Gamification: applicazioni sociali e mobili

L'obiettivo di questa tesi, in base all'analisi di atti di convegni e workshop, lettura di libri e articoli pubblicati in siti Web, in materie di gamification, è per prima cosa, spiegare il concetto della gamification, partendo da alcune definizioni date da ricercatori e progettisti di videogiochi, cercando di capire sia i fattori positivi, sia i fattori negativi. Si vogliono elencare e spiegare gli elementi di gioco che compongono la gamification, con particolare attenzione alle meccaniche, come punti, distintivi, premi e dinamiche, come competenza, espressione di sè, status sociale, elementi collegati tra di loro, analizzando quali meccaniche originano certe dinamiche. Si cercherà anche di analizzare la gamification sotto gli aspetti psicologici e di User Experience che innescano le motivazioni intrinseche ed estrinseche delle persone, le prime azionate dalle meccaniche, le seconde azionate dalle dinamiche della gamification e l'importanza di ciò nella progettazione di applicazioni gamificate. Si vogliono esaminare ed illustrare in generale, progetti i quali adottano tecniche di gamification, che spaziano dal fitness fino ad attività di marketing per capire i benefici riscontrati. Si vuole inoltre scoprire se ci sono dei validi presupposti per sviluppare App gamificate per smarphone, che sfruttino alcune specifiche tecniche dei dispositivi mobili come, connettività, il GPS ed i sensori come ad esempio, l'accelerometro ed altre tecnologie come il lettore NFC, QR-code. Infine, come caso di studio, saranno testate tre app per smarphone, Foursquare, tramite la quale un utente può consultare e lasciare consigli sui luoghi nelle sue vicinanze, Swarm, tramite la quale un utente oltre ad effettuare il check-in in un luogo, può vedere se ci sono amici nelle vicinanze e Waze, tramite la quale un utente può inviare ed apprendere informazioni relative al traffico.

Progettazione e sviluppo di un sistema software di pagamenti basato su nfc - applicazione utente

L’obiettivo di questa tesi è quello di descrivere la progettazione e lo sviluppo di un’applicazione per la gestione di un sistema che permetta agli utenti di effettuare operazioni di pagamento, ricarica, check-in e altre funzionalità. Tutte queste operazioni saranno implementate tramite l’utilizzo della tecnologia NFC (Near Field Communication). Il sistema prevede un'applicazione "cassa" per le transazioni e un'applicazione "utente" per permettere al cliente di visualizzare i dati relativi al proprio conto. In questa tesi sarà analizzata l'applicazione "utente".

Progettazione e sviluppo di un sistema software di pagamenti basato su NFC - applicazione esercente

La tesi in questione ha l'obiettivo di descrivere la progettazione e lo sviluppo di un’applicazione per la gestione di un sistema che permetta agli utenti di effettuare vari tipi di operazioni, tra i quali pagamento, ricarica, check-in e altre funzionalità. Tutte queste operazioni saranno implementate tramite l’utilizzo della tecnologia NFC (Near Field Communication). Il sistema prevede un'applicazione "cassa" per gestire le varie transazioni e un'applicazione "utente" per permettere ai clienti di visualizzare i dati relativi al proprio conto. Dopo una breve introduzione nella quale verrà descritto il sistema nel suo complesso, la presente tesi si occuperà di analizzare nel dettaglio lo sviluppo dell'applicazione "cassa".

Nuove soluzioni per il DigitalMarketing del turismo

Un'idea che si è trasformata in progetto, chiamato "SmartApp", che consiste nella progettazione ed implementazione di un'applicazione iOS, la quale gestisce e facilita alcuni servizi utili all'utente in vacanza. Viene descritto il sistema di check-in all'interno di un esercizio, oltre ai vantaggi che l'utente può favorire tramite l'app, in correlazione ad alcune attività di digital marketing contemporanee.

