The construction and optimization of a surface plasmon resonance sensor for the studies of bio-molecular interactions

Bio-molecular interactions exist ubiquitously in all biological systems. This dissertation project was to construct a powerful surface plasmon resonance (SPR) sensor. The SPR system is used to study bio-molecular interactions in real time and without labeling. Surface plasmon is the oscillation of free electrons in metals coupled with surface electromagnetic waves. These surface electromagnetic waves provide a sensitive probe to study bio-molecular interactions on metal surfaces. This project resulted in the successful construction and optimization of a homemade SPR sensor and the development of several new powerful protocols to study bio-molecular interactions. It was discovered through this project that the limitations of earlier SPR sensors are related not only to the instrumentation design and operating procedures, but also to the complex behaviors of bio-molecules on sensor surfaces that were very different from that in solution. Based on these discoveries the instrumentation design and operating procedures were fully optimized. A set of existing sensor surface treatment protocols were tested and evaluated and new protocols were developed in this project. The new protocols have demonstrated excellent performance to study biomolecular interactions. The optimized home-made SPR sensor was used to study protein-surface interactions. These protein-surface interactions are responsible for many complex organic cell activities. The co-existence of different driving forces and their correlation with the structure of the protein and the surface make the understanding of the fundamental mechanism of protein-surface interactions a very challenging task. Using the improved SPR sensor, the electrostatic interaction and hydrophobic interaction were studied separately. The results of this project directly confirmed the theoretical predictions for electrostatic force between the protein and surface. In addition, this project demonstrated that the strength of the protein-surface hydrophobic interaction does not solely depend on the hydrophobicity as reported earlier. Surface structure also plays a significant role.

KOSMOS Finland 2012 mesocosm study: primary production and respiration

Anthropogenic carbon dioxide (CO2) emissions are reducing the pH in the world's oceans. The plankton community is a key component driving biogeochemical fluxes, and the effect of increased CO2 on plankton is critical for understanding the ramifications of ocean acidification on global carbon fluxes. We determined the plankton community composition and measured primary production, respiration rates and carbon export (defined here as carbon sinking out of a shallow, coastal area) during an ocean acidification experiment. Mesocosms (~ 55 m3) were set up in the Baltic Sea with a gradient of CO2 levels initially ranging from ambient (~ 240 µatm), used as control, to high CO2 (up to ~ 1330 µatm). The phytoplankton community was dominated by dinoflagellates, diatoms, cyanobacteria and chlorophytes, and the zooplankton community by protozoans, heterotrophic dinoflagellates and cladocerans. The plankton community composition was relatively homogenous between treatments. Community respiration rates were lower at high CO2 levels. The carbon-normalized respiration was approximately 40 % lower in the high CO2 environment compared with the controls during the latter phase of the experiment. We did not, however, detect any effect of increased CO2 on primary production. This could be due to measurement uncertainty, as the measured total particular carbon (TPC) and combined results presented in this special issue suggest that the reduced respiration rate translated into higher net carbon fixation. The percent carbon derived from microscopy counts (both phyto- and zooplankton), of the measured total particular carbon (TPC) decreased from ~ 26 % at t0 to ~ 8 % at t31, probably driven by a shift towards smaller plankton (< 4 µm) not enumerated by microscopy. Our results suggest that reduced respiration lead to increased net carbon fixation at high CO2. However, the increased primary production did not translate into increased carbon export, and did consequently not work as a negative feedback mechanism for increasing atmospheric CO2 concentration.

Assessing trends in land use change in the Borana rangeland Ethiopia as one cause of greenhouse gas emissions and carbon sequestration variations

