1. |
|
|
2. |
- Imanishi, T., et al.
(author)
-
Integrative annotation of 21,037 human genes validated by full-length cDNA clones
- 2004
-
In: PLoS biology. - : Public Library of Science (PLoS). - 1544-9173 .- 1545-7885. ; 2:6, s. 856-875
-
Journal article (peer-reviewed)abstract
- The human genome sequence defines our inherent biological potential; the realization of the biology encoded therein requires knowledge of the function of each gene. Currently, our knowledge in this area is still limited. Several lines of investigation have been used to elucidate the structure and function of the genes in the human genome. Even so, gene prediction remains a difficult task, as the varieties of transcripts of a gene may vary to a great extent. We thus performed an exhaustive integrative characterization of 41,118 full-length cDNAs that capture the gene transcripts as complete functional cassettes, providing an unequivocal report of structural and functional diversity at the gene level. Our international collaboration has validated 21,037 human gene candidates by analysis of high-quality full-length cDNA clones through curation using unified criteria. This led to the identification of 5,155 new gene candidates. It also manifested the most reliable way to control the quality of the cDNA clones. We have developed a human gene database, called the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/). It provides the following: integrative annotation of human genes, description of gene structures, details of novel alternative splicing isoforms, non-protein-coding RNAs, functional domains, subcellular localizations, metabolic pathways, predictions of protein three-dimensional structure, mapping of known single nucleotide polymorphisms (SNPs), identification of polymorphic microsatellite repeats within human genes, and comparative results with mouse full-length cDNAs. The H-InvDB analysis has shown that up to 4% of the human genome sequence (National Center for Biotechnology Information build 34 assembly) may contain misassembled or missing regions. We found that 6.5% of the human gene candidates (1,377 loci) did not have a good protein-coding open reading frame, of which 296 loci are strong candidates for non-protein-coding RNA genes. In addition, among 72,027 uniquely mapped SNPs and insertions/deletions localized within human genes, 13,215 nonsynonymous SNPs, 315 nonsense SNPs, and 452 indels occurred in coding regions. Together with 25 polymorphic microsatellite repeats present in coding regions, they may alter protein structure, causing phenotypic effects or resulting in disease. The H-InvDB platform represents a substantial contribution to resources needed for the exploration of human biology and pathology.
|
|
3. |
- Kirsten, Franz, 1983, et al.
(author)
-
A repeating fast radio burst source in a globular cluster
- 2022
-
In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 602:7898, s. 585-589
-
Journal article (peer-reviewed)abstract
- Fast radio bursts (FRBs) are flashes of unknown physical origin1. The majority of FRBs have been seen only once, although some are known to generate multiple flashes2,3. Many models invoke magnetically powered neutron stars (magnetars) as the source of the emission4,5. Recently, the discovery6 of another repeater (FRB 20200120E) was announced, in the direction of the nearby galaxy M81, with four potential counterparts at other wavelengths6. Here we report observations that localized the FRB to a globular cluster associated with M81, where it is 2 parsecs away from the optical centre of the cluster. Globular clusters host old stellar populations, challenging FRB models that invoke young magnetars formed in a core-collapse supernova. We propose instead that FRB 20200120E originates from a highly magnetized neutron star formed either through the accretion-induced collapse of a white dwarf, or the merger of compact stars in a binary system7. Compact binaries are efficiently formed inside globular clusters, so a model invoking them could also be responsible for the observed bursts.
|
|
4. |
|
|
5. |
- Pleunis, Z., et al.
(author)
-
LOFAR Detection of 110-188MHz emission and frequency-dependent activity from FRB20180916B
- 2021
-
In: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 911:1
-
Journal article (peer-reviewed)abstract
- The object FRB 20180916B is a well-studied repeating fast radio burst source. Its proximity (∼150 Mpc), along with detailed studies of the bursts, has revealed many clues about its nature, including a 16.3 day periodicity in its activity. Here we report on the detection of 18 bursts using LOFAR at 110-188 MHz, by far the lowest-frequency detections of any FRB to date. Some bursts are seen down to the lowest observed frequency of 110 MHz, suggesting that their spectra extend even lower. These observations provide an order-of-magnitude stronger constraint on the optical depth due to freëCfree absorption in the source's local environment. The absence of circular polarization and nearly flat polarization angle curves are consistent with burst properties seen at 300-1700 MHz. Compared with higher frequencies, the larger burst widths (∼40-160 ms at 150 MHz) and lower linear polarization fractions are likely due to scattering. We find ∼2-3 rad m variations in the Faraday rotation measure that may be correlated with the activity cycle of the source. We compare the LOFAR burst arrival times to those of 38 previously published and 22 newly detected bursts from the uGMRT (200-450 MHz) and CHIME/FRB (400-800 MHz). Simultaneous observations show five CHIME/FRB bursts when no emission is detected by LOFAR. We find that the burst activity is systematically delayed toward lower frequencies by about 3 days from 600 to 150 MHz. We discuss these results in the context of a model in which FRB 20180916B is an interacting binary system featuring a neutron star and high-mass stellar companion.
|
|
6. |
|
|
7. |
|
|
8. |
- Abdillahi, Suado M., et al.
