Upconverting Phosphor Technology: Exceptional Photoluminescent Properties Light Up Homogeneous Bioanalytical Assays

The aim of the present study was to demonstrate the wide applicability of the novel photoluminescent labels called upconverting phosphors (UCPs) in proximity-based bioanalytical assays. The exceptional features of the lanthanide-doped inorganic UCP compounds stem from their capability for photon upconversion resulting in anti-Stokes photoluminescence at visible wavelengths under near-infrared (NIR) excitation. Major limitations related to conventional photoluminescent labels are avoided, rendering the UCPs a competitive next-generation label technology. First, the background luminescence is minimized due to total elimination of autofluorescence. Consequently, improvements in detectability are expected. Second, at the long wavelengths (>600 nm) used for exciting and detecting the UCPs, the transmittance of sample matrixes is significantly greater in comparison with shorter wavelengths. Colored samples are no longer an obstacle to the luminescence measurement, and more flexibility is allowed even in homogeneous assay concepts, where the sample matrix remains present during the entire analysis procedure, including label detection. To transform a UCP particle into a biocompatible label suitable for bioanalytical assays, it must be colloidal in an aqueous environment and covered with biomolecules capable of recognizing the analyte molecule. At the beginning of this study, only UCP bulk material was available, and it was necessary to process the material to submicrometer-sized particles prior to use. Later, the ground UCPs, with irregular shape, wide size-distribution and heterogeneous luminescence properties, were substituted by a smaller-sized spherical UCP material. The surface functionalization of the UCPs was realized by producing a thin hydrophilic coating. Polymer adsorption on the UCP surface is a simple way to introduce functional groups for bioconjugation purposes, but possible stability issues encouraged us to optimize an optional silica-encapsulation method which produces a coating that is not detached in storage or assay conditions. An extremely thin monolayer around the UCPs was pursued due to their intended use as short-distance energy donors, and much attention was paid to controlling the thickness of the coating. The performance of the UCP technology was evaluated in three different homogeneous resonance energy transfer-based bioanalytical assays: a competitive ligand binding assay, a hybridization assay for nucleic acid detection and an enzyme activity assay. To complete the list, a competitive immunoassay has been published previously. Our systematic investigation showed that a nonradiative energy transfer mechanism is indeed involved, when a UCP and an acceptor fluorophore are brought into close proximity in aqueous suspension. This process is the basis for the above-mentioned homogeneous assays, in which the distance between the fluorescent species depends on a specific biomolecular binding event. According to the studies, the submicrometer-sized UCP labels allow versatile proximity-based bioanalysis with low detection limits (a low-nanomolar concentration for biotin, 0.01 U for benzonase enzyme, 0.35 nM for target DNA sequence).

Unconventional integrin-ligand interactions

Integrins are cell surface adhesion and signaling receptors. Cells use integrins to attach to the extracellular matrix and to other cells, as well as for sensing their environment. In addition to adhesion and migration, integrins have been shown to be important for many biological processes including apoptosis, cell proliferation, and differentiation into specific tissues. Many important next generation biological drugs inhibit integrin functions. Thus, research into interactions between integrins and their ligands under different physiological and pathological conditions is not only of academic interest, but is also important for the field of drug discovery. In this Ph.D. project, the functions of integrin-ligand interactions were studied under different physiologically interesting conditions including 1) human echovirus 1 binding to integrin α2β1, 2) integrin α2β1 binding to collagen under flow conditions, 3) integrin α2β1 binding to a ligand in the presence of the angiogenesis inhibitor histidine rich glycoprotein (HRG) and 4) integrin binding to posttranslationally citrullinated ligands. As a result of the project, we could show that for each condition the integrin-ligand interaction is somewhat unconventional. 1) Echovirus 1 binds only to non-activated conformations of integrin α2β1. 2) Surprisingly, the non-activated conformation is also the primary conformation of integrin α2β1 when it binds to collagen under flow conditions, like when platelets adhere to subendothelial collagen in vascular injuries. In addition, the pre-activation of integrin α2β1 does not increase adhesion under flow. 3) HRG binds to integrin α2β1 through a low-affinity interaction that inhibits integrin binding to collagen. This shows that low affinity interactions could be biologically relevant and possibly regulate angiogenesis. 4) The citrullination of collagen, a posttranslational modification reported to occur in rheumatoid arthritis, specifically inhibits the binding of integrin α10β1 and α11β1, but does not affect the binding of α1β1 ja α2β1. On the other hand, the citrullination of isoDGR in fibronectin and RGD in pro-TGF- β:n inhibit integrin binding completely. Citrullination seems to be an inflammation related process and integrin ligands become citrullinated frequently in vivo. This Ph.D. thesis suggests that unconventional interaction mechanisms between integrins and their ligands, such as posttranslational modifications, low affinity interactions, and non-activated integrin conformations, can have an important role in pathological processes. The study of these kinds of integrin-ligand interactions is important for understanding biological phenomena more deeply. The research might also be beneficial for the development of integrin based therapies for treating diseases.

