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Variable screening based on Gaussian Centered L-moments [article]

Hyowon An, Kai Zhang, Hannu Oja, J. S. Marron
2019 arXiv   pre-print
An important challenge in big data is identification of important variables. In this paper, we propose methods of discovering variables with non-standard univariate marginal distributions. The conventional moments-based summary statistics can be well-adopted for that purpose, but their sensitivity to outliers can lead to selection based on a few outliers rather than distributional shape such as bimodality. To address this type of non-robustness, we consider the L-moments. Using these in
more » ... , however, has a limitation because they do not take zero values at the Gaussian distributions to which the shape of a marginal distribution is most naturally compared. As a remedy, we propose Gaussian Centered L-moments which share advantages of the L-moments but have zeros at the Gaussian distributions. The strength of Gaussian Centered L-moments over other conventional moments is shown in theoretical and practical aspects such as their performances in screening important genes in cancer genetics data.
arXiv:1908.11048v1 fatcat:36jhpur5knbjrbmlhdki6hdmdy

Phage lysin that specifically eliminates Clostridium botulinum Group I cells

Zhen Zhang, Meeri Lahti, François P. Douillard, Hannu Korkeala, Miia Lindström
2020 Scientific Reports  
AbstractClostridium botulinum poses a serious threat to food safety and public health by producing potent neurotoxin during its vegetative growth and causing life-threatening neuroparalysis, botulism. While high temperature can be utilized to eliminate C. botulinum spores and the neurotoxin, non-thermal elimination of newly germinated C. botulinum cells before onset of toxin production could provide an alternative or additional factor controlling the risk of botulism in some applications. Here
more » ... e introduce a putative phage lysin that specifically lyses vegetative C. botulinum Group I cells. This lysin, called CBO1751, efficiently kills cells of C. botulinum Group I strains at the concentration of 5 µM, but shows little or no lytic activity against C. botulinum Group II or III or other Firmicutes strains. CBO1751 is active at pH from 6.5 to 10.5. The lytic activity of CBO1751 is tolerant to NaCl (200 mM), but highly susceptible to divalent cations Ca2+ and Mg2+ (50 mM). CBO1751 readily and effectively eliminates C. botulinum during spore germination, an early stage preceding vegetative growth and neurotoxin production. This is the first report of an antimicrobial lysin against C. botulinum, presenting high potential for developing a novel antibotulinal agent for non-thermal applications in food and agricultural industries.
doi:10.1038/s41598-020-78622-6 pmid:33299101 fatcat:u3bjh65djjgz7jam5hh2gdmpm4

c-Jun N-terminal kinase mediates constitutive human eosinophil apoptosis

Hannele Hasala, Xianzhi Zhang, Seppo Saarelainen, Eeva Moilanen, Hannu Kankaanranta
2007 Pulmonary Pharmacology & Therapeutics  
In conjunction with our present results, Zhang et al.  ... 
doi:10.1016/j.pupt.2006.06.004 pmid:16934508 fatcat:4eh2kh27orfjrmfionhl3rg4uu

Plasmid-Borne Type E Neurotoxin Gene Clusters in Clostridium botulinum Strains

Zhen Zhang, Hannamari Hintsa, Ying Chen, Hannu Korkeala, Miia Lindström
2013 Applied and Environmental Microbiology  
ABSTRACTA collection of 36Clostridium botulinumtype E strains was examined by pulsed-field gel electrophoresis (PFGE) and Southern hybridization with probes targeted tobotEandorfX1in the neurotoxin gene cluster. Three strains were found to contain neurotoxin subtype E1 gene clusters in large plasmids of about 146 kb in size.
doi:10.1128/aem.00080-13 pmid:23563942 pmcid:PMC3675925 fatcat:olzvc2dcazemjh27bozh4ynqfa

Cardiac radiomics: an interactive approach for 4D data exploration

Lennart Tautz, Hannu Zhang, Markus Hüllebrand, Matthias Ivantsits, Sebastian Kelle, Titus Kuehne, Volkmar Falk, Anja Hennemuth
2020 Current Directions in Biomedical Engineering  
AbstractCardiac diseases manifest in a multitude of interconnected changes in morphology and dynamics. Radiomics approaches are a promising technique to analyze such changes directly from image data. We propose novel features to specifically describe moving cardiac structures, and an interactive 4D visualization method to explore such data. Prototypical tests with an open data set containing different diseases show that our approach can be a fast and useful tool for the 4D analysis of heterogeneous cohort data.
doi:10.1515/cdbme-2020-0008 fatcat:lvlpahlvhjerff54y6marh3aom

Histone deacetylase inhibitors induce apoptosis in human eosinophils and neutrophils

