Biomolecule-nanoparticle hybrids for electrochemical biosensors

Inorganic nanoparticles (NPs) with attractive electronic, optical, magnetic, thermal and catalytic properties have attracted great interest due to their important applications in physics, chemistry, biology, medicine, materials science and interdisciplinary fields. Biomolecule-NP hybrid systems, which combine recognition and catalytic properties of biomolecules with electronic, optical, magnetic and catalytic properties of NPs, are particularly new materials with synergistic properties originating from the components of the hybrid composites. The biomolecule-NP hybrid system has excellent prospects for interfacing biological recognition events with electronic signal transduction so as to design a new generation of bioelectronic devices with high sensitivity.

Gestão de stocks e a sua envolvente – estudo de caso de uma PME da indústria de calçado ortopédico

Dissertação apresentada ao Instituto Superior de Contabilidade para a obtenção do Grau de Mestre em Auditoria Professor orientador: Mestre Manuel Gregório

Explorando vertentes matemáticas nos códigos de barras

Pós-graduação em Matemática em Rede Nacional - IBILCE

Sequence capture and next-generation resequencing of multiple tagged nucleic acid samples for mutation screening of urea cycle disorders

Molecular genetic testing is commonly used to confirm clinical diagnoses of inherited urea cycle disorders (UCDs); however, conventional mutation screenings encompassing only the coding regions of genes may not detect disease-causing mutations occurring in regulatory elements and introns. Microarray-based target enrichment and next-generation sequencing now allow more-comprehensive genetic screening. We applied this approach to UCDs and combined it with the use of DNA bar codes for more cost-effective, parallel analyses of multiple samples.

