| 1. |
- Svensson, Daniel, 1979, et al.
(författare)
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Performance Evaluation of MHT and GM-CPHD in a Ground Target Tracking Scenario
- 2009
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Ingår i: Proceedings of the 12th International Conference on Information Fusion. - 9780982443804 ; , s. 300-307
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Konferensbidrag (refereegranskat)abstract
- Performance evaluations of multi-target tracking algorithms are often limited to consider comparisons within the same algorithm family. In this paper, two conceptually different multi-target tracking algorithms are evaluated, namely a multiple-hypothesis tracking (MHT) algorithm and the Gaussian mixture cardinalized probability hypothesis density (GM-CPHD) filter. As a reference, a conventional single-hypothesis tracking algorithm is included in the evaluation. The performance is assessed using the root-mean square error of the estimated number of targets, and the recently published optimal subpattern assignment (OSPA) measure. The scenario under consideration is tracking of nine closely spaced ground targets, using simulated measurements from an airborne radar. By observing the estimation of the number of targets, as well as of the target states, conclusions are drawn regarding the behavior of MHT and GM-CPHD. For example, GM-CPHD is more responsive to changes in the number of targets, whereas MHT is less responsive, but produces a more stable output.
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| 2. |
- Svensson, Per Anders, 1959, et al.
(författare)
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Identification of genes predominantly expressed in human macrophages
- 2004
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Ingår i: Atherosclerosis. - : Elsevier BV. ; 177, s. 287-290
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Tidskriftsartikel (refereegranskat)abstract
- Identification of cell and tissue specific genes may provide novel insights to signaling systems and functions. Macrophages play a key role in many diseases including atherosclerosis. Using DNA microarrays we compared the expression of approximately 10,000 genes in 56 human tissues and identified 23 genes with predominant expression in macrophages. The identified genes include both genes known to be macrophage specific and genes previously not well described in this cell type. Tissue distribution of two genes, liver X receptor (LXR) alpha and interleukin-1 receptor antagonist (IL1RN), was verified by real-time RT-PCR. We conclude that comparison of expression profiles from a large number of tissues can be used to identify genes that are predominantly expressed in certain tissues. Identification of novel macrophage specific genes may increase our understanding of the role of this cell in different diseases.
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| 3. |
- Zamora, Juan Carlos, et al.
(författare)
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Considerations and consequences of allowing DNA sequence data as types of fungal taxa
- 2018
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Ingår i: IMA Fungus. - : INT MYCOLOGICAL ASSOC. - 2210-6340 .- 2210-6359. ; 9:1, s. 167-185
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Tidskriftsartikel (refereegranskat)abstract
- Nomenclatural type definitions are one of the most important concepts in biological nomenclature. Being physical objects that can be re-studied by other researchers, types permanently link taxonomy (an artificial agreement to classify biological diversity) with nomenclature (an artificial agreement to name biological diversity). Two proposals to amend the International Code of Nomenclature for algae, fungi, and plants (ICN), allowing DNA sequences alone (of any region and extent) to serve as types of taxon names for voucherless fungi (mainly putative taxa from environmental DNA sequences), have been submitted to be voted on at the 11th International Mycological Congress (Puerto Rico, July 2018). We consider various genetic processes affecting the distribution of alleles among taxa and find that alleles may not consistently and uniquely represent the species within which they are contained. Should the proposals be accepted, the meaning of nomenclatural types would change in a fundamental way from physical objects as sources of data to the data themselves. Such changes are conducive to irreproducible science, the potential typification on artefactual data, and massive creation of names with low information content, ultimately causing nomenclatural instability and unnecessary work for future researchers that would stall future explorations of fungal diversity. We conclude that the acceptance of DNA sequences alone as types of names of taxa, under the terms used in the current proposals, is unnecessary and would not solve the problem of naming putative taxa known only from DNA sequences in a scientifically defensible way. As an alternative, we highlight the use of formulas for naming putative taxa (candidate taxa) that do not require any modification of the ICN.
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| 4. |
- Al-Amin, Rasel A., Researcher, 1983-, et al.