(author)
-
Collagen VI Contains Multiple Host Defense Peptides with Potent In Vivo Activity
- 2018
-
In: Journal of Immunology. - : AMER ASSOC IMMUNOLOGISTS. - 0022-1767 .- 1550-6606. ; 201:3, s. 1007-1020
-
Journal article (peer-reviewed)abstract
- Collagen VI is a ubiquitous extracellular matrix component that forms extensive microfibrillar networks in most connective tissues. In this study, we describe for the first time, to our knowledge, that the collagen VI von Willebrand factor type A like domains exhibit a broad-spectrum antimicrobial activity against Gram-positive and Gram-negative bacteria in human skin infections in vivo. In silico sequence and structural analysis of VWA domains revealed that they contain cationic and amphipathic peptide sequence motifs, which might explain the antimicrobial nature of collagen VI. In vitro and in vivo studies show that these peptides exhibited significant antibacterial activity against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa through membrane disruption. Our findings shed new light on the role of collagen VI derived peptides in innate host defense and provide templates for development of peptide-based antibacterial therapies.
|
|
9. |
- Banas, Magdalena, et al.
(author)
-
Chemerin Is an Antimicrobial Agent in Human Epidermis
- 2013
-
In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:3
-
Journal article (peer-reviewed)abstract
- Chemerin, a chemoattractant ligand for chemokine-like receptor 1 (CMKLR1) is predicted to share similar tertiary structure with antibacterial cathelicidins. Recombinant chemerin has antimicrobial activity. Here we show that endogenous chemerin is abundant in human epidermis, and that inhibition of bacteria growth by exudates from organ cultures of primary human skin keratinocytes is largely chemerin-dependent. Using a panel of overlapping chemerin-derived synthetic peptides, we demonstrate that the antibacterial activity of chemerin is primarily mediated by Val 66 -Pro 85, which causes direct bacterial lysis. Therefore, chemerin is an antimicrobial agent in human skin.
|
|
10. |
- Chettiyam Thodi, Muhamed Fasil, et al.
(author)
-
Using RS and GIS Techniques to Assess and Monitor Coastal Changes of Coastal Islands in the Marine Environment of a Humid Tropical Region
- 2023
-
In: Water. - : MDPI. - 2073-4441. ; 15:21
-
Journal article (peer-reviewed)abstract
- Vypin, Vallarpadam, and Bolgatty are significant tropical coastal islands situated in the humid tropical Kerala region of India, notable for their environmental sensitivity. This study conducted a comprehensive assessment of shoreline alterations on these islands by integrating Remote Sensing (RS) and Geographic Information Systems (GIS) techniques. Utilizing satellite imagery from the LANDSAT series with a spatial resolution of 30 m, the analysis spanned the years from 1973 to 2019. The Digital Shoreline Analysis System (DSAS) tool, integrated into the ArcGIS software, was employed to monitor and analyze shoreline shifts, encompassing erosion and accretion. Various statistical parameters, including Net Shoreline Movement (NSM), End Point Rate (EPR), and Linear Regression Rate (LRR), were utilized to evaluate these changes. Additionally, the study aimed to discern the root causes of shoreline modifications in the study area, encompassing disturbances and the construction of new structures on these islands. The results conclusively demonstrated the substantial impact endured by these coastal islands, with accretion on both sides leading to the creation of new landmasses. This manuscript effectively illustrates that these islands have experienced marine transgression, notably evidenced by accretion. Anthropogenic activities were identified as the primary drivers behind the observed shoreline changes, underscoring the need for careful management and sustainable practices in these fragile coastal ecosystems.
|
|
11. |
- Dagar, Janardan, et al.
