| 1. |
- Almung, Magnus, et al.
(författare)
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I solitärens skugga : Nyttobyggnadens kreativa restaurering
- 2015
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Rapport (populärvet., debatt m.m.)abstract
- Ekonomibyggnader har alltid behövts för de huvudbyggnader som finns inom våra bevarade kulturmiljöer. Några nyttobyggnader uppskattas och används fortfarande, andra betraktas som problematiska överloppsbyggnader, många rivs. Alltför få har dokumenterats eller fått sin historia klarlagd vilket undanhållit viktig kunskap om samhällets framväxt. Vi vill synliggöra och betona vikten av att bevara och utveckla hela bebyggelsemiljöer, ofta med ett antal hus utöver huvudbyggnaden och tillhörande yttre miljö i staden eller på landet. Denna rapport visar kursdeltagarnas projektarbeten om nyttobyggnader. De har dokumenterat med traditionella och nya arbetsmetoder, inventerat och intervjuat, läst och besökt arkiv, värderat, analyserat och därefter föreslagit hur man ska ta hand om och utveckla nyttobyggnaderna i sina kulturmiljöer.
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| 2. |
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| 3. |
- Canalias, Carlota Canalias, et al.
(författare)
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Highly efficient periodically poled KTP-isomorphs with large apertures and extreme domain aspect-ratios
- 2018
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Ingår i: Nonlinear Frequency Generation and Conversion: Materials and Devices XVII. - : SPIE - International Society for Optical Engineering. - 9781510615175
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Konferensbidrag (refereegranskat)abstract
- Since the early 1990's, a substantial effort has been devoted to the development of quasi-phased-matched (QPM) nonlinear devices, not only in ferroelectric oxides like LiNbO3, LiTaO3 and KTiOPO4 (KTP), but also in semiconductors as GaAs, and GaP. The technology to implement QPM structures in ferroelectric oxides has by now matured enough to satisfy the most basic frequency-conversion schemes without substantial modification of the poling procedures. Here, we present a qualitative leap in periodic poling techniques that allows us to demonstrate devices and frequency conversion schemes that were deemed unfeasible just a few years ago. Thanks to our short-pulse poling and coercive-field engineering techniques, we are able to demonstrate large aperture (5 mm) periodically poled Rb-doped KTP devices with a highly-uniform conversion efficiency over the whole aperture. These devices allow parametric conversion with energies larger than 60 mJ. Moreover, by employing our coercive-field engineering technique we fabricate highlyefficient sub-μm periodically poled devices, with periodicities as short as 500 nm, uniform over 1 mm-Thick crystals, which allow us to realize mirrorless optical parametric oscillators with counter-propagating signal and idler waves. These novel devices present unique spectral and tuning properties, superior to those of conventional OPOs. Furthermore, our techniques are compatible with KTA, a KTP isomorph with extended transparency in the mid-IR range. We demonstrate that our highly-efficient PPKTA is superior both for mid-IR and for green light generation-as a result of improved transmission properties in the visible range. Our KTP-isomorph poling techniques leading to highly-efficient QPM devices will be presented. Their optical performance and attractive damage thresholds will be discussed.
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| 4. |
- Canalias, Carlota, et al.
(författare)
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Sub-wavelength domain engineering in KTP isomorphs : QPM devices with counter-propagating photons
- 2013
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Ingår i: 2013 Conference on Lasers and Electro-Optics Pacific Rim (CLEO-PR). - New York : IEEE. - 9781467364751 ; , s. 6600156-
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Konferensbidrag (refereegranskat)abstract
- We review the recent advances in fabrication of ferroelectric-domain gratings of sub-μm periodicity in KTP and Rb-doped KTP for counter-propagating second-order nonlinear optical interactions. Their performance as QPM devices will be discussed.
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| 5. |
- Deyra, Loïc, et al.
(författare)
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High power single-crystal fiber CW 946 nm laser and blue generation based on Rubidium-doped PPKTP
- 2013
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Ingår i: 2013 Conference on Lasers and Electro-Optics Europe and International Quantum Electronics Conference. - : IEEE conference proceedings.
