Chemical and physiological aspects of isomers of conjugated fatty acids

Conjugated fatty acid (CFA) is the general term to describe the positional and geometric isomers of polyunsaturated fatty acids with conjugated double bonds. The CFAs of linoleic acid (CLAs) are found naturally in foods derived from ruminant animals, meat, or dairy products. The CFAs of α-linolenic acid (CLNAs) are found exclusively in various types of seed oils of plants. There are many investigations to assess the effects to health from CFAs consumption, which have been associated with physiological processes that are involved with non transmissible chronic diseases such as cancer, atherosclerosis, inflammation, and obesity. Conclusive studies about the CFAs effects in the body are still scarce and further research about their participation in physiological processes are necessary. This review aimed to discuss the influence of conjugated fatty acids on physiological processes in animal organism.

Purple urine bag syndrome in end-stage chronic kidney disease

Introduction: When faced with violet, purple or purplish-blue urine, clinicians should consider urinary tract infection in their differential diagnosis. Case report: A 60-year-old woman with end-stage kidney disease and non-adherence to renal replacement therapy was admitted to our hospital for placement of hemodialysis catheter. During her hospitalization she had purple urine, and purple urine bag syndrome (PUBS) was diagnosed. She was effectively treated with antibiotics and her urine returned to a dark yellow color. Discussion: Although this condition is often easily treated, diagnosing PUBS in chronic renal patients probably means an increased serum concentration of indoxyl sulfate, metabolite that is involved in the progression of both CKD and cardiovascular disease. Conclusion: Hence, in the context of our renal patients, perhaps PUBS is not as benign as supposed.

Biomarkers, medical treatment and fetal intrapartum surveillance in intrahepatic cholestasis of pregnancy

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific disorder characterized by maternal pruritus and elevated liver enzymes. It usually begins in the third trimester of pregnancy and resolves spontaneously after delivery. ICP is considered benign for the pregnant woman, but it is associated with an increased risk for unexplained term stillbirth and preterm delivery. There are no specific laboratory markers to diagnose ICP. The diagnosis is currently based on the presence of maternal pruritus and elevated values of alanine aminotransaminases (ALT) and serum bile acids (BA). Recently, ursodeoxycholic acid (UDCA) has been used for treatment. Mechanisms leading to intrauterine fetal death (IUFD) may be multifactorial and are unknown at present. For this thesis, 415 pregnant women with ICP were studied. The aim was to evaluate the value of the liver enzyme glutathione S-transferase alpha (GSTA) as a specific marker of ICP and to assess the effect of maternal UDCA therapy on maternal laboratory values and fetal outcome. The specific markers predisposing the fetus to heart arrhythmia were studied by comparing waveform analysis of fetal electrocardiograms (FECG) during labor in pregnancies complicated by ICP with controls. The levels of maternal GSTA were high and the values correlated with the value of ALT in patients with ICP. UDCA therapy reduced the values of the liver enzymes and alleviated maternal pruritus, but it did not influence maternal hormonal values. Although the newborns experienced an uneventful perinatal outcome, severe ICP was still associated with preterm birth and admission to the neonatal intensive care unit (NICU). There were no significant differences in intrapartum FECG findings between fetuses born to ICP women and controls.

Escravidão "suave" no Brasil: Gilberto Freyre tinha razão?

This article examines the question of the supposedly benign character of Brazilian slavery in contrast with North America slavery. In economic analyses of slavery, coercion toward slaves is viewed as a means to achieve maximum output, especially in large-scale agriculture. In small slave holdings, however, coercion was generally inefficient for that purpose, and positive incentives tended to be preferred. It is argued that, as recent evidence on Brazil has shown that small slave holdings prevailed in various regions and periods, this may lend empirical support to the notion of a relatively benign slavery, using more incentives than coercion.

