| 1. |
- Aare, Sudhakar Reddy, 1978-
(author)
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Intensive Care Unit Muscle Wasting : Skeletal Muscle Phenotype and Underlying Molecular Mechanisms
- 2012
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Doctoral thesis (other academic/artistic)abstract
- Acute quadriplegic myopathy (AQM), or critical illness myopathy, is a common debilitating acquired disorder in critically ill intensive care unit (ICU) patients characterized by generalized muscle wasting and weakness of limb and trunk muscles. A preferential loss of the thick filament protein myosin is considered pathognomonic of this disorder, but the myosin loss is observed relatively late during the disease progression. In attempt to explore the potential role of factors considered triggering AQM in sedated mechanically ventilated (MV) ICU patients, we have studied the early effects, prior to the myosin loss, of neuromuscular blockade (NMB), corticosteroids (CS) and sepsis separate or in combination in a porcine experimental ICU model. Specific interest has been focused on skeletal muscle gene/protein expression and regulation of muscle contraction at the muscle fiber level. This project aims at improving our understanding of the molecular mechanisms underlying muscle specific differences in response to the ICU intervention and the role played by the different triggering factors.The sparing of masticatory muscle fiber function was coupled to an up-regulation of heat shock protein genes and down-regulation of myostatin are suggested to be key factors in the relative sparing of masticatory muscles. Up-regulation of chemokine activity genes and down-regulation of heat shock protein genes play a significant role in the limb muscle dysfunction associated with sepsis. The effects of corticosteroids in the development of limb muscle weakness reveals up-regulation of kinase activity and transcriptional regulation genes and the down-regulation of heat shock protein, sarcomeric, cytoskeletal and oxidative stress responsive genes. In contrast to limb and craniofacial muscles, the respiratory diaphragm muscle responded differently to the different triggering factors. MV itself appears to play a major role for the diaphragm muscle dysfunction. By targeting these genes, future experiments can give an insight into the development of innovative treatments expected at protecting muscle mass and function in critically ill ICU patients.
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| 2. |
- Andreasson, Eskil, et al.
(author)
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Is it possible to open beverage packages virtually? Physical tests in combination with virtual tests in Abaqus.
- 2012
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Conference paper (peer-reviewed)abstract
- The opening mechanism in a beverage package, where a mixed mode failure occurs, is a rather complex phenomenon. A better knowledge in respect of fracture mechanics is needed for the proactive prediction of the overall opening performance. Reliable material data used for virtual simulation of the opening mechanism is extracted by characterization and calibration of the packaging materials. Knowledge of how to choose appropriate constitutive models for the continuum material and how the damage initiates and propagates to various loading conditions is of great interest. The virtual tests, replicating the physical tests, are performed with the aid of the finite element method. Non-linear material response, anisotropic material behaviour, large deformation and fracture mechanics are identified effects that are all included in the virtual model. The results presented in this paper show possible selections of material models in conjunction with material damage models, adequately describing thin polymer films behaviour. Comparison between the physical test and the virtual test, exerted to fracture Mode I – Centre Cracked Tension, showed a good correlation for the chosen modeling technique.
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| 3. |
- Ay, Hakan, et al.
(author)
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Pathogenic Ischemic Stroke Phenotypes in the NINDS-Stroke Genetics Network
- 2014
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In: Stroke. - 0039-2499. ; 45:12, s. 3589-3596
-
Journal article (peer-reviewed)abstract
- BACKGROUND AND PURPOSE: NINDS (National Institute of Neurological Disorders and Stroke)-SiGN (Stroke Genetics Network) is an international consortium of ischemic stroke studies that aims to generate high-quality phenotype data to identify the genetic basis of pathogenic stroke subtypes. This analysis characterizes the etiopathogenetic basis of ischemic stroke and reliability of stroke classification in the consortium. METHODS: Fifty-two trained and certified adjudicators determined both phenotypic (abnormal test findings categorized in major pathogenic groups without weighting toward the most likely cause) and causative ischemic stroke subtypes in 16954 subjects with imaging-confirmed ischemic stroke from 12 US studies and 11 studies from 8 European countries using the web-based Causative Classification of Stroke System. Classification reliability was assessed with blinded readjudication of 1509 randomly selected cases. RESULTS: The distribution of pathogenic categories varied by study, age, sex, and race (P<0.001 for each). Overall, only 40% to 54% of cases with a given major ischemic stroke pathogenesis (phenotypic subtype) were classified into the same final causative category with high confidence. There was good agreement for both causative (κ 0.72; 95% confidence interval, 0.69-0.75) and phenotypic classifications (κ 0.73; 95% confidence interval, 0.70-0.75). CONCLUSIONS: This study demonstrates that pathogenic subtypes can be determined with good reliability in studies that include investigators with different expertise and background, institutions with different stroke evaluation protocols and geographic location, and patient populations with different epidemiological characteristics. The discordance between phenotypic and causative stroke subtypes highlights the fact that the presence of an abnormality in a patient with stroke does not necessarily mean that it is the cause of stroke.
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| 4. |
- Baxtera, Shannon A., et al.
(author)
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Regulation of the lymphatic endothelial cell cycle by the PROX1 homeodomain protein
- 2011
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In: Biochimica et Biophysica Acta. Molecular Cell Research. - : Elsevier. - 0167-4889 .- 1879-2596. ; 1813:1, s. 201-212
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Journal article (peer-reviewed)abstract
- The homeobox transcription factor PROX1 is essential for the development and maintenance of lymphatic vasculature. How PROX1 regulates lymphatic endothelial cell fate remains undefined. PROX1 has been shown to upregulate the expression of Cyclin E, which mediates the G1 to S transition of the cell cycle. Here we demonstrate that PROX1 activates the mouse Cyclin E1 (Ccne1) promoter via two proximal E2F-binding sites. We have determined that the N-terminal region of PROX1 is sufficient to activate a 1-kb Ccne1 promoter, whereas the homeodomain is dispensable for activation. We have identified that the Prospero domain 1 (PD1) is required for the nuclear localization of PROX1. Our comparison of two DNA-binding-deficient constructs of PROX1 showed a cell-type-specific difference between these two proteins in both their localization and function. We demonstrated that siRNA-mediated knockdown of PROX1 in lymphatic endothelial cells decreases progression from G1 to S phase of the cell cycle. We conclude that PROX1 activates the Ccne1 promoter independent of DNA binding, and our results illustrate a novel role for PROX1 in the regulation of lymphatic endothelial cell proliferation.
