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| 4. |
- Robbe, P, et al.
(author)
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Whole-genome sequencing of chronic lymphocytic leukemia identifies subgroups with distinct biological and clinical features
- 2022
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In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 54:11, s. 1675-
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Journal article (peer-reviewed)abstract
- The value of genome-wide over targeted driver analyses for predicting clinical outcomes of cancer patients is debated. Here, we report the whole-genome sequencing of 485 chronic lymphocytic leukemia patients enrolled in clinical trials as part of the United Kingdom’s 100,000 Genomes Project. We identify an extended catalog of recurrent coding and noncoding genetic mutations that represents a source for future studies and provide the most complete high-resolution map of structural variants, copy number changes and global genome features including telomere length, mutational signatures and genomic complexity. We demonstrate the relationship of these features with clinical outcome and show that integration of 186 distinct recurrent genomic alterations defines five genomic subgroups that associate with response to therapy, refining conventional outcome prediction. While requiring independent validation, our findings highlight the potential of whole-genome sequencing to inform future risk stratification in chronic lymphocytic leukemia.
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| 9. |
- Fu, Michael, 1963, et al.
(author)
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Adherence to optimal heart rate control in heart failure with reduced ejection fraction : insight from a survey of heart rate in heart failure in Sweden (HR-HF study)
- 2017
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In: Clinical Research in Cardiology. - : SPRINGER HEIDELBERG. - 1861-0684 .- 1861-0692. ; 106:12, s. 960-973
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Journal article (peer-reviewed)abstract
- Despite that heart rate (HR) control is one of the guideline-recommended treatment goals for heart failure (HF) patients, implementation has been painstakingly slow. Therefore, it would be important to identify patients who have not yet achieved their target heart rates and assess possible underlying reasons as to why the target rates are not met. The survey of HR in patients with HF in Sweden (HR-HF survey) is an investigator-initiated, prospective, multicenter, observational longitudinal study designed to investigate the state of the art in the control of HR in HF and to explore potential underlying mechanisms for suboptimal HR control with focus on awareness of and adherence to guidelines for HR control among physicians who focus on the contributing role of beta-blockers (BBs). In 734 HF patients the mean HR was 68 +/- 12 beats per minute (bpm) (37.2% of the patients had a HR > 70 bpm). Patients with HF with reduced ejection fraction (HFrEF) (n = 425) had the highest HR (70 +/- 13 bpm, with 42% > 70 bpm), followed by HF with preserved ejection fraction and HF with mid-range ejection fraction. Atrial fibrillation, irrespective of HF type, had higher HR than sinus rhythm. A similar pattern was observed with BB treatment. Moreover, non-achievement of the recommended target HR (< 70 bpm) in HFrEF and sinus rhythm was unrelated to age, sex, cardiovascular risk factors, cardiovascular diseases, and comorbidities, but was related to EF and the clinical decision of the physician. Approximately 50% of the physicians considered a HR of > 70 bpm optimal and an equal number considered a HR of > 70 bpm too high, but without recommending further action. Furthermore, suboptimal HR control cannot be attributed to the use of BBs because there was neither a difference in use of BBs nor an interaction with BBs for HR > 70 bpm compared with HR < 70 bpm. Suboptimal control of HR was noted in HFrEF with sinus rhythm, which appeared to be attributable to physician decision making rather than to the use of BBs. Therefore, our results underline the need for greater attention to HR control in patients with HFrEF and sinus rhythm and thus a potential for improved HF care.
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| 12. |
- Shev, S, et al.
