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1.
  • Hussein, Mohamed Ahmed Mohamady, et al. (författare)
  • Dual-drug delivery of Ag-chitosan nanoparticles and phenytoin via core-shell PVA/PCL electrospun nanofibers
  • 2021
  • Ingår i: Carbohydrate Polymers. - : Elsevier BV. - 0144-8617 .- 1879-1344. ; 270
  • Tidskriftsartikel (refereegranskat)abstract
    • Dual-drug delivery systems were constructed through coaxial techniques, which were convenient for the model drugs used the present work. This study aimed to fabricate core-shell electrospun nanofibrous membranes displaying simultaneous cell proliferation and antibacterial activity. For that purpose, phenytoin (Ph), a well-known proliferative agent, was loaded into a polycaprolactone (PCL) shell membrane, and as-prepared silver-chitosan nanoparticles (Ag-CS NPs), as biocidal agents, were embedded in a polyvinyl alcohol (PVA) core layer. The morphology, chemical composition, mechanical and thermal properties of the nanofibrous membranes were characterized by FESEM/STEM, FTIR and DSC. The coaxial PVA-Ag CS NPs/PCL-Ph nanofibers (NFs) showed more controlled Ph release than PVA/PCL-Ph NFs. There was notable improvement in the morphology, thermal, mechanical, antibacterial properties and cytobiocompatibility of the fibers upon incorporation of Ph and Ag-CS NPs. The proposed core-shell PVA/PCL NFs represent promising scaffolds for tissue regeneration and wound healing by the effective dual delivery of phenytoin and Ag-CS NPs.
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  • Uzun, Sena, et al. (författare)
  • A case report of a chronic migraine patient treated with three different anti-CGRP monoclonal antibodies : which parameters better represent the efficacy?
  • 2023
  • Ingår i: Frontiers in Neurology. - 1664-2295. ; 14
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To report the efficacy of different anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) on headache frequency, intensity, and duration. Background: Blockade of CGRP receptors or neuropeptide with anti-CGRP mAbs have been successfully used for several years for the prevention of chronic and episodic migraine. The response is usually assessed by improvement seen in the number of days with headache per month. However, clinical praxis indicates that sole reliance on the frequency of headaches might be insufficient to interpret the efficacy of these treatments. Methods: Retrospective review of a case with a meticulous headache diary who has tried three different anti-CGRP mAbs for chronic migraine prevention. Results: The patient has been diagnosed with chronic migraine and was first treated with erenumab, followed by fremanezumab and thereafter galcanezumab due to several reasons. In addition to significant improvement in all three parameters analyzed with anti-CGRP mAb treatment, the most important and valuable effect on the patient's quality of life was decreased duration and frequency of headaches. At present, the patient is receiving fremanezumab treatment with an excellent tolerability. Conclusion: There is a clear need for careful follow-up and detailed daily records of headaches showing the frequency, duration, and severity for the evaluation of anti-CGRP mAbs treatment. This study shows the importance of this information in order for medical professionals to make an informed decision regarding the best course of anti-CGRP mAbs treatment in cases of side effects or lack of efficacy.
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4.
  • Abohalaka, Reshed, et al. (författare)
  • The effects of fatty acid amide hydrolase and monoacylglycerol lipase inhibitor treatments on lipopolysaccharide-induced airway inflammation in mice.
  • 2020
  • Ingår i: Pulmonary pharmacology & therapeutics. - : Elsevier BV. - 1522-9629 .- 1094-5539. ; 62
  • Tidskriftsartikel (refereegranskat)abstract
    • Cannabinoids and the endocannabinoid system significantly contributes to the airway inflammation. Fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) are two main enzymes responsible for the metabolism of the endocannabinoids anandamide (AEA) and 2-arachydonoyl glycerol (2-AG), respectively. In the present study, we aimed to investigate the effects of local and systemic FAAH and MAGL inhibitor treatments in experimental airway inflammation and tracheal hyperreactivity in mice. Airway inflammation was induced by intranasal (i.n.) lipopolysaccharide (LPS) application (60 μl; 0,1 mg/ml in PBS) to mice and the control group received PBS. Systemic (intraperitoneal (i.p.)) or local (i.n.) FAAH inhibitor URB597 and MAGL inhibitor JZL184 treatments were administered 1h before LPS/PBS application. Fourty 8 h after LPS/PBS application, tracheas were removed to assess airway reactivity, and the lungs and bronchoalveolar lavage (BAL) fluids were isolated for histopathological evaluation, cytokine and endocannabinoid measurements. LPS application lead to an increase in 5-hydroxytryptamine (5-HT) contractions in isolated tracheal rings while carbachol contractions remained unchanged. The increased 5-HT contractions were prevented by both systemic and local URB597 and JZL184 treatments. Systemic treatment with URB597 and JZL184, and local treatment with JZL184 reduced peribronchial and paranchymal inflammation in the LPS group while i.n. application of URB597 worsened the inflammation in the lungs. Systemic URB597 treatment increased lung AEA level whereas it had no effect on 2-AG level. However, JZL184 treatment increased 2-AG level by either systemic or local application, and also elevated AEA level. Inflammation-induced increase in neutrophil numbers was only prevented by systemic URB597 treatment. However, both URB597 and JZL184 treatments abolished the increased TNF-α level either they are administered systemically or locally. These results indicate that FAAH and MAGL inhibition may have a protective effect in airway inflammation and airway hyperreactivity, and therefore their therapeutic potential for airway diseases should be further investigated.
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5.
  • Abohalaka, Reshed, et al. (författare)
  • The effects of systemic and local fatty acid amide hydrolase and monoacylglycerol lipase inhibitor treatments on the metabolomic profile of lungs.
  • 2022
  • Ingår i: Biomedical chromatography : BMC. - : Wiley. - 1099-0801 .- 0269-3879. ; 36:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The contribution of the endocannabinoid system to both physiology and pathological processes in the respiratory system makes it a promising target for inflammatory airway diseases. Previously, we have shown that increasing the tissue endocannabinoid levels by fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) inhibitors can prevent airway inflammation and hyperreactivity. In this study, the changes in the levels of major metabolites of endocannabinoids by systemic and local FAAH or MAGL inhibitor treatments were evaluated. Mice were treated with either the FAAH inhibitor URB597 or the MAGL inhibitor JZL184 by local (intranasal) or systemic (intraperitoneal) application. Bronchoalveolar lavage (BAL) fluids and lungs were isolated afterward in order to perform histopathological and metabolomic analyses. There were no significant histopathological changes in the lungs and neutrophil, and macrophage and lymphocyte numbers in BAL fluid were not altered after local and systemic treatments. However, GC-MS-based metabolomics profile allowed us to identify 102 metabolites in lung samples, among which levels of 75 metabolites were significantly different from the control. The metabolites whose levels were changed by treatments were mostly related to the endocannabinoid system and energy metabolism. Therefore, these changes may contribute to the anti-inflammatory effects of URB597 and JZL184 treatments in mice.
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6.
  • Abramsson, Mia L, et al. (författare)
  • Charge engineering reveals the roles of ionizable side chains in electrospray ionization mass spectrometry
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • The role of ionizable side chains in the electrospray ionization mass spectrometry of intact proteins remains hotly debated but has not been conclusively addressed because multiple chargeable sites are present in virtually all proteins. Using engineered soluble proteins, we show that ionizable side chains are completely dispensable for charging under native conditions, but if present, they are preferential protonation sites. The absence of ionizable side chains results in identical charge state distributions under native-like and denaturing conditions, whilst co-existing conformers can be distinguished using ion mobility separation. An excess of ionizable side chains, on the other hand, effectively modulates protein ion stability. We conclude that the sum of charges is governed solely by Coulombic terms, while their locations affect the stability of the protein in the gas phase.
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7.
