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  • Aimonen, Kukka, et al. (författare)
  • Role of Surface Chemistry in the In Vitro Lung Response to Nanofibrillated Cellulose
  • 2021
  • Ingår i: Nanomaterials. - : MDPI. - 2079-4991. ; 11:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Wood-derived nanofibrillated cellulose (NFC) has emerged as a sustainable material with a wide range of applications and increasing presence in the market. Surface charges are introduced during the preparation of NFC to facilitate the defibrillation process, which may also alter the toxicological properties of NFC. In the present study, we examined the in vitro toxicity of NFCs with five surface chemistries: nonfunctionalized, carboxymethylated, phosphorylated, sulfoethylated, and hydroxypropyltrimethylammonium-substituted. The NFC samples were characterized for surface functional group density, surface charge, and fiber morphology. Fibril aggregates predominated in the nonfunctionalized NFC, while individual nanofibrils were observed in the functionalized NFCs. Differences in surface group density among the functionalized NFCs were reflected in the fiber thickness of these samples. In human bronchial epithelial (BEAS-2B) cells, all NFCs showed low cytotoxicity (CellTiter-GloVR luminescent cell viability assay) which never exceeded 10% at any exposure time. None of the NFCs induced genotoxic effects, as evaluated by the alkaline comet assay and the cytokinesis-block micronucleus assay. The nonfunctionalized and carboxymethylated NFCs were able to increase intracellular reactive oxygen species (ROS) formation (chloromethyl derivative of 2 ',7 '-dichlorodihydrofluorescein diacetate assay). However, ROS induction did not result in increased DNA or chromosome damage.
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  • Amaral, Rita, et al. (författare)
  • Profiling Persistent Asthma Phenotypes in Adolescents : A Longitudinal Diagnostic Evaluation from the INSPIRERS Studies
  • 2021
  • Ingår i: International Journal of Environmental Research and Public Health. - : MDPI. - 1661-7827 .- 1660-4601. ; 18:3
  • Tidskriftsartikel (refereegranskat)abstract
    • We aimed to identify persistent asthma phenotypes among adolescents and to evaluate longitudinally asthma-related outcomes across phenotypes. Adolescents (13-17 years) from the prospective, observational, and multicenter INSPIRERS studies, conducted in Portugal and Spain, were included (n = 162). Latent class analysis was applied to demographic, environmental, and clinical variables, collected at a baseline medical visit. Longitudinal differences in clinical variables were assessed at a 4-month follow-up telephone contact (n = 128). Three classes/phenotypes of persistent asthma were identified. Adolescents in class 1 (n = 87) were highly symptomatic at baseline and presented the highest number of unscheduled healthcare visits per month and exacerbations per month, both at baseline and follow-up. Class 2 (n = 32) was characterized by female predominance, more frequent obesity, and uncontrolled upper/lower airways symptoms at baseline. At follow-up, there was a significant increase in the proportion of controlled lower airway symptoms (p < 0.001). Class 3 (n = 43) included mostly males with controlled lower airways symptoms; at follow-up, while keeping symptom control, there was a significant increase in exacerbations/month (p = 0.015). We have identified distinct phenotypes of persistent asthma in adolescents with different patterns in longitudinal asthma-related outcomes, supporting the importance of profiling asthma phenotypes in predicting disease outcomes that might inform targeted interventions and reduce future risk.
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  • Armisen, David, et al. (författare)
  • Transcriptome-based phylogeny of the semi-aquatic bugs (Hemiptera Heteroptera: Gerromorpha) reveals patterns of lineage expansion in a series of new adaptive zones
  • 2022
  • Ingår i: Molecular biology and evolution. - : Oxford University Press. - 0737-4038 .- 1537-1719. ; 39:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Key innovations enable access to new adaptive zones and are often linked to increased species diversification. As such, innovations have attracted much attention, yet their concrete consequences on the subsequent evolutionary trajectory and diversification of the bearing lineages remain unclear. Water striders and relatives (Hemiptera: Heteroptera: Gerromorpha) represent a monophyletic lineage of insects that transitioned to live on the water-air interface and that diversified to occupy ponds, puddles, streams, mangroves and even oceans. This lineage offers an excellent model to study the patterns and processes underlying species diversification following the conquest of new adaptive zones. However, such studies require a reliable and comprehensive phylogeny of the infraorder. Based on whole transcriptomic datasets of 97 species and fossil records, we reconstructed a new phylogeny of the Gerromorpha that resolved inconsistencies and uncovered strong support for previously unknown relationships between some important taxa. We then used this phylogeny to reconstruct the ancestral state of a set of adaptations associated with water surface invasion (fluid locomotion, dispersal and transition to saline waters) and sexual dimorphism. Our results uncovered important patterns and dynamics of phenotypic evolution, revealing how the initial event of water surface invasion enabled multiple subsequent transitions to new adaptive zones on the water surfaces. This phylogeny and the associated transcriptomic datasets constitute highly valuable resources, making Gerromorpha an attractive model lineage to study phenotypic evolution.
