No description available.

No description available.

Cellular growth, development, differentiation, and death are mediated to some degree by the interaction of soluble factors with plasma membrane receptors. Traditionally the cellular response to chemical cues has been studied by exposing entire culture dishes to a desired reagent. While the addition of soluble reagents homogenously to cell culture dishes provides a basis for understanding much of cell biology, greater spatial resolution of reagent delivery is necessary in order to elucidate mechanisms on the subcellular scale. This dissertation explores techniques that may improve the quality and precision of delivering soluble factors to cultured cells in order to better understand the complex processes of cell biology. These advancements were made possible by applying high intensity, focused laser light to soluble materials to achieve microscopic three-dimensional (µ-3D) printing. In combination with a previously developed microfluidic cell dosing platform, microstructures were designed and µ-3D printed to hydrodynamically focus reagent streams for cell dosing. Structures were also µ-3D printed within micrometers of living cells from a solution of gelatin and bovine serum albumin with minimal cytotoxicity. When µ-3D printed, these proteins displayed both temperature and pH-responsive properties. In order to allow for on-the-fly control of reagent stream size and temporal pulse width, microstructures were µ-3D printed from temperature-responsive N- isoproplyacrylamide. To further improve the temporal resolution of the system, a technique for cycling between reagents with millisecond exchange times using laminar flow microfluidics was developed. The utility of these techniques was demonstrated by staining rat Schwann cells and mouse neuroblastoma rat glioma hybrid cells (NG108-15) with focused streams of fluorescent dyes. These advancements may allow future experiments to determine the placement of soluble factors necessary for bacterial quorum sensing or stem cell differentiation. / text

<p>For prevention and treatment of thrombotic diseases with an anticoagulant drug it is important that an adequate dose is given to avoid occurrence or recurrence of thrombosis, without increasing the risk of bleeding and other adverse events to unacceptable levels. The aim of this thesis was to develop mathematical models that describe the dose-concentration (pharmacokinetic) and concentration-response (pharmacodynamic) relationships of direct thrombin inhibitors, in order to estimate optimal dosages for treatment and long-term secondary prevention of venous thromboembolism (VTE).</p><p>Population pharmacokinetic-pharmacodynamic models were developed, based on data from clinical investigations in healthy volunteers and patients receiving intravenous inogatran, subcutaneous melagatran and/or its oral prodrug ximelagatran. The benefit-risk profiles of different ximelagatran dosages were estimated using clinical utility functions. These functions were based on the probabilities and fatal consequences of thrombosis, bleeding and elevation of the hepatic enzyme alanine aminotransferase (ALAT).</p><p>The studies demonstrate that the pharmacokinetics of melagatran and ximelagatran were predictable and well correlated to renal function. The coagulation marker, activated partial thromboplastin time (APTT), increased non-linearly with increasing thrombin inhibitor plasma concentration. Overall, the systemic melagatran exposure (AUC) and APTT were similarly predictive of thrombosis and bleedings. The identified relationship between the risk of ALAT-elevation and melagatran AUC suggests that the incidence approaches a maximum at high exposures. The estimated clinical utility was favourable compared to placebo in the overall study population and in special subgroups of patients following fixed dosing of ximelagatran for long-term secondary prevention of VTE. Individualized dosing was predicted to add limited clinical benefit in this indication.</p><p>The models developed can be used to support the studied dosage and for selection of alternative dosing strategies that may improve the clinical outcome of ximelagatran treatment. In addition, the models may be extrapolated to aid the dose selection in clinical trials with other direct thrombin inhibitors.</p>

Extending electronic devices beyond the limitations of current micro-electronics manufacturing will require detailed knowledge of how to make contacts to semiconductor surfaces. In this work, we investigated several methods by which such connections to silicon surfaces could be achieved. Scanning tunneling microscopy (STM) was our main experimental tool, allowing direct imaging of the surfaces at the atomic level. First, the growth of self-forming linear nanostructures of organic molecules on silicon surfaces offers a possibility of creating devices with hybrid organic-silicon functionality. We have studied the growth of many different molecules on a variety of hydrogen-terminated silicon surfaces: H-Si(100)-2x1, H-Si(100)-3x1, and H-Si(111)-1x1. We found molecular growth patterns affected by steric crowding, by sample doping level, or by exposure to ion-pump created radicals. We formed the first contiguous "L-shaped" molecular lines, and used an external electric field to direct molecular growth. We attempted to study a novel method for nanoscale information transfer along molecular lines based on excitation energy transfer. The second part of the work focuses on the development and use of a new multiple-probe STM instrument. The design and the custom STM control software written for it are described. Connections to Si surfaces were achieved with a combination of lithographically defined metal contacts and STM tips. Two-dimensional surface conductivity of the Si(111)-7x7 surface was measured, and the effect of modifying the surface with organic molecules was investigated. A novel method, scanning tunneling fractional current imaging (STFCI), was developed to further study surface conductance. This method allowed us to determine, for the first time, that the resistance of steps on the Si(111)-7x7 surface is significantly higher than that of the surface alone.