(author)
-
Compositional and Interfacial Engineering Yield High-Performance and Stable p-i-n Perovskite Solar Cells and Mini-Modules
- 2021
-
In: ACS applied materials & interfaces. - : American Chemical Society (ACS). - 1944-8244 .- 1944-8252. ; 13:11, s. 13022-13033
-
Journal article (peer-reviewed)abstract
- Through the optimization of the perovskite precursor composition and interfaces to selective contacts, we achieved a p-i-n-type perovskite solar cell (PSC) with a 22.3% power conversion efficiency (PCE). This is a new performance record for a PSC with an absorber bandgap of 1.63 eV. We demonstrate that the high device performance originates from a synergy between (1) an improved perovskite absorber quality when introducing formamidinium chloride (FACl) as an additive in the "triple cation" Cs0.05FA0.79MA0.16PbBr0.51I2.49 (Cs-MAFA) perovskite precursor ink, (2) an increased open-circuit voltage, VOC, due to reduced recombination losses when using a lithium fluoride (LiF) interfacial buffer layer, and (3) high-quality hole-selective contacts with a self-assembled monolayer (SAM) of [2-(9H-carbazol-9-yl)ethyl]phosphonic acid (2PACz) on ITO electrodes. While all devices exhibit a high performance after fabrication, as determined from current-density voltage, J-V, measurements, substantial differences in device performance become apparent when considering longer-term stability data. A reduced long-term stability of devices with the introduction of a LiF interlayer is compensated for by using FACl as an additive in the metal-halide perovskite thin-film deposition. Optimized devices maintained about 80% of the initial average PCE during maximum power point (MPP) tracking for >700 h. We scaled the optimized device architecture to larger areas and achieved fully laser patterned series-interconnected mini-modules with a PCE of 19.4% for a 2.2 cm2 active area. A robust device architecture and reproducible deposition methods are fundamental for high performance and stable large-area single junction and tandem modules based on PSCs.
|
|
12. |
- Gela, Anele, et al.
(author)
-
Eotaxin-3 (CCL26) exerts innate host defense activities that are modulated by mast cell proteases
- 2015
-
In: Allergy. - : Wiley. - 1398-9995 .- 0105-4538. ; 70:2, s. 161-170
-
Journal article (peer-reviewed)abstract
- BackgroundDuring bacterial infections of the airways, a Th1-profiled inflammation promotes the production of several host defense proteins and peptides with antibacterial activities including -defensins, ELR-negative CXC chemokines, and the cathelicidin LL-37. These are downregulated by Th2 cytokines of the allergic response. Instead, the eosinophil-recruiting chemokines eotaxin-1/CCL11, eotaxin-2/CCL24, and eotaxin-3/CCL26 are expressed. This study set out to investigate whether these chemokines could serve as innate host defense molecules during allergic inflammation. MethodsAntibacterial activities of the eotaxins were investigated using viable count assays, electron microscopy, and methods assessing bacterial permeabilization. Fragments generated by mast cell proteases were characterized, and their potential antibacterial, receptor-activating, and lipopolysaccharide-neutralizing activities were investigated. ResultsCCL11, CCL24, and CCL26 all showed potent bactericidal activity, mediated through membrane disruption, against the airway pathogens Streptococcus pneumoniae, Staphylococcus aureus, Nontypeable Haemophilus influenzae, and Pseudomonas aeruginosa. CCL26 retained bactericidal activity in the presence of salt at physiologic concentrations, and the region holding the highest bactericidal activity was the cationic and amphipathic COOH-terminus. Proteolysis of CCL26 by chymase and tryptase, respectively, released distinct fragments of the COOH- and NH2-terminal regions. The COOH-terminal fragment retained antibacterial activity while the NH2-terminal had potent LPS-neutralizing properties in the order of CCL26 full-length protein. An identical fragment to NH2-terminal fragment generated by tryptase was obtained after incubation with supernatants from activated mast cells. None of the fragments activated the CCR3-receptor. ConclusionsTaken together, the findings show that the eotaxins can contribute to host defense against common airway pathogens and that their activities are modulated by mast cell proteases.
|
|
13. |
- Gopinath, A., et al.
(author)
-
Shape-based regularization of electron tomographic reconstruction
- 2012
-
In: IEEE Transactions on Medical Imaging. - 0278-0062 .- 1558-254X. ; 31:12, s. 2241-2252
-
Journal article (peer-reviewed)abstract
- We introduce a tomographic reconstruction method implemented using a shape-based regularization technique. Spatial models of known features in the structure being reconstructed are integrated into the reconstruction process as regularizers. Our regularization scheme is driven locally through shape information obtained from segmentation and compared with a known spatial model. We demonstrated our method on tomography data from digital phantoms, simulated data, and experimental electron tomography (ET) data of virus complexes. Our reconstruction showed reduced blurring and an improvement in the resolution of the reconstructed volume was also measured. This method also produced improved demarcation of spike boundaries in viral membranes when compared with popular techniques like weighted back projection and the algebraic reconstruction technique. Improved ET reconstructions will provide better structure elucidation and improved feature visualization, which can aid in solving key biological issues. Our method can also be generalized to other tomographic modalities.
|
|
14. |
|
|
15. |
- Papareddy, Praveen, et al.