Evaluation of Machine Learning Classifiers for Mobile Network Intrusion Detection Systems

Mobile malwares are increasing with the growing number of Mobile users. Mobile malwares can perform several operations which lead to cybersecurity threats such as, stealing financial or personal information, installing malicious applications, sending premium SMS, creating backdoors, keylogging and crypto-ransomware attacks. Knowing the fact that there are many illegitimate Applications available on the App stores, most of the mobile users remain careless about the security of their Mobile devices and become the potential victim of these threats. Previous studies have shown that not every antivirus is capable of detecting all the threats; due to the fact that Mobile malwares use advance techniques to avoid detection. A Network-based IDS at the operator side will bring an extra layer of security to the subscribers and can detect many advanced threats by analyzing their traffic patterns. Machine Learning(ML) will provide the ability to these systems to detect unknown threats for which signatures are not yet known. This research is focused on the evaluation of Machine Learning classifiers in Network-based Intrusion detection systems for Mobile Networks. In this study, different techniques of Network-based intrusion detection with their advantages, disadvantages and state of the art in Hybrid solutions are discussed. Finally, a ML based NIDS is proposed which will work as a subsystem, to Network-based IDS deployed by Mobile Operators, that can help in detecting unknown threats and reducing false positives. In this research, several ML classifiers were implemented and evaluated. This study is focused on Android-based malwares, as Android is the most popular OS among users, hence most targeted by cyber criminals. Supervised ML algorithms based classifiers were built using the dataset which contained the labeled instances of relevant features. These features were extracted from the traffic generated by samples of several malware families and benign applications. These classifiers were able to detect malicious traffic patterns with the TPR upto 99.6% during Cross-validation test. Also, several experiments were conducted to detect unknown malware traffic and to detect false positives. These classifiers were able to detect unknown threats with the Accuracy of 97.5%. These classifiers could be integrated with current NIDS', which use signatures, statistical or knowledge-based techniques to detect malicious traffic. Technique to integrate the output from ML classifier with traditional NIDS is discussed and proposed for future work.

Kokoeksomisekvenointi varhaislapsuuden selvittämättömissä kuolemantapauksissa

Suomessa esiintyy vuosittain 8-15 selittämätöntä alle yhden vuoden ikäisen lapsen äkkikuolemaa ja noin viidesosa kohdunsisäisten kuolemien syistä jää arvoitukseksi. Arvellaan, että näiden kuolemantapausten taustalla on harvinaisia geneettisiä sairauksia. Tässä työssä tutkittiin Turun Yliopistollisen Keskussairaalan varhaislapsuuden ja loppuraskauden lasten ja sikiöiden kuolemantapauksia vuosilta 2000-2012 niistä potilaista, joista ruumiinavaus lisätutkimuksineen ei ollut paljastanut kuolinsyytä. Tarkempaan tutkimukseen valikoitui neljä potilasta, joista eristettiin DNA:ta kokoeksomisekvenointia varten. Tuloksia verrattiin perimän normaalivaihteluun ja poikkeavat löydökset, joilla voisi olla merkitystä potilaiden kuoleman kannalta, määritettiin. Kolmesta eri potilaasta löydettiin alustavasti merkittäväksi tulkittavat geenivirheet. Potilaalla 1 oli kromosomi 6q24-q25 alueen deleetio, jossa sydämen kehityksen kannalta olennaisen TAB2-geenin toiminta häiriintyy ja potilaille kehittyy vakava synnynäinen sydänvika. Potilaalla 2 oli yhden emäksen mutaatio CPT1A-geenissä, joka aiheuttaa CPT1A-proteiinin puutoksen. CPT1A osallistuu mitokondrioiden kalvoilla pitkäketjuisten rasvahappojen kuljetukseen ja häiriöt sen toiminnassa aiheuttavat merkittäviä energiatasapainon häiriöitä. CPT1A-puutoksen on kuvattu aiheuttavan äkkikuolemia varhaislapsuudesta aikuisuuteen. Potilaalla 3 oli DPP6-geenin yhden emäksen mutaatio. TAB2-geenin häiriö on todennäköisesti ollut merkittävänä tekijänä aiheuttamassa potilaan 1 kliiniset löydökset ja voinut myötävaikuttaa kuolemaan. Myös CPT1A-puutos on mahdollisesti vaikuttanut potilaan 2 kuolemaan. DPP6-geenivirheen ajateltiin aiheuttavan ajoittaista kammiovärinää (paroxysmal ventricular fibrillation type 2), mutta myöhemmin uusissa tutkimuksissa kävi ilmi, että mutaatio ei ole patogeeninen. Vaikka kokoeksomisekvenointimenetelmässä on vielä merkittäviä puutoksia kuolinsyytutkimukseen sovellettaessa ja se soveltuu paremmin tutkimuskäyttöön kuin kliiniseen työhön, se avaa kokonaan uusia mahdollisuuksia aiemmin tuntemattomien lapsen kuolemaan johtavien sairauksien diagnostiikassa.