Optimal Sub-Pixel arrangements and coding for ultra-high resolution three-dimensional OLED displays

Information display technology is a rapidly growing research and development field. Using state-of-the-art technology, optical resolution can be increased dramatically by organic light-emitting diode - since the light emitting layer is very thin, under 100nm. The main question is what pixel size is achievable technologically? The next generation of display will considers three-dimensional image display. In 2D , one is considering vertical and horizontal resolutions. In 3D or holographic images, there is another dimension – depth. The major requirement is the high resolution horizontal dimension in order to sustain the third dimension using special lenticular glass or barrier masks, separate views for each eye. The high-resolution 3D display offers hundreds of more different views of objects or landscape. OLEDs have potential to be a key technology for information displays in the future. The display technology presented in this work promises to bring into use bright colour 3D flat panel displays in a unique way. Unlike the conventional TFT matrix, OLED displays have constant brightness and colour, independent from the viewing angle i.e. the observer's position in front of the screen. A sandwich (just 0.1 micron thick) of organic thin films between two conductors makes an OLE Display device. These special materials are named electroluminescent organic semi-conductors (or organic photoconductors (OPC )). When electrical current is applied, a bright light is emitted (electrophosphorescence) from the formed Organic Light-Emitting Diode. Usually for OLED an ITO layer is used as a transparent electrode. Such types of displays were the first for volume manufacture and only a few products are available in the market at present. The key challenges that OLED technology faces in the application areas are: producing high-quality white light achieving low manufacturing costs increasing efficiency and lifetime at high brightness. Looking towards the future, by combining OLED with specially constructed surface lenses and proper image management software it will be possible to achieve 3D images.

Uso de la matriz extracelular como material para ingeniería de tejidos

Introducción: La evaluación de injertos vasculares de submucosa de intestino delgado para la regeneración de vasos sanguíneos ha producido una permeabilidad variable (0-100%) que ha sido concurrente con la variabilidad en las técnicas de fabricación. Metodología: Investigamos los efectos de fabricación en permeabilidad y regeneración en un diseño experimental de 22factorial que combino: 1) preservación (P) o remoción (R) de la capa estratum compactum del intestino, y 2) deshidratada (D) o hidratada (H), dentro de cuatro grupos de estudio (PD, RD, PH, RH). Los injertos fueron implantados en las Arterias Carótidas de porcinos (ID 4.5mm, N=4, 7d). Permeabilidad, trombogenicidad, reacción inflamatoria, vascularización, infiltración de fibroblastos, perfil de polarización de macrófagos y fuerza tensil biaxial fueron evaluadas. Resultados: Todos los injertos PD permanecieron permeables (4/4), pero tuvieron escasa vascularización e infiltración de fibroblastos. El grupo RD permaneció permeable (4/4), presentó una extensa vascularización e infiltración de fibroblastos, y el mayor número del fenotipo de macrófagos (M2) asociado a regeneración. El grupo RH presentó menor permeabilidad (3/4), una extensa vascularización e infiltración de fibroblastos, y un perfil dominante de M2. El grupo PH presentó el menor grado de permeabilidad, y a pesar de mayor infiltración celular que PD, exhibió un fenotipo de macrófagos dominante adverso. La elasticidad de los injertos R evolucionó de una manera similar a las Carótidas nativas (particularmente RD, mientras que los injertos P mantuvieron su rigidez inicial. Discusión: Concluimos que los parámetros de fabricación afectan drásticamente los resultados, siendo los injertos RD los que arrojaron mejores resultados.

