Bioorthogonal Small Molecule Imaging Agents Allow Single-Cell Imaging of MET

The hepatocyte growth factor receptor (MET) is a receptor tyrosine kinase (RTK) that has emerged as an important cancer target. Consequently, a number of different inhibitors varying in specificity are currently in clinical development. However, to date, it has been difficult to visualize MET expression, intracellular drug distribution and small molecule MET inhibition. Using a bioorthogonal approach, we have developed two companion imaging drugs based on both mono- and polypharmacological MET inhibitors. We show exquisite drug and target co-localization that can be visualized at single-cell resolution. The developed agents may be useful chemical biology tools to investigate single-cell pharmacokinetics and pharmacodynamics of MET inhibitors

Polarization-sensitive spectral interferometry

A polarization sensitive spectral interferometer apparatus and method for analyzing a sample by optical energy reflected from the sample. The polarization sensitive spectral interferometer apparatus and method determines polarization properties of the sample by optical energy reflected from the sample.Board of Regents, University of Texas Syste

Polarization-sensitive spectral interferometry as a function of depth for tissue identification

A polarization sensitive spectral interferometer apparatus and method for analyzing a sample by optical energy reflected from the sample. The polarization sensitive spectral interferometer apparatus and method determines polarization properties of the sample by optical energy reflected from the sample. The method for analyzing a sample with a spectral interferometer identifies the tissue type of the sample by the polarization properties as a function of depth from the sample.Board of Regents, University of Texas Syste

Polarization-sensitive spectral interferometry

A polarization sensitive spectral interferometer apparatus and method for analyzing a sample. The polarization sensitive spectral interferometer apparatus and method determines polarization properties of the sample.Board of Regents, University of Texas Syste

聴覚障害児の視点取得の発達的特徴に関する研究 －読書力と課題の違いによる検討－

この博士論文は内容の要約のみの公開（または一部非公開）になっています筑波大学 (University of Tsukuba)201

Single cell imaging of Bruton's Tyrosine Kinase using an irreversible inhibitor

A number of Bruton's tyrosine kinase (BTK) inhibitors are currently in development, yet it has been difficult to visualize BTK expression and pharmacological inhibition in vivo in real time. We synthesized a fluorescent, irreversible BTK binder based on the drug Ibrutinib and characterized its behavior in cells and in vivo. We show a 200 nM affinity of the imaging agent, high selectivity, and irreversible binding to its target following initial washout, resulting in surprisingly high target-to-background ratios. In vivo, the imaging agent rapidly distributed to BTK expressing tumor cells, but also to BTK-positive tumor-associated host cells

Rational Perturbation of the Fluorescence Quantum Yield in Emission‐Tunable and Predictable Fluorophores (Seoul‐Fluors) by a Facile Synthetic Method Involving C—H Activation†

Abstract Fluorescence imaging enables the uniquely sensitive observation of functional‐ and molecular‐recognition events in living cells. However, only a limited range of biological processes have been subjected to imaging because of the lack of a design strategy and difficulties in the synthesis of biosensors. Herein, we report a facile synthesis of emission‐tunable and predictable Seoul‐Fluors, 9‐aryl‐1,2‐dihydrolopyrrolo[3,4‐b]indolizin‐3‐ones, with various R1 and R2 substituents by coinage‐metal‐catalyzed intramolecular 1,3‐dipolar cycloaddition and subsequent palladium‐mediated C—H activation. We also showed that the quantum yields of Seoul‐Fluors are controlled by the electronic nature of the substituents, which influences the extent of photoinduced electron transfer. On the basis of this understanding, we demonstrated our design strategy by the development of a Seoul‐Fluor‐based chemosensor 20 for reactive oxygen species that was not accessible by a previous synthetic route

The Importance and the Developability of Interpersonal Competency at Work: Implications for Higher Education