(author)
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Second-generation hepatitis C Elisa antibody tests confirmed by the four-antigen recombinant immunoblot assay correlate well with hepatitis C viremia and chronic liver disease in Swedish blood donors
- 1993
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In: Vox Sanguinis. - 1423-0410. ; 65:1, s. 32-37
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Journal article (peer-reviewed)abstract
- Seventy-three Swedish blood donors (52 men, 21 women; median age 36 years) repeatedly reactive for hepatitis C antibodies (anti-HCV C-100-3) were tested with a second-generation (2nd-gen) anti-HCV Elisa and a 4-band recombinant immunoblot assay (RIBA 2). These results were correlated to serum alanine aminotransferase (S-ALAT), liver morphology and viremia as detected by 'nested' polymerase chain reaction (PCR) based on primers from a 5'-noncoding sequence of the HCV genome. Thirty-five of 46 (76%) donors with positive 2nd-gen Elisa tests confirmed by RIBA 2 were PCR positive whereof 27 had histological findings compatible with chronic persistent hepatitis (CPH) and 7 had chronic active hepatitis (CAH). Ten of 56 (18%) 2nd-gen Elisa-positive donors were RIBA 2 negative (or indeterminate) and none of these had chronic hepatitis nor were PCR positive. Seventeen of 73 (23%) donors were 1st-gen Elisa positive but 2nd-gen Elisa negative. All of these were PCR negative and only 1 (6%) had chronic hepatitis (CPH). An elevated S-ALAT level (reference < 0.7 mu kat/l) was found in 26 2nd-gen Elisa and RIBA 2-positive donors of which 18 had CPH and 7 had CAH and all 25 were PCR positive. A normal S-ALAT level was found in 9 of 34 (26%) donors with chronic hepatitis (all had CPH) and positive PCR. We have found that blood donors with positive 2nd-gen anti-HCV Elisa tests confirmed by RIBA-2 and especially with a concomitant elevated S-ALAT are highly likely to be viremic as demonstrated by PCR and to have chronic hepatitis.
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| 15. |
- Bestas, Burcu, et al.
(author)
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Splice-correcting oligonucleotides restore BTK function in X-linked agammaglobulinemia model
- 2014
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In: Journal of Clinical Investigation. - 0021-9738 .- 1558-8238. ; 124:9, s. 4067-4081
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Journal article (peer-reviewed)abstract
- X-linked agammaglobulinemia (XLA) is an inherited immunodeficiency that results from mutations within the gene encoding Bruton's tyrosine kinase (BTK). Many XLA-associated mutations affect splicing of BTK pre-mRNA and severely impair B cell development. Here, we assessed the potential of antisense, splice-correcting oligonucleotides (SCOs) targeting mutated BTKtranscripts for treating XLA. Both the SCO structural design and chemical properties were optimized using 2'-O-methyl, locked nucleic acid, or phosphorodiamidate morpholino backbones. In order to have access to an animal model of XLA, we engineered a transgenic mouse that harbors a BAC with an authentic, mutated, splice-defective human BTK gene. BTK transgenic mice were bred onto a Btk knockout background to avoid interference of the orthologous mouse protein. Using this model, we determined that BTK-specific SCOs are able to correct aberrantly spliced BTK in B lymphocytes, including pro-B cells. Correction of BTK mRNA restored expression of functional protein, as shown both by enhanced lymphocyte survival and reestablished BTK activation upon B cell receptor stimulation. Furthermore, SCO treatment corrected splicing and restored BTK expression in primary cells from patients with XLA. Together, our data demonstrate that SCOs can restore BTK function and that BTK-targeting SCOs have potential as personalized medicine in patients with XLA.
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| 16. |
- Biague, A, et al.
(author)
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High sexual risk taking and diverging trends of HIV-1 and HIV-2 in the military of Guinea Bissau
- 2010
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In: Journal of infection in developing countries. - : Journal of Infection in Developing Countries. - 1972-2680. ; 4:5, s. 301-308
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Journal article (peer-reviewed)abstract
- Background: HIV and other sexually transmitted infections are a growing problem in the military personnel of Africa, and information about this problem in Guinea-Bissau is lacking. The aims of this study were to determine the prevalence and trends of the HIV epidemics in the military forces of Guinea Bissau and to explore possible risk factors for HIV infection. Methodology: Repeated cross-sectional surveys of HIV-1 and HIV-2 were conducted between 1992 and 2005, and knowledge, sexual behaviour and risk factors for HIV-1 and HIV-2 in military personnel in Guinea-Bissau were assessed. Results: The seroprevalence of HIV-1, HIV-2 and HIV-1+HIV-2 dual reactivity was 1.1%, 8.4% and 0.1% in 1992-95, and in 2005 7.7%, 5.1% and 1.9%, respectively. Both the increase of HIV-1 and the decline of HIV-2 between 1992-95 and 2005 were significant when adjusted for age (p < 0.001 for both changes). Only a minority did not know how HIV transmits, but sexual risk taking was high. Several significant risk factors were found in univariate analyses for HIV-1 and HIV-2, but the only risk factor that remained significant after multivariate regression analysis was previous contact with a prostitute among HIV-1-positive subjects (single and dually reactive) (p < 0.01). Conclusion: The increasing trend of HIV-1 and the high risky sexual behavior illustrate the need for improvement in HIV/AIDS prevention efforts among military personnel in Guinea Bissau.
