| 1. |
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| 2. |
- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 3. |
- Pham, M. K., et al.
(författare)
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Certified reference material for radionuclides in fish flesh sample IAEA-414 (mixed fish from the Irish Sea and North Sea)
- 2006
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Ingår i: Proceedings of the 15th International Conference on Radionuclide Metrology and its Applications (Applied Radiation and Isotopes). - Amsterdam : Elsevier BV. - 1872-9800 .- 0969-8043. ; 64:10-11, s. 1253-1259
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Konferensbidrag (refereegranskat)abstract
- A certified reference material (CRM) for radionuclides in fish sample IAEA-414 (mixed fish from the Irish Sea and North Seas) is described and the results of the certification process are presented. Nine radionuclides (K-40, Cs-137, Th-232, U-234, U-235, U-238, Pu-238, Pu239+240 and Am-241) were certified for this material. Information on massic activities with 95% confidence intervals is given for six other radionuclides (Sr-90, Pb-210(Po-210), Ra-226, Pu-239, Pu-240 Pu-241). Less frequently reported radionuclides (Tc-99, I-129, Th-228, Th-230 and Np-217) and information on some activity and mass ratios are also included. The CRM can be used for quality assurance/quality control of the analysis of radionuclides in fish sample, for the development and validation of analytical methods and for training purposes. The material is available from IAEA, Vienna, in 100 g units.
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| 4. |
- Caretta, Martina Angela, et al.
(författare)
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Water
- 2022
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Ingår i: Climate Change 2022: Impacts, Adaptation and Vulnerability : Contribution of Working Group II to the Sixth Assessment Report of the Intergovernmental Panel on Climate Change - Contribution of Working Group II to the Sixth Assessment Report of the Intergovernmental Panel on Climate Change.
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 5. |
- Ebrahimi-Fakhari, Darius, et al.
(författare)
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Defining the clinical, molecular and imaging spectrum of adaptor protein complex 4-associated hereditary spastic paraplegia
- 2020
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Ingår i: Brain. - OXFORD ENGLAND : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 143:10, s. 2929-2944
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Tidskriftsartikel (refereegranskat)abstract
- Bi-allelic loss-of-function variants in genes that encode subunits of the adaptor protein complex 4 (AP-4) lead to prototypical yet poorly understood forms of childhood-onset and complex hereditary spastic paraplegia: SPG47 (AP4B1), SPG50 (AP4M1), SPG51 (AP4E1) and SPG52 (AP4S1). Here, we report a detailed cross-sectional analysis of clinical, imaging and molecular data of 156 patients from 101 families. Enrolled patients were of diverse ethnic backgrounds and covered a wide age range (1.0-49.3 years). While the mean age at symptom onset was 0.8 +/- 0.6 years [standard deviation (SD), range 0.2-5.0], the mean age at diagnosis was 10.2 +/- 8.5 years (SD, range 0.1-46.3). We define a set of core features: early-onset developmental delay with delayed motor milestones and significant speech delay (50% non-verbal); intellectual disability in the moderate to severe range; mild hypotonia in infancy followed by spastic diplegia (mean age: 8.4 +/- 5.1 years, SD) and later tetraplegia (mean age: 16.1 +/- 9.8 years, SD); postnatal microcephaly (83%); foot deformities (69%); and epilepsy (66%) that is intractable in a subset. At last follow-up, 36% ambulated with assistance (mean age: 8.9 +/- 6.4 years, SD) and 54% were wheelchair-dependent (mean age: 13.4 +/- 9.8 years, SD). Episodes of stereotypic laughing, possibly consistent with a pseudobulbar affect, were found in 56% of patients. Key features on neuroimaging include a thin corpus callosum (90%), ventriculomegaly (65%) often with colpocephaly, and periventricular white-matter signal abnormalities (68%). Iron deposition and polymicrogyria were found in a subset of patients. AP4B1-associated SPG47 and AP4M1-associated SPG50 accounted for the majority of cases. About two-thirds of patients were born to consanguineous parents, and 82% carried homozygous variants. Over 70 unique variants were present, the majority of which are frameshift or nonsense mutations. To track disease progression across the age spectrum, we defined the relationship between disease severity as measured by several rating scales and disease duration. We found that the presence of epilepsy, which manifested before the age of 3 years in the majority of patients, was associated with worse motor outcomes. Exploring genotype-phenotype correlations, we found that disease severity and major phenotypes were equally distributed among the four subtypes, establishing that SPG47, SPG50, SPG51 and SPG52 share a common phenotype, an 'AP-4 deficiency syndrome'. By delineating the core clinical, imaging, and molecular features of AP-4-associated hereditary spastic paraplegia across the age spectrum our results will facilitate early diagnosis, enable counselling and anticipatory guidance of affected families and help define endpoints for future interventional trials.