(författare)
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Monitoring drug–target interactions through target engagement-mediated amplification on arrays and in situ
- 2022
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Ingår i: Nucleic Acids Research. - : Oxford University Press. - 0305-1048 .- 1362-4962. ; 50:22, s. e129-e129
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Tidskriftsartikel (refereegranskat)abstract
- Drugs are designed to bind their target proteins in physiologically relevant tissues and organs to modulate biological functions and elicit desirable clinical outcomes. Information about target engagement at cellular and subcellular resolution is therefore critical for guiding compound optimization in drug discovery, and for probing resistance mechanisms to targeted therapies in clinical samples. We describe a target engagement-mediated amplification (TEMA) technology, where oligonucleotide-conjugated drugs are used to visualize and measure target engagement in situ, amplified via rolling-circle replication of circularized oligonucleotide probes. We illustrate the TEMA technique using dasatinib and gefitinib, two kinase inhibitors with distinct selectivity profiles. In vitro binding by the dasatinib probe to arrays of displayed proteins accurately reproduced known selectivity profiles, while their differential binding to fixed adherent cells agreed with expectations from expression profiles of the cells. We also introduce a proximity ligation variant of TEMA to selectively investigate binding to specific target proteins of interest. This form of the assay serves to improve resolution of binding to on- and off-target proteins. In conclusion, TEMA has the potential to aid in drug development and clinical routine by conferring valuable insights in drug–target interactions at spatial resolution in protein arrays, cells and in tissues.
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| 5. |
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| 6. |
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| 7. |
- Ali, Muhammad, et al.
(författare)
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Leveraging large multi-center cohorts of Alzheimer disease endophenotypes to understand the role of Klotho heterozygosity on disease risk.
- 2022
-
Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 17:5
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Tidskriftsartikel (refereegranskat)abstract
- Two genetic variants in strong linkage disequilibrium (rs9536314 and rs9527025) in the Klotho (KL) gene, encoding a transmembrane protein, implicated in longevity and associated with brain resilience during normal aging, were recently shown to be associated with Alzheimer disease (AD) risk in cognitively normal participants who are APOE ε4 carriers. Specifically, the participants heterozygous for this variant (KL-SVHET+) showed lower risk of developing AD. Furthermore, a neuroprotective effect of KL-VSHET+ has been suggested against amyloid burden for cognitively normal participants, potentially mediated via the regulation of redox pathways. However, inconsistent associations and a smaller sample size of existing studies pose significant hurdles in drawing definitive conclusions. Here, we performed a well-powered association analysis between KL-VSHET+ and five different AD endophenotypes; brain amyloidosis measured by positron emission tomography (PET) scans (n = 5,541) or cerebrospinal fluid Aβ42 levels (CSF; n = 5,093), as well as biomarkers associated with tau pathology: the CSF Tau (n = 5,127), phosphorylated Tau (pTau181; n = 4,778) and inflammation: CSF soluble triggering receptor expressed on myeloid cells 2 (sTREM2; n = 2,123) levels. Our results found nominally significant associations of KL-VSHET+ status with biomarkers for brain amyloidosis (e.g., CSF Aβ positivity; odds ratio [OR] = 0.67 [95% CI, 0.55-0.78], β = 0.72, p = 0.007) and tau pathology (e.g., biomarker positivity for CSF Tau; OR = 0.39 [95% CI, 0.19-0.77], β = -0.94, p = 0.007, and pTau; OR = 0.50 [95% CI, 0.27-0.96], β = -0.68, p = 0.04) in cognitively normal participants, 60-80 years old, who are APOE e4-carriers. Our work supports previous findings, suggesting that the KL-VSHET+ on an APOE ε4 genotype background may modulate Aβ and tau pathology, thereby lowering the intensity of neurodegeneration and incidence of cognitive decline in older controls susceptible to AD.
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| 8. |
- Anders, Emma, et al.