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Konferensbidrag (refereegranskat)abstract
- Blue lasers have numerous applications in spectroscopy, underwater communication and material processing. Direct emission in the blue region can be achieved with laser diodes, with powers up to the watt level [1]. Higher powers require efficient laser operating around 950 nm to be frequency doubled to the blue spectrum, which usually suffer from a lower gain than conventional 1μm lasers. Generally, intracavity frequency doubling set-ups and pulsed operation are used to increase the second harmonic generation efficiency, with output powers up to 4 W in cw[2] and 1.3W in pulsed regime [3]. In the past few years, both lasers materials and non linear crystals have progressed enough to allow the very simple extracavity frequency doubling of continuous wave lasers in periodically poled materials to acceptable powers[4].
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| 6. |
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| 7. |
- Ekström, Simon, et al.
(författare)
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Integrated selective enrichment target - a microtechnology platform for matrix-assisted laser desorption/ionization-mass spectrometry applied on protein biomarkers in prostate diseases
- 2004
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Ingår i: Electrophoresis. - : Wiley. - 0173-0835. ; 25:21-22, s. 3769-3777
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Tidskriftsartikel (refereegranskat)abstract
- The performance of a miniaturized sample processing platform for matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS), manufactured by silicon microfabrication, called integrated selective enrichment target (ISET) technology was evaluated in a biological context. The ISET serves as both sample treatment device and MALDI-MS target, and contains an array of 96 perforated nanovials, which each can be filled with 40 nL of reversed-phase beads. This methodology minimizes the number of sample transfers and the total surface area available for undesired adsorption of the analytes in order to provide high-sensitivity analysis. ISET technology was successfully applied for characterization of proteins coisolated by affinity chromatography of prostate-specific antigen (PSA) from human seminal fluid. The application of ISET sample preparation enabled multiple analyses to be performed on a limited sample volume, which resulted in the discovery that prolactin inducible protein (PIP) was coisolated from the samples.
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| 8. |
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| 9. |
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| 10. |
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| 11. |
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| 12. |
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| 13. |
- Liljestrand, Charlotte, et al.
(författare)
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Ion-Exchange Induced Coercive Field Gratings for QPM Devices in Rb-doped KTP
- 2016
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Ingår i: 2016 CONFERENCE ON LASERS AND ELECTRO-OPTICS (CLEO). - Washington, D.C. : IEEE conference proceedings. - 9781943580118
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Konferensbidrag (refereegranskat)abstract
- We demonstrate 3.16 mu m periodic poling in RKTP using a coercive field grating induced by ion-exchange. The process results in a linear refractive index change over the sample thickness, adding extra tunability to the QPM device.
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| 14. |
- Liljestrand, Charlotte, 1986-, et al.
(författare)
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Periodic poling of Rb-doped KTiOPO4 by coercive field engineering
- 2016
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Ingår i: Optics Express. - : Optical Society of America. - 1094-4087. ; 24:13, s. 14682-14689
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Tidskriftsartikel (refereegranskat)abstract
- We demonstrate fine-pitch periodic poling of bulk Rb-doped KTiOPO4 using a coercive field grating induced by ion-exchange. These samples were used for quasi phase matched (QPM) second harmonic generation at 795 nm with a normalized conversion efficiency of 1.7% W−1cm−1. Additionally, the ion-exchange introduced a refractive index change over the sample thickness resulting in a phasematching wavelength shift of 0.21 nm, adding extra tunability to the QPM device.
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| 15. |
- Loizou, Christos, et al.