  • Abramsson, Mia L., et al. (författare)
  • Charge Engineering Reveals the Roles of Ionizable Side Chains in Electrospray Ionization Mass Spectrometry
  • 2021
  • Ingår i: JACS Au. - : American Chemical Society (ACS). - 2691-3704. ; 1:12, s. 2385-2393
  • Tidskriftsartikel (refereegranskat)abstract
    • In solution, the charge of a protein is intricately linked to its stability, but electrospray ionization distorts this connection, potentially limiting the ability of native mass spectrometry to inform about protein structure and dynamics. How the behavior of intact proteins in the gas phase depends on the presence and distribution of ionizable surface residues has been difficult to answer because multiple chargeable sites are present in virtually all proteins. Turning to protein engineering, we show that ionizable side chains are completely dispensable for charging under native conditions, but if present, they are preferential protonation sites. The absence of ionizable side chains results in identical charge state distributions under native-like and denaturing conditions, while coexisting conformers can be distinguished using ion mobility separation. An excess of ionizable side chains, on the other hand, effectively modulates protein ion stability. In fact, moving a single ionizable group can dramatically alter the gas-phase conformation of a protein ion. We conclude that although the sum of the charges is governed solely by Coulombic terms, their locations affect the stability of the protein in the gas phase.
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  • Akkoyun, S., et al. (författare)
  • AGATA - Advanced GAmma Tracking Array
  • 2012
  • Ingår i: Nuclear Instruments and Methods in Physics Research, Section A: Accelerators, Spectrometers, Detectors and Associated Equipment. - : Elsevier BV. - 0168-9002 .- 0167-5087 .- 1872-9576. ; 668, s. 26-58
  • Tidskriftsartikel (refereegranskat)abstract
    • The Advanced GAmma Tracking Array (AGATA) is a European project to develop and operate the next generation γ-ray spectrometer. AGATA is based on the technique of γ-ray energy tracking in electrically segmented high-purity germanium crystals. This technique requires the accurate determination of the energy, time and position of every interaction as a γ ray deposits its energy within the detector volume. Reconstruction of the full interaction path results in a detector with very high efficiency and excellent spectral response. The realisation of γ-ray tracking and AGATA is a result of many technical advances. These include the development of encapsulated highly segmented germanium detectors assembled in a triple cluster detector cryostat, an electronics system with fast digital sampling and a data acquisition system to process the data at a high rate. The full characterisation of the crystals was measured and compared with detector- response simulations. This enabled pulse-shape analysis algorithms, to extract energy, time and position, to be employed. In addition, tracking algorithms for event reconstruction were developed. The first phase of AGATA is now complete and operational in its first physics campaign. In the future AGATA will be moved between laboratories in Europe and operated in a series of campaigns to take advantage of the different beams and facilities available to maximise its science output. The paper reviews all the achievements made in the AGATA project including all the necessary infrastructure to operate and support the spectrometer. © 2011 Elsevier B.V. All rights reserved.
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10.
  • Aktaş, Vezir, et al. (författare)
  • Saldırgan Olan ve Olmayan Çocuklarda Düşmanca Niyet Yükleme Yanlılığının Cinsiyete Bağlı Olarak İncelenmesi (Hostile attributional bias in aggressive and nonaggressive children)
  • 2005
  • Ingår i: Türk Psikoloji Dergisi (Turkish Journal of Psychology). - 1300-4433. ; 20:55, s. 43-59
  • Tidskriftsartikel (refereegranskat)abstract
    • Bu çalışmada olumsuz niyet yükleme eğiliminin çocukların sosyal ilişkilerinde saldırgan olup olmamalarına ve cinsiyetlerine göre değişip değişmediği incelenmiştir. Ayrıca, bu çalışmada fiziksel, pasif ve sözel saldırganlık türlerinde düşmanca yüklemede bulunma açısından saldırganlık düzeyi ve cinsiyete göre bir farklılık gözlenip gözlenmeyeceği de araştırılmıştır. Bu amaçla, ilköğretim 5. sınıfta okuyan 236 kız ve 293 erkek öğrenciye sosyometrik bir saldırganlık ölçeği ve 11 resimden oluşan bir resim anketi uygulanmıştır. Verilere 2 (saldırganlık düzeyi: saldırgan-saldırgan değil) x 2 (cinsiyet: kız-erkek) faktörlü araştırma desenine uygun varyans analizleri uygulanmıştır. Bulgular, sosyal ilişkileri açısından saldırgan olarak tanınan çocukların olumsuz tepkileri içeren davranış seçeneklerini (kişisel nedenlere ve olumsuz niyete yapılan yüklemeler) saldırgan olmayan çocuklara kıyasla daha fazla seçtiklerini göstermiştir. Bu bulgu daha önce yapılan çalışmalardan elde edilen bulgularla da uyuşmaktadır. Saldırganlığın alt boyutları açısından bakıldığında ise sadece fiziksel saldırganlık gösteren çocuklar, fiziksel saldırganlık göstermeyen çocuklara kıyasla daha fazla olumsuz yüklemelerde bulunmuşlardır. Dolayısıyla bu çalışmada aktif yönelimli saldırganlığın da tepkisel saldırganlık gibi düşmanca yükleme yanlılığıyla ilişkili olabileceği yönünde bir bulgu elde edilmiştir. Araştırmada düşmanca niyet yükleme eğiliminde cinsiyet temel etkisi de gözlenmiştir. Sosyal ilişkileri açısından genel olarak saldırgan tanınan erkekler, saldırgan tanınan kızlardan daha fazla düşmanca niyet yüklemesinde bulunma eğilimi göstermişlerdir.
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11.
  • Albayrak, Sahin, et al. (författare)
  • Smart middleware for mutual service-network awareness in evolving 3GPP networks : network aware applications & application aware networks
  • 2008
  • Ingår i: 2008 3rd International Conference on Communication System Software and Middleware and workshops. - Piscataway, NJ : IEEE Communications Society. ; , s. 44-50
  • Konferensbidrag (refereegranskat)abstract
    • We have designed a smart middleware and are working on implementing and deploying it as a landmark architectural piece run by nodes of the Future Internet. The middleware we propose aims as a main goal at making applications and services fully network-aware in the sense that they utilize network resources and tune their own demands based on what the underlying networks can offer. On the other hand, the smart middleware makes networks service aware in the sense that networks also adapt their configuration to service demands. Challenges of the Future Internet such as scalability, increased interoperability, and smart collaboration between engines are addressed by our middleware. Focusing on 3GPP networks including IP Multimedia Subsystem (IMS) networks, this paper presents the architectural design of our middleware and shows in two showcases how and why it is capable of addressing future challenges. Scenarios such as service and network-aware coordinated load balancing and "always-best-connected" as a service verify the merits of our smart middleware design.
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12.
  • Alpay, Sahin (författare)
  • Turkar i Stockholm : En studie av invandrare, politik och samhälle
  • 1980
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The present study which is a product of the research project "Political Resocialization of Immigrants (PRI)" carried out at the Political Science Department of the Stockholm University is based primarily on interviews in 1976 with Turkish immigrants in the 18—67 age group domiciled in the Stockholm municipality. The questions this study addresses itself are: — Which pre-migration and migration characteristics of Turkish immigrants in Stockholm are of special importance with respect to their political resocialization? — What are the living conditions of Turks in Stockholm and what are their perceptions and subjective evaluations of these conditions? — In what ways and to what extent do Turks participate in politics in Sweden? — What are the consequences of Turkish immigrants' background characteristics, living conditions and subjective evaluations of these conditions for their political resocialization? The study consists of nine chapters. The first three provide an introduction to this field of research, a discussion of theoretical points of departure, and an account of methods of data-collection. Next two chapters give background information on emigration from Turkey and immigration to Sweden and Stockholm. Chapter six presents data on the Turks' living conditions. They appear to be highly concentrated in the unskilled manual occupations and certain residential areas. Their social contacts are largely limited to relations with fellow countrymen, and they display very poor knowledge of the Swedish language. Chapter seven gives data on the Turks' perceptions and subjective evaluations of their living conditions. Results reveal a relatively high degree of satisfaction primarily with the material welfare they have attained in Sweden, and a rather strong attachment to Turkish culture and identity. Chapter eight discusses the political-cultural background of Turks and provides data on their political participation in Sweden. Findings indicate lower levels of political information, exposure, interest and activity among the Turks as compared to other immigrant groups under study in the PRI-project. The final chapter summarizes the results of the study which show that the political resocialization of Turkish immigrants has so far made little progress. Their political-cultural background characteristics and their living conditions in Stockholm are closely related with their political relearning. 
