11 research outputs found
The etiology of esophageal cancer in high- and low- risk areas of Jiangsu province, China
No full text [Background]Esophageal cancer (EC) remains one of the most common and fatal malignancies worldwide. The geographic variation in EC occurrence is striking, and China is an area with one of the highest incidences of EC. A number of epidemiological studies have been conducted toward EC in the past decades, results suggested that tobacco smoking, alcohol drinking, unhealthy dietary factors and chronic injuries of the esophageal mucosa are important in the development of this disease. Genetic polymorphisms in enzymes involved in metabolism of carcinogens may also influence individual susceptibility. However, the effects of major lifestyle and hereditary risk factors on the development of EC remain poorly understood in China. Moreover, little attention has been paid to the etiological heterogeneity between similar areas with great risk gradient. [Methods]From 2003 to 2007, a large population-based case-control study of EC has been conducted in a selected high-risk area and a selected low-risk area of Jiangsu Province, one of the highest cancer incidence areas in China. In total, 1,520 cases and 3,879 controls were recruited. In this thesis, we evaluated the role of major lifestyle factors such as tobacco smoking, alcohol drinking and dietary factors, as well as inherited determinants including family history of cancer and genetic polymorphisms of alcohol-metabolizing related genes on the risk of EC. In addition, we investigated how much of the risk gradient between two areas could be explained by variation in the distributions of major risk factors. [Results] Tobacco smoking and alcohol drinking moderately increased the risk of EC, while the positive associations were only found among men but not among women. Dietary factors were observed to play important roles in the development of EC. Specific dietary habits i.e., fast eating speed, and hot eating and/or drinking substantially elevated EC risk and could explain more than 20% of EC cases each. High intake of salty foods and fried foods, low consumption of raw garlic were also observed to increase the risk of EC. In addition to environmental and lifestyle factors, we confirmed that a positive family history can significantly increase EC risk, and found the inheritance may modify the effect of some unhealthy lifestyles. Moreover, we further explored the relationship between EC and single nucleotide polymorphismsof ADH1B, ADH1C and ALDH2 genes. Results showed that the slow metabolizing ADH1B G allele, ADH1C G allele and ALDH2 A allele significantly increased EC risk among moderate-to-heavy alcohol drinkers, and a significant interaction was observed between ALDH2 gene and alcohol consumption. Lastly, we found that more than 60% of EC cases could be attributable to major lifestyle risk factors in the study population; furthermore, dissimilar distribution of several lifestyle factors, together with variations of hereditary factors may be largely responsible for the incidence difference between two study areas. [Conclusion]The findings in this thesis confirm that unhealthy lifestyles including smoking, alcohol drinking and some dietary factors are the predominant risk factors of EC in China, and a large proportion of incidence difference between regions at varying risk could be attributed to the different prevalence of lifestyle factors. As most of the identified risk factors are modifiable, these could be translated into risk reduction prevention programs in China, and a substantial proportion of new EC cases are expected to be prevented by eliminating or avoiding these risk factors in the population. </p
Evidence for molecular distortion involving the carbonyl group in triplet states of carbonyl derivatives of naphthalene obtained from time resolved vibrational spectroscopic studies