(författare)
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Incidence of tonsillar cancer in northern Sweden : Impact of human papilloma virus
- 2015
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Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 10:6, s. 3565-3572
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Tidskriftsartikel (refereegranskat)abstract
- The incidence rate of tonsillar cancer is increasing worldwide. The current study identifies a parallel increase in the incidence of tonsillar cancer, human papilloma virus (HPV) and p16 expression among a population from northern Sweden, a sparsely populated area, confirming the strong association between p16 and HPV infection in tonsillar tissue. Data from the Swedish Cancer Registry was assessed to identify cases of tonsillar cancer in the northern territorial area of Sweden. HPV DNA was extracted from paraffin embedded diagnostic biopsies and detected by polymerase chain reaction using general primers Gp5+/6+ and CpI/IIG. Expression of p16 was identified by immunochemistry. Patients were grouped into urban or rural residence categories. A total of 214 cases were identified, comprising 155 (72.4%) men and 59 (27.6%) women, and 65 of these patients, who presented between 2000 and 2012, were analyzed. The overall median age for the analyzed patients was 58 years; 48 (74%) were males (median age, 57.5 years) and 17 (26%) were females (median age, 65 years). Of the 65 specimens, 59 (91%) were positive for HPV, and 62 (95%) expressed p16. The incidence of tonsillar cancer in the cohort demonstrated a 2-fold increase between 1990 and 2013; specifically, a 2.7-fold increase was observed in men whilst the female group exhibited only a small increase. These findings demonstrate a strong association between p16 expression and HPV infection in tonsillar malignancies. The incidence of HPV-positive tonsillar cancer has increased in recent years, even in sparsely populated regions, as demonstrated in northern Sweden.
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| 16. |
- Malm, Johan, et al.
(författare)
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Developments in biobanking workflow standardization providing sample integrity and stability
- 2013
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Ingår i: Journal of Proteomics. - : Elsevier BV. - 1874-3919 .- 1876-7737. ; 95:SI, s. 38-45
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Tidskriftsartikel (refereegranskat)abstract
- Recommendations and outlines for standardization in biobanking processes are presented by a research team with long-term experience in clinical studies. These processes have important bearing on the use of samples in developing assays. These measurements are useful to document states of health and disease that are beneficial for academic research, commercial healthcare, drug development industry and government regulating agencies. There is a need for increasing awareness within proteomic and genomic communities regarding the basic concepts of collecting, storing and utilizing clinical samples. Quality control and sample suitability for analysis need to be documented and validated to ensure data integrity and establish contexts for interpretation of results. Standardized methods in proteomics and genomics are required to be practiced throughout the community allowing datasets to be comparable and shared for analysis. For example, sample processing of thousands of clinical samples, performed in 384 high-density sample tube systems in a fully automated workflow, preserves sample content and is presented showing validation criteria. Large studies will be accompanied by biological and molecular information with corresponding clinical records from patients and healthy donors. These developments position biobanks of human patient samples as an increasingly recognized major asset in disease research, future drug development and within patient care. Biological significance: The current manuscript is of major relevance to the proteomic and genomic fields, as it outlines the standardization aspects of biobanking and the requirements that are needed to run future clinical studies that will benefit the patients where OMICS science will play a major role. A global view of the field is given where best practice and conventional acceptances are presented along with ongoing large-scale biobanking projects. The authors represent broadly stakeholders that cover the academic, pharma, biotech and healthcare fields with extensive experience and deliveries. This contribution will be a milestone paper to the proteomic and genomic scientists to present data in the future that will have impact to the life science area.This article is part of a Special Issue entitled: Standardization and Quality Control in Proteomics.
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| 17. |
- Marko-Varga, György, et al.
(författare)
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Standardization and Utilization of Biobank Resources in Clinical Protein Sciene with Examples of Emerging Applications
- 2012
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 11:11, s. 5124-5134
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Tidskriftsartikel (refereegranskat)abstract
- Biobanks are a major resource to access and measure biological constituents that can be used to monitor the status of health and disease, both in unique individual samples and within populations. Most “omic” activities rely on access to these collections of stored samples to provide the basis for establishing the ranges and frequencies of expression. Furthermore, information about the relative abundance and form of protein constituents found in stored samples provides an important historical index for comparative studies of inherited, epidemic, and developing disease. Standardizations of sample quality, form, and analysis are an important unmet need and requirement for gaining full benefit from collected samples. Coupled to this standard is the provision of annotation describing clinical status and metadata of measurements of clinical phenotype that characterizes the sample. Today we have not yet achieved consensus on how to collect, manage, and build biobank archives in order to reach goals where these efforts are translated into value for the patient. Several initiatives (OBBR, ISBER, BBMRI) that disseminate best practice examples for biobanking are expected to play an important role in ensuring the need to preserve the sample integrity of biosamples stored for periods that reach one or several decades. These developments will be of great value and importance to programs such as the Chromosome Human Protein Project (C-HPP) that will associate protein expression in healthy and disease states with genetic foci along of each of the human chromosomes.