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  • Arnell, Robert, et al. (författare)
  • Analytical Characterization of Chiral Drug-Protein Interactions: Comparison between the Optical Biosensor (Surface Plasmon Resonance) Assay and the HPLC Perturbation Method
  • 2006
  • Ingår i: Analytical Chemistry. ; 78:5, s. 1682-1689
  • Tidskriftsartikel (refereegranskat)abstract
    • Two modern, fundamentally different methods were used for a detailed investigation of enantioselective drug-protein interactions, a surface plasmon resonance (SPR)-based Biacore 2000 biosensor assay and the previously validated HPLC perturbation method (HPLC-PM). This is the first time SPR has been used for this purpose. The fundamental features of the two methods were investigated, and the consequences for operation and data evaluation were addressed. With HPLC-PM, chiral data could be obtained directly from the racemic mixture, whereas a separate analysis of each pure enantiomer was required to obtain chiral data with SPR. It was shown that if chirality is not attributed in the SPR analysis, misleading average racemic binding constants will be obtained. Both drug and protein consumption were considerably higher with HPLC-PM. HPLC-PM was found to be best suited for measurements of weak affinity interactions, whereas the SPR method was best for strong interactions. With both methods, the presence of DMSO in the samples severely affected the interactions, introducing errors. The binding of the -blockers alprenolol and propranolol to Cel7a cellulase was used as a model system. These methods gave results that agreed quite well qualitatively, but considerable quantitative deviations were sometimes obtained.
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  • Bairagi, Samiran, et al. (författare)
  • Formation of quaternary Zn(AlxGa1−x)2O4 epilayers driven by thermally induced interdiffusion between spinel ZnGa2O4 epilayer and Al2O3 substrate
  • 2023
  • Ingår i: Materials Today Advances. - : Elsevier. - 2590-0498. ; 20
  • Tidskriftsartikel (refereegranskat)abstract
    • Zinc aluminogallate, Zn(AlxGa1−x)2O4 (ZAGO), a single-phase spinel structure, offers considerable potential for high-performance electronic devices due to its expansive compositional miscibility range between aluminum (Al) and gallium (Ga). Direct growth of high-quality ZAGO epilayers however remains problematic due to the high volatility of zinc (Zn). This work highlights a novel synthesis process for high-quality epitaxial quaternary ZAGO thin films on sapphire substrates, achieved through thermal annealing of a ZnGa2O4 (ZGO) epilayer on sapphire in an ambient air setting. In-situ annealing x-ray diffraction measurements show that the incorporation of Al in the ZGO epilayer commenced at 850 °C. The Al content (x) in ZAGO epilayer gradually increased up to around 0.45 as the annealing temperature was raised to 1100 °C, which was confirmed by transmission electron microscopy (TEM) and energy dispersive x-ray spectroscopy. X-ray rocking curve measurement revealed a small full width at half maximum value of 0.72 °, indicating the crystal quality preservation of the ZAGO epilayer with a high Al content. However, an epitaxial intermediate �–(AlxGa1−x)2O3 layer (� - AGO) was formed between the ZAGO and sapphire substrate. This is believed to be a consequence of the interdiffusion of Al and Ga between the ZGO thin film and sapphire substrate. Using density functional theory, the substitution cost of Ga in sapphire was determined to be about 0.5 eV lower than substitution cost of Al in ZGO. Motivated by this energetically favorable substitution, a formation mechanism of the ZAGO and AGO layers was proposed. Spectroscopic ellipsometry studies revealed an increase in total thickness of the film from 105.07 nm (ZGO) to 147.97 nm (ZAGO/AGO) after annealing to 1100 °C, which were corroborated using TEM. Furthermore, an observed increase in the direct (indirect) optical bandgap from 5.06 eV (4.7 eV) to 5.72 eV (5.45 eV) with an increasing Al content in the ZAGO layer further underpins the formation of a quaternary ZAGO alloy with a tunable composition.
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  • Bastos, Jorge Tiago, et al. (författare)
  • Road safety performance in Brazil : towards a composite indicator
  • 2016
  • Konferensbidrag (refereegranskat)abstract
    • The monitoring of the road safety level in Brazil and particularly in its member states traditionally focuses on the available traffic fatality rates. However, this approach does not offer practical suggestions on how to improve road safety. In this context, the usage of Road Safety Performance Indicators (SPIs) is a growing and promising tendency. This research deals with the construction of a set of SPIs intended to serve as good indicators of the operational conditions of the road traffic system in each of the 27 Brazilian states. The set of 28 selected SPIs represents three domains (road user, environment and vehicle) and consists of further subdivisions. The hierarchical structure of the 28 indicators manifests the traditional distinction between the road user (RU), the environment (E) and the vehicle (V) domain of SPIs. In the first domain (1st to 10th indicator), road user behavior decomposes into alcohol (A), cell-phone (CP), protective systems (PS) and speeding (S). Protective systems decompose into seatbelt (SB) and helmet (H). In the second domain, environmental SPIs decompose into road (R) and health system (HS). Road (11th to 20ht indicator), decomposes into central division (CD), signing (SG) and roadside (RS). Signing decomposes into road markings (RM) and vertical signs (VS). Road markings decompose into central (C) and lateral (L). Health system (21st to 23rd indicator) decomposes into health professionals (HP) and health expenditure (HE). In the third domain, vehicle related SPIs (24th to 27th indicator), decompose into fleet composition (FC) and age of the fleet (AF). This paper aims to describe this innovative SPI research in Brazil, using data envelopment analysis to aggregate the SPIs into a composite indicator, as well as to show the potential for supporting future improvements on the theme.
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  • Basu, Alex, et al. (författare)
  • Hemocompatibility of Ca2+-Crosslinked Nanocellulose Hydrogels : Toward Efficient Management of Hemostasis
  • 2017
  • Ingår i: Macromolecular Bioscience. - : Wiley. - 1616-5187 .- 1616-5195. ; 17:11
  • Tidskriftsartikel (refereegranskat)abstract
    • The present work investigates Ca2+-crosslinked nanofibrillated cellulose hydrogels as potential hemostatic wound dressings by studying core interactions between the materials and a central component of wounds and wound healing—the blood. Hydrogels of wood-derived anionic nanofibrillated cellulose (NFC) and NFC hydrogels that incorporate kaolin or collagen are studied in an in vitro whole blood model and with platelet-free plasma assays. The evaluation of thrombin and factor XIIa formation, platelet reduction, and the release of activated complement system proteins, shows that the NFC hydrogel efficiently triggered blood coagulation, with a rapid onset of clot formation, while displaying basal complement system activation. By using the NFC hydrogel as a carrier of kaolin, the onset of hemostasis is further boosted, while the NFC hydrogel containing collagen exhibits blood activating properties comparable to the anionic NFC hydrogel. The herein studied NFC hydrogels demonstrate great potential for being part of advanced wound healing dressings that can be tuned to target certain wounds (e.g., strongly hemorrhaging ones) or specific phases of the wound healing process for optimal wound management.