A framework for cyber-physical system simulation

In these last years, systems engineering has became one of the major research domains. The complexity of systems has increased constantly and nowadays Cyber-Physical Systems (CPS) are a category of particular interest: these, are systems composed by a cyber part (computer-based algorithms) that monitor and control some physical processes. Their development and simulation are both complex due to the importance of the interaction between the cyber and the physical entities: there are a lot of models written in different languages that need to exchange information among each other. Normally people use an orchestrator that takes care of the simulation of the models and the exchange of informations. This orchestrator is developed manually and this is a tedious and long work. Our proposition is to achieve to generate the orchestrator automatically through the use of Co-Modeling, i.e. by modeling the coordination. Before achieving this ultimate goal, it is important to understand the mechanisms and de facto standards that could be used in a co-modeling framework. So, I studied the use of a technology employed for co-simulation in the industry: FMI. In order to better understand the FMI standard, I realized an automatic export, in the FMI format, of the models realized in an existing software for discrete modeling: TimeSquare. I also developed a simple physical model in the existing open source openmodelica tool. Later, I started to understand how works an orchestrator, developing a simple one: this will be useful in future to generate an orchestrator automatically.

Part two: Against the motion. External diameter for AAA size

Aneurysm diameter measurement is quick and easy, but suffers from the pitfalls of being "too rough and ready". When semi-automated segmentation took 7-10 minutes to estimate volume, it was not a practical tool for busy, routine clinical practice. Today, the availability of automatic segmentation in seconds is bound to make volume measurement, along with 3D ultrasonography, the tools of the future. There can be no debate.

Comparing the factorial structure, invariance, and predictive validity of transtheoretical model constructs for alcohol use across restricted and unrestricted settings

With substance abuse treatment expanding in prisons and jails, understanding how behavior change interacts with a restricted setting becomes more essential. The Transtheoretical Model (TTM) has been used to understand intentional behavior change in unrestricted settings, however, evidence indicates restrictive settings can affect the measurement and structure of the TTM constructs. The present study examined data from problem drinkers at baseline and end-of-treatment from three studies: (1) Project CARE (n = 187) recruited inmates from a large county jail; (2) Project Check-In (n = 116) recruited inmates from a state prison; (3) Project MATCH, a large multi-site alcohol study had two recruitment arms, aftercare (n = 724 pre-treatment and 650 post-treatment) and outpatient (n = 912 pre-treatment and 844 post-treatment). The analyses were conducted using cross-sectional data to test for non-invariance of measures of the TTM constructs: readiness, confidence, temptation, and processes of change (Structural Equation Modeling, SEM) across restricted and unrestricted settings. Two restricted (jail and aftercare) and one unrestricted group (outpatient) entering treatment and one restricted (prison) and two unrestricted groups (aftercare and outpatient) at end-of-treatment were contrasted. In addition TTM end-of-treatment profiles were tested as predictors of 12 month drinking outcomes (Profile Analysis). Although SEM did not indicate structural differences in the overall TTM construct model across setting types, there were factor structure differences on the confidence and temptation constructs at pre-treatment and in the factor structure of the behavioral processes at the end-of-treatment. For pre-treatment temptation and confidence, differences were found in the social situations factor loadings and in the variance for the confidence and temptation latent factors. For the end-of-treatment behavioral processes, differences across the restricted and unrestricted settings were identified in the counter-conditioning and stimulus control factor loadings. The TTM end-of-treatment profiles were not predictive of drinking outcomes in the prison sample. Both pre and post-treatment differences in structure across setting types involved constructs operationalized with behaviors that are limited for those in restricted settings. These studies suggest the TTM is a viable model for explicating addictive behavior change in restricted settings but calls for modification of subscale items that refer to specific behaviors and caution in interpreting the mean differences across setting types for problem drinkers. ^

Modeling Techniques for the High-Resolution Interpretation of Cryo-Electron Microscopy Reconstructions