Landnutzungsänderungen sind eine wesentliche Ursache von Treibhausgasemissionen. Die Umwandlung von Ökosystemen mit permanenter natürlicher Vegetation hin zu Ackerbau mit zeitweise vegetationslosem Boden (z.B. nach der Bodenbearbeitung vor der Aussaat) führt häufig zu gesteigerten Treibhausgasemissionen und verminderter Kohlenstoffbindung. Weltweit dehnt sich Ackerbau sowohl in kleinbäuerlichen als auch in agro-industriellen Systemen aus, häufig in benachbarte semiaride bis subhumide Rangeland Ökosysteme. Die vorliegende Arbeit untersucht Trends der Landnutzungsänderung im Borana Rangeland Südäthiopiens. Bevölkerungswachstum, Landprivatisierung und damit einhergehende Einzäunung, veränderte Landnutzungspolitik und zunehmende Klimavariabilität führen zu raschen Veränderungen der traditionell auf Tierhaltung basierten, pastoralen Systeme. Mittels einer Literaturanalyse von Fallstudien in ostafrikanischen Rangelands wurde im Rahmen dieser Studie ein schematisches Modell der Zusammenhänge von Landnutzung, Treibhausgasemissionen und Kohlenstofffixierung entwickelt. Anhand von Satellitendaten und Daten aus Haushaltsbefragungen wurden Art und Umfang von Landnutzungsänderungen und Vegetationsveränderungen an fünf Untersuchungsstandorten (Darito/Yabelo Distrikt, Soda, Samaro, Haralo, Did Mega/alle Dire Distrikt) zwischen 1985 und 2011 analysiert. In Darito dehnte sich die Ackerbaufläche um 12% aus, überwiegend auf Kosten von Buschland. An den übrigen Standorten blieb die Ackerbaufläche relativ konstant, jedoch nahm Graslandvegetation um zwischen 16 und 28% zu, während Buschland um zwischen 23 und 31% abnahm. Lediglich am Standort Haralo nahm auch „bare land“, vegetationslose Flächen, um 13% zu. Faktoren, die zur Ausdehnung des Ackerbaus führen, wurden am Standort Darito detaillierter untersucht. GPS Daten und anbaugeschichtlichen Daten von 108 Feldern auf 54 Betrieben wurden in einem Geographischen Informationssystem (GIS) mit thematischen Boden-, Niederschlags-, und Hangneigungskarten sowie einem Digitales Höhenmodell überlagert. Multiple lineare Regression ermittelte Hangneigung und geographische Höhe als signifikante Erklärungsvariablen für die Ausdehnung von Ackerbau in niedrigere Lagen. Bodenart, Entfernung zum saisonalen Flusslauf und Niederschlag waren hingegen nicht signifikant. Das niedrige Bestimmtheitsmaß (R²=0,154) weist darauf hin, dass es weitere, hier nicht erfasste Erklärungsvariablen für die Richtung der räumlichen Ausweitung von Ackerland gibt. Streudiagramme zu Ackergröße und Anbaujahren in Relation zu geographischer Höhe zeigen seit dem Jahr 2000 eine Ausdehnung des Ackerbaus in Lagen unter 1620 müNN und eine Zunahme der Schlaggröße (>3ha). Die Analyse der phänologischen Entwicklung von Feldfrüchten im Jahresverlauf in Kombination mit Niederschlagsdaten und normalized difference vegetation index (NDVI) Zeitreihendaten dienten dazu, Zeitpunkte besonders hoher (Begrünung vor der Ernte) oder niedriger (nach der Bodenbearbeitung) Pflanzenbiomasse auf Ackerland zu identifizieren, um Ackerland und seine Ausdehnung von anderen Vegetationsformen fernerkundlich unterscheiden zu können. Anhand der NDVI Spektralprofile konnte Ackerland gut Wald, jedoch weniger gut von Gras- und Buschland unterschieden werden. Die geringe Auflösung (250m) der Moderate Resolution Imaging Spectroradiometer (MODIS) NDVI Daten führte zu einem Mixed Pixel Effect, d.h. die Fläche eines Pixels beinhaltete häufig verschiedene Vegetationsformen in unterschiedlichen Anteilen, was deren Unterscheidung beeinträchtigte. Für die Entwicklung eines Echtzeit Monitoring Systems für die Ausdehnung des Ackerbaus wären höher auflösende NDVI Daten (z.B. Multispektralband, Hyperion EO-1 Sensor) notwendig, um kleinräumig eine bessere Differenzierung von Ackerland und natürlicher Rangeland-Vegetation zu erhalten. Die Entwicklung und der Einsatz solcher Methoden als Entscheidungshilfen für Land- und Ressourcennutzungsplanung könnte dazu beitragen, Produktions- und Entwicklungsziele der Borana Landnutzer mit nationalen Anstrengungen zur Eindämmung des Klimawandels durch Steigerung der Kohlenstofffixierung in Rangelands in Einklang zu bringen.