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15.
  • Arndt, Tina, et al. (författare)
  • Spidroin N-terminal domain forms amyloid-like fibril based hydrogels and provides a protein immobilization platform
  • 2022
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13
  • Tidskriftsartikel (refereegranskat)abstract
    • Recombinant spider silk proteins (spidroins) have multiple potential applications in development of novel biomaterials, but their multimodal and aggregation-prone nature have complicated production and straightforward applications. Here, we report that recombinant miniature spidroins, and importantly also the N-terminal domain (NT) on its own, rapidly form self-supporting and transparent hydrogels at 37 °C. The gelation is caused by NT α-helix to β-sheet conversion and formation of amyloid-like fibrils, and fusion proteins composed of NT and green fluorescent protein or purine nucleoside phosphorylase form hydrogels with intact functions of the fusion moieties. Our findings demonstrate that recombinant NT and fusion proteins give high expression yields and bestow attractive properties to hydrogels, e.g., transparency, cross-linker free gelation and straightforward immobilization of active proteins at high density.
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16.
  • Arslan, Mehmet Enes, et al. (författare)
  • In Vitro Transcriptome Analysis of Cobalt Boride Nanoparticles on Human Pulmonary Alveolar Cells
  • 2022
  • Ingår i: Materials. - : MDPI AG. - 1996-1944. ; 15:23
  • Tidskriftsartikel (refereegranskat)abstract
    • Nanobiotechnology influences many different areas, including the medical, food, energy, clothing, and cosmetics industries. Considering the wide usage of nanomaterials, it is necessary to investigate the toxicity potentials of specific nanosized molecules. Boron-containing nanoparticles (NPs) are attracting much interest from scientists due to their unique physicochemical properties. However, there is limited information concerning the toxicity of boron-containing NPs, including cobalt boride (Co2B) NPs. Therefore, in this study, Co2B NPs were characterized using X-ray crystallography (XRD), transmission electron microscope (TEM), scanning electron microscope (SEM), and energy-dispersive X-ray spectroscopy (EDX) techniques. Then, we performed 3-(4,5-dimethyl-thiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT), lactate dehydrogenase (LDH) release, and neutral red (NR) assays for assessing cell viability against Co2B NP exposure on cultured human pulmonary alveolar epithelial cells (HPAEpiC). In addition, whole-genome microarray analysis was carried out to reveal the global gene expression differentiation of HPAEpiC cells after Co2B NP application. The cell viability tests unveiled an IC50 value for Co2B NPs of 310.353 mg/L. The results of our microarray analysis displayed 719 gene expression differentiations (FC >= 2) among the analyzed 40,000 genes. The performed visualization and integrated discovery (DAVID) analysis revealed that there were interactions between various gene pathways and administration of the NPs. Based on gene ontology biological processes analysis, we found that the P53 signaling pathway, cell cycle, and cancer-affecting genes were mostly affected by the Co2B NPs. In conclusion, we suggested that Co2B NPs would be a safe and effective nanomolecule for industrial applications, particularly for medical purposes.
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17.
  • Ashina, Messoud, et al. (författare)
  • Real-world effectiveness of fremanezumab for the preventive treatment of migraine : Interim analysis of the pan-European, prospective, observational, phase 4 PEARL study
  • 2023
  • Ingår i: Cephalalgia. - 0333-1024. ; 43:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The ongoing Pan-European Real Life (PEARL) phase 4 study is evaluating fremanezumab effectiveness and safety for the prevention of episodic and chronic migraine. This interim analysis reports primary, secondary and exploratory endpoints from when 500 participants completed at least six months of treatment. Methods: Adults with episodic migraine or chronic migraine maintaining daily headache diaries were enrolled upon initiation of fremanezumab. Primary endpoint: proportion of participants with ≥50% reduction in monthly migraine days during the six-month period after fremanezumab initiation. Secondary endpoints: mean change from baseline across months 1–12 in monthly migraine days, acute migraine medication use, and headache-related disability. Exploratory endpoint: mean change in headache severity from baseline across months 1–12. Safety was assessed through adverse events reported. Results: Overall, 897 participants were enrolled and 574 included in the effectiveness analyses (episodic migraine, 25.8%; chronic migraine, 74.2%). Of participants with data available, 175/313 (55.9%) achieved ≥50% monthly migraine days reduction during the six-month period post-initiation. Across months 1–12, there were sustained reductions in mean monthly migraine days, acute medication use, disability scores, and headache severity. Few adverse events were reported. Conclusion: PEARL interim results support the effectiveness and safety of fremanezumab for migraine prevention in a real-world population across several European countries. Trial registration: encepp.eu: EUPAS35111.
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18.
  • Atis, Muge, et al. (författare)
  • Effects of methyl-beta-cyclodextrin on blood-brain barrier permeability in angiotensin II-induced hypertensive rats
  • 2019
  • Ingår i: Brain Research. - : ELSEVIER SCIENCE BV. - 0006-8993 .- 1872-6240. ; 1715, s. 148-155
  • Tidskriftsartikel (refereegranskat)abstract
    • The blood-brain barrier (BBB) permeability primarily increases in cerebral venules during acute hypertension. Methyl-beta-cyclodextrin (M beta CD), a cholesterol-depleting agent, decreases the expression of caveolins disrupting caveolar structures. We aimed to determine the effects of M beta CD on the BBB permeability of angiotensin (ANG) II-induced hypertensive rats. Three minutes after M beta CD administration (5 mg/kg), acute hypertension was induced by ANG II (60 mu g/kg). Evans blue (EB) and horseradish peroxidase (HRP) tracers were used to assess BBB permeability. Immunohistochemistry for caveolin (Cav)-1 and tight junction protein claudin-5 was performed. EB dye content significantly increased in both cerebral cortices and left hippocampus in M beta CD (P < 0.05), right cerebral cortex and both hippocampi in ANG II (P < 0.05; P < 0.01), and both cerebral cortices and hippocampi in M beta CD plus ANG II groups compared with controls (P < 0.05; P < 0.01). A significant decrease in claudin-5 immunostaining intensity was observed in animals treated with M beta CD compared with controls (P < 0.05). Cav-1 immunostaining intensity increased in ANG II group (P < 0.05). Ultrastructurally, HRP reaction products were observed in endothelial cells of the microvessels in the hippocampus region in M beta CD group while the tracer was mainly localized in astrocytes and neurons in ANG II, and M beta CD plus ANG II groups. The endothelial cells of the venules in the cerebral cortex of the animals in the latter experimental groups also showed an abundance of caveolar vesicles devoid of HRP reaction products. Our results revealed that M beta CD did not provide overall protective effects on BBB integrity in acute hypertension and even led to BBB disruption in normotensive animals.