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| 5. |
- Bhowal, S., et al.
(author)
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Development of collective structures over noncollective excitations in Nd-139
- 2011
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In: Physical Review C (Nuclear Physics). - 0556-2813. ; 84:2
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Journal article (peer-reviewed)abstract
- High-spin states in Nd-139 were investigated using the reaction Zr-96(Ca-48,5n) at a beam energy of 195 MeV and gamma-ray coincidences were acquired with the Euroball spectrometer. Apart from several dipole bands at medium excitation energy, three quadrupole bands have been observed at high spin. Linking transitions connecting two of the high-spin bands to low-energy states have been observed. Calculations based on the cranked-Nilsson-Strutinsky formalism have been used to assign configurations for the high-spin quadrupole bands.
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| 6. |
- Brannon, A Rose, et al.
(author)
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Molecular Stratification of Clear Cell Renal Cell Carcinoma by Consensus Clustering Reveals Distinct Subtypes and Survival Patterns.
- 2010
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In: Genes & cancer. - : Sage. - 1947-6027 .- 1947-6019. ; 1:2, s. 152-163
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Journal article (peer-reviewed)abstract
- Clear cell renal cell carcinoma (ccRCC) is the predominant RCC subtype, but even within this classification, the natural history is heterogeneous and difficult to predict. A sophisticated understanding of the molecular features most discriminatory for the underlying tumor heterogeneity should be predicated on identifiable and biologically meaningful patterns of gene expression. Gene expression microarray data were analyzed using software that implements iterative unsupervised consensus clustering algorithms to identify the optimal molecular subclasses, without clinical or other classifying information. ConsensusCluster analysis identified two distinct subtypes of ccRCC within the training set, designated clear cell type A (ccA) and B (ccB). Based on the core tumors, or most well-defined arrays, in each subtype, logical analysis of data (LAD) defined a small, highly predictive gene set that could then be used to classify additional tumors individually. The subclasses were corroborated in a validation data set of 177 tumors and analyzed for clinical outcome. Based on individual tumor assignment, tumors designated ccA have markedly improved disease-specific survival compared to ccB (median survival of 8.6 vs 2.0 years, P = 0.002). Analyzed by both univariate and multivariate analysis, the classification schema was independently associated with survival. Using patterns of gene expression based on a defined gene set, ccRCC was classified into two robust subclasses based on inherent molecular features that ultimately correspond to marked differences in clinical outcome. This classification schema thus provides a molecular stratification applicable to individual tumors that has implications to influence treatment decisions, define biological mechanisms involved in ccRCC tumor progression, and direct future drug discovery.
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| 7. |
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| 8. |
- Bysani, Madhusudhan Reddy
(author)
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Genome-Wide Studies of Transcriptional Regulation in Human Liver Cells by High-throughput Sequencing
- 2013
-
Doctoral thesis (other academic/artistic)abstract
- The human genome contains slightly more than 20 000 genes that are expressed in a tissue specific manner. Transcription factors play a key role in gene regulation. By mapping the transcription factor binding sites genome-wide we can understand their role in different biological processes. In this thesis we have mapped transcription factors and histone marks along with nucleosome positions and RNA levels. In papers I and II, we used ChIP-seq to map five liver specific transcription factors that are crucial for liver development and function. We showed that the mapped transcription factors are involved in metabolism and other cellular processes. We showed that ChIP-seq can also be used to detect protein-protein interactions and functional SNPs. Finally, we showed that the epigenetic histone mark studied in paper I is associated with transcriptional activity at promoters. In paper III, we mapped nucleosome positions before and after treatment with transforming growth factor β (TGFβ) and found that many nucleosomes changed positions when expression changed. After treatment with TGFβ, the transcription factor HNF4α was replaced by a nucleosome in some regions. In paper IV, we mapped USF1 transcription factor and three active chromatin marks in normal liver tissue and in liver tissue of patients diagnosed with alcoholic steatohepatitis. Using gene ontology, we as expected identified many metabolism related genes as active in normal samples whereas genes in cancer pathways were active in steatohepatitis tissue. Cancer is a common complication to the disease and early signs of this were found. We also found many novel and GWAS catalogue SNPs that are candidates to be functional. In conclusion, our results have provided information on location and structure of regulatory elements which will lead to better knowledge on liver function and disease.
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| 9. |
- Bysani, Madhu Sudhan Reddy, et al.
(author)
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ChIP-seq in steatohepatitis and normal liver tissue identifies candidate disease mechanisms related to progression to cancer
- 2013
-
In: BMC Medical Genomics. - : Springer Science and Business Media LLC. - 1755-8794. ; 6, s. 50-
-
Journal article (peer-reviewed)abstract
- Background: Steatohepatitis occurs in alcoholic liver disease and may progress to liver cirrhosis and hepatocellular carcinoma. Its molecular pathogenesis is to a large degree unknown. Histone modifications play a key role in transcriptional regulations as marks for silencing and activation of gene expression and as marks for functional elements. Many transcription factors (TFs) are crucial for the control of the genes involved in metabolism, and abnormality in their function may lead to disease. Methods: We performed ChIP-seq of the histone modifications H3K4me1, H3K4me3 and H3K27ac and a candidate transcription factor (USF1) in liver tissue from patients with steatohepatitis and normal livers and correlated results to mRNA-expression and genotypes. Results: We found several regions that are differentially enriched for histone modifications between disease and normal tissue, and qRT-PCR results indicated that the expression of the tested genes strongly correlated with differential enrichment of histone modifications but is independent of USF1 enrichment. By gene ontology analysis of differentially modified genes we found many disease associated genes, some of which had previously been implicated in the etiology of steatohepatitis. Importantly, the genes associated to the strongest histone peaks in the patient were over-represented in cancer specific pathways suggesting that the tissue was on a path to develop to cancer, a common complication to the disease. We also found several novel SNPs and GWAS catalogue SNPs that are candidates to be functional and therefore needs further study. Conclusion: In summary we find that analysis of chromatin features in tissue samples provides insight into disease mechanisms.