Physical Design Methodologies for Low Power and Reliable 3D ICs

As the semiconductor industry struggles to maintain its momentum down the path following the Moore's Law, three dimensional integrated circuit (3D IC) technology has emerged as a promising solution to achieve higher integration density, better performance, and lower power consumption. However, despite its significant improvement in electrical performance, 3D IC presents several serious physical design challenges. In this dissertation, we investigate physical design methodologies for 3D ICs with primary focus on two areas: low power 3D clock tree design, and reliability degradation modeling and management. Clock trees are essential parts for digital system which dissipate a large amount of power due to high capacitive loads. The majority of existing 3D clock tree designs focus on minimizing the total wire length, which produces sub-optimal results for power optimization. In this dissertation, we formulate a 3D clock tree design flow which directly optimizes for clock power. Besides, we also investigate the design methodology for clock gating a 3D clock tree, which uses shutdown gates to selectively turn off unnecessary clock activities. Different from the common assumption in 2D ICs that shutdown gates are cheap thus can be applied at every clock node, shutdown gates in 3D ICs introduce additional control TSVs, which compete with clock TSVs for placement resources. We explore the design methodologies to produce the optimal allocation and placement for clock and control TSVs so that the clock power is minimized. We show that the proposed synthesis flow saves significant clock power while accounting for available TSV placement area. Vertical integration also brings new reliability challenges including TSV's electromigration (EM) and several other reliability loss mechanisms caused by TSV-induced stress. These reliability loss models involve complex inter-dependencies between electrical and thermal conditions, which have not been investigated in the past. In this dissertation we set up an electrical/thermal/reliability co-simulation framework to capture the transient of reliability loss in 3D ICs. We further derive and validate an analytical reliability objective function that can be integrated into the 3D placement design flow. The reliability aware placement scheme enables co-design and co-optimization of both the electrical and reliability property, thus improves both the circuit's performance and its lifetime. Our electrical/reliability co-design scheme avoids unnecessary design cycles or application of ad-hoc fixes that lead to sub-optimal performance. Vertical integration also enables stacking DRAM on top of CPU, providing high bandwidth and short latency. However, non-uniform voltage fluctuation and local thermal hotspot in CPU layers are coupled into DRAM layers, causing a non-uniform bit-cell leakage (thereby bit flip) distribution. We propose a performance-power-resilience simulation framework to capture DRAM soft error in 3D multi-core CPU systems. In addition, a dynamic resilience management (DRM) scheme is investigated, which adaptively tunes CPU's operating points to adjust DRAM's voltage noise and thermal condition during runtime. The DRM uses dynamic frequency scaling to achieve a resilience borrow-in strategy, which effectively enhances DRAM's resilience without sacrificing performance. The proposed physical design methodologies should act as important building blocks for 3D ICs and push 3D ICs toward mainstream acceptance in the near future.

Efficient and precise interactive hand tracking through joint, continuous optimization of pose and correspondences

Fully articulated hand tracking promises to enable fundamentally new interactions with virtual and augmented worlds, but the limited accuracy and efficiency of current systems has prevented widespread adoption. Today's dominant paradigm uses machine learning for initialization and recovery followed by iterative model-fitting optimization to achieve a detailed pose fit. We follow this paradigm, but make several changes to the model-fitting, namely using: (1) a more discriminative objective function; (2) a smooth-surface model that provides gradients for non-linear optimization; and (3) joint optimization over both the model pose and the correspondences between observed data points and the model surface. While each of these changes may actually increase the cost per fitting iteration, we find a compensating decrease in the number of iterations. Further, the wide basin of convergence means that fewer starting points are needed for successful model fitting. Our system runs in real-time on CPU only, which frees up the commonly over-burdened GPU for experience designers. The hand tracker is efficient enough to run on low-power devices such as tablets. We can track up to several meters from the camera to provide a large working volume for interaction, even using the noisy data from current-generation depth cameras. Quantitative assessments on standard datasets show that the new approach exceeds the state of the art in accuracy. Qualitative results take the form of live recordings of a range of interactive experiences enabled by this new approach.

SmartForge: An event-driven architecture for simulator-based process optimization

In the metal industry, and more specifically in the forging one, scrap material is a crucial issue and reducing it would be an important goal to reach. Not only would this help the companies to be more environmentally friendly and more sustainable, but it also would reduce the use of energy and lower costs. At the same time, the techniques for Industry 4.0 and the advancements in Artificial Intelligence (AI), especially in the field of Deep Reinforcement Learning (DRL), may have an important role in helping to achieve this objective. This document presents the thesis work, a contribution to the SmartForge project, that was performed during a semester abroad at Karlstad University (Sweden). This project aims at solving the aforementioned problem with a business case of the company Bharat Forge Kilsta, located in Karlskoga (Sweden). The thesis work includes the design and later development of an event-driven architecture with microservices, to support the processing of data coming from sensors set up in the company's industrial plant, and eventually the implementation of an algorithm with DRL techniques to control the electrical power to use in it.