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| 17. |
- Guenot, Diego, et al.
(author)
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Probing electron correlation on the attosecond time scale
- 2014
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In: High Intensity Lasers and High Field Phenomena, HILAS 2014. - 9781557529954
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Conference paper (peer-reviewed)abstract
- We present experimental measurements and theoretical calculations of single and double ionization time delays in various noble gases using an interferometric method. The measured delays allow us to extract information on the electron correlation.
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| 18. |
- Hansson, J., et al.
(author)
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Monitoring of kindreds with hereditary predisposition for cutaneous melanoma and dysplastic nevus syndrome: results of a Swedish preventive program
- 2007
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In: J Clin Oncol. ; 25:19, s. 2819-2824
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Journal article (peer-reviewed)abstract
- PURPOSE: To evaluate a program initiated in 1987 by the Swedish Melanoma Study Group aiming to provide preventive surveillance to kindreds with hereditary cutaneous melanoma and dysplastic nevus syndrome. PATIENTS AND METHODS: Overall, 2,080 individuals belonging to 280 melanoma families were followed for 14 years between 1987 and 2001 at 12 participating centers. Data were registered in a central database. RESULTS: Among 1,912 skin lesions excised during follow-up, 41 melanomas were removed in 32 individuals. Of these, 15 (37%) were in situ melanomas and 26 (63%) invasive melanomas. The median tumor thickness of invasive melanomas was 0.5 mm. Ulceration was absent in 24 of 26 invasive melanomas (92%) and 12 (46%) lacked vertical growth phase. Compared with melanomas in the general Swedish population, the melanomas identified in these kindreds during follow-up had better prognostic characteristics. All melanomas except one were diagnosed in families with two or more first-degree relatives with melanoma. Diagnosis of melanoma occurred in three of eight kindreds with germline CDKN2A mutations, supporting that families with such mutations are at increased risk for melanoma development. Of the 32 individuals who developed melanoma during follow-up, 21 (66%) had had at least one previously diagnosed melanoma. CONCLUSION: This study shows that a coordinated program aimed at detecting and offering skin surveillance in kindreds with hereditary cutaneous melanoma results in a low incidence of melanomas during the follow-up period and that the tumors that do arise have favorable prognostic characteristics.
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| 22. |
- Mansson, A, et al.
(author)
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Actin-based molecular motors for cargo transportation in nanotechnology - Potentials and challenges
- 2005
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In: IEEE Transactions on Advanced Packaging. - 1521-3323. ; 28:4, s. 547-555
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Journal article (peer-reviewed)abstract
- Here, we review the use of actin-based motors, (myosins; e.g., the molecular motor of muscle) in. nanotechnology. The review starts from the viewpoints of the molecular motors as being important devices responsible of cargo transportation in the cell and end in discussions about their employment in nanotechnological applications. First, we describe basic biophysics of the myosin motors with focus on their involvement in cargo transportation in the living cell, leading us over into a discussion about in vitro motility assays. These are biological test systems where the myosin-induced translocation of actin filaments is studied on an artificial surface outside the cell. Then follows a review about modified motility assays for production of ordered motion. Here, we discuss ours and others' work with regards to making micro- and nanostructured surfaces and channels where the position and direction of movement produced by molecular motors is controlled. In this section, we consider the role of the channel size in promoting unidirectional myosin-induced motion of actin filaments. Furthermore, we consider the usefulness of surface modifications, e.g., various silanization procedures in order to promote and hinder molecular motility, respectively. Particularly, we describe our latest test system being both morphologically and chemically nanostructured giving us unsurpassed possibilities to perform functional studies as well as extremely good spatio-temporal control. Then follows a section about nanotechnological cargo transportation systems based on the actomyosin motor system. For instance, we present results of attaching fluorescent quantum dots as cargoes to the actin filaments. In this section, we also discuss the possibilities of having cargo attachment and detachment being performed on demand. Finally, we consider the usefulness of molecular motors for lab-on-a-chip applications and the requirements for incorporating these motors in commercially viable devices. In this context, the significant potential of the actomyosin motor system to overcome traditional limitations of micro- and nanofluidics is stressed.