(författare)
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Globular C1q receptor (p33) binds and stabilizes pro-inflammatory MCP-1 : a novel mechanism for regulation of MCP-1 production and function
- 2018
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Ingår i: Biochemical Journal. - 0264-6021. ; 475:4, s. 775-786
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Tidskriftsartikel (refereegranskat)abstract
- The protein gC1qR (globular C1q receptor), also named p33, was originally identified as a binding partner of the globular heads of C1q in the complement system. gC1qR/p33 is abundantly expressed in many cell types, but the functional importance of this protein is not completely understood. Here, we investigate the impact of gC1qR/p33 on the production and function of the pathophysiologically important chemokine monocyte chemoattractant protein-1 (MCP-1) and the underlying molecular mechanisms. Knockdown of gC1qR/p33 negatively regulated the production of MCP-1, but had no effect on the expression of transcript for MCP-1 in human periodontal ligament cells, suggesting a translational/post-translational mechanism of action. Laser scanning confocal microscopy showed considerable cytosolic co-localization of gC1qR/p33 and MCP-1, and co-immunoprecipitation disclosed direct physical interaction between gC1qR/p33 and MCP-1. Surface plasmon resonance analysis revealed a high-affinity binding (KD = 10.9 nM) between gC1qR/p33 and MCP-1. Using a transwell migration assay, we found that recombinant gC1qR/p33 enhances MCP-1-induced migration of human THP-1 monocytes, pointing to a functional importance of the interaction between gC1qR/p33 and MCP-1. An in vitro assay revealed a rapid turnover of the MCP-1 protein and that gC1qR/ p33 stabilizes MCP-1, hence preventing its degradation. We propose that endogenous gC1qR/p33 physically interacts with MCP-1 causing stabilization of the MCP-1 protein and stimulation of its activity in human periodontal ligament cells, suggesting a novel gC1qR/p33-mediated pro-inflammatory mechanism of action.
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| 9. |
- Andric, Stefan, et al.
(författare)
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Performance, Analysis, and Modeling of III-V Vertical Nanowire MOSFETs on Si at Higher Voltages
- 2022
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Ingår i: IEEE Transactions on Electron Devices. - 0018-9383. ; 69:6, s. 3055-3055
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Tidskriftsartikel (refereegranskat)abstract
- Heterostructure engineering in III-V vertical nanowire (VNW) MOSFETs enables tuning of transconductance and breakdown voltage. In this work, an InxGa 1−x As channel with a Ga-composition grading ( x= 1–0.4) in the channel and drain region, combined with field plate engineering, enables breakdown voltage above 2.5 V, while maintaining transconductance of about 1 mS/ μm , in VNW MOSFETs. The field plate consists of a vertically integrated SiO2 layer and a gate contact, which screens the electric field in the drain region, extending the device operating voltage. By scaling the field plate, a transconductance of 2 mS/ μm , alongside the breakdown voltage of 1.5 V, is obtained, demonstrating the benefit of field engineering in the drain. The scalability of the field plate and the gate is measured, showing an ON-resistance increase by 23 Ω⋅μm , and transconductance decrease by 5 μS/μm , per nm field plate length. This behavior is captured in a new and modified virtual source model, where device transmission and drain resistance are altered to capture the field plate scaling effect. The modeling is applied to nanowire (NW) devices with field plate lengths ranging from 5 to 115 nm, capturing accurately essential device performance parameters. Finally, a modified band-to-band (BTB) tunneling approach is used to accurately describe the device behavior above 1.5 V.
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| 10. |
- Arnelo, Urban, et al.
(författare)
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Intraoperative pancreatoscopy can improve the detection of skip lesions during surgery for intraductal papillary mucinous neoplasia : a pilot study
- 2023
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Ingår i: Pancreatology (Print). - : Elsevier. - 1424-3903 .- 1424-3911. ; 23:6, s. 704-711
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Intraoperative pancreatoscopy is a promising procedure that might guide surgical resection for suspected main duct (MD) and mixed type (MT) intraductal papillary mucinous neoplasms (IPMNs). The aim of the present study was to assess the diagnostic yield and clinical impact of intraoperative pancreatoscopy in patients operated on for MD and MT-IPMNs.Methods: This is a retrospective cohort study. Patients undergoing surgery for suspected MD or MT-IPMN underwent intraoperative pancreatoscopy and frozen section analysis. In all patients who required extended resection due to pancreatoscopic findings, we compared the final histology with the results of the intraoperative frozen section analysis.Results: In total, 46 patients, 48% females, mean age (range) 67 years (45–82 years) underwent intraoperative pancreatoscopy. No mortality or procedure related complications were observed. Pancreatoscopy changed the operative course in 30 patients (65%), leading to extended resections in 20 patients (43%) and to parenchyma sparing procedures in 10 patients (22%). Analyzing the group of patients who underwent extended resections, 7 (35%) displayed lesions that needed further surgical treatment (six high grade dysplasia and one with G1 pancreatic neuroendocrine tumor) and among those 7, just 1 (14%) would have been detected exclusively with histological frozen section analysis of the transection margin. The combination of both pancreatoscopy and frozen section analysis lead to 86% sensitivity and 92% specificity for the detection of pathological tissue in the remnant pancreas.Conclusion: Intraoperative pancreatoscopy is a safe and feasible procedure and might allow the detection of skip lesions during surgery for suspect MD-involving IPMNs.
