Immobilization of Homogeneous Monomeric, Oligomeric and Fibrillar Aβ Species for Reliable SPR Measurements

There is strong evidence that the amyloid-beta peptide (Aß) plays a central role in the pathogenesis of Alzheimer’s disease (AD). In this context, a detailed quantitative description of the interactions with different Aß species is essential for characterization of physiological and artificial ligands. However, the high aggregation propensity of Aß in concert with its susceptibility to structural changes due to even slight changes in solution conditions has impeded surface plasmon resonance (SPR) studies with homogeneous Aß conformer species. Here, we have adapted the experimental procedures to state-of-the-art techniques and established novel approaches to reliably overcome the aforementioned challenges. We show that the application of density gradient centrifugation (DGC) for sample purification and the use of a single chain variable fragment (scFv) of a monoclonal antibody directed against the amino-terminus of Aß allows reliable SPR measurements and quality control of the immobilized Aß aggregate species at any step throughout the experiment

Diagnostic performance and reliability of ultrasonography for fatty degeneration of the rotator cuff muscles

BACKGROUND: Diagnostic evaluation of rotator cuff muscle quality is important to determine indications for potential operative repair. Ultrasonography has developed into an accepted and useful tool for evaluating rotator cuff tendon tears; however, its use for evaluating rotator muscle quality has not been well established. The purpose of this study was to investigate the diagnostic performance and observer reliability of ultrasonography in grading fatty degeneration of the posterior and superior rotator cuff muscles. METHODS: The supraspinatus, infraspinatus, and teres minor muscles were prospectively evaluated with magnetic resonance imaging (MRI) and ultrasonography in eighty patients with shoulder pain. The degree of fatty degeneration on MRI was graded by four independent raters on the basis of the modified Goutallier grading system. Ultrasonographic evaluation of fatty degeneration was performed by one of three radiologists with use of a three-point scale. The two scoring systems were compared to determine the diagnostic performance of ultrasonography. The interobserver and intraobserver reliability of MRI grading by the four raters were determined. The interobserver reliability of ultrasonography among the three radiologists was determined in a separate group of thirty study subjects. The weighted Cohen kappa, percentage agreement, sensitivity, and specificity were calculated. RESULTS: The accuracy of ultrasonography for the detection of fatty degeneration, as assessed on the basis of the percentage agreement with MRI, was 92.5% for the supraspinatus and infraspinatus muscles and 87.5% for the teres minor. The sensitivity was 84.6% for the supraspinatus, 95.6% for the infraspinatus, and 87.5% for the teres minor. The specificity was 96.3% for the supraspinatus, 91.2% for the infraspinatus, and 87.5% for the teres minor. The agreement between MRI and ultrasonography was substantial for the supraspinatus and infraspinatus (kappa = 0.78 and 0.71, respectively) and moderate for the teres minor (kappa = 0.47). The interobserver reliability for MRI was substantial for the supraspinatus and infraspinatus (kappa = 0.76 and 0.77, respectively) and moderate for the teres minor (kappa = 0.59). For ultrasonography, the interobserver reliability was substantial for all three muscles (kappa = 0.71 for the supraspinatus, 0.65 for the infraspinatus, and 0.72 for the teres minor). CONCLUSIONS: The diagnostic performance of ultrasonography in identifying and grading fatty degeneration of the rotator cuff muscles was comparable with that of MRI. Ultrasonography can be used as the primary diagnostic imaging modality for fatty changes in rotator cuff muscles. LEVEL OF EVIDENCE: Diagnostic Level II. See Instructions for Authors for a complete description of levels of evidence

Die Synthese von Wärmepumpenkreislauf und Organic Rankine Cycle in einer Carnot-Batterie