Toward a new generation of world climate research and computing facilities

The impending threat of global climate change and its regional manifestations is among the most important and urgent problems facing humanity. Society needs accurate and reliable estimates of changes in the probability of regional weather variations to develop science-based adaptation and mitigation strategies. Recent advances in weather prediction and in our understanding and ability to model the climate system suggest that it is both necessary and possible to revolutionize climate prediction to meet these societal needs. However, the scientific workforce and the computational capability required to bring about such a revolution is not available in any single nation. Motivated by the success of internationally funded infrastructure in other areas of science, this paper argues that, because of the complexity of the climate system, and because the regional manifestations of climate change are mainly through changes in the statistics of regional weather variations, the scientific and computational requirements to predict its behavior reliably are so enormous that the nations of the world should create a small number of multinational high-performance computing facilities dedicated to the grand challenges of developing the capabilities to predict climate variability and change on both global and regional scales over the coming decades. Such facilities will play a key role in the development of next-generation climate models, build global capacity in climate research, nurture a highly trained workforce, and engage the global user community, policy-makers, and stakeholders. We recommend the creation of a small number of multinational facilities with computer capability at each facility of about 20 peta-flops in the near term, about 200 petaflops within five years, and 1 exaflop by the end of the next decade. Each facility should have sufficient scientific workforce to develop and maintain the software and data analysis infrastructure. Such facilities will enable questions of what resolution, both horizontal and vertical, in atmospheric and ocean models, is necessary for more confident predictions at the regional and local level. Current limitations in computing power have placed severe limitations on such an investigation, which is now badly needed. These facilities will also provide the world's scientists with the computational laboratories for fundamental research on weather–climate interactions using 1-km resolution models and on atmospheric, terrestrial, cryospheric, and oceanic processes at even finer scales. Each facility should have enabling infrastructure including hardware, software, and data analysis support, and scientific capacity to interact with the national centers and other visitors. This will accelerate our understanding of how the climate system works and how to model it. It will ultimately enable the climate community to provide society with climate predictions, which are based on our best knowledge of science and the most advanced technology.

Attacking human implants: a new generation of cybercrime

Human ICT implants, such as RFID implants, cochlear implants, cardiac pacemakers, Deep Brain Stimulation, bionic limbs connected to the nervous system, and networked cognitive prostheses, are becoming increasingly complex. With ever-growing data processing functionalities in these implants, privacy and security become vital concerns. Electronic attacks on human ICT implants can cause significant harm, both to implant subjects and to their environment. This paper explores the vulnerabilities which human implants pose to crime victimisation in light of recent technological developments, and analyses how the law can deal with emerging challenges of what may well become the next generation of cybercrime: attacks targeted at technology implanted in the human body. After a state-of-the-art description of relevant types of human implants and a discussion how these implants challenge existing perceptions of the human body, we describe how various modes of attacks, such as sniffing, hacking, data interference, and denial of service, can be committed against implants. Subsequently, we analyse how these attacks can be assessed under current substantive and procedural criminal law, drawing on examples from UK and Dutch law. The possibilities and limitations of cybercrime provisions (eg, unlawful access, system interference) and bodily integrity provisions (eg, battery, assault, causing bodily harm) to deal with human-implant attacks are analysed. Based on this assessment, the paper concludes that attacks on human implants are not only a new generation in the evolution of cybercrime, but also raise fundamental questions on how criminal law conceives of attacks. Traditional distinctions between physical and non-physical modes of attack, between human bodies and things, between exterior and interior of the body need to be re-interpreted in light of developments in human implants. As the human body and technology become increasingly intertwined, cybercrime legislation and body-integrity crime legislation will also become intertwined, posing a new puzzle that legislators and practitioners will sooner or later have to solve.

Dyslexia and remediation/education: where next?

Interventions to support students with reading difficulties have existed for over 70 years. This paper rehearses the need for interventions to be grounded in theory and empirical evidence about reading processes. The suggestion that the next generation of interventions should go beyond simple context-independent small unit phonics teaching to cover context-dependent larger phonological units is evaluated. Examples of contemporary interventions that involve large units, and morphology are presented. Current interventions reported target students with literacy difficulties regardless of a diagnosis of dyslexia.