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  • Aydemir, Esra, et al. (författare)
  • Impact of silencing eEF2K expression on the malignant properties of chordoma
  • 2023
  • Ingår i: Molecular Biology Reports. - : Springer Science and Business Media LLC. - 0301-4851 .- 1573-4978. ; 50:4, s. 3011-3022
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Eukaryotic elongation factor 2 kinase (eukaryotic elongation factor 2 kinase, eEF2K) is a calcium calmodulin dependent protein kinase that keeps the highest energy consuming cellular process of protein synthesis under check through negative regulation. eEF2K pauses global protein synthesis rates at the translational elongation step by phosphorylating its only kown substrate elongation factor 2 (eEF2), a unique translocase activity in ekaryotic cells enabling the polypeptide chain elongation. Therefore, eEF2K is thought to preserve cellular energy pools particularly upon acute development of cellular stress conditions such as nutrient deprivation, hypoxia, or infections. Recently, high expression of this enzyme has been associated with poor prognosis in an array of solid tumor types. Therefore, in a growing number of studies tremendous effort is being directed to the development of treatment methods aiming to suppress eEF2K as a novel therapeutic approach in the fight against cancer. Methods: In our study, we aimed to investigate the changes in the tumorigenicity of chordoma cells in presence of gene silencing for eEF2K. Taking a transient gene silencing approach using siRNA particles, eEF2K gene expression was suppressed in chordoma cells. Results: Silencing eEF2K expression was associated with a slight increase in cellular proliferation and a decrease in death rates. Furthermore, no alteration in the sensitivity of chordoma cells to chemotherapy was detected in response to the decrease in eEF2K expression which intriguingly promoted suppression of cell migratory and invasion related properties. Conclusion: Our findings indicate that the loss of eEF2K expression in chordoma cell lines results in the reduction of metastatic capacity.
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21.
  • Barthoma, Soner, et al. (författare)
  • Integration Policies – Trends, Problems and Challenges : An Integrated Report of 9 Country Cases
  • 2020
  • Rapport (refereegranskat)abstract
    • This report provides a snapshot for some of the primary findings, trends and challenges with regard to immigrant integration that have been studied in nine country cases, based on research conducted within the framework of the Horizon2020 RESPOND project. These countries are Sweden, Germany, Italy, Greece, Austria, Poland, the UK, Turkey and Iraq. All nine country reports study integration in five thematic domains (labour market, education, housing, psychosocial health and citizenship) by looking at policies (macro level), practices (meso) and experiences of refugees and asylum seekers (micro level). This integrated report relies on data discussed in the macro sections of these country reports, and systematically analyses the same thematic fields in each country by looking at:a) Legal and institutional frameworks for each thematic field (labour market, education, housing, psychosocial health, and citizenship);b) The main trends in these domains, andc) Problems and challenges that refugees face (based on the interview material at micro and meso levels).Each section ends with an informative summative table. Overall, the integrated report provides a rich overview of country cases, and thus, can be read either as a whole or as separate sections.
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22.
  • Barucci, Valentina, et al. (författare)
  • On free resolutions of some semigroup rings
  • 2014
  • Ingår i: Journal of Pure and Applied Algebra. - : Elsevier BV. - 0022-4049 .- 1873-1376. ; 218:6, s. 1107-1116
  • Tidskriftsartikel (refereegranskat)abstract
    • For some numerical semigroup rings of small embedding dimension, namely those of embedding dimension 3, and symmetric or pseudosymmetric of embedding dimension 4, presentations has been determined in the literature. We extend these results by giving the whole graded minimal free resolutions explicitly. Then we use these resolutions to determine some invariants of the semigroups and certain interesting relations among them. Finally, we determine semigroups of small embedding dimensions which have strongly indispensable resolutions.
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23.
  • Belivermis, M., et al. (författare)
  • Physiological and gene expression responses of the mussel Mytilus galloprovincialis to low pH and low dissolved oxygen
  • 2023
  • Ingår i: Marine Pollution Bulletin. - : Elsevier BV. - 0025-326X. ; 187
  • Tidskriftsartikel (refereegranskat)abstract
    • The prevalence and frequency of hypoxia events have increased worldwide over the past decade as a conse-quence of global climate change and coastal biological oxygen depletions. On the other hand, anthropogenic emissions of CO2 and consequent accumulation in the sea surface result in a perturbation of the seawater car-bonate system, including a decrease in pH, known as ocean acidification. While the effect of decreases in pH and dissolved oxygen (DO) concentration is better understood, their combined effects are still poorly resolved. Here, we exposed adult mussels (Mytilus galloprovincialis) to two pHs (8.27 and 7.63) and DO concentrations (7.65 and 2.75 mg L- 1) over 17 days in a full-factorial design. These levels correspond to extremes of the present natural variability and are relevant in the context of ocean acidification and hypoxia. No mortality was observed during the experiment. However, sublethal effects were observed for clearance and oxygen consumption rates, as well as total haemocytes count and haemocytes viability and gene expression in mussels exposed to the combination of low pH and low DO. Respiration and excretion rates were not significantly impacted by low pH and DO, alone or in combination. Overall, low pH alone led to a decrease in all tested physiological parameters while low DO alone led to a decline in clearance rate, haemocyte parameters and an increase in carbohydrate content. Both pa-rameters led to up-or down-regulation of most of the selected genes. Not surprisingly, the combined effect of low pH and low DO could not be predicted by a simple arithmetic additive response at the effect level, highlighting more complex and non-linear effects.
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24.
  • Benzoni, G., et al. (författare)
  • First Measurement of Beta Decay Half-lives in Neutron-rich Tl and Bi Isotopes
  • 2012
  • Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 715:4-5, s. 293-297
  • Tidskriftsartikel (refereegranskat)abstract
    • Neutron-rich isotopes around lead, beyond N = 126, have been studied exploiting the fragmentation of an uranium primary beam at the FRS-RISING setup at GSI. For the first time beta-decay half-lives of Bi-219 and Tl-211,Tl-212,Tl-213 isotopes have been derived. The half-lives have been extracted using a numerical simulation developed for experiments in high-background conditions. Comparison with state of the art models used in r-process calculations is given, showing a systematic underestimation of the experimental values, at variance from close-lying nuclei. (c) 2012 Elsevier B.V. All rights reserved.
  •  
25.
  • Birkenbach, B., et al. (författare)
  • Spectroscopy of the neutron-rich actinide nucleus U-240 following multinucleon-transfer reactions
  • 2015
  • Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 92:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Nuclear structure information for the neutron-rich actinide nuclei is important since it is the benchmark for theoretical models that provide predictions for the heaviest nuclei. Purpose: gamma-ray spectroscopy of neutron-rich heavy nuclei in the actinide region. Method: Multinucleon-transfer reactions in Zn-70 + U-238 and Xe-136 + U-238 have been measured in two experiments performed at the INFN Legnaro, Italy. In the Zn-70 experiment the high-resolution HPGe Clover Array (CLARA) coupled to the magnetic spectrometer PRISMA was employed. In the Xe-136 experiment the high-resolution Advanced Gamma Tracking Array (AGATA) was used in combination with PRISMA and the Detector Array for Multinucleon Transfer Ejectiles (DANTE). Results: The ground-state band (g.s. band) of U-240 was measured up to the 20(+) level and a tentative assignment was made up to the (24(+)) level. Results from gamma gamma coincidence and from particle coincidence analyses are shown. Moments of inertia (MoI) show a clear upbend. Evidence for an extended first negative-parity band of U-240 is found. Conclusions: A detailed comparison with latest calculations shows best agreement with cranked relativistic Hartree-Bogoliubov (CRHB) calculations for the g.s. band properties. The negative-parity band shows the characteristics of a K-pi = 0 band based on an octupole vibration.
  •  
26.
  • Bolla, Jani Reddy, et al. (författare)
  • A Mass-Spectrometry-Based Approach to Distinguish Annular and Specific Lipid Binding to Membrane Proteins
  • 2020
  • Ingår i: Angewandte Chemie International Edition. - : Wiley. - 1433-7851 .- 1521-3773. ; 59:9, s. 3523-3528
  • Tidskriftsartikel (refereegranskat)abstract
    • Membrane proteins engage in a variety of contacts with their surrounding lipids, but distinguishing between specifically bound lipids, and non-specific, annular interactions is a challenging problem. Applying native mass spectrometry to three membrane protein complexes with different lipid-binding properties, we explore the ability of detergents to compete with lipids bound in different environments. We show that lipids in annular positions on the presenilin homologue protease are subject to constant exchange with detergent. By contrast, detergent-resistant lipids bound at the dimer interface in the leucine transporter show decreased k(off) rates in molecular dynamics simulations. Turning to the lipid flippase MurJ, we find that addition of the natural substrate lipid-II results in the formation of a 1:1 protein-lipid complex, where the lipid cannot be displaced by detergent from the highly protected active site. In summary, we distinguish annular from non-annular lipids based on their exchange rates in solution.
