Ph. D., Faculty of Health Sciences, University of the Witwatersrand, 2008. / The human chromosome complement contains nonrandom genomic regions that are prone to breaks and recurrently altered in tumors. These chromosomal “hot spots” are preferentially involved in early events of genomic instability and point to genes in their vicinity that may participate to carcinogenesis. Amplicons and deletions are frequently generated at “hot spots”, including common fragile sites (CFS), and are thought to host cancer genes whose rearrangements drive cell proliferation and promote the initiation and progression of cancer. Chromosomal “hot spots” in South African cancer patients, were investigated in this study with a view to characterizing underlying gene alterations. A chromosome 12p amplicon was mapped and array comparative genomic hybridization (aCGH) was pioneered to identify candidate genes in the amplicon. Genes of the 12p stem cell gene cluster (NANOG, STELLAR and GDF3) were involved in striking similarity to what has been reported in testicular germ cell tumors and suggest that they may be more commonly involved in different types of cancer. Two tumor suppressor genes, FHIT and WWOX, are located at the two most commonly expressed fragile sites, FRA3B and FRA16D respectively. Alterations in these fragile site associated genes have been reported in a variety of tumors including lung, esophageal, gastric, breast and cervical cancers most frequently as a result of submicroscopic deletions. Genomic deletions at CFS have been mostly investigated using loss of heterozygosity assays that do not necessarily inform on gene exon deletions. A new method was developed based on multiplex ligation-dependent probe amplification (MLPA) that screens for exon deletions/amplifications of genes at CFS. The assay was validated on five esophageal squamous carcinoma cell lines and showed deletions in the FRA3B-associated gene FHIT in four of the cell lines. Two geographically distinct South African cohorts of esophageal squamous cell carcinoma were then screened for FHIT/WWOX exon deletions and a visual basic (VBA) encoded program was written to automate MPLA products analysis. A high frequency of intragenic deletions in FHIT and/or WWOX (73%) was observed in the Eastern Cape cohort. FHIT deletions were seen in 27% of specimens from the Gauteng cohort, which by contrast did not show WWOX deletions. This difference may however reflect a difference in sampling collection. The breakpoints of a translocation t(3;11)(p14;p15.1) present in an ovarian carcinoma cell line was characterized using the above MLPA assay, aCGH and the polymerase chain reaction. The translocation was found to interrupt the FHIT gene making it the 5th cancer associated translocation involving FHIT. The evaluation of gene relative copy number by aCGH and MLPA were highly correlated further validating the power of the MLPA assay in fresh tissue. The involvement of critical genes at “hot spots” in SA cancer patients was high in the context of this study raising questions about the possible role of environmental exposure. The new MLPA assay may assist to expand the screening of critical genes at fragile sites in the future.

The development, implementation, and performance evaluation of new techniques for the location of hot spots in proteins and exons in DNA using digital filters are presented. The application of bandpass notch (BPN) digital filters for locating hot spots in proteins is first investigated. A technique is proposed for designing the appropriate BPN filter for a specific protein sequence in which the area under the amplitude response is minimized to achieve maximum selectivity for a chosen stability margin. The minimization is performed using the golden-section search. A tuning technique is also proposed for improving the accuracy of the BPN filter. The tuning is carried out using a least-squares polynomial model. Several example protein sequences are used to illustrate these techniques. BPN filters are then employed for locating exons in DNA. An additional step of lowpass filtering is introduced in order to detect the strength of the bandpass filtered signal as a function of nucleotide location. For the character-to-numerical mapping, the application of the electron-ion interaction potentials (EIIPs) of the nucleotides as well as their binary sequences is investigated. The performance of the techniques is then evaluated using metrics such as sensitivity, specificity, accuracy, precision, and computational efficiency. These metrics are used in conjunction with the so-called receiver operating characteristic (ROC) technique to establish a reliable framework for the comparisons. For exon location, a technique based on the short-time discrete Fourier transform (STDFT) reported in the literature is also included in the comparison. The effect of using different window functions on the prediction accuracy of the technique is explored. Using a set of examples, it is shown that BPN filters predict short exons with better accuracy than the STDFT. The test dataset comprised 66 protein sequences and 160 DNA sequences obtained from the protein data bank and the HMR195 database, respectively. Results show that among the techniques considered, BPN filters perform best for the location of both protein hot spots and DNA exons in terms of accuracy and computational efficiency. User-friendly MATLAB implementations of the techniques incorporating graphical interfaces are also described. Optimized numerical mapping schemes are proposed for exon location using both EIIP as well as binary sequences. Characteristic numerical values are obtained for the four nucleotides using a training procedure in which the prediction accuracy is maximized using a quasi-Newton algorithm based on the Broyden-Fletcher-Goldfarb-Shanno updating formula. A training set of 80 DNA sequences is chosen from the HMR195 database and the objective function is formulated using the ROC technique. The procedure is initialized using EIIP values. Unbiased testing of the optimized values is carried out using a test set that has no overlap with the training set. Simulation results show that the optimized values yield more accurate exon locations than those obtained using the actual EIIP values. In addition, they perform significantly better than a set of existing optimized complex values. By employing a similar strategy to optimize the weights of the binary sequences, it is shown that, in practice, only three out of four binary sequences are necessary to obtain accurate estimates of exon locations. Consequently, a computational saving of 25% can be achieved, which is substantial considering that DNA sequences encountered in practice are very long in nature. / Graduate

