Investigation of ion induced bending mechanism for nanostructures

Ion induced bending is a promising controlled technique for manipulating nanoscale structures. However, the underlying mechanism of the process is not well understood. In this letter, we report a detailed study of the bending mechanism of Si nanowires (NWs) under Ga+ irradiation. The microstructural changes in the NW due to ion beam irradiation are studied and molecular dynamics simulations are used to explore the ion–NW interaction processes. The simulation results are compared with the microstructural studies of the NW. The investigations inform a generic understanding of the bending process in crystalline materials, which we suggest to be feasible as a versatile manipulation and integration technique in nanotechnology

In Vivo Conditioning of Tissue-engineered Heart Muscle Improves Contractile Performance

The ability to engineer cardiac tissue in vitro is limited by the absence of a vasculature. In this study we describe an in vivo model which allows neovascularization of engineered cardiac tissue. Three-dimensional cardiac tissue, termed “cardioids,” was engineered in vitro from the spontaneous delamination of a confluent monolayer of cardiac cells. Cardioids were sutured onto a support framework and then implanted in a subcutaneous pocket in syngeneic recipient rats. Three weeks after implantation, cardioids were recovered for in vitro force testing and histological evaluation. Staining for hematoxylin and eosin demonstrated the presence of viable cells within explanted cardioids. Immunostaining with von Willebrand factor showed the presence of vascularization. Electron micrographs revealed the presence of large amounts of aligned contractile proteins and a high degree of intercellular connectivity. The peak active force increased from an average value of 57 µN for control cardioids to 447 µN for explanted cardioids. There was also a significant increase in the specific force. There was a significant decrease in the time to peak tension and half relaxation time. Explanted cardioids could be electrically paced at frequencies of 1–5 Hz. Explanted cardioids exhibited a sigmoidal response to calcium and positive chronotropy in response to epinephrine. As the field of cardiac tissue engineering progresses, it becomes desirable to engineer larger diameter tissue equivalents and to induce angiogenesis within tissue constructs. This study describes a relatively simple in vivo model, which promotes the neovascularization of tissue-engineered heart muscle and subsequent improvement in contractile performance.  Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74650/1/j.1525-1594.2005.00148.x.pd

Vergleichende Qualitätsuntersuchungen von alten und neuen Gemüsesorten zur Entwicklung von Zuchtzielen für den ökologischen Gemüsebau

Am Beispiel der Gemüsearten Möhren und Kohl wurden alte und neue Sorten sowie Sorten aus biologisch-dynamischer Selektion auf ihre Qualitätsmerkmale hin verglichen. Der Anbau erfolgte nach biologisch-dynamischen Landbaumethoden auf dem Dottenfelderhof in Bad Vilbel. Im Projekt kam ein breites Methodenspektrum zum Einsatz, das Geschmacksuntersuchungen mittels Humansensorik und instrumenteller Analytik umfasste. Diese Untersuchungen geben Aufschluss über die Zusammenhänge verschiedener äußerer und innerer Qualitätsmerkmale von insgesamt 39 Möhren- und 30 Kohlsorten. Bei Möhren wurden durch die Humansensorik in beiden Jahren Hybridsorten (Espredo, Bolero) aufgrund ihrer hohen Süße als die jeweils beliebteste Sorte ermittelt. Diese Feststellung ist in Übereinstimmung mit Ergebnissen der Ernährungswissenschaft, dass allgemein eine Prefärenz zu sehr süßen Nahrungsmitteln zu verzeichnen ist. Aus der Sicht des ökologischen Landbaus werden allerdings samenfeste Sorten bevorzugt, die neben dem süßen Geschmack auch ein typisches Aroma charakterisiert aufweisen. Die am Dottenfelderhof angewendete Selektion auf Geschmack zeigt hierbei insbesondere bei den Rodelika-Typen einen deutlichen Züchtungsfortschritt in Richtung auf eine höhere sensorische Qualität. Durch die Aromaanalytik mittels Festphasen-Mikroextraktion konnten die Terpene Myrcen und Caryophyllen als Negativkomponenten (Off-flavour) ermittelt werden. Hier sollte geprüft werden, inwieweit sich diese Inhaltsstoffe als Markersubstanzen für eine Geschmacksselektion eignen. Bei Kohl zeichnet sich die Sorte Holsteiner Platter durch die höchste Beliebtheit aus. Zwischen dem Gehalt an Glusosinolaten (gesundheitlich positiv und negativ wirksame Inhaltsstoffe) und den anderen Qualitätsparametern, insbesondere dem Geschmack, besteht kein strenger Zusammenhang. Im Ertrag stehen die samenfesten Sorten gleichrangig neben den Hybridsorten. Eine weitere Bearbeitung bezüglich der Uniformität der samenfesten Sorten wäre aber wünschenswert. Auf Grundlage der Ergebnisse können Ziele für eine qualitätsorientierte Züchtung im ökologischen Gemüsebau erarbeitet werden