Evaluation of a stage II screening protocol for prostate cancer

In 2003, prostate cancer (PCa) is estimated to be the most commonly diagnosed cancer and third leading cause of cancer death in Canada. During PCa population screening, approximately 25% of patients with a normal digital rectal examination (DRE) and intermediate serum prostate specific antigen (PSA) level have PCa. Since all patients typically undergo biopsy, it is expected that approximately 75% of these procedures are unnecessary. The purpose of this study was to compare the degree of efficacy of clinical tests and algorithms in stage II screening for PCa while preventing unnecessary biopsies from occurring. The sample consisted of 201 consecutive men who were suspected of PCa based on the results of a DRE and serum PSA. These men were referred for venipuncture and transrectal ultrasound (TRUS). Clinical tests included TRUS, agespecific reference range PSA (Age-PSA), prostate specific antigen density (PSAD), and free-to-total prostate specific antigen ratio (%fPSA). Clinical results were evaluated individually and within algorithms. Cutoffs of 0.12 and 0.15 ng/ml/cc were employed for PSAD. Cutoffs that would provide a minimum sensitivity of 0.90 and 0.95, respectively were utilized for %fPSA. Statistical analysis included ROC curve analysis, calculated sensitivity (Sens), specificity (Spec), and positive likelihood ratio (LR), with corresponding confidence intervals (Cl). The %fPSA, at a 23% cutoff ({ Sens=0.92; CI, 0.06}, {Spec=0.4l; CI, 0.09}, {LR=1.56; CI, O.ll}), proved to be the most efficacious independent clinical test. The combination of PSAD (cutoff 0.15 ng/ml/cc) and %fPSA (cutoff 23%) ({Sens=0.93; CI, 0.06}, {Spec=0.38; CI, 0.08}, {LR=1.50; CI, 0.10}) was the most efficacious clinical algorithm. This study advocates the use of %fPSA at a cutoff of 23% when screening patients with an intermediate serum PSA and benign DRE.

Interactions of diploid embryonal carcinoma cells and normal cell mass cells with 2.5 day mouse embryos following aggregation

Spontaneous teratocarcinomas are ovarian or testicular tumors which have their origins in germ cells. The tumors contain a disorganized array of benign differentiated cells as well as an undifferentiated population of malignant stem cells, the embryonal carcinoma or EC cells. These pluripotent stem cells in tissue culture share many properties with the transient pluripotent cells of the early embryo, and might therefore serve as models for the investigation of developmental events ill vitro. The property of EC cells of prime interest in this study is an in vivo phenomenon. Certain EC cell lines are known to be regulated ill vivo and to differentiate normally in association with normal embryonic cells, resulting in chimeric mice. These mice have two genetically distinct cell populations, one of which is derived from the originally malignant EC cells. This has usually been accomplished by injection of the EC cells into the Day 3 blastocyst. In this study, the interactions between earlier stage embryos and EC cells have been tested by aggregating clumps of EC cells with Day 2 embryos. The few previous aggregation studies produced a high degree of abnormality in chimeric embryos, but the EC cells employed had known chromosomal abnormalities. In this study, two diploid EC cell lines (P19 and Pi0) were aggregated with 2.5 day mouse embryos, and were found to behave quite differently in the embryonic environment. P19 containing aggregates generally resorbed early, and the few embryos recovered at midgestation were normal and non-chimeric. Pi0 containing aggregates survived in high numbers to midgestation, and the Pi0 cells were very successful in colonizing the embryo. All these embryos were chimeric, and the contribution by the EC cells to each chimera was very high. However, these heavily chimeric embryos were all abnormal. Blastocyst injection had previously produced some abnormal embryos with high Pl0 contributions in addition to the live born mice, which had lower EC contributions. This study now adds more support to the hypothesis that high EC contributions may be incompatible with normal development. The possibility that the abnormalities were due to the mixing of temporally asynchronous embryonic cell types in the aggregates was tested by aggregating normal pluripotent cells taken from 3.5 day embryos with 2.5 day embryos. Early embryo loss was very high, and histological studies showed that the majority of these embryos died by 6.5 days development. Some embryos escaped this early death such that some healthy chimeras were recovered, in contrast to recovery of abnormal chimeric embryos following Pl0-morula aggregations, and non-chimeric embryos following P19-morula aggregations. This somewhat surprising adverse effect on development following aggregation of normal cell types suggests that there are developmental difficulties associated with the mixing of asynchronous cell types in aggregates. However, the greater magnitude of the adverse effects when the aggregates contained tumor derived cells suggests that EC cells should not be considered the complete equivalent of the pluripotent cells of the early embryo.

