Identifying the molecular components that matter: a statistical modelling approach to linking functional genomics data to cell physiology

Functional genomics technologies, in which thousands of mRNAs, proteins, or metabolites can be measured in single experiments, have contributed to reshape biological investigations. One of the most important issues in the analysis of the generated large datasets is the selection of relatively small sub-sets of variables that are predictive of the physiological state of a cell or tissue. In this thesis, a truly multivariate variable selection framework using diverse functional genomics data has been developed, characterized, and tested. This framework has also been used to prove that it is possible to predict the physiological state of the tumour from the molecular state of adjacent normal cells. This allows us to identify novel genes involved in cell to cell communication. Then, using a network inference technique networks representing cell-cell communication in prostate cancer have been inferred. The analysis of these networks has revealed interesting properties that suggests a crucial role of directional signals in controlling the interplay between normal and tumour cell to cell communication. Experimental verification performed in our laboratory has provided evidence that one of the identified genes could be a novel tumour suppressor gene. In conclusion, the findings and methods reported in this thesis have contributed to further understanding of cell to cell interaction and multivariate variable selection not only by applying and extending previous work, but also by proposing novel approaches that can be applied to any functional genomics data

Multivariate Radiological-Based Models for the Prediction of Future Knee Pain: Data from the OAI

In this work, the potential of X-ray based multivariate prognostic models to predict the onset of chronic knee pain is presented. Using X-rays quantitative image assessments of joint-space-width (JSW) and paired semiquantitative central X-ray scores from the Osteoarthritis Initiative (OAI), a case-control study is presented. The pain assessments of the right knee at the baseline and the 60-month visits were used to screen for case/control subjects. Scores were analyzed at the time of pain incidence (T-0), the year prior incidence (T-1), and two years before pain incidence (T-2). Multivariate models were created by a cross validated elastic-net regularized generalized linear models feature selection tool. Univariate differences between cases and controls were reported by AUC, C-statistics, and ODDs ratios. Univariate analysis indicated that the medial osteophytes were significantly more prevalent in cases than controls: C-stat 0.62, 0.62, and 0.61, at T-0, T-1, and T-2, respectively. The multivariate JSW models significantly predicted pain: AUC = 0.695, 0.623, and 0.620, at T-0, T-1, and T-2, respectively. Semiquantitative multivariate models predicted paint with C-stat = 0.671, 0.648, and 0.645 at T-0, T-1, and T-2, respectively. Multivariate models derived from plain X-ray radiography assessments may be used to predict subjects that are at risk of developing knee pain

Fabricación y caracterización de pilas de combustible de óxido sólido microtubulares soportadas en el cátodo Nd2NiO4

En este estudio se trata de fabricar una pila microtubular utilizando materiales electrocerámicos no convencionales. El trabajo se centra en pilas soportadas en el cátodo. El material elegido para dicho cátodo es el niquelato de neodimio defectivo, el Nd1.95NiO4+δ (NNO). El objetivo fundamental es la fabricación y caracterización de pilas de óxido sólido microtubulares soportadas en NNO demostrando en primer lugar la posibilidad de su fabricación y en segundo lugar demostrar estas celdas pueden ser competitivas con las prestaciones de pilas de otros materiales descritas en la literatura. El principal problema a resolver será el adecuar los métodos de fabricación del dispositivo al comportamiento de estos nuevos materiales desde el punto de vista de su resistencia química y mecánica, compatibilidad termomecánica y propiedades electroquímicas. Este proyecto se plantea como un trabajo multidisciplinar, dentro del ámbito de la ciencia de materiales, con actuaciones que abarcan aspectos de química básica, tecnología de pilas de combustible, reología de suspensiones, técnicas de fabricación de elementos cerámicos, caracterización microestructural mediante microscopía electrónica (SEM) y óptica, además de la caracterización electroquímica del dispositivo. En los últimos años ha habido un gran interés en pilas SOFC´s (Pilas de combustible de óxido sólido) debido fundamentalmente a su elevada eficiencia energética y a su versatilidad en uso de combustibles que van desde el hidrógeno hasta los hidrocarburos

Expression and differential cell distribution of low-threshold Ca2+ channels in mammalian male germ cells and sperm