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| 6. |
- Mariathasan, Sanjeev, et al.
(författare)
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TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells
- 2018
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 554:7693, s. 544-548
-
Tidskriftsartikel (refereegranskat)abstract
- Therapeutic antibodies that block the programmed death-1 (PD-1)-programmed death-ligand 1 (PD-L1) pathway can induce robust and durable responses in patients with various cancers, including metastatic urothelial cancer. However, these responses only occur in a subset of patients. Elucidating the determinants of response and resistance is key to improving outcomes and developing new treatment strategies. Here we examined tumours from a large cohort of patients with metastatic urothelial cancer who were treated with an anti-PD-L1 agent (atezolizumab) and identified major determinants of clinical outcome. Response to treatment was associated with CD8 + T-effector cell phenotype and, to an even greater extent, high neoantigen or tumour mutation burden. Lack of response was associated with a signature of transforming growth factor β (TGFβ) signalling in fibroblasts. This occurred particularly in patients with tumours, which showed exclusion of CD8 + T cells from the tumour parenchyma that were instead found in the fibroblast-and collagen-rich peritumoural stroma; a common phenotype among patients with metastatic urothelial cancer. Using a mouse model that recapitulates this immune-excluded phenotype, we found that therapeutic co-Administration of TGFβ-blocking and anti-PD-L1 antibodies reduced TGFβ signalling in stromal cells, facilitated T-cell penetration into the centre of tumours, and provoked vigorous anti-Tumour immunity and tumour regression. Integration of these three independent biological features provides the best basis for understanding patient outcome in this setting and suggests that TGFβ shapes the tumour microenvironment to restrain anti-Tumour immunity by restricting T-cell infiltration.
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| 7. |
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| 8. |
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| 9. |
- Berger, Ashton C, et al.
(författare)
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A Comprehensive Pan-Cancer Molecular Study of Gynecologic and Breast Cancers.
- 2018
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Ingår i: Cancer Cell. - : Elsevier BV. - 1535-6108 .- 1878-3686. ; 33:4, s. 690-705.e9
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Tidskriftsartikel (refereegranskat)abstract
- We analyzed molecular data on 2,579 tumors from The Cancer Genome Atlas (TCGA) of four gynecological types plus breast. Our aims were to identify shared and unique molecular features, clinically significant subtypes, and potential therapeutic targets. We found 61 somatic copy-number alterations (SCNAs) and 46 significantly mutated genes (SMGs). Eleven SCNAs and 11 SMGs had not been identified in previous TCGA studies of the individual tumor types. We found functionally significant estrogen receptor-regulated long non-coding RNAs (lncRNAs) and gene/lncRNA interaction networks. Pathway analysis identified subtypes with high leukocyte infiltration, raising potential implications for immunotherapy. Using 16 key molecular features, we identified five prognostic subtypes and developed a decision tree that classified patients into the subtypes based on just six features that are assessable in clinical laboratories.
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| 10. |
- Hegde, Gurumurthy, 1979, et al.
(författare)
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Photoinduced Effects in the Vicinity of the Smectic-A-Smectic-CA* Transition; Polarization
- 2006
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Ingår i: Physical Review E. - 1550-7998. ; 73:1
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Tidskriftsartikel (refereegranskat)abstract
- We report detailed measurements of the photoinduced effects on the electric polarization, tilt angle, response time, and rotational viscosity in the vicinity of the smectic-A–antiferroelectric-smectic-C Sm-CA * transition of a guest-host system consisting of photoactive azobenzene-based guest molecules and nonphotoactive host molecules. In the Sm-CA * phase all the parameters, except the tilt angle, exhibit both the primary and secondary photoferroelectric effects. The tilt angle dependence of the polarization in the absence of light and in light-on conditions have been analyzed in terms of the predictions of the generalized mean-field and microscopic models.
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| 11. |
- Mandal, Santi M, et al.
