Rapid and simple HPLC-UV and LC-MS methods were developed and validated for the quantification of ertapenem (Invanz™) in human plasma. Ertapenem is a unique drug in that current dosing recommendations call for a 1g dose for normal renal function patients, despite body weight. These assays, which involve a protein precipitation followed by liquid-liquid extraction, allow for fast therapeutic drug monitoring of ertapenem in patients, which is especially useful in special populations. Both methods were sufficient to baseline resolve meropenem (internal standard) and ertapenem, and were validated over 3days using a six-point calibration curve (0.5-50μg/mL). Validation was collected using four different points on the calibrations curve yielding acceptable precision (<15% inter-day and intra-day; <20% for lower limit of quantitation, LLOQ) as well as accuracy (<15% inter-day and intra-day; <20% for LLOQ). The lower limit of detection (LOD) was determined to be 0.1 and 0.05μg/mL for the HPLC-UV and LC-MS methods, respectively. The developed HPLC-UV and LC-MS methods for ertapenem quantification are fast, accurate and reproducible over the calibration range and can be used to determine ertapenem plasma concentrations for monitoring clinical efficacy.

Rapid and simple HPLC-UV and LC-MS methods were developed and validated for the quantification of ertapenem (Invanz™) in human plasma. Ertapenem is a unique drug in that current dosing recommendations call for a 1g dose for normal renal function patients, despite body weight. These assays, which involve a protein precipitation followed by liquid-liquid extraction, allow for fast therapeutic drug monitoring of ertapenem in patients, which is especially useful in special populations. Both methods were sufficient to baseline resolve meropenem (internal standard) and ertapenem, and were validated over 3days using a six-point calibration curve (0.5-50μg/mL). Validation was collected using four different points on the calibrations curve yielding acceptable precision (<15% inter-day and intra-day; <20% for lower limit of quantitation, LLOQ) as well as accuracy (<15% inter-day and intra-day; <20% for LLOQ). The lower limit of detection (LOD) was determined to be 0.1 and 0.05μg/mL for the HPLC-UV and LC-MS methods, respectively. The developed HPLC-UV and LC-MS methods for ertapenem quantification are fast, accurate and reproducible over the calibration range and can be used to determine ertapenem plasma concentrations for monitoring clinical efficacy.

Commercially available methylphenidate (MPH) exists as a racemic mixture composed of the d- and l-threo enantiomers. Various pharmacokinetic studies of MPH have shown a greater pharmacological potency of the d-threo enantiomer. Furthermore, it was deduced that the stereoselective cleavage of MPH to produce ritalinic acid (RA) by human carboxylesterase results in a higher oral bioavailability of the d-threo enantiomer. As a requirement for pharmaceutical regulation authorities, efforts have been made to determine the differential biological distribution of d- and l-threo MPH and RA enantiomers. In support of these efforts, numerous analytical procedures have been developed for the chiral separation and quantification of MPH enantiomers in a variety of biological matrices. The available methodologies accomplish the enantioseparation and quantification of MPH using gas chromatography, liquid chromatography or capillary electrophoretic techniques coupled with a variety of detectors. The current review discusses the technical procedures involved, and the sensitivity and selectivity of these assays.

UV exposure via sunbathing and utilization of sun lamps and tanning beds are considered important risk factors for the development of skin cancer. Psychosocial models of UV exposure are often based on theories of health behavior, but theory from the body image field can be useful as well. The current study examines models that prospectively predict sunbathing and indoor tanning behaviors using constructs and interrelationships derived from the tripartite theory of body image, theory of reasoned action, health belief model, revised protection motivation theory, and a proposed integration of several health behavior models. The results generally support a model in which intentions mediate the relationship between appearance attitudes and tanning behaviors, appearance reasons to tan and intentions mediate the relationship between sociocultural influences and tanning behaviors, and appearance reasons not to tan and intentions mediate the role of perceived threat on behaviors. The implications of these findings are considered.

