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Objetivo: Estudiar los factores de riesgo maternos del parto pretérmino en el Hospital Nacional Santa Rosa de Lima durante el año 2014 Métodos: Estudio caso-control en 20 casos con parto pretérmino y 20 controles con parto a término. Se revisaron las historias clínicas y se elaboró una hoja de datos en SPSS.21 para el análisis descriptivo con nivel de significancia p<0.05. Se consideró como factor de riesgo si OR e IC95% eran > 1. Se realizó el análisis de regresión logística binaria para evaluar la potencia individual de los factores y eliminar los factores confusores. Resultados: Los factores de riesgo maternos pregestacionales significativos para nuestra serie fueron: nivel socio-económico bajo (OR=5.57 e IC95%=1.420-21.860), antecedentes de parto pretérmino (OR=35.29 e IC95%=3.868-321.932) y antecedentes maternos de infección urinaria pregestacional. Los factores de riesgo maternos gestacionales significativos para nuestra serie fueron: control prenatal inadecuado (OR=9.00 e IC95%=1.638-49.446) e infección urinaria (OR=4.64 e IC95%=1.023-21.004) Conclusiones: Los factores de riesgo materno del parto pretérmino en el Hospital Nacional Santa Rosa de Lima fueron: antecedente de parto pretérmino, el antecedente materno de infección urinaria pregestacional y un control prenatal inadecuado. / Objective: To study the maternal risk factors of preterm delivery in Santa Rosa de Lima National Hospital during 2014 Methods: Case-control study in 20 patients with preterm labor and 20 controls who delivered at term. The medical records were reviewed and a data sheet was prepared in SPSS.21 for descriptive analysis with significance level of p <0.05. It was considered as a risk factor if OR and 95% CI were> 1. The binary logistic regression analysis to assess the individual power factor and eliminate confounding factors was performed. Results: Significant factors pregestational maternal risk for our series were: socio-economic level (OR = 5.57 and 95% CI = 1420-21860), history of preterm delivery (OR = 35.29 and 95% CI = 3868-321932) and background prepregnancy maternal urinary infection. The significant maternal risk factors for gestational our series were: inadequate prenatal care (OR = 9.00 and 95% CI = 1638-49446) and urinary tract infection (OR = 4.64 and 95% CI = 1023-21004) Conclusions: Maternal risk factors of preterm delivery in Santa Rosa de Lima National Hospital were: history of preterm birth, maternal prepregnancy history of urinary tract infection and inadequate prenatal care. Keywords: preterm delivery risk factor, case-control study.

Approved for public release, distribution unlimited / The purpose of this thesis is to analyze data related to sleep patterns of warfighters deployed to the Southwest Asia (SWA) Area of Operation. To this end, we collected subjective survey data from warfighters operating in Iraq and Kuwait from 25 August - 15 October 2003 (n = 273). Participants were asked about unit-level sleep planning, sleep/wake patterns, and lifestyle factors. Using the survey results, we are able to gain insight regarding the four primary research questions: 1) Is sleep deprivation a significant problem for forces in the SWA region; 2) Do current sleep logistics support a unit's ability to accomplish assigned missions; 3) Are there differences in sleep patterns between subset populations; and 4) Does the current survey method support the research objectives. To address these questions, we used analysis techniques such as principal components analysis, factor analysis, and parametric and nonparametric hypothesis testing. We tested the reliability of the subjective survey results by comparing self-reported survey data with actigraphy data corresponding to the same time period (n = 34 paired observations). This thesis also provides insight regarding the use of sleep logistics as a force multiplier during continuous/sustained operations by discussing known fatigue countermeasures and their role in improving individual and unit performance effectiveness.