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| 18. |
- Müller, Sebastian, et al.
(författare)
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Highly efficient continuous wave blue second-harmonic generation in fs-laser written periodically poled Rb:KTiOPO4 waveguides
- 2014
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Ingår i: Optics Letters. - 0146-9592 .- 1539-4794. ; 39:5, s. 1274-1277
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Tidskriftsartikel (refereegranskat)abstract
- Waveguides were inscribed into a 9.5 mm long periodically poled KTiOPO4 crystal with a Ti:sapphire femtosecond-laser. Waveguiding was achieved between two parallel written tracks with spacings of 17–19 μm. The fundamental power of 1.6 W for frequency doubling in the waveguide was delivered by a continuous wave Ti:sapphire laser at a wavelength of 943.18 nm. A maximum output power of 76 mW in the blue spectral region was achieved. This corresponds to a single pass normalized conversion efficiency of 4.6% W−1 cm−2.
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| 19. |
- Nilsson, C. L., et al.
(författare)
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Chromosome 19 Annotations with Disease Speciation: A First Report from the Global Research Consortium
- 2013
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 12:1, s. 134-149
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Tidskriftsartikel (refereegranskat)abstract
- A first research development progress report of the Chromosome 19 Consortium with members from Sweden, Norway, Spain, United States, China and India, a part of the Chromosome-centric Human Proteome Project (C-HPP) global initiative, is presented (http://www.c-hpp.org). From the chromosome 19 peptide-targeted library constituting 6159 peptides, a pilot study was conducted using a subset with 125 isotope-labeled peptides. We applied an annotation strategy with triple quadrupole, ESI-Qtrap, and MALDI mass spectrometry platforms, comparing the quality of data within and in between these instrumental set-ups. LC–MS conditions were outlined by multiplex assay developments, followed by MRM assay developments. SRM was applied to biobank samples, quantifying kallikrein 3 (prostate specific antigen) in plasma from prostate cancer patients. The antibody production has been initiated for more than 1200 genes from the entire chromosome 19, and the progress developments are presented. We developed a dedicated transcript microarray to serve as the mRNA identifier by screening cancer cell lines. NAPPA protein arrays were built to align with the transcript data with the Chromosome 19 NAPPA chip, dedicated to 90 proteins, as the first development delivery. We have introduced an IT-infrastructure utilizing a LIMS system that serves as the key interface for the research teams to share and explore data generated within the project. The cross-site data repository will form the basis for sample processing, including biological samples as well as patient samples from national Biobanks.
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| 20. |
- Ressine, Anton, et al.
(författare)
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Macro/Nano-Structured Silicon as Solid Support for Antibody Arrays: Surface Design, Reproducibility, and Assay Characteristics Enabling Discovery of Kallikrein Gene Products for Prostate Disease Diagnostics
- 2005
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Ingår i: Nanobiotechnology. - 1551-1286. ; 1:1, s. 93-104
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Tidskriftsartikel (refereegranskat)abstract
- To facilitate high-throughput biomarker discovery and high-density protein-chip array analyses of complex biological samples, a novel macro- and nanoporous silicon surface for protein microarrays was developed. The surface offers three-dimensional surface enlarging properties and spot confinement, enabling both high sensitivity bioassays and design of high density arrays. Reproducible manufacturing of the protein chip surface was accomplished as demonstrated by the low imprecision when standard IgG bioassays were performed at 100 pM antigen level on a series of protein chips scanned at widely different locations within a silicon wafer, as well as between different wafers from two different manufacturers. The relative standard deviation (RSD) of fluorescence spot intensity within an array on a chip was less than 20%. Mean spot intensity RSD was 19% for all 25 microarray chips in the study. Within-manufacturer-lot RSDs in chips from either manufacturer were <15% of mean spot intensity. The detection limit and dynamic range of the novel protein chip surface were examined to evaluate whether they match criteria required in a search for novel biomarkers such as for prostate cancer. Monoclonal IgG against prostate-specific antigen (PSA) was arrayed on the porous silicon chips. These were subsequently incubated in serum samples containing widely different levels of fluorescence-labeled PSA. Detection of PSA in serum at concentrations from 0.7 ng/mL (26 pM) up to 104-fold higher levels verified assay characteristics required in the search for prostate biomarkers (e.g., kallikrein gene products) at clinically relevant levels.
