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- Dahlin, Andreas, 1980
(författare)
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Nanoplasmonic Biosensors compatible with Artificial Cell Membranes
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Within life science, there is currently an intense search for novel techniques that enable efficient and reliable analysis of biomolecular interactions. Such methods have future applications within medical diagnostics and drug development, as well as within proteomic research in general. Lately, several concepts have emerged that are based on monitoring molecular binding to surfaces via optical, mechanical or electrical signal transduction. In particular, the plasmons associated with metallic nanoparticles are of interest since they offer a convenient way to monitor biomolecular interactions, also in a miniaturized format, by optical spectroscopy.This thesis describes the development of a biosensor based on the optical properties of nanoscale apertures in continuous metal films. The fabrication and characterization of the nanostructure is described, as well as surface modification protocols based on thiol chemistry for material-specific functionalization. In addition, an experimental setup for spectroscopy is presented together with data analysis algorithms for minimizing noise.It is emphasized that, from an experimental sensing perspective, nanoholes and nanoparticles have essentially the same plasmonic properties. However, the nanoholes offer several advantages because of the fact that the structure is physically different. In particular, it is shown how various artificial cell membranes can be spontaneously formed inside nanoholes. This makes the sensor compatible with studies of processes related to biological membranes. In this context, membrane-bound proteins are of special interest since they constitute a third of our genome and represent the target of half of the most common medical drugs. Potential future applications of the artificial membranes on the plasmonic nanostructures are discussed, with focus on probing transport across the membrane.
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| 4. |
- Hallvig, D., et al.
(författare)
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Sleepy driving on the real road and in the simulator - A comparison
- 2013
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Ingår i: Accident Analysis and Prevention. - : Elsevier BV. - 0001-4575 .- 1879-2057. ; 50, s. 44-50
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Tidskriftsartikel (refereegranskat)abstract
- Sleepiness has been identified as one of the most important factors contributing to road crashes. However, almost all work on the detailed changes in behavior and physiology leading up to sleep related crashes has been carried out in driving simulators. It is not clear, however, to what extent simulator results can be generalized to real driving. This study compared real driving with driving in a high fidelity, moving base, driving simulator with respect to driving performance, sleep related physiology (using electroencephalography and electrooculography) and subjective sleepiness during night and day driving for 10 participants. The real road was emulated in the simulator. The results show that the simulator was associated with higher levels of subjective and physiological sleepiness than real driving. However, both for real and simulated driving, the response to night driving appears to be rather similar for subjective sleepiness and sleep physiology. Lateral variability was more responsive to night driving in the simulator, while real driving at night involved a movement to the left in the lane and a reduction of speed, both of which effects were absent in the simulator. It was concluded that the relative validity of simulators is acceptable for many variables, but that in absolute terms simulators cause higher sleepiness levels than real driving. Thus, generalizations from simulators to real driving must be made with great caution.
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| 5. |
- Cappelletto, Elia, et al.
(författare)
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Impact of Post Manufacturing Handling of Protein-Based Biologic Drugs on Product Quality and User Centricity
- 2024
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Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier. - 0022-3549 .- 1520-6017.
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Tidskriftsartikel (refereegranskat)abstract
- This article evaluates the current gaps around the impact of post-manufacturing processes on the product qualities of protein-based biologics, with a focus on user centricity. It includes the evaluation of the regulatory guidance available, describes a collection of scientific literature and case studies to showcase the impact of post-manufacturing stresses on product and dosing solution quality. It also outlines the complexity of clinical handling and the need for communication, and alignment between drug providers, healthcare professionals, users, and patients. Regulatory agencies provide clear expectations for drug manufacturing processes, however, guidance supporting post-product manufacturing handling is less defined and often misaligned. This is problematic as the pharmaceutical products experience numerous stresses and processes which can potentially impact drug quality, safety and efficacy. This article aims to stimulate discussion amongst pharmaceutical developers, health care providers, device manufacturers, and public researchers to improve these processes. Patients and caregivers' awareness can be achieved by providing relevant educational material on pharmaceutical product handling.
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| 8. |
- Björn, Niclas, et al.