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| 23. |
- Mansson, A, et al.
(author)
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In vitro sliding of actin filaments labelled with single quantum dots
- 2004
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In: Biochemical and Biophysical Research Communications. - : Elsevier BV. - 1090-2104 .- 0006-291X. ; 314:2, s. 529-534
-
Journal article (peer-reviewed)abstract
- We recently refined the in vitro motility assay for studies of actomyosin function to achieve rectified myosin induced sliding of actin filaments. This paves the way, both for detailed functional studies of actomyosin and for nanotechnological applications. In the latter applications it would be desirable to use actin filaments for transportation of cargoes (e.g., enzymes) between different predetermined locations on a chip. We here describe how single quantum dot labelling of isolated actin filaments simultaneously provides handles for cargo attachment and bright and photostable fluorescence labels facilitating cargo detection and filament tracking. Labelling was achieved with preserved actomyosin function using streptavidin-coated CdSe quantum dots (Qdots). These nanocrystals have several unique physical properties and the present work describes their first use for functional studies of isolated proteins outside the cell. The results, in addition to the nanotechnology developments, open for new types of in vitro assays of isolated biomolecules. (C) 2003 Elsevier Inc. All rights reserved.
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| 24. |
- Mansson, A., et al.
(author)
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Neutral third party versus treating institution for evaluating quality of life after radical cystectomy
- 2004
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In: Eur Urol. - 0302-2838. ; 46:2, s. 195-9
-
Journal article (peer-reviewed)abstract
- OBJECTIVE: To evaluate the possible impact of a neutral third party on the patients' responses to health-related quality of life (HRQL) instruments. METHODS: 119 patients operated at the Department of Urology in Lund with radical cystectomy and continent urinary tract reconstruction (continent cutaneous diversion or orthotopic bladder substitution) for locally advanced bladder cancer were included in the study. They were randomly divided in two groups, similar with regard to gender, age, length of follow-up, and type of reconstruction. The EORTC instruments QLQ-C30 and QLQ-BLM30 were sent to the patients. One group; "Lund patients", received the instruments from the Department of Urology in Lund, while the other group; "Stockholm patients", received the instruments from a neutral third party, i.e. "The Project Health and Well-Being" at the Karolinska Institutet in Stockholm. RESULTS: Response rates were high in both groups, 59 out of 60 among Lund patients and 57 out of 59 among Stockholm patients. There were statistically significantly more bowel problems reported in the Stockholm patients than in the Lund patients (p<0.05) in the QLQ-C30 instrument. Regarding type of reconstruction, the Stockholm patients with continent cutaneous diversion scored higher for constipation than the Lund patients (p<0.05), and the Stockholm patients with bladder substitution scored lower for emotional functioning and higher for dyspnoea and economical problems than the Lund patients (p<0.05. There were no statistically significant differences between the Lund patients and the Stockholm patients in the QLQ-BLM30 instrument. CONCLUSION: Though few factors differed between the two groups, the results may indicate that different results are obtained when a study is totally administered and analyzed by a neutral third party as compared with the surgeon or his or her institution. Larger studies are needed to further test this hypothesis.
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| 31. |
- Thomberg, T., et al.