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| 11. |
- Arpegard, Johannes, et al.
(författare)
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Cystatin C Predicts Incident Cardiovascular Disease in Twins
- 2016
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Ingår i: Journal of the American Heart Association. - 2047-9980. ; 5:6
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Tidskriftsartikel (refereegranskat)abstract
- Background - Cystatin C is associated with both renal function and atherosclerotic cardiovascular disease (ASCVD). We have previously shown a genetic correlation between cystatin C and prevalent ASCVD. The objective of this article is to study whether variation in cystatin C or creatinine predicts incident ASCVD when controlled for genetic factors.Methods and Results - The predictive value of cystatin C and creatinine for incident ASCVD was studied in 11 402 Swedish twins, free of CVD at baseline, in an adjusted Cox-regression model during a median follow-up of 71 months. Twin pairs discordant for incident stroke, myocardial infarction and ASCVD during follow-up were identified and within-pair comparisons regarding cystatin C and creatinine levels were performed. We also investigated whether contact frequency and degree of shared environment influences were associated with similarity in cystatin C levels. In univariate analysis, cystatin C predicted incident ASCVD hazard ratio 1.57, 95% CI 1.47-1.67. When adjusted for traditional Framingham risk factors as covariates, cystatin C remained a predictor of incident stroke hazard ratio 1.45, 95% CI (1.25-1.70), ASCVD hazard ratio 1.26, 95% CI (1.13-1.41), and myocardial infarction hazard ratio 1.16, 95% CI (1.01-1.33). In twins discordant for incident stroke, cystatin C at baseline was higher in the twin who experienced a stroke compared to the healthy co-twin (1.11 +/- 0.3 mg/L versus 1.06 +/- 0.3 mg/L), whereas creatinine was lower in the twin who developed CVD compared to their healthy co-twins (76.1 +/- 16.9 mu mol/L versus 79.4 +/- 20.3 mu mol/L).Conclusions - Variation in cystatin C relates to incident ASCVD and to stroke when adjusted for genetic confounding. In identical twins, cystatin C may be a sensitive marker of early hypertensive end-organ damage and small-vessel disease, whereas creatinine level may reflect nutritional status. The findings in disease-discordant monozygotic twins indicate that unique, possibly preventable, environmental factors are important.
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| 12. |
- Babadi, Aein S., et al.
(författare)
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Impact of doping and diameter on the electrical properties of GaSb nanowires
- 2017
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Ingår i: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 110:5
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Tidskriftsartikel (refereegranskat)abstract
- The effect of doping and diameter on the electrical properties of vapor-liquid-solid grown GaSb nanowires was characterized using long channel back-gated lateral transistors and top-gated devices. The measurements showed that increasing the doping concentration significantly increases the conductivity while reducing the control over the channel potential and shifting the threshold voltage, as expected. The highest average mobility was 85 cm2/V·s measured for an unintentionally doped GaSb nanowire with a diameter of 45 nm, whereas medium doped nanowires with large diameters (81 nm) showed a value of 153 cm2/V·s. The mobility is found to be independent of nanowire diameter in the range of 36 nm-68 nm, while the resistivity is strongly reduced with increasing diameter attributed to the surface depletion of charge carriers. The data are in good agreement with an analytical calculation of the depletion depth. A high transconductance was achieved by scaling down the channel length to 200 nm, reaching a maximum value of 80 μS/μm for a top-gated GaSb nanowires transistor with an ON-resistance of 26 kΩ corresponding to 3.9 Ω.mm. The lowest contact resistance obtained was 0.35 Ω·mm for transistors with the highest doping concentration.
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| 13. |
- Bañuls, Mari Carmen, et al.