Police officers endure various threats ranging from verbal abuse to physical attacks, which can escalate and lead to police officer stress. Despite the abundant research exploring the relationship between high-stress occupations and environmental health, adequate exploration of the relationship between officer stress and hot spot policing (HSP; area with an above-average level of crime) has yet to occur. The purpose of this correlational study was to use Cohen and McKay's conceptualization of the stress-buffering hypothesis to explore whether HSP mitigates the negative impact of job stress, leading to improved officer performance and ultimately improved relationships between the police and communities as well as lower crime rates. Posting of a SurveyMonkey link in law enforcement only, social-media communities (with administrator permission) facilitated data collection for the 151 respondents. Findings indicated that the overall regression model was significant; however, the simple correlation between HSP and officer stress (.118) indicated that HSP alone does not account for unique variance (there was a value of .014 or 1.4% of the variation in officer stress). The social change implications of this study include recommendations to police department administrations to continue to explore efforts to reduce officer stress, which could lead to improved officer performance and police and community relationships.

Slow seismic velocity anomalies are commonly imaged beneath subducting slabs in tomographic studies, yet a unifying explanation for their distribution has not been agreed upon. In South America two such anomalies have been imaged associated with subduction of the Nazca Ridge in Peru and the Juan Fernandez Ridge in Chile. Here we present new seismic images of the subslab slow velocity anomaly beneath Chile, which give a unique view of the nature of such anomalies. Slow seismic velocities within a large hole in the subducted Nazca slab connect with a subslab slow anomaly that appears correlated with the extent of the subducted Juan Fernandez Ridge. The hole in the slab may allow the subslab material to rise into the mantle wedge, revealing the positive buoyancy of the slow material. We propose a new model for subslab slow velocity anomalies beneath the Nazca slab related to the entrainment of hot spot material.

Tornadoes are one of the most frequent and destructive disasters in the United States. Like other environmental calamities, tornadoes too act as push factors for migration. The objectives of this study are to define tornado hot spots in the US, to analyze migration effectiveness in the tornado hot spots and non-hot spots, and to explore how tornado and other socio-economic factors influence migration decision. Both quantitative and qualitative methods were used. Internal revenue service migration data, SPC tornado data, and Census Bureau data were used in the study. The results indicate that there are significant differences between migration patterns in the tornado hot spots and rest of the country: tornado hot spots are losing population to other regions. The results also indicated that along with the traditional socio-economic push and pull factors of migration, tornado occurrences also influenced people’s migration decision in the United States.

Denna forskningsöversikt handlar om effektiviteten av platsbaserat polisiärt arbete, som fokuserar på små geografiska områden med hög kriminalitet. Har platsbaserat polisiärt arbete en brottsminskande effekt? Minskar bara en viss typ av kriminalitet? Flyttar brottsligheten bara på sig? - Genom lämpliga sökord och välkända databaser valdes de studier ut som hade bra utvärderingsdesigner. Resultatet blev 14 studier varav 9 randomiserade experiment, 4 kvasiexperimentella studier och 1 metaanalys. Översikten visar på en delad bild när det kommer till signifikant effekt vid brottsminskning. Sammanfattningsvis är 6 studier signifikanta med liten effekt och 4 icke signifikanta när det kommer till total brottslighet. Problemorienterat arbete och samarbete med andra instanser ger bäst resultat. Att enbart arbeta platsbaserat påverkar inte all brottslighet, andra instanser/metoder behövs. / This research review is about the effectiveness of hot spot policing. Does hot spot policing have an effect on crime? Does only one type of crime decline? Does crime just move from one place to another? Through suitable keywords and well known databases, studies with good research designs were chosen. The result was 14 in all, 9 randomized controlled trials, 4 quasi-experiments and 1 meta-analysis. The review shows a divided picture when it comes to significance in crimeprevention. In summary: 6 studies are significantly small and 4 non-significant when it comes to the total of crime. To work problem-oriented and to work with other authorities is most effective. Only place-based work does not affect all crime, other authorities/methods are needed.

