An Evaluation of Forecasting Methods that Could be Used in the Brazilian Air Force Uniform Distribution Process

Every year the Brazilian Air Force (BAF) spends the equivalent of approximately 15 million dollars for uniforms. These purchases come from a tight budget, are executed through public procurement processes, and are tied to Brazilian acquisition regulations, which are often very strict. For this reason, lead times are unpredictable. It can take anywhere from one month to a year to replenish an item. The purpose of this research is to analyze the forecasting process performed at a BAF military organization named Sub-directorate of Supply (SDS) with the intent of building an algorithm comprised of a selection of forecasting models in order to help SDS optimize its inventory investments. With this in mind, monthly sales, prices, and inventory records from January of 2010 to July of 2015 were extracted from a database and converted to a standard spreadsheet format. Several forecasting models were evaluated and applied to randomly selected items from the database to create the algorithm. In the final analysis, it was concluded that two models precisely depicted the behavior of sales in BAF’s stores. These two models were then utilized to develop the forecasting tool that may prove valuable in future BAF uniform purchasing decisions

Implicações translacionais de uma nova ferramenta de detecção de célula: tumorais circulantes no monitoramento do câncer de próstata

Introduction: prostate cancer (PCa) early diagnosis is essential to boost patients’ life expectance. Although, current biomarkers and diagnosis methods do not present reliable sensibility and specificity, making the diagnosis rather imprecise. Recent methodologies have been using circulating tumor cells (CTCs), not for screening of PCa, but as prognosis indicators, employing a vast array of techniques to capture those cells. However, the search for a new biomarkers or diagnosis methods able to screen, diagnosis, assist in prognosis and in the disease monitoring still one of the major technical and scientific objectives to be achieved. Objective: To present a new biomarker for PCa, the aptamer A4, previous screened in the prostate cancer cell line PC3, using 3DCell SELEX. And to able to detect, by flow cytometry, CTCs in blood samples of PCa patients undergoing various treatment regimen. Material and methods: the study evaluated 34 PCa patients and 16 health controls. Blood samples were collected in EDTA tubes, and after erythrocytes lysis, nucleated cells were incubated with A4 aptamer conjugated with biotin, them the cells were washed and incubated with streptavidin-FITC for later flow cytometer analysis. Percentage of CTCs were compared between patient’s groups and correlated against age, PSA levels, staging and treatment regimen (hormonal blockade, radiotherapy and surgery). Detection limit above 1% of CTCs was considered positive, based on the percentage observed on all of the 16 negative controls. Results: all patients were positively diagnosed independently of therapy time or staging, except for one patient undergoing hormonal blockade therapy, which does not present detectable CTCs. CTCs percentage presented high correlation against age (R=0.75) and with PSA levels (R=0.80) with exponential behavior, although, six patients with high CTCs count presented PSA levels <0.02 ng/mL, and were considered was biochemical errors. Conclusion: Our preliminary results indicated high accuracy (98%) and demonstrate a potential application of this technology for diagnosis and screening, as well as in the monitoring of PCa evolution, which should be better investigated in the risk population.Dissertação (Mestrado)Introdução: O diagnóstico precoce de câncer de próstata (CaP) é essencial para aumentar a sobrevida dos pacientes, mas os marcadores e métodos atuais não possuem sensibilidade e especificidade suficientes, tornando o diagnóstico ainda muito impreciso. Recentemente, as células tumorais circulantes (CTCs) têm surgido não como método de rastreio do CaP, mas sim como marcadores de prognóstico utilizando um arsenal de diversos alvos para a captura dessas células. Contudo, a busca por um método ou marcadores comuns para o rastreio, diagnóstico, prognóstico e monitoramento da doença ainda se apresenta com um dos principais objetivos técnico-científicos a ser alcançado. Objetivo: apresentar um novo marcador, o aptâmero A4 selecionado previamente por 3DCell SELEX na linhagem PC3, e avaliar sua capacidade de detectar CTCs por citometria de fluxo no sangue de pacientes com CaP virgens de tratamento e sob diferentes regimes terapêuticos. Material e métodos: o estudo avaliou 34 homens com CaP e 16 homens sem alterações prostáticas. Foi coletado o sangue em tubo com EDTA, e após proceder a lise de hemácias, as células nucleadas de cada paciente foram incubadas com o aptâmero A4 conjugado à biotina, e em seguida lavadas e incubadas com estreptoavidina-FITC para posterior análise em citometria de fluxo. Os percentuais de CTCs foram comparados entre os dois grupos de pacientes e correlacionados com idade, níveis de PSA, estadiamento e procedimentos terapêuticos adotados (bloqueio hormonal, radioterapia e cirurgia). O limite de detecção acima de 1% de CTCs foi considerado positivo, utilizando como base o percentual observado em todos os 16 controles negativos. Resultados: todos os pacientes foram diagnosticados como positivos independentemente do tempo de terapia ou do estadiamento, exceto um paciente sob bloqueio hormonal que não apresentou CTCs. O percentual de CTCs apresentou alta correlação com idade (R=0,75) e com os níveis de PSA (R=0,80) de forma exponencial, embora seis pacientes com altos índices de células circulantes apresentaram PSA<0,02ng/mL, considerados como falha bioquímica. Conclusão: nossos resultados preliminares indicam uma acurácia elevada de 98% e demonstra um grande potencial de aplicação dessa nova tecnologia diagnóstica tanto no rastreamento, quanto no monitoramento do tratamento do CaP, o qual deverá ser melhor investigado em população de risco