Investigations on PVP/Y3BO6:Eu3+, a red Luminescent composite for lighting devices based on near UV-LEDs

This work deals with a red phosphor. Y3BO6:Eu3+, and its corresponding poly(N-vinylpyrrolidone) (PVP)/Y3BO6:Eu3+ luminescent composite film suitable for applications in the next generation of Hg-free lamps based on near ultraviolet (UV) light emitting diodes (LEDs). Well crystallized samples of Y3BO6 powders with the Eu3+ content up to 20 mol% were prepared by the Pechini method. After structural, morphological and optical characterization, the best doping rate of Eu3+ in the matrix was determined to be 15 mol%. This optimal powder, which is highly friable, was easily ground into fine particles and homogeneously dispersed into a PVP polymer solution to give rise to a polymer phosphor composite. Structural and optical features of the composite film have been studied and compared to those of a pristine PVP film and Y3BO6:Eu3+ powder. All the characterization (XRD, SAXS, luminescence...) proved that the red phosphor particles are well incorporated into the polymer composite film which exhibited the characteristic red emission of Eu3+ under UV light excitation. Furthermore, photostability of the polymer/phosphor composite film under UV-LED irradiation was evaluated from exposure to accelerated artificial photoageing at wavelengths above 300 nm.

Constraining the absolute neutrino mass scale and Majorana CP violating phases by future 0νββ decay experiments

Assuming that neutrinos are Majorana particles, in a three-generation framework, current and future neutrino oscillation experiments can determine six out of the nine parameters which fully describe the structure of the neutrino mass matrix. We try to clarify the interplay among the remaining parameters, the absolute neutrino mass scale and two CP violating Majorana phases, and how they can be accessed by future neutrinoless double beta (0vυββ) decay experiments, for the normal as well as for the inverted order of the neutrino mass spectrum. Assuming the oscillation parameters to be in the range presently allowed by atmospheric, solar, reactor, and accelerator neutrino experiments, we quantitatively estimate the bounds on m 0, the lightest neutrino mass, that can be inferred if the next generation 0υββ decay experiments can probe the effective Majorana mass (m ee) down to ∼1 meV. In this context we conclude that in the case that neutrinos are Majorana particles, (a) if m 0≳300 meV, i.e., within the range directly attainable by future laboratory experiments as well as astrophysical observations, then m ee≳30 meV must be observed, (b) if m 0 ≤ 300 meV, results from future 0υββ decay experiments combined with stringent bounds on the neutrino oscillation parameters, especially the solar ones, will place much stronger limits on the allowed values of m 0 than these direct experiments. For instance, if a positive signal is observed around m ee = 10 meV, we estimate 3≲m 0/meV≲65 at 95% C.L.; on the other hand, if no signal is observed down to m ee = 10 meV, then m 0≲55 meV at 95% C.L.

Multicentric Carpotarsal Osteolysis Is Caused by Mutations Clustering in the Amino-Terminal Transcriptional Activation Domain of MAFB

Multicentric carpotarsal osteolysis (MCTO) is a rare skeletal dysplasia characterized by aggressive osteolysis, particularly affecting the carpal and tarsal bones, and is frequently associated with progressive renal failure. Using exome capture and next-generation sequencing in five unrelated simplex cases of MCTO, we identified previously unreported missense mutations clustering within a 51 base pair region of the single exon of MAFB, validated by Sanger sequencing. A further six unrelated simplex cases with MCTO were also heterozygous for previously unreported mutations within this same region, as were affected members of two families with autosomal-dominant MCTO. MAFB encodes a transcription factor that negatively regulates RANKL-induced osteoclastogenesis and is essential for normal renal development. Identification of this gene paves the way for development of novel therapeutic approaches for this crippling disease and provides insight into normal bone and kidney development.

Wireless systems for the fourth generation

Today, third generation networks are consolidated realities, and user expectations on new applications and services are becoming higher and higher. Therefore, new systems and technologies are necessary to move towards the market needs and the user requirements. This has driven the development of fourth generation networks. ”Wireless network for the fourth generation” is the expression used to describe the next step in wireless communications. There is no formal definition for what these fourth generation networks are; however, we can say that the next generation networks will be based on the coexistence of heterogeneous networks, on the integration with the existing radio access network (e.g. GPRS, UMTS, WIFI, ...) and, in particular, on new emerging architectures that are obtaining more and more relevance, as Wireless Ad Hoc and Sensor Networks (WASN). Thanks to their characteristics, fourth generation wireless systems will be able to offer custom-made solutions and applications personalized according to the user requirements; they will offer all types of services at an affordable cost, and solutions characterized by flexibility, scalability and reconfigurability. This PhD’s work has been focused on WASNs, autoconfiguring networks which are not based on a fixed infrastructure, but are characterized by being infrastructure less, where devices have to automatically generate the network in the initial phase, and maintain it through reconfiguration procedures (if nodes’ mobility, or energy drain, etc..., cause disconnections). The main part of the PhD activity has been focused on an analytical study on connectivity models for wireless ad hoc and sensor networks, nevertheless a small part of my work was experimental. Anyway, both the theoretical and experimental activities have had a common aim, related to the performance evaluation of WASNs. Concerning the theoretical analysis, the objective of the connectivity studies has been the evaluation of models for the interference estimation. This is due to the fact that interference is the most important performance degradation cause in WASNs. As a consequence, is very important to find an accurate model that allows its investigation, and I’ve tried to obtain a model the most realistic and general as possible, in particular for the evaluation of the interference coming from bounded interfering areas (i.e. a WiFi hot spot, a wireless covered research laboratory, ...). On the other hand, the experimental activity has led to Throughput and Packet Error Rare measurements on a real IEEE802.15.4 Wireless Sensor Network.