2007The purpose of this study was to derive behavior indicators of interpersonal competency based on competency model used by business organizations in Korea and to explore the importance and the developability of those indicators. Five interviewees who were Human Resource Development(HRD) professionals provided behavior indicators of interpersonal competency according to the competency model of the organizations. Three experts examined the set of statements for redundancies and synthesized the ideas for identifying representative indicators. Finally, 36 participants were asked to rate the importance and the developability of each statement upon the organizational situation on a 5-point Likert-type scale ranging from 1 to 5. Descriptive statistics, mean difference profile analysis, and the Go-Zone analysis were used to represent the importance and the developability of interpersonal competency at work. The findings provided practical indicators of interpersonal competency in Korean business organizations and understandings of their importance and developability perceived by HR professionals in Korea. Applications of the findings to organizations and implications for higher education were discussed

Psychosis-Induced Exertional Rhabdomyolysis without Acute Kidney Injury or Myoglobinuria.

BACKGROUND Rhabdomyolysis is a clinical syndrome that results from skeletal muscle breakdown and the release of intracellular enzymes into systemic circulation [1,2]. We present a case of non-traumatic rhabdomyolysis with transaminitis, without myoglobinuria or acute kidney injury. Cases reports of rhabdomyolysis with elevation of serum creatine kinase (hyperCKemia) in the absence of myoglobinuria or renal failure are limited in the literature. CASE REPORT A 21-year-old man presented to the Emergency Department following an acute psychotic episode. One week earlier, his bloodwork had been within normal limits. Biochemical investigations on admission revealed hyperCKemia (590 000 U/L), transaminitis (AST, 628; ALT, 160), and normal creatinine (0.83), without myoglobinuria. Non-traumatic rhabdomyolysis was suspected, and the patient was treated with aggressive intravenous fluid resuscitation and transferred to Inpatient Psychiatry on day 10 of hospitalization. The complete metabolic panel was trended daily, without indication of kidney injury. The creatine kinase (CK) and liver function tests trended downward. CONCLUSIONS This report presents a rare case of exertional rhabdomyolysis with CK levels nearly 3000 times the upper limit of normal, without myoglobinuria or acute kidney injury. Acute kidney injury is a dangerous complication of rhabdomyolysis. Traditionally, clinicians use serum CK levels to predict the likelihood of acute kidney injury and/or renal failure in rhabdomyolysis. Ultimately, this patient was diagnosed with exertional rhabdomyolysis with hyperCKemia and transaminitis without myoglobinuria or acute kidney injury. More research is needed to elucidate the protective patient characteristics against rhabdomyolysis-associated acute kidney injury, associations between CK and myoglobinuria, and diagnostic criteria for psychosis-associated hyperCKemia

A foundation for provitamin A biofortification of maize: genome-wide association and genomic prediction models of carotenoid levels.

Efforts are underway for development of crops with improved levels of provitamin A carotenoids to help combat dietary vitamin A deficiency. As a global staple crop with considerable variation in kernel carotenoid composition, maize (Zea mays L.) could have a widespread impact. We performed a genome-wide association study (GWAS) of quantified seed carotenoids across a panel of maize inbreds ranging from light yellow to dark orange in grain color to identify some of the key genes controlling maize grain carotenoid composition. Significant associations at the genome-wide level were detected within the coding regions of zep1 and lut1, carotenoid biosynthetic genes not previously shown to impact grain carotenoid composition in association studies, as well as within previously associated lcyE and crtRB1 genes. We leveraged existing biochemical and genomic information to identify 58 a priori candidate genes relevant to the biosynthesis and retention of carotenoids in maize to test in a pathway-level analysis. This revealed dxs2 and lut5, genes not previously associated with kernel carotenoids. In genomic prediction models, use of markers that targeted a small set of quantitative trait loci associated with carotenoid levels in prior linkage studies were as effective as genome-wide markers for predicting carotenoid traits. Based on GWAS, pathway-level analysis, and genomic prediction studies, we outline a flexible strategy involving use of a small number of genes that can be selected for rapid conversion of elite white grain germplasm, with minimal amounts of carotenoids, to orange grain versions containing high levels of provitamin A