Essential biological processes are governed by organized, dynamic interactions between multiple biomolecular systems. Complexes are thus formed to enable the biological function and get dissembled as the process is completed. Examples of such processes include the translation of the messenger RNA into protein by the ribosome, the folding of proteins by chaperonins or the entry of viruses in host cells. Understanding these fundamental processes by characterizing the molecular mechanisms that enable then, would allow the (better) design of therapies and drugs. Such molecular mechanisms may be revealed trough the structural elucidation of the biomolecular assemblies at the core of these processes. Various experimental techniques may be applied to investigate the molecular architecture of biomolecular assemblies. High-resolution techniques, such as X-ray crystallography, may solve the atomic structure of the system, but are typically constrained to biomolecules of reduced flexibility and dimensions. In particular, X-ray crystallography requires the sample to form a three dimensional (3D) crystal lattice which is technically di‑cult, if not impossible, to obtain, especially for large, dynamic systems. Often these techniques solve the structure of the different constituent components within the assembly, but encounter difficulties when investigating the entire system. On the other hand, imaging techniques, such as cryo-electron microscopy (cryo-EM), are able to depict large systems in near-native environment, without requiring the formation of crystals. The structures solved by cryo-EM cover a wide range of resolutions, from very low level of detail where only the overall shape of the system is visible, to high-resolution that approach, but not yet reach, atomic level of detail. In this dissertation, several modeling methods are introduced to either integrate cryo-EM datasets with structural data from X-ray crystallography, or to directly interpret the cryo-EM reconstruction. Such computational techniques were developed with the goal of creating an atomic model for the cryo-EM data. The low-resolution reconstructions lack the level of detail to permit a direct atomic interpretation, i.e. one cannot reliably locate the atoms or amino-acid residues within the structure obtained by cryo-EM. Thereby one needs to consider additional information, for example, structural data from other sources such as X-ray crystallography, in order to enable such a high-resolution interpretation. Modeling techniques are thus developed to integrate the structural data from the different biophysical sources, examples including the work described in the manuscript I and II of this dissertation. At intermediate and high-resolution, cryo-EM reconstructions depict consistent 3D folds such as tubular features which in general correspond to alpha-helices. Such features can be annotated and later on used to build the atomic model of the system, see manuscript III as alternative. Three manuscripts are presented as part of the PhD dissertation, each introducing a computational technique that facilitates the interpretation of cryo-EM reconstructions. The first manuscript is an application paper that describes a heuristics to generate the atomic model for the protein envelope of the Rift Valley fever virus. The second manuscript introduces the evolutionary tabu search strategies to enable the integration of multiple component atomic structures with the cryo-EM map of their assembly. Finally, the third manuscript develops further the latter technique and apply it to annotate consistent 3D patterns in intermediate-resolution cryo-EM reconstructions. The first manuscript, titled An assembly model for Rift Valley fever virus, was submitted for publication in the Journal of Molecular Biology. The cryo-EM structure of the Rift Valley fever virus was previously solved at 27Å-resolution by Dr. Freiberg and collaborators. Such reconstruction shows the overall shape of the virus envelope, yet the reduced level of detail prevents the direct atomic interpretation. High-resolution structures are not yet available for the entire virus nor for the two different component glycoproteins that form its envelope. However, homology models may be generated for these glycoproteins based on similar structures that are available at atomic resolutions. The manuscript presents the steps required to identify an atomic model of the entire virus envelope, based on the low-resolution cryo-EM map of the envelope and the homology models of the two glycoproteins. Starting with the results of the exhaustive search to place the two glycoproteins, the model is built iterative by running multiple multi-body refinements to hierarchically generate models for the different regions of the envelope. The generated atomic model is supported by prior knowledge regarding virus biology and contains valuable information about the molecular architecture of the system. It provides the basis for further investigations seeking to reveal different processes in which the virus is involved such as assembly or fusion. The second manuscript was recently published in the of Journal of Structural Biology (doi:10.1016/j.jsb.2009.12.028) under the title Evolutionary tabu search strategies for the simultaneous registration of multiple atomic structures in cryo-EM reconstructions. This manuscript introduces the evolutionary tabu search strategies applied to enable a multi-body registration. This technique is a hybrid approach that combines a genetic algorithm with a tabu search strategy to promote the proper exploration of the high-dimensional search space. Similar to the Rift Valley fever virus, it is common that the structure of a large multi-component assembly is available at low-resolution from cryo-EM, while high-resolution structures are solved for the different components but lack for the entire system. Evolutionary tabu search strategies enable the building of an atomic model for the entire system by considering simultaneously the different components. Such registration indirectly introduces spatial constrains as all components need to be placed within the assembly, enabling the proper docked in the low-resolution map of the entire assembly. Along with the method description, the manuscript covers the validation, presenting the benefit of the technique in both synthetic and experimental test cases. Such approach successfully docked multiple components up to resolutions of 40Å. The third manuscript is entitled Evolutionary Bidirectional Expansion for the Annotation of Alpha Helices in Electron Cryo-Microscopy Reconstructions and was submitted for publication in the Journal of Structural Biology. The modeling approach described in this manuscript applies the evolutionary tabu search strategies in combination with the bidirectional expansion to annotate secondary structure elements in intermediate resolution cryo-EM reconstructions. In particular, secondary structure elements such as alpha helices show consistent patterns in cryo-EM data, and are visible as rod-like patterns of high density. The evolutionary tabu search strategy is applied to identify the placement of the different alpha helices, while the bidirectional expansion characterizes their length and curvature. The manuscript presents the validation of the approach at resolutions ranging between 6 and 14Å, a level of detail where alpha helices are visible. Up to resolution of 12 Å, the method measures sensitivities between 70-100% as estimated in experimental test cases, i.e. 70-100% of the alpha-helices were correctly predicted in an automatic manner in the experimental data. The three manuscripts presented in this PhD dissertation cover different computation methods for the integration and interpretation of cryo-EM reconstructions. The methods were developed in the molecular modeling software Sculptor (http://sculptor.biomachina.org) and are available for the scientific community interested in the multi-resolution modeling of cryo-EM data. The work spans a wide range of resolution covering multi-body refinement and registration at low-resolution along with annotation of consistent patterns at high-resolution. Such methods are essential for the modeling of cryo-EM data, and may be applied in other fields where similar spatial problems are encountered, such as medical imaging.