No full textThe C=O stretching vibration appears in the infrared spectra of 2-naphthaldehyde (1), 2-acetonaphthone (2), 2-naphthoic acid (3), methyl 2-naphthoate (4) and 1,2-dihydro-3H-benz[e]inden-3-one (5) in the state T-1(pi pi*) between 1600 and 1700 cm(-1). There is a strong line in the Raman spectrum of 1-5 in the state S-0 arising from the C=O stretching mode, but such a line is lacking in their resonance Raman spectra when they are in the state T-1. This is attributed to a large amplitude out-of-plane twist of the C=O group in 1-4 and to a pyramidalization of the C atom in the C=O group of 5 in the equilibrium geometry of the state T-1.PT: J; CR: 1993, MOPAC 93 VERSION 6 1 ALBRECHT AC, 1961, J CHEM PHYS, V34, P1476 ARNOLD DR, 1968, ADV PHOTOCHEM, V6, P301 BEHRINGER J, 1972, INTRO THEORY RAMAN E, P1 BENSASSON RV, 1980, J CHEM SOC F1, V76, P1801 BEUKLER CA, 1970, SURVEY ORGANIC SYNTH, P807 CATALIOTTI R, 1984, J MOL SPECTROSC, V103, P56 CHAPMAN OL, 1967, REC CHEM PROGR, V28, P167 CHRISTENSEN SD, 1983, J RAMAN SPECTROSC, V14, P53 CI XP, 1989, CHEM PHYS LETT, V158, P263 DEVAQUET A, 1972, J AM CHEM SOC, V94, P5160 DIRAC PAM, 1927, P R SOC LOND A-CONTA, V114, P710 DOPP D, 1990, J PHOTOCH PHOTOBIO A, V53, P59 DOPP D, 1992, CHEM BER-RECL, V125, P983 DUBEN AJ, 1974, EXCITED STATES, V1, P295 FISHER MR, 1985, J CHEM PHYS, V82, P4721 FORMOSINHO SJ, 1991, ADV PHOTOCHEM, V16, P67 GEORGE MW, 1993, CHEM LETT, P873 GRABOWSKI ZR, 1979, J LUMIN, V18, P420 GRABOWSKI ZR, 1979, NOUV J CHIM, V3, P443 GUSTAFSON TL, 1983, J CHEM PHYS, V79, P1559 GUSTAFSON TL, 1984, J CHEM PHYS, V81, P3438 HAMAGUCHI H, 1984, CHEM PHYS LETT, V106, P153 HELLER HG, 1981, J CHEM SOC P2, P341 HOPKINS JB, 1986, CHEM PHYS LETT, V124, P79 HUPPERT D, 1981, J CHEM PHYS, V75, P5714 KARTHA VB, 1973, CAN J CHEM, V51, P1749 KAWASHIMA H, 1990, CHEM PHYS LETT, V165, P59 KEARNS DR, 1966, J AM CHEM SOC, V88, P5087 KITAMURA M, 1973, B CHEM SOC JPN, V46, P3056 KRAINOV EP, 1964, OPT SPECTROSC, V16, P415 KRAMERS HA, 1925, Z PHYS, V31, P681 LEDGER MB, 1972, J CHEM SOC F1, V539, P539 LIM EC, 1977, EXCITED STATES, V3, P305 LUI YH, 1974, J MOL SPECTROSC, V49, P214 MYERS AB, 1985, J CHEM PHYS, V83, P5000 NEVILLE AG, 1990, J AM CHEM SOC, V113, P1869 PAGE C, 1988, THESIS U SAARLAND SA PARKER CA, 1968, J CHEM SOC CHEM COMM, P749 PLANTENGA FL, 1984, J PHOTOCHEM, V24, P133 RAYNER DM, 1986, J PHYS CHEM-US, V90, P2882 RETTIG W, 1979, CHEM PHYS LETT, V62, P115 RETTIG W, 1982, J PHYS CHEM-US, V86, P1970 ROBINSON GW, 1958, CAN J CHEM, V36, P31 ROTKIEWICZ K, 1975, CHEM PHYS LETT, V34, P55 SALTIEL J, 1970, MOL PHOTOCHEM, V2, P331 SCHMID ED, 1977, SPECTRY, V6, P314 SHENG SJ, 1978, CHEM PHYS LETT, V57, P168 TAHARA T, 1987, J PHYS CHEM-US, V91, P5875 TAHARA T, 1988, CHEM PHYS LETT, V152, P135 TAHARA T, 1990, J PHYS CHEM-US, V94, P170 TAKEMURA T, 1982, CHEM PHYS LETT, V91, P390 TANG J, 1970, RAMAN SPECTROSCOPY, V2 VANEIJK AMJ, 1987, J AM CHEM SOC, V109, P6635 VANEIJK AMJ, 1988, J CHEM SOC FARAD T 2, V84, P1129 VANEIJK AMJ, 1990, J CHEM SOC FARADAY T, V86, P2083 VANZEYL PHM, 1984, CHEM PHYS LETT, V105, P127 VISSER RJ, 1980, J CHEM SOC FARAD T 2, V76, P453 VISSER RJ, 1983, J CHEM SOC FARAD T 2, V79, P347 VISSER RJ, 1985, CHEM PHYS LETT, V113, P330 WAGNER BD, 1994, J AM CHEM SOC, V116, P6433 WEISENBORN PCM, 1988, CHEM PHYS, V126, P425 WEISENBORN PCM, 1989, CHEM PHYS, V133, P437 YAMAUCHI S, 1988, J PHYS CHEM-US, V92, P2129 ZINK JI, 1991, ADV PHOTOCHEM, V16, P119; NR: 65; TC: 5; J9: CHEM PHYS; PG: 18; GA: RE469Source type: Electronic(1
Gradual and Step-wise Halophilization Enables Escherichia coli ATCC 8739 to Adapt to 11% NaCl