For prevention and treatment of thrombotic diseases with an anticoagulant drug it is important that an adequate dose is given to avoid occurrence or recurrence of thrombosis, without increasing the risk of bleeding and other adverse events to unacceptable levels. The aim of this thesis was to develop mathematical models that describe the dose-concentration (pharmacokinetic) and concentration-response (pharmacodynamic) relationships of direct thrombin inhibitors, in order to estimate optimal dosages for treatment and long-term secondary prevention of venous thromboembolism (VTE). Population pharmacokinetic-pharmacodynamic models were developed, based on data from clinical investigations in healthy volunteers and patients receiving intravenous inogatran, subcutaneous melagatran and/or its oral prodrug ximelagatran. The benefit-risk profiles of different ximelagatran dosages were estimated using clinical utility functions. These functions were based on the probabilities and fatal consequences of thrombosis, bleeding and elevation of the hepatic enzyme alanine aminotransferase (ALAT). The studies demonstrate that the pharmacokinetics of melagatran and ximelagatran were predictable and well correlated to renal function. The coagulation marker, activated partial thromboplastin time (APTT), increased non-linearly with increasing thrombin inhibitor plasma concentration. Overall, the systemic melagatran exposure (AUC) and APTT were similarly predictive of thrombosis and bleedings. The identified relationship between the risk of ALAT-elevation and melagatran AUC suggests that the incidence approaches a maximum at high exposures. The estimated clinical utility was favourable compared to placebo in the overall study population and in special subgroups of patients following fixed dosing of ximelagatran for long-term secondary prevention of VTE. Individualized dosing was predicted to add limited clinical benefit in this indication. The models developed can be used to support the studied dosage and for selection of alternative dosing strategies that may improve the clinical outcome of ximelagatran treatment. In addition, the models may be extrapolated to aid the dose selection in clinical trials with other direct thrombin inhibitors.

Atmospheric CO₂ enrichment is employed by greenhouse tomato growers to increase fruit yields, and CO₂ applications are managed according to atmospheric set points or CO₂ injection rates. These methods do not immediately focus on the targets of CO₂ applications: plant performance and the regulation of plant carbon status. This thesis explores several plant-based approaches that may have potential for use in the management of CO₂ in greenhouse tomato production. Three plant-based approaches to CO₂ management were explored in commercial and experimental tomato greenhouses. These were: (1) simulation modeling, (2) non-destructive analysis of growth and (3) the status of plant carbon reserves. A cost and benefit analysis (c/b) using simulation modeling was carried out using grower-collected greenhouse environment and yield data. Simulation modeling was useful for retrospectively determining c/b of several CO₂ scenarios. The model was effective in predicting long term yields, but not short term yield variations, which limits its application for CO₂ management. Non-destructive measures of growth: stem length and diameter, leaf area and fruit load were found to be too sluggish for daily CO₂ dosing decision-making. Finally, plants growing under CO₂ enrichment can deposit substantial carbon as starch in their leaves. Plant carbon status was evaluated by determining the spatial distribution of leaf starch in the shoot and by following its variation diurnally and after the onset of CO₂ enrichment. As starch is difficult to measure by a grower, leaf mass per unit area (LMA) was also monitored for assessment as a surrogate measure for starch. Leaves in positions 7 to 9 were identified as the most meaningful in the shoot to sample. Diurnal profiles indicated these leaves carryover substantial starch from one day to the next. Monitoring starch at its peak time of accumulation (14 h to 16 h), at sunset and sunrise will indicate how much the peak starch reserves are used overnight. If starch remains high between peak and sunrise the following day, then the plants are in a carbon-surplus state and CO₂ enrichment could be postponed. For upper canopy leaves LMA is substantially influenced by starch and thus is a promising surrogate.