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  • Basu, Alex, et al. (författare)
  • In Vitro and in Vivo Evaluation of the Wound Healing Properties of Nanofibrillated Cellulose Hydrogels
  • 2018
  • Ingår i: ACS Applied Bio Materials. - : American Chemical Society (ACS). - 2576-6422. ; 1:6, s. 1853-1863
  • Tidskriftsartikel (refereegranskat)abstract
    • Current trends in wound care research move toward the development of wound healing dressings designed to treat different types of wounds (e.g., burns and chronic wounds) and toward tailoring treatments for different stages of the wound healing process. In this context, the development of advanced nanotherapeutic materials is highlighted as a promising strategy to efficiently control specific phases of the wound healing process. Here, Ca2+-cross-linked wood-derived nanofibrillated cellulose (NFC) hydrogels are evaluated as wound healing dressings. In vitro biocompatibility assays were performed to study the interaction of the NFC hydrogels with cellular processes that are tightly related to wound healing. Moreover, an in vivo dermo-epidermic full thickness wound healing model in rat was used to uncover the wound healing ability of the Ca2+-cross-linked NFC hydrogels. The in vitro experiments showed that the NFC hydrogels were able to support fibroblast and keratinocyte proliferation. A potential effect of the hydrogels on triggering keratinocyte differentiation was furthermore proposed. In vivo, the NFC hydrogels stimulated healing without causing any adverse local tissue effects, potentially owing to their moisture-donating properties and the herein discussed aiding effect of the Ca2+-cross-linker on epidermal generation. Thus, this work extensively demonstrates the wound healing ability of NFC hydrogels and presents an important milestone in the research on NFC toward advanced wound healing applications.
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  • Basu, Alex (författare)
  • Ion-Crosslinked Nanocellulose Hydrogels for Advanced Wound Care Applications
  • 2018
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • A current trend in the field of wound care is the development of wound healing materials that are designed to address specific types of wounds or underlying pathologies to achieve improved healing. At the same time, there is a societal drive to replace synthetic materials with renewable alternatives. The work presented in this thesis was therefore carried out to investigate the use of wood nanocellulose, produced from the world’s most abundant biopolymer, cellulose, in advanced wound care applications.Wood-based nanofibrillated cellulose (NFC) was chemically functionalized and crosslinked using calcium to obtain a self-standing hydrogel. The NFC hydrogel was evaluated in terms of its physicochemical properties, biocompatibility, blood interactions, bacterial interactions, in vivo wound healing ability and, finally, as a protein carrier. Parallel with the assessment of the NFC hydrogel, modified versions of the material were tested to investigate the tunability of the above-mentioned characteristics.The ability of the hydrogel to maintain a moist wound bed was demonstrated. Evaluation of the biocompatibility showed that the material was cytocompatible and did not trigger inflammatory mechanisms. Furthermore, the NFC hydrogel supported cell proliferation, and was shown to possess hemostatic properties. It was also discovered that the material had a slight bacteriostatic effect and the ability to act as a barrier against bacteria. When tested in vivo, the hydrogel was found to significantly improve wound healing.Modifications through the incorporation of additives to the hydrogel matrix, as well as exchange of the crosslinking ion, were shown to influence the biological response to the material. Moreover, the results presented here demonstrate the possibility of using the NFC hydrogel as a protein carrier; the easily adjustable charge property being identified as a central parameter for manipulation to regulate the release profile.In conclusion, this work has demonstrated the extensive wound healing ability of the calcium-crosslinked NFC hydrogel, and represents an important milestone in the research on NFC towards advanced wound care applications. It is expected that the easily modifiable nature of the material can be exploited to further develop the NFC hydrogel to suit the treatment needs for a broad range of wound types.
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  • Basu, Alex, et al. (författare)
  • Ion-crosslinked wood-derived nanocellulose hydrogels with tunable antibacterial properties : Candidate materials for advanced wound care applications
  • 2018
  • Ingår i: Carbohydrate Polymers. - : Elsevier BV. - 0144-8617 .- 1879-1344. ; 181, s. 345-350
  • Tidskriftsartikel (refereegranskat)abstract
    • Development of advanced dressings with antimicrobial properties for the treatment of infected wounds is an important approach in the fight against evolution of antibiotic resistant bacterial strains. Herein, the effects of ion-crosslinked nanocellulose hydrogels on bacteria commonly found in infected wounds were investigated in vitro. By using divalent calcium or copper ions as crosslinking agents, different antibacterial properties against the bacterial strains Staphylococcus epidermidis and Pseudomonas aeruginosa were obtained. Calcium crosslinked hydrogels were found to retard S. epidermidis growth (up to 266% increase in lag time, 36% increase in doubling time) and inhibited P. aeruginosa biofilm formation, while copper crosslinked hydrogels prevented S. epidermidis growth and were bacteriostatic towards P. aeruginosa (49% increase in lag time, 78% increase in doubling time). The wound dressing candidates furthermore displayed barrier properties towards both S. epidermidis and P. aeruginosa, hence making them interesting for further development of advanced wound dressings with tunable antibacterial properties.