  •  
27.
  • Browne, F., et al. (författare)
  • Pairing Forces Govern Population of Doubly Magic Ca-54 from Direct Reactions
  • 2021
  • Ingår i: Physical Review Letters. - : American Physical Society (APS). - 0031-9007 .- 1079-7114. ; 126:25
  • Tidskriftsartikel (refereegranskat)abstract
    • Direct proton-knockout reactions of Sc-55 at similar to 220 MeV/nucleon were studied at the RIKEN Radioactive Isotope Beam Factory. Populated states of Ca-54 were investigated through -ray and invariant-mass spectroscopy. Level energies were calculated from the nuclear shell model employing a phenomenological intemucleon interaction. Theoretical cross sections to states were calculated from distorted-wave impulse approximation estimates multiplied by the shell model spectroscopic factors, which describe the wave function overlap of the Sc-55 ground state with states in Ca-54. Despite the calculations showing a significant amplitude of excited neutron configurations in the ground-state of Sc-55, valence proton removals populated predominantly the ground state of Ca-54. This counterintuitive result is attributed to pairing effects leading to a dominance of the ground-state spectroscopic factor. Owing to the ubiquity of the pairing interaction, this argument should be generally applicable to direct knockout reactions from odd-even to even-even nuclei.
  •  
28.
  • Bruce, A. M., et al. (författare)
  • Beta Decay of 102Y Produced in Projectile Fission of 238U
  • 2012
  • Ingår i: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6596 .- 1742-6588. ; 381
  • Tidskriftsartikel (refereegranskat)abstract
    • The population of 102Zr following the β decay of 102Y produced in the projectile fission of 238U at the GSI facility in Darmstadt, Germany has been studied. 102Y is known to ß decay into 102Zr via two states, one of high spin and the other low spin. These states preferentially populate different levels in the 102Zr daughter. In this paper the intensities of transitions in 102Zr observed are compared with those from the decay of the low-spin level studied at the TRISTAN facility at Brookhaven National Laboratory and of the high-spin level studied at the JOSEF separator at the Kernforschungsanlage Jülich.
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29.
  • Buddenkotte, Thomas, et al. (författare)
  • Deep learning-based segmentation of multisite disease in ovarian cancer
  • 2023
  • Ingår i: EUROPEAN RADIOLOGY EXPERIMENTAL. - : Springer Nature. - 2509-9280. ; 7:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: To determine if pelvic/ovarian and omental lesions of ovarian cancer can be reliably segmented on computed tomography (CT) using fully automated deep learning-based methods.Methods: A deep learning model for the two most common disease sites of high-grade serous ovarian cancer lesions (pelvis/ovaries and omentum) was developed and compared against the well-established “no-new-Net” framework and unrevised trainee radiologist segmentations. A total of 451 CT scans collected from four different institutions were used for training (n = 276), evaluation (n = 104) and testing (n = 71) of the methods. The performance was evaluated using the Dice similarity coefficient (DSC) and compared using a Wilcoxon test.Results: Our model outperformed no-new-Net for the pelvic/ovarian lesions in cross-validation, on the evaluation and test set by a significant margin (p values being 4 × 10–7, 3 × 10–4, 4 × 10–2, respectively), and for the omental lesions on the evaluation set (p = 1 × 10–3). Our model did not perform significantly differently in segmenting pelvic/ovarian lesions (p = 0.371) compared to a trainee radiologist. On an independent test set, the model achieved a DSC performance of 71 ± 20 (mean ± standard deviation) for pelvic/ovarian and 61 ± 24 for omental lesions.Conclusion: Automated ovarian cancer segmentation on CT scans using deep neural networks is feasible and achieves performance close to a trainee-level radiologist for pelvic/ovarian lesions.Relevance statement: Automated segmentation of ovarian cancer may be used by clinicians for CT-based volumetric assessments and researchers for building complex analysis pipelines.Key points:The first automated approach for pelvic/ovarian and omental ovarian cancer lesion segmentation on CT images has been presented.Automated segmentation of ovarian cancer lesions can be comparable with manual segmentation of trainee radiologists.Careful hyperparameter tuning can provide models significantly outperforming strong state-of-the-art baselines. Graphical Abstract: [Figure not available: see fulltext.]
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30.
  • Cakmakli, Gül Yalcin, et al. (författare)
  • Spectral Analysis of Lithium Tremor
  • 2021
  • Ingår i: Archives of Neuropsychiatry. - : Turk Noropsikiyatri Dernegi. - 1309-4866. ; 58, s. 268-273
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Lithium has proven efficacy in bipolar affective disorder (BAD) but induces tremor as a side effect in a quarter of patients. Lithium tremor (LT) shares some clinical characteristics of essential tremor (ET) and Parkinson’s disease tremor (PT), which might cause difficulties in differential diagnosis. Furthermore, current knowledge of LT is lacking detailed electrophysiological characterization. Here, we present detailed spectral attributes of accelerometric tremor recordings as a diagnostic tool for LT. Methods: 10 patients (7 males, 3 females) between ages of 29–68, who were on lithium for BAD for 2–12 years, were evaluated for hand tremor with the spectral analysis of accelerometric recordings with different postures. Tremor severity was rated clinically on WHIGET (Washington Heights-Inwood Genetic Study of Essential Tremor) scale. Results were analyzed in comparison to results of ET (n=19) and PT (n=19) patients from our database. Results: LT was most prominent at extensor postures with an average peak frequency (PF) of 8.0±0.3 Hz and an extremely low amplitude, high harmonic components and high noise level. The average PF of LT was similar to that of ET (7.3±0.4 Hz), but higher than that of PT (5.3±0.2 Hz) (p<0.0001). With weight loading, the PF of LT showed an increase of 1.3 Hz. Average amplitude of PT was higher than that of both LT and ET (p<0.0001); harmonic components of LT was comparable to PT whereas noise levels were similar to that of ET. Mean WHIGET score of LT (6.5±0.5) was significantly lower than that of ET (13.1±1) (p<0.0001). Conclusion: Electrophysiological features detected by accelerometry may help in differential diagnosis of LT from ET and PT. Keywords: Lithium tremor, accelerometry, tremorogram, peak frequency, harmonic components
  •  
31.
  • Cederfjäll, Erik, et al. (författare)
  • Continuous DOPA synthesis from a single AAV: dosing and efficacy in models of Parkinson's disease.
  • 2013
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 3
  • Tidskriftsartikel (refereegranskat)abstract
    • We used a single adeno-associated viral (AAV) vector co-expressing tyrosine hydroxylase (TH) and GTP cyclohydrolase 1 (GCH1) to investigate the relationship between vector dose, and the magnitude and rate of recovery in hemi-parkinsonian rats. Intrastriatal injections of >1E10 genomic copies (gc) of TH-GCH1 vector resulted in complete recovery in drug-naïve behavior tests. Lower vector dose gave partial to no functional improvement. Stereological quantification revealed no striatal NeuN+ cell loss in any of the groups, whereas a TH-GCH1 dose of >1E11 gc resulted in cell loss in globus pallidus. Thus, a TH-GCH1 dose of 1E10 gc gave complete recovery without causing neuronal loss. Safety and efficacy was also studied in non-human primates where the control vector resulted in co-expression of the transgenes in caudate-putamen. In the TH-GCH1 group, GCH1 expression was robust but TH was not detectable. Moreover, TH-GCH1 treatment did not result in functional improvement in non-human primates.
  •  
32.
  • Cederfjäll, Erik, et al. (författare)
  • Design of a Single AAV Vector for Coexpression of TH and GCH1 to Establish Continuous DOPA Synthesis in a Rat Model of Parkinson's Disease.