(författare)
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Role of human DNA glycosylase Nei-like 2 (NEIL2) and single strand break repair protein polynucleotide kinase 3'-phosphatase in maintenance of mitochondrial genome.
- 2012
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Ingår i: The Journal of biological chemistry. - 1083-351X. ; 287:4, s. 2819-29
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Tidskriftsartikel (refereegranskat)abstract
- The repair of reactive oxygen species-induced base lesions and single strand breaks (SSBs) in the nuclear genome via the base excision (BER) and SSB repair (SSBR) pathways, respectively, is well characterize, and important for maintaining genomic integrity. However, the role of mitochondrial (mt) BER and SSBR proteins in mt genome maintenance is not completely clear. Here we show the presence of the oxidized base-specific DNA glycosylase Nei-like 2 (NEIL2) and the DNA end-processing enzyme polynucleotide kinase 3'-phosphatase (PNKP) in purified human mitochondrial extracts (MEs). Confocal microscopy revealed co-localization of PNKP and NEIL2 with the mitochondrion-specific protein cytochrome c oxidase subunit 2 (MT-CO2). Further, chromatin immunoprecipitation analysis showed association of NEIL2 and PNKP with the mitochondrial genes MT-CO2 and MT-CO3 (cytochrome c oxidase subunit 3); importantly, both enzymes also associated with the mitochondrion-specific DNA polymerase γ. In cell association of NEIL2 and PNKP with polymerase γ was further confirmed by proximity ligation assays. PNKP-depleted ME showed a significant decrease in both BER and SSBR activities, and PNKP was found to be the major 3'-phosphatase in human ME. Furthermore, individual depletion of NEIL2 and PNKP in human HEK293 cells caused increased levels of oxidized bases and SSBs in the mt genome, respectively. Taken together, these studies demonstrate the critical role of NEIL2 and PNKP in maintenance of the mammalian mitochondrial genome.
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| 12. |
- Vaduganathan, Muthiah, et al.
(författare)
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Time to Clinical Benefit of Dapagliflozin in Patients With Heart Failure With Mildly Reduced or Preserved Ejection Fraction : A Prespecified Secondary Analysis of the DELIVER Randomized Clinical Trial.
- 2022
-
Ingår i: JAMA cardiology. - : American Medical Association (AMA). - 2380-6583 .- 2380-6591. ; 7:12, s. 1259-1263
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Dapagliflozin was recently shown to reduce cardiovascular death or worsening heart failure (HF) events in patients with HF with mildly reduced or preserved ejection fraction in the Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure (DELIVER) trial. Objective: To evaluate the time course of benefits of dapagliflozin on clinically relevant outcomes in this population. Design, Setting, and Participants: The DELIVER trial was a global phase 3 clinical trial that randomized patients with HF with mildly reduced or preserved ejection fraction to dapagliflozin or matching placebo. Inclusion criteria included symptomatic HF, left ventricular ejection fraction greater than 40%, elevated natriuretic peptide levels, and evidence of structural heart disease. In this prespecified secondary analysis of the DELIVER trial, to examine the timeline to onset of clinical benefit with dapagliflozin, hazard ratios (HR) and 95% CIs were iteratively estimated for the primary composite end point and worsening HF events alone with truncated data at every day postrandomization. Time to first and sustained statistical significance of dapagliflozin for these end points were then examined. Participants were enrolled from August 2018 to December 2020, and for this secondary analysis, data were analyzed from April to September 2022. Interventions: Dapagliflozin, 10 mg, once daily or matching placebo. Main Outcomes and Measures: The primary outcome was time to first occurrence of cardiovascular death or worsening HF (hospitalization for HF or urgent HF visit requiring intravenous HF therapies). Results: Overall, 6263 patients were randomized across 350 centers in 20 countries. Of 6263 included patients, 2747 (43.9%) were women, and the mean (SD) age was 71.7 (9.6) years. During a median (IQR) of 2.3 (1.7-2.8) years’ follow- up, 1122 primary end point events occurred, with an incidence rate per 100 patient-years of 8.7 (95% CI, 8.2-9.2). Time to first nominal statistical significance for the primary end point was 13 days (HR, 0.45; 95% CI, 0.20-0.99; P = .046), and significance was sustained from day 15 onwards. First and sustained statistical significance was reached for worsening HF events (HR, 0.45; 95% CI, 0.21-0.96; P = .04) by day 16 after randomization. Significant benefits for the primary end point and worsening HF events were sustained at 30 days, 90 days, 6 months, 1 year, 2 years, and final follow-up (primary end point: HR, 0.82; 95% CI, 0.73-0.92; worsening HF events: HR, 0.79; 95% CI, 0.69-0.91). Conclusions and Relevance: In the DELIVER trial, dapagliflozin led to early and sustained reductions in clinical events in patients with HF with mildly reduced or preserved ejection fraction with statistically significant reductions observed within 2 weeks of treatment initiation. Trial Registration: ClinicalTrials.gov Identifier: NCT03619213.