(author)
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The anti SARS-CoV-2 activity of nanofibrous filter materials activated with metal clusters
- 2023
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In: ATMOSPHERIC ENVIRONMENT-X. - : Elsevier BV. - 2590-1621. ; 17
-
Journal article (peer-reviewed)abstract
- Nanofibrous filter materials were prepared by electrospinning a solution of 28 wt% poly(vinylidene fluoride) in N,N-dimethylacetamide with and without the addition of 2 wt% AgNO3, Cu(NO3)(2)center dot 2.5H(2)O or ZnCl2. X-ray diffraction, scanning electron microscopy with energy dispersive X-ray spectroscopy, inductively coupled plasma mass spectroscopy, thermogravimetric analysis, contact angle measurement, nitrogen sorption, and mercury intrusion porosimetry methods were used for the characterization of physical structure as well as the chemical composition of the electrospun materials. Particle filtration efficiency and antiviral activity against the SARS-CoV-2 alpha variant were tested in order to estimate the suitability of the prepared electrospun filter mate-rials for application as indoor air filtration systems with virucidal properties. All filter materials prepared with salts demonstrated very high particle filtration efficiency (>= 98.0%). The best antiviral activity was demonstrated by a material containing Cu(NO3)(2)center dot 2.5H(2)O in the spinning solution, which displayed the decrease in the number of infectious virions by three orders of magnitude after a contact time of 12 h. Materials with the addition of AgNO3 and ZnCl2 decreased the number of infectious virions after the same contact time by only-8 and-11 times, respectively.
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| 37. |
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| 38. |
- Berntsen, Magnus H., et al.
(author)
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A spin- and angle-resolving photoelectron spectrometer
- 2010
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In: Review of Scientific Instruments. - : AIP Publishing. - 0034-6748 .- 1089-7623. ; 81:3
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Journal article (peer-reviewed)abstract
- A new type of hemispherical electron energy analyzer that permits angle and spin resolved photoelectron spectroscopy has been developed. The analyzer permits standard angle resolved spectra to be recorded with a two-dimensional detector in parallel with spin detection using a mini-Mott polarimeter. General design considerations as well as technical solutions are discussed and test results from the Au(111) surface state are presented.
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| 43. |
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| 44. |
- Bunk, Richard, et al.
(author)
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Actomyosin motility on nanostructured surfaces
- 2003
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In: Biochemical and Biophysical Research Communications. - 1090-2104. ; 301:3, s. 783-788
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Journal article (peer-reviewed)abstract
- We have here, for the first time, used nanofabrication techniques to reproduce aspects of the ordered actomyosin arrangement in a muscle cell. The adsorption of functional heavy meromyosin (HMM) to five different resist polymers was first assessed. One group of resists (MRL-6000.1XP and ZEP-520) consistently exhibited high quality motility of actin filaments after incubation with HMM. A second group (PMMA-200, PMMA-950, and MRI-9030) generally gave low quality of motility with only few smoothly moving filaments. Based on these findings electron beam lithography was applied to a bi-layer resist system with PMMA-950 on top of MRL-6000.1XP. Grooves (100-200 nm wide) in the PMMA layer were created to expose the MRL-6000.1XP surface for adsorption of HMM and guidance of actin filament motility. This guidance was quite efficient allowing no U-turns of the filaments and approximately 20 times higher density of moving filaments in the grooves than on the surrounding PMMA.
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| 45. |
- Bunk, Richard, et al.
(author)
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Guiding molecular motors with nano-imprinted structures
- 2005
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In: Japanese Journal of Applied Physics. - 0021-4922. ; 44:5A, s. 3337-3340
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Journal article (peer-reviewed)abstract
- This work, for the first time, demonstrates that nano-imprinted samples, with 100 nm wide polymer lines, can act as guides for molecular motors consisting of motor proteins actin and myosin. The motor protein function was characterized using fluorescence microscopy and compared to actomyosin motility on non-structured nitrocellulose surfaces. Our results open for further use of the nano-imprint technique in the production of disposable chips for bio-nanotechnological applications and miniaturized biological test systems. We discuss how the nano-imprinted motor protein assay system may be optimized and also how it compares to previously tested assay systems involving low-resolution UV-lithography and low throughput but high-resolution electron beam lithography.
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| 46. |
- Bunk, Richard, et al.