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| 21. |
- Rifes, Pedro, et al.
(författare)
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Identifying secreted biomarkers of dopaminergic ventral midbrain progenitor cells
- 2023
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Ingår i: Stem Cell Research & Therapy. - 1757-6512. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundVentral midbrain (VM) dopaminergic progenitor cells derived from human pluripotent stem cells have the potential to replace endogenously lost dopamine neurons and are currently in preclinical and clinical development for treatment of Parkinson’s Disease (PD). However, one main challenge in the quality control of the cells is that rostral and caudal VM progenitors are extremely similar transcriptionally though only the caudal VM cells give rise to dopaminergic (DA) neurons with functionality relevant for cell replacement in PD. Therefore, it is critical to develop assays which can rapidly and reliably discriminate rostral from caudal VM cells during clinical manufacturing.MethodsWe performed shotgun proteomics on cell culture supernatants from rostral and caudal VM progenitor cells to search for novel secreted biomarkers specific to DA progenitors from the caudal VM. Key hits were validated by qRT-PCR and ELISA.ResultsWe identified and validated novel secreted markers enriched in caudal VM progenitor cultures (CPE, LGI1 and PDGFC), and found these markers to correlate strongly with the expression of EN1, which is a predictive marker for successful graft outcome in DA cell transplantation products. Other markers (CNTN2 and CORIN) were found to conversely be enriched in the non-dopaminergic rostral VM cultures. Key novel ELISA markers were further validated on supernatant samples from GMP-manufactured caudal VM batches.ConclusionAs a non-invasive in-process quality control test for predicting correctly patterned batches of caudal VM DA cells during clinical manufacturing, we propose a dual ELISA panel measuring LGI1/CORIN ratios around day 16 of differentiation.
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| 22. |
- Sugihara, Yutaka, et al.
(författare)
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A New Look at Drugs Targeting Malignant Melanoma – An Application for Mass Spectrometry Imaging
- 2014
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Ingår i: Proteomics. - : Wiley. - 1615-9861 .- 1615-9853. ; 14:17-18, s. 1963-1970
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Forskningsöversikt (refereegranskat)abstract
- Malignant melanoma (MM) patients are being treated with an increasing number of personalized medicine (PM) drugs, several of which are small molecule drugs developed to treat patients with specific disease genotypes and phenotypes. In particular, the clinical application of protein kinase inhibitors (PKI) has been highly effective for certain subsets of MM patients. Vemurafenib, a PKI targeting BRAF mutated protein, has shown significant efficacy in slowing disease progression. In this paper we provide an overview of this new generation of targeted drugs, and demonstrate the first data on localization of personalized medicine drugs within tumor compartments. In this study, we have introduced matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to provide new information on one of the drugs currently used in the PM treatment of MM, vemurafenib. In a proof-of-concept in vitro study, MALDI-MSI was used to identify vemurafenib applied to metastatic lymph nodes tumors of subjects attending the regional hospital network of Southern Sweden. The paper provides evidence of BRAF overexpression in tumors isolated from MM patients and localization of the specific drug targeting BRAF, vemurafenib, using mass spectrometry fragment ion signatures. Our ability to determine drug uptake at the target sites of directed therapy provides important opportunity for increasing our understanding about the mode of action of drug activity within the disease environment.
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| 23. |
- Svensson-Höglund, Sahra, et al.