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| 13. |
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| 14. |
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| 15. |
- Chen, Changchun, et al.
(författare)
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An ER Complex of ODR-4 and ODR-8/Ufm1 Specific Protease 2 Promotes GPCR Maturation by a Ufm1-Independent Mechanism
- 2014
-
Ingår i: PLOS Genetics. - : Public Library of Science. - 1553-7390 .- 1553-7404. ; 10:3
-
Tidskriftsartikel (refereegranskat)abstract
- Despite the importance of G-protein coupled receptors (GPCRs) their biogenesis is poorly understood. Like vertebrates, C. elegans uses a large family of GPCRs as chemoreceptors. A subset of these receptors, such as ODR-10, requires the odr-4 and odr-8 genes to be appropriately localized to sensory cilia. The odr-4 gene encodes a conserved tail-anchored transmembrane protein; the molecular identity of odr-8 is unknown. Here, we show that odr-8 encodes the C. elegans ortholog of Ufm1-specific protease 2 (UfSP2). UfSPs are cysteine proteases identified biochemically by their ability to liberate the ubiquitin-like modifier Ufm1 from its pro-form and protein conjugates. ODR-8/UfSP2 and ODR-4 are expressed in the same set of twelve chemosensory neurons, and physically interact at the ER membrane. ODR-4 also binds ODR-10, suggesting that an ODR-4/ODR-8 complex promotes GPCR folding, maturation, or export from the ER. The physical interaction between human ODR4 and UfSP2 suggests that this complex's role in GPCR biogenesis may be evolutionarily conserved. Unexpectedly, mutant versions of ODR-8/UfSP2 lacking catalytic residues required for protease activity can rescue all odr-8 mutant phenotypes tested. Moreover, deleting C. elegans ufm-1 does not alter chemoreceptor traffic to cilia, either in wild type or in odr-8 mutants. Thus, UfSP2 proteins have protease- and Ufm1-independent functions in GPCR biogenesis.
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| 16. |
- Chen, Changchun, et al.
(författare)
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IL-17 is a neuromodulator of Caenorhabditis elegans sensory responses
- 2017
-
Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 542:7639, s. 43-48
-
Tidskriftsartikel (refereegranskat)abstract
- Interleukin-17 (IL-17) is a major pro-inflammatory cytokine: it mediates responses to pathogens or tissue damage, and drives autoimmune diseases. Little is known about its role in the nervous system. Here we show that IL-17 has neuromodulator-like properties in Caenorhabditis elegans. IL-17 can act directly on neurons to alter their response properties and contribution to behaviour. Using unbiased genetic screens, we delineate an IL-17 signalling pathway and show that it acts in the RMG hub interneurons. Disrupting IL-17 signalling reduces RMG responsiveness to input from oxygen sensors, and renders sustained escape from 21% oxygen transient and contingent on additional stimuli. Over-activating IL-17 receptors abnormally heightens responses to 21% oxygen in RMG neurons and whole animals. IL-17 deficiency can be bypassed by optogenetic stimulation of RMG. Inducing IL-17 expression in adults can rescue mutant defects within 6 h. These findings reveal a non-immunological role of IL-17 modulating circuit function and behaviour.
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| 17. |
- Hegde, Gurumurthy, 1979, et al.
(författare)
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Dual Frequency Addressable Optical Device
- 2005
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Ingår i: Journal of Applied Physics. - 1089-7550. ; 97:9
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Tidskriftsartikel (refereegranskat)abstract
- We propose a photonic switch employing a liquid-crystalline material. The material exhibits a change in the sign of the dielectric anisotropy switching from a positive to a negative value at a certain crossover frequency. By application of an electric field this phenomenon can be used to alter the orientation of the sample between two orthogonal directions leading to a large change in the optical transmission characteristics of the medium. Here we demonstrate that this feature can be realized by an unpolarized ultraviolet UV beam, owing to the photoisomerization of the constituent azobenzene molecules. Possible usage of this for optically driven display devices and image-storage applications are suggested.
