isomeric forms. Moreover, we demonstrate the impact of the host cell line (CHO and HEK-293) on the IgG G1F gycan profile at the isomer level. This work illustrates the potential of our approach for glycan analysis of mAbs.
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| 38. |
- Jensterle, M, et al.
(author)
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The Relationship between COVID-19 and Hypothalamic-Pituitary-Adrenal Axis: A Large Spectrum from Glucocorticoid Insufficiency to Excess-The CAPISCO International Expert Panel
- 2022
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In: International journal of molecular sciences. - : MDPI AG. - 1422-0067. ; 23:13
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Journal article (peer-reviewed)abstract
- Coronavirus disease 2019 (COVID-19) is a highly heterogeneous disease regarding severity, vulnerability to infection due to comorbidities, and treatment approaches. The hypothalamic–pituitary–adrenal (HPA) axis has been identified as one of the most critical endocrine targets of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that might significantly impact outcomes after infection. Herein we review the rationale for glucocorticoid use in the setting of COVID-19 and emphasize the need to have a low index of suspicion for glucocorticoid-induced adrenal insufficiency, adjusting for the glucocorticoid formulation used, dose, treatment duration, and underlying health problems. We also address several additional mechanisms that may cause HPA axis dysfunction, including critical illness-related corticosteroid insufficiency, the direct cytopathic impacts of SARS-CoV-2 infection on the adrenals, pituitary, and hypothalamus, immune-mediated inflammations, small vessel vasculitis, microthrombotic events, the resistance of cortisol receptors, and impaired post-receptor signaling, as well as the dissociation of ACTH and cortisol regulation. We also discuss the increased risk of infection and more severe illness in COVID-19 patients with pre-existing disorders of the HPA axis, from insufficiency to excess. These insights into the complex regulation of the HPA axis reveal how well the body performs in its adaptive survival mechanism during a severe infection, such as SARS-CoV-2, and how many parameters might disbalance the outcomes of this adaptation.
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| 39. |
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| 40. |
- Vassiliades, C., et al.
(author)
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A climate sensitive design approach to BIPV : Investigating the nexus between solar energy and thermal comfort in cities in Sweden and Cyprus
- 2023
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In: Building and Environment. - : Elsevier. - 0360-1323 .- 1873-684X. ; 243
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Journal article (peer-reviewed)abstract
- The research performed attempts to answer the question of how building integration of active solar systems may affect the thermal comfort in open areas and the interstitial space between buildings in urban environments. This is done by using computer simulation and in-situ observations at the extreme northern and southern geographies of Europe, namely in Luleå, Sweden and in Limassol, Cyprus. A typical example of the urban grid of each city is chosen and active solar systems are integrated on the facades of buildings, respectively foreach case. The thermal conditions at street level are then simulated, using Envi-MET, before and after systems integration, with the aim of assessing the differences between low and high insolation conditions, using the Physiological Equivalent Temperature (PET) indicator. Subsequently, the thermal conditions in the public space between buildings were once again assessed, with reduced emissivity values for the building integrated PV panels. The results point to the fact that the building integration of PVs lacking low emissivity coatings can have an impact in the thermal comfort of users in the locations specified, especially in the summer, wherein it is shown to be negligible in the southern case study but more significant in the northern one.
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| 41. |
- Yalovenko, N., et al.
(author)
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Analyzing glycans cleaved from a biotherapeutic protein using ultrahigh-resolution ion mobility spectrometry together with cryogenic ion spectroscopy
- 2020
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In: Analyst. - : Royal Society of Chemistry (RSC). - 0003-2654. ; 145:20, s. 6493-6499
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Journal article (peer-reviewed)abstract
- Glycans covalently attached to protein biotherapeutics have a significant impact on their biological activity, clearance, and safety. As a result, glycosylation is categorized as a critical quality attribute that needs an adequate analytical approach to guarantee product quality. However, the isomeric complexity and branched structure of glycans makes their analysis a significant challenge. In this work, we propose a multidimensional approach for monitoring released glycans that combines ultrahigh-resolution ion mobility spectrometry (IMS) and cryogenic vibrational spectroscopy, and we demonstrate this technique by characterizing fourN-glycans cleaved from the therapeutic fusion protein etanercept that range in abundance from 1% to 22% of the totalN-glycan content. The recorded vibrational spectra exhibit well-resolved transitions that can be used as a fingerprint to identify a particular glycan. This work represents an important advance in the analysis of N-linked glycans cleaved from biopharmaceutical proteins that could eventually be used as tool for monitoring biopharmaceutical glycoforms.
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| 42. |
- Yatsyna, Vasyl, et al.
(author)
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High-Throughput Multiplexed Infrared Spectroscopy of Ion Mobility-Separated Species Using Hadamard Transform
- 2022
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In: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 94:6, s. 2912-2917
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Journal article (peer-reviewed)abstract
- Coupling vibrational ion spectroscopy with highresolution ion mobility separation offers a promising approach for detailed analysis of biomolecules in the gas phase. Improvements in the ion mobility technology have made it possible to separate isomers with minor structural differences, and their interrogation with a tunable infrared laser provides vibrational fingerprints for unambiguous database-enabled identification. Nevertheless, wide analytical application of this technique requires high-throughput approaches for acquisition of vibrational spectra of all species present in complex mixtures. In this work, we present a novel multiplexed approach and demonstrate its utility for cryogenic ion spectroscopy of peptides and glycans in mixtures. Since the method is based on Hadamard transform multiplexing, it yields infrared spectra with an increased signal-to-noise ratio compared to a conventional signal averaging approach.
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