Atmospheric CO₂ enrichment is employed by greenhouse tomato growers to increase fruit yields, and CO₂ applications are managed according to atmospheric set points or CO₂ injection rates. These methods do not immediately focus on the targets of CO₂ applications: plant performance and the regulation of plant carbon status. This thesis explores several plant-based approaches that may have potential for use in the management of CO₂ in greenhouse tomato production. Three plant-based approaches to CO₂ management were explored in commercial and experimental tomato greenhouses. These were: (1) simulation modeling, (2) non-destructive analysis of growth and (3) the status of plant carbon reserves. A cost and benefit analysis (c/b) using simulation modeling was carried out using grower-collected greenhouse environment and yield data. Simulation modeling was useful for retrospectively determining c/b of several CO₂ scenarios. The model was effective in predicting long term yields, but not short term yield variations, which limits its application for CO₂ management. Non-destructive measures of growth: stem length and diameter, leaf area and fruit load were found to be too sluggish for daily CO₂ dosing decision-making. Finally, plants growing under CO₂ enrichment can deposit substantial carbon as starch in their leaves. Plant carbon status was evaluated by determining the spatial distribution of leaf starch in the shoot and by following its variation diurnally and after the onset of CO₂ enrichment. As starch is difficult to measure by a grower, leaf mass per unit area (LMA) was also monitored for assessment as a surrogate measure for starch. Leaves in positions 7 to 9 were identified as the most meaningful in the shoot to sample. Diurnal profiles indicated these leaves carryover substantial starch from one day to the next. Monitoring starch at its peak time of accumulation (14 h to 16 h), at sunset and sunrise will indicate how much the peak starch reserves are used overnight. If starch remains high between peak and sunrise the following day, then the plants are in a carbon-surplus state and CO₂ enrichment could be postponed. For upper canopy leaves LMA is substantially influenced by starch and thus is a promising surrogate.

No description available.

Objective of the work: The purpose of this quantitative retrospective comparative study was to register possible cases of augmentedted renal clearance (ARC) in patients of Hospital of Lithuanian University of Health Sciences and analyse the differences in assessments of cases of Augmented Renal Clearance and the drug therapy problems related to ARC. Tasks: To achieve the objective, several tasks were performed: 1) to register possible ARC patients cases as assessed by Cocroft-Gault and their possible associated reasons; 2) to analyse differences in three equations used for GFR estimation: Cocroft-Gault, MDRD simplified, and CKD-EPI. 3) compare the therapies of the patients and determine the drugs that are in risk of being underdosed when ARC is present. Methodology: An ARC survey (appendix 1) was filled about patients from various departments of Clinics during the period of 2013 03 04 – 2014 08 15. All patients were selected according serum creatinine values that were 50 µmol/l. or less. Two goups of patients were assigned for analysis: patients were grouped according Cocroft - Gault creatinine clearance values: (1) ARC group A CrCl >130 ml./min and (2) comparative Non-ARC group B CrCl 90-130 ml./min. Data were analyzed by using descriptive and comparative statistical analysis, considering statistically significant difference between the groups if p value was <0.05. Results and conclusions: 1. In the research group and comparative groups were 31 patients selected... [to full text] / Darbo tikslas: Šio kiekybinio retrospektyvaus palyginamojo darbo tikslas buvo surinkti duomenis apie padidinto inkstų klirenso PIK atvejus Lietuvos sveikatos mokslų universiteto ligonines Kauno klinikose. Buvo siekiama išanalizuoti sirtumus tarp skirtingų PIK įvertinimo būdų ir įvertinti galimas su PIK susijusias terapijos problemas. Uždaviniai: norint pasiekti užsibrėžtus tikslus šie uždaviniai buvo iškelti: 1) užregistruoti PIK atvejus ir nustatyti jų galimas priežastis. 2) apskaičiuoti GFG trimis skirtingomis formulėmis (Cocroft-Gault, MDRD, CKD-EPI) ir išanalizuoti skirtumus. 3) palyginti pacientų terapijas ir nustatyti, kurie vaistai galimai yra subterapinio dozavimo rizikoje Metodika: PIK anketa ( 1 priedas) buvo pildoma apie pacientus iš skirtingų Kauno klinikų skyrių, laikotarpiu nuo 2013 03 04 iki 2014 08 15. Visi pacientai buvo parinkti pagal kreatinino kiekį serume – 50 μmol/l.. ir mažiau. Dvi pacientų grupės buvo parinktos analizei: pacientai buvo sugrupuoti pagal kreatinino klirensą į (1) PIK A grupę – CrCl > 130 ml./min. ir (2) palyginamąją B grupę – CrCl 90-130 ml./min. Duomenys buvo analizuojami naudojant palyginamąją ir aprašomąją statistiką. Skirtumai tarp grupių buvo laikomi statistiškai reikšmingi, kai p reikšmė buvo <0.05. Rezultatai ir išvados: 1. Abiejose grupėse buvo surinkta po 31 pacientą (iš viso 62 pacientai). Remiantis darbo rezultatais, galima daryti išvadą, kad PIK (kai GFG yra 130ml/min. ir daugiau) nustatymui naudojant Cocroft-Gault formulę... [toliau žr. visą tekstą]