No full textIntroduction: Escherichia coli (E. coli) is a non-halophilic microbe and is used to indicate faecal contamination. Salt (sodium chloride, NaCl) is a common food additive and is used in preservatives to counter microbial growth. Previous studies had shown that pathogenic E. coli has a higher salt tolerance than non-pathogenic E. coli. The effect of howE. coli interacts with the salt present in the human diet is under-studied. Thus, it is important to investigate this relationship.
Methods: In this study, we observed the genetic changes and growth kinetics of E. coli ATCC 8739 under 3% - 11% NaCl over 80 passages. Growth kinetics was estimated by generation time, cell density and minimum inhibitory concentration (MIC) of NaCl.
Results: Our results suggested that E. coli was able to adapt from 1% NaCl to 11% NaCl with an increment of 1% NaCl per month. Our MIC results suggested that E. coli was able to grow at NaCl concentration of more than 7.5% based on the Area under Curve (AUC) from 5% at passage 44 (cultured in 5% NaCl) to 13% at passage 72 (cultured at 7% NaCl).
Conclusion: We conclude that E. coli ATCC 8739 can be adapted to grow in 11% NaCl by incremental adaptation
Measurement of inclusive and leading subjet fragmentation in pp and Pb–Pb collisions at √sNN = 5.02 TeV
No full textThis article presents new measurements of the fragmentation properties of jets in both proton-proton (pp) and heavy-ion collisions with the ALICE experiment at the LHC. We report distributions of the fraction zr of transverse momentum carried by subjets of radius r within jets of radius R. Charged-particle jets are reconstructed at midrapidity using the anti-kT algorithm with jet radius R=0.4, and subjets are reconstructed by reclustering the jet constituents using the anti-kT algorithm with radii r=0.1 and r=0.2. In pp collisions, we measure both the inclusive and leading subjet distributions. We compare these measurements to perturbative calculations at next-to-leading logarithmic accuracy, which suggest a large impact of threshold resummation and hadronization effects on the zr distribution. In heavy-ion collisions, we measure the leading subjet distributions, which allow access to a region of harder jet fragmentation than has been probed by previous measurements of jet quenching via hadron fragmentation distributions. The zr distributions enable extraction of the parton-to-subjet fragmentation function and allow for tests of the universality of jet fragmentation functions in the quark-gluon plasma (QGP). We find no significant modification of zr distributions in Pb-Pb compared to pp collisions. However, the distributions are also consistent with a hardening trend for zr<0.95, as predicted by several jet quenching models. As zr→1 our results indicate that any such hardening effects cease, exposing qualitatively new possibilities to disentangle competing jet quenching mechanisms. By comparing our results to theoretical calculations based on an independent extraction of the parton-to-jet fragmentation function, we find consistency with the universality of jet fragmentation and no indication of factorization breaking in the QGP
Copyright and shared networking technologies
No full textPhDThe technological zeitgeist has transformed the social-cultural, legal and commercial aspects of society today. Networking technologies comprise one of the most influential factors in this. Although this transformation can be discounted as a mere historical phenomenon dating back to the advent of the printing press, empirical data concerning usage of these technologies shows that there has been a radical shift in the ability to control the dissemination of copyright works. Networking technologies allow, in an unprecedented manner, user-initiated activities including perfect replications, instantaneous dissemination, and abundant storage. They are immune to technological attempts to dismantle them, and impervious to legal attempts to control and harness them. They affect a global audience, which in turn, undermine at negligible costs, the legal and business parameters of copyright owners.