The crystal and molecular structure of thiamine hydroiodide /|nWilliam Edward Lee. -- 260 St. Catharines [Ont.] : Dept. of Chemistry, Brock University,

The x-ray crystal structure of thiamine hydroiodide,C1ZH18N40S12' has been determined. The unit cell parameters are a = 13.84 ± 0.03, o b = 7.44 ± 0.01, c = 20.24 ± 0.02 A, 8 = 120.52 ± 0.07°, space group P2/c, z = 4. A total of 1445 reflections having ,2 > 2o(F2), 26 < 40° were collected on a Picker four-circle diffractometer with MoKa radiation by the 26 scan technique. The structure was solved by the heavy atom method. The iodine and sulphur atoms were refined anisotropically; only the positional parameters were refined for the hydrogen atoms. Successive least squares cycles yielded an unweighted R factor of 0.054. The site of protonation of the pyrimidine ring is the nitrogen opposite the amino group. The overall structure conforms very closely to the structures of other related thiamine compounds. The bonding surrounding the iodine atoms is distorted tetrahedral. The iodine atoms make several contacts with surrounding atoms most of them at or near the van der Waal's distances A thiaminium tetrachlorocobaltate salt was produced whose molecular and crystal structure was j~dged to be isomorphous to thiaminium tetrachlorocadmate.

Transfection of newt blastema mesenchyme using the techniques of lipofection and direct gene transfer

The regenerating amphibian limb provides a useful system for studying genes involved in the establishment of positional information. While a number of candidate genes that may playa role in pattern formation have been identified, their function in vivo is unknown in this system. To better ascertain the role of these genes, it would be useful to be able to alter their normal patterns of expression in vivo and to assess the effects of this misexpression on limb pattern. In order to achieve this, a method of introducing a plasmid containing the eDNA of a gene of interest into a newt blastema (a growth zone of mesenchymal progenitor cells) is needed. Unfortunately, most commonly used transfection techniques cannot be used with newt blastema cells. In this study, I have used the techniques of lipofection and direct gene transfer to introduce plasmid DNA containing reporter genes into the cells of a regenerating newt limb. The technique of lipofection was most effective when the blastema cells were transfected in vitro. The optimal ratio for transfection was shown to be 1:3 DNA:Lipofectin (W/w) , and an increase in the amount of DNA present in the mixture (1:3 ratio maintained) resulted in a corresponding increase in gene expression. The technique of direct gene transfer was used to transfect newt blastema cells with and without prior complex formation with Lipofectin. Injection of plasmid DNA alone provided the most 3 promising results. It was possible to introduce plasmid DNA containing the reporter gene ~-galactosidase and achieve significant gene expression in cells associated with the injection site. In the future, it would be interesting to use this technique to inject plasmid DNA containing a gene which may have a role in pattern formation into specific areas of the newt blastema and to analyze the resulting limb pattern that emerges.