(author)
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Guiding motor-propelled molecules with nanoscale precision through silanized bi-channel structures
- 2005
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In: Nanotechnology. - : IOP Publishing. - 0957-4484 .- 1361-6528. ; 16:6, s. 710-717
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Journal article (peer-reviewed)abstract
- We report on the design and fabrication of a channel structure for high precision guidance and achieving excellent confinement properties for motor-propelled molecular shuttles. The techniques used to manufacture the channel structure are mainly e-beam lithography and selective monolayer functionalization. The structure consists of two lateral layers of concentric channels on a SiO2 surface made biocompatible with the molecular motors. The quality and advantages of the design are demonstrated by experiments using the motor proteins actin and myosin. The special channel geometry leads to stable biochemical conditions with full motor protein functionality. ATP is sufficiently supplied to all parts of the structure by dedicated service channels, as is the venting of ADP and P-i (inorganic phosphorus). Channels of different widths (100-700 nm) and shapes are fabricated and measurements made on them.
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| 47. |
- Bunk, Richard, et al.
(author)
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Towards a 'nano-traffic' system powered by molecular motors
- 2003
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In: Microelectronic Engineering. - 1873-5568. ; 67-8, s. 899-904
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Journal article (peer-reviewed)abstract
- In this work, we reconstructed in vitro the behavior of two motor proteins-myosin and actin-responsible for the mechanical action of muscle cells. By transferring this in vivo system to an artificial environment, we were able to study the interaction between the proteins in more detail, as well as investigating the central mechanism of force production. Nm-patterning by e-beam lithography (EBL) could restore parts of the in vivo protein order, essential for potential nanotechnological applications. Much work was put into establishing the necessary compatibility between the biological and nano-lithographical processes. A range of EBL-resists were tested for protein compatibility. One particular kind (MRL-6000.1XP) supported good actin filament motility, while another (PMMA-950) behaved in the opposite way. Taking advantage of these findings, nm-sized lines were created in a double-layer structure of the two resists. The lines were found to act as binding sites for myosin, and as rectifying guides for the linearized motion of actin filaments. Velocities around 5 mum/s were measured. (C) 2003 Elsevier Science B.V. All rights reserved.
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| 48. |
- C. Lin, Yin, et al.
(author)
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A global network of transcription factors, involving E2A, EBF1 and Foxo1, that orchestrates B cell fate
- 2010
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In: Nature Immunology. - : Nature Publishing Group. - 1529-2908 .- 1529-2916. ; 11:7, s. 635-U109
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Journal article (peer-reviewed)abstract
- It is now established that the transcription factors E2A, EBF1 and Foxo1 have critical roles in B cell development. Here we show that E2A and EBF1 bound regulatory elements present in the Foxo1 locus. E2A and EBF1, as well as E2A and Foxo1, in turn, were wired together by a vast spectrum of cis-regulatory sequences. These associations were dynamic during developmental progression. Occupancy by the E2A isoform E47 directly resulted in greater abundance, as well as a pattern of monomethylation of histone H3 at lysine 4 (H3K4) across putative enhancer regions. Finally, we divided the pro-B cell epigenome into clusters of loci with occupancy by E2A, EBF and Foxo1. From this analysis we constructed a global network consisting of transcriptional regulators, signaling and survival factors that we propose orchestrates B cell fate.
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| 49. |
- Carlberg, Patrick, et al.
(author)
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Nanoimprint - a tool for realizing nano-bio research
- 2004
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In: 2004 4th IEEE Conference on Nanotechnology. - 0780385365 ; , s. 199-200
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Conference paper (peer-reviewed)abstract
- In this paper, we present a status report on how implementation of nanoimprint lithography has advanced our research. Contact guidance nerve growth experiments have so far primarily been done on micrometer-structured surfaces. We have made a stamp with 17 areas of different, submicron, line width and spacing covering a total 2.6 mm
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| 50. |
- Chang, J., et al.
(author)
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Electronic structure near the 1/8-anomaly in La-based cuprates
- 2008
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In: New Journal of Physics. - : IOP Publishing. - 1367-2630. ; 10
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Journal article (peer-reviewed)abstract
- We report an angle-resolved photoemission study of the electronic structure of the pseudogap state in La1.48Nd0.4Sr0.12CuO4 (T-c < 7 K). Two opposite dispersing Fermi arcs are the main result of this study. Several scenarios that can explain this observation are discussed.
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