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| 18. |
- Hegde, Gurumurthy, 1979, et al.
(författare)
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Dynamic Self-Assembly of the Liquid Crystalline Smectic-A Phase
- 2005
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Ingår i: Advanced Materials. - 1521-4095. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- A photoinduced transition in an azobenzene-containing liquid crystal leads to a phase that does not exist in the thermal cycle. The smectic A phase is induced and stabilized only in the presence of UV light, producing fan-shaped focal conic textures typical of the SmA phase, as observed by polarized-light microscopy (see Figure). This dynamic self-assembly is explained by photoinduced nanophase segregation and a frustrated spin-gas model.
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| 19. |
- Hegde, Gurumurthy, 1979, et al.
(författare)
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Electrooptical modes of ferroelectric liquid crystal display based on bi-and multistability
- 2007
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Ingår i: Euro Display. ; S11:1
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Konferensbidrag (refereegranskat)abstract
- The multistability effect exists under certain conditions in ferroelectric liquid crystal display cells (FLCDC) that means memorization of any light transmission level after the driving voltage switching off. This effect is responsible for three new electrooptical modes with continuous, memorized and reversible gray scale. The modes differ among themselves under the shape of the gray scale curve that can be either S (double or single) or V-shaped dependently on boundary conditions and crystallooptical parameters of the cell. Origin of these modes is under consideration.
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| 20. |
- Hegde, Gurumurthy, 1979, et al.
(författare)
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Evidence of Worm-like micellar behavior in Chromonic liquid Crystals: Rheological, X-ray
- 2007
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Ingår i: J.Phys.Chem.B. ; 111:33
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Tidskriftsartikel (refereegranskat)abstract
- We report rheological, X-ray, and dielectric investigations on a chromonic liquid-crystalline system formed by aqueous solutions of a food coloring agent, Sunset Yellow, in the absence and upon addition of salt. The salt-concentration dependence of the steady-state viscosity at low shear rates has a non-monotonic variation and is qualitatively similar to the behavior seen in wormlike micellar systems, a surprising result since chromonic systems are expected to be non-micellar in character. More interestingly, for a particular low concentration of the salt (20 mM), the viscosity increases by 3 orders of magnitude in comparison with that of the pure chromonic material. The dynamic (oscillatory) rheological data bring out features which can be described in terms of a microstructure formation. X-ray and dielectric studies show that certain characters of the aggregates formed by the Sunset Yellow molecules are not altered by the addition of salt.
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| 21. |
- Hegde, Gurumurthy, 1979, et al.
(författare)
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Influence of a long-chain alkane on the photoinduced nematic-isotropic transition
- 2004
-
Ingår i: Physical Review E. - 1550-7998. ; 69:2
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Tidskriftsartikel (refereegranskat)abstract
- We investigated the phenomenon of photoinduced nematic-isotropic (N-I) transition for different concentrations of a long-chain alkane, viz., octadecane ~OD!, and a host liquid crystalline material having a small quantity ~4.5 mol%! of a photoactive azo compound. As expected, the N-I transition temperature diminishes with increasing concentration of OD. Data of time-resolved measurements of the dielectric constant through both the UV-activated trans-cis transformation and the thermal back relaxation process are presented. With increasing concentration of OD, although the response time for the former process increases slightly by less than a factor of 2, the thermal back relaxation shows a greater increase by more than an order of magnitude. As a possible explanation for this surprising result, we discuss an argument based on the structural incompatibility of the constituents of the system investigated.
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| 22. |
- Hegde, Gurumurthy, 1979, et al.