AbstractNumerous sperm functions including the acrosome reaction (AR) are associated with Ca2+ influx through voltage-gated Ca2+ (CaV) channels. Although the electrophysiological characterization of Ca2+ currents in mature sperm has proven difficult, functional studies have revealed the presence of low-threshold (CaV3) channels in spermatogenic cells. However, the molecular identity of these proteins remains undefined. Here, we identified by reverse transcription polymerase chain reaction the expression of CaV3.3 mRNA in mouse male germ cells, an isoform not previously described in these cells. Immunoconfocal microscopy revealed the presence of the three CaV3 channel isoforms in mouse spermatogenic cells. In mature mouse sperm only CaV3.1 and CaV3.2 were detected in the head, suggesting its participation in the AR. CaV3.1 and CaV3.3 were found in the principal and the midpiece of the flagella. All CaV3 channels are also present in human sperm, but only to a minor extent in the head. These findings were corroborated by immunogold transmission electron microscopy. Tail localization of CaV3 channels suggested they may participate in motility, however, mibefradil and gossypol concentrations that inhibit CaV3 channels did not significantly affect human sperm motility. Only higher mibefradil doses that can block high-threshold (HVA) CaV channels caused small but significant motility alterations. Antibodies to HVA channels detected CaV1.3 and CaV2.3 in human sperm flagella

Herbarium Areqvipense (HUSA): computerization and representativeness of its collection

Las colecciones científicas y entre ellas los herbarios representan importantes fuentes de información y enseñanza para los investigadores y profesionales en ciencias biológicas. El Herbarium Areqvipense (HUSA), registrado en el Index Herbariorum desde el año 2004, alberga una de las colecciones más importantes del Perú. En este trabajo brindamos información de la colección y damos a conocer su representatividad para la flora peruana. El HUSA cuenta con más de 11000 especímenes registrados, distribuidos en más de 2300 especies, correspondientes en su mayor parte a Magnoliophyta y Pteridophyta (ca. 98%), y en menor proporción por Basidiomycetes y Ascomycetes (Hongos y Líquenes) y Bryophyta (Musgos). Los especímenes provienen de 23 departamentos del Perú, donde Arequipa presenta el mayor número de individuos colectados (3375), equivalente al 31% de la colección. Las familias Asteraceae y de Solanaceae son las mejor representadas con 1571 y 964 especímenes, respectivamente. La mayor cantidad de especímenes georeferenciados corresponden a la zona de vida Bosque muy húmedo bajo tropical con el 15%, seguido por el Bosque muy húmedo premontano tropical con el 8%. Se dan además a conocer los tipos presentes en la colección, así como una reseña del desarrollo del HUSA desde su creación.Scientific collections and herbaria are essential sources of information and education for researchers and practitioners in biological sciences. The Herbarium Areqvipense (HUSA), registered at Index Herbariorum since 2004, holds one of the most important collections in Peru. In this paper we provide information about the collection, and its representativeness for the Peruvian flora. HUSA has more than 11000 specimens recorded to date, with more than 2300 determined species, consisting mostly of Magnoliophyta and Pteridophyta (ca. 98%), and a smaller proportion of Basidiomycetes, Ascomycetes (fungi and lichens) and Bryophyta (mosses). The collection includes specimens from 23 departments of Peru, where the samples belonging to Arequipa have the largest number of individuals collected (3375) accounting for 31% of the collection. Asteraceae and Solanaceae are the most collected with 1571 and 964 specimens, respectively. The majority of geo-referenced specimens came from the tropical wet forest with 15%, followed by the tropical pre-montane wet forest with 8%. We also provide a list of the nomenclatural types and a brief summary of the history and development of HUSA since its creation

Incorporating Breast Asymmetry Studies into CADx Systems

Breast cancer is one of the global leading causes of death among women, and an early detection is of uttermost importance to reduce mortality rates. Screening mammograms, in which radiologists rely only on their eyesight, are one of the most used early detection methods. However, characteristics, such as the asymmetry between breasts, a feature that could be very difficult to visually quantize, is key to breast cancer detection. Due to the highly heterogeneous and deformable structure of the breast itself, incorporating asymmetry measurements into an automated detection system is still a challenge. In this study, we proposed the use of a bilateral registration algorithm as an effective way to automatically measure mirror asymmetry. Furthermore, this information was fed to a machine learning algorithm to improve the accuracy of the model. In this study, 449 subjects (197 with calcifications, 207 with masses, and 45 healthy subjects) from a public database were used to train and evaluate the proposed methodology. Using this procedure, we were able to independently identify subjects with calcifications (accuracy = 0.825, AUC = 0.882) and masses (accuracy = 0.698, AUC = 0.807) from healthy subjects