(författare)
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Futures of Fixing : Exploring the life of product users in circular economy repair society scenarios
- 2022
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- A Circular Economy (CE) constitutes one pathway towards realising sustainable productionand consumption. Here, the repair of broken products (compared to replacement) consti-tutes an important strategy to keep products in the economy for longer, thereby reducingwaste, as well as the need to extract resources and emit pollution in the manufacture of areplacement product. In today’s world, repair does not necessarily constitute the naturalresponse to product breakage. However, increasing legislative efforts and grassroots move-ments are attempting to change that and make repair accessible, affordable and culturallyacceptable. The question is what such a society – where repair is normalised – would be like.
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| 24. |
- Végvári, Ákos, et al.
(författare)
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Experimental Models to Study Drug Distributions in Tissue Using MALDI Mass Spectrometry
- 2013
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 12:12, s. 5626-5633
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Tidskriftsartikel (refereegranskat)abstract
- Requirements for patient safety and improved efficacy are steadily increasing in modern healthcare and are key drivers in modern drug development. New drug characterization assays are central in providing evidence of the specificity and selectivity of drugs. Meeting this need, matrix-assisted laser desorption ionization-mass spectrometry imaging (MALDI-MSI) is used to study drug localization within micro-environmental tissue compartments. Thin sections of human lung tumor and rat xenograft tissues were exposed to pharmaceutical drugs by either spotting or submerging. These drugs, the epidermal growth factor receptor antagonists, erlotinib (Tarceva™) and gefitinib (Iressa™), and the acetylcholine receptor antagonist, tiotropium were characterized by microenvironment localization. Intact tissue blocks were also immersed in drug solution followed by sectioning. MALDI-MSI was then performed using a Thermo MALDI LTQ Orbitrap XL instrument to localize drug distribution patterns. We propose three MALDI-MSI models measuring drug disposition that have been used to map the selected compounds within tissue compartments of tumors isolated from lung cancer patients.
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| 25. |
- Végvári, Ákos, et al.
(författare)
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Identification of prostate specific antigen (PSA) isoforms in complex biological samples utilizing complementary platforms
- 2010
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Ingår i: Journal of Proteomics. - : Elsevier BV. - 1874-3919. ; 73:6, s. 1137-1147
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Tidskriftsartikel (refereegranskat)abstract
- Measurements of the prostate-specific antigen (PSA) levels in blood are widely used as diagnostic, predictive and prognostic marker of prostate disease. The selective detection of molecular forms of PSA can contribute clinically to meaningful enhancements of the conventional PSA-test. As it is plausible that an in-depth search for structural variants of PSA gene products may increase our ability to discriminate distinct patho-biological basis and stages of prostate diseases, we have developed a multi-step protocol comprising gel-based methods followed by mass spectrometric identification. Our current aim was to provide a comprehensive identification of PSA variants occurring in seminal fluid. We provide a proof-of-principle for this multiple step analytical approach to identify multiple PSA variants from complex biological samples that revealed distinct molecular characteristics. In addition, sequence-annotated protein bands in SDS–PAGE gels were compared to those detected by Western blots, and by monitoring the enzymatic activity in zymogram gels, using gelatin as a substrate. The high accuracy annotations were obtained by fast turnaround MALDI-Orbitrap analysis from excised and digested gel bands. Multiple PSA forms were identified utilizing a combination of MASCOT and SEQUEST search engines.
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| 26. |
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| 27. |
- Welinder, Charlotte, et al.
(författare)
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A protein deep sequencing evaluation of metastatic melanoma tissues.
- 2015
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:4
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Tidskriftsartikel (refereegranskat)abstract
- Malignant melanoma has the highest increase of incidence of malignancies in the western world. In early stages, front line therapy is surgical excision of the primary tumor. Metastatic disease has very limited possibilities for cure. Recently, several protein kinase inhibitors and immune modifiers have shown promising clinical results but drug resistance in metastasized melanoma remains a major problem. The need for routine clinical biomarkers to follow disease progression and treatment efficacy is high. The aim of the present study was to build a protein sequence database in metastatic melanoma, searching for novel, relevant biomarkers. Ten lymph node metastases (South-Swedish Malignant Melanoma Biobank) were subjected to global protein expression analysis using two proteomics approaches (with/without orthogonal fractionation). Fractionation produced higher numbers of protein identifications (4284). Combining both methods, 5326 unique proteins were identified (2641 proteins overlapping). Deep mining proteomics may contribute to the discovery of novel biomarkers for metastatic melanoma, for example dividing the samples into two metastatic melanoma "genomic subtypes", ("pigmentation" and "high immune") revealed several proteins showing differential levels of expression. In conclusion, the present study provides an initial version of a metastatic melanoma protein sequence database producing a total of more than 5000 unique protein identifications. The raw data have been deposited to the ProteomeXchange with identifiers PXD001724 and PXD001725.