  • 2012
  • Ingår i: Molecular Therapy. - : Elsevier BV. - 1525-0024 .- 1525-0016. ; 20:7, s. 1315-1326
  • Tidskriftsartikel (refereegranskat)abstract
    • Preclinical efficacy of continuous delivery of 3,4-dihydroxyphenylalanine (DOPA) with adeno-associated viral (AAV) vectors has recently been documented in animal models of Parkinson's disease (PD). So far, all studies have utilized a mix of two monocistronic vectors expressing either of the two genes, tyrosine hydroxylase (TH) and GTP cyclohydrolase-1 (GCH1), needed for DOPA production. Here, we present a novel vector design that enables efficient DOPA production from a single AAV vector in rats with complete unilateral dopamine (DA) lesions. Functional efficacy was assessed with drug-induced and spontaneous motor behavioral tests where vector-treated animals showed near complete and stable recovery within 1 month. Recovery of motor function was associated with restoration of extracellular DA levels as assessed by online microdialysis. Histological analysis showed robust transgene expression not only in the striatum but also in overlying cortical areas. In globus pallidus, we noted loss of NeuN staining, which might be due to different sensitivity in neuronal populations to transgene expression. Taken together, we present a single AAV vector design that result in efficient DOPA production and wide-spread transduction. This is a favorable starting point for continued translation toward a therapeutic application, although future studies need to carefully review target region, vector spread and dilution with this approach.
  •  
33.
  • Cederfjäll, Erik, et al. (författare)
  • Key factors determining the efficacy of gene therapy for continuous DOPA delivery in the Parkinsonian brain
  • 2012
  • Ingår i: Neurobiology of Disease. - : Elsevier BV. - 0969-9961. ; 48:2, s. 222-227
  • Forskningsöversikt (refereegranskat)abstract
    • L-DOPA is currently the standard treatment for alleviating the motor symptoms in Parkinson's disease. The therapeutic efficacy, however, diminishes as the disease progresses. It has been suggested that the beneficial effect of L-DOPA could be reestablished by changing the mode of administration. Indeed, continuous delivery of L-DOPA has been shown to be an effective way to circumvent many of the side effects seen with traditional oral administration, which results in an intermittent supply of the dopamine precursor to the brain. However, all currently tested continuous dopaminergic stimulation approaches rely on peripheral administration. This is not ideal since it gives rise to off target effects and is difficult to maintain long-term. Thus, there is an unmet need for an effective continuous administration method with an acceptable side effect profile. Viral-mediated gene therapy is a promising alternative paradigm that can meet this demand. Encouraging preclinical studies in animal models of Parkinson's disease showed therapeutic efficacy after expression of the genes encoding the enzymes required for biosynthesis of dopamine. Although the first phase I clinical trials using these approaches have been conducted, clear positive data in placebo controlled efficacy studies is still lacking. We are now at a critical junction and need to carefully review the preclinical data from the clinical translation perspective and identify the key factors that will determine the potential for success in gene therapy for Parkinson's disease. (C) 2011 Published by Elsevier Inc.
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34.
  • Ceruti, S., et al. (författare)
  • Isospin Mixing in Zr-80 : From Finite to Zero Temperature
  • 2015
  • Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 115:22
  • Tidskriftsartikel (refereegranskat)abstract
    • The isospin mixing was deduced in the compound nucleus Zr-80 at an excitation energy of E* = 54 MeV from the gamma decay of the giant dipole resonance. The reaction Ca-40 + Ca-40 at E-beam = 136 MeV was used to form the compound nucleus in the isospin I = 0 channel, while the reaction Cl-37 + Ca-44 at E-beam = 95 MeV was used as the reference reaction. The. rays were detected with the AGATA demonstrator array coupled with LaBr3:Ce detectors. The temperature dependence of the isospin mixing was obtained and the zero-temperature value deduced. The isospin-symmetry-breaking correction delta(C) used for the Fermi superallowed transitions was extracted and found to be consistent with beta-decay data.
  •  
35.
  • Çetin, Elif, et al. (författare)
  • Turkey – Country Report : Legal and Policy Framework of Migration Governance
  • 2018
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • This country report focuses on developments that took place during the period of 2011-2017 in the field of migration in Turkey. Traditionally a country of emigration, starting from the early 1990s, it has also become an important country of immigration, asylum and transit. Most recently, the increasing pressure of the refugee challenge, particularly given the high number of arrivals from Syria, has put the country once again under international spotlights. This report provides relevant migration statistics that are available as open source data. It briefly reviews the socio-economic, political and cultural characteristic of the country as well as its brief migration history. The report also delves into a detailed analysis of the constitutional, legal and institutional framework of Turkey’s national migration management system, which has gone through significant transition in the last few years. The report points out that due to Turkey’s geographical limitation to the 1951 Geneva Convention Relating to the Status of Refugees (1951 Convention), and its associated 1967 Protocol; Turkey does not grant refugee status to people fleeing from conflicts and persecution in non-European countries. But it does provide ‘conditional refugee status’ along with ‘refugee’ and ‘subsidiary’ protection. The report reveals a key duality regarding European and non-European asylum seekers to be an important characteristic of Turkey’s asylum system. The first group can obtain ‘refugee’ status’; while the second group can only obtain ‘conditional refugee status’. However, regardless of their nationality, due to the Syrian mass migration, Syrian refugees1 are given another international protection status, which is called ‘temporary protection’. The report concludes by highlighting that part of Turkey’s recent migration policy efforts are tied to encouragement coming from the EU for Turkey to improve conditions regarding access to the asylum process and status determination as well as enhancement of its facilities forasylum-seekers’ protection. Although these developments bring Turkey closer to satisfying the EU demands on migration and asylum policy, Turkey is still expected to abolish the geographical limitation of the 1951 Convention to create a full-fledged asylum system and to solve remaining implementation problems. Ensuring equal and fair access to asylum procedures and facilitating the full access of asylum-seekers to legal aid remain priorities still to be achieved.
  •  
36.
  • Chishti, M.M.R., et al. (författare)
  • Response of the FAst TIMing Array (FATIMA) for DESPEC at FAIR Phase-0
  • 2023
  • Ingår i: Nuclear Instruments & Methods in Physics Research. Section A: Accelerators, Spectrometers, Detectors, and Associated Equipment. - : Elsevier B.V.. - 0168-9002 .- 1872-9576. ; 1056
  • Tidskriftsartikel (refereegranskat)abstract
    • The Monte-Carlo simulated response for γ-ray detection of the FAst TIMing Array (FATIMA) for exploitation within the DEcay SPECtroscopy (DESPEC) experimental system at the FAIR Phase-0 facility at Darmstadt, Germany is presented. In this configuration, FATIMA consisted of 36 LaBr3(Ce) detectors surrounding the AIDA, position-sensitive charged-particle active stopper. The decay of the Iπ=8+ isomer-fed decay cascade in 96Pd, measured in the first DESPEC experiment at the FAIR-0 facility was used to validate the simulations. The experimental data yielded in-situ full-energy peak efficiency values for FATIMA of 11.2(11)%, 6.8(7)%, 3.8(4)% and 2.1(4)% at 106, 325, 684 and 1415 keV respectively, consistent with the values derived from the simulated response.
  •  
37.