The Role of Individual Variables, Organizational Variables and Moral Intensity Dimensions in Libyan Management Accountants’ Ethical Decision Making

This study investigates the association of a broad set of variables with the ethical decision making of management accountants in Libya. Adopting a cross-sectional methodology, a questionnaire including four different ethical scenarios was used to gather data from 229 participants. For each scenario, ethical decision making was examined in terms of the recognition, judgment and intention stages of Rest’s model. A significant relationship was found between ethical recognition and ethical judgment and also between ethical judgment and ethical intention, but ethical recognition did not significantly predict ethical intention—thus providing support for Rest’s model. Organizational variables, age and educational level yielded few significant results. The lack of significance for codes of ethics might reflect their relative lack of development in Libya, in which case Libyan companies should pay attention to their content and how they are supported, especially in the light of the under-development of the accounting profession in Libya. Few significant results were also found for gender, but where they were found, males showed more ethical characteristics than females. This unusual result reinforces the dangers of gender stereotyping in business. Personal moral philosophy and moral intensity dimensions were generally found to be significant predictors of the three stages of ethical decision making studied. One implication of this is to give more attention to ethics in accounting education, making the connections between accounting practice and (in Libya) Islam. Overall, this study not only adds to the available empirical evidence on factors affecting ethical decision making, notably examining three stages of Rest’s model, but also offers rare insights into the ethical views of practising management accountants and provides a benchmark for future studies of ethical decision making in Muslim majority countries and other parts of the developing world

Prophets vs. profits: How market competition influences leaders' disciplining behavior towards ethical transgressions

We investigate how market competition influences the way organizational leaders discipline moral transgressions of employees. In a cross-sectional study among organizational leaders at various hierarchical levels (Study 1), we find that strong market competition is related to an instrumental decision frame (business practices being perceived as focused on serving the organization’s interest). This decision frame explains why strong market competition is related to leaders’ perceptions of the evaluation of wrongdoing in terms of instrumental rather than moral concerns. In two subsequent experiments (Study 2 and 3), we find that high (relative to low) market competition makes leaders’ disciplining of moral transgressions contingent upon the instrumentality of the transgression to the organization. We find that the same transgression is punished less severely when it resulted in profit for the organization than when it resulted in loss. This research is among the first to identify conditions that determine the disciplinary responses of organization leaders to employees’ moral transgressions, and it feeds the debate on whether market competition - a fundamental characteristic of capitalist economies - promotes the display of moral or immoral behavior within organization

Trustworthiness of randomized trials in endocrinology—A systematic survey

Background Trustworthy (i.e. low risk of bias) randomized clinical trials (RCTs) play an important role in evidence-based decision making. We aimed to systematically assess the risk of bias of trials published in high-impact endocrinology journals. Methods We searched the MEDLINE/PubMed database between 2014 and 2016 for phase 2–4 RCTs evaluating endocrine-related therapies. Reviewers working independently and in duplicate used the Cochrane Risk of Bias Tool (CCRBT) to determine the extent to which the methods reported protected the results of each RCT from bias. Results We assessed 292 eligible RCTs, of which 40% (116) were judged to be at low risk, 43% (126) at moderate, and 17% (50) at high risk of bias. Blinding of outcome assessment was the least common domain reported 43% (125), while selective reporting of outcomes was the most common 97% (282). In multivariable analysis, RCTs with a parallel design (OR 2.4; 95% CI; 1.2–4.6) and funded by for-profit sources (OR 2.2; 95% CI; 1.3–3.6) were more likely to be at low risk of bias. Conclusions Trustworthy evidence should ultimately shape care to improve the likelihood of desirable patient outcomes. Six out-of 10 RCTs published in top endocrine journals are at moderate/ high-risk of bias. Improving this should be a priority in endocrine researc