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| 10. |
- Carrizo, Daniel, et al.
(author)
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Compound-specific bromine isotope compositions of one natural and six = dustrially synthesised organobromine substances
- 2011
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In: Environmental Chemistry. - 1448-2517 .- 1449-8979. ; 8:2, s. 127-132
-
Journal article (peer-reviewed)abstract
- AB The stable bromine isotopic composition (delta(81)Br) was determined for six industrially synthesised brominated organic compounds (BOCs) and one natural BOC by gas-chromatography multi-collector inductively coupled plasma mass spectrometry (GC-mcICP-MS). The delta(81)Br compositions of brominated benzenes, phenols (both natural and industrial), anisoles, and naphthalenes were constrained with the standard differential measurement approach using as reference a monobromobenzene sample with an independently determined delta(81)Br value (-0.39 parts per thousand v. Standard Mean Ocean Bromide, SMOB). The delta(81)Br values for the industrial BOCs ranged from -4.3 to -0.4 parts per thousand. The average delta(81)Br value for the natural compound (2,4-dibromophenol) was 0.2 +/- 1.6% (1 s.d.), and for the identical industrial compound (2,4-dibromophenol) -1.1 +/- 0.9 parts per thousand (1 s.d.), with a statistically significant difference of similar to 1.4 (P<0.05). The delta(81)Br of four out of six industrial compounds was found to be significantly different from that of the natural sample. These novel results establish the bromine isotopic variability among the industrially produced BOCs in relation to a natural sample.
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| 11. |
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| 12. |
- Chen, Shula, et al.
(author)
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Efficient upconvertion of photoluminescence via two-photon-absorption in bulk and nanorod ZnO
- 2012
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In: Applied physics. B, Lasers and optics (Print). - : Springer. - 0946-2171 .- 1432-0649. ; 108:4, s. 919-924
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Journal article (peer-reviewed)abstract
- Efficient upconversion of photoluminescence from donor-bound excitons is revealed in bulk and nanorod ZnO. Based on excitation power-dependent PL measurements performed with different energies of excitation photons, two-photon absorption (TPA) and two-step TPA (TS-TPA) processes are concluded to be responsible for the upconversion. The TS-TPA process is found to occur via a defect/impurity (or defects/impurities) with an energy level (or levels) lying within 1.14–1.56 eV from one of the band edges, without involving photon recycling. One of the possible defect candidates could be VZn. A sharp energy threshold, different from that for the corresponding one-photon absorption, is observed for the TPA process and is explained in terms of selection rules for the involved optical transitions.
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| 13. |
- Cosner, Casey C., et al.
(author)
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Evolution of Concise and Flexible Synthetic Strategies for Trichostatic Acid and the Potent Histone Deacetylase Inhibitor Trichostatin A
- 2013
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In: European Journal of Organic Chemistry. - : Wiley. - 1434-193X .- 1099-0690. ; :1, s. 162-172
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Journal article (peer-reviewed)abstract
- (R)-(+)-Trichostatic acid and (R)-(+)-trichostatin A (TSA) are natural products that have attracted considerable attention in the field of epigenetic therapies. TSA in particular is a naturally occurring hydroxamic acid having potent activity as a histone deacetylase inhibitor (HDACi) and having significant potential for treatment of a myriad of genetically based diseases. Development of TSA and other trichostatic acid derivatives into useful small-molecule therapies has been hindered by the low natural abundance and high cost associated with these compounds. We report herein our collective efforts towards the development of concise and scalable routes for the synthesis of trichostatic acid and TSA in both racemic and enantioenriched forms. Three independent synthetic pathways were developed with varying degrees of efficiency and convergency. In the first synthesis, the key step was a vinylogous Horner-Wadsworth-Emmons condensation. A Marshall propargylation reaction was used as the key step in the second synthesis, and Pd-catalyzed a-alkenylation of a ketone zinc enolate by using various functionalized alkenyl or dienyl halides was developed for the third synthesis. The second pathway proved to be readily amenable to an enantioselective modification, and both the second and third pathways were straightforwardly adapted for the facile preparation of new analogues of trichostatic acid and TSA.
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| 14. |
- Czubryt, Michael P., et al.
(author)
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Regulation of Cardiomyocyte Glut4 Expression by ZAC1
- 2010
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In: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 285:22, s. 16942-16950
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Journal article (peer-reviewed)abstract
- The transcription factor ZAC1 is expressed in a variety of tissues including the developing heart, but its physiological role is unclear. We examined the role of ZAC1 in regulating expression of the insulin-responsive glucose transporter GLUT4 and whether ZAC1 expression is altered in cardiomyocyte hypertrophy. We demonstrated expression of Zac1 mRNA and protein in rat cardiomyocytes by PCR and Western blotting, respectively. Using a combination of chromatin immunoprecipitation and luciferase assays, we showed that ZAC1 regulates Glut4 expression via a specific binding site in the Glut4 promoter. Overexpression of ZAC1 increased Glut4 mRNA and protein expression and resulted in increased glucose uptake in cardiomyocytes as determined by a fluorescent analog uptake assay. Induction of hypertrophy by phenylephrine or isoproterenol resulted in increased Zac1 expression. We identified a novel putative promoter in the Zac1 gene and demonstrated increased binding of MEF2 to this promoter in response to hypertrophic stimulation. MEF2 regulated transactivation of the Zac1 promoter and ZAC1 protein expression. This work identifies ZAC1 as a novel and previously unknown regulator of cardiomyocyte Glut4 expression and glucose uptake. Our results also implicate MEF2 as a regulator of ZAC1 expression in response to induction of hypertrophy.
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| 15. |
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| 16. |
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| 17. |
- Dubba, Krishna Sandeep Reddy, et al.