(author)
-
A human antithrombin isoform dampens inflammatory responses and protects from organ damage during bacterial infection
- 2019
-
In: Nature Microbiology. - : Springer Science and Business Media LLC. - 2058-5276. ; 4:12, s. 2442-2455
-
Journal article (peer-reviewed)abstract
- Severe infectious diseases are often characterized by an overwhelming and unbalanced systemic immune response to microbial infections. Human antithrombin (hAT) is a crucial coagulation inhibitor with anti-inflammatory activities. Here we identify three hAT-binding proteins (CD13, CD300f and LRP-1) on human monocytes that are involved in blocking the activity of nuclear factor-kappa B. We found that the modulating effect is primarily restricted to the less abundant beta-isoform (h beta AT) of hAT that lacks N-glycosylation at position 135. Individuals with a mutation at this position have increased production of h beta AT and analysis of their blood, which was stimulated ex vivo with lipopolysaccharide, showed a decreased inflammatory response. Similar findings were recorded when heterozygotic mice expressing hAT or h beta AT were challenged with lipopolysaccharide or infected with Escherichia coli bacteria. Our results finally demonstrate that in a lethal E. coli infection model, survival rates increased when mice were treated with h beta AT one hour and five hours after infection. The treatment also resulted in a reduction of the inflammatory response and less severe organ damage.
|
|
16. |
- Sjövall, Hanna Maria, 1977, et al.
(author)
-
A Kinetic Model for the Selective Catalytic Reduction of NOx with NH3 over an Fe-zeolite Catalyst
- 2010
-
In: Industrial & Engineering Chemistry Research. - : American Chemical Society (ACS). - 1520-5045 .- 0888-5885. ; 49:1, s. 39-52
-
Journal article (peer-reviewed)abstract
- The selective catalytic reduction of NOx with ammonia over all Fe-zeolite catalyst was investigated experimentally and a transient kinetic model was developed. The model includes reactions that describe ammonia storage and oxidation, NO oxidation, selective catalytic reduction (SCR) of NO and NO2, formation of N2O, ammonia inhibition and ammonium nitrate formation. The model call account for a broad range of experimental conditions in the presence of H2O, CO2 and O-2 at temperatures from 150 to 650 degrees C. The catalyst stores ammonia at temperatures up to 400 degrees C and shows ammonia oxidation activity from 350 degrees C. The catalyst is also active for the oxidation of NO to NO2 and the oxidation reaches equilibrium at 500 degrees C. The SCR of NO is already active at 150 degrees C and the introduction of equal amounts of NO and NO2 greatly enhances the conversion of NOx at temperatures up to 300 degrees C. The formation of N2O is negligible if small fractions of NO2 are fed to the reactor, but a significant amount of N2O is formed at high NO2 to NO ratios. An ammonia inhibition oil the SCR of NO is observed at 200 degrees C. This kinetic model contains 12 reactions and is able to describe the experimental results Well. The model was validated using short transient experiments and experimental conditions not used in the parameter estimation and predicted these new conditions adequately.
|
|
17. |
|
|
18. |
- Thaduri, Adithya, et al.
(author)
-
Support vector regression degradation modeling for constant fraction discriminator
- 2012
-
In: Communications in Dependability and Quality Management. - 1450-7196. ; 15:1, s. 101-122
-
Journal article (peer-reviewed)abstract
- In the nuclear industries, the electronic signal processing unit plays a key role in the data processing, data analysis, control mechanism and more importantly safety of the nuclear reactor. The processing unit comprises of different modules that process pulse and current signals from detector and constant fraction discriminator which has higher criticality is one of them. Earlier the reliability was calculated using MilHdbk 217 standard and found discrepancies to the field failure. This paper studies the failure phenomenon using physics of failure approach by studying degradation and failure analysis and conducting the experiments using modified physics of failure methodology. Support vector machine (SVM) is a machine learning phenomenon using statistical learning theory. In this paper, failure data is fed to SVM for regression models intended for life prediction. From the parametric analysis, it was found that Sequential minimal optimization with RBF kernel represent the best model for degradation of the CFD. This method provides higher accuracy compared to response surface methodology.
|
|