Life cycle assessment (LCA) of a bio-fuel cell fed with waste biomass: potential for scale-up and process optimization

In this Thesis, a life cycle analysis (LCA) of a biofuel cell designed by a team from the University of Bologna was done. The purpose of this study is to investigate the possible environmental impacts of the production and use of the cell and a possible optimization for an industrial scale-up. To do so, a first part of the paper was devoted to studying the present literature on biomass, and fuel cell treatments and then LCA studies on them. The experimental part presents the work done to create the Life Cycle Inventory and Life Cycle Impact Assessment. Several alternative scenarios were created to study process optimization. Reagents and energy supply were changed. To examine whether this technology can be competitive, a comparison was made with some biofuel cell use scenarios with traditional biomass treatment technologies. The result of this study is that this technology is promising from an environmental point of view in case it is possible to recover nutrients in output, without excessive energy consumption, and to minimize the use of energy used to prepare the solution.

Hegemonia e contra-hegemonia na construção de políticas de esporte e lazer : a experiência do Consórcio Brasília = Hegemony and counter-hegemony in the process of sport and leisure policy-making : the experience of the Consortium Brasilia

Universidade Estadual de Campinas . Faculdade de Educação Física

Searching for molecular markers in head and neck squamous cell carcinomas (HNSCC) by statistical and bioinformatic analysis of larynx-derived SAGE libraries

Background: Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignancies in humans. The average 5-year survival rate is one of the lowest among aggressive cancers, showing no significant improvement in recent years. When detected early, HNSCC has a good prognosis, but most patients present metastatic disease at the time of diagnosis, which significantly reduces survival rate. Despite extensive research, no molecular markers are currently available for diagnostic or prognostic purposes. Methods: Aiming to identify differentially-expressed genes involved in laryngeal squamous cell carcinoma (LSCC) development and progression, we generated individual Serial Analysis of Gene Expression (SAGE) libraries from a metastatic and non-metastatic larynx carcinoma, as well as from a normal larynx mucosa sample. Approximately 54,000 unique tags were sequenced in three libraries. Results: Statistical data analysis identified a subset of 1,216 differentially expressed tags between tumor and normal libraries, and 894 differentially expressed tags between metastatic and non-metastatic carcinomas. Three genes displaying differential regulation, one down-regulated (KRT31) and two up-regulated (BST2, MFAP2), as well as one with a non-significant differential expression pattern (GNA15) in our SAGE data were selected for real-time polymerase chain reaction (PCR) in a set of HNSCC samples. Consistent with our statistical analysis, quantitative PCR confirmed the upregulation of BST2 and MFAP2 and the downregulation of KRT31 when samples of HNSCC were compared to tumor-free surgical margins. As expected, GNA15 presented a non-significant differential expression pattern when tumor samples were compared to normal tissues. Conclusion: To the best of our knowledge, this is the first study reporting SAGE data in head and neck squamous cell tumors. Statistical analysis was effective in identifying differentially expressed genes reportedly involved in cancer development. The differential expression of a subset of genes was confirmed in additional larynx carcinoma samples and in carcinomas from a distinct head and neck subsite. This result suggests the existence of potential common biomarkers for prognosis and targeted-therapy development in this heterogeneous type of tumor.

The BRAzilian Seismographic Integrated Systems (BRASIS): infrastructure and data management

In geophysics and seismology, raw data need to be processed to generate useful information that can be turned into knowledge by researchers. The number of sensors that are acquiring raw data is increasing rapidly. Without good data management systems, more time can be spent in querying and preparing datasets for analyses than in acquiring raw data. Also, a lot of good quality data acquired at great effort can be lost forever if they are not correctly stored. Local and international cooperation will probably be reduced, and a lot of data will never become scientific knowledge. For this reason, the Seismological Laboratory of the Institute of Astronomy, Geophysics and Atmospheric Sciences at the University of Sao Paulo (IAG-USP) has concentrated fully on its data management system. This report describes the efforts of the IAG-USP to set up a seismology data management system to facilitate local and international cooperation.