(author)
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Interleaved Inductive-Abductive Reasoning for Learning Complex Event Models
- 2011
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In: Inductive Logic Programming. - Berlin, Heidelberg : Springer. - 9783642319501 - 9783642319518 ; , s. 113-129
-
Conference paper (peer-reviewed)abstract
- We propose an interleaved inductive-abductive model for reasoning about complex spatio-temporal narratives. Typed Inductive Logic Programming (Typed-ILP) is used as a basis for learning the domain theory by generalising from observation data, whereas abductive reasoning is used for noisy data correction by scenario and narrative completion thereby improving the inductive learning to get semantically meaningful event models. We apply the model to an airport domain consisting of video data for 15 turn-arounds from six cameras simultaneously monitoring logistical processes concerned with aircraft arrival, docking, departure etc and a verbs data set with 20 verbs enacted out in around 2500 vignettes. Our evaluation and demonstration focusses on the synergy afforded by the inductive-abductive cycle, whereas our proposed model provides a blue-print for interfacing common-sense reasoning about space, events and dynamic spatio-temporal phenomena with quantitative techniques in activity recognition.
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| 18. |
- Ekelin, Annelie, et al.
(author)
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The Augment Project : Co-Constructive Mapping and Support of Accessibility and Participation
- 2010
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In: Lecture Notes in Computer Science. - Berlin, Heidelberg : Springer Verlag. ; , s. 95-103, s. 95-103
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Conference paper (peer-reviewed)abstract
- This paper presents an ongoing multi-disciplinary research-and development project in which we are exploring emerging methods and practices for participatory design of tools and content of accessibility information in India and Sweden, based on user created content. The initial development of the AUGMENT-Project also includes the production of a prototype for sharing information. The joint set up and unfolding of public digital spaces and co-operative creation of processes and infrastructure for user-driven accessibility information is making use of existing handheld mobile phones which offer the possibility to upload pictures and comments via an application with a map-based interface. The research initiative is exploring and comparing cross-cultural participatory methods for cultivation of shared transformational spaces. The paper discusses both the notion of user-driven content and co-creation of tools and methods, drawing upon the tradition of Scandinavian Systems Design, explicitly arguing for direct user-representation in systems development.
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| 19. |
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| 20. |
- Farahani, Ensieh, et al.
(author)
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Cell adhesion molecules and their relation to (cancer) cell stemness
- 2014
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In: Carcinogenesis. - : Oxford University Press. - 0143-3334 .- 1460-2180. ; 35:4, s. 747-759
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Research review (peer-reviewed)abstract
- Despite decades of search for anticancer drugs targeting solid tumors, this group of diseases remains largely incurable, especially if in advanced, metastatic stage. In this review, we draw comparison between reprogramming and carcinogenesis, as well as between stem cells (SCs) and cancer stem cells (CSCs), focusing on changing garniture of adhesion molecules. Furthermore, we elaborate on the role of adhesion molecules in the regulation of (cancer) SCs division (symmetric or asymmetric), and in evolving interactions between CSCs and extracellular matrix. Among other aspects, we analyze the role and changes of expression of key adhesion molecules as cancer progresses and metastases develop. Here, the role of cadherins, integrins, as well as selected transcription factors like Twist and Snail is highlighted, not only in the regulation of epithelial-to-mesenchymal transition but also in the avoidance of anoikis. Finally, we briefly discuss recent developments and new strategies targeting CSCs, which focus on adhesion molecules or targeting tumor vasculature.
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| 21. |
- Feroci, M., et al.
(author)
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LOFT - The large observatory for x-ray timing
- 2012
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In: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE - International Society for Optical Engineering. - 9780819491442 ; , s. 84432D-
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Conference paper (peer-reviewed)abstract
- The LOFT mission concept is one of four candidates selected by ESA for the M3 launch opportunity as Medium Size missions of the Cosmic Vision programme. The launch window is currently planned for between 2022 and 2024. LOFT is designed to exploit the diagnostics of rapid X-ray flux and spectral variability that directly probe the motion of matter down to distances very close to black holes and neutron stars, as well as the physical state of ultradense matter. These primary science goals will be addressed by a payload composed of a Large Area Detector (LAD) and a Wide Field Monitor (WFM). The LAD is a collimated (<1 degree field of view) experiment operating in the energy range 2-50 keV, with a 10 m2 peak effective area and an energy resolution of 260 eV at 6 keV. The WFM will operate in the same energy range as the LAD, enabling simultaneous monitoring of a few-steradian wide field of view, with an angular resolution of <5 arcmin. The LAD and WFM experiments will allow us to investigate variability from submillisecond QPO's to yearlong transient outbursts. In this paper we report the current status of the project.
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| 22. |
- Feroci, M., et al.
(author)
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The large observatory for x-ray timing
- 2014
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In: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 9780819496126
-
Conference paper (peer-reviewed)abstract
- The Large Observatory For x-ray Timing (LOFT) was studied within ESA M3 Cosmic Vision framework and participated in the final downselection for a launch slot in 2022-2024. Thanks to the unprecedented combination of effective area and spectral resolution of its main instrument, LOFT will study the behaviour of matter under extreme conditions, such as the strong gravitational field in the innermost regions of accretion flows close to black holes and neutron stars, and the supranuclear densities in the interior of neutron stars. The science payload is based on a Large Area Detector (LAD, 10 m2 effective area, 2-30 keV, 240 eV spectral resolution, 1° collimated field of view) and a Wide Field Monitor (WFM, 2-50 keV, 4 steradian field of view, 1 arcmin source location accuracy, 300 eV spectral resolution). The WFM is equipped with an on-board system for bright events (e.g. GRB) localization. The trigger time and position of these events are broadcast to the ground within 30 s from discovery. In this paper we present the status of the mission at the end of its Phase A study.
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| 23. |
- Filippov, Stanislav, et al.