"The whole earth as village" : a chronotopic analysis of Marshall McLuhan's "Global Village" and Patrick McGoohan's The Prisoner

Marshall McLuhan's "global village", and his theories on communications and technology, in conjunction with Patrick McGoohan's television series The Prisoner (ATV, 1967-1968) are explored in this thesis. The Prisoner, brainchild of McGoohan, is about the abduction and confinement of a British government agent imprisoned within the impenetrable boundaries of a benign but totalitarian city -state called "The Village". The purpose of his abduction and imprisonment is for the extraction of information regarding his resignation as a government spy. Marshall McLuhan originally popularized the phrase "the global village" in The Gutenberg Galaxy: The Making o/the Topographic Man (1962), asserting that, "The new electronic interdependence recreates the world in the image of a global village" (p. 31). This thesis argues that valid parallels exist between McGoohan's conception of "village", as manifested in The Prisoner, and McLuhan's global village. The comprehensive methodological stratagem for this thesis includes Marshall McLuhan's "mosaic" approach, Mikhail Bakhtin's concept ofthe "chronotope", as well as a Foucauldian genealogicallhistorical discourse analysis. In the process of deconstructing McLuhan's texts and The Prisoner as products of the 1960s, an historical "constellation" (to use Walter Benjamin's concept) of the same present has been executed. By employing this synthesized methodology, conjunctions have been made between McLuhan's theories and the series' main themes of bureaucracy as dictatorship, the perversion of science and technology, freedom as illusion, and the individual in opposition to the collective. A thorough investigation of the global village and The Prisoner will determine whether or not Marshall McLuhan and/or Patrick McGoohan visualize the village as an enslaving technological reality.

A Foucauldian Analysis of Power and Representation in an Attempt to Run a Photovoice Project with Youth

This project evolved out of a search for ways to conduct research on “others” in a way that does not exploit, stigmatize or misrepresent their experience. This thesis is an ethnographic study in leisure research and youth work and an experiment in running a photovoice project. Photovoice is a participatory visual method that embodies the emancipatory ideal of empowering others through self-representation. The literature on photovoice lacks a comprehensive discussion on the complexity of power and representation. Postmodern theorists have proposed that participatory methods are not benign and that initiatives are acts of power in themselves that produce effects (Cook & Kothari, 2001). A Foucauldian analysis of power is used to deconstruct the researcher’s practice and reflect on why and how youth are “engaged”. This project seeks to embrace the principle of working “with” others, but also work from a postmodern perspective that acknowledges power and representation as ongoing problems.

A Shift in Role: The Perspectives of Ontario Secondary Principals Working in Data-Driven Environments

This study occurred in 2009 and questioned how Ontario secondary school principals perceived their role had changed, over a 7 year period, in response to the increased demands of data-driven school environments. Specifically, it sought to identify principals' perceptions on how high-stakes testing and data-driven environments had affected their role, tasks, and accountability responsibilities. This study contextualized the emergence of the Education Quality and Accountability Offices (EQAO) as a central influence in the creation of data-driven school environments, and conceptualized the role of the principal as using data to inform and persuade a shift in thinking about the use of data to improve instruction and student achievement. The findings of the study suggest that data-driven environments had helped principals reclaim their positional power as instructional leaders, using data as an avenue back into the classroom. The use of data shifted the responsibilities of the principal to persuade teachers to work collaboratively to improve classroom instruction in order to demonstrate accountability.