(författare)
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Quantum information perspective on meson melting
- 2023
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Ingår i: Physical Review D. - 2470-0010. ; 108:7
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Tidskriftsartikel (refereegranskat)abstract
- We propose to use quantum information notions to characterize thermally induced melting of nonperturbative bound states at high temperatures. We apply tensor networks to investigate this idea in static and dynamical settings within the Ising quantum field theory, where bound states are confined fermion pairs - mesons. An equilibrium signature of meson melting is identified in the temperature dependence of the thermal-state second Rényi entropy, which varies from exponential to power-law scaling. Out of equilibrium, we identify as the relevant signature the transition from an oscillatory to a linear growing behavior of reflected entropy after a thermal quench. These analyses apply more broadly, which brings new ways of describing in-medium meson phenomena in quantum many-body and high-energy physics.
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| 14. |
- Bataille, Christopher, et al.
(författare)
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Net-zero deep decarbonization pathways in Latin America : Challenges and opportunities
- 2020
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Ingår i: Energy Strategy Reviews. - : Elsevier BV. - 2211-467X .- 2211-4688. ; 30
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Tidskriftsartikel (refereegranskat)abstract
- This synthesis paper presents the objectives, approach and cross-cutting results of the Latin American Deep Decarbonization Pathways project (DDP-LAC). It synthesizes and compares detailed national and sectoral deep decarbonization pathways (DDPs) to 2050 compatible with the Paris Agreement objectives and domestic development priorities in Argentina, Colombia, Costa Rica, Ecuador, Mexico and Peru. The first five countries analysed in detail the energy system and agriculture, forestry and land use (AFOLU) at a high level, while Peru focussed on a detailed analysis of AFOLU given its predominance in its GHG emissions. While economy-wide results were produced, this paper focuses on the electricity, passenger transport, and AFOLU results because of their current emissions, potential to grow, and identification of successful strategies for decarbonization (e.g. switching to clean electricity and other net-zero emissions fuels across the economy; urban planning, mode shifting, and electrification in passenger transport; and intensive sustainable agriculture, assignment of land use rights and their enforcement and afforestation in AFOLU). It also highlights where significant emissions remain in 2050, notably in industry, AFOLU, freight, and oil and gas production, all areas for future research. It derives insights for the design of domestic policy packages and identifies priorities for international cooperation. This analysis provides critical information for Long-Term Strategies, Nationally Determined Contributions and Global Stocktaking in the context of the Paris Agreement.
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| 15. |
- Berg, Martin, et al.
(författare)
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A transmission line method for evaluation of vertical InAs nanowire contacts
- 2015
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Ingår i: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 107:23
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Tidskriftsartikel (refereegranskat)abstract
- In this paper, we present a method for metal contact characterization to vertical semiconductor nanowires using the transmission line method (TLM) on a cylindrical geometry. InAs nanowire resistors are fabricated on Si substrates using a hydrogen silsesquioxane (HSQ) spacer between the bottom and top contact. The thickness of the HSQ is defined by the dose of an electron beam lithography step, and by varying the separation thickness for a group of resistors, a TLM series is fabricated. Using this method, the resistivity and specific contact resistance are determined for InAs nanowires with different doping and annealing conditions. The contacts are shown to improve with annealing at temperatures up to 300 degrees C for 1min, with specific contact resistance values reaching down to below 1 Omega mu m(2). (C) 2015 AIP Publishing LLC.
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| 16. |
- Berg, Martin, et al.
(författare)
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Electrical Characterization and Modeling of Gate-Last Vertical InAs Nanowire MOSFETs on Si
- 2016
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Ingår i: IEEE Electron Device Letters. - 0741-3106. ; 37:8, s. 966-969
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Tidskriftsartikel (refereegranskat)abstract
- Vertical InAs nanowire transistors are fabricated on Si using a gate-last method, allowing for lithography-based control of the vertical gate length. The best devices combine good ON- and OFF-performance, exhibiting an ON-current of 0.14 mA/μm, and a sub-threshold swing of 90 mV/dec at 190 nm LG. The device with the highest transconductance shows a peak value of 1.6 mS/μm. From RF measurements, the border trap densities are calculated and compared between devices fabricated using the gate-last and gate-first approaches, demonstrating no significant difference in trap densities. The results thus confirm the usefulness of implementing digital etching in thinning down the channel dimensions.