Las formas del salario en la agricultura pampeana : Su rol en el disciplinamiento, el aumento de la productividad y el abaratamiento de la fuerza de trabajo

Las transformaciones socio-económicas, políticas y gremiales acaecidas a fines de los '70 inauguraron un período desfavorable para las condiciones de trabajo de los obreros agrícolas. Se desarrolló una tendencia hacia la disminución de los tiempos requeridos por cada tarea, la discontinuación del proceso productivo, la estacionalización de la demanda de empleo y una mayor especialización de la fuerza de trabajo. La fragmentación extrema del proceso productivo derivó así en el astillamiento del ciclo laboral de los trabajadores en términos de ingresos y de empleadores. En este contexto, fueron logrando imponerse y naturalizarse distintas formas y niveles de remuneración para cada una de las tareas agrícolas, aun en los casos en que un trabajador las realizara todas para un mismo patrón como peón permanente, y singularmente en los casos de los obreros temporarios que se enfrentan a distintos empleadores para desarrollar cada una de las labores con las que construyen su ciclo laboral. Nos proponemos analizar el rol que la combinación de estas formas y niveles salariales ha venido cumpliendo para el abaratamiento de la fuerza de trabajo agrícola en su conjunto, así como en su estímulo a una mayor productividad y en la frustración de conflictos abiertos o a gran escala entre esta fracción de la clase obrera rural y sus patrones, a pesar de las condiciones de trabajo desfavorables que verificamos en este estudio

Las formas del salario en la agricultura pampeana : Su rol en el disciplinamiento, el aumento de la productividad y el abaratamiento de la fuerza de trabajo

Las transformaciones socio-económicas, políticas y gremiales acaecidas a fines de los '70 inauguraron un período desfavorable para las condiciones de trabajo de los obreros agrícolas. Se desarrolló una tendencia hacia la disminución de los tiempos requeridos por cada tarea, la discontinuación del proceso productivo, la estacionalización de la demanda de empleo y una mayor especialización de la fuerza de trabajo. La fragmentación extrema del proceso productivo derivó así en el astillamiento del ciclo laboral de los trabajadores en términos de ingresos y de empleadores. En este contexto, fueron logrando imponerse y naturalizarse distintas formas y niveles de remuneración para cada una de las tareas agrícolas, aun en los casos en que un trabajador las realizara todas para un mismo patrón como peón permanente, y singularmente en los casos de los obreros temporarios que se enfrentan a distintos empleadores para desarrollar cada una de las labores con las que construyen su ciclo laboral. Nos proponemos analizar el rol que la combinación de estas formas y niveles salariales ha venido cumpliendo para el abaratamiento de la fuerza de trabajo agrícola en su conjunto, así como en su estímulo a una mayor productividad y en la frustración de conflictos abiertos o a gran escala entre esta fracción de la clase obrera rural y sus patrones, a pesar de las condiciones de trabajo desfavorables que verificamos en este estudio

Las formas del salario en la agricultura pampeana : Su rol en el disciplinamiento, el aumento de la productividad y el abaratamiento de la fuerza de trabajo