Genexpressionsanalyse boviner mesenchymaler Stammzellen und deren in-vitro-differenzierten Folgelinien

Mesenchymale Stamzellen (MSC) sind Vertreter der adulten Stammzellen. Sie bergen durch ihre große Plastizität ein immenses Potential für die klinische Nutzung in Form von Stammzelltherapien. Zellen dieses Typs kommen vornehmlich im Knochenmark der großen Röhrenknochen vor und können zu Knochen, Knorpel und Fettzellen differenzieren. MSC leisten einen wichtigen Beitrag im Rahmen regenerativer Prozesse, beispielsweise zur Heilung von Frakturen. Breite Studien demonstrieren bereits jetzt auch bei komplexeren Erkrankungen (z.B. Osteoporose) therapeutisch vielversprechende Einsatzmöglichkeiten. Oft kommen hierbei aus MSC gezielt differenzierte Folgelinien aus Zellkulturen zum Einsatz. Dies bedingt eine kontrollierte Steuerung der Differenzierungsprozesse in vitro. Der Differenzierung einer Stammzelle liegt eine komplexe Veränderung ihrer Genexpression zugrunde. Genexpressionsmuster zur Erhaltung und Proliferation der Stammzellen müssen durch solche, die der linienspezifischen Differenzierung dienen, ersetzt werden. Die mit der Differenzierung einhergehende, transkriptomische Neuausrichtung ist für das Verständnis der Prozesse grundlegend und wurde bislang nur unzureichend untersucht. Ziel der vorliegenden Arbeit ist eine transkriptomweite und vergleichende Genexpressionsanalyse Mesenchymaler Stammzellen und deren in vitro differenzierten Folgelinien mittels Plasmid - DNA Microarrays und Sequenziertechniken der nächsten Generation (RNA-Seq, Illumina Plattform). In dieser Arbeit diente das Hausrind (Bos taurus) als Modellorganismus, da es genetisch betrachtet eine hohe Ähnlichkeit zum Menschen aufweist und Knochenmark als Quelle von MSC gut verfügbar ist. Primärkulturen Mesenchymaler Stammzellen konnten aus dem Knochenmark von Rindern erfolgreich isoliert werden. Es wurden in vitro Zellkultur - Versuche durchgeführt, um die Zellen zu Osteoblasten, Chondrozyten und Adipozyten zu differenzieren. Zur Genexpressionsanalyse wurde RNA aus jungen MSC und einer MSC Langzeitkultur („alte MSC“), sowie aus den differenzierten Zelllinien isoliert und für nachfolgende Experimente wo nötig amplifiziert. Der Erfolg der Differenzierungen konnte anhand der Genexpression von spezifischen Markergenen und mittels histologischer Färbungen belegt werden. Hierbei zeigte sich die Differenzierung zu Osteoblasten und Adipozyten erfolgreich, während die Differenzierung zu Chondrozyten trotz diverser Modifikationen am Protokoll nicht erfolgreich durchgeführt werden konnte. Eine vergleichende Hybridisierung zur Bestimmung differentieller Genexpression (MSC vs. Differenzierung) mittels selbst hergestellter Plasmid - DNA Microarrays ergab für die Osteogenese mit Genen wie destrin und enpp1, für die undifferenzierten MSC mit dem Gen sema3c neue Kandidatengene, deren biologische Funktion aufzuklären in zukünftigen Experimenten vielversprechende Ergebnisse liefern sollte. Die Analyse der transkriptomweiten Genexpression mittels NGS lieferte einen noch umfangreicheren Einblick ins Differenzierungsgeschehen. Es zeigte sich eine hohe Ähnlichkeit im Expressionsprofil von jungen MSC und Adipozyten, sowie zwischen den Profilen der alten MSC (eine Langzeitkultur) und Osteoblasten. Die alten MSC wiesen deutliche Anzeichen für eine spontane Differenzierung in die osteogene Richtung auf. Durch Analyse der 100 am stärksten exprimierten Gene jeder Zelllinie ließen sich für junge MSC und Adipozyten besonders Gene der extrazellulären Matrix (z.B col1a1,6 ; fn1 uvm.) auffinden. Sowohl Osteoblasten, als auch die alten MSC exprimieren hingegen verstärkt Gene mit Bezug zur oxidativen Phosphorylierung, sowie ribosomale Proteine. Eine Betrachtung der differentiellen Genexpression (junge MSC vs. Differenzierung) mit anschließender Pathway Analyse und Genontologie Anreicherungsstatistik unterstützt diese Ergebnisse vor allem bei Osteoblasten, wo nun jedoch zusätzlich auch Gene zur Regulation der Knochenentwicklung und Mineralisierung in den Vordergrund treten. Für Adipozyten konnte mit Genen des „Jak-STAT signaling pathway“, der Fokalen Adhäsion, sowie Genen des „Cytokine-cytokine receptor interaction pathway“ sehr spannende Einsichten in die Biologie dieses Zelltyps erlangt werden, die sicher weiterer Untersuchungen bedürfen. In undifferenzierten MSC konnte durch differentielle Genexpressionsanalyse die Rolle des nicht kanonischen Teils des WNT Signalweges als für die Aufrechterhaltung des Stammzellstatus potentiell äußerst einflussreich ermittelt werden. Die hier diskutierten Ergebnisse zeigen beispielhaft, dass besonders mittels Genexpressionsanalyse im Hochdurchsatzverfahren wertvolle Einblicke in die komplexe Biologie der Stammzelldifferenzierung möglich sind. Als Grundlage für nachfolgende Arbeiten konnten interessante Gene ermittelt und Hypothesen zu deren Einfluss auf Stammzelleigenschaften und Differenzierungsprozesse aufgestellt werden. Um einen besseren Einblick in den Differenzierungsverlauf zu ermöglichen, könnten künftig NGS Analysen zu unterschiedlichen Differenzierungszeitpunkten durchgeführt werden. Zudem wären weitere Anstrengungen zur erfolgreichen Etablierung der chondrogenen Differenzierung zur vollständigen Analyse der Genexpression des trilinearen Differenzierungspotentials von MSC wünschenswert.