„RFID - Systematische Versuche für den zuverlässigen Einsatz in der Logistik“

Mit zunehmender Komplexität und Vielfalt der Logistikprozesse steigt der Stellenwert der eingesetzten Informationstechnologien. Die den Warenfluss begleitenden bzw. vorhereilenden Informationen sind erforderlich, um Waren identifizieren und Unternehmensressourcen optimal einsetzen zu können. Als Beispiel ist der klassische Wareneingang zu nennen. Durch die Avisierung von Menge und Art eingehender Waren können der Einsatz des Personals zur Entladung und Vereinnahmung sowie die erforderlichen Ressourcen (Ladehilfsmittel, Flurförderzeuge, usw.) im Vorfeld geplant und bereitgestellt werden. Der Informationsfluss ist demnach als Qualitätsmerkmal und als Wirtschaftlichkeitsfaktor zu verstehen. Die Schnittstelle zwischen dem physischen Warenfluss und dem Informationsfluss auf EDV-Basis bildet die Identifikationstechnologien. In der Industrie verbreitete Identifikationstechnologien bestehen in der Regel aus einem Datenträger und einem Erfassungsgerät. Der Datenträger ist am physischen Objekt fixiert. Das Erfassungsgerät liest die auf dem Datenträger befindlichen Objektinformationen und wandelt sie in einen Binär-Code um, der durch nachgelagerte EDV weiterverarbeitet wird. Die momentan in der Industrie und im Handel am häufigsten verwendete Identifikationstechnologie ist der Barcode. In den letzten Jahren tritt die RFID-Technologie in den Fokus der Industrie und des Handels im Bereich Materialfluss und Logistik. Unter „Radio Frequency IDentification“ wird die Kommunikation per Funkwellen zwischen Datenträger (Transponder) und Lesegerät verstanden. Mittels der RFID-Technologie ist der Anwender, im Gegensatz zum Barcode, in der Lage, Informationen auf dem Transponder ohne Sichtkontakt zu erfassen. Eine Ausrichtung der einzelnen Artikel ist nicht erforderlich. Zudem können auf bestimmten Transpondertypen weitaus größere Datenmengen als auf einem Barcode hinterlegt werden. Transponder mit hoher Speicherkapazität eignen sich in der Regel, um die auf ihnen hinterlegten Daten bei Bedarf aktualisieren zu k��nnen. Eine dezentrale Datenorganisation ist realisierbar. Ein weiterer Vorteil der RFID-Technologie ist die Möglichkeit, mehrere Datenträger im Bruchteil einer Sekunde zu erfassen. In diesem Fall spricht man von einer Pulkerfassung. Diese Eigenschaft ist besonders im Bereich Warenein- und -ausgang von Interesse. Durch RFID ist es möglich, Ladeeinheiten, z. B. Paletten mit Waren, durch einen Antennenbereich zu fördern, und die mit Transpondern versehenen Artikel zu identifizieren und in die EDV zu übertragen. Neben der Funktionalität einer solchen Technologie steht in der Industrie vor allem die Wirtschaftlichkeit im Vordergrund. Transponder sind heute teuerer als Barcodes. Zudem müssen Investitionen in die für den Betrieb von RFID erforderliche Hard- und Software einkalkuliert werden. Daher muss der Einsatz der RFID-Technologie Einsparungen durch die Reorganisation der Unternehmensprozesse nach sich ziehen. Ein Schwachpunkt der RFID-Technologie ist momentan je nach Anwendung die mangelnde Zuverlässigkeit und Wiederholgenauigkeit bei Pulklesungen. Die Industrie und der Handel brauchen Identifikationstechnologien, deren Erfassungsrate im Bereich nahe 100 % liegt. Die Gefahr besteht darin, dass durch ein unzuverlässiges RFID-System unvollständige bzw. fehlerhafte Datensätze erzeugt werden können. Die Korrektur der Daten kann teurer sein als die durch die Reorganisation der Prozesse mittels RFID erzielten Einsparungen. Die Erfassungsrate der Transponder bei Pulkerfassungen wird durch mehrere Faktoren beeinflusst, die im Folgenden detailliert dargestellt werden. Das Institut für Fördertechnik und Logistik (IFT) in Stuttgart untersucht m��gliche Einflussgrößen auf die Erkennungsraten bei Pulkerfassungen. Mit den gewonnenen Erkenntnissen sollen mögliche Schwachstellen bei der Erkennung mehrerer Transponder im Vorfeld einer Implementierung in die Logistikprozesse eines Unternehmens eliminiert werden. With increasing complexity and variety of the logistics processes the significance of the used information technologies increases. The information accompanying the material flow is necessary in order to be able to identify goods and to be able to use corporate resources optimally. The classical goods entrance is to be mentioned as an example. The notification of amount and kind of incoming goods can be used for previously planning and providing of the personnel and necessary resources. The flow of information is to be understood accordingly as a high-quality feature and as an economic efficiency factor. With increasing complexity and variety of the logistics processes the significance of the used information technologies increases. The information accompanying the material flow is necessary in order to be able to identify goods and to be able to use corporate resources optimally. The classical goods entrance is to be mentioned as an example. The notification of amount and kind of incoming goods can be used for previously planning and providing of the personnel and necessary resources. The flow of information is to be understood accordingly as a high-quality feature and as an economic efficiency factor.

X + Y Bar

X + Y has attitude, enigma and re-establishes a venue drenched in a Valley persona etched over seven decades and surrounded by bars of a new generation. This is a bar without judgement, dress codes and without absolute refinement.

Bending the Rules of Cell Protrusions : Molecular Mechanisms and Biological Roles of Inverse-BAR Proteins in Cell Morphogenesis

Plasma membrane adopts myriad of different shapes to carry out essential cellular processes such as nutrient uptake, immunological defence mechanisms and cell migration. Therefore, the details how different plasma membrane structures are made and remodelled are of the upmost importance. Bending of plasma membrane into different shapes requires substantial amount of force, which can be provided by the actin cytoskeleton, however, the molecules that regulate the interplay between the actin cytoskeleton and plasma membrane have remained elusive. Recent findings have placed new types of effectors at sites of plasma membrane remodelling, including BAR proteins, which can directly bind and deform plasma membrane into different shapes. In addition to their membrane-bending abilities, BAR proteins also harbor protein domains that intimately link them to the actin cytoskeleton. The ancient BAR domain fold has evolved into at least three structurally and functionally different sub-groups: the BAR, F-BAR and I-BAR domains. This thesis work describes the discovery and functional characterization of the Inverse-BAR domains (I-BARs). Using synthetic model membranes, we have shown that I-BAR domains bind and deform membranes into tubular structures through a binding-surface composed of positively charged amino acids. Importantly, the membrane-binding surface of I-BAR domains displays an inverse geometry to that of the BAR and F-BAR domains, and these structural differences explain why I-BAR domains induce cell protrusions whereas BAR and most F-BAR domains induce cell invaginations. In addition, our results indicate that the binding of I-BAR domains to membranes can alter the spatial organization of phosphoinositides within membranes. Intriguingly, we also found that some I-BAR domains can insert helical motifs into the membrane bilayer, which has important consequences for their membrane binding/bending functions. In mammals there are five I-BAR domain containing proteins. Cell biological studies on ABBA revealed that it is highly expressed in radial glial cells during the development of the central nervous system and plays an important role in the extension process of radial glia-like C6R cells by regulating lamellipodial dynamics through its I-BAR domain. To reveal the role of these proteins in the context of animals, we analyzed MIM knockout mice and found that MIM is required for proper renal functions in adult mice. MIM deficient mice displayed a severe urine concentration defect due to defective intercellular junctions of the kidney epithelia. Consistently, MIM localized to adherens junctions in cultured kidney epithelial cells, where it promoted actin assembly through its I-BAR andWH2 domains. In summary, this thesis describes the mechanism how I-BAR proteins deform membranes and provides information about the biological role of these proteins, which to our knowledge are the first proteins that have been shown to directly deform plasma membrane to make cell protrusions.

