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| 2. |
- Lange, S, et al.
(författare)
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The kinase domain of titin controls muscle gene expression and protein turnover
- 2005
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Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 308:5728, s. 1599-1603
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Tidskriftsartikel (refereegranskat)abstract
- The giant sarcomeric protein titin contains a protein kinase domain (TK) ideally positioned to sense mechanical load. We identified a signaling complex where TK interacts with the zinc-finger protein nbr1 through a mechanically inducible conformation. Nbr1 targets the ubiquitin-associated p62/SQSTM1 to sarcomeres, and p62 in turn interacts with MuRF2, a muscle-specific RING-B-box E3 ligase and ligand of the transactivation domain of the serum response transcription factor (SRF). Nuclear translocation of MuRF2 was induced by mechanical inactivity and caused reduction of nuclear SRF and repression of transcription. A human mutation in the titin protein kinase domain causes hereditary muscle disease by disrupting this pathway.
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| 3. |
- Manni, F, et al.
(författare)
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Hyperspectral Imaging for Glioblastoma Surgery: Improving Tumor Identification Using a Deep Spectral-Spatial Approach
- 2020
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Ingår i: Sensors (Basel, Switzerland). - : MDPI AG. - 1424-8220. ; 20:23
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Tidskriftsartikel (refereegranskat)abstract
- The primary treatment for malignant brain tumors is surgical resection. While gross total resection improves the prognosis, a supratotal resection may result in neurological deficits. On the other hand, accurate intraoperative identification of the tumor boundaries may be very difficult, resulting in subtotal resections. Histological examination of biopsies can be used repeatedly to help achieve gross total resection but this is not practically feasible due to the turn-around time of the tissue analysis. Therefore, intraoperative techniques to recognize tissue types are investigated to expedite the clinical workflow for tumor resection and improve outcome by aiding in the identification and removal of the malignant lesion. Hyperspectral imaging (HSI) is an optical imaging technique with the power of extracting additional information from the imaged tissue. Because HSI images cannot be visually assessed by human observers, we instead exploit artificial intelligence techniques and leverage a Convolutional Neural Network (CNN) to investigate the potential of HSI in twelve in vivo specimens. The proposed framework consists of a 3D–2D hybrid CNN-based approach to create a joint extraction of spectral and spatial information from hyperspectral images. A comparison study was conducted exploiting a 2D CNN, a 1D DNN and two conventional classification methods (SVM, and the SVM classifier combined with the 3D–2D hybrid CNN) to validate the proposed network. An overall accuracy of 80% was found when tumor, healthy tissue and blood vessels were classified, clearly outperforming the state-of-the-art approaches. These results can serve as a basis for brain tumor classification using HSI, and may open future avenues for image-guided neurosurgical applications.
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| 4. |
- Manti, M., et al.
(författare)
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Excess of ovarian nerve growth factor impairs embryonic development and causes reproductive and metabolic dysfunction in adult female mice
- 2020
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Ingår i: FASEB Journal. - : John Wiley & Sons. - 0892-6638 .- 1530-6860. ; 34:11, s. 14440-14457
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Tidskriftsartikel (refereegranskat)abstract
- Nerve growth factor (NGF) is critical for the development and maintenance of the peripheral sympathetic neurons. NGF is also involved in the ovarian sympathetic innervation and in the development and maintenance of folliculogenesis. Women with the endocrine disorder, polycystic ovary syndrome (PCOS), have an increased sympathetic nerve activity and increased ovarian NGF levels. The role of ovarian NGF excess in the PCOS pathophysiology and in the PCOS-related features is unclear. Here, using transgenic mice overexpressesing NGF in the ovarian theca cells (17NF mice), we assessed the female embryonic development, and the reproductive and metabolic profile in adult females. Ovarian NGF excess caused growth restriction in the female fetuses, and a delayed gonocyte and primary oocyte maturation. In adulthood, the 17NF mice displayed irregular estrous cycles and altered ovarian expression of steroidogenic and epigenetic markers. They also exhibited an increased sympathetic output with increased circulating dopamine, and metabolic dysfunction reflected by aberrant adipose tissue morphology and function, impaired glucose metabolism, decreased energy expenditure, and hepatic steatosis. These findings indicate that ovarian NGF excess leads to adverse fetal development and to reproductive and metabolic complications in adulthood, mirroring common features of PCOS. This work provides evidence that NGF excess may be implicated in the PCOS pathophysiology.
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| 5. |
- Reichel, L., et al.