The Carnot Battery is an energy storage technology that is experiencing growing interest. The combination of heat pump cycle (HPC) and Organic Rankine Cycle (ORC) is a subset of this technology. In this case, an HPC is used to charge a thermal storage tank using surplus electricity and low-temperature heat. The ORC discharges the storage tank and releases the electrical energy. In terms of their components, the two processes offer the possibility of a reversible combination. This reduces the investment costs of the plant, but at the same time poses certain challenges for the planner and operator. In order to explore the planning process and to collect first operational experiences, such a reversible HPC-ORC pilot plant is built within the scope of this work. The aim of the plant is to find out to what extent the two processes can be combined as a Carnot Battery and what needs to be taken into account in the process. Important preliminary considerations of the planning process are presented, such as criteria for fluid selection, determination of operating conditions, and component selection. The plant will be equipped with an oil-lubricated reversible screw machine and plate heat exchangers as reversible condensers and evaporators. This work provides the first experience of the operation of such a plant. With regard to the overall system, the mass balance between the different operating conditions is shown to be a relevant point. In addition, the main reversible components (screw machine and heat exchanger) are studied in more detail. An analytical model is combined with thermographic measurements to determine the degree of filling of the heat exchangers. The geometry of the reversible screw machine is studied in detail with respect to the different pressure ratios in the two operating states. A minimally invasive optimization of the opening geometry is worked out, which could confirm its positive effects in experimental investigations.Die Carnot-Batterie ist eine Energiespeichertechnologie, die elektrische Energie in Form von Wärme speichert. Die Kombination aus Wärmepumpenkreislauf (HPC), Organic Rankine Cycle (ORC) und einem sensiblen Wärmespeicher ist eine Variante dieser Technologie, die insbesondere für kleinere bis mittlere Skalen attraktiv ist. Zur Beladung des Speichers erhöht der linksläufige Wärmepumpen-Kreisprozess unter Verwendung von Abwärme und elektrischer Energie die Temperatur des Speichermediums. Der rechtsläufige ORC-Kreisprozess entlädt den Speicher bei Bedarf, indem thermische wieder in elektrische Energie gewandelt wird. Die beiden Kreisprozesse besitzen eine deutliche Übereinstimmung hinsichtlich der verwendeten Komponenten. Dies ermöglicht theoretisch eine Kombination der Prozesse in einer einzigen Anlage. Durch die reversible Verwendung von Komponenten können die Investitionskosten der Anlage gesenkt werden, es treten aber gleichzeitig gewisse Herausforderungen bei der Auswahl der Komponenten und dem Betrieb der Anlage auf. Um den Planungsprozess zu studieren und erste praktische Betriebserfahrungen zu sammeln, wird im Rahmen dieser Arbeit eine solche reversible HPC-ORC-Pilotanlage aufgebaut. Ziel dieser Forschung ist es, herauszufinden, inwieweit sich die beiden Prozesse als Carnot-Batterie kombinieren lassen und was dabei zu beachten ist. Im vorliegenden Werk werden die wichtigsten Vorüberlegungen zur Planung vorgestellt: Die Kriterien für die Auswahl des Arbeitsfluids, eine Methode zur Festlegung der Betriebsbedingungen sowie eine Diskussion zur Auswahl der Hauptkomponenten. Die Anlage wird mit einer ölgeschmierten reversiblen Schraubenmaschine und Plattenwärmeübertragern als reversible Kondensatoren und Verdampfer ausgerüstet. Zahlreiche Messreihen liefern erste Erfahrungen mit dem Betrieb einer solchen Anlage. Im Hinblick auf das Gesamtsystem erweist sich der Unterschied der Arbeitsfluidmasse in den verschiedenen Betriebszuständen als ein relevanter Punkt. Darüber hinaus werden die wichtigsten reversiblen Komponenten (Schraubenmaschine und Wärmeübertrager) genauer untersucht: Ein analytisches Modell wird mit thermographischen Messungen kombiniert, um den Füllstand eines Wärmeübertragers zu bestimmen und Aussagen über die Auslastung dieser Komponente im reversiblen Betrieb zu treffen. Die Geometrie der reversiblen Schraubenmaschine wird im Hinblick auf die unterschiedlichen Druckverhältnisse in den beiden Betriebszuständen detailliert betrachtet. Es wird eine minimalinvasive Optimierung der Öffnungsgeometrie erarbeitet, die ihre positiven Auswirkungen insbesondere auf den Betrieb als ORC-Expander in experimentellen Untersuchungen bestätigen kann

Genetic regulation of pituitary gland development in human and mouse

Normal hypothalamopituitary development is closely related to that of the forebrain and is dependent upon a complex genetic cascade of transcription factors and signaling molecules that may be either intrinsic or extrinsic to the developing Rathke’s pouch. These factors dictate organ commitment, cell differentiation, and cell proliferation within the anterior pituitary. Abnormalities in these processes are associated with congenital hypopituitarism, a spectrum of disorders that includes syndromic disorders such as septo-optic dysplasia, combined pituitary hormone deficiencies, and isolated hormone deficiencies, of which the commonest is GH deficiency. The highly variable clinical phenotypes can now in part be explained due to research performed over the last 20 yr, based mainly on naturally occurring and transgenic animal models. Mutations in genes encoding both signaling molecules and transcription factors have been implicated in the etiology of hypopituitarism, with or without other syndromic features, in mice and humans. To date, mutations in known genes account for a small proportion of cases of hypopituitarism in humans. However, these mutations have led to a greater understanding of the genetic interactions that lead to normal pituitary development. This review attempts to describe the complexity of pituitary development in the rodent, with particular emphasis on those factors that, when mutated, are associated with hypopituitarism in humans

Revealing natural processes to the contemporary observer : Wal-Mart & stormwater runoff management

Thesis (M. Arch.)--Massachusetts Institute of Technology, Dept. of Architecture, 2002.Includes bibliographical references (p. 122-124).The natural landscape is a depository of natural processes at work--water flows and erodes earth; winds blow and deposit sands. The earth's surface reveals former and current environmental forces, many of which take millennia to construct. Many times, however, human development interrupts these complex interactions between earth forces. Current development for the most part is completely blind to natural processes, which in the long term often creates exponential complications for the environment and human settlements. This thesis seeks to reveal natural processes at work in the environment through infrastructure elements and architectural form . As increasing pressure is placed upon undeveloped tracts of land in our rural communities,development proposals that work in conj unction with and not against natural processes becomes increasingly salient. Such development offers intriguing and challenging design opportunities in the context of finding a pragmatic middle ground between economically viable development and utopian ideals of environmental management. This thesis is a point of departure that programmatically seeks to offer a symbiotic relationship between seemingly disparate activities, specifically a Wal-Mart development and a department of natural resources complex. Issues of stormwater management and quality are explored through a water management system in a proposed commercial/retail development for the Wal-Mart corporation. A Wisconsin Department of Natural Resources administration office, water quality management research facility and an intersecting bike/recreation trail serve to elucidate the pedagogy influencing the direction of this investigation.by Daniel Gerald Steger.M.Arch

Die Einflussfaktoren eines Sozialdienstes für nachhaltige Integration

Wie gelingt es Sozialdiensten, dass ihre Klientinnen und Klienten nicht mehr auf Sozialhilfe angewiesen sind? Und es auf Dauer bleiben? Eine Studie der BFH hat die relevanten Faktoren eingehend untersucht. Sie fand zehn Einflussgrössen, mit denen Sozialdienste die Chance einer mittel- bis langfristigen Ablösung erhöhen können