Las transformaciones socio-económicas, políticas y gremiales acaecidas a fines de los '70 inauguraron un período desfavorable para las condiciones de trabajo de los obreros agrícolas. Se desarrolló una tendencia hacia la disminución de los tiempos requeridos por cada tarea, la discontinuación del proceso productivo, la estacionalización de la demanda de empleo y una mayor especialización de la fuerza de trabajo. La fragmentación extrema del proceso productivo derivó así en el astillamiento del ciclo laboral de los trabajadores en términos de ingresos y de empleadores. En este contexto, fueron logrando imponerse y naturalizarse distintas formas y niveles de remuneración para cada una de las tareas agrícolas, aun en los casos en que un trabajador las realizara todas para un mismo patrón como peón permanente, y singularmente en los casos de los obreros temporarios que se enfrentan a distintos empleadores para desarrollar cada una de las labores con las que construyen su ciclo laboral. Nos proponemos analizar el rol que la combinación de estas formas y niveles salariales ha venido cumpliendo para el abaratamiento de la fuerza de trabajo agrícola en su conjunto, así como en su estímulo a una mayor productividad y en la frustración de conflictos abiertos o a gran escala entre esta fracción de la clase obrera rural y sus patrones, a pesar de las condiciones de trabajo desfavorables que verificamos en este estudio

High-Speed Rail Versus Air Transportation: Case Study of Madrid–Barcelona, Spain.

Travel time savings, better quality of the supplied services, greater comfort for the users, and improved accessibility are the main factors of success of High Speed Rail(HSR)links. This paper presents the results from a revealed and stated preference survey conducted to both HSR and air transport users in the Madrid Barcelona corridor. The data gathered from the stated preference survey was used to calibrate a modal choice model aiming at explaining competition between HSR and air transportation in the corridor. From the model, the authors obtain that prices and service frequency are the most important variables to compete with the other mode. In addition, they found that check-in and security controls at the airport are a crucial variable for the users in their modal choice. Other policies, such as the improvement of parking facilities at the train stations, play a secondary role.

Military and government applications of human-machine communication by voice.

This paper describes a range of opportunities for military and government applications of human-machine communication by voice, based on visits and contacts with numerous user organizations in the United States. The applications include some that appear to be feasible by careful integration of current state-of-the-art technology and others that will require a varying mix of advances in speech technology and in integration of the technology into applications environments. Applications that are described include (1) speech recognition and synthesis for mobile command and control; (2) speech processing for a portable multifunction soldier's computer; (3) speech- and language-based technology for naval combat team tactical training; (4) speech technology for command and control on a carrier flight deck; (5) control of auxiliary systems, and alert and warning generation, in fighter aircraft and helicopters; and (6) voice check-in, report entry, and communication for law enforcement agents or special forces. A phased approach for transfer of the technology into applications is advocated, where integration of applications systems is pursued in parallel with advanced research to meet future needs.

Infrared microspectroscopy of inflammatory process and colon tumors.

According to the last global burden of disease published by the World Health Organization, tumors were the third leading cause of death worldwide in 2004. Among the different types of tumors, colorectal cancer ranks as the fourth most lethal. To date, tumor diagnosis is based mainly on the identification of morphological changes in tissues. Considering that these changes appears after many biochemical reactions, the development of vibrational techniques may contribute to the early detection of tumors, since they are able to detect such reactions. The present study aimed to develop a methodology based on infrared microspectroscopy to characterize colon samples, providing complementary information to the pathologist and facilitating the early diagnosis of tumors. The study groups were composed by human colon samples obtained from paraffin-embedded biopsies. The groups are divided in normal (n=20), inflammation (n=17) and tumor (n=18). Two adjacent slices were acquired from each block. The first one was subjected to chemical dewaxing and H&E staining. The infrared imaging was performed on the second slice, which was not dewaxed or stained. A computational preprocessing methodology was employed to identify the paraffin in the images and to perform spectral baseline correction. Such methodology was adapted to include two types of spectral quality control. Afterwards the preprocessing step, spectra belonging to the same image were analyzed and grouped according to their biochemical similarities. One pathologist associated each obtained group with some histological structure based on the H&E stained slice. Such analysis highlighted the biochemical differences between the three studied groups. Results showed that severe inflammation presents biochemical features similar to the tumors ones, indicating that tumors can develop from inflammatory process. A spectral database was constructed containing the biochemical information identified in the previous step. Spectra obtained from new samples were confronted with the database information, leading to their classification into one of the three groups: normal, inflammation or tumor. Internal and external validation were performed based on the classification sensitivity, specificity and accuracy. Comparison between the classification results and H&E stained sections revealed some discrepancies. Some regions histologically normal were identified as inflammation by the classification algorithm. Similarly, some regions presenting inflammatory lesions in the stained section were classified into the tumor group. Such differences were considered as misclassification, but they may actually evidence that biochemical changes are in course in the analyzed sample. In the latter case, the method developed throughout this thesis would have proved able to identify early stages of inflammatory and tumor lesions. It is necessary to perform additional experiments to elucidate this discrepancy between the classification results and the morphological features. One solution would be the use of immunohistochemistry techniques with specific markers for tumor and inflammation. Another option includes the recovering of the medical records of patients who participated in this study in order to check, in later times to the biopsy collection, whether they actually developed the lesions supposedly detected in this research.