Simultaneous preconcentration of copper, zinc, cadmium, and nickel in water samples by cloud point extraction using 4-(2-pyridylazo)-resorcinol and their determination by inductively coupled plasma optic emission spectrometry

A procedure for simultaneous separation/preconcentration of copper. zinc, cadmium, and nickel in water samples, based on cloud point extraction (CPE) as a prior step to their determination by inductively coupled plasma optic emission spectrometry (ICP-OES), has been developed. The analytes reacted with 4-(2-pyridylazo)-resorcinol (PAR) at pH 5 to form hydrophobic chelates, which were separated and preconcentrated in a surfactant-rich phase of octylphenoxypolyethoxyethanol (Triton X-I 14). The parameters affecting the extraction efficiency of the proposed method, such as sample pH, complexing agent concentration, buffer amount, surfactant concentration, temperature, kinetics of complexation reaction, and incubation time were optimized and their respective values were 5, 0.6 mmol L(-1). 0.3 mL, 0.15% (w/v), 50 degrees C, 40 min, and 10 min for 15 mL of preconcentrated solution. The method presented precision (R.S.D.) between 1.3% and 2.6% (n = 9). The concentration factors with and without dilution of the surfactant-rich phase for the analytes ranged from 9.4 to 10.1 and from 94.0 to 100.1, respectively. The limits of detection (L.O.D.) obtained for copper, zinc, cadmium, and nickel were 1.2, 1.1, 1.0. and 6.3 mu g L(-1), respectively. The accuracy of the procedure was evaluated through recovery experiments on aqueous samples. (C) 2009 Published by Elsevier B.V.

Fatty acid profile and qualitative characteristics of meat from zebu steers fed with different oilseeds

The objective of this study was to evaluate the effects of dietary addition of ground oilseed sources on the quality, fatty acid profile, and CLA content of meat from zebu steers. Thirty-one zebu steers with an initial average age of 23 mo and an initial BW of 365 kg were used in this study. The experimental period was 84 d, which was preceded by an adaption period of 28 d. The diet was provided ad libitum with a forage: concentrate ratio of 40:60. Corn silage was used as the forage source. Four different concentrates were formulated for each treatment: without additional lipids (control) or with ground soybeans (SB), ground cottonseed (CS), or ground linseed (LS). The SB, CS, and LS diets were formulated to have 6.5% ether extract on a total dietary DM basis. The experiment was set up as a completely randomized design. After slaughter, samples were taken from the longissimus thoracis muscle for the measurement of fatty acid concentration and the evaluation of meat quality. The luminosity index was greater in the control and LS diets (P < 0.01). The greatest percentages of myristic acid (C14:0), palmitic acid (C16:0), trans octadecenoic acid (C18:1 trans-10, trans-11, or trans-12), and SFA in the subcutaneous fat were observed in the CS treatment (P < 0.01). Moreover, the least percentages of oleic acid (C18:1 cis-9) and total unsaturated fatty acids in the subcutaneous fat were observed in the CS diet (P < 0.01). The meat linoleic acid and a-linolenic acid percentages were greatest in the SB and LS treatments, respectively (P < 0.001). The unsaturated fatty acid: SFA ratio was smallest for the CS diet (P < 0.01). A gradual increase in oxidation was observed as a function of storage time; however, the diets did not affect the rancidity of the meat (P > 0.05). The fatty acid profile of subcutaneous fat was impaired by the addition of CS. Supplying ground oilseeds did not increase the content of CLA in the meat.

Both beta(2)- and beta(1)-adrenergic receptors mediate hastened relaxation and phosphorylation of phospholamban and troponin I in ventricular myocardium of fallot infants, consistent with selective coupling of beta(2)-adrenergic receptors to G(s)-protein