The problem is whether it will now be possible to establish a copyright framework which balances the interests of the following groups: (a) copyright owners in their control of the dissemination of their works; (b) authors demanding remuneration for the exploitation of their works; (c) users wishing to consume works with clear immunity guidelines using networked technologies; (d) technologists striving to continuously innovate without legal and policy restrictions.
Copyright law is not a mechanism for preserving the status quo or a particular business model. It is, as suggested above, a reflection of the needs and interests of authors, copyright owners, entertainment industries, users and technologists. This thesis examines whether the balance between these actors can be achieved and, if so, how it can be implemented within international, regional and national copyright laws. It finds that a balance can be struck; but that this balance should be aligned along three key concepts: user integrity; technological innovation; and authors‘ and owners‘ remuneration. The proposal is that the optimal method for achieving this triptych is the introduction and global implementation of a reasonable and unobtrusive system of remuneration
Applications of Artificial Neural Networks (ANNs) in exploring materials property-property correlations
No full textThe copyright of this thesis rests with the author and no quotation from it or information derived from it may be published without the prior written consent of the authorThe discoveries of materials property-property correlations usually require prior
knowledge or serendipity, the process of which can be time-consuming, costly,
and labour-intensive. On the other hand, artificial neural networks (ANNs) are
intelligent and scalable modelling techniques that have been used extensively to
predict properties from materials’ composition or processing parameters, but are
seldom used in exploring materials property-property correlations. The work
presented in this thesis has employed ANNs combinatorial searches to explore the
correlations of different materials properties, through which, ‘known’ correlations
are verified, and ‘unknown’ correlations are revealed. An evaluation criterion is
proposed and demonstrated to be useful in identifying nontrivial correlations.
The work has also extended the application of ANNs in the fields of data
corrections, property predictions and identifications of variables’ contributions. A
systematic ANN protocol has been developed and tested against the known
correlating equations of elastic properties and the experimental data, and is found
to be reliable and effective to correct suspect data in a complicated situation where
no prior knowledge exists. Moreover, the hardness increments of pure metals due
to HPT are accurately predicted from shear modulus, melting temperature and
Burgers vector. The first two variables are identified to have the largest impacts
on hardening. Finally, a combined ANN-SR (symbolic regression) method is
proposed to yield parsimonious correlating equations by ruling out redundant
variables through the partial derivatives method and the connection weight
approach, which are based on the analysis of the ANNs weight vectors. By
applying this method, two simple equations that are at least as accurate as other
models in providing a rapid estimation of the enthalpies of vaporization for
compounds are obtained.School of Engineering and Materials Science of Queen
Mary, University of London and China Scholarship Council (CSC), for providing
Queen Mary - China Scholarship Council Joint PhD Scholarsh
New insights on the influence of low frequency pulsed current on the characteristics of PEO coatings formed on AZ31B
