Comparative modular analysis of gene expression in vertebrate development

The focus of my PhD research was the concept of modularity. In the last 15 years, modularity has become a classic term in different fields of biology. On the conceptual level, a module is a set of interacting elements that remain mostly independent from the elements outside of the module. I used modular analysis techniques to study gene expression evolution in vertebrates. In particular, I identified ``natural'' modules of gene expression in mouse and human, and I showed that expression of organ-specific and system-specific genes tends to be conserved between such distance vertebrates as mammals and fishes. Also with a modular approach, I studied patterns of developmental constraints on transcriptome evolution. I showed that none of the two commonly accepted models of the evolution of embryonic development (``evo-devo'') are exclusively valid. In particular, I found that the conservation of the sequences of regulatory regions is highest during mid-development of zebrafish, and thus it supports the ``hourglass model''. In contrast, events of gene duplication and new gene introduction are most rare in early development, which supports the ``early conservation model''. In addition to the biological insights on transcriptome evolution, I have also discussed in detail the advantages of modular approaches in large-scale data analysis. Moreover, I re-analyzed several studies (published in high-ranking journals), and showed that their conclusions do not hold out under a detailed analysis. This demonstrates that complex analysis of high-throughput data requires a co-operation between biologists, bioinformaticians, and statisticians.

Agenda web modular

El proyecto consiste en la realización de una agenda web modular, utilizando para ello las tecnologías de la plataforma J2EE mediante frameworks (Hibernate y Spring) y un patrón de arquitectura (MVC). La agenda se ha realizado para ser gestionada por un servidor Apache Tomcat y sus datos almacenados en MySQL.

FM127: Systemic metal ion levels in patients with modular neck total hip arthroplasties: a prospective cohort study

There is increasing evidence that modular neck stems are prone to corrosion-related complications. Recent studies showed elevated metal ions levels and occasional pseudotumor formation in patients with such implants. The purpose of this study was to compare systemic metal-ion levels in patients after primary THA with modular neck stems to those of patients after non-modular implants. To our knowledge, this is the first cohort study including a control group, THA without CoCr heads and dry-assembled neck-stem connections. Methods: 50 patients after THA at a minimum follow-up of 1 year have been selected for the study. Patients with multiple prosthesis or other implants have been deselected. All received a cementless SPS stem from Symbios (Ti6Al4V). 40 patients have the modular neck (CoCr) version and 10 a monobloc version. All bearings were either ceramic-ceramic or ceramic-polyethylene to minimize other sources of CoCr ion release. In the modular group, the neck was chosen pre-operatively based on a 3D planning, allowing for a dry assembly of the stem and neck on the back table before implantation. A plasma system coupled to mass spectrometry was used for a complete elementary quantification in blood and serum separately. Clinical outcome was measured using the Oxford Hip Score. Results : Complete data sets of 29 patients (24 in the modular neck-group (10male, mean age 63y, 35-84y) and 5 in the monobloc-group (3 male, 69 y, 51-83y) are available to date. Mean Co blood levels were .95 ug/L (.14-12.4) in the modular group vs .27 ug/L (.10-.73) in the monobloc group (p=.2). Respective values for Cr were significantly higher in the modular group (.99 g/L; range .75-1.21) compared to those in the monobloc group (.74 g/L ;.62-.86; p=.001). No significant difference was found when comparing serum levels. 5/24 patients had Co levels above 1 g/L (12/24 for Cr), which is by some considered as a relevant elevation. The maximum Co level was measured in an asymptomatic patient. The Oxford Hip Scores were similar in both groups. Conclusion: Cr levels were significantly elevated in the modular neck group compared to those in the monobloc group. 1/24 patients with a modular prosthesis exhibited Co levels, which are beyond the threshold accepted even for metal-on-metal bearing couples. These results have contributed to our decision to abandon the use of modular neck stems. Routine follow-up including annual measurements of systemic CoCr concentrations should be considered.

Arquitectura, integració i implementació d'un projecte modular J2EE

L'objectiu principal del TFC consisteix en la creació d'una complexa estructura modular J2EE basada i mantinguda per Maven, amb la utilització com frameworks Spring, Hibernate i Flex principalment. Aquesta estructura permet reprendre el desenvolupament inicial, nous desenvolupaments i manteniments d'una aplicació, amb un cost temporal mínim per la part de l'equip de desenvolupament.

Una Proposta d'avaluació per competències a la universitat en una estructura modular

En aquest treball presentem una proposta d’avaluació per competències en una estructura modular que és fruit de la nostra experiència com a professors universitaris. Volem oferir un instrument d’avaluació conjunta per a tot l’equip de professors de mòdul que sigui vàlid, àgil i operatiu i que permeti donar feedback a cada estudiant del seu procés d’aprenentatge. Després de presentar els trets més singulars de la nostra institució i exposar alguns referents teòrics en relació a l’avaluació de competències, indiquem quines són les competències que hem seleccionat i aprofundim en la metodologia de treball i avaluació de les mateixes. Aquesta metodologia varia segons els espais acadèmics: gran grup, grup mig i seminari. A cadascun d’aquests espais es treballen i s’avaluen unes competències determinades, tot i que d’una forma més genèrica totes es desenvolupen conjuntament ens els tres àmbits. Considerem que és fonamental assenyalar que no es tracta d’avaluar “per assignatures” ni “per activitats”, sinó d’avaluar les competències que es desenvolupen a través de les matèries i de les propostes de treball que s’especifiquen en el pla docent.. L’ instrument d’avaluació que presentem possibilita la participació de tot el professorat implicat en el mateix mòdul i alhora permet que cada professor utilitzi els seus propis indicadors d’avaluació, aconseguint harmonitzar les dinàmiques de treball individuals i de grup.