Mutações inativadoras no gene MKRN3 são causa de puberdade precoce central familial

A maioria dos casos de puberdade precoce central (PPC) em meninas permanece idiopática. A hipótese de uma causa genética vem se fortalecendo após a descoberta de alguns genes associados a este fenótipo, sobretudo aqueles implicados com o sistema kisspeptina (KISS1 e KISS1R). Entretanto, apenas casos isolados de PPC foram relacionados à mutação na kisspeptina ou em seu receptor. Até recentemente, a maioria dos estudos genéticos em PPC buscava genes candidatos selecionados com base em modelos animais, análise genética de pacientes com hipogonadismo hipogonadotrófico, ou ainda, nos estudos de associação ampla do genoma. Neste trabalho, foi utilizado o sequenciamento exômico global, uma metodologia mais moderna de sequenciamento, para identificar variantes associadas ao fenótipo de PPC. Trinta e seis indivíduos com a forma de PPC familial (19 famílias) e 213 casos aparentemente esporádicos foram inicialmente selecionados. A forma familial foi definida pela presença de mais de um membro afetado na família. DNA genômico foi extraído dos leucócitos do sangue periférico de todos os pacientes. O estudo de sequenciamento exômico global realizado pela técnica ILLUMINA, em 40 membros de 15 famílias com PPC, identificou mutações inativadoras em um único gene, MKRN3, em cinco dessas famílias. Pesquisa de mutação no MKRN3 realizada por sequenciamento direto em duas famílias adicionais (quatro pacientes) identificou duas novas variantes nesse gene. O MKRN3 é um gene de um único éxon, localizado no cromossomo 15 em uma região crítica para a síndrome de Prader Willi. O gene MKRN3 sofre imprinting materno, sendo expresso apenas pelo alelo paterno. A descoberta de mutações em pacientes com PPC familial despertou o interesse para a pesquisa de mutações nesse gene em 213 pacientes com PPC aparentemente esporádica por meio de reação em cadeia de polimerase seguida de purificação enzimática e sequenciamento automático direto (Sanger). Três novas mutações e duas já anteriormente identificadas, incluindo quatro frameshifts e uma variante missense, foram encontradas, em heterozigose, em seis meninas não relacionadas. Todas as novas variantes identificadas estavam ausentes nos bancos de dados (1000 Genomes e Exome Variant Server). O estudo de segregação familial em três dessas meninas com PPC aparentemente esporádica e mutação no MKRN3 confirmou o padrão de herança autossômica dominante com penetrância completa e transmissão exclusiva pelo alelo paterno, demonstrando que esses casos eram, na verdade, também familiares. A maioria das mutações encontradas no MKRN3 era do tipo frameshift ou nonsense, levando a stop códons prematuros e proteínas truncadas e, portanto, confirmando a associação com o fenótipo. As duas mutações missenses (p.Arg365Ser e p.Phe417Ile) identificadas estavam localizadas em regiões de dedo ou anel de zinco, importantes para a função da proteína. Além disso, os estudos in silico dessas duas variantes demonstraram patogenicidade. Todos os pacientes com mutação no MKRN3 apresentavam características clínicas e hormonais típicas de ativação prematura do eixo reprodutivo. A mediana de idade de início da puberdade foi de 6 anos nas meninas (variando de 3 a 6,5) e 8 anos nos meninos (variando de 5,9 a 8,5). Tendo em vista o fenômeno de imprinting, análise de metilação foi também realizada em um subgrupo de 52 pacientes com PPC pela técnica de MS-MLPA, mas não foram encontradas alterações no padrão de metilação. Em conclusão, este trabalho identificou um novo gene associado ao fenótipo de PPC. Atualmente, mutações inativadoras no MKRN3 representam a causa genética mais comum de PPC familial (33%). O MKRN3 é o primeiro gene imprintado associado a distúrbios puberais em humanos. O mecanismo preciso de ação desse gene na regulação da secreção de GnRH necessita de estudos adicionais