Triquinanes from linear alkylidene carbenes via trimethylenemethane diyls.
The intramolecular [2+3] cycloaddition reaction of the trimethylenemethane diyl generated from the intramolecular cyclopropanation reaction of alkylidene carbene produced linearly fused triquinanes regio- and stereoselectively. The current tandem cycloaddition reaction was applied to a 14-step total synthesis of hirsutene from methallyl alcohol.

title: Development of tripeptidyl farnesyltransferase inhibitors.
abstract: The first example of tripeptide inhibitors of farnesyltransferase with sub-micromolar inhibition activity was developed based on the fact that CVFM is not a substrate for farnesyltransferase.

title: Angularly fused triquinanes from linear substrates through trimethylenemethane diyl [2 + 3] cycloaddition reaction.
abstract: Angularly fused triquinanes were synthesized from linear dienes and phenyl(propynyl)iodonium salt through trimethylenemethane (TMM) diyl mediated [2 + 3] cycloaddition reaction. TMM diyl intermediates were obtained from alkylidene carbenes generated from reactions of alkynyliodonium salts with nucleophiles.

title: One-pot three-component tandem metathesis/Diels-Alder reaction.
abstract: [reaction: see text] A tandem enyne, diene-ene metathesis reaction followed by Diels-Alder reaction accomplished a stereoselective three-component reaction protocol with four stereocenters.

title: A stereoselective enyne cross metathesis.
abstract: [reaction: see text] Intermolecular enyne metathesis reaction of alkynes with olefins catalyzed by second-generation Grubbs catalyst (1) proceeded stereoselectively under ethylene atmosphere to produce 1,3-disubstituted butadienes with E stereochemistry.

title: A Facile Construction of the Quadranoid Skeleton: Application to the Total Synthesis of (+/-)-Suberosenone.
abstract: A tandem free radical cyclization-rearrangement sequence was designed and executed to produce tricyclo[4.3.2.0(1,5)]undecane 7 from cyclopentene 6A in a single operation. The total synthesis of suberosenone was accomplished from 7.

title: Improved Precursor Directed Biosynthesis in E. coli via Directed Evolution
abstract: Erythromycin and related macrolide antibiotics are widely used polyketide natural products. We have evolved an engineered biosynthetic pathway in Escherichia coli that yields erythromycin analogs from simple synthetic precursors. Multiple rounds of mutagenesis and screening led to the identification of new mutant strains with improved efficiency for precursor-directed biosynthesis. Genetic and biochemical analysis suggested that the phenotypically relevant alterations in these mutant strains were localized exclusively to the host-vector system, and not to the polyketide synthase. We also demonstrate the utility of this improved system through engineered biosynthesis of a novel alkynyl erythromycin derivative with comparable antibacterial activity to its natural counterpart. In addition to reinforcing the power of directed evolution for engineering macrolide biosynthesis, our studies have identified a new lead substance for investigating structure–function relationships in the bacterial ribosome.

title: Differential distribution of human mitochondrial DNA in somatic tissues and hairs.
abstract: To investigate mitochondrial DNA (mtDNA) distribution within tissues during life, we observed length heteroplasmy in a polycytosine tract of the mitochondrial HV2 region by size-based separation of PCR products, using a mutagenic primer which was designed to avoid stutter production. Blood, brain, heart, liver, skeletal muscle and hair shaft samples were collected during autopsies of 25 individuals. Here, we demonstrate differences in the level of mtDNA length heteroplasmy both within and between individuals and tissues. We also show that mtDNA is distributed randomly in varying proportions in various somatic tissues during growth, resulting in an imbalance in the composition of mtDNA pools among tissues. This mtDNA distribution appears not to be strictly random, and can be explained by the random somatic segregation of nucleoids. On the other hand, significant qualitative/quantitative mtDNA peak pattern variations in hair shafts are thought to be a result of the different developmental origins of hairs. Each hair shaft may have a restricted or clonal set of mtDNA molecules derived from a discrete group of stem cells.

title: Classification of Focal Prostatic Lesions on Transrectal Ultrasound (TRUS) and the Accuracy of TRUS to Diagnose Prostate Cancer
abstract: To improve the diagnostic efficacy of transrectal ultrasound (TRUS)-guided targeted prostatic biopsies, we have suggested the use of a new scoring system for the prediction of malignancies regarding the characteristics of focal suspicious lesions as depicted on TRUS.  A total of 350 consecutive patients with or without prostate cancer who underwent targeted biopsies for 358 lesions were included in the study. The data obtained from participants were randomized into two groups; the training set (n = 240) and the test set (n = 118). The characteristics of focal suspicious lesions were evaluated for the training set and the correlation between TRUS findings and the presence of a malignancy was analyzed. Multiple logistic regression analysis was used to identify variables capable of predicting prostatic cancer. A scoring system that used a 5-point scale for better malignancy prediction was determined from the training set. Positive predictive values for malignancy prediction and the diagnostic accuracy of the scored components with the use of receiver operating characteristic curve analysis were evaluated by test set analyses.  Subsequent multiple logistic regression analysis determined that shape, margin irregularity, and vascularity were factors significantly and independently associated with the presence of a malignancy. Based on the use of the scoring system for malignancy prediction derived from the significant TRUS findings and the interactions of characteristics, a positive predictive value of 80% was achieved for a score of 4 when applied to the test set. The area under the receiver operating characteristic curve (AUC) for the overall lesion score was 0.81.  We have demonstrated that a scoring system for malignancy prediction developed for the characteristics of focal suspicious lesions as depicted on TRUS can help predict the outcome of TRUS-guided biopsies.

title: Detection and characterization of focal hepatic lesions by T2-weighted imaging: comparison of navigator-triggered turbo spin-echo, breath-hold turbo spin-echo, and HASTE sequences.
abstract: The aim of this study is to evaluate the diagnostic performance of T(2)-weighted (T(2)-w) images obtained using navigator-triggered turbo spin-echo (TSE), breath-hold TSE (BH-TSE), and BH haft-Fourier single-shot TSE sequences for the detection and characterization of focal hepatic lesions. Two blinded reviewers independently analyzed three types of T(2)-w image sets totaling 86 solid and 75 nonsolid lesions in 59 patients. Receiver operating characteristic curves were established to analyze reviewer and sequence results.

title: Detection and characterization of focal hepatic lesions: comparative study of MDCT and gadobenate dimeglumine-enhanced MR imaging.
abstract: The aim of this study was to compare the diagnostic performance of multidetector row helical CT (MDCT) and gadobenate dimeglumine-enhanced magnetic resonance (MR) imaging (in the detection and characterization of focal liver lesions. Two blind reviewers analyzed the MDCT and MR images of a total of 44 malignant and 85 benign lesions in 46 patients independently. Receiver operating characteristic curves were established to analyze the results for each reviewer and modality.