(författare)
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Genes and variants in hematopoiesis-related pathways are associated with gemcitabine/carboplatin-induced thrombocytopenia
- 2020
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Ingår i: The Pharmacogenomics Journal. - : Nature Publishing Group. - 1470-269X .- 1473-1150. ; 20:2, s. 179-191
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Tidskriftsartikel (refereegranskat)abstract
- Chemotherapy-induced myelosuppression, including thrombocytopenia, is a recurrent problem during cancer treatments that may require dose alterations or cessations that could affect the antitumor effect of the treatment. To identify genetic markers associated with treatment-induced thrombocytopenia, we whole-exome sequenced 215 non-small cell lung cancer patients homogeneously treated with gemcitabine/carboplatin. The decrease in platelets (defined as nadir/baseline) was used to assess treatment-induced thrombocytopenia. Association between germline genetic variants and thrombocytopenia was analyzed at single-nucleotide variant (SNV) (based on the optimal false discovery rate, the severity of predicted consequence, and effect), gene, and pathway levels. These analyses identified 130 SNVs/INDELs and 25 genes associated with thrombocytopenia (P-value < 0.002). Twenty-three SNVs were validated in an independent genome-wide association study (GWAS). The top associations include rs34491125 in JMJD1C (P-value = 9.07 × 10−5), the validated variants rs10491684 in DOCK8 (P-value = 1.95 × 10−4), rs6118 in SERPINA5 (P-value = 5.83 × 10−4), and rs5877 in SERPINC1 (P-value = 1.07 × 10−3), and the genes CAPZA2 (P-value = 4.03 × 10−4) and SERPINC1 (P-value = 1.55 × 10−3). The SNVs in the top-scoring pathway “Factors involved in megakaryocyte development and platelet production” (P-value = 3.34 × 10−4) were used to construct weighted genetic risk score (wGRS) and logistic regression models that predict thrombocytopenia. The wGRS predict which patients are at high or low toxicity risk levels, for CTCAE (odds ratio (OR) = 22.35, P-value = 1.55 × 10−8), and decrease (OR = 66.82, P-value = 5.92 × 10−9). The logistic regression models predict CTCAE grades 3–4 (receiver operator characteristics (ROC) area under the curve (AUC) = 0.79), and large decrease (ROC AUC = 0.86). We identified and validated genetic variations within hematopoiesis-related pathways that provide a solid foundation for future studies using genetic markers for predicting chemotherapy-induced thrombocytopenia and personalizing treatments.
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| 9. |
- Munthe, Christian, 1962, et al.
(författare)
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The Return of Lombroso? Ethical Aspects of (Visions of) Preventive Forensic Screening
- 2015
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Ingår i: Public Health Ethics. - : Oxford University Press (OUP). - 1754-9973 .- 1754-9981. ; 8:3, s. 270-283
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Tidskriftsartikel (refereegranskat)abstract
- The vision of legendary criminologist Cesare Lombroso to use scientific theories of individual causes of crime as a basis for screening and prevention programmes targeting individuals at risk for future criminal behaviour has resurfaced, following advances in genetics, neuroscience and psychiatric epidemiology. This article analyses this idea and maps its ethical implications from a public health ethical standpoint. Twenty-seven variants of the new Lombrosian vision of forensic screening and prevention are distinguished, and some scientific and technical limitations are noted. Some lures, biases and structural factors, making the application of the Lombrosian idea likely in spite of weak evidence are pointed out and noted as a specific type of ethical aspect. Many classic and complex ethical challenges for health screening programmes are shown to apply to the identified variants and the choice between them, albeit with peculiar and often provoking variations. These variations are shown to actualize an underlying theoretical conundrum in need of further study, pertaining to the relationship between public health ethics and the ethics and values of criminal law policy.
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| 10. |
- Chandolias, Konstantinos, et al.
(författare)
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Protective effect of a reverse membrane bioreactor against toluene and naphthalene in anaerobic digestion
- 2022
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Ingår i: Biotechnology and Applied Biochemistry. - : Wiley. - 1470-8744 .- 0885-4513. ; 69:3, s. 1267 -1274
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Tidskriftsartikel (refereegranskat)abstract
- Raw syngas contains tar contaminants including toluene and naphthalene, which inhibit its conversion to methane. Cell encasement in a hydrophilic reverse membrane bioreactor (RMBR) could protect the cells from hydrophobic contaminants. This study aimed to investigate the inhibition of toluene and naphthalene and the effect of using RMBR. In this work, toluene and naphthalene were added at concentrations of 0.5–1.0 and 0.1–0.2 g/L in batch operation. In continuous operation, concentration of 0–6.44 g/L for toluene and 0–1.28 g/L for naphthalene were studied. The results showed that no inhibition was observed in batch operation for toluene and naphthalene at concentrations up to 1 and 0.2 g/L, respectively. In continuous operation of free cell bioreactors (FCBRs), inhibition of toluene and naphthalene started at 2.05 and 0.63 g/L, respectively. When they were present simultaneously, inhibition of toluene and naphthalene occurred at concentrations of 3.14 and 0.63 g/L, respectively. In continuous RMBRs, no inhibition for toluene and less inhibition for naphthalene were observed, resulting in higher methane production from RMBR than that of FCBR. These results indicated that RMBR system gave a better protection effect against inhibitors compared with FCBR.
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