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| 28. |
- Welinder, Charlotte, et al.
(författare)
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Analysis of Alpha-Synuclein in Malignant Melanoma - Development of a SRM Quantification Assay.
- 2014
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:10
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Tidskriftsartikel (refereegranskat)abstract
- Globally, malignant melanoma shows a steady increase in the incidence among cancer diseases. Malignant melanoma represents a cancer type where currently no biomarker or diagnostics is available to identify disease stage, progression of disease or personalized medicine treatment. The aim of this study was to assess the tissue expression of alpha-synuclein, a protein implicated in several disease processes, in metastatic tissues from malignant melanoma patients. A targeted Selected Reaction Monitoring (SRM) assay was developed and utilized together with stable isotope labeling for the relative quantification of two target peptides of alpha-synuclein. Analysis of alpha-synuclein protein was then performed in ten metastatic tissue samples from the Lund Melanoma Biobank. The calibration curve using peak area ratio (heavy/light) versus concentration ratios showed linear regression over three orders of magnitude, for both of the selected target peptide sequences. In support of the measurements of specific protein expression levels, we also observed significant correlation between the protein and mRNA levels of alpha-synuclein in these tissues. Investigating levels of tissue alpha-synuclein may add novel aspect to biomarker development in melanoma, help to understand disease mechanisms and ultimately contribute to discriminate melanoma patients with different prognosis.
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| 29. |
- Welinder, Charlotte, et al.
(författare)
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Correlation of histopathologic characteristics to protein expression and function in malignant melanoma
- 2017
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:4
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Tidskriftsartikel (refereegranskat)abstract
- Background Metastatic melanoma is still one of the most prevalent skin cancers, which upon progression has neither a prognostic marker nor a specific and lasting treatment. Proteomic analysis is a versatile approach with high throughput data and results that can be used for characterizing tissue samples. However, such analysis is hampered by the complexity of the disease, heterogeneity of patients, tumors, and samples themselves. With the long term aim of quest for better diagnostics biomarkers, as well as predictive and prognostic markers, we focused on relating high resolution proteomics data to careful histopathological evaluation of the tumor samples and patient survival information. Patients and methods Regional lymph node metastases obtained from ten patients with metastatic melanoma (stage III) were analyzed by histopathology and proteomics using mass spectrometry. Out of the ten patients, six had clinical follow-up data. The protein deep mining mass spectrometry data was related to the histopathology tumor tissue sections adjacent to the area used for deep-mining. Clinical follow-up data provided information on disease progression which could be linked to protein expression aiming to identify tissue-based specific protein markers for metastatic melanoma and prognostic factors for prediction of progression of stage III disease.Results In this feasibility study, several proteins were identified that positively correlated to tumor tissue content including IF6, ARF4, MUC18, UBC12, CSPG4, PCNA, PMEL and MAGD2. The study also identified MYC, HNF4A and TGFB1 as top upstream regulators correlating to tumor tissue content. Other proteins were inversely correlated to tumor tissue content, the most significant being; TENX, EHD2, ZA2G, AOC3, FETUA and THRB. A number of proteins were significantly related to clinical outcome, among these, HEXB, PKM and GPNMB stood out, as hallmarks of processes involved in progression from stage III to stage IV disease and poor survival. Conclusion In this feasibility study, promising results show the feasibility of relating proteomics to histopathology and clinical outcome, and insight thus can be gained into the molecular processes driving the disease. The combined analysis of histological features including the sample cellular composition with protein expression of each metastasis enabled the identification of novel, differentially expressed proteins. Further studies are necessary to determine whether these putative biomarkers can be utilized in diagnostics and prognostic prediction of metastatic melanoma.
