Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of Initiation Sites for DNA Replication in the Human dnmt1 (DNA-methyltransferase) Locus*

Vertebrates have developed multiple mechanisms to coordinate the replication of epigenetic and genetic information.Dnmt1 encodes the maintenance enzyme DNA-methyltransferase, which is responsible for propagating the DNA methylation pattern and the epigenetic information that it encodes during replication. Direct sequence analysis and bisulfite mapping of the 5′ region of DNA-methyltransferase 1 (dnmt1) have indicated the presence of many sequence elements associated with previously characterized origins of DNA replication. This study tests the hypothesis that thednmt1 region containing these elements is an origin of replication in human cells. First, we demonstrate that a vector containing this dnmt1 sequence is able to support autonomous replication when transfected into HeLa cells. Second, using a gel retardation assay, we show that it contains a site for binding of origin-rich sequences binding activity, a recently purified replication protein. Finally, using competitive polymerase chain reaction, we show that replication initiates in this region in vivo. Based on these lines of evidence, we propose that initiation sites for DNA replication are located between the first intron and exon 7 of the human dnmt1 locus.
Reissuable Biometrics through Image-Based Handwritten Signature Verification

The privacy invasion of the biometric technology is getting public concerns due to the fact that biometric characteristics are immutable. In other words, their compromise is permanent. Reissuable biometrics was devised to make the reissuable or replaceable of biometric templates possible once they are found compromised. Biometric Strengthening is a form of reissuable biometrics. It strengthens the biometric templates by transforming the original template values to form a new set of values through the Gaussian distribution. The performance of Biometric Strengthening is evaluated in three possible intrusion scenarios. Probabilistic neural network (PNN) is employed as classifier. The compatibility of Biometric Strengthening and PNN shows the potential of using them in real world application. The experiments are tested on own image-based handwritten signature data set due to the lack of benchmark database.
Retirement Challenges and Sustainable Development in Nigeria

The aim of this paper is to give an overview of the challenges faced by retirees in Nigeria. The methodology employed by the research work is secondary data and observation. Some of the recommendations of the research work include planning for retirement, estimating your sources of income, developing friendship, establishing business in own area of specialization and so on. Keyword s : Retirement, Sustainable Development.
Discovery of a Novel Small-Molecule Inhibitor that Targets PP2A–β-Catenin Signaling and Restricts Tumor Growth and Metastasis

Molecular hybridization of different pharmacophores to tackle both tumor growth and metastasis by a single molecular entity can be very effective and unique if the hybrid product shows drug-like properties. Here, we report synthesis and discovery of a novel small-molecule inhibitor of PP2A–β-catenin signaling that limits both in vivo tumor growth and metastasis. Our molecular hybridization approach resulted in cancer cell selectivity and improved drug-like properties of the molecule. Inhibiting PP2A and β-catenin interaction by selectively engaging PR55α-binding site, our most potent small-molecule inhibitor diminished the expression of active β-catenin and its target proteins c-Myc and Cyclin D1. Furthermore, it promotes robust E-cadherin upregulation on the cell surface and increases β-catenin–E-Cadherin association, which may prevent dissemination of metastatic cells. Altogether, we report synthesis and mechanistic insight of a novel drug-like molecule to differentially target β-catenin functionality via interacting with a particular subunit of PP2A. Mol Cancer Ther; 16(9); 1791–805. ©2017 AACR.
Prospective, controlled, multi‐center study on the effect of an amino‐acid‐based formula in infants with cow's milk allergy/intolerance and atopic dermatitis

