| 1. |
- Linder, Nina, et al.
(författare)
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Deep learning for detecting tumour-infiltrating lymphocytes in testicular germ cell tumours
- 2019
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Ingår i: Journal of Clinical Pathology. - : BMJ Publishing Group Ltd. - 0021-9746 .- 1472-4146. ; 72:2, s. 157-164
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: To evaluate if a deep learning algorithm can be trained to identify tumour-infiltrating lymphocytes (TILs) in tissue samples of testicular germ cell tumours and to assess whether the TIL counts correlate with relapse status of the patient.METHODS: TILs were manually annotated in 259 tumour regions from 28 whole-slide images (WSIs) of H&E-stained tissue samples. A deep learning algorithm was trained on half of the regions and tested on the other half. The algorithm was further applied to larger areas of tumour WSIs from 89 patients and correlated with clinicopathological data.RESULTS: A correlation coefficient of 0.89 was achieved when comparing the algorithm with the manual TIL count in the test set of images in which TILs were present (n=47). In the WSI regions from the 89 patient samples, the median TIL density was 1009/mm2. In seminomas, none of the relapsed patients belonged to the highest TIL density tertile (>2011/mm2). TIL quantifications performed visually by three pathologists on the same tumours were not significantly associated with outcome. The average interobserver agreement between the pathologists when assigning a patient into TIL tertiles was 0.32 (Kappa test) compared with 0.35 between the algorithm and the experts, respectively. A higher TIL density was associated with a lower clinical tumour stage, seminoma histology and lack of lymphovascular invasion.CONCLUSIONS: Deep learning-based image analysis can be used for detecting TILs in testicular germ cell cancer more objectively and it has potential for use as a prognostic marker for disease relapse.
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| 2. |
- Abrahamsson, Johan, 1977-
(författare)
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Kinetic Energy Storage and Magnetic Bearings : for Vehicular Applications
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- One of the main challenges in order to make electric cars competitive with gas-powered cars is in the improvement of the electric power system. Although many of the energy sources currently used in electric vehicles have sufficientlyhigh specific energy, their applicability is limited due to low specific power. It would therefore be advantageous to create a driveline with the main energy storage separated from a smaller energy buffer, designed to have high power capabilities and to withstand frequent and deep discharge cycles. It has been found that rotating kinetic energy storage in flywheels is very well suited for this type of application.A composite shell, comprising an inner part made of glassfiber and an outer part made of carbonfiber, was analyzed analytically and numerically, designed, and constructed. The shell was fitted onto a metallic rotor using shrinkfitting. The cost of the shell, and the complexity of assembly, was reduced by winding the glass- and carbonfiber consecutively on a mandrel, and curing the complete assembly simultaneously. Thereby, the shell obtained an internal segmentation, without the need for fitting several concentric parts onto each other. The radial stress inside the composite shell was kept compressive thanks to a novel approach of using the permanent magnets of the integrated electric machine to provide radial mechanical load during rotation.Two thrust bearing units (one upper and one lower) comprising one segmented unit with the permanent magnets in a cylindrical Halbach configuration and one non-segmented unit in a up/down configuration were optimized, constructed and tested. Each thrust bearing unit generated 1040 N of repelling force, and a positive axial stiffness of 169 N/mm at the nominal airgap of 5 mm. Two radial active magnetic bearings (one upper and one lower) were optimized, constructed and tested. By parameterizing the shape of the actuators, a numerical optimization of force over resistive loss from the bias currentcould be performed. The optimized shape of the electromagnets was produced by watercutting sheets of laminated steel. A maximum current stiffness of120 N/A at a bias current of 1.5 A was achieved.
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| 3. |
- Cijvat, Pieternella, et al.
(författare)
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Miljöföreläsningar med simulerad klimatkonferens i elektronik undervisning
- 2009
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Ingår i: Lärande i LTH. ; :8, december 2009, s. 5-5
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Tidskriftsartikel (refereegranskat)abstract
- Kursen ”Elektronikprojekt och hållbar utveckling” ges för årskurs tre på elektroteknikprogrammet. Kursen består av två delar, en projektdel och en föreläsningsdel. Under projektdelen arbetar teknologerna i grupper om fyra med olika projekt i elektronik. Föreläsningsdelen består av sju stycken tvåtimmarsföreläsningar som ägnas åt miljökunskap. Vi kommer här att redogöra för hur föreläsningsdelen genomfördes.
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| 4. |
- Cijvat, Pieternella, et al.