Prostate Cancer and the Search for Novel Biomarkers

The primary objective of this research project was to identify prostate cancer (PCa) -specific biomarkers from urine. This was done using a multi-faceted approach that targeted (1) the genome (DNA); (2) the transcriptome (mRNA and miRNA); and (3) the proteome. Toward this end, urine samples were collected from ten healthy individuals, eight men with PCa and twelve men with enlarged, non-cancerous prostates or with Benign Prostatic Hyperplasia (BPH). Urine samples were also collected from the same patients (PCa and BPH) as part of a two-year follow-up. Initially urinary nucleic acids and proteins were assessed both qualitatively and quantitatively for characteristics either unique or common among the groups. Subsequently macromolecules were pooled within each group and assessed for either protein composition via LC-MS/MS or microRNA (miRNA) expression by microarray. A number of potential candidates including miRNAs were identified as being deregulated in either pooled PCa or BPH with respect to the healthy control group. Candidate biomarkers were then assessed among individual samples to validate their utility in diagnosing PCa and/or differentiating PCa from BPH. A number of potential targets including deregulation of miRNAs 1825 and 484, and mRNAs for Fibronectin and Tumor Protein 53 Inducible Nuclear Protein 2 (TP53INP2) appeared to be indicative of PCa. Furthermore, deregulation of miR-498 appeared to be indicative of BPH. The sensitivities and specificities associated with using deregulation in many of these targets to subsequently predict PCa or BPH were also determined. This research project has identified a number of potential targets, detectable in urine, which merit further investigation towards the accurate identification of PCa and its discrimination from BPH. The significance of this work is amplified by the non-invasive nature of the sample source from which these candidates were derived, urine. Many cancer biomarker discovery studies have tended to focus primarily on blood (plasma or serum) and/or tissue samples. This is one of the first PCa biomarker studies to focus exclusively on urine as a sample source.

HUMAN GENOME VARIATIONS AND EVOLUTION WITH A FOCUS ON THE ANALYSIS OF TRANSPOSABLE ELEMENTS

Genome sequence varies in numerous ways among individuals although the gross architecture is fixed for all humans. Retrotransposons create one of the most abundant structural variants in the human genome and are divided in many families, with certain members in some families, e.g., L1, Alu, SVA, and HERV-K, remaining active for transposition. Along with other types of genomic variants, retrotransponson-derived variants contribute to the whole spectrum of genome variants in humans. With the advancement of sequencing techniques, many human genomes are being sequenced at the individual level, fueling the comparative research on these variants among individuals. In this thesis, the evolution and functional impact of structural variations is examined primarily focusing on retrotransposons in the context of human evolution. The thesis comprises of three different studies on the topics that are presented in three data chapters. First, the recent evolution of all human specific AluYb members, representing the second most active subfamily of Alus, was tracked to identify their source/master copy using a novel approach. All human-specific AluYb elements from the reference genome were extracted, aligned with one another to construct clusters of similar copies and each cluster was analyzed to generate the evolutionary relationship between the members of the cluster. The approach resulted in identification of one major driver copy of all human specific Yb8 and the source copy of the Yb9 lineage. Three new subfamilies within the AluYb family – Yb8a1, Yb10 and Yb11 were also identified, with Yb11 being the youngest and most polymorphic. Second, an attempt to construct a relation between transposable elements (TEs) and tandem repeats (TRs) was made at a genome-wide scale for the first time. Upon sequence comparison, positional cross-checking and other relevant analyses, it was observed that over 20% of all TRs are derived from TEs. This result established the first connection between these two types of repetitive elements, and extends our appreciation for the impact of TEs on genomes. Furthermore, only 6% of these TE-derived TRs follow the already postulated initiation and expansion mechanisms, suggesting that the others are likely to follow a yet-unidentified mechanism. Third, by taking a combination of multiple computational approaches involving all types of genetic variations published so far including transposable elements, the first whole genome sequence of the most recent common ancestor of all modern human populations that diverged into different populations around 125,000-100,000 years ago was constructed. The study shows that the current reference genome sequence is 8.89 million base pairs larger than our common ancestor’s genome, contributed by a whole spectrum of genetic mechanisms. The use of this ancestral reference genome to facilitate the analysis of personal genomes was demonstrated using an example genome and more insightful recent evolutionary analyses involving the Neanderthal genome. The three data chapters presented in this thesis conclude that the tandem repeats and transposable elements are not two entirely distinctly isolated elements as over 20% TRs are actually derived from TEs. Certain subfamilies of TEs themselves are still evolving with the generation of newer subfamilies. The evolutionary analyses of all TEs along with other genomic variants helped to construct the genome sequence of the most recent common ancestor to all modern human populations which provides a better alternative to human reference genome and can be a useful resource for the study of personal genomics, population genetics, human and primate evolution.