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  • Basu, Alex, et al. (författare)
  • On the use of ion-crosslinked nanocellulose hydrogels for wound healing solutions : Physicochemical properties and application-oriented biocompatibility studies
  • 2017
  • Ingår i: Carbohydrate Polymers. - : Elsevier BV. - 0144-8617 .- 1879-1344. ; 174, s. 299-308
  • Tidskriftsartikel (refereegranskat)abstract
    • Calcium ion-crosslinked nanofibrillated cellulose (NFC) hydrogels were investigated as potential materials for wound healing dressings. The physicochemical properties of the hydrogels were examined by rheology and water retention tests. Skin cells and monocytes were selected for application-oriented bio-compatibility studies. The NFC hydrogels presented entangled fibrous networks and solid-like behavior. Water retention tests showed the material's potential to maintain a suitable moist environment for different type of wounds. The hydrogels did not affect dermal fibroblasts monolayer cultures upon directcontact, as cell monolayers remained intact after application, incubation and removal of the materials. Inflammatory response studies with blood-derived mononuclear cells revealed the inert nature of the hydrogels in terms of cytokine secretion and reactive oxygen species production. Results highlight the great potential of ion-crosslinked NFC hydrogels for the development of advanced wound dressings, where further functionalization of the material could lead to improved properties towards the healing of specific wound types.
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  • Basu, Alex, et al. (författare)
  • Towards Tunable Protein-Carrier Wound Dressings Based on Nanocellulose Hydrogels Crosslinked with Calcium Ions
  • 2018
  • Ingår i: Nanomaterials. - : MDPI. - 2079-4991. ; 8:7
  • Tidskriftsartikel (refereegranskat)abstract
    • A Ca2+-crosslinked wood-based nanofibrillated cellulose (NFC) hydrogel was investigated to build knowledge toward the use of nanocellulose for topical drug delivery applications in a chronic wound healing context. Proteins of varying size and isoelectric point were loaded into the hydrogel in a simple soaking procedure. The release of the proteins from the hydrogel was monitored and kinetics determining parameters of the release processes were assessed. The integrity of the hydrogel and proteins were also studied. The results showed that electrostatic interactions between the proteins and the negatively-charged NFC hydrogel structure played a central role in the loading process. The release of the proteins were governed by Fickian diffusion. An increased protein size, as well as a positive protein charge facilitated a slower and more sustained release process from the hydrogel matrix. At the same time, the positively-charged protein was shown to increase the post-loading hydrogel strength. Released proteins maintained structural stability and activity, thus indicating that the Ca2+-crosslinked NFC hydrogel could function as a carrier of therapeutic proteins without compromising protein function. It is foreseen that, by utilizing tunable charge properties of the NFC hydrogel, release profiles can be tailored to meet very specific treatment needs.
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  • Blach, S., et al. (författare)
  • Global change in hepatitis C virus prevalence and cascade of care between 2015 and 2020: a modelling study
  • 2022
  • Ingår i: Lancet Gastroenterology & Hepatology. - : Elsevier BV. - 2468-1253. ; 7:5, s. 396-415
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Since the release of the first global hepatitis elimination targets in 2016, and until the COVID-19 pandemic started in early 2020, many countries and territories were making progress toward hepatitis C virus (HCV) elimination. This study aims to evaluate HCV burden in 2020, and forecast HCV burden by 2030 given current trends. Methods This analysis includes a literature review, Delphi process, and mathematical modelling to estimate HCV prevalence (viraemic infection, defined as HCV RNA-positive cases) and the cascade of care among people of all ages (age =0 years from birth) for the period between Jan 1, 2015, and Dec 31, 2030. Epidemiological data were collected from published sources and grey literature (including government reports and personal communications) and were validated among country and territory experts. A Markov model was used to forecast disease burden and cascade of care from 1950 to 2050 for countries and territories with data. Model outcomes were extracted from 2015 to 2030 to calculate population-weighted regional averages, which were used for countries or territories without data. Regional and global estimates of HCV prevalence, cascade of care, and disease burden were calculated based on 235 countries and territories. Findings Models were built for 110 countries or territories: 83 were approved by local experts and 27 were based on published data alone. Using data from these models, plus population-weighted regional averages for countries and territories without models (n=125), we estimated a global prevalence of viraemic HCV infection of 0.7% (95% UI 0.7-0.9), corresponding to 56.8 million (95% UI 55.2-67.8) infections, on Jan 1, 2020. This number represents a decrease of 6.8 million viraemic infections from a 2015 (beginning of year) prevalence estimate of 63.6 million (61.8-75.8) infections (0.9% [0.8-1.0] prevalence). By the end of 2020, an estimated 12.9 million (12.5-15.4) people were living with a diagnosed viraemic infection. In 2020, an estimated 641 000 (623 000-765 000) patients initiated treatment. Interpretation At the beginning of 2020, there were an estimated 56.8 million viraemic HCV infections globally. Although this number represents a decrease from 2015, our forecasts suggest we are not currently on track to achieve global elimination targets by 2030. As countries recover from COVID-19, these findings can help refocus efforts aimed at HCV elimination. Copyright (C) 2022 Elsevier Ltd. All rights reserved.