<p>Technologies for engineering new functions into proteins are advancing biological research, biotechnology, and medicine at an astounding rate. Building on fundamental research of natural protein structure and function, scientists are identifying new protein domains with previously undescribed properties and engineering new proteins with expanded functionalities. Such tools are enabling the precise study of fundamental aspects of cellular behavior and the development of a new class of gene therapies that manipulate the expression of endogenous genes. The applications of these gene regulation technologies include but are not limited to controlling cell fate decisions, reprogramming cell lineage commitment, monitoring cellular states, and stimulating expression of therapeutic factors. </p><p>While the field has come a long way in the past 20 years, there are still many limitations. Historically, gene therapy and gene replacement therapies have relied on over-expression of natural transcription factors that activate specific endogenous gene networks. However, natural transcription factors are often inadequate for generating efficient, fast, and homogenous cellular responses. Furthermore, most natural transcription factors have complex structures and functions that are difficult to improve or alter by rational design. This thesis presents three novel and widely applicable methods for engineering transcription factors for programming cell fate decisions in primary human cells. MyoD is the master transcription factor defining the myogenic lineage. Expression of MyoD in certain non-myogenic lineages induces a coordinated change in differentiation state. We use MyoD as a model for developing our protein engineering techniques because myogenesis is a well-studied pathway that is characterized by an easily detected change in phenotype from mono-nucleated to multinucleated cells. Furthermore, efficient generation of myocytes in vitro presents an attractive patient-specific method by which to treat muscle-wasting diseases such as muscular dystrophy.</p><p>We first demonstrate that we can improve the ability of MyoD to convert human dermal fibroblasts and human adipose-derived stem cells into myocyte-like cells. By fusing potent modular activation domains to the MyoD protein, we increased myogenic gene expression, myofiber formation, cell fusion, and global reprogramming of the myogenic gene network. The engineered MyoD transcription factor induced myogenisis in a little as ten days, a process that takes three or more weeks with the natural MyoD protein. </p><p>While increasing the potency of transcriptional activation is one mechanism by which to improve transcription factor function, there are many other possible routes such as increasing DNA-binding affinity, increasing protein stability, altering interactions with co-factors, or inducing post-translational modifications. Endogenous regulatory pathways are complex, and it is difficult to predict specific amino acid changes that will produce the desired outcome. Therefore, we designed and implemented a high-throughput directed evolution system in mammalian cells that allowed us to enrich for MyoD variants that are successful at inducing expression of the myogenic gene network. Directed evolution presents a well-established and currently unexplored approach for uncovering amino acid substitutions that improve the intrinsic properties of transcription factors themselves without any prior knowledge. After ten rounds of selection, we identified amino acid substitutions in MyoD that increase expression of a subset of myogenic gene markers in primary human cells.</p><p>Rather than guide cell fate decisions by expressing an exogenous factor, it may be beneficial to activate expression of the endogenous gene locus. In comparison to delivering the transcription factor cDNA, expression from the endogenous locus may induce chromatin remodeling and activation of positive feedback loops to stimulate autologous expression more quickly. Recent discoveries of the principles of protein-DNA interactions in various species and systems has guided the development of methods for engineering designer enzymes that can be targeted to any DNA target site. We make use of the RNA-guided Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 system to induce expression of the endogenous MyoD gene in human induced pluripotent stem cells (iPSCs). Through complementary base pairing, chimeric guide RNAs (gRNAs) direct a Cas9 transcriptional activator to a target DNA sequence, leading to endogenous gene expression. A current limitation of CRISPR/Cas9-based gene regulation is the potency of transcriptional activation and delivery of the CRISPR/Cas9 components. To address these limitations, we first developed a platform to express Cas9 and up to four gRNAs from a single lentiviral vector. We then optimized the gRNAs and Cas9 transcriptional activator to induce endogenous MyoD expression and differentiate iPSCs into myocyte-like cells. </p><p>In summary, the objective of this work is to develop protein engineering techniques to improve both natural and synthetic transcription factor function for programming cell fate decisions in primary human cells. While we focus on myogenesis, each method can be easily adapted to other transcription factors and gene networks. Engineered transcription factors that induce fast and efficient remodeling of gene networks have widespread applications in the fields of biotechnology and regenerative medicine. Continuing to develop these tools for modulating gene expression will lead to an expanded number of disease models and eventually the efficient generation of patient-specific cellular therapies.</p> / Dissertation