No full textIn this work, anodic oxide layers on the surface of an AZ31 magnesium alloy were obtained by plasma electrolytic oxidation (PEO) process under low frequency pulsed current. For this, electrolytical solutions containing hexamethylenetetramine and sodium fluoride were used. The morphology and chemical composition of formed coatings were examined by scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD). Also, salt spray test, hydrogen evolution and electrochemical tests (potentiodynamic polarization and electrochemical impedance spectroscopy) were conducted in order to study the corrosion behavior of the coated samples. It was found that the use of low frequency pulsed current for the PEO process reduces the film porosity and increases its thickness, compared with PEO films obtained by continuous anodization. The effect of the pulsed current signal was also analyzed for a two steps PEO process, observing changes in the morphological characteristics of the coatings which allow a better corrosion according electrochemical tests (short term corrosion measurements). However, long term tests results as hydrogen evolution and salt spray tests, indicated the opposite. Both the film porosity and thickness were affected by either the pulsing of the current or the use of a two-step process. © 2020 The Author(s). Published by IOP Publishing Ltd
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Investigating the properties of cancer stem cells and epithelial to mesenchymal transition in human prostate cancer
No full textIn recent years, the cancer stem cell hypothesis has emerged as a compelling but controversial model of cancer progression. Contrary to the clonal evolution model, the cancer stem cell hypothesis postulates that, akin to normal tissues, tumours are hierarchical and only a rare subpopulation of cells, so-called “cancer stem cells” (CSCs), possess the unique biological properties required for tumourigenesis. In addition to tumour initiation, cancer stem cells are held solely accountable for tumour differentiation, tumour maintenance, tumour spread and tumour relapse following therapy. Of late, there has been much evidence to suggest that cancer cells reactivate the latent embryonic programme, epithelial to mesenchymal transition (EMT), in order to acquire the invasive and migratory properties necessary for the successful completion of the invasion-metastasis cascade. Intriguingly, the EMT programme was recently implicated in the generation of cells with the properties of stem cells in a breast cancer model, therefore, it is evident that multiple populations of CSCs may exist within a given tumour. Since metastasis is accountable for the vast majority of cancer-associated mortalities and CSCs are implicated in therapy failure and subsequent cancer relapse, it is apparent that epithelial to mesenchymal transition and cancer stem cells are of utmost clinical relevance
Innovative approaches to monitor mutant huntingtin and to facilitate its degradation in Huntington's disease models
No full textHuntington’s disease (HD) is a dominant genetic neurodegenerative disease caused by a mutation in the exon 1 of the huntingtin gene. The clinical symptoms, such as motor disturbances (chorea), cognitive decline and psychiatric impairments are usually developed by the patients in mid-life. Mutant huntingtin protein presents an amplification of a polyglutamine repeat at its N-terminus, which induces conformational changes and leads to neurotoxicity, impairment of cell homeostasis and neuronal cell death. The neuropathology of HD is characterized by a progressive degeneration of the brain starting from the striatum and spreading to other regions such as cortex, hypothalamus and cerebellum. In addition to the diffused brain atrophy, HD patients are also affected by multiple peripheral symptoms which contribute to worsening disease progression and eventually lead to death approximately two decades after onset.
The mechanisms leading to the toxicity induced by mutant huntingtin are not well understood. However the acquisition of a misfolded conformation and the formation of intracellular inclusions constituted by shorter fragments of the mutant protein are considered important in the neurodegenerative process.
In my thesis project I have investigated mechanisms to enhance the cellular degradation of mutant huntingtin. A second focus was on the development of an immunoassay to detect and quantify aggregates in HD models.