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  • Blasi Romero, Anna (författare)
  • Bioactive nanocellulose materials for the treatment of chronic wounds
  • 2023
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Chronic wounds represent a burden for the healthcare system and significantly affect the quality of life of the patients. There is currently a lack of efficient treatments but new, improved therapeutic approaches are under development. Suggested innovative wound care therapies consist on the topical administration of bioactive compounds aimed at restoring the balance in the wound environment and promoting the healing. However, their effectiveness is limited due to the highly oxidative and proteolytic environment in the chronic wound. In the work presented in this thesis, a series of bioactive nanocellulose-based materials were developed with the aim of addressing some of the present demands in chronic wound care. Wood-derived cellulose nanofibrils (CNFs) were functionalized with selected bioactive molecules expected to endow CNFs with the ability to modulate the chronic wound environment. Different chemical approaches were explored to combine CNFs with the following biomolecules: the amino acid cysteine, the peptide oligoproline and the host defense peptide KR-12. Materials were characterized in terms of chemical structure, degree of substitution and bioactivity.The immobilization of cysteine onto CNFs (cys-CNF) provided the material with radical oxygen species (ROS) scavenging properties and the ability to inhibit protease activity, properties that were related to the presence of free thiol groups on the nanofibers. Storage conditions in an inert atmosphere or in the form of aerogel were proposed to assure the long-term activity of the cys-CNF material.  Investigations on the use of the ROS-sensitive oligoproline to crosslink CNFs provided optimized protocols to maximize peptide substitution and the degree of crosslinking. The oligoproline-CNF materials were sensitive to ROS-mediated cleavage and provided a protective effect to cells exposed to oxidative conditions. Moreover, the feasibility of preparing ROS-responsive drug delivery hydrogels based on the oligoproline-CNF was demonstrated, with indications that tuning the length of the oligoproline peptide could be exploited to tailor the release rate of small proteins.  CNF materials with antibacterial properties and the ability to modulate the response of pro-inflammatory macrophages were obtained by immobilizing KR-12 derivatives onto CNFs. This study highlighted the importance in the selection of the conjugation chemistry to preserve the activity of the peptide once immobilized. To conclude, this work has contributed with valuable strategies to develop bioactive CNF-based materials with the potential of paving the way for advanced solutions in the field of chronic wound care. 
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  • Blasi-Romero, Anna, et al. (författare)
  • In Vitro Investigation of Thiol-Functionalized Cellulose Nanofibrils as a Chronic Wound Environment Modulator
  • 2021
  • Ingår i: Polymers. - : MDPI. - 2073-4360. ; 13:2
  • Tidskriftsartikel (refereegranskat)abstract
    • There is currently a huge need for new, improved therapeutic approaches for the treatment of chronic wounds. One promising strategy is to develop wound dressings capable of modulating the chronic wound environment (e.g., by controlling the high levels of reactive oxygen species (ROS) and proteases). Here, we selected the thiol-containing amino acid cysteine to endow wood-derived cellulose nanofibrils (CNF) with bioactivity toward the modulation of ROS levels and protease activity. Cysteine was covalently incorporated into CNF and the functionalized material, herein referred as cys-CNF, was characterized in terms of chemical structure, degree of substitution, radical scavenging capacity, and inhibition of protease activity. The stability of the thiol groups was evaluated over time, and an in vitro cytotoxicity study with human dermal fibroblasts was performed to evaluate the safety profile of cys-CNF. Results showed that cys-CNF was able to efficiently control the activity of the metalloprotease collagenase and to inhibit the free radical DPPH (1,1-Diphenyl-2-picrylhydrazyl radical), activities that were correlated with the presence of free thiol groups on the nanofibers. The stability study showed that the reactivity of the thiol groups challenged the bioactivity over time. Nevertheless, preparing the material as an aerogel and storing it in an inert atmosphere were shown to be valid approaches to increase the stability of the thiol groups in cys-CNF. No signs of toxicity were observed on the dermal fibroblasts when exposed to cys-CNF (concentration range 0.1-0.5 mg/mL). The present work highlights cys-CNF as a promising novel material for the development of bioactive wound dressings for the treatment of chronic wounds.
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32.
  • Blasi Romero, Anna, et al. (författare)
  • KR-12 derivatives endow nanocellulose with antibacterial and anti-inflammatory properties : Role of conjugation chemistry
  • 2023
  • Ingår i: ACS Applied Materials and Interfaces. - 1944-8244 .- 1944-8252. ; 15:20, s. 24186-24196
  • Tidskriftsartikel (refereegranskat)abstract
    • This work combines the wound-healing-related properties of the host defense peptide KR-12 with wood-derived cellulose nanofibrils (CNFs) to obtain bioactive materials, foreseen as a promising solution to treat chronic wounds. Amine coupling through carbodiimide chemistry, thiol-ene click chemistry, and Cu(I)-catalyzed azide-alkyne cycloaddition were investigated as methods to covalently immobilize KR-12 derivatives onto CNFs. The effects of different coupling chemistries on the bioactivity of the KR12-CNF conjugates were evaluated by assessing their antibacterial activities against Escherichia coli and Staphylococcus aureus. Potential cytotoxic effects and the capacity of the materials to modulate the inflammatory response of lipopolysaccharide (LPS)-stimulated RAW 245.6 macrophages were also investigated. The results show that KR-12 endowed CNFs with antibacterial activity against E. coli and exhibited anti-inflammatory properties and those conjugated by thiol-ene chemistry were the most bioactive. This finding is attributed to a favorable peptide conformation and accessibility (as shown by molecular dynamics simulations), driven by the selective chemistry and length of the linker in the conjugate. The results represent an advancement in the development of CNF-based materials for chronic wound care. This study provides new insights into the effect of the conjugation chemistry on the bioactivity of immobilized host defense peptides, which we believe to be of great value for the use of host defense peptides as therapeutic agents.