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| 17. |
- Berg, Martin, et al.
(författare)
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Self-aligned, gate-last process for vertical InAs nanowire MOSFETs on Si
- 2016
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Ingår i: Technical Digest - International Electron Devices Meeting, IEDM. - 9781467398930 ; 2016-February
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Konferensbidrag (refereegranskat)abstract
- In this work, we present a novel self-aligned gate-last fabrication process for vertical nanowire metal-oxide-semiconductor field-effect transistors. The fabrication method allows for exposure dose-defined gate lengths and a local diameter reduction of the intrinsic channel segment, while maintaining thicker highly doped access regions. Using this process, InAs nanowire transistors combining good on-and off-performance are fabricated demonstrating Q = gm,max/SS = 8.2, which is higher than any previously reported vertical nanowire MOSFET.
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| 18. |
- Bonagas, Nadilly, et al.
(författare)
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Pharmacological targeting of MTHFD2 suppresses acute myeloid leukemia by inducing thymidine depletion and replication stress
- 2022
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Ingår i: NATURE CANCER. - : Springer Science and Business Media LLC. - 2662-1347. ; 3:2, s. 156-
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Tidskriftsartikel (refereegranskat)abstract
- The folate metabolism enzyme MTHFD2 (methylenetetrahydrofolate dehydrogenase/cyclohydrolase) is consistently overexpressed in cancer but its roles are not fully characterized, and current candidate inhibitors have limited potency for clinical development. In the present study, we demonstrate a role for MTHFD2 in DNA replication and genomic stability in cancer cells, and perform a drug screen to identify potent and selective nanomolar MTHFD2 inhibitors; protein cocrystal structures demonstrated binding to the active site of MTHFD2 and target engagement. MTHFD2 inhibitors reduced replication fork speed and induced replication stress followed by S-phase arrest and apoptosis of acute myeloid leukemia cells in vitro and in vivo, with a therapeutic window spanning four orders of magnitude compared with nontumorigenic cells. Mechanistically, MTHFD2 inhibitors prevented thymidine production leading to misincorporation of uracil into DNA and replication stress. Overall, these results demonstrate a functional link between MTHFD2-dependent cancer metabolism and replication stress that can be exploited therapeutically with this new class of inhibitors. Helleday and colleagues describe a nanomolar MTHFD2 inhibitor that causes replication stress and DNA damage accumulation in cancer cells via thymidine depletion, demonstrating a potential therapeutic strategy in AML tumors in vivo.
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| 19. |
- Borg, Mattias, et al.
(författare)
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Autonomy in PhD-education – Supervising for Independence
- 2016
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Ingår i: LTHs 9:e Pedagogiska Inspirationskonferens. ; , s. 9-13
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Konferensbidrag (refereegranskat)abstract
- According to the Swedish higher ordinance of education the development of autonomy of PhD students is of high importance. Graduates should be able to formulate new ideas and to independently assess and evaluate scientific results. Therefore it is interesting to investigate how the relationship between student and supervisor impacts the development of autonomy. In this work, we have evaluated the impact of the supervision relationship by a supervisor/studentalignment test (N=25) where both students and their supervisors perform a self-evaluation of the student’s level of autonomy and the supervisor’s supervision style. The test results show that the autonomy is greater for students with longer experience and also more aligned with the level of autonomy as perceived by their supervisors. The misalignment between the assessment done by students and supervisors decreases with age and time spent as a PhD student. However, we find that the misalignment increases when supervisors have many concurrent PhD students. We observe no statistical differences with respect to gender or nationality.
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| 20. |
- Braegelmann, Johannes, et al.