Cow's milk allergy/intolerance is treated by complete avoidance of cow's milk proteins. Because cow's milk is an important food for infants, its avoidance may lead to an increased risk of growth impairment. Whilst there is evidence for the beneficial effects of extensively hydrolyzed cow's milk formulae (eHF) in infants with cow's milk allergy/intolerance, little is known about the effects of amino‐acid‐based formulae (AA) in such infants. We therefore performed a prospective, controlled, multi‐center trial to study the efficacy of AA in comparison with eHF, on the growth and clinical symptoms of 73 infants (median age 5.7 months) with cow's milk allergy/intolerance and atopic dermatitis. Cow's milk allergy/intolerance was proven in all infants by double‐blind, placebo‐controlled food‐challenge. We observed a significant improvement in the SCORAD index in both groups, from a mean of 24.6, at entry, to a mean of 10.7 (p < 0.0001) after 6 months. In the AA group there was a significant increase in the length standard deviation score (p < 0.04), whilst there was no difference in the eHF group. The weight‐for‐length values were stable in both groups. The energy intake during the study was similar in both groups. Both an AA and eHF resulted in a significant clinical improvement in infants with an early onset of symptoms of cow's milk allergy/intolerance. Feeding an AA resulted in improved growth compared with feeding eHF, despite similar dietary intakes, and may therefore be considered as a beneficial alternative in infants with severe cow's milk allergy intolerance.
Peptidergic modulation of male sexual behavior in Lymnaea stagnalis: structural and functional characterization of –FVamide neuropeptides

In the simultaneous hermaphrodite snail Lymnaea stagnalis, copulation as a male is controlled by neurons that send axons to the male copulatory organs via a single penis nerve. Using direct mass spectrometry of a penis nerve sample, we show that one of the molecular ions has a mass corresponding to GAPRFVamide, previously identified from the buccal ganglia, and named Lymnaea inhibitory peptide (LIP). The identity of this peptide is confirmed by partial peptide purification from the penis nerve, followed by post source decay mass spectrometry. We cloned the LIP‐encoding cDNA, which predicts a prohormone that gives rise to five copies of LIP (now re‐named LIP A), two other –FVamide peptides (LIPs B and C), and five structurally unrelated peptides. The LIP gene is expressed in neurons of the right cerebral ventral lobe that send their axons into the penis nerve. We show that the LIP A peptide is present in these neurons and in the penis nerve, and confirmed the presence of LIP B and C in the penis nerve by post source decay mass spectrometry. Finally, we demonstrate that LIP A, B and C inhibit the contractions of the penis retractor muscle, thereby implicating their role in male copulation behavior.
A Framework for Understanding Practical Knowledge

This paper explains the key dimensions of practical knowledge. It is argued that practical knowledge and practice are two sides of the same phenomenon and possess objective and subjective dimensions. The development of this paper involved an in-depth review of the workplace learning, cognitive education and practice-based management literatures supported by Giddens and Habermas' insights on action. The proposed framework complements practice-oriented management research. This paper integrates parallel literatures from different theoretical backgrounds in order to explain the main dimensions of practical knowledge. It is argued that PK is constituted by a knowledge dimension and a practice dimension, each of which can, in turn, have explicit and tacit features. By taking a dynamic perspective, this paper suggests an ever-evolving composition of practice and PK, in which explicit and tacit procedural knowledge, together with varied forms of explicit and tacit practice, acquire different configurations depending on embodied capacities, such as skills, tacit understandings, dispositions and the specific space-time and resource limitations. The proposed framework might assist in the task of selecting appropriated learning mechanism for different types of practices, since it recognises different configurations of practice and their associated PK.
Trends in the design of RFID tags

This communication is mainly dedicated to the design of RFID tags, in particular the antennas that allow the tag to be fed, communicate and exchange data with the reader. Good performance tags require optimized antenna that take into account numerous constraints as well as the environment of the application under consideration. Conventional tags based on IC chips as well as chipless or RF barccode are discussed. The last part of the communication will consider how to transform a tag into an RFID sensor thanks to a specific modification and accurate design of the tag antenna.
Multi-Axis Sinusoidal Whole-Body Vibrations: Part I — How Long Should the Vibration and Rest Exposures Be for Reliable Discomfort Measures?