(author)
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Effects of Ni-coating on ZnO nanowires : A Raman scattering study
- 2013
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In: Journal of Applied Physics. - : American Institute of Physics (AIP). - 0021-8979 .- 1089-7550. ; 113:21, s. 214302-1-214302-6
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Journal article (peer-reviewed)abstract
- Structural properties of ZnO/Ni core/shell nanowires (NWs) are studied in detail by means of Raman spectroscopy. It is shown that formation of the Ni shell leads to passivation of surface states responsible for the observed enhanced intensity of the A1(LO) Raman mode of the bare ZnO NWs. It also causes appearance of 490 cm−1 and 710 cm−1 modes that are attributed to local vibrational modes of a defect/impurity (or defects/impurities). This defect is concluded to be preferably formed in annealed ZnO/Ni NWs and is unlikely to contain a Ni atom, as the same Raman modes were also reported for the Ni-free ZnO nanostructures. From our resonant Raman studies, we also show that the ZnO/Ni core/shell NWs exhibit an enhanced Raman signal with a multiline structure involving A1(LO). This observation is attributed to combined effects of an enhanced Fröhlich interaction at the ZnO/Ni heterointerface and coupling of the scattered light with local surface plasmons excited in the Ni shell. The plasmonic effect is also suggested to allow detection of carbon-related species absorbed at the surface of a single ZnO/Ni NW, promising for applications of such structures as efficient nano-sized gas sensors.
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| 24. |
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| 25. |
- Gorny, Xenia, et al.
(author)
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AKAP79/150 interacts with the neuronal calcium-binding protein caldendrin
- 2012
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In: Journal of Neurochemistry. - : Wiley. - 0022-3042 .- 1471-4159. ; 122:4, s. 714-726
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Journal article (peer-reviewed)abstract
- The A kinase-anchoring protein AKAP79/150 is a postsynaptic scaffold molecule and a key regulator of signaling events. At the postsynapse it coordinates phosphorylation and dephosphorylation of receptors via anchoring kinases and phosphatases near their substrates. Interactions between AKAP79 and two Ca2+ -binding proteins caldendrin and calmodulin have been investigated here. Calmodulin is a known interaction partner of AKAP79/150 that has been shown to regulate activity of the kinase PKC in a Ca2+-dependent manner. Pull-down experiments and surface plasmon resonance biosensor analyses have been used here to demonstrate that AKAP79 can also interact with caldendrin, a neuronal calcium-binding protein implicated in regulation of Ca2+ -influx and release. We demonstrate that calmodulin and caldendrin compete for a partially overlapping binding site on AKAP79 and that their binding is differentially dependent on calcium. Therefore, this competition is regulated by calcium levels. Moreover, both proteins have different binding characteristics suggesting that the two proteins might play complementary roles. The postsynaptic enrichment, the complex binding mechanism, and the competition with calmodulin, makes caldendrin an interesting novel player in the signaling toolkit of the AKAP interactome.
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| 26. |
- Guduru, Shiva Krishna Reddy, et al.
(author)
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Tetrahydroquinoline-Derived Macrocyclic Toolbox : The Discovery of Antiangiogenesis Agents in Zebrafish Assay
- 2013
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In: ACS Medicinal Chemistry Letters. - : American Chemical Society (ACS). - 1948-5875. ; 4:7, s. 666-670
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Journal article (peer-reviewed)abstract
- A novel approach to incorporate the macrocyclic rings onto the privileged substructure, i.e. tetrahydroquinoline scaffold, is developed. The presence of an amino acid-derived moiety in the macrocyclic skeleton provides an opportunity to modulate the nature of the chiral side chain. Further, evaluation in a zebrafish screen identified three active small molecules (2.5b, 3.2d, and 4.2) as antiangiogenesis agents at 2.5 mu M.
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| 27. |
- Hamadani, Mehdi, et al.
(author)
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Early Failure of Frontline Rituximab-Containing Chemo-immunotherapy in Diffuse Large B Cell Lymphoma Does Not Predict Futility of Autologous Hematopoietic Cell Transplantation
- 2014
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In: Biology of blood and marrow transplantation. - : Elsevier BV. - 1083-8791 .- 1523-6536. ; 20:11, s. 1729-1736
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Journal article (peer-reviewed)abstract
- The poor prognosis for patients with diffuse large B cell lymphoma (DLBCL) who relapse within 1 year of initial diagnosis after first-line rituximab-based chemo-immunotherapy has created controversy about the role of autologous transplantation (HCT) in this setting. We compared autologous HCT outcomes for chemosensitive DLBCL patients between 2000 and 2011 in 2 cohorts based on time to relapse from diagnosis. The early rituximab failure (ERF) cohort consisted of patients with primary refractory disease or those with first relapse within 1 year of initial diagnosis. The ERF cohort was compared with those relapsing >1 year after initial diagnosis (late rituximab failure [LRF] cohort). ERF and LRF cohorts included 300 and 216 patients, respectively. Nonrelapse mortality (NRM), progression/relapse, progression-free survival (PFS), and overall survival (OS) of ERF versus LRF cohorts at 3 years were 9% (95% confidence interval [CI], 6% to 13%) versus 9% (95% CI, 5% to 13%), 47% (95% CI, 41% to 52%) versus 39% (95% CI, 33% to 46%), 44% (95% CI, 38% to 50%) versus 52% (95% CI, 45% to 59%), and 50% (95% CI, 44% to 56%) versus 67% (95% CI, 60% to 74%), respectively. On multivariate analysis, ERF was not associated with higher NRM (relative risk [RR], 1.31; P = .34). The ERF cohort had a higher risk of treatment failure (progression/relapse or death) (RR, 2.08; P < .001) and overall mortality (RR, 3.75; P < .001) within the first 9 months after autologous HCT. Beyond this period, PFS and OS were not significantly different between the ERF and LRF cohorts. Autologous HCT provides durable disease control to a sizeable subset of DLBCL despite ERF (3-year PFS, 44%) and remains the standard-of-care in chemosensitive DLBCL regardless of the timing of disease relapse.
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| 28. |
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| 29. |
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| 30. |
- Huffman, Mark D, et al.
(author)
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A cross-sectional study of the microeconomic impact of cardiovascular disease hospitalization in four low- and middle-income countries.