(författare)
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Pan-Cancer Analysis of the Mediator Complex Transcriptome Identifies CDK19 and CDK8 as Therapeutic Targets in Advanced Prostate Cancer
- 2017
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Ingår i: Clinical Cancer Research. - : American Association for Cancer Research Inc.. - 1078-0432 .- 1557-3265. ; 23:7, s. 1829-1840
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The Mediator complex is a multiprotein assembly, which serves as a hub for diverse signaling pathways to regulate gene expression. Because gene expression is frequently altered in cancer, a systematic understanding of the Mediator complex in malignancies could foster the development of novel targeted therapeutic approaches.Experimental Design: We performed a systematic deconvolution of the Mediator subunit expression profiles across 23 cancer entities (n = 8,568) using data from The Cancer Genome Atlas (TCGA). Prostate cancer-specific findings were validated in two publicly available gene expression cohorts and a large cohort of primary and advanced prostate cancer (n = 622) stained by immunohistochemistry. The role of CDK19 and CDK8 was evaluated by siRNA-mediated gene knockdown and inhibitor treatment in prostate cancer cell lines with functional assays and gene expression analysis by RNAseq.Results: Cluster analysis of TCGA expression data segregated tumor entities, indicating tumor-type-specific Mediator complex compositions. Only prostate cancerwasmarked by high expression of CDK19. In primary prostate cancer, CDK19 was associated with increased aggressiveness and shorter disease-free survival. During cancer progression, highest levels of CDK19 and of its paralog CDK8were present inmetastases. In vitro, inhibition ofCDK19 and CDK8 by knockdown or treatment with a selective CDK8/ CDK19 inhibitor significantly decreased migration and invasion.Conclusions: Our analysis revealed distinct transcriptional expression profiles of the Mediator complex across cancer entities indicating differential modes of transcriptional regulation. Moreover, it identified CDK19 and CDK8 to be specifically overexpressed during prostate cancer progression, highlighting their potential as novel therapeutic targets in advanced prostate cancer.
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| 21. |
- Bukontaite, Rasa, et al.
(författare)
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Phylogeny, distribution and speciation in the endemic diving beetle genus Pachynectes on Madagascar
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Madagascar is well known for high levels of endemism in both the flora and fauna. More specifically most of Madagascars' endemic species have extremely restricted regional distributions, which is a characteristic of this large island’s biodiversity. Biologists are still struggling to understand the speciation processes that have produced this pattern of diversity. Several general hypotheses have been developed trying to explain the origin and microendemism of Malagasy species. Two main hypotheses focus on watersheds and climate gradients. Here, we use a phylogeny in combination with data on spatial distribution of the endemic diving beetle genus Pachynectes (Coleoptera: Dytiscidae: Bidessini) to critically evaluate the watershed versus the climatic gradient hypotheses of this river dwelling insect radiation. Based on field sampling from expeditions between 2006 and 2014, we first show that the species diversity in this genus is at least three times higher than previously believed. We reconstructed a molecular phylogeny based on five gene fragments and recovered three main clades: a western clade, an eastern clade and a "keeled" clade diagnosable based on an elytral keel. The western and keeled clades both occur mainly in the drier western parts of the country, while species in the eastern clade are typical of rivers in the eastern humid rainforest. Notably, sister species were always allopatrically distributed along either latitudinal or longitudinal-altitudinal gradients. Based on species distribution modelling (SDM) and our phylogenetic data, we conclude that the microendemic patterns of Pachynectes species are unlikely to be explained by the watershed hypothesis. In contrast, the four main bioclimatic regions are more likely to have been causally involved in the past speciation processes and might explain the current distribution pattern in this insect genus.
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| 22. |
- Bulgakova, Nadya, 1956, et al.
(författare)
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Possible role of charge transport in enhanced carbon nanotube growth
- 2006
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Ingår i: Applied Physics A. - : Springer Science and Business Media LLC. - 0947-8396 .- 1432-0630. ; 85, s. 109-116
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Tidskriftsartikel (refereegranskat)abstract
- We consider the role of electric fields during metal-catalysed thermal chemical vapour deposition growth of carbon nanotubes and show that enhanced growth occurs from a negatively biased electrode. An electric field, applied externally to the growing tubes and/or generated as a result of electron emission or self-biasing, may strongly affect the carbon supply through the catalyst nanoparticle, enhancing the growth rate. Different aspects of the growth process are analysed: the nature of the nanoparticle catalysis, carbon dissolution kinetics, electron emission from the nanotube tips, charge transport in the nanotube-catalytic nanoparticle system and carbon drift and diffusion through the catalyst under the action of the electric field. A fundamental tenet for modelling of charge-transport dynamics during the nanotube growth process is proposed.
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| 23. |
- Choi, A., et al.