Generation of Flat and Curved Membranes by Inverse-BAR Domain Proteins

Biological membranes are tightly linked to the evolution of life, because they provide a way to concentrate molecules into partially closed compartments. The dynamic shaping of cellular membranes is essential for many physiological processes, including cell morphogenesis, motility, cytokinesis, endocytosis, and secretion. It is therefore essential to understand the structure of the membrane and recognize the players that directly sculpt the membrane and enable it to adopt different shapes. The actin cytoskeleton provides the force to push eukaryotic plasma membrane in order to form different protrusions or/and invaginations. It has now became evident that actin directly co-operates with many membrane sculptors, including BAR domain proteins, in these important events. However, the molecular mechanisms behind BAR domain function and the differences between the members of this large protein family remain largely unresolved. In this thesis, the structure and functions of the I-BAR domain family members IRSp53 and MIM were thoroughly analyzed. By using several methods such as electron microscopy and systematic mutagenesis, we showed that these I-BAR domain proteins bind to PI(4,5)P2-rich membranes, generate negative membrane curvature and are involved in the formation of plasma membrane protrusions in cells e.g. filopodia. Importantly, we characterized a novel member of the BAR-domain superfamily which we named Pinkbar. We revealed that Pinkbar is specifically expressed in kidney and epithelial cells, and it localizes to Rab13-positive vesicles in intestinal epithelial cells. Remarkably, we learned that the I-BAR domain of Pinkbar does not generate membrane curvature but instead stabilizes planar membranes. Based on structural, mutagenesis and biochemical work we present a model for the mechanism of the novel membrane deforming activity of Pinkbar. Collectively, this work describes the mechanism by which I-BAR domain proteins deform membranes and provides new information about the biological roles of these proteins. Intriguingly, this work also gives evidence that significant functional plasticity exists within the I-BAR domain family. I-BAR proteins can either generate negative membrane curvature or stabilize planar membrane sheets, depending on the specific structural properties of their I-BAR domains. The results presented in this thesis expand our knowledge on membrane sculpting mechanisms and shows for the first time how flat membranes can be generated in cells.

Inexact-aware architecture design for ultra-low power bio-signal analysis

This study introduces an inexact, but ultra-low power, computing architecture devoted to the embedded analysis of bio-signals. The platform operates at extremely low voltage supply levels to minimise energy consumption. In this scenario, the reliability of static RAM (SRAM) memories cannot be guaranteed when using conventional 6-transistor implementations. While error correction codes and dedicated SRAM implementations can ensure correct operations in this near-threshold regime, they incur in significant area and energy overheads, and should therefore be employed judiciously. Herein, the authors propose a novel scheme to design inexact computing architectures that selectively protects memory regions based on their significance, i.e. their impact on the end-to-end quality of service, as dictated by the bio-signal application characteristics. The authors illustrate their scheme on an industrial benchmark application performing the power spectrum analysis of electrocardiograms. Experimental evidence showcases that a significance-based memory protection approach leads to a small degradation in the output quality with respect to an exact implementation, while resulting in substantial energy gains, both in the memory and the processing subsystem.