Hannu Kankaanranta, Mirkka Janka-Junttila, Pinja Ilmarinen-Salo, Kazuhiro Ito, Ulla Jalonen, Misako Ito, Ian M Adcock, Eeva Moilanen, Xianzhi Zhang
2010 Journal of Inflammation  
doi:10.1186/1476-9255-7-9 pmid:20181093 pmcid:PMC2841159 fatcat:jln7paevvrfjpkaaoyn25jkg3m

Involvement of Clostridium botulinum ATCC 3502 Sigma Factor K in Early-Stage Sporulation

David G. Kirk, Elias Dahlsten, Zhen Zhang, Hannu Korkeala, Miia Lindström
2012 Applied and Environmental Microbiology  
ABSTRACTA key survival mechanism ofClostridium botulinum, the notorious neurotoxic food pathogen, is the ability to form heat-resistant spores. While the genetic mechanisms of sporulation are well understood in the model organismBacillus subtilis, nothing is known about these mechanisms inC. botulinum.Using the ClosTron gene-knockout tool,sigK, encoding late-stage (stage IV) sporulation sigma factor K inB. subtilis, was disrupted inC. botulinumATCC 3502 to produce two different mutants with
more » ... inct insertion sites and orientations. Both mutants were unable to form spores, and their elongated cell morphology suggested that the sporulation pathway was blocked at an early stage. In contrast,sigK-complemented mutants sporulated successfully. Quantitative real-time PCR analysis ofsigKin the parent strain revealed expression at the late log growth phase in the parent strain. Analysis ofspo0A, encoding the sporulation master switch, in thesigKmutant and the parent showed significantly reduced relative levels ofspo0Aexpression in thesigKmutant compared to the parent strain. Similarly,sigFshowed significantly lower relative transcription levels in thesigKmutant than the parent strain, suggesting that the sporulation pathway was blocked in thesigKmutant at an early stage. We conclude that σKis essential for early-stage sporulation inC. botulinumATCC 3502, rather than being involved in late-stage sporulation, as reported for the sporulation model organismB. subtilis. Understanding the sporulation mechanism ofC. botulinumprovides keys to control the public health risks that the spores of this dangerous pathogen cause through foods.
doi:10.1128/aem.00304-12 pmid:22544236 pmcid:PMC3370484 fatcat:uuqgx66dcvaq7jhm5vzw53zwly

Menopausal hormone therapy and women's health: An umbrella review

Guo-Qiang Zhang, Jin-Liang Chen, Ying Luo, Maya B. Mathur, Panagiotis Anagnostis, Ulugbek Nurmatov, Madar Talibov, Jing Zhang, Catherine M. Hawrylowicz, Mary Ann Lumsden, Hilary Critchley, Aziz Sheikh (+6 others)
2021 PLoS Medicine  
(PDF) Validation: Guo-Qiang Zhang, Jin-Liang Chen, Ying Luo, Maya B. Mathur, Panagiotis Anagnostis, Jing Zhang, Bright I. Nwaru. 4.  ... 
doi:10.1371/journal.pmed.1003731 pmid:34339416 pmcid:PMC8366967 fatcat:rky33wzmybg65cy4u5wbckgzju

The glucocorticoid RU24858 does not distinguish between transrepression and transactivation in primary human eosinophils

Mirkka Janka-Junttila, Eeva Moilanen, Hannele Hasala, Xianzhi Zhang, Ian Adcock, Hannu Kankaanranta
2006 Journal of Inflammation  
Glucocorticoids are used to treat chronic inflammatory diseases such as asthma. Induction of eosinophil apoptosis is considered to be one of the main mechanisms behind the anti-asthmatic effect of glucocorticoids. Glucocorticoid binding to its receptor (GR) can have a dual effect on gene transcription. Activated GR can activate transcription (transactivation), or by interacting with other transcription factors such as NF-kappaB suppress transcription (transrepression). RU24858 has been reported
more » ... to transrepress but to have little or no transactivation capability in other cell types. The dissociated properties of RU24858 have not been previously studied in non-malignant human cells. As the eosinophils have a very short lifetime and many of the modern molecular biological methods cannot be used, a "dissociated steroid" would be a valuable tool to evaluate the mechanism of action of glucocorticoids in human eosinophils. The aim of this study was to elucidate the ability of RU24858 to activate and repress gene expression in human eosinophils in order to see whether it is a dissociated steroid in human eosinophils. Human peripheral blood eosinophils were isolated under sterile conditions and cultured in the presence and/or absence RU24858. For comparison, dexamethasone and mometasone were used. We measured chemokine receptor-4 (CXCR4) and Annexin 1 expression by flow cytometry and cytokine production by ELISA. Apoptosis was measured by DNA fragmentation and confirmed by morphological analysis. RU24858 (1 microM) increased CXCR4 and Annexin 1 expression on eosinophils to a similar extent as mometasone (1 microM) and dexamethasone (1 microM). Like dexamethasone and mometasone, RU24858 did suppress IL-8 and MCP-1 production in eosinophils. RU24858 also increased spontaneous eosinophil apoptosis to a similar degree as dexamethasone and mometasone, but unlike dexamethasone and mometasone it did not reverse IL-5- or GM-CSF-induced eosinophil survival. Our results suggest that in human eosinophils RU24858 acts as transactivator and transrepressor like classical glucocorticoids. Thus, RU24858 seems not to be a "dissociated steroid" in primary human eosinophils in contrast to that reported in animal cells. In addition, functionally RU24858 seems to be a less potent glucocorticoid as it did not reverse IL-5- and GM-CSF-afforded eosinophil survival similarly to dexamethasone and mometasone.
doi:10.1186/1476-9255-3-10 pmid:16834783 pmcid:PMC1559619 fatcat:4zfbc5y4vbbs3myq2llkqwoiau