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  • Bordé, P., et al. (författare)
  • Transiting exoplanets from the CoRoT space mission: XXIX. The hot Jupiters CoRoT-30 b and CoRoT-31 b
  • 2020
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 635
  • Tidskriftsartikel (refereegranskat)abstract
    • We report the discovery as well as the orbital and physical characterizations of two new transiting giant exoplanets, CoRoT-30 b and CoRoT-31 b, with the CoRoT space telescope. Methods. We analyzed two complementary data sets: photometric transit light curves measured by CoRoT, and radial velocity curves measured by the HARPS spectrometer. To derive the absolute masses and radii of the planets, we modeled the stars from available magnitudes and spectra. Results. We find that CoRoT-30 b is a warm Jupiter on a close-to-circular 9.06-day orbit around a G3V star with a semi-major axis of about 0.08 AU. It has a radius of 1.01 ± 0.08 RJ, a mass of 2.90 ± 0.22 MJ, and therefore a mean density of 3.45 ± 0.65 g cm-3. The hot Jupiter CoRoT-31 b is on a close-to-circular 4.63-day orbit around a G2 IV star with a semi-major axis of about 0.05 AU. It has a radius of 1.46 ± 0.30 RJ, a mass of 0.84 ± 0.34 MJ, and therefore a mean density of 0.33 ± 0.18 g cm-3. Conclusions. Neither system seems to support the claim that stars hosting planets are more depleted in lithium. The radii of both planets are close to that of Jupiter, but they differ in mass; CoRoT-30 b is ten times denser than CoRoT-31 b. The core of CoRoT-30 b would weigh between 15 and 75 Earth masses, whereas relatively weak constraints favor no core for CoRoT-31 b. In terms of evolution, the characteristics of CoRoT-31 b appear to be compatible with the high-eccentricity migration scenario, which is not the case for CoRoT-30 b. The angular momentum of CoRoT-31 b is currently too low for the planet to evolve toward synchronization of its orbital revolution with stellar rotation, and the planet will slowly spiral-in while its host star becomes a red giant. CoRoT-30 b is not synchronized either: it looses angular momentum owing to stellar winds and is expected reach steady state in about 2 Gyr. CoRoT-30 and 31, as a pair, are a truly remarkable example of diversity in systems with hot Jupiters.
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  • Brena, Beatriz M., et al. (författare)
  • ITREOH building of regional capacity to monitor recreational water : development of a non-commercial microcystin ELISA and its impact on public health policy
  • 2006
  • Ingår i: International journal of occupational and environmental health. - 1077-3525 .- 2049-3967. ; 12:4, s. 377-385
  • Tidskriftsartikel (refereegranskat)abstract
    • In 2001, a University of California, Davis-University of the Republic, Montevideo, partnership created a Fogarty ITREOH program to exploit the potential of ELISA to provide a low-cost environmental analysis attractive to economically distressed countries of temperate South America. This paper describes the development and validation of an ELISA method for the determination of Cyanobacteria microcystin toxins in algal blooms, which release hepatotoxic metabolites that can reach toxic levels in rivers, lakes, or coastal estuaries used for recreation or water supplies. The assay made possible the first systematic monitoring of water from the Rio de la Plata at Montevideo over two summers. The project has been integrated into a bi-national effort to monitor the Rio de la Plata.
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36.
  • Bruggmann, P., et al. (författare)
  • Historical epidemiology of hepatitis C virus (HCV) in selected countries
  • 2014
  • Ingår i: Journal of Viral Hepatitis. - Hoboken : Wiley-Blackwell. - 1352-0504 .- 1365-2893. ; 21, s. 5-33
  • Tidskriftsartikel (refereegranskat)abstract
    • Chronic infection with hepatitis C virus (HCV) is a leading indicator for liver disease. New treatment options are becoming available, and there is a need to characterize the epidemiology and disease burden of HCV. Data for prevalence, viremia, genotype, diagnosis and treatment were obtained through literature searches and expert consensus for 16 countries. For some countries, data from centralized registries were used to estimate diagnosis and treatment rates. Data for the number of liver transplants and the proportion attributable to HCV were obtained from centralized databases. Viremic prevalence estimates varied widely between countries, ranging from 0.3% in Austria, England and Germany to 8.5% in Egypt. The largest viremic populations were in Egypt, with 6358000 cases in 2008 and Brazil with 2106000 cases in 2007. The age distribution of cases differed between countries. In most countries, prevalence rates were higher among males, reflecting higher rates of injection drug use. Diagnosis, treatment and transplant levels also differed considerably between countries. Reliable estimates characterizing HCV-infected populations are critical for addressing HCV-related morbidity and mortality. There is a need to quantify the burden of chronic HCV infection at the national level.
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37.
  • Cabra, D. C., et al. (författare)
  • Half-metal phases in a quantum wire with modulated spin-orbit interaction
  • 2017
  • Ingår i: Physical Review B. - 2469-9950. ; 96:20
  • Tidskriftsartikel (refereegranskat)abstract
    • We propose a spin filter device based on the interplay of a modulated spin-orbit interaction and a uniform external magnetic field acting on a quantum wire. Half-metal phases, where electrons with only a selected spin polarization exhibit ballistic conductance, can be tuned by varying the magnetic field. These half-metal phases are proven to be robust against electron-electron repulsive interactions. Our results arise from a combination of explicit band diagonalization, bosonization techniques, and extensive density matrix renormalization group computations.
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38.