Twelve-month clinical outcomes after coronary stenting with the Genous Bio-engineered R Stent in patients with a bifurcation lesion: from the e-HEALING (Healthy Endothelial Accelerated Lining Inhibits Neointimal Growth) registry

Background The e-Healthy Endothelial Accelerated Lining Inhibits Neointimal Growth (e-HEALING) registry was designed to capture clinical data on the use of the endothelial progenitor cell capture stent (ECS) in routine clinical practice. In this analysis, we investigated the 12-month clinical outcomes in patients treated with an ECS for a bifurcation lesion. Methods The worldwide, prospective, nonrandomized e-HEALING registry aimed to enrol 5000 patients treated for coronary artery disease with one or more ECS between October 2005 and October 2007. Clinical follow-up was obtained at 1, 6, and 12 months. The primary endpoint was target vessel failure (TVF), defined as the composite of cardiac death, myocardial infarction, and target vessel revascularization at 12 months. Results A total of 573 patients were treated for at least one bifurcation lesion and were assessed in the current analysis. Baseline characteristics showed a median age of 65 years; 21% were diabetic patients and 36% had unstable angina. A total of 63% of the bifurcation lesions were located in the left artery descending and the mean stent length was 20.7 +/- 12.6 mm. At 12 months, TVF was 12.7% and target lesion revascularization was 7.5%. Definite or probable stent thrombosis occurred in 1.7% of the patients. Moreover, one or more stents per lesion [hazard ratio (HR): 2.79, 95% confidence interval (CI): 1.60-4.86, P < 0.001], predilatation (HR: 0.39, 95% CI: 0.17-0.87, P = 0.023), and lesions located in the right coronary artery (HR: 4.56, 95% CI: 1.07-19.5, P = 0.041) were independent predictors of TVF. Conclusion In the e-HEALING registry, coronary bifurcation stenting with the ECS results in favorable clinical outcomes and low incidences of repeat revascularization and stent thrombosis. Coron Artery Dis 23:201-207 (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

The utility and challenges of using ICD codes in child maltreatment research : a review of existing literature

Objective: The objectives of this article are to explore the extent to which the International Statistical Classification of Diseases and Related Health Problems (ICD) has been used in child abuse research, to describe how the ICD system has been applied and to assess factors affecting the reliability of ICD coded data in child abuse research.----- Methods: PubMed, CINAHL, PsychInfo and Google Scholar were searched for peer reviewed articles written since 1989 that used ICD as the classification system to identify cases and research child abuse using health databases. Snowballing strategies were also employed by searching the bibliographies of retrieved references to identify relevant associated articles. The papers identified through the search were independently screened by two authors for inclusion, resulting in 47 studies selected for the review. Due to heterogeneity of studies metaanalysis was not performed.----- Results: This paper highlights both utility and limitations of ICD coded data. ICD codes have been widely used to conduct research into child maltreatment in health data systems. The codes appear to be used primarily to determine child maltreatment patterns within identified diagnoses or to identify child maltreatment cases for research.----- Conclusions: A significant impediment to the use of ICD codes in child maltreatment research is the under-ascertainment of child maltreatment by using coded data alone. This is most clearly identified and, to some degree, quantified, in research where data linkage is used. Practice Implications: The importance of improved child maltreatment identification will assist in identifying risk factors and creating programs that can prevent and treat child maltreatment and assist in meeting reporting obligations under the CRC.

The Criminal Codes : Commentary and Materials

This edition has been substantially revised to increase overall clarity and to ensure a balanced examination of the criminal law in the 'Code' states, Queensland and Western Australia. The work has been brought up-to-date in all areas and provides valuable comment on the recent wide-reaching reforms to the law of homicide in Western Australia. Significant developments in both states discussed in this edition include: The abolition of wilful murder and infanticide, and the new definition of murder (WA); The introduction of the new offence of unlawful assault causing death (WA); The abolition of provocation to murder (WA), and whether this excuse still has a part to play (Qld); The reformulation of the excuse of self-defence, and the introduction of excessive self-defence (WA); The creation of offences for drink spiking (Qld and WA); and Current and proposed sentencing considerations (Qld and WA). Fundamental principles of the criminal law are illustrated throughout the book by selected extracts from the Codes and case law, while additional materials foster critical reflection on the law and the need for reform.