- 2011
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:6
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To estimate individual and household economic impact of cardiovascular disease (CVD) in selected low- and middle-income countries (LMIC).BACKGROUND: Empirical evidence on the microeconomic consequences of CVD in LMIC is scarce.METHODS AND FINDINGS: We surveyed 1,657 recently hospitalized CVD patients (66% male; mean age 55.8 years) from Argentina, China, India, and Tanzania to evaluate the microeconomic and functional/productivity impact of CVD hospitalization. Respondents were stratified into three income groups. Median out-of-pocket expenditures for CVD treatment over 15 month follow-up ranged from 354 international dollars (2007 INT$, Tanzania, low-income) to INT$2,917 (India, high-income). Catastrophic health spending (CHS) was present in >50% of respondents in China, India, and Tanzania. Distress financing (DF) and lost income were more common in low-income respondents. After adjustment, lack of health insurance was associated with CHS in Argentina (OR 4.73 [2.56, 8.76], India (OR 3.93 [2.23, 6.90], and Tanzania (OR 3.68 [1.86, 7.26] with a marginal association in China (OR 2.05 [0.82, 5.11]). These economic effects were accompanied by substantial decreases in individual functional health and productivity.CONCLUSIONS: Individuals in selected LMIC bear significant financial burdens following CVD hospitalization, yet with substantial variation across and within countries. Lack of insurance may drive much of the financial stress of CVD in LMIC patients and their families.
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| 31. |
- Jagarlamudi, Krishna, et al.
(author)
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Genetically modified mouse models for premature ovarian failure (POF)
- 2010
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In: Molecular and Cellular Endocrinology. - : Elsevier BV. - 0303-7207 .- 1872-8057. ; 315:1-2, s. 1-10
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Journal article (peer-reviewed)abstract
- Premature ovarian failure (POF) is a complex disorder that affects approximately 1% of women. POF is characterized by the depletion of functional ovarian follicles before the age of 40 years, and clinically, patients may present with primary amenorrhea or secondary amenorrhea. Although some genes have been hypothesized to be candidates responsible for POF, the etiology of most of the cases is idiopathic, with the underlying causes still unidentified because of the heterogeneity of the disease. In this review, we consider some mutant mouse models that exhibit phenotypes which are comparable to human POF, and we suggest that the use of these mouse models may help us to gain a better understanding of the molecular mechanisms underlying POF in humans.
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| 32. |
- Jangamreddy, Jaganmohan Reddy, et al.
(author)
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Mapping of Apoptin interaction with BCR-ABL1, and development of apoptin-based targeted therapy
- 2014
-
In: Oncotarget. - 1949-2553. ; 5:16, s. 7198-7211
-
Journal article (peer-reviewed)abstract
- Majority of chronic myeloid leukemia patients experience an adequate therapeutic effect from imatinib however, 26-37% of patients discontinue imatinib therapy due to a suboptimal response or intolerance. Here we investigated derivatives of apoptin, a chicken anemia viral protein with selective toxicity towards cancer cells, which can be directed towards inhibiting multiple hyperactive kinases including BCR-ABL1. Our earlier studies revealed that a proline-rich segment of apoptin interacts with the SH3 domain of fusion protein BCR-ABL1 (p210) and acts as a negative regulator of BCR-ABL1 kinase and its downstream targets. In this study we show for the first time, the therapeutic potential of apoptin-derived decapeptide for the treatment of CML by establishing the minimal region of apoptin interaction domain with BCR-ABL1. We further show that the apoptin decapeptide is able to inhibit BCR-ABL1 down stream target c-Myc with a comparable efficacy to full-length apoptin and Imatinib. The synthetic apoptin is able to inhibit cell proliferation in murine (32Dp210), human cell line (K562), and ex vivo in both imatinib-resistant and imatinib sensitive CML patient samples. The apoptin based single or combination therapy may be an additional option in CML treatment and eventually be feasible as curative therapy.
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| 33. |
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| 34. |
- Jesorka, Aldo, 1967, et al.
(author)
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Water coordinated zinc dioxo-chlorin and porphyrin self-assemblies as chlorosomal mimics: Variability of supramolecular interactions
- 2012
-
In: Photochemical and Photobiological Sciences. - : Springer Science and Business Media LLC. - 1474-9092 .- 1474-905X. ; 11:6, s. 1069-1080
-
Journal article (peer-reviewed)abstract
- Semisynthetic zinc chlorins are shown for the first time to self-assemble in the absence of an intrinsic hydroxy group, which is always present in the chlorosomal bacteriochlorophylls (BChl's) c, d and e. Instead, the presently studied compounds have carbonyl groups. These cannot function as hydrogen bond donating groups. However due to interspacing water molecules bound to the zinc ion, double hydrogen bonding can occur to adjacent tetrapyrrolic macrocycles equipped with carbonyl recognition groups. Solution studies comprising UV-Vis absorption, electronic circular dichroism (ECD) and FT-IR show that different aggregates are formed in hydrated solvents in comparison to dry nonpolar solvents. Single crystal X-ray studies show variable supramolecular interactions either with interspacing water molecules coordinating the Zn ion within a porphyrin or with the 17 2 carbonyl group of a chlorin ligating the Zn ion. Our findings have implications for a minimalistic design of self-assembling chromophores, which can act as efficient light-harvesting units.
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| 35. |
- Jokilaakso, Nima, et al.
(author)
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Ultra-localized single cell electroporation using silicon nanowires
- 2013
-
In: Lab on a Chip. - : Royal Society of Chemistry (RSC). - 1473-0197 .- 1473-0189. ; 13:3, s. 336-339
-
Journal article (peer-reviewed)abstract
- Analysis of cell-to-cell variation can further the understanding of intracellular processes and the role of individual cell function within a larger cell population. The ability to precisely lyse single cells can be used to release cellular components to resolve cellular heterogeneity that might be obscured when whole populations are examined. We report a method to position and lyse individual cells on silicon nanowire and nanoribbon biological field effect transistors. In this study, HT-29 cancer cells were positioned on top of transistors by manipulating magnetic beads using external magnetic fields. Ultra-rapid cell lysis was subsequently performed by applying 600-900 mV(pp) at 10 MHz for as little as 2 ms across the transistor channel and the bulk substrate. We show that the fringing electric field at the device surface disrupts the cell membrane, leading to lysis from irreversible electroporation. This methodology allows rapid and simple single cell lysis and analysis with potential applications in medical diagnostics, proteome analysis and developmental biology studies.
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| 36. |
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| 37. |
- Kao-Walter, Sharon, et al.