Utilization of Probabilistic Models in Short Read Assembly from Second-Generation Sequencing

With the advent of cheaper and faster DNA sequencing technologies, assembly methods have greatly changed. Instead of outputting reads that are thousands of base pairs long, new sequencers parallelize the task by producing read lengths between 35 and 400 base pairs. Reconstructing an organism’s genome from these millions of reads is a computationally expensive task. Our algorithm solves this problem by organizing and indexing the reads using n-grams, which are short, fixed-length DNA sequences of length n. These n-grams are used to efficiently locate putative read joins, thereby eliminating the need to perform an exhaustive search over all possible read pairs. Our goal was develop a novel n-gram method for the assembly of genomes from next-generation sequencers. Specifically, a probabilistic, iterative approach was utilized to determine the most likely reads to join through development of a new metric that models the probability of any two arbitrary reads being joined together. Tests were run using simulated short read data based on randomly created genomes ranging in lengths from 10,000 to 100,000 nucleotides with 16 to 20x coverage. We were able to successfully re-assemble entire genomes up to 100,000 nucleotides in length.

New generation genomic platforms in investigation of complex diseases and BEN.

(Full text is available at http://www.manu.edu.mk/prilozi). New generation genomic platforms enable us to decipher the complex genetic basis of complex diseases and Balkan Endemic Nephropathy (BEN) at a high-throughput basis. They give valuable information about predisposing Single Nucleotide Polymorphisms (SNPs), Copy Number Variations (CNVs) or Loss of Heterozygosity (LOH) (using SNP-array) and about disease-causing mutations along the whole sequence of candidate-genes (using Next Generation Sequencing). This information could be used for screening of individuals in risk families and moving the main medicine stream to the prevention. They also might have an impact on more effective treatment. Here we discuss these genomic platforms and report some applications of SNP-array technology in a case with familial nephrotic syndrome. Key words: complex diseases, genome wide association studies, SNP, genomic arrays, next generation sequ-encing.