Quantum Fields in Extreme Backgrounds

Quantum field theories behave in interesting and nontrivial ways in the presence of intense electric and/or magnetic fields. Describing such behavior correctly, particularly at finite (nonzero) temperature and density, is of importance for particle physics, nuclear physics, astrophysics, condensed matter physics, and cosmology. Incorporating these conditions as external parameters also provides useful probes into the nonperturbative structure of gauge theories. In this work, formalism for describing matter in a variety of extreme conditions is developed and implemented. We develop several expansions of one-loop finite temperature effects for spinor particles in the presence of magnetic fields, including the effects of confinement, encoded in a nontrivial Polyakov loop. The worldline instanton formalism is extended to the case of finite temperature, which yields a long-sought thermal extension to the celebrated formula of Schwinger for pair production in a constant electric field. The technique is further extended to include the effects of finite density and confinement, as well as some restricted classes of nonabelian electric fields. A persistent source of difficulty in the study of gauge theories at finite density, and/or in the presence of external electric fields, is the so-called sign problem. We advance a novel duality-based approach for lattice simulation of scalar field theories with complex actions, which yields new insights on the old problem of spatial modulations arising in systems with competing interactions. The approach shows promise for simulating scalar theories at finite density and in the presence of external electric fields, and is capable of handling systems in the universality class of the $i\phi^3$ theory, which determines the critical indices of the Lee-Yang edge transition

Biosynthesis of a G-Quadruplex—forming sequence and its stabilization by ligands

In addition to the Watson and Crick B-form duplex DNA, G-quadruplexes are four-stranded DNA structures formed in vivo by the self-assembly of guanine-rich sequences. These can be formed by one, two or four separate strands of DNA and present a diversity of topologies, defined by the strand orientation, loop size and sequence. G-quadruplexes can be found in telomeres, immunoglobulin switch regions and gene promoter regions. The biological relevant location on the genome makes these high-order structures an attractive target for drug design and the development of highly specific ligands that bind and stabilize G-quadruplex with therapeutic activity. Herein, the biosynthesis of a novel G-rich quadruplex-forming DNA sequence 58Sγ3 is described by plasmid amplification. The recovery and purification of 58Sγ3 oligonucleotide using size-exclusion chromatography is presented. The G-quadruplex formation is promoted and its topology is determined by circular dichroism. The stabilization of the G-quadruplex structure with quinoline and naphthalene-based derivatives is studied using melting analysis, G4-FID and PCR-stop assays. The results suggest that 58Sγ3 folds into a parallel-stranded G-quadruplex structure in 500 mM KCl buffer and that naphthalene-based ligands bind and stabilize the G-quadruplex structure. The ligands are also found to be quadruplex-specific over duplex DNA and inhibit Taq DNA polymerase. This work provides evidence for G-quadruplex formation within the immunoglobulin switch regions. Furthermore, it is suggested that the novel ligands here reported act as potent specific G-quadruplex binders and may also potentially be used to inhibit genes transcription in tumor cells.Além da forma B Watson e Crick do ADN duplex, os G-quadruplexes são estruturas de ADN de quatro cadeias, formadas in vivo pela auto-associação de sequências ricas em guaninas. Estas podem ser formadas por uma, duas ou quatro cadeias distintas de ADN e apresentar uma diversidade de topologias, definidas pela orientação da cadeia, tamanho dos loops e a sequência. G-quadruplexes podem ser encontrados nos telómeros, regiões de troca das imunoglobulinas e nas regiões dos promotores génicos. A localização biologicamente relevante no genoma faz com que estas estruturas altamente ordenadas sejam um alvo atrativo do desenho de fármacos e o desenvolvimento de ligandos altamente específicos que ligam e estabilizam o G-quadruplex com ação terapêutica. Neste trabalho, descreve-se a biossíntese da nova sequência de ADN rica em guaninas e formadora de G-quadruplex 58Sγ3, utilizando amplificação por plasmídeo. A recuperação e purificação do oligonucleótido 58Sγ3 é efetuada por cromatografia de exclusão molecular. A formação de G-quadruplex é promovida e a sua topologia é determinada por dicroísmo circular. A estabilização da estrutura do G-quadruplex com ligandos derivados de quinolina e naftaleno é estudada utilizando ensaios de estabilização térmica no dicroísmo circular, G4-FID e PCR-stop. Os resultados sugerem que 58Sγ3 adota uma estrutura G-quadruplex paralela em tampão 500 mM KCl e que os ligandos de naftaleno ligam e estabilizam a estrutura do G-quadruplex. Os ligandos demonstraram também ser específicos do G-quadruplex em relação ao ADN duplex além de inibir a Taq ADN polimerase. Este trabalho fornece evidência da formação de G-quadruplex nas regiões de troca das imunoglobulinas. Além disso, sugere que os derivados de naftaleno atuam como ligandos do G-quadruplex e que podem ser potencialmente utilizados para inibir a transcrição de genes em células tumorais

The Fubini's Theorem for the Even Index Lie Subgroup

In this paper we present a new proof to generalize the Fubini's Theorem for the even index subgroup of a compact Lie group, using a recent result on the semi-direct product of groups. We also present some applications of this result for the invariant theory.Comment: 10 page