Adverse tissue reaction to corrosion at the neck-stem junction after modular primary total hip arthroplasty.

Complications related to the neck-stem junction of modular stems used for total hip arthroplasty (THA) are generating increasing concern. A 74-year-old male had increasing pain and a cutaneous reaction around the scar 1 year after THA with a modular neck-stem. Imaging revealed osteolysis of the calcar and a pseudo-tumour adjacent to the neck-stem junction. Serum cobalt levels were elevated. Revision surgery to exchange the stem and liner and to resect the pseudo-tumour was performed. Analysis of the stem by scanning electron microscopy and by energy dispersive X-ray and white light interferometry showed fretting corrosion at the neck-stem junction contrasting with minimal changes at the head-neck junction. Thus, despite dry assembly of the neck and stem on the back table at primary THA, full neck-stem contact was not achieved, and the resulting micromotion at the interface led to fretting corrosion. This case highlights the mechanism of fretting corrosion at the neck-stem interface responsible for adverse local tissue reactions. Clinical and radiological follow-up is mandatory in patients with dual-modular stems.

Modelo para una autoevaluación modular en una institución educativa (BADI)

Una eficaz acción educativa obliga necesariamente a plantearse en profundidad la autoevaluación como modelo de cambio y la participación de todos los estamentos de la comunidad educativa. Un mayor o menor grado de participación viene a ser un indicador que nos permite valorar cualquier propuesta de «calidad», «reforma» o «innovación». El modelo B.A.D.I. yen especial su instrumento modular, responde a las exigencias particulares de reflexión, análisis y toma de decisiones que se realiza en cada centro para responder adecuadamente a cualquier planteamiento innovador. Los principios fundamentales de este modelo se resumen en: A. Es un modelo de concepción organicista, estamental, con definición ideológica. B. Responde a un enfoque fundamentalmente rogeriano. C. Participa de los enfoques social, abierto, dinámico, cultural y positivo. Comparte la teoría moderna de la organización y sus indicadores se agrupan en cuatro fases: Criterial, presupuestaria, metodológica e informativa. D. Se identifica con los modelos centrados en la evaluación de cambio, de forma especial con la autoevaluación. La flexibilidad que caracteriza al modelo viene dado por el instrumento modular de área o de criterio, como resultado de la participación y el consenso de todos los estamentos de la institución educativa.

A modular tethering complex for endosomal recycling.

How proteins migrate through the interconnected organelles of the endolysosomal system is poorly understood. A piece of the puzzle has been added with the identification of a complex of tethering factors that functions in the recycling of proteins towards the cell surface.

Harmonising the Modular Product Range

Työn tavoitteena on analysoida KONEen hissien ovituoteperheitä ja harmonisoida modulaarista ovituotevalikoimaa niin, että tulos olisi mahdollisimman suotuisa KONEelle sekä sen sidosryhmille. Harmonisointi toteutetaan, koska KONEen tuotevalikoima on erittäin laaja ja monimutkainen ja siitä syystä erittäin kallis ja vaikea hallita ja ylläpitää. Tavoitteena on selvittää myös termejä modulaarisuus ja tuotealusta olennaisen kirjallisuuden pohjalta. Nykyään yritysten täytyy kehittää tuotevalikoimaa jatkuvasti. Yrityksen koko tuotevalikoiman varioituvuus tulisi kuitenkin pitää järkevissä rajoissa. Moduuleita ja tuotealustoja pitäisi käyttää jakamaan tuotteiden avainelementtejä ja lisäämään varioituvuutta helposti hallittavalla tavalla. Kannattamattomat ja matalavolyymiset tuotteet kuluttavat yrityksen niukkoja resursseja. Tällaiset tuotteet tulisi poistaa tuotevalikoimasta, mutta ei ilman harkintaa. Kannattama-tonkin tuote voi olla erittäin arvokas asiakkaalle ja tällaisen tuotteen hylkääminen voi olla yritykselle pitkällä tähtäimellä erittäin kohtalokasta. Työn tuloksena oli harmonisointiehdotus KONEen AMD-oville ja selvitys harmonisoinnin vaikutuksista. Harmonisointi KONEella päätettiin toteuttaa siten, että matalavolyymiset tuotteet siirrettiin erikoistuotteiden valikoimaan. Myös kustannusanalyysi tukee harmonisointipäätöstä laskentajärjestelmän puutteista huolimatta.