Indiana University-Purdue University Indianapolis (IUPUI) / Despite the lifecycle of the hepatitis B virus (HBV) being extensively investigated and described, there remains a significant gap in our knowledge of arguably one of the most crucial steps in the HBV lifecycle, the formation and maintenance of a covalently closed circular DNA (cccDNA) reservoir. Advancements in our understanding of host factors and pathways involved in cccDNA formation have been made through hypothesis driven studies and shRNA/siRNA screenings. We sought to create a targeted-unbiased assay to directly observe host factor-rcDNA interactions. This was achieved through an rcDNA Co-Immunoprecipitation paired Mass Spectrometry (rcDNA-CoIP/MS) assay. We created a DNA oligo complimentary to the open portion of the HBV rcDNA, labeled with biotin, to facilitate easy precipitation of nuclear rcDNA and complexed proteins. Proteins precipitated were analyzed through liquid chromatography paired mass spectrometry (LC/MS). Along with previously reported host factors, several factors of DNA damage repair pathways/complexes were also identified. A component of the UV-DDB complex, DDB1, surfaced as a hit. UV-DDB/rcDNA binding was confirmed through ChIP-qPCR. DDB2, the DNA damage binding component of the UV-DDB complex was knocked out in HepG2-NTCP and HepAD38 cells. This resulted in a significant decrease in the formation of cccDNA in DDB2 knockout cell lines following infection or induction. The subsequent reduction of downstream indicators of cccDNA formation such as viral RNA and proteins, HBcAg and HBeAg, showed a consistent decrease with cccDNA levels. Ectopic expression of DDB2 in the knockout cell lines rescued HBV phenotypes of cccDNA levels and its downstream indicators. Inactive mutant DDB2 plasmids were also transfected into the DDB2 K/O cell lines and failed to rescue cccDNA indicators. We therefore showed through a novel assay that we can discover novel viral rcDNA-host interactions, such as the UV-DDB complex recruiting DNA repair pathways to “repair” rcDNA to cccDNA.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20559号 / 医博第4244号 / 新制||医||1022(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 高田 穣, 教授 萩原 正敏, 教授 松本 智裕 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Synthetische anorganische Knochenersatzmaterialien auf Calcium-Phosphat- und Magnesium-Phosphat-Basis wurden in der hier vorliegenden Dissertation mit verschiedenen handelsüblichen Antibiotika versetzt und deren Freisetzungsverhalten charakterisiert. Zudem wurde der Einfluss des Antibiotikazusatzes auf bestimmte materialcharakteristische Eigenschaften untersucht, hierbei fanden die Quecksilberporosimetrie, die Röntgendiffraktometrie und die Rasterelektronenmikroskopie ihre Anwendung. Insbesondere für die Knochenersatzmaterialien auf Calcium-Phosphat-Basis sollte eine klinisch praktikable und demnach möglichst einfache Methode etabliert werden, um die Kombination mit einem Antibiotikum durchzuführen. Die Detektion der Antibiotika erfolgte mit Hilfe eines UV/VIS-Spektrophotometers. Zudem wurde für einige ausgewählte Kombinationen aus Antibiotikum und Knochenersatzmaterial durch einen Agardiffusionstest die antibakterielle Wirkung nach der Freisetzung aus dem jeweiligen Trägermaterial bestätigt. / Synthetic inorganic bone substitute materials based on calcium phosphate and magnesium phosphate were mixed with various commercially available antibiotics and their release behavior was characterized in the present dissertation. In addition, the influence of the antibiotic addition on certain material characteristic properties was investigated using mercury porosimetry, X-ray diffractometry and scanning electron microscopy. For the calcium-phosphate-based bone substitutes in particular, the aim was to establish a clinically practicable and therefore as simple as possible method for carrying out the combination with an antibiotic. Antibiotics were detected using a UV/VIS spectrophotometer. In addition, for some selected combinations of antibiotic and bone substitute material, an agar diffusion test was used to confirm the antibacterial effect after release from the respective carrier material.

Individual and multiple stress factor effects of temperature on cotton growth and development were studied in four cotton cultivars. In Experiment I, seedling emergence rate and shoot and root morphological growth traits were measured on plants grown at five day/night temperatures from 20/12 to 40/32 °C. In Experiment II, multiple stress factors (CO2, temperature, UV-B radiation) and their interactions were evaluated during the seedling growth stage. Seed emergence and above- and below-ground growth and developmental traits were recorded in both experiments. Linear (TM-1 and PHY496W3R) and quadratic (DP1522B2XF and ST47447) functions best described seed emergence rate with an increase in temperature. Similar responses were also observed for many root traits among the cultivars. Based on vigor and principal component analysis, DP1522B2XF was identified as the most tolerant, PHY496W3R and ST4747GLB2 as moderately tolerant, and TM-1 as the least tolerant cultivar to multiple environmental stresses.

This publication is dedicated to investigate strong light-matter coupling with excitons in 2D materials. This work starts with an introduction to the fundamentals of excitons in 2D materials, microcavities and strong coupling in chapter 2. The experimental methods used in this work are explained in detail in chapter 3. Chapter 4 covers basic investigations that help to select appropriate materials and cavities for the following experiments. In chapter 5, results on the formation of exciton-polaritons in various materials and cavity designs are presented. Chapter 6 covers studies on the spin-valley properties of exciton-polaritons including effects such as valley polarization, valley coherence and valley-dependent polariton propagation. Finally, the formation of hybrid-polaritons and their condensation are presented in chapter 7. / Diese Veröffentlichung beschäftigt sich mit starker Licht-Materie Kopplung mit Exzitonen in 2D Materialien. Dies Arbeit beginnt mit einer Einführung in Exzitonen in 2D Materialien, in Mikrokavitäten und starke Licht-Materie Kopplung (Kapitel 1). Die verwendeten, experimentellen Methoden werden in Kapitel 3 beschrieben. Kapitel 4 deckt Voruntersuchungen ab, die helfen die richtigen Materialien und Mikrokavitäten für die folgenden Experimente auszuwählen. In Kapitel 5 werden die Ergebnisse zur Erzeugung von Exziton-Polaritonen in verschiednen Materialen und Kavitäten gezeigt. Kapitel 6 beschäftigt sich mit Untersuchungen der Spin-Tal Eigenschaften der Exziton-Polaritonen, inkl. Effekte wie Tal Polarisation und Koherenz. Abschließend wird in Kapitel 7 die Erzeugung von Hybrid-Polaritonen und deren Kondensation dargestellt.

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