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| 30. |
- Welinder, Charlotte, et al.
(författare)
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Establishing a Southern Swedish Malignant Melanoma OMICS and Biobank Clinical Capability
- 2013
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Ingår i: Clinical and Translational Medicine. - : Wiley. - 2001-1326. ; 2:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The Southern Swedish Malignant Melanoma (SSMM) research team is a truly cross functional group with members from oncology, clinical, surgery, bioinformatics, proteomics, and genomics initiatives. The SSMM’s objectives and goals are to develop, build and utilize cutting edge biobanks and OMICS platforms to better understand disease pathology and drug mechanisms. Within the research team there are members who daily diagnose patients with suspect melanomas, do follow-ups on malignant melanoma patients and remove primary or metastatic lesions by surgery. This inter-disciplinary clinical patient care ensures a competence build as well as a best practice procedure where the patient benefits. The science output in these resulting study outcomes further strengthens the build of healthcare benefit in the complex challenges of malignant melanoma pathophysiology that is addressed by the novel personalized medicines entering the market. These patient biobank archives will be fully automated with novel ultralow temperature biobank storage units and used as a clinical resource. Methods: Clinical materials from patients before, during and after treatments, with clinical end points are being collected. Tissue samples as well as bio-fluid samples such as blood fractions, plasma, serum and whole blood will be archived in 384-high density sample tube formats. We are developing standardized approaches for patient selections, patient sampling, sample-processing and analysis platforms with dedicated protein assays and genomics platforms that will hold value for the research community. Results: An IT-infrastructure using a laboratory information management system (LIMS) has been established, that will be the key interface for the research teams in order to share and explore data generated within the project. The cross-site data repository in Lund will form the basis for sample processing, together with biological samples in southern Sweden, including blood fractions and tumor tissues. Clinical registries are being associated with the biobank materials, including pathology reports on disease diagnosis on the MM patients. Conclusions: We provide data on the developments of protein profiling and targeted protein target assays on isolated melanoma tumors, as well as reference blood standards that is used by the team members in the respective laboratories. These pilot data show biobank access and feasibility of performing quantitative proteomics in MM biobank repositories collected in southern Sweden.
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- Welinder, Charlotte, et al.
(författare)
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Feasibility Study on Measuring Selected Proteins in Malignant Melanoma Tissue by SRM Quantification.
- 2014
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 13:3, s. 1315-1326
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Tidskriftsartikel (refereegranskat)abstract
- Currently there are no clinically recognized molecular biomarkers for malignant melanoma (MM) for either diagnosing disease stage or measuring response to therapy. The aim of this feasibility study was to develop targeted selected reaction monitoring (SRM) assays for identifying candidate protein biomarkers in metastatic melanoma tissue lysate. In a pilot study applying the SRM assay, the tissue expression of nine selected proteins [complement 3 (C3), T-cell surface glycoprotein CD3 epsilon chain E (CD3E), dermatopontin, minichromosome maintenance complex component (MCM4), premelanosome protein (PMEL), S100 calcium binding protein A8 (S100A8), S100 calcium binding protein A13 (S100A13), transgelin-2 and S100B] was quantified in a small cohort of metastatic malignant melanoma patients. The SRM assay was developed using a TSQ Vantage triple quadrupole mass spectrometer that generated highly accurate peptide quantification. Repeated injection of internal standards spiked into matrix showed relative standard deviation (RSD) from 6% to 15%. All nine target proteins were identified in tumor lysate digests spiked with heavy peptide standards. The multiplex SRM peptide assay panel was then measured and quantified on a set of frozen MM tissue samples obtained from the Malignant Melanoma Biobank collected in Lund, Sweden. All nine proteins could be accurately quantified using the new SRM assay format. This study provides preliminary data on the heterogeneity of biomarker expression within MM patients. The S100B protein, which is clinically used as the pathology identifier of MM, was identified in 9 out of 10 MM tissue lysates. The use of the targeted SRM assay provides potential advancements in the diagnosis of MM that can aid in future assessments of disease in melanoma patients.
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