Background-In adult human heart, both beta(1)- and beta(2)-adrenergic receptors mediate hastening of relaxation; however, it is unknown whether this also occurs in infant heart. We compared the effects of stimulation of beta(1)- and beta(2)-adrenergic receptors on relaxation and phosphorylation of phospholamban and troponin I in ventricle obtained from infants with tetralogy of Fallot. Methods and Results-Myocardium dissected from the right ventricular outflow tract of 27 infants (age range 2-1/2 to 35 months) with tetralogy of Fallot was set up to contract 60 times per minute. Selective stimulation of beta(1)-adrenergic receptors with (-)-norepinephrine (NE) and beta(2)-adrenergic receptors with (-)-epinephrine (EPI) evoked phosphorylation of phospholamban (at serine-16 and threonine-17) and troponin I and caused concentration-dependent increases in contractile force (-log EC50 [mol/L] NE 5.5+/-0.1, n=12; -EPI 5.6+/-0.1, n=13 patients), hastening of the time to reach peak force (-log EC50 [mol/L] NE 5.8+/--0.2; EPI 5.8+/-0.2) and 50% relaxation (-log EC50 [mol/L] NE 5.7+/-0.2: EPI 5.8+/-0.1), Ventricular membranes from Fallot infants, labeled with (-)-[I-125]-cyanopindolol, revealed a greater percentage of beta(1)- (71%) than beta(2)-adrenergic receptors (29%). Binding of (-)-epinephrine to beta(2)-receptors underwent greater GTP shifts than binding of (-)-norepinephrine to beta(1)-receptors. Conclusions-Despite their low density, beta(2)-adrenergic receptors are nearly as effective as beta(1)-adrenergic receptors of infant Fallot ventricle in enhancing contraction, relaxation, and phosphorylation of phospholamban and troponin I, consistent with selective coupling to G(s)-protein.

Ultrasonic Chemical Vapor Deposition-coated Tip versus High- and Low-speed Carbide Burs for Apicoectomy: Time Required for Resection and Scanning Electron Microscopy Analysis of the Root-end Surfaces

This study compared ultrasonic chemical vapor deposition (CVD)-coated tip (CVDentus #8.1117-1; Clorovale Diamantes Ind. e Com. Ltda Epp, Sao Jose dos Campos, SP, Brazil) versus high-speed (#FG700L) and low-speed (#699) carbide burs for apicoectomy, evaluating the time required for resection and analyzing the root-end surfaces by scanning electron microscopy. Thirty extracted human premolars had the canals instrumented and obturated and were randomly assigned to 3 groups (n = 10), according to the instrument used for root-end resection. The time required for resection of the apical 2 mm of each root was recorded. The resected apical segments were dried, sputter coated with gold, and examined with a scanning electron microscope at X 350 magnification. A four-point (0-3) scoring system was used to evaluate the apical surface smoothness. The results were analyzed statistically by the Kruskal-Wallis test and two-by-two comparisons analyses were performed using the Miller test. The significance level was set at 5%. Root-end resection with the high-speed bur was significantly faster (p < 0.05) compared with the low-speed bur and CVD tip. The carbide burs produced significantly smoother root-end surfaces than the CVD tip (p < 0.05). The low-speed bur produced the smoothest root-end surfaces, whereas the roughest and most irregular root ends (p < 0.05) were obtained with the CVD tip. However, no statistically significant difference (p > 0.05) was found between the high- and low-speed burs regarding the surface roughness of the resected root ends (p > 0.05). In conclusion, under the tested conditions, ultrasonic root-end resection took a longer time and resulted in rougher surfaces compared with the use of carbide burs at both high and low speed. (J Endod 2009;35:265-268)

(-)-CGP 12177 increases contractile force and hastens relaxation of human myocardial preparations through a propranolol-resistant state of the beta1-adrenoceptor

Two forms of the activated beta(1)-adrenoceptor exist, one that is stabilized by (-)-noradrenaline and is sensitive to blockade by (-)-propranolol and another which is stabilized by partial agonists such as (-)-pindolol and (-)-CGP 12177 but is relatively insensitive to (-)-propranolol. We investigated the effects of stimulation of the propranolol-resistant PI-adrenoceptor in the human heart. Myocardium from non-failing and failing human hearts were set up to contract at 1 Hz. In right atrium from non-ailing hearts in the presence of 200 nM (-)-propranolol, (-)-CGP 12177 caused concentration-dependent increases in contractile force (-logEC(50)[M] 7.3+/-0.1, E-max 23+/-1% relative to maximal (-)-isoprenaline stimulation of beta(1)- and beta(2)-adrenoceptors, n=86 patients), shortening of the time to reach peak force (-logEC(50)[M] 7.4+/-0.1, E-max 37+/-5%, n=61 patients) and shortening of the time to reach 50% relaxation (t(50%), -logEC(50)[M] 7.3+/-0.1, E-max 33+/-2%, n=61 patients). The potency and maxima of the positive inotropic effects were independent of Ser49Gly- and Gly389Arg-beta(1)-adrenoceptor polymorphisms but were potentiated by the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (-logEC(50)[M] 7.7+/-0.1, E-max 68+/-6%, n=6 patients, P