Memoria para optar al título de periodista / El autor no autoriza el acceso a texto completo de su documento / Desde la creación del Canal 2 de Televisión (en ese tiempo Rock & Pop), en agosto de 1995, nuestra diaria ocupación ha sido la de desarrollar programas de televisión. En su particular diseño, el proyecto Rock & Pop, como canal de televisión abierta, abría la posibilidad de ser una alternativa de expresión para gente e ideas que, con bastante probabilidad, nunca hubieran podido acceder a los medios tradicionales. Más allá de los errores técnicos o de planificación que acompañaron los primeros meses de transmisión, al poco andar el canal evidenció que la gente que se había involucrado en el proyecto –incluidos nosotros- poco o nada sabía del medio. Esta falencia, sin embargo, permitió afrontar el tema televisivo sin los prejuicios económicos y estéticos propios de la gente más ligada al ambiente, y aunque el canal no tuvo en ningún caso un éxito financiero, dentro de él pudieron realizarse valiosos aportes a la producción televisiva. Ingresamos a trabajar como peridistas de apoyo al programa Gato Por Liebre. Este fue un espacio magazinesco centrado en la política, conducido por Angel Carcavilla, Carolina Delpiano y Rafael Gumucio. En él, nuestras funciones eran diversas: notas periodísticas, libretos, videos de humor y voces en off. La veta humorística de Gato por Liebre, planteó la necesidad de realizar un programa dedicado exclusivamente a ese corte, en que se privilegiara una preocupación por la realidad chilena sin depender de la contingencia noticiosa. El resultado fue Plan Z, un programa de muy bajo presupuesto, en el que los realizadores escribíamos los libretos, actuábamos las situaciones y editábamos el producto terminado. Plan Z nos permitió explorar la narrativa televisiva de ficción, como asimismo acentuó la experimentación visual en la edición. Ambos programas obtuvieron críticas destacadas y fueron considerados entre los proyectos de mayor importancia del canal. Finalmente, se completaron cinco temporadas de Gato por Liebre, y dos de Plan Z alternadamente, antes de que el equipo se desarticulara debido a los distintos intereses profesionales de sus participantes. A fines de 1997, los tres conductores –y rostros más reconocibles de nuestros programas- abandonaron el canal. Nosotros nos quedamos.

The purpose of this work is to determine experimentally the depression of the neutron density by a detecting foil. The depression factor is known as the "self-shading" of the foil.

Wounding of the cornea generates lateral electric fields (EFs) and initiates the expression of hepatocyte growth factor (HGF) and keratinocyte growth factor (KGF; Chiang et al., 1992; Wilson et al., 1999a). Therefore, these biologically generated EFs and endogenous growth factors may be of particular significance during wound healing. In the presence of an EF (150 mV/mm) cultured corneal epithelial cells (CECs) oriented perpendicular, directed cathodally and migrated at an enhanced rate. The induction times, induction thresholds and response patterns for these behaviours in increasing field strengths, indicated that they may operate through separate and parallel pathways. The application of either HGF or KGF enhanced the rate of CEC migration but neither affected the extent of CEC orientation or directionality. The distribution of HGF receptors (HGFR) was found to be exclusive to the cell body in the presence of an EF, the receptors accumulated cathodally. Moreover, the asymmetrical accumulation of HGFR in the presence of an EF correlated with the direction of CEC migration. The application of both HGF and an EF activated extracellular-signal regulated kinase (ERK) a mitogen-activated protein kinase. Furthermore, in the presence of an EF the observed ERK activation was greater in the cathodal facing half of the CECs. Inhibition of ERK reduced the extent of HGF and EF-enhanced CEC migration rate but did not alter EF-induced CEC cathodal directionality or perpendicular orientation. The HGF- and EF-enhancement of CEC migration rate may involve the activation of ERK and with the downstream liberation of leukotrienes and phosphorylation of MLCK, would culminate in actin contraction and polymerisation respectively. The potential clinical relevance for this work would concern the topical application of HGF and exogenous application of EFs to corneal epithelial wounds in order to augment healing in patients where this process is slow or deficient.