I analyzed the data obtained form a high through-put screen aimed to identify small molecular weight compounds decreasing mutant huntingtin levels in cells. Among all compounds screened, only inhibitors of heat shock protein 90 (Hsp90) showed a significant effect on mutant huntingtin clearance. I therefore investigated the mechanisms of Hsp90 chaperone inhibition and the reduction of soluble mutant huntigtin levels. Data from biochemical assays demonstrated that mutant huntingtin degradation is enhanced upon compound treatment and that the protein is cleared through the ubiquitin-proteasome system. This was independent from the heat shock response induced after pharmacological Hsp90 inhibition. Co-immunoprecipitation experiments suggested that mutant huntingtin is a client protein of Hsp90. The results were replicated in different cellular models including full length mutant huntingtin expressed from the endogenous locus, thus highlighting the importance of Hsp90 in stabilizing soluble mutant huntingtin and suggesting the possible application of Hsp90 inhibitors as therapies in HD.
In the second project I developed a sensitive method to detect mutant protein aggregates in HD models. To this purpose I implemented the already established time resolved fluorescence resonance energy transfer (TR-FRET) based immunoassay for the detection of soluble mutant and wild-type huntingtin. A mixture of either donor or acceptor fluorophore labeled single monoclonal antibody directed against an epitope exposed on the huntingtin aggregate surface was used. This strategy allowed for energy transfer and therefore a measurable TR-FRET signal, only in presence of mutant aggregated protein. I could demonstrate the sensitivity of the bioassay on a microtiter set up both as a single assay and in a duplex combination with the previously developed TR-FRET assay for soluble huntingtin.
I applied the TR-FRET for aggregated huntingtin to samples from R6/2 and HdhQ150 mice, expressing exon 1 and full length mutant huntingtin, respectively. In brain homogenates from both models there was an age-dependent, inverse correlation between soluble and aggregated mutant huntingtin. These findings supported the importance of the relation between aggregated and soluble protein in disease progression. Furthermore, I detected the inverse correlation also in peripheral tissues of R6/2 mice where the presence of aggregates was previously demonstrated with other methods. An in-depth analysis of R6/2 samples in a combination of TR-FRET and size exclusion chromatography suggested a differential specificity of the two antibody combinations used for different aggregate populations. The TR-FRET method provides a new means to characterize the aggregation process as well as to test the efficacy of possible disease modifying treatments for HD
Cortical Brain Abnormalities in 4474 Individuals With Schizophrenia and 5098 Control Subjects via the Enhancing Neuro Imaging Genetics Through Meta Analysis (ENIGMA) Consortium
No full textBACKGROUND: The profile of cortical neuroanatomical abnormalities in schizophrenia is not fully understood, despite hundreds of published structural brain imaging studies. This study presents the first meta-analysis of cortical thickness and surface area abnormalities in schizophrenia conducted by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Schizophrenia Working Group.
METHODS: The study included data from 4474 individuals with schizophrenia (mean age, 32.3 years; range, 11-78 years; 66% male) and 5098 healthy volunteers (mean age, 32.8 years; range, 10-87 years; 53% male) assessed with standardized methods at 39 centers worldwide.
RESULTS: Compared with healthy volunteers, individuals with schizophrenia have widespread thinner cortex (left/right hemisphere: Cohen's d = -0.530/-0.516) and smaller surface area (left/right hemisphere: Cohen's d = -0.251/-0.254), with the largest effect sizes for both in frontal and temporal lobe regions. Regional group differences in cortical thickness remained significant when statistically controlling for global cortical thickness, suggesting regional specificity. In contrast, effects for cortical surface area appear global. Case-control, negative, cortical thickness effect sizes were two to three times larger in individuals receiving antipsychotic medication relative to unmedicated individuals. Negative correlations between age and bilateral temporal pole thickness were stronger in individuals with schizophrenia than in healthy volunteers. Regional cortical thickness showed significant negative correlations with normalized medication dose, symptom severity, and duration of illness and positive correlations with age at onset.
CONCLUSIONS: The findings indicate that the ENIGMA meta-analysis approach can achieve robust findings in clinical neuroscience studies; also, medication effects should be taken into account in future genetic association studies of cortical thickness in schizophrenia