Orientadores: Goran Neshich, João Alexandre Ribeiro Gonçalves Barbosa / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-21T21:50:32Z (GMT). No. of bitstreams: 1 Pereira_JoseGeraldodeCarvalho_M.pdf: 10985777 bytes, checksum: 2610df8bda1ef229c4bcdc8c6c5d8325 (MD5) Previous issue date: 2012 / Resumo: A propriedade das proteínas de se ligarem umas as outras de forma altamente específica, formando complexos estáveis, é uma característica fundamental para todos os processos biológicos. Uma melhor compreensão da formação do complexo abre perspectivas para muitas aplicações práticas, entre elas o design racional de novos fármacos. Trabalhos anteriores demonstraram, através de experimentos de varredura por alaninas, que um pequeno número de resíduos das interfaces protéicas contribui com a maior parte da energia de ligação e por isso foram chamados de hot spots. Devido à importância desses resíduos para as interações proteína-proteína, diversos métodos computacionais têm sido propostos para predizer os hot spots complementando assim o procedimento experimental. Entre esses, estão métodos physics-based como dinâmica molecular, e também métodos knowledge-based, onde dados experimentais são utilizados para treinar métodos computacionais que aprendem as regras para classificar corretamente os hot spots e usados posteriormente para classificar novos casos em estruturas de complexos protéicos. Entre os algoritmos de aprendizado computacionais mais utilizados estão árvores de decisão, redes neurais, máquinas de vetor de suporte. Nesse trabalho, desenvolvemos métodos de predição de hot spots utilizando máquinas de vetor de suporte, que foram abastecidas na entrada com um conjunto de 186 descritores estruturais extraídos do banco de dados STING_DB e também com 112 novos descritores propostos neste trabalho. Os métodos propostos nesse trabalho apresentaram desempenho superior aos métodos de predição de hot spots mais conhecidos da literatura, como KFC, Minerva, Rosetta e FOLDEF. Além disso, a análise estatística dos descritores e também a seleção dos descritores mais eficientes na tarefa de classificar hot spots permitiu que observássemos diversas características que são distintas entre resíduos que são hot spots e os que não são. Entre estas características, a entalpia de hidratação ao redor do resíduo sugere que essa região é mais hidrofílica em hot spots. Essa região, que para hot spots é denominada de anel-O, tem a função de impedir o contato do solvente com o hot spot e por isso, alguns autores acreditavam tratar-se de uma região hidrofóbica, algo que os resultados deste trabalho não confirmaram. Futuramente, os novos descritores propostos neste trabalho serão agregados ao STING_DB e o método de predição de hot spots será integrado ao STING permitindo a predição de hot spots de todos os complexos protéicos depositados no Protein Data Bank (PDB) assim como de complexos protéicos fornecidos pelo usuário / Abstract: The property of the proteins to bind each other in a highly specific way, forming stable complexes, is a key feature for all biological processes. A better understanding of the formation of protein complexes provides many practical applications, including the rational design of new drugs. Through experiments of alanine scanning, it was shown that a small number of residues belonging to protein interfaces contribute decisively to the binding energy and so were called hot spots. Because of the importance of these residues for protein-protein interactions many computational methods have been proposed to predict the hot spots and thus complement the experimental procedure. These include physics-based methods such as molecular dynamics and also knowledge-based methods where experimental data are used to train computational methods that learn the rules for correctly classifying the hot spots and are then used to classify new cases in structures of protein complexes. Among the computational learning algorithms most frequently used are decision trees, neural networks, support vector machines, among others. In this work, we developed methods to predict hot spots using support vector machines, using at the input 186 structural descriptors extracted from the STING_DB and 112 new descriptors proposed in this work. The methods proposed here showed superior performance to methods of predicting hot spots best known from the literature, such as KFC, Minerva, Rosetta and FOLDEF. In addition, statistical analysis of the descriptors and also the selection of the descriptors more efficient in the task of classifying hot spots allowed us to observe several characteristics that are distinct for residues that are hot spots. Among these features, the enthalpy of hydration suggests that the region around hot spots is more hydrophilic. This region, which for hot spots is called O-ring, serves to prevent the contact of the solvent with the hot spot and therefore some authors believe that this was a hydrophobic region whereas results presented here show otherwise. In future, the new descriptors described in this work will be added to the STING_DB and the method of prediction of hot spots will be integrated with STING allowing the prediction of hot spots of all protein complexes deposited in the Protein Data Bank (PDB) as well as protein complexes supplied by the user / Mestrado / Bioinformatica / Mestre em Genética e Biologia Molecular