Laboratory-based whole-body vibration studies often involve complex experimental designs, dozens of vibration exposures and multiple sessions. Shortening the test vibration duration would increase experimental efficiency by permitting more trials in the same time period. This study evaluated reported discomfort based on different sinusoidal vibration durations and amounts of rest between successive vibrations. Ten subjects were exposed to four blocks of vibration trials (15/20 second vibration and 5/10 second rest durations). Each block of 37 trials included repeated single axis, planar, and 6 degree of freedom multi-axial vibrations. These repeated trials were analysed to evaluate whether discomfort varied between the different blocks. We did not observe any statistically significant differences in discomfort between the different vibration and rest durations. This finding is useful for designing future vibration experiments. Part II of this study evaluates the relationship between discomfort and vibration exposure.
Automatic Design of Hybrid Metaheuristics from Algorithmic Components

Metaheuristic algorithms are traditionally designed following a manual, iterative algorithm development process. While this process sometimes leads to high performing algorithms, it is labor-intensive, error-prone, difficult to reproduce, and explores only a limited number of design alternatives. In this article, we advocate the automatic design of hybrid metaheuristic algorithms. For an effective design process, we propose as main ingredients a unified view on metaheuristic algorithms, an effective implementation of the metaheuristic components but also of problem-specific algorithm components inside a flexible algorithm framework, and the exploitation of automated algorithm configuration techniques. With these ingredients we show that, for various, rather different combinatorial optimization problems, we can automatically generate high-performance metaheuristic algorithms that reach and in various cases surpass the performance of current state-of-the-art algorithms for the respective problems. Our results also indicate that a paradigm shift in how effective metaheuristic algorithms are designed is possible, which has significant advantages such as reproducibility, unification of existing approaches, and reduction in the development time of high-performing algorithms.
DNA adduct formation in primary mouse embryo cells induced by 7H‐dibenzo[c,g]carbazole and its organ‐specific carcinogenic derivatives

The nuclease P1 modification of the 32P‐postlabeling technique was used to study the biological activity of 7H‐dibenzo[c,g]carbazole (DBC) and some of its derivatives, including N‐methyldibenzo[c,g]carbazole (N‐MeDBC), 5,9‐dimethyldibenzo[c,g]carbazole (5,9‐diMeDBC), 5,9, N‐trimethyldibenzo[c,g] carbazole (5, 9, N‐triMeDBC), 6‐methoxydibenzo[c, g]carbazole (6‐McODBC), N‐acetyldibenzo[c,g]carbazole (N‐AcDBC), N‐hydroxymethyldibenzo[c,g]carbazole (N‐HMeDBC) in primary mouse embryo cells. A very good correlation was found between carcinogenic specificity in vivo of these N‐heterocyclic aromatic hydrocarbons and their DNA‐adduction in vitro. Primary mouse embryo cells were able to metabolize and detect tissue‐specific sarcomagens N‐MeDBC and 6‐MeODBC as well as derivatives with both sarcomagenic and hepatocarcinogenic activity, DBC, N‐AcDBC, and N‐HMeDBC. The strong specific hepatocarcinogen 5,9‐diMeDBC in vivo, did not induce any DNA‐adducts in the embryo cells, which suggests that the enzymatic composition of the target tissue probobly is the determining factor in the organ specificity of this derivative. 5,9,N‐triMeDBC, derivative without any carcinogenic activity in vivo, did not induce any DNA‐adducts in primary mouse embryo cells. Pretreatment of cells with 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD) apparently stimulated DNA‐adduct formation in the cells exposed to DBC, 6‐MeODBC, and N‐MeDBC. No or a very slight effect of TCDD on DNA‐adduct formation was found in cells exposed to N‐HMeDBC and N‐AcDBC. Preliminary results have shown that TCDD slightly induced cytochrome P4501A1 linked ethoxyresorufin O‐deethylase (EROD) activity in primary mouse embryo cells. These data suggest the role of cytochrome P4501A1 in the metabolism of DBC derivatives with sarcomagenic activity. Environ. Mal. Mutagen. 30:56–64, 1997 © 1997 Wiley‐Liss, Inc.
Genome-Wide Analysis of Pancreatic Cancer Using Microarray-Based Techniques