(författare)
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Nonequilibrium Liquid Crystalline Layered Phase Stabilized by Light
- 2007
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Ingår i: J.Phys.Chem.B. ; 111:2
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Tidskriftsartikel (refereegranskat)abstract
- The ability of light to alter/stabilize a particular thermodynamic phase is a power tool to investigate condensed matter from a new dimension. This field of photoinduced phase transitions is currently an important area of research. Being elastically soft and having subtle changes between its many phases a liquid crystal material is an attractive medium to investigate such light-driven phase transitions. The attraction is partly due to the large birefringence changes accompanying these transitions that are useful in developing photonic devices. In all of the cases reported to date, the photoinduced transition always leads to a phase that in any case exists in the thermal cycle. Recently we reported the first exception to such an established phenomenon (AdV. Mater. 2005, 17, 2086). The guest-host ternary mixture consisting of the photoactive azobenzene guest molecules does not exhibit smectic A phase in the absence of UV radiation. However, the smectic A phase is induced and stabilized only in the presence of UV light. In this paper, we map out hitherto unexplored temperature versus UV intensity phase diagrams for various mixtures, which illustrate that light mimics, in a limited sense, the role of a thermodynamic parameter such as, for example, pressure. The threshold UV intensity required to photodrive the appearance of the smectic A phase is seen to have a strong concentration dependence. Our studies also suggest the possibility of observing a double critical point by employing the UV intensity as a fine-tuning parameter.
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| 23. |
- Hegde, Gurumurthy, 1979, et al.
(författare)
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Photo Induced Effects in Nematic Liquid Crystals
- 2005
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Ingår i: Phase Transitions. - 1029-0338. ; 78:6
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Forskningsöversikt (refereegranskat)abstract
- Temperature, concentration of the solvent and pressure are the parameters that are well known to bring about phase transitions in liquid-crystalline systems. In recent years a new parameter has been added to this list: light. The principle behind these photoinduced transitions is the light-driven shape transformation of certain photoactive materials like, e.g., azobenzene. In this article, we present results of various aspects of our recent investigations on such photoinduced transitions in the nematic phase and highlight the feature that light is a new tool to study phase transitions and the associated critical phenomena
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| 24. |
- Hegde, Gurumurthy, 1979, et al.
(författare)
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Polymer network as a template for control of photoconductivity
- 2004
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Ingår i: Liquid Crystals. - 1366-5855. ; 31:9
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Tidskriftsartikel (refereegranskat)abstract
- We report a novel method of confining a photoconducting liquid crystalline material using a polymer templating approach. The attractive feature of this approach is that the magnitude of the photocurrent of the photoconducting material does not diminish, i.e. it is unaltered by the polymer matrix. The results are compared with another method of encapsulation that was recently reported and wherein the photoconductivity decreases upon having the photoconducting material in the polymer matrix. The difference in the behaviour between the two methods is explained using a nanophase segregation model. The method described is particularly suitable for creating patterned photoconductors.
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| 25. |
- Mondal, B, et al.
(författare)
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Integrative functional genomic analysis identifies epigenetically regulated fibromodulin as an essential gene for glioma cell migration.
- 2017
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Ingår i: Oncogene. - : Springer Science and Business Media LLC. - 0950-9232 .- 1476-5594. ; 36, s. 71-83
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Tidskriftsartikel (refereegranskat)abstract
- An integrative functional genomics study of multiple forms of data are vital for discovering molecular drivers of cancer development and progression. Here, we present an integrated genomic strategy utilizing DNA methylation and transcriptome profile data to discover epigenetically regulated genes implicated in cancer development and invasive progression. More specifically, this analysis identified fibromodulin (FMOD) as a glioblastoma (GBM) upregulated gene because of the loss of promoter methylation. Secreted FMOD promotes glioma cell migration through its ability to induce filamentous actin stress fiber formation. Treatment with cytochalasin D, an actin polymerization inhibitor, significantly reduced the FMOD-induced glioma cell migration. Small interfering RNA and small molecule inhibitor-based studies identified that FMOD-induced glioma cell migration is dependent on integrin-FAK-Src-Rho-ROCK signaling pathway. FMOD lacking C-terminus LRR11 domain (ΔFMOD), which does not bind collagen type I, failed to induce integrin and promote glioma cell migration. Further, FMOD-induced integrin activation and migration was abrogated by a 9-mer wild-type peptide from the FMOD C-terminus. However, the same peptide with mutation in two residues essential for FMOD interaction with collagen type I failed to compete with FMOD, thus signifying the importance of collagen type I-FMOD interaction in integrin activation. Chromatin immunoprecipitation-PCR experiments revealed that transforming growth factor beta-1 (TGF-β1) regulates FMOD expression through epigenetic remodeling of FMOD promoter that involved demethylation and gain of active histone marks with a simultaneous loss of DNMT3A and EZH2 occupancy, but enrichment of Sma- and Mad-related protein-2 (SMAD2) and CBP. FMOD silencing inhibited the TGF-β1-mediated glioma cell migration significantly. In univariate and multivariate Cox regression analysis, both FMOD promoter methylation and transcript levels predicted prognosis in GBM. Thus, this study identified several epigenetically regulated alterations responsible for cancer development and progression. Specifically, we found that secreted FMOD as an important regulator of glioma cell migration downstream of TGF-β1 pathway and forms a potential basis for therapeutic intervention in GBM.