(författare)
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From soft to hard magnetic Fe-Co-B by spontaneous strain : a combined first principles and thin film study
- 2015
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Ingår i: Journal of Physics. - : IOP Publishing. - 0953-8984 .- 1361-648X. ; 27:47
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Tidskriftsartikel (refereegranskat)abstract
- In order to convert the well-known Fe-Co-B alloy from a soft to a hard magnet, we propose tetragonal strain by interstitial boron. Density functional theory reveals that when B atoms occupy octahedral interstitial sites, the bcc Fe-Co lattice is strained spontaneously. Such highly distorted Fe-Co is predicted to reach a strong magnetocrystalline anisotropy which may compete with shape anisotropy. To probe this theoretical suggestion experimentally, epitaxial films are examined. A spontaneous strain up to 5% lattice distortion is obtained for B content up to 4 at%, which leads to uniaxial anisotropy constants exceeding 0.5 MJ m(-3). However, a further addition of B results in a partial amorphisation, which degrades both anisotropy and magnetisation.
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| 8. |
- Björk-Eriksson, Thomas, 1960, et al.
(författare)
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The lack of correlation between proliferation (Ki-67, PCNA, LI, Tpot), p53 expression and radiosensitivity for head and neck cancers
- 1999
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Ingår i: Br J Cancer. - 0007-0920. ; 80:9, s. 1400-4
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Tidskriftsartikel (refereegranskat)abstract
- A study was made of the relationship between measurements of radiosensitivity versus proliferation and p53 status in head and neck cancers. Inherent tumour radiosensitivity was assessed as surviving fraction at 2 Gy (SF2) using a clonogenic soft agar assay (n = 77). The results were compared to data on proliferation obtained by both flow cytometry (labelling index (LI), the potential doubling time (Tpot) n = 55) and immunohistochemistry (Ki-67 and PCNA; n = 68), together with immunohistochemical p53 expression (n = 68). There were no overall significant differences in the median values of the various parameters analysed for the different sites within the head and neck region, disease stages, grades of tumour differentiation or nodal states. A subgroup analysis showed that oropharyngeal (n = 22) versus oral cavity (n = 35) tumours were more radiosensitive (P = 0.056) and had a higher Ki-67 index (P = 0.001). Node-positive tumours had higher LI (P = 0.021) and a trend towards lower Tpot (P = 0.067) values than node-negative ones. No correlations were seen between SF2 and any of the parameters studied. The long-standing dogma of an increased radiosensitivity of rapidly proliferating cells in contrast to slowly proliferating cells was not confirmed. The study shows that parallel measurements of different biological markers can be obtained for a large number of patients with head and neck cancers. The independence of the various parameters studied suggests that there may be potential for their combined use as prognostic factors for the outcome of radiotherapy.
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| 10. |
- Burstrom, G, et al.
(författare)
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Feasibility and accuracy of a robotic guidance system for navigated spine surgery in a hybrid operating room: a cadaver study
- 2020
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1, s. 7522-
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Tidskriftsartikel (refereegranskat)abstract
- The combination of navigation and robotics in spine surgery has the potential to accurately identify and maintain bone entry position and planned trajectory. The goal of this study was to examine the feasibility, accuracy and efficacy of a new robot-guided system for semi-automated, minimally invasive, pedicle screw placement. A custom robotic arm was integrated into a hybrid operating room (OR) equipped with an augmented reality surgical navigation system (ARSN). The robot was mounted on the OR-table and used to assist in placing Jamshidi needles in 113 pedicles in four cadavers. The ARSN system was used for planning screw paths and directing the robot. The robot arm autonomously aligned with the planned screw trajectory, and the surgeon inserted the Jamshidi needle into the pedicle. Accuracy measurements were performed on verification cone beam computed tomographies with the planned paths superimposed. To provide a clinical grading according to the Gertzbein scale, pedicle screw diameters were simulated on the placed Jamshidi needles. A technical accuracy at bone entry point of 0.48 ± 0.44 mm and 0.68 ± 0.58 mm was achieved in the axial and sagittal views, respectively. The corresponding angular errors were 0.94 ± 0.83° and 0.87 ± 0.82°. The accuracy was statistically superior (p < 0.001) to ARSN without robotic assistance. Simulated pedicle screw grading resulted in a clinical accuracy of 100%. This study demonstrates that the use of a semi-automated surgical robot for pedicle screw placement provides an accuracy well above what is clinically acceptable.
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