Sex Disparities in Asthma Development and Clinical Outcomes: Implications for Treatment Strategies

Guo-Qiang Zhang, Saliha Selin Özuygur Ermis, Madeleine Rådinger, Apostolos Bossios, Hannu Kankaanranta, Bright Nwaru
2022 Journal of Asthma and Allergy  
Disclosure Professor Hannu Kankaanranta reports personal fees, non-financial support from AstraZeneca, personal fees from Boehringer-Ingelheim, personal fees from Chiesi, personal fees from GlaxoSmithKline  ... 
doi:10.2147/jaa.s282667 pmid:35210789 pmcid:PMC8863331 fatcat:lbf7ohwgyvhohnwxapzdosgjii

Positive Regulation of Botulinum Neurotoxin Gene Expression by CodY in Clostridium botulinum ATCC 3502

Zhen Zhang, Elias Dahlsten, Hannu Korkeala, Miia Lindström, D. W. Schaffner
2014 Applied and Environmental Microbiology  
ABSTRACTBotulinum neurotoxin, produced mainly by the spore-forming bacteriumClostridium botulinum, is the most poisonous biological substance known. Here, we show that CodY, a global regulator conserved in low-G+C Gram-positive bacteria, positively regulates the botulinum neurotoxin gene expression. Inactivation ofcodYresulted in decreased expression ofbotA, encoding the neurotoxin, as well as in reduced neurotoxin synthesis. Complementation of thecodYmutation intransrescued neurotoxin
more » ... , and overexpression ofcodYintranscaused elevated neurotoxin production. Recombinant CodY was found to bind to a 30-bp region containing thebotAtranscription start site, suggesting regulation of the neurotoxin gene transcription through direct interaction. GTP enhanced the binding affinity of CodY to thebotApromoter, suggesting that CodY-dependent neurotoxin regulation is associated with nutritional status.
doi:10.1128/aem.02838-14 pmid:25281376 pmcid:PMC4249235 fatcat:vvpnzp4avncapogxnjpnptyomy

Niobium doping induced mirror twin boundaries in MBE grown WSe2 monolayers

Bo Wang, Yipu Xia, Junqiu Zhang, Hannu-Pekka Komsa, Maohai Xie, Yong Peng, Chuanhong Jin
2020 Nano Reseach  
Mirror twin boundary (MTB) brings unique 1D physics and properties into two-dimensional transition metal dichalcogenides (TMDCs), but they were rarely observed in non-Mo-based TMDCs. Herein, by post-growth Nb doping, high density 4|4E-W and 4|4P-Se MTBs were introduced into molecular beam epitaxy (MBE) grown WSe2 monolayers. Of them, 4|4E-W MTB with a novel structure was discovered experimentally for the first time, while 4|4P-Se MTBs present a random permutations of W and Nb, forming a 1D
more » ... system. Comparison between the doped and non-doped WSe2 confirmed that Nb dopants are essential for MTB formation. Furthermore, quantitative statistics reveal the areal density of MTBs is directly proportional to the concentration of Nb dopants. To unravel the injection pathway of Nb dopants, first-principles calculations about a set of formation energies for excess Nb atoms with different configurations were conducted, based on which a model explaining the origin of MTBs introduced by excess metal was built. We conclude that the formation of MTBs is mainly driven by the collective evolution of excess Nb atoms introduced into the lattice of host WSe2 crystal and subsequent displacement of metal atoms (W or Nb). This study provides a novel way to tailor the MTBs in 2D TMDC materials via proper metal doping and presents a new opportunities for exploring the intriguing properties.
doi:10.1007/s12274-020-2639-6 fatcat:pmsrdlhbfjc7dnlatu3k5hzj3y