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| 26. |
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| 27. |
- Pozhidaev, E. P., et al.
(författare)
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Light Scattering of Short Helix Pitch Ferroelectric Liquid Crystal
- 2009
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Ingår i: MOLECULAR CRYSTALS AND LIQUID CRYSTALS. - : Informa UK Limited. - 1542-1406 .- 1563-5287. ; 510, s. 12-20
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Tidskriftsartikel (refereegranskat)abstract
- Two new light scattering modes have been discovered in short helix pitch (p0 ≅ 350 nm) ferroelectric liquid crystal (FLC). One of the modes arises because of a special kind of the FLC structure non-uniformity that originates inherently as a new phenomenon if the helix pitch is very small. Another mode relates to the helix twisting after the driving voltage switching off.
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| 28. |
- Rahmathullah, Abu Sajana, 1986, et al.
(författare)
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A low-complexity algorithm for intrusion detection in a PIR-based Wireless Sensor Network
- 2009
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Ingår i: Intelligent Sensors, Sensor Networks and Information Processing (ISSNIP), 2009, Melbourne, Australia. - 9781424435173 ; , s. 337 - 342
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Konferensbidrag (refereegranskat)abstract
- We present a low-complexity algorithm for intrusion detection in the presence of clutter arising from wind-blown vegetation, using passive infra-red (PIR) sensors in a wireless sensor network (WSN). The algorithm is based on a combination of Haar transform (HT) and support-vector-machine (SVM) based training and was field tested in a network setting comprising of 15-20 sensing nodes. Also contained in this paper is a closed-form expression for the signal generated by an intruder moving at a constant velocity. It is shown how this expression can be exploited to determine the direction of motion information and the velocity of the intruder from the signals of three well-positioned sensors.
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| 29. |
- Sandmann, Thomas, et al.
(författare)
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Patients With Proneural Glioblastoma May Derive Overall Survival Benefit From the Addition of Bevacizumab to First-Line Radiotherapy and Temozolomide : Retrospective Analysis of the AVAglio Trial
- 2015
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Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology. - 0732-183X .- 1527-7755. ; 33:25, s. 2735-2744
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The AVAglio (Avastin in Glioblastoma) and RTOG-0825 randomized, placebo-controlled phase III trials in newly diagnosed glioblastoma reported prolonged progression-free survival (PFS), but not overall survival (OS), with the addition of bevacizumab to radiotherapy plus temozolomide. To establish whether certain patient subgroups derived an OS benefit from the addition of bevacizumab to first-line standard-of-care therapy, AVAglio patients were retrospectively evaluated for molecular subtype, and bevacizumab efficacy was assessed for each patient subgroup. Patients and Methods: A total of 349 pretreatment specimens (bevacizumab arm, n = 171; placebo arm, n = 178) from AVAglio patients (total, N = 921) were available for biomarker analysis. Samples were profiled for gene expression and isocitrate dehydrogenase 1 (IDH1) mutation status and classified into previously identified molecular subtypes. PFS and OS were assessed within each subtype. Results: A multivariable analysis accounting for prognostic covariates revealed that bevacizumab conferred a significant OS advantage versus placebo for patients with proneural IDH1 wild-type tumors (17.1 v 12.8 months, respectively; hazard ratio, 0.43; 95% CI, 0.26 to 0.73; P = .002). This analysis also revealed an interaction between the proneural subtype biomarker and treatment arm (P = .023). The group of patients with mesenchymal and proneural tumors derived a PFS benefit from bevacizumab compared with placebo; however, this translated to an OS benefit in the proneural subset only. Conclusion: Retrospective analysis of AVAglio data suggests that patients with IDH1 wild-type proneural glioblastoma may derive an OS benefit from first-line bevacizumab treatment. The predictive value of the proneural subtype observed in AVAglio should be validated in an independent data set.
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