  • Çınar, Elif, et al. (författare)
  • Neuroinflammation in Parkinson’s Disease and its Treatment Opportunities
  • 2022
  • Ingår i: Balkan medical journal. - : Galenos Yayinevi. - 2146-3123 .- 2146-3131. ; 39:5, s. 318-333
  • Tidskriftsartikel (refereegranskat)abstract
    • Parkinson’s disease (PD) is a complex, chronic, and progressive neurodegenerative disease that is characterized by irreversible dopaminergic neuronal loss in the substantia nigra. Alpha-synuclein is normally a synaptic protein that plays a key role in PD due to pathological accumulation as oligomers or fibrils. Clustered alpha-synuclein binds to the Toll-like receptors and activates the microglia, which initiates a process that continues with pro-inflammatory cytokine production and secretion. Pro-inflammatory cytokine overproduction and secretion induce cell death and accelerate PD progression. Microglia are found in a resting state in physiological conditions. Microglia became activated by stimulating Toll-like receptors on it under pathological conditions, such as alpha-synuclein aggregation, environmental toxins, or oxidative stress. The interaction between Toll-like receptors and its downstream pathway triggers an activation series, leads to nuclear factor-kappa B activation, initiates the inflammasome formation, and increases cytokine levels. This consecutive inflammatory process leads to dopaminergic cell damage and cell death. Microglia become overactive in response to chronic inflammation, which is observed in PD and causes excessive cytotoxic factor production, such as reactive oxidase, nitric oxide, and tumor necrosis factor-alpha. This inflammatory process contributes to the exacerbation of pathology by triggering neuronal damage or death. Current treatments, such as dopaminergic agonists, anticholinergics, or monoamine oxidase inhibitors alleviate PD symptoms, but they can not stop the disease progression. Finding a radical treatment option or stopping the progression is essential when considering that PD is the second most reported neurodegenerative disorder. Many cytokines are released during inflammation, and they can start the phagocytic process, which caused the degradation of infected cells along with healthy ones. Therefore, targeting the pathological mechanisms, such as microglial activation, mitochondrial dysfunction, and oxidative stress, that should be involved in the treatment program is important. Neuroinflammation is one of the key factors involved in PD pathogenesis as well as alpha-synuclein accumulation, synaptic dysfunction, or dopaminergic neuronal loss, especially in the substantia nigra. Therefore, evaluating the therapeutic efficiency of the mechanisms is important, such as microglial activation and nuclear factor-kappa B pathway or inflammasome formation inhibition, and cytokine release interruption against neuroinflammation may create new treatment possibilities for PD. This study examined the pathological relation between PD and neuroinflammation, and targeting neuroinflammation as an opportunity for PD treatments, such as Toll-like receptor antagonists, NOD-like receptor family pyrin domain containing-3 inflammasome inhibitors, cytokine inhibitors, peroxisome proliferator-activated receptor-γ agonists, reactive oxygen species inhibitors, and nonsteroidal anti-inflammatory drugs.
  •  
38.
  • Cooper, Callum, et al. (författare)
  • Virulence plasmid stability in environmentally occurring Bacillus anthracis from North East Turkey
  • 2017
  • Ingår i: Antonie van Leeuwenhoek. International Journal of General and Molecular Microbiology. - : Springer Science and Business Media LLC. - 0003-6072 .- 1572-9699. ; 110:1, s. 167-170
  • Tidskriftsartikel (refereegranskat)abstract
    • The Bacillus anthracis virulence plasmid pXO2, which encodes for a polypeptide capsule, can be lost during long term laboratory storage. To determine if pXO2 is lost in nature we screened B. anthracis isolates obtained from B. anthracis spores from contaminated animal burial sites in Turkey for their ability to express a capsule upon primary culture. A total of 672 B. anthracis colonies were examined of which ten produced a mixed mucoid (capsule +ve)/non-mucoid (capsule -ve) phenotype and a further one colony yielded non-mucoid colonies upon repeated culture. Screening by PCR using pXO2 specific primers revealed that seven of these isolates had eliminated the plasmid. Of the four colonies which were positive by PCR, one regained the ability to express a capsule upon repeated culture suggesting that the defect was reversible. This is an important observation as capsule expression is a principal marker of virulence and in the absence of PCR serves as a key diagnostic marker. The results of this preliminary study suggest that pXO2 is lost in nature and that further studies are need to determine the mechanisms by which this occurs.
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39.
  •  
40.
  • Crespi, F. C. L., et al. (författare)
  • 1(-) and 2(+) discrete states in Zr-90 populated via the (O-17, O-17 'gamma) reaction
  • 2015
  • Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 91:2
  • Tidskriftsartikel (refereegranskat)abstract
    • 2(+) and 1(-) states in Zr-90 were populated via the (O-17, O-17 'gamma) reaction at 340 MeV. The gamma decay was measured with high resolution using the AGATA (advanced gamma tracking array demonstrator array). Differential cross sections were obtained at few different angles for the scattered particle. The results of the elastic scattering and inelastic excitation of 2(+), 3(,)(-) and 1(-) states are compared with distorted-wave Born approximation (DWBA) calculations, using both the standard collective form factor and a form factor obtained by folding microscopically calculated transition densities. This allowed to extract the isoscalar component of the 1(-) state at 6.424 MeV. The comparison of the present (17O, 17O 'gamma) data with existing (gamma,gamma') and (p, p') data in the corresponding region of the gamma continuum (6-11 MeV), characterized by a large E1 component, shows completely different behaviors of the cross section as a function of the nuclear excitation energy. The comparison of the data with DWBA calculations suggests a decrease of the isoscalar strength in the cross section with increasing excitation energy.
  •  
41.
  • Crespi, F. C. L., et al. (författare)
  • Isospin Character of Low-Lying Pygmy Dipole States in Pb-208 via Inelastic Scattering of O-17 Ions
  • 2014
  • Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 113:1, s. 012501-
  • Tidskriftsartikel (refereegranskat)abstract
    • The properties of pygmy dipole states in Pb-208 were investigated using the Pb-208(O-17, O-17'gamma) reaction at 340 MeV and measuring the gamma decay with high resolution with the AGATA demonstrator array. Cross sections and angular distributions of the emitted gamma rays and of the scattered particles were measured. The results are compared with (gamma, gamma') and (p, p') data. The data analysis with the distorted wave Born approximation approach gives a good description of the elastic scattering and of the inelastic excitation of the 2(+) and 3(-) states. For the dipole transitions a form factor obtained by folding a microscopically calculated transition density was used for the first time. This has allowed us to extract the isoscalar component of the 1(-) excited states from 4 to 8 MeV.
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42.
  •  
43.
  • DiJulio, Douglas, et al. (författare)
  • Electromagnetic properties of vibrational bands in Er-170
  • 2011
  • Ingår i: European Physical Journal A. - : Springer Science and Business Media LLC. - 1434-6001 .- 1434-601X. ; 47:2, s. 25-
  • Tidskriftsartikel (refereegranskat)abstract
    • Excited states of the nucleus Er-170 have been studied by Coulomb excitation using the GASP gamma-ray detector system at the Laboratori Nazionali di Legnaro. The ground-state band along with a low-lying K-pi = 0(+) band and gamma-vibrational band were populated during the experiment. Based on the measured gamma-ray yields, a set of interband and intraband matrix elements has been extracted using the Coulomb excitation code GOSIA. The resulting E2 matrix elements are compared to collective model predictions.
  •  
44.
  • Doncel, Maria, et al. (författare)
  • Lifetime Measurements in Neutron-rich Cu Isotopes
  • 2013
  • Ingår i: Acta Physica Polonica B. - 0587-4254 .- 1509-5770. ; 44:3, s. 505-510
  • Tidskriftsartikel (refereegranskat)abstract
    • The nuclear structure of neutron-rich nuclei close to the double-magic nucleus Ni-78 has been investigated by measuring the lifetime of excited states. In this contribution, it will be presented the lifetime of the J(pi) = 7/2(-) excited state at 981 keV of the Cu-71 isotope, measured using the AGATA Demonstrator coupled to the PRISMA spectrometer and the Koln plunger setup. This is the first time this combined setup has been used for a lifetime measurement.
  •  
45.