(author)
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Stress and Stability Analysis of a Building Column with a Pre-folded Origami Pattern
- 2012
-
Conference paper (peer-reviewed)abstract
- A tubular structure by applying the pre-folded origami pattern has been developed at the department of Engineering Science, University of Oxford (see Figure 1). Most of the application is in vehicles. For further application possibility in the fields of Building, bridge, Subway or underground structure, stress and stability analysis were performed. Different cases were calculated by theory of instability and Finite Element Method. Different design solutions were introduced and their strength and stability properties were compared by loading the structure with a compression force on the top of the column. The objective of this work is to find a good solution in safety, sustainability and economy point of view. Failure risk due to the eventually pre-crack in structure will also be discussed by the theory of fracture mechanics.
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| 38. |
- Katangoori, Rahul Reddy, et al.
(author)
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Conceptual study on an origami patterns of type I tapered square tub with and without a crack
- 2013
-
In: Applied Mechanics and Materials. - : Trans Tech Publications, Switzerland. ; , s. 184-188
-
Conference paper (peer-reviewed)abstract
- Thin-walled tubes with origami patterns are popular design for the energy observing devices. However, less study has been done when they subjected to cracks. In this work, the origami square tube with different height to wall thickness ratio are first studied to investigate the collapse modes and deformation mode. Further more, stress concentration areas are identified by numerical simulations. Finally, horizontal and vertical crack was implemented in one of the side in order to study the effect on the deformation mode.
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| 39. |
- Kotte, Jaswini Reddy Swathi, et al.
(author)
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Performance analysis of conventional CMA and RLS in single carrier LTE uplink systems
- 2011
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Conference paper (peer-reviewed)abstract
- In wireless communication, channel equalization is one of the most challenging tasks because the broadcast channels are often subjected to multipath fading and several bandwidth limitations. Our project is mainly concerned with the Single Carrier Long Term Evolution (SC-LTE) uplink system model and its performance analysis when Fractionally Spaced Constant Modulus Algorithm (FS-CMA) and Recursive Least Squares Algorithm (RLS) are implemented. FS-CMA (CMA (1, 2) and CMA (2, 2)) and RLS algorithms are used individually to eliminate noise caused by multipath fading and Additive White Gaussian Noise (AWGN) in the stationary channel. The performance of conventional FS-CMA and RLS algorithm are compared using Bit Error Rate (BER) vs. Signal to Noise Ratio (SNR), Convergence, Equalizer output, Peak to Average Power Ratio (PAPR) vs. SNR
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| 40. |
- Krampert, Monika, et al.
(author)
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Smad7 Regulates the Adult Neural Stem/Progenitor Cell Pool in a Transforming Growth Factor β- and Bone Morphogenetic Protein-Independent Manner
- 2010
-
In: Molecular and Cellular Biology. - : American Society for Microbiology. - 0270-7306 .- 1098-5549. ; 30:14, s. 3685-3694
-
Journal article (peer-reviewed)abstract
- Members of the transforming growth factor beta (TGF-beta) family of proteins modulate the proliferation, differentiation, and survival of many different cell types. Neural stem and progenitor cells (NPCs) in the adult brain are inhibited in their proliferation by TGF-beta and by bone morphogenetic proteins (BMPs). Here, we investigated neurogenesis in a hypomorphic mouse model for the TGF-beta and BMP inhibitor Smad7, with the hypothesis that NPC proliferation might be reduced due to increased TGF-beta and BMP signaling. Unexpectedly, we found enhanced NPC proliferation as well as an increased number of label-retaining cells in vivo. The enhanced proliferation potential of mutant cells was retained in vitro in neurosphere cultures. We observed a higher sphere-forming capacity as well as faster growth and cell cycle progression. Use of specific inhibitors revealed that these effects were independent of TGF-beta and BMP signaling. The enhanced proliferation might be at least partially mediated by elevated signaling via epidermal growth factor (EGF) receptor, as mutant cells showed higher expression and activation levels of the EGF receptor. Conversely, an EGF receptor inhibitor reduced the proliferation of these cells. Our data indicate that endogenous Smad7 regulates neural stem/progenitor cell proliferation in a TGF-beta- and BMP-independent manner.
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| 41. |
- Maddala, Sainath, et al.
(author)
-
A simulator for depicting and comparing adaptive algorithms in signal processing
- 2011
-
Conference paper (peer-reviewed)abstract
- In real time applications signal characteristic and signal noise cannot be determined and predicted which makes very hard while designing digital filters for noise suppression. To outstrip these problem adaptive filters are preferable in which filter coefficients are designed based on the situation by using adaptive algorithms. In this paper a simulator containing adaptive algorithms(Least Mean Square(LMS), Normalized Least Mean Square(NLMS), Recursive Least Square(RLS) , Signed Least Mean Square(SLMS), Signed Normalized Least Mean Square(SNLMS)) using different applications was developed in MATLAB using Graphical User Interphone(GUI). Performance of all algorithms had been observed and some of the results obtained for different applications had been depicted by using real time noise corrupted voice signal. This proposed simulator helps the end user for depicting and comparing adaptive algorithms for real time applications. Pros and cons of each algorithm are observed manually without any motive of mathematical and paper results.