Designing a modular, open and expandable Bluetooth-platform

Lähitulevaisuudessa langattomien järjestelmien kaupalliset mahdollisuudet tulevat olemaan valtavia. Tutkiaksemme tulevia tarpeita, tässä diplomityössä esitellään kuinka voidaan suunnitella ja toteuttaa avoin langaton asiakas-palvelin järjestelmä. Järjestelmänä päätettiin käyttää Bluetooth:ia. Tutkituista langattomista standardeista Bluetooth sopii parhaiten akkukäyttöiselle laitteelle, jonka tulee olla monipuolinen. Lisäksi Bluetooth:iin on liitetty suuria kaupallisia odotuksia ja yksi työn tavoitteista olikin tutkia, ovatko nämä odotukset realistisia. Bluetooth:iin havaittiin liittyvän paljon ylimainontaa ja, sen todettiin olevan monimutkainen. Sillä on kuitenkin paljon ominaisuuksia ja erilaisten käyttöprofiilien avulla sitä voidaan käyttää monenlaisiin tehtäviin. Suunniteltu järjestelmä ajaa socket-palvelinta Bluetooth-yhteyden päällä. Tietyntyyppiseen liikenteeseen erikoistuneet socket:t tarjoavat vaaditun laajennattavuuden. Palvelin toteutetiin Linux-säikeenä ja se hallitsee Bluetooth protokollapinoa sekä sovelluksia, joita suoritetaan palvelimella. Näiden sovelluksien palvelut ovat muiden käytössä Bluetooth:n kautta.

Population Variation and Genetic Control of Modular Chromatin Architecture in Humans.

Chromatin state variation at gene regulatory elements is abundant across individuals, yet we understand little about the genetic basis of this variability. Here, we profiled several histone modifications, the transcription factor (TF) PU.1, RNA polymerase II, and gene expression in lymphoblastoid cell lines from 47 whole-genome sequenced individuals. We observed that distinct cis-regulatory elements exhibit coordinated chromatin variation across individuals in the form of variable chromatin modules (VCMs) at sub-Mb scale. VCMs were associated with thousands of genes and preferentially cluster within chromosomal contact domains. We mapped strong proximal and weak, yet more ubiquitous, distal-acting chromatin quantitative trait loci (cQTL) that frequently explain this variation. cQTLs were associated with molecular activity at clusters of cis-regulatory elements and mapped preferentially within TF-bound regions. We propose that local, sequence-independent chromatin variation emerges as a result of genetic perturbations in cooperative interactions between cis-regulatory elements that are located within the same genomic domain.

Are we modular lying cues detectors ? The answer is "yes sometimes"

We quickly form first impressions about newly encountered people guiding our subsequent behaviour (approach, avoidance). Such instant judgments might be innate and automatic, being performed unconsciously and independently to other cognitive processes. Lying detection might be subject to such a modular process. Unfortunately, numerous studies highlighted problems with lying detection paradigms such as high error rates and learning effects. Additionally, humans should be motivated doing both detecting others' lies and dis- guising own lies. Disguising own lies might even be more challenging than detecting other people's lies. Thus, when trying to disguise cheating behaviour, liars might display a mixture of disguising (fake) trust cues and uncontrolled lying cues making the interpretation of the expression difficult (perceivers are guessing). In two consecutive online studies, we tested whether seeing an increasing amount (range 0-4) of lying cues (LC) and non-lying cues (NLC) on a standard face results in enhanced guessing behaviour (studies 1 and 2) and that enhanced guessing is accompanied by slower responding (study 2). Results showed that pronounced guessing and slowest responding occurred for faces with an intermediate number and not with the highest number of LC and NLC. In particular, LC were more impor- tant than NLC to uncertain lying decisions. Thus, only a few LC may interfere with automatic processing of lying detection (irrespective of NLC), probably because too little lying cue information is yet available.

Tissue-specific regulatory circuits reveal variable modular perturbations across complex diseases.

Mapping perturbed molecular circuits that underlie complex diseases remains a great challenge. We developed a comprehensive resource of 394 cell type- and tissue-specific gene regulatory networks for human, each specifying the genome-wide connectivity among transcription factors, enhancers, promoters and genes. Integration with 37 genome-wide association studies (GWASs) showed that disease-associated genetic variants-including variants that do not reach genome-wide significance-often perturb regulatory modules that are highly specific to disease-relevant cell types or tissues. Our resource opens the door to systematic analysis of regulatory programs across hundreds of human cell types and tissues (http://regulatorycircuits.org).

The modular forming press for paperboard packages

In this master’s thesis the structural and functional features of a forming tool are developed to meet the needs of modern packaging production for paperboard packaging are studied. The goal of the study is to develop a new type of machine for the manufacture of the paperboard package by pressing. In the structure of the developed forming press the possibility to modify the packaging as well as the requirements of industrial production, food hygiene and other operational matters are accounted for. The press has been sized based on the main dimensions of a single food-grade paperboard tray. In the LUT Packaging Laboratory the forming press is designed suitable for on-line operation. In addition, suggestions for further development of packaging line and equipment have been made based on the information gathered during this thesis study.