  • Cabrera, J., et al. (författare)
  • Transiting exoplanets from the CoRoT space mission: XXVII. CoRoT-28b, a planet orbiting an evolved star, and CoRoT-29b, a planet showing an asymmetric transit
  • 2015
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 579
  • Tidskriftsartikel (refereegranskat)abstract
    • © ESO, 2015. Context. We present the discovery of two transiting extrasolar planets by the satellite CoRoT. Aims. We aim at a characterization of the planetary bulk parameters, which allow us to further investigate the formation and evolution of the planetary systems and the main properties of the host stars. Methods. We used the transit light curve to characterize the planetary parameters relative to the stellar parameters. The analysis of HARPS spectra established the planetary nature of the detections, providing their masses. Further photometric and spectroscopic ground-based observations provided stellar parameters (log g, Teff, vsini) to characterize the host stars. Our model takes the geometry of the transit to constrain the stellar density into account, which when linked to stellar evolutionary models, determines the bulk parameters of the star. Because of the asymmetric shape of the light curve of one of the planets, we had to include the possibility in our model that the stellar surface was not strictly spherical. Results. We present the planetary parameters of CoRoT-28b, a Jupiter-sized planet (mass 0.484 ± 0.087 MJup; radius 0.955 ± 0.066 RJup) orbiting an evolved star with an orbital period of 5.208 51 ± 0.000 38 days, and CoRoT-29b, another Jupiter-sized planet (mass 0.85 ± 0.20 MJup; radius 0.90 ± 0.16 RJup) orbiting an oblate star with an orbital period of 2.850 570 ± 0.000 006 days. The reason behind the asymmetry of the transit shape is not understood at this point. Conclusions. These two new planetary systems have very interesting properties and deserve further study, particularly in the case of the star CoRoT-29.
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39.
  • Cardin, Velia, et al. (författare)
  • A working memory role for superior temporal cortex in deaf individuals independently of linguistic content
  • 2015
  • Konferensbidrag (refereegranskat)abstract
    • Studies of sign languages have been used to test traditional cognitive models of working memory (WM) that distinguish between verbal and visuospatial WM (e.g. Baddeley, 2003), without considering that sign languages operate in the visuospatial domain. Previous studies have shown that WM mental representations and processes are largely similar for signed and spoken languages (e.g. Rönnberg et al., 2004). However, it is not clear to what extent visual WM processes aid and support sign language WM.Here we characterise the neural substrates supporting sign language and visual WM, and the mechanisms that subserve differential processing for signers and for deaf individuals. We conducted a functional magnetic resonance imaging (fMRI) experiment with three groups of participants: deaf native signers, hearing native signers and hearing non-signers. Participants performed a 2-back WM task and a control task on two sets of stimuli: signs from British Sign Language or non-sense objects. Stimuli were composed of point-lights to control for differences in visual features.Our results show activation in a fronto-parietal network for WM processing in all groups, independently of stimulus type, in agreement with previous literature. We also replicate previous findings in deaf signers showing a stronger right posterior superior temporal cortex (STC) activation for visuospatial processing, and stronger bilateral STC activation for sign language stimuli.Group comparisons further reveal stronger activations in STC for WM in deaf signers, but not for the groups of hearing individuals. This activation is independent of the linguistic content of the stimuli, being observed in both WM conditions: signs and objects. These results suggest a cognitive role for STC in deaf signers, beyond sign language processing.
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40.
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41.
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42.
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43.
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44.
  • Csizmadia, S., et al. (författare)
  • Transiting exoplanets from the CoRoT space mission XXVIII. CoRoT-33b, an object in the brown dwarf desert with 2:3 commensurability with its host star
  • 2015
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 584
  • Tidskriftsartikel (refereegranskat)abstract
    • We report the detection of a rare transiting brown dwarf with a mass of 59 M-Jup and radius of 1.1 R-Jup around the metal-rich, [Fe/H] = +0.44, G9V star CoRoT-33. The orbit is eccentric (e = 0.07) with a period of 5.82 d. The companion, CoRoT-33b, is thus a new member in the so-called brown dwarf desert. The orbital period is within 3% to a 3:2 resonance with the rotational period of the star. CoRoT-33b may be an important test case for tidal evolution studies. The true frequency of brown dwarfs close to their host stars (P
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45.
  • Dahl, Maria, et al. (författare)
  • Correction of pathology in mice displaying Gaucher disease type 1 by a clinically-applicable lentiviral vector
  • 2021
  • Ingår i: Molecular Therapy - Methods and Clinical Development. - : Elsevier BV. - 2329-0501. ; 20, s. 312-323
  • Tidskriftsartikel (refereegranskat)abstract
    • This study evaluates a clinically applicable lentiviral vector for treatment of Gaucher disease type 1. Hematopoietic stem cells transduced with the vector and transplanted into a mouse model successfully halted or reversed pathology. These data were used as proof-of-concept for regulatory filing enabling the commencement of an international phase 1/2 clinical trial.
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46.
  • de Almeida Jr, Edward Ferraz, et al. (författare)
  • On Decorating a Honeycomb AlN Monolayer with Hydrogen and Fluorine Atoms: Ab Initio and Experimental Aspects
  • 2024
  • Ingår i: Materials. - : MDPI. - 1996-1944. ; 17:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Mono- and few-layer hexagonal AlN (h-AlN) has emerged as an alternative "beyond graphene" and "beyond h-BN" 2D material, especially in the context of its verification in ultra-high vacuum Scanning Tunneling Microscopy and Molecular-beam Epitaxy (MBE) experiments. However, graphitic-like AlN has only been recently obtained using a scalable and semiconductor-technology-related synthesis techniques, such as metal-organic chemical vapor deposition (MOCVD), which involves a hydrogen-rich environment. Motivated by these recent experimental findings, in the present work, we carried out ab initio calculations to investigate the hydrogenation of h-AlN monolayers in a variety of functionalization configurations. We also investigated the fluorination of h-AlN monolayers in different decoration configurations. We find that a remarkable span of bandgap variation in h-AlN, from metallic properties to nar-row-bandgap semiconductor, and to wide-bandgap semiconductor can be achieved by its hy-drogenation and fluorination. Exciting application prospects may also arise from the findings that H and F decoration of h-AlN can render some such configurations magnetic. We complemented this modelling picture by disclosing a viable experimental strategy for the fluorination of h-AlN.
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47.
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48.