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| 42. |
- Muppani, Naveen Reddy
(author)
-
Transcriptional regulation of cell life and death decisions by p73
- 2013
-
Doctoral thesis (other academic/artistic)abstract
- p73 is the second member to be identified within the p53 family and shares structure and functions with p53. P73 generates various isoforms, which include full-length transcriptionally active (TA) isoforms and amino-terminal transactivation domain-deficient (ΔN) isoforms. TA isoforms of p73 are considered to act as tumor suppressors, whereas the ∆N isoforms of p73 act functionally analogous to other oncoproteins by counteracting the tumor suppressive functions of p53 and TAp73. In contrast to the P53, which is frequently mutated in a variety of human cancers, P73 mutations are very rarely found. However, altered expression of p73 or expression of abnormal p73 splicing variants is frequently detected in different type of cancers. In some cancer cell lines overexpression of TAp73α confers resistance to anticancer chemotherapeutic agents. In our interest to identify transcriptional activities and molecular mechanisms of p73 isoforms that influence drug-induced apoptosis, we found that TAp73α inhibits drug-induced apoptosis by inducing the expression of Hsp72, a cell survival protein, in small cell lung carcinoma cells. TAp73α can also prevent caspase-2-induced apoptosis via inhibiting its enzymatic activity. In contrast, TAp73β induces the expression of p57kip2, which holds tumor suppressor properties. The pro-apoptotic effects of the TAp73β isoform seem to partially depend on the induction of p57Kip2. We discovered that different p73 isoforms transactivate cell cycle and apoptosis regulating gene promoters with different capability in a cell type-specific manner. Furthermore, we identified a functional cooperation between p53 family members, in which transcriptional activity of a DBD mutated isoform of TAp73α depends on the p53 status of the cell to transactivate cell cycle regulating P21 gene promoter. In conclusion, our findings help to understand the isoform-specific transcriptional activities of p73 that determines its pro- and anti-apoptotic effects, upon drug treatment. These findings are expected to help in the development of new strategies to target cancer efficiently based on the p73 isoform present in the tumour and based on the context of the cell.
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| 43. |
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| 44. |
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| 45. |
- Ohshiro, Kazufumi, et al.
(author)
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Acetylation-dependent oncogenic activity of metastasis-associated protein 1 co-regulator.
- 2010
-
In: EMBO reports. - : EMBO. - 1469-3178 .- 1469-221X. ; 11:9, s. 691-7
-
Journal article (peer-reviewed)abstract
- High expression of metastasis-associated protein 1 co-regulator (MTA1), a component of the nuclear remodelling and histone deacetylase complex, has been associated with human tumours. However, the precise role of MTA1 in tumorigenesis remains unknown. In this study, we show that induced levels of MTA1 are sufficient to transform Rat1 fibroblasts and that the transforming potential of MTA1 is dependent on its acetylation at Lys626. Underlying mechanisms of MTA1-mediated transformation include activation of the Ras-Raf pathway by MTA1 but not by acetylation-inactive MTA1; this was due to the repression of Galphai2 transcription, which negatively influences Ras activation. We observed that acetylated MTA1-histone deacetylase (HDAC) interaction was required for the recruitment of the MTA1-HDAC complex to the Galphai2 regulatory element and consequently for the repression of Galphai2 transcription and expression leading to activation of the Ras-Raf pathway. The findings presented in this study provide for the first time--to the best of our knowledge--evidence of acetylation-dependent oncogenic activity of a cancer-relevant gene product.
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| 46. |
- Rafi, Dudekula Mohammad, et al.
(author)
-
Benefits and limitations of automated software testing : Systematic literature review and practitioner survey
- 2012
-
In: 2012 7th International Workshop on Automation of Software Test (AST). - Zurich. - 9781467318211 ; , s. 36-42
-
Conference paper (peer-reviewed)abstract
- There is a documented gap between academic and practitioner views on software testing. This paper tries to close the gap by investigating both views regarding the benefits and limits of test automation. The academic views are studied with a systematic literature review while the practitioners views are assessed with a survey, where we received responses from 115 software professionals. The results of the systematic literature review show that the source of evidence regarding benefits and limitations is quite shallow as only 25 papers provide the evidence. Furthermore, it was found that benefits often originated from stronger sources of evidence (experiments and case studies), while limitations often originated from experience reports. We believe that this is caused by publication bias of positive results. The survey showed that benefits of test automation were related to test reusability, repeatability, test coverage and effort saved in test executions. The limitations were high initial invests in automation setup, tool selection and training. Additionally, 45% of the respondents agreed that available tools in the market offer a poor fit for their needs. Finally, it was found that 80% of the practitioners disagreed with the vision that automated testing would fully replace manual testing.
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| 47. |
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| 48. |
- Razzaghian, Hamid Reza, et al.
(author)
-
Post-Zygotic and Inter-Individual Structural Genetic Variation in a Presumptive Enhancer Element of the Locus between the IL10Rβ and IFNAR1 Genes
- 2013
-
In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:9, s. e67752-
-
Journal article (peer-reviewed)abstract
- Although historically considered as junk-DNA, tandemly repeated sequence motifs can affect human phenotype. For example, variable number tandem repeats (VNTR) with embedded enhancers have been shown to regulate gene transcription. The post-zygotic variation is the presence of genetically distinct populations of cells in an individual derived from a single zygote, and this is an understudied aspect of genome biology. We report somatically variable VNTR with sequence properties of an enhancer, located upstream of IFNAR1. Initially, SNP genotyping of 63 monozygotic twin pairs and multiple tissues from 21 breast cancer patients suggested a frequent post-zygotic mosaicism. The VNTR displayed a repeated 32 bp core motif in the center of the repeat, which was flanked by similar variable motifs. A total of 14 alleles were characterized based on combinations of segments, which showed post-zygotic and inter-individual variation, with up to 6 alleles in a single subject. Somatic variation occurred in similar to 24% of cases. In this hypervariable region, we found a clustering of transcription factor binding sites with strongest sequence similarity to mouse Foxg1 transcription factor binding motif. This study describes a VNTR with sequence properties of an enhancer that displays post-zygotic and inter-individual genetic variation. This element is within a locus containing four related cytokine receptors: IFNAR2, IL10R beta, IFNAR1 and IFNGR2, and we hypothesize that it might function in transcriptional regulation of several genes in this cluster. Our findings add another level of complexity to the variation among VNTR-based enhancers. Further work may unveil the normal function of this VNTR in transcriptional control and its possible involvement in diseases connected with these receptors, such as autoimmune conditions and cancer.
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| 49. |
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| 50. |
- Reddy, A. Satyanarayana, et al.
(author)
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Ultrathin titania coating for high-temperature stable SiO(2)/Pt nanocatalysts
- 2011
-
In: Chemical Communications. - : Royal Society of Chemistry (RSC). - 1359-7345 .- 1364-548X. ; 47, s. 8412-8414
-
Journal article (peer-reviewed)abstract
- The facile synthesis of silica supported platinum nanoparticles with ultrathin titania coating to enhance metal-support interactions suitable for high temperature reactions is reported, as thermal and structure stability of metal nanoparticles is important for catalytic reactions.
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