Assessment of causality of natriuretic peptides and atrial fibrillation and heart failure: a Mendelian randomization study in the FINRISK cohort

Aims Natriuretic peptides are extensively studied biomarkers for atrial fibrillation (AF) and heart failure (HF). Their role in the pathogenesis of both diseases is not entirely understood and previous studies several single-nucleotide poly-morphisms (SNPs) at the NPPA-NPPB locus associated with natriuretic peptides have been identified. We investigated the causal relationship between natriuretic peptides and AF as well as HF using a Mendelian randomization approach.Methods and results N-terminal pro B-type natriuretic peptide (NT-proBNP) (N= 6669), B-type natriuretic peptide (BNP) (N= 6674), and mid-regional pro atrial natriuretic peptide (MR-proANP) (N= 6813) were measured in the FINRISK 1997 cohort. N=30 common SNPs related to NT-proBNP, BNP, and MR-proANP were selected from studies. We performed six Mendelian randomizations for all three natriuretic peptide biomarkers and for both outcomes, AF and HF, separately. Polygenic risk scores (PRSs) based on multiple SNPs were used as genetic instrumental variable in Mendelian randomizations. Polygenic risk scores were significantly associated with the three natriuretic peptides. Polygenic risk scores were not significantly associated with incident AF nor HF. Most cardiovascular risk factors showed significant confounding percentages, but no association with PRS. A causal relation except for small causal betas is unlikely.Conclusion In our Mendelian randomization approach, we confirmed an association between common genetic variation at the NPPA-NPPB locus and natriuretic peptides. A strong causal relationship between natriuretic peptides and incidence of AF as well as HF at the community-level was ruled out. Therapeutic approaches targeting natriuretic peptides will therefore very likely work through indirect mechanisms

Chronic multichannel neural recordings from soft regenerative microchannel electrodes during gait

Reliably interfacing a nerve with an electrode array is one of the approaches to restore motor and sensory functions after an injury to the peripheral nerve. Accomplishing this with current technologies is challenging as the electrode-neuron interface often degrades over time, and surrounding myoelectric signals contaminate the neuro-signals in awake, moving animals. The purpose of this study was to evaluate the potential of microchannel electrode implants to monitor over time and in freely moving animals, neural activity from regenerating nerves. We designed and fabricated implants with silicone rubber and elastic thin-film metallization. Each implant carries an eight-by-twelve matrix of parallel microchannels (of 120\u2009 7\u2009110\u2009\u3bcm2 cross-section and 4\u2009mm length) and gold thin-film electrodes embedded in the floor of ten of the microchannels. After sterilization, the soft, multi-lumen electrode implant is sutured between the stumps of the sciatic nerve. Over a period of three months and in four rats, the microchannel electrodes recorded spike activity from the regenerating sciatic nerve. Histology indicates mini-nerves formed of axons and supporting cells regenerate robustly in the implants. Analysis of the recorded spikes and gait kinematics over the ten-week period suggests firing patterns collected with the microchannel electrode implant can be associated with different phases of gait

Rapid and Sensitive Detection of Yersinia pestis Using Amplification of Plague Diagnostic Bacteriophages Monitored by Real-Time PCR

BACKGROUND: Yersinia pestis, the agent of plague, has caused many millions of human deaths and still poses a serious threat to global public health. Timely and reliable detection of such a dangerous pathogen is of critical importance. Lysis by specific bacteriophages remains an essential method of Y. pestis detection and plague diagnostics. METHODOLOGY/PRINCIPAL FINDINGS: The objective of this work was to develop an alternative to conventional phage lysis tests--a rapid and highly sensitive method of indirect detection of live Y. pestis cells based on quantitative real-time PCR (qPCR) monitoring of amplification of reporter Y. pestis-specific bacteriophages. Plague diagnostic phages phiA1122 and L-413C were shown to be highly effective diagnostic tools for the detection and identification of Y. pestis by using qPCR with primers specific for phage DNA. The template DNA extraction step that usually precedes qPCR was omitted. phiA1122-specific qPCR enabled the detection of an initial bacterial concentration of 10(3) CFU/ml (equivalent to as few as one Y. pestis cell per 1-microl sample) in four hours. L-413C-mediated detection of Y. pestis was less sensitive (up to 100 bacteria per sample) but more specific, and thus we propose parallel qPCR for the two phages as a rapid and reliable method of Y. pestis identification. Importantly, phiA1122 propagated in simulated clinical blood specimens containing EDTA and its titer rise was detected by both a standard plating test and qPCR. CONCLUSIONS/SIGNIFICANCE: Thus, we developed a novel assay for detection and identification of Y. pestis using amplification of specific phages monitored by qPCR. The method is simple, rapid, highly sensitive, and specific and allows the detection of only live bacteria