  • Ericzon, Bo-Göran, et al. (författare)
  • Liver transplantation for hereditary transthyretin amyloidosis : after 20 years still the best therapeutic alternative?
  • 2015
  • Ingår i: Transplantation. - 0041-1337 .- 1534-6080. ; 99:9, s. 1847-1854
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Until recently, liver transplantation (Ltx) was the only available treatment for hereditary transthyretin (TTR) amyloidosis; today, however, several pharmacotherapies are tested. Herein, we present survival data from the largest available database on transplanted hereditary TTR patients to serve as a base for comparison.METHODS: Liver transplantation was evaluated in a 20-year retrospective analysis of the Familial Amyloidosis Polyneuropathy World Transplant Registry.RESULTS: From April 1990 until December 2010, data were accumulated from 77 liver transplant centers. The Registry contains 1940 patients, and 1379 are alive. Eighty-eight Ltx were performed in combination with a heart and/or kidney transplantation. Overall, 20-year survival after Ltx was 55.3%. Multivariate analysis revealed modified body mass index, early onset of disease (<50 years of age), disease duration before Ltx, and TTR Val30Met versus non-TTR Val30Met mutations as independent significant survival factors. Early-onset patients had an expected mortality rate of 38% that of the late-onset group (P < 0.001). Furthermore, Val30Met patients had an expected mortality rate of 61% that of non-TTR Val30Met patients (P < 0.001). With each year of duration of disease before Ltx, expected mortality increased by 11% (P < 0.001). With each 100-unit increase in modified body mass index at Ltx, the expected mortality decreased to 89% of the expected mortality (P < 0.001). Cardiovascular death was markedly more common than that observed in patients undergoing Ltx for end-stage liver disease.CONCLUSIONS: Long-term survival after Ltx, especially for early-onset TTR Val30Met patients, is excellent. The risk of delaying Ltx by testing alternative treatments, especially in early-onset TTR Val30Met patients, requires consideration.
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49.
  • Erjefält, Jonas S., et al. (författare)
  • Diffuse alveolar damage patterns reflect the immunological and molecular heterogeneity in fatal COVID-19
  • 2022
  • Ingår i: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 83
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Severe COVID-19 lung disease exhibits a high degree of spatial and temporal heterogeneity, with different histological features coexisting within a single individual. It is important to capture the disease complexity to support patient management and treatment strategies. We provide spatially decoded analyses on the immunopathology of diffuse alveolar damage (DAD) patterns and factors that modulate immune and structural changes in fatal COVID-19. Methods: We spatially quantified the immune and structural cells in exudative, intermediate, and advanced DAD through multiplex immunohistochemistry in autopsy lung tissue of 18 COVID-19 patients. Cytokine profiling, viral, bacteria, and fungi detection, and transcriptome analyses were performed. Findings: Spatial DAD progression was associated with expansion of immune cells, macrophages, CD8+ T cells, fibroblasts, and (lymph)angiogenesis. Viral load correlated positively with exudative DAD and negatively with disease/hospital length. In all cases, enteric bacteria were isolated, and Candida parapsilosis in eight cases. Cytokines correlated mainly with macrophages and CD8+T cells. Pro-coagulation and acute repair were enriched pathways in exudative DAD whereas intermediate/advanced DAD had a molecular profile of elevated humoral and innate immune responses and extracellular matrix production. Interpretation: Unraveling the spatial and molecular immunopathology of COVID-19 cases exposes the responses to SARS-CoV-2-induced exudative DAD and subsequent immune-modulatory and remodeling changes in proliferative/advanced DAD that occur side-by-side together with secondary infections in the lungs. These complex features have important implications for disease management and the development of novel treatments. Funding: CNPq, Bill and Melinda Gates Foundation, HC-Convida, FAPESP, Regeneron Pharmaceuticals, and the Swedish Heart & Lung Foundation.
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50.
  • Feldman, M, et al. (författare)
  • Community health worker knowledge, attitudes and practices towards COVID-19: Learnings from an online cross-sectional survey using a digital health platform, UpSCALE, in Mozambique
  • 2021
  • Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 16:2, s. e0244924-
  • Tidskriftsartikel (refereegranskat)abstract
    • Healthcare workers (HCWs) are at the frontline of the Coronavirus Disease 2019 (COVID-19) pandemic response, yet there is a paucity of literature on their knowledge, attitudes and practices (KAP) in relation to the pandemic. Community Health Workers (CHWs) in Mozambique are known locally as agentes polivalentes elementares (APEs). While technical guidance surrounding COVID-19 is available to support APEs, communicating this information has been challenging due to restrictions on travel, face-to-face group meetings and training, imposed from May to August 2020. A digital health platform, upSCALE, that already supports 1,213 APEs and 299 supervisors across three provinces, is being used to support APEs on effective COVID-19 management by delivering COVID-19 sensitive SMS messages, training modules and a COVID-19 KAP survey. The KAP survey, conducted from June 2020 to August 2020, consisted of 10 questions. Of 1,065 active upSCALE APEs, 28% completed the survey. Results indicate that only a small proportion of APEs listed the correct COVID-19 symptoms, transmission routes and appropriate prevention measures (n = (25%), n = (16%) and n = (39%), respectively) specifically included in national health education materials. Misconceptions were mainly related to transmission routes, high risk individuals and asymptomatic patients. 84% said they followed all government prevention guidelines. The results from the KAP survey were used to support the rapid development and deployment of targeted COVID-19 awareness and education materials for the APEs. A follow-up KAP survey is planned for November 2020. Adapting the existing upSCALE platform enabled a better understanding, in real time, of the KAP of APEs around COVID-19 management. Subsequently, supporting delivery of tailored messages and education, vital for ensuring a successful COVID-19 response.
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