Quantitative Detection of Cirrhosis: Towards the Development of Computer-Assisted Detection Method

Hannu T. Huhdanpaa, Peng Zhang, Venkataramu N. Krishnamurthy, Chris Douville, Binu Enchakolody, Chris Chou, Sampathkumar Ethiraj, Stewart Wang, Grace L. Su
2014 Journal of digital imaging  
There are distinct morphologic features of cirrhosis on CT examinations; however, such impressions may be subtle or subjective. The purpose of this study is to build a computer-aided diagnosis (CAD) method to help radiologists with this diagnosis. One hundred sixty-seven abdominal CT examinations were randomly divided into training (n=88) and validation (n=79) sets. Livers were analyzed for morphological markers of cirrhosis and logistic regression models were created. Using the area under
more » ... (AUC) for model performance, the best model had 0.89 for the training set and 0.85 for the validation set. For radiology reports, sensitivity of reporting cirrhosis was 0.45 and specificity 0.99. Using the predictive model adjunctively, radiologists' sensitivity increased to 0.63 and specificity slightly decreased to 0.97. This study demonstrates that quantifying morphological features in livers may be utilized for diagnosing cirrhosis and for developing a CAD method for it.
doi:10.1007/s10278-014-9696-x pmid:24811859 pmcid:PMC4171427 fatcat:6nfg6pfx2nei5olawacpfiwvge

Alternative Sigma Factors SigF, SigE, and SigG Are Essential for Sporulation in Clostridium botulinum ATCC 3502

David G. Kirk, Zhen Zhang, Hannu Korkeala, Miia Lindström, M. W. Griffiths
2014 Applied and Environmental Microbiology  
ABSTRACTClostridium botulinumproduces heat-resistant endospores that may germinate and outgrow into neurotoxic cultures in foods. Sporulation is regulated by the transcription factor Spo0A and the alternative sigma factors SigF, SigE, SigG, and SigK in most spore formers studied to date. We constructed mutants ofsigF,sigE, andsigGinC. botulinumATCC 3502 and used quantitative reverse transcriptase PCR and electron microscopy to assess their expression of the sporulation pathway on
more » ... and morphological levels. In all three mutants the expression ofspo0Awas disrupted. ThesigFandsigEmutants failed to inducesigGandsigKbeyond exponential-phase levels and halted sporulation during asymmetric cell division. In thesigGmutant, peak transcription ofsigEwas delayed andsigKlevels remained lower than that in the parent strain. ThesigGmutant forespore was engulfed by the mother cell and possessed a spore coat but no peptidoglycan cortex. The findings suggest that SigF and SigE ofC. botulinumATCC 3502 are essential for early sporulation and late-stage induction ofsigK, whereas SigG is essential for spore cortex formation but not for coat formation, as opposed to previous observations inB. subtilis sigGmutants. Our findings add to a growing body of evidence that regulation of sporulation inC. botulinumATCC 3502, and among the clostridia, differs from theB. subtilismodel.
doi:10.1128/aem.01015-14 pmid:24928875 pmcid:PMC4135750 fatcat:mh2yqlqvr5fydieq2rfy54t4qm

Solvent-mediated assembly of atom-precise gold–silver nanoclusters to semiconducting one-dimensional materials

Peng Yuan, Ruihua Zhang, Elli Selenius, Pengpeng Ruan, Yangrong Yao, Yang Zhou, Sami Malola, Hannu Häkkinen, Boon K. Teo, Yang Cao, Nanfeng Zheng
2020 Nature Communications  
Bottom-up design of functional device components based on nanometer-sized building blocks relies on accurate control of their self-assembly behavior. Atom-precise metal nanoclusters are well-characterizable building blocks for designing tunable nanomaterials, but it has been challenging to achieve directed assembly to macroscopic functional cluster-based materials with highly anisotropic properties. Here, we discover a solvent-mediated assembly of 34-atom intermetallic gold-silver clusters
more » ... cted by 20 1-ethynyladamantanes into 1D polymers with Ag-Au-Ag bonds between neighboring clusters as shown directly by the atomic structure from single-crystal X-ray diffraction analysis. Density functional theory calculations predict that the single crystals of cluster polymers have a band gap of about 1.3 eV. Field-effect transistors fabricated with single crystals of cluster polymers feature highly anisotropic p-type semiconductor properties with ≈1800-fold conductivity in the direction of the polymer as compared to cross directions, hole mobility of ≈0.02 cm2 V-1 s-1, and an ON/OFF ratio up to ≈4000. This performance holds promise for further design of functional cluster-based materials with highly anisotropic semiconducting properties.
doi:10.1038/s41467-020-16062-6 pmid:32376829 fatcat:3ycj2guxsjdppbgtf33zqgucby
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