  • Ebrahimi-Fakhari, Darius, et al. (författare)
  • Defining the clinical, molecular and imaging spectrum of adaptor protein complex 4-associated hereditary spastic paraplegia
  • 2020
  • Ingår i: Brain. - OXFORD ENGLAND : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 143:10, s. 2929-2944
  • Tidskriftsartikel (refereegranskat)abstract
    • Bi-allelic loss-of-function variants in genes that encode subunits of the adaptor protein complex 4 (AP-4) lead to prototypical yet poorly understood forms of childhood-onset and complex hereditary spastic paraplegia: SPG47 (AP4B1), SPG50 (AP4M1), SPG51 (AP4E1) and SPG52 (AP4S1). Here, we report a detailed cross-sectional analysis of clinical, imaging and molecular data of 156 patients from 101 families. Enrolled patients were of diverse ethnic backgrounds and covered a wide age range (1.0-49.3 years). While the mean age at symptom onset was 0.8 +/- 0.6 years [standard deviation (SD), range 0.2-5.0], the mean age at diagnosis was 10.2 +/- 8.5 years (SD, range 0.1-46.3). We define a set of core features: early-onset developmental delay with delayed motor milestones and significant speech delay (50% non-verbal); intellectual disability in the moderate to severe range; mild hypotonia in infancy followed by spastic diplegia (mean age: 8.4 +/- 5.1 years, SD) and later tetraplegia (mean age: 16.1 +/- 9.8 years, SD); postnatal microcephaly (83%); foot deformities (69%); and epilepsy (66%) that is intractable in a subset. At last follow-up, 36% ambulated with assistance (mean age: 8.9 +/- 6.4 years, SD) and 54% were wheelchair-dependent (mean age: 13.4 +/- 9.8 years, SD). Episodes of stereotypic laughing, possibly consistent with a pseudobulbar affect, were found in 56% of patients. Key features on neuroimaging include a thin corpus callosum (90%), ventriculomegaly (65%) often with colpocephaly, and periventricular white-matter signal abnormalities (68%). Iron deposition and polymicrogyria were found in a subset of patients. AP4B1-associated SPG47 and AP4M1-associated SPG50 accounted for the majority of cases. About two-thirds of patients were born to consanguineous parents, and 82% carried homozygous variants. Over 70 unique variants were present, the majority of which are frameshift or nonsense mutations. To track disease progression across the age spectrum, we defined the relationship between disease severity as measured by several rating scales and disease duration. We found that the presence of epilepsy, which manifested before the age of 3 years in the majority of patients, was associated with worse motor outcomes. Exploring genotype-phenotype correlations, we found that disease severity and major phenotypes were equally distributed among the four subtypes, establishing that SPG47, SPG50, SPG51 and SPG52 share a common phenotype, an 'AP-4 deficiency syndrome'. By delineating the core clinical, imaging, and molecular features of AP-4-associated hereditary spastic paraplegia across the age spectrum our results will facilitate early diagnosis, enable counselling and anticipatory guidance of affected families and help define endpoints for future interventional trials.
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46.
  • Egea, Joaquim, et al. (författare)
  • Regulation of EphA 4 kinase activity is required for a subset of axon guidance decisions suggesting a key role for receptor clustering in Eph function
  • 2005
  • Ingår i: Neuron. - : Elsevier BV. - 0896-6273 .- 1097-4199. ; 47:4, s. 515-528
  • Tidskriftsartikel (refereegranskat)abstract
    • Signaling by receptor tyrosine kinases (RTKs) is mediated by their intrinsic kinase activity. Typically, kinase-activating mutations result in ligand-independent signaling and gain-of-function phenotypes. Like other RTKs, Ephs require kinase activity to signal, but signaling by Ephs in vitro also requires clustering by their membrane bound ephrin ligands. The relative importance of Eph kinase activity and clustering for in vivo functions is unknown. We find that knockin mice expressing a mutant form of EphA4 (EphA4(EE)), whose kinase is constitutively activated in the absence of ephrinB ligands, are deficient in the development of thalamocortical projections and some aspects of central pattern generator rhythmicity. Surprisingly, other functions of EphA4 were regulated normally by EphA4(EE), including midline axon guidance, hindlimb locomotion, in vitro growth cone collapse, and phosphorylation of ephexin1. These results suggest that signaling of Eph RTKs follows a multistep process of induced kinase activity and higher-order clustering different from RTKs responding to soluble ligands.
  •  
47.
  • Elkotob, Muslim, et al. (författare)
  • A parameter injection algorithm for real-time traffic in 802.11 open access networks
  • 2007
  • Ingår i: GLOBECOM 2007. - Piscataway, NJ : IEEE Communications Society. - 1424410428 - 1424410436 ; , s. 2558-2564
  • Konferensbidrag (refereegranskat)abstract
    • An Open Access Network (OAN) is characterized by the fact that private WLANs and broadband access lines are made available for public use, enabling bypassing mobile users to profit from continuous coverage. Our insight is that in wireless OANs, the overhead required for the launching or reconfiguration of a real-time session can be drastically reduced. We propose an algorithm which performs parameter injection into a multimedia data stream instead of following the classical negotiation path typically used. A solution to change the session characteristics of an application that adapts to varying network conditions was developed, including a QoS solution with SIP and MIP to optimize the session characteristics by taking into account the changed conditions in the network. With our approach, we achieve a reduction of a factor of 2.5 for session signaling delay, and excellent jitter values in the range of 10-15 milliseconds as our implementation results show.
  •  
48.
  • Elkotob, Muslim, et al. (författare)
  • Improving TCP goodput in 802.11 access networks
  • 2007
  • Ingår i: IEEE International Conference on Communications. - Piscataway, NJ : IEEE Communications Society. - 1424403537 ; , s. 4494-4499
  • Konferensbidrag (refereegranskat)abstract
    • The widespread deployment of the IEEE 802.11 protocol has made it the de facto standard for wireless network access and allows Internet users to move freely (at least within a hotspot coverage). The convenience brought about by the IEEE 802.11 protocol is also accompanied by new technical challenges such as poor performance of the widely used transport protocol TCP due to the limited and varying bandwidth resources of the wireless medium. In this work, we seek to enhance efficiency of bandwidth usage for TCP over wireless links and improve TCP goodput. Our insight is that TCP acknowledgments can be spared on wireless links to save precious bandwidth resource of these links. We propose a simple technique that leverages the layer coordination between TCP and MAC to suppress TCP acknowledgments. Our technique is transparent to both TCP and MAC and does not require their modification or replacement.
  •  
49.
  • Elkotob, Muslim, et al. (författare)
  • SCAN : semantics- and context-aware networks : motivation, requirements, and architecture
  • 2006
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • We argue that the current Internet architecture is ill-suited for many emerging applications since they have requirements such as security, group communication, mobility, and quality of service (QoS) that were not considered in its original architectural design. We believe that the root of the current Internet's inability to accommodate requirements of emerging applications lies in the (mis)interpretation of the end-to-end arguments, a set of design principles for placement of function within a system, on which the Internet architecture was built. Further, we articulate a new interpretation of the end-to-end arguments and propose a new network architecture that allows semantic information to be communicated across protocol layers. We present a few service scenarios and demonstrate that the new network architecture can accommodate requirements of emerging applications. We reason about the necessary architectural components of such a network and discuss how they can be put together to create a unified framework that provides support for semantics- and context-aware applications.
  •  
50.
  • Elkotob, Muslim, et al. (författare)
  • The open access network architectural paradigm viewed versus peer approaches
  • 2006
  • Ingår i: Telektronikk. - 0085-7130 .- 1891-8220. ; 102:3-4, s. 33-47
  • Tidskriftsartikel (refereegranskat)abstract
    • Currently, the demand for wireless ubiquitous connectivity is increasing; moreover, as new types of applications and services emerge, the need for more bandwidth is steadily growing too. All of this promotes broadband deployment, integration with other access technologies, and additionally paves the way for new paradigms which solve the modern communication requirements of users. Among the paradigms currently successful and promising are Open Access Networks and Wireless Mesh Networks. OBAN (Open Broadband Access Network) [3] is the leading solution in the OAN trend. On the other hand, competing solutions are emerging especially ‘quick-and-dirty' drafted models which are trying to penetrate the market. Among those solutions is FON [4], whose core idea is identical to that of OBAN, but which only focuses on establishing a circle-of-trust among private users so as to increase the number of coverage spots. OBAN on the other hand focuses on supporting seamless handover, quality of service awareness and a sufficient level of security for residential as well as roaming users. This article analyzes from an architectural as well as a functional perspective the different trends and points out pros and cons of peer approaches compared to OBAN.
  •  
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