(författare)
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Miljöföreläsningar med simulerad klimatkonferens i elektronikundervisning
- 2009
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Ingår i: Proceedings Utvecklingskonferens 09. - 9789197797429 ; , s. 185-192
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Konferensbidrag (refereegranskat)abstract
- Kursen ”Ingenjörsmässig analys” ges för årskurs tre på elektroteknikprogrammet. Kursen är obligatorisk och kursmålen är av övergripande karaktär. Teknologerna ska tränas i att arbeta i grupp, söka information, redovisa skriftligt och presentera muntligt. Kursen består av två delar, en projektdel och en föreläsningsdel. Under projektdelen arbetar teknologerna i grupper om fyra med olika projekt i elektronik. Föreläsningsdelen består av sju stycken tvåtimmarsföreläsningar som ägnas åt miljökunskap. Vi kommer här endast behandla föreläsningsdelen. Teknologerna fick i grupper om fyra i uppgift att analysera en miljöaspekt. Resultatet av analysen fick de sedan redovisa skriftligt på en A4-sida och dessutom muntligt inför hela klassen. Detta innebar att kursen fick inslag av deltagarundervisning. Den sista föreläsningen genomfördes ett rollspel som simulerade förhandlingar i FN:s klimatorgan (UNFCCC). Teknologerna fick i grupper om fyra representera olika länders regeringar. En grupp fick representera FN:s generalsekretariat och en annan fick representera FN:s klimatpanel (IPCC). En grupp var ”journalister”. Denna grupp videofilmade och fotograferade under konferensen. Efter konferensen skrev de en kort tidningsartikel. Varje föreläsning gavs en A4-sida med frågor ut. Under föreläsningen gavs svaren på dessa frågor. I början av nästa föreläsning genomfördes en skriftlig dugga under vilken varje teknolog fick svara på tre av dessa frågor. Föreläsningarna handlade om såväl allmän miljökunskap som specifik miljökunskap kopplad till elektronik. Vår idé för att skapa god inlärning var att aktivera studenterna.
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| 5. |
- Dumitriu, Dani, et al.
(författare)
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Deciduous tooth biomarkers reveal atypical fetal inflammatory regulation in autism spectrum disorder.
- 2023
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Ingår i: iScience. - : Cell Press. - 2589-0042. ; 26:3
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Tidskriftsartikel (refereegranskat)abstract
- Atypical regulation of inflammation has been proposed in the etiology of autism spectrum disorder (ASD); however, measuring the temporal profile of fetal inflammation associated with future ASD diagnosis has not been possible. Here, we present a method to generate approximately daily profiles of prenatal and early childhood inflammation as measured by developmentally archived C-reactive protein (CRP) in incremental layers of deciduous tooth dentin. In our discovery population, a group of Swedish twins, we found heightened inflammation in the third trimester in children with future ASD diagnosis relative to controls (n = 66; 14 ASD cases; critical window: -90 to -50 days before birth). In our replication study, in the US, we observed a similar increase in CRP in ASD cases during the third trimester (n = 47; 23 ASD cases; -128 to -21 days before birth). Our results indicate that the third trimester is a critical period of atypical fetal inflammatory regulation in ASD.
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| 6. |
- Gad, Helge, et al.
(författare)
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MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool
- 2014
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 508:7495, s. 215-221
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Tidskriftsartikel (refereegranskat)abstract
- Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. Although MTH1 is non-essential in normal cells, we show that cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death. We validate MTH1 as an anticancer target in vivo and describe small molecules TH287 and TH588 as first-in-class nudix hydrolase family inhibitors that potently and selectively engage and inhibit the MTH1 protein in cells. Protein co-crystal structures demonstrate that the inhibitors bindin the active site of MTH1. The inhibitors cause incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses in patient-derived mouse xenografts. This study exemplifies the non-oncogene addiction concept for anticancer treatment and validates MTH1 as being cancer phenotypic lethal.
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| 7. |
- Gunnarsson, Rebeqa, et al.
(författare)
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Array-based genomic screening at diagnosis and during follow-up in chronic lymphocytic leukemia
- 2011
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Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 96:8, s. 1161-1169
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Tidskriftsartikel (refereegranskat)abstract
- Background High-resolution genomic microarrays enable simultaneous detection of copy-number aberrations such as the known recurrent aberrations in chronic lymphocytic leukemia [del(11q), del(13q), del(17p) and trisomy 12], and copy-number neutral loss of heterozygosity. Moreover, comparison of genomic profiles from sequential patients' samples allows detection of clonal evolution. Design and Methods We screened samples from 369 patients with newly diagnosed chronic lymphocytic leukemia from a population-based cohort using 250K single nucleotide polymorphism-arrays. Clonal evolution was evaluated in 59 follow-up samples obtained after 5-9 years. Results At diagnosis, copy-number aberrations were identified in 90% of patients; 70% carried known recurrent alterations, including del(13q) (55%), trisomy 12 (10.5%), del(11q) (10%), and del(17p) (4%). Additional recurrent aberrations were detected on chromosomes 2 (1.9%), 4 (1.4%), 8 (1.6%) and 14 (1.6%). Thirteen patients (3.5%) displayed recurrent copy-number neutral loss of heterozygosity on 13q, of whom 11 had concurrent homozygous del(13q). Genomic complexity and large 13q deletions correlated with inferior outcome, while the former was linked to poor-prognostic aberrations. In the follow-up study, clonal evolution developed in 8/24 (33%) patients with unmutated IGHV, and in 4/25 (16%) IGHV-mutated and treated patients. In contrast, untreated patients with mutated IGHV (n=10) did not acquire additional aberrations. The most common secondary event, del(13q), was detected in 6/12 (50%) of all patients with acquired alterations. Interestingly, aberrations on, for example, chromosome 6q, 8p, 9p and 10q developed exclusively in patients with unmutated IGHV. Conclusions Whole-genome screening revealed a high frequency of genomic aberrations in newly diagnosed chronic lymphocytic leukemia. Clonal evolution was associated with other markers of aggressive disease and commonly included the known recurrent aberrations.
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