Hot spots policing is a popular and effective evidence-based police intervention with several benefits. However, since the primary resource of the intervention is intensified police presence leading to an increase in citizen-police interactions, critics have argued that the intervention negatively affects police-citizen relationships and public perceptions and attitudes toward the police. To advance research on the effects of hot spots policing, this study examines the impacts of the hot spots policing intervention on residents’ trust in, and fear of, the police. The study utilized a secondary dataset from a U.S. DOJ/NIJ-funded project in New York City, NY (2012-2018) examining the effects of hot spots policing and police-resident familiarity on offender decision making and crime prevention. The results of chi-square test of association and ordinal logistic regression analyses show that the hot spots policing intervention has no significant impact on residents’ reported level of trust in, and fear of, the police. In addition, the impacts of residents’ age, race, gender, as well as familiarity are also analyzed. Further, the interaction between the intervention and police-resident familiarity does not significantly moderate the relationship between hot spots policing and residents’ reported level of trust in, and fear towards, the police. The implications of these findings are also discussed.

Approved for public release; distribution is unlimited / During the month of July 1987 an acoustical experiment was conducted by the United States Naval Research Laboratory (NRL) in the East Greenland Sea Marginal Ice Zone (MIZ) . Ambient noise "hot spots" or concentrated areas of relatively high noise levels were found along the ice edge using a towed array. Ambient noise levels were obtained on 27 and 28 July using AN/SSQ-57A and AN/SSQ-57XN5 calibrated sonobuoys . The temperature structure of the area was determined using XBT (ship) and AXBT (P3C aircraft) buoys placed inside and outside the ice edge. The ice edge was determined from coincident satellite photos, 90 GHz microwave imagery and P3 radar ice edge maps. Weather data (sea state and wind speed and direction) were recorded on the ship. The data seem to indicate a correlation between the high ambient noise levels of the hot spots and the presence of a large topographically controlled mesoscale eddy located at the southeastern extent of the MIZ. / http://archive.org/details/spatialvariabili00bigg / Lieutenant, United States Navy

När orsakerna till brottslighet har studerats har kriminologisk forskning och teori traditionellt fokuserat på individuella egenskaper och på riskfaktorer hos brottslingar, eller på olika socioekonomiska faktorer. Kriminologisk forskning om brottslighetens geografiska fördelning har dock ökat och fått större utrymme och acceptans både bland forskare och bland de samhällsinstanser som arbetar mot brottslighet. Hot spots utgörs av små områden där det sker mycket fler brott än i omgivande områden. Flera studier har visat att några få områden står för merparten av brottsligheten när enskilda brottstyper studeras. Syftet med denna studie var att analysera hur brottsligheten koncentrerar sig geografiskt i Sundsvall, samt att jämföra hur brottslighetens fördelning har förändrats mellan åren 2010 och 2015. Studien bygger på en analys av anmälningar inkomna till polisen i Sundsvall under perioderna 1 januari till 31 december 2010 samt 1 januari till 31 december 2015. Anmälningarna som studerades delades sedan upp i de fyra brottstyperna våldsbrott, narkotikabrott, inbrott samt tillgreppsbrott. Resultatet visade att brottsanmälningarna i Sundsvall koncentrerade sig till hot spots. Var dessa hot spots var placerade geografiskt skiljer sig åt mellan olika brottstyper, men en viss överrepresentation av anmälningar kunde ses på ett antal platser oavsett brottstyp. Varje undersökt brottstyp diskuteras utifrån socialekologisk teori och Crime pattern theory. I diskussionen ges även förslag på i vilka situationer det kan vara effektivt att använda sig av platsbaserat polisiärt arbete och i vilka situationer andra preventiva åtgärder kan vara mer effektiva. / <p>2016-06-01</p>