Background/Aims: Microarray-based comparative genomic hybridisation (CGH) has allowed high-resolution analysis of DNA copy number alterations across the entire cancer genome. Recent advances in bioinformatics tools enable us to perform a robust and highly sensitive analysis of array CGH data and facilitate the discovery of novel cancer-related genes. Methods: We analysed a total of 29 pancreatic ductal adenocarcinoma (PDAC) samples (6 cell lines and 23 microdissected tissue specimens) using 1-Mb-spaced CGH arrays. The transcript levels of all genes within the identified regions of genetic alterations were then screened using our Pancreatic Expression Database. Results: In addition to 238 high-level amplifications and 35 homozygous deletions, we identified 315 minimal common regions of ‘non-random’ genetic alterations (115 gains and 200 losses) which were consistently observed across our tumour samples. The small size of these aberrations (median size of 880 kb) contributed to the reduced number of candidate genes included (on average 12 Ensembl-annotated genes). The database has further specified the genes whose expression levels are consistent with their copy number status. Such genes were UQCRB, SQLE, DDEF1, SLA, ERICH1 and DLC1, indicating that these may be potential target candidates within regions of aberrations. Conclusion: This study has revealed multiple novel regions that may indicate the locations of oncogenes or tumour suppressor genes in PDAC. Using the database, we provide a list of novel target genes whose altered DNA copy numbers could lead to significant changes in transcript levels in PDAC.
Internet addiction as a manageable resource: a focus on social network services

Purpose – The purpose of this paper is to reinterpret addiction to social network services (SNSs), not from the traditional clinical perspective as a disorder, but from a management perspective as consumer behaviour to examine its possibility as a manageable resource.Design/methodology/approach – A survey was conducted on heavy users of SNSs. Based on the data the authors performed an exploratory factor analysis to define SNS addiction and to construct its dimensions.Findings – The authors termed SNS addiction as an “addictive consumption trait” (ACT) of SNS and its underlying dimensions are salience, euphoria, immersion, compulsion, and association.Research limitations/implications – The authors used SNS user behaviour as the sample for their empirical analysis. However there is a variety of other internet services available and different internet services may show different consumer behaviour. Therefore, for future research, the authors suggest conducting a comparative study on the influence of addictio.
University ’ s repository of research publications and other research outputs Self-Directed Learning in Trial FutureLearn courses Conference or Workshop Item

Self-Directed Learning (SDL) in Massive Open Online Courses (MOOC) is gaining interest, as online learning is increasingly learner-centred and autonomous. Most SDL research starts from the premise that SDL happens more frequently in connectivism MOOC (cMOOC) than in the more instructor-led MOOCs. In this study the authors look at SDL experiences from learners enrolled in two MOOC courses during the early trials of the FutureLearn platform. The meaning and experiences of the phenomenon of being enrolled as a learner in FutureLearn was gathered through various research instruments (online survey, learning logs, one-on-one interviews). The resulting data was collected pre-, during, and postcourse. The key categories for each sub-question of the research are shared in the results and analysis section. This study concluded that SDL is indeed taking place in FutureLearn courses, which points towards SDL happening beyond the connectivist MOOCs.
Event category learning

This research investigated the learning of event categories, in particular, categories of simple animated events, each involving a causal interaction between 2 characters. Four experiments examined whether correlations among attributes of events are easier to learn when they form part of a rich correlational structure than when they are independent of other correlations. Event attributes (e.g., state change, path of motion) were chosen to reflect distinctions made by verbs. Participants were presented with an unsupervised learning task and were then tested on whether the organization of correlations affected learning. Correlations forming part of a system of correlations were found to be better learned than isolated correlations. This finding of facilitation from correlational structure is explained in terms of a model that generates internal feedback to adjust the salience of attributes. These experiments also provide evidence regarding the role of object information in events, suggesting that this role is mediated by object category representations.
The Microstructure of the UK Gilt Market

This paper is a detailed study of trading patterns in the gilt market - based on all transactions in three gilts (6% Treasury 1999, 9 1/2% Treasury 2005, and 2 1/2% Index-linked 2016) from October 1993 to October 1994. The main finding of the paper is that order flow in the gilt market does not appear to have any significant effect on prices, market makers seem to use other information (such as public announcements and the price of the long gilt future) to set prices. The paper also finds that spreads are far narrower in the gilt market than in the equity market and that there is some tendency for spreads to fall with trade size (rather than rise as is found in the equity markets). Both these findings are consistent with a lack of information in order flow (since market makers are unlikely to lose money to more informed traders in the gilt market and so can offer better prices). Other findings include a tendency for turnover to be highest on Wednesdays and for intra-day turnover to show a 'U'-shaped pattern with trading concentrated in the early morning and late afternoon. It also finds a tendency for spreads to be wider when turnover is high.
Integrating Image-Based High-Content Screening with Mouse Models Identifies 5-Hydroxydecanoate as a Neuroprotective Drug for Paclitaxel-Induced Neuropathy