(författare)
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Suppression of the magneto resistance in high electric fields of polyacetylene nanofibers
- 2010
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Ingår i: SYNTHETIC METALS. - 0379-6779. ; 160:11-12, s. 1349-1353
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Tidskriftsartikel (refereegranskat)abstract
- We present results of non-linear magneto resistance (MR) of polyacetylene nanofibers in high magnetic field up to H = 30 T at low temperature T = 1.5 K. The MR was proven to be of the spin origin; it reaches 16% at highest H. Unexpectedly, the MR was suppressed by increasing electric field E, vanishing at E ≳ 5 × 104 V/cm. It is understood that the doping induced spinless charged soliton pairs, which are initially confined to a certain distance because of the interchain phase correlations, and are deconfined in high electric fields, resulting in a vanishing magneto resistance (VMR). The role of the specific, degenerate ground state of the polyacetylene is confirmed by parallel studies of the different magneto resistances of polyaniline nanofibers which contrarily is not affected by the electric field. © 2010 Elsevier B.V. All rights reserved.
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| 24. |
- Degerman, Johan, 1976, et al.
(författare)
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Extended Target Tracking using Principal Components
- 2011
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Ingår i: Proceedings of the 14th International Conference on Information Fusion. - 9781457702679 ; , s. Art. no. 5977659-
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Konferensbidrag (refereegranskat)abstract
- The increased resolution in today’s radar systemsenables tracking of small targets. However, tracking both smalland large targets in a dense target scenario raises considerablechallenges. The data association of tracks to measurement groupsis highly dependent on good target extension models for filteringand likelihood computation. In our attempt to design a trackerfor extended targets, we start by adopting the results from thetechnique referred to as random matrices, which enables us toseparate the filtering into an extension and a kinematical part.We re-define the measurement model and discard the assumptionof independent Gaussian-distributed plots. Instead we assume theprincipal components to be Gaussian distributed. Then, througha heuristic approach, we create a two-stage Kalman filter, wherethe first stage estimates the principal components, and the secondstage estimates the centre of gravity, using the output fromthe first stage as measurement uncertainty. The advantage ofhaving a Kalman filter with data-driven measurement noise overa standard Kalman filter is demonstrated using simulated data,where a significant improvement in terms of smaller errors andreduced track loss is shown.
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| 25. |
- Dey, Anil, et al.
(författare)
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Combining axial and radial nanowire heterostructures: Radial Esaki diodes and tunnel field-effect transistors
- 2013
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Ingår i: Nano Letters. - : American Chemical Society (ACS). - 1530-6992 .- 1530-6984. ; 13:12, s. 5919-5924
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Tidskriftsartikel (refereegranskat)abstract
- The ever-growing demand on high-performance electronics has generated transistors with very impressive figures of merit. The continued scaling of the supply voltage of field-effect transistors, such as tunnel field-effect transistors (TFETs), requires the implementation of advanced transistor architectures including FinFETs and nanowire devices. Moreover, integration of novel materials with high electron mobilities, such as III-V semiconductors and graphene, are also being considered to further enhance the device properties. In nanowire devices, boosting the drive current at a fixed supply voltage or maintaining a constant drive current at a reduced supply voltage may be achieved by increasing the cross-sectional area of a device, however at the cost of deteriorated electrostatics. A gate-all-around nanowire device architecture is the most favorable electrostatic configuration to suppress short channel effects, however, the arrangement of arrays of parallel vertical nanowires to address the drive current predicament will require additional chip area. The use of a core-shell nanowire with a radial heterojunction in a transistor architecture provides an attractive means to address the drive current issue without compromising neither chip area nor device electrostatics. In addition to design advantages of a radial transistor architecture, we in this work illustrate the benefit in terms of drive current per unit chip area and compare the experimental data for axial GaSb/InAs Esaki diodes and TFETs to their radial counterparts and normalize the electrical data to the largest cross-sectional area of the nanowire, i.e. the occupied chip area, assuming a vertical device geometry. Our data on lateral devices show that radial Esaki diodes deliver almost 7 times higher peak current, Jpeak = 2310 kA/cm2, than the maximum peak current of axial GaSb/InAs(Sb) Esaki diodes per unit chip area. The radial TFETs also deliver high peak current densities Jpeak = 1210 kA/cm2 while their axial counterparts at most carry Jpeak = 77 kA/cm2, normalized to the largest cross-sectional area of the nanowire.
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