Electrospinning has the capacity to create fibers of natural or synthetic polymers with dimensions that are similar to analogous fibers in native tissue. Mats consisting of fibers of these sub-micron dimensions have shown promise in provoking little immune response and in offering a habitable environment for cell proliferation. Fibrinogen is a natural protein capable of being electrospun and offers the benefit of existing as part of the natural coagulation cascade. Mats of fibrinogen could be utilized as possible hemostatic dressings or as an early scaffold for cell migration for either wound repair or tissue engineering. The addition of antibiotic into such a dressing/scaffold could prevent infection during healing/incorporation. The goal of this study was to determine any effect that the addition of the antibiotic tetracycline hydrochloride (0%, 2.5%, 5%, 10% by weight) would have on the mechanical properties of electrospun fibrinogen (110 mg/mL, 120 mg/mL, and 130 mg/mL concentrations). Also, the time release of tetracycline from electrospun fibrinogen was investigated. The results show no significant effect of tetracycline loading on the mechanical properties of electrospun fibrinogen under the conditions of this study. The results of the release study demonstrate that initial tetracycline release is dependent upon loading percentage. The release data also demonstrate that the amount of tetracycline released is approximately 20-30% of the tetracycline in the original solution and that the release occurs within approximately 4 hours, with no significant release thereafter. This study demonstrates the feasibility of tetracycline in electrospun fibrinogen for the purposes of short term drug release in fibrinogen-based technologies.

Pluripotent embryonic stem (ES) cells are heterogeneous mixtures of naïve and lineage-primed states defined by distinct transcription factor expression profiles. However, the events that prime pluripotent cells for differentiation are not well understood. Id proteins, which are inhibitors of basic helix-loop-helix (bHLH) transcription factors, contribute to pluripotency by blocking differentiation. Using Yeast-Two-Hybrid screening, our lab identified Tcf15 as an Id-regulated transcription factor. In this study, I first examined the expression of Tcf15 during differentiation in vitro and during early development in vivo in the mouse. Tcf15 expression is higher in primed pluripotent embryonic stem (ES) cells than in naïve ES cells or epiblast stem cells (EpiSCs). In addition, Tcf15 is expressed heterogeneously in ES cells and is also detected in the inner cell mass (ICM) of E4.5 mouse embryos. Expression of Tcf15 was upregulated during early stages of differentiation and downregulated before cells committed to any specific lineage. Using Tcf15-Venus reporter cells, I found that expression of Tcf15 is specifically associated with a novel subpopulation of ES cells primed for somatic lineages. Gain of function and loss of function studies were then performed to perturb Tcf15 expression in ES cells in order to assess the function of Tcf15 in self-renewal and during differentiation. An inducible Id-resistant form of Tcf15 accelerates somatic lineage commitment by maturating naïve pluripotent ES cells transit toward primed epiblast and later on epiblastderived somatic lineages whilst suppressing differentiation towards extraembryonic endoderm. Preliminary loss of function studies also suggest that down-regulation of Tcf15 may promote a naïve state within pluripotent cells. I investigated the mechanism by which Tcf15 expression becomes associated with the epiblast-primed state by identifying the upstream regulators and downstream targets of Tcf15. Tcf15 expression is dependent on FGF signalling. Microarray analysis identified that Tcf15 downregulates the naïve pluripotency determinant Nanog and upregulates the epiblast determinant Otx2. Taken together, our results suggest that Tcf15 acts in opposition to the pluripotency network to prime pluripotent cells towards differentiation.

Approved for public release; distribution is unlimited / "Human body motion tracking using inertial sensors requires an attitude estimation filter capable of tracking in all orientations. One way to represent orientation is to use Euler angles, but they have singularities and therefore are not suitable for human body tracking applications. Quaternions can be used to represent orientation without incurring singularities. A quaternion-based Kalman filter has been designed for this purpose and implemented in this thesis. Also, a new suboptimal algorithm to compute the quaternions based on magnetometer and accelerometer data is implemented. This new algorithm called "Factored Quaternion Algorithm" is computationally simpler than previous methods and provides a decoupling property from magnetometer and accelerometer data." p. i. / Lieutenant Junior Grade, Mexican Navy