Chemotherapy-induced neurotoxicity is a common adverse effect of cancer treatment. No medication has been shown to be effective in the prevention or treatment of chemotherapy-induced neurotoxicity. This study aimed to discover potential neuroprotective drugs for paclitaxel-induced neurotoxicity. An image-based high-content platform was first developed to screen for potential neuroprotective drugs. The screening system comprised of automated image acquisition and multiparameter analysis, including neuronal viability, neurite outgrowth, and synaptogenesis. By this platform, we obtained a candidate list from compound libraries. In the drug screening from compound libraries of ion channel ligands, REDOX and GABAergic ligands, 5-hydroxydecanoate (5-HD) exhibited the most significant neuroprotective effects against paclitaxel-induced neurotoxicity in both cortical and dorsal root ganglion (DRG) neurons. In mouse behavioral tests, 5-HD restored the thermal sensitivity and alleviated mechanical allodynia induced by paclitaxel. Electron micrographs of sciatic nerve revealed that 5-HD reduced the damages caused by paclitaxel in the nonmyelinated and smaller myelinated fibers. The mechanistic study on DRG neurons suggested that 5-HD rescued the dysregulation of intracellular calcium homeostasis provoked by paclitaxel. Importantly, 5-HD did not jeopardize the antitumor effect of paclitaxel in tumor xenograft models. In conclusion, we established an imaged-based high-content screening platform and a protocol for verifying the neuroprotective effect in vivo, by which 5-HD was identified and validated as a potential neuroprotective drug for paclitaxel-induced neuropathy. Mol Cancer Ther; 14(10); 2206–14. ©2015 AACR.
Non-residents' attitudes towards heritage: exploring tourist typologies by cultural consumption.

SAŽETAK: Koristeći multidimenzionalnu analizu, ova studija istražuje ponašanje turista na povijesnim lokalitetima u regiji Campania. Kao rezultat klaster analize identifi cirane su četiri skupine nerezidentnih kulturnih posjetitelja. Analiza potvrđuje da proces odabira povijesnog lokaliteta varira ovisno o karakteristikama posjetitelja – ne samo socio-demografskim, već i onim vezanim uz prethodna turistička iskustva. Usmjeravajući se na dva klastera – „upoznate“ i „usko segmentirane“ turiste – predlažu se moguće ekonomske interpretacije različitih modela ponašanja u procesu konzumacije nasljeđa. Zaključci sugeriraju da su akumulirano znanje i emocionalna povezanost s lokalitetom, kao dio šireg više nego lokalnog nasljeđa, ključne varijable kod donošenja odluka turista te da se potražnja ne može jednostavno stimulirati mjerama ponude.
Policy and Service Satisfaction Survey

The Policy and Service Satisfaction Survey (PSSS) investigates public knowledge and perceptions of the Government of Tanzania’s Poverty Reduction Strategy (PRS) and other policy initiatives. PSSS also documents people’s views on the availability, quality and cost of basic social and economic services under PRS. PSSS surveyed 3,002 households in seven Tanzanian mainland regions. In total, 665 households were sampled in Dar es Salaam urban wards, 467 in urban wards in the other six regions, and 1,870 households in rural wards. The survey took place in August-September 2003. Regions were sampled using the poverty profiles from the Poverty and Human Development Report 2002. Dar es Salaam, Kilimanjaro and Mbeya Regions were chosen from the top of the rankings, Singida and Mara from the middle, and Rukwa and Lindi from the bottom. This report summarises the main PSSS results from the household survey and focus groups held in these research sites. The information presented is disaggregated by locality - Dar es Salaam, other towns and rural areas – and by the sex of head of household. The report is descriptive. Further analysis will try to explain the perceptions and opinions of respondents on the basis of the distribution of welfare and poverty levels between households.