Heart Valve Tissue Engineering: Concepts, Approaches, Progress, and Challenges

Potential applications of tissue engineering in regenerative medicine range from structural tissues to organs with complex function. This review focuses on the engineering of heart valve tissue, a goal which involves a unique combination of biological, engineering, and technological hurdles. We emphasize basic concepts, approaches and methods, progress made, and remaining challenges. To provide a framework for understanding the enabling scientific principles, we first examine the elements and features of normal heart valve functional structure, biomechanics, development, maturation, remodeling, and response to injury. Following a discussion of the fundamental principles of tissue engineering applicable to heart valves, we examine three approaches to achieving the goal of an engineered tissue heart valve: (1) cell seeding of biodegradable synthetic scaffolds, (2) cell seeding of processed tissue scaffolds, and (3) in-vivo repopulation by circulating endogenous cells of implanted substrates without prior in-vitro cell seeding. Lastly, we analyze challenges to the field and suggest future directions for both preclinical and translational (clinical) studies that will be needed to address key regulatory issues for safety and efficacy of the application of tissue engineering and regenerative approaches to heart valves. Although modest progress has been made toward the goal of a clinically useful tissue engineered heart valve, further success and ultimate human benefit will be dependent upon advances in biodegradable polymers and other scaffolds, cellular manipulation, strategies for rebuilding the extracellular matrix, and techniques to characterize and potentially non-invasively assess the speed and quality of tissue healing and remodeling

Allosteric Inhibitors of NMDA Receptor Functions

NMDA receptors are glutamate-activated ion-channels involved in many essential brain functions including learning, memory, cognition, and behavior. Given this broad range of function it is not surprising that the initial attempts to correct NMDA receptor-mediated pathologies with en-mass receptor blockade were derailed by unacceptable side effects. Recent successes with milder or more targeted pharmaceuticals and increasing knowledge of how these receptors operate offer new incentives for rational development of effective NMDA receptor-targeted therapies. In this article we review evidence that L-alanine, a glycine-site partial agonist and pregnanolone sulfate, a use-dependent allosteric inhibitor, while attenuating NMDA receptor activity to similar levels elicit remarkably dissimilar functional outcomes. We suggest that detailed understanding of NMDA receptor activation mechanisms and of structural correlates of function will help better match modulator with function and neurological condition and may unleash the yet untapped potential of NMDA receptor pharmaceutics

Myocardial Engineering in Vivo: Formation and Characterization of Contractile, Vascularized Three-Dimensional Cardiac Tissue

Engineering cardiac tissue in three dimensions is limited by the ability to supply nourishment to the cells in the center of the construct. This limits the radius of an in vitro engineered cardiac construct to approximately 40 µm. This study describes a method of engineering contractile three-dimensional cardiac tissue with the incorporation of an intrinsic vascular supply. Neonatal cardiac myocytes were cultured in vivo in silicone chambers, in close proximity to an intact vascular pedicle. Silicone tubes were filled with a suspension of cardiac myocytes in fibrin gel and surgically placed around the femoral artery and vein of adult rats. At 3 weeks, the tissues in the chambers were harvested for in vitro contractility evaluation and processed for histologic analysis. By 3 weeks, the chambers had become filled with living tissue. Hematoxylin and eosin staining showed large amounts of muscle tissue situated around the femoral vessels. Electron micrographs revealed well-organized intracellular contractile machinery and a high degree of intercellular connectivity. Immunostaining for von Willebrand factor demonstrated neovascularization throughout the constructs. With electrical stimulation, the constructs were able to generate an average active force of 263 µN with a maximum of 843 µN. Electrical pacing was successful at frequencies of 1 to 20 Hz. In addition, the constructs exhibited positive inotropy in response to ionic calcium and positive chronotropy in response to epinephrine. As engineering of cardiac replacement tissue proceeds, vascularization is an increasingly important component in the development of three-dimensional structures. This study demonstrates the in vivo survival, vascularization, organization, and functionality of transplanted myocardial cells.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63336/1/ten.2005.11.803.pd