Discovery of genes related to formothion resistance in oriental fruit fly (Bactrocera dorsalis) by a constrained functional genomics analysis.

Artificial selection can provide insights into how insecticide resistance mechanisms evolve in populations. The underlying basis of such phenomena can involve complex interactions of multiple genes, and the resolution of this complexity first necessitates confirmation that specific genes are involved in resistance mechanisms. Here, we used a novel approach invoking a constrained RNA sequencing analysis to refine the discovery of specific genes involved in insecticide resistance. Specifically, for gene discovery, an additional constraint was added to the traditional comparisons of susceptible vs. resistant flies by the incorporation of a line in which insecticide susceptibility was 'recovered' within a resistant line by the removal of insecticide stress. In our analysis, the criterion for the classification of any gene as related to insecticide resistance was based on evidence for differential expression in the resistant line as compared with both the susceptible and recovered lines. The incorporation of this additional constraint reduced the number of differentially expressed genes putatively involved in resistance to 464, compared with more than 1000 that had been identified previously using this same species. In addition, our analysis identified several key genes involved in metabolic detoxification processes that showed up-regulated expression. Furthermore, the involvement of acetylcholinesterase, a known target for modification in insecticide resistance, was associated with three key nonsynonymous amino acid substitutions within our data. In conclusion, the incorporation of an additional constraint using a 'recovered' line for gene discovery provides a higher degree of confidence in genes identified to be involved in insecticide resistance phenomena.

Combining scanning tunneling microscopy and synchrotron radiation for high-resolution imaging and spectroscopy with chemical, electronic, and magnetic contrast.

The combination of high-brilliance synchrotron radiation with scanning tunneling microscopy opens the path to high-resolution imaging with chemical, electronic, and magnetic contrast. Here, the design and experimental results of an in-situ synchrotron enhanced x-ray scanning tunneling microscope (SXSTM) system are presented. The system is designed to allow monochromatic synchrotron radiation to enter the chamber, illuminating the sample with x-ray radiation, while an insulator-coated tip (metallic tip apex open for tunneling, electron collection) is scanned over the surface. A unique feature of the SXSTM is the STM mount assembly, designed with a two free-flex pivot, providing an angular degree of freedom for the alignment of the tip and sample with respect to the incoming x-ray beam. The system designed successfully demonstrates the ability to resolve atomic-scale corrugations. In addition, experiments with synchrotron x-ray radiation validate the SXSTM system as an accurate analysis technique for the study of local magnetic and chemical properties on sample surfaces. The SXSTM system's capabilities have the potential to broaden and deepen the general understanding of surface phenomena by adding elemental contrast to the high-resolution of STM.

Clinical significance of signal pattern of high-risk human papillomavirus using a novel fluorescence in situ hybridization assay in cervical cytology.

The present study aimed to evaluate a novel fluorescence in situ hybridization (FISH) assay for detecting the high-risk human papillomavirus (HR-HPV) DNA and signal pattern in cervical cytology specimens and for identifying cervical intraepithelial neoplasia (CIN) lesions. One hundred and ninety-six liquid-based cytology specimens with CIN were recruited. The signal pattern (punctate, mixed punctate and diffuse, and diffuse) detected by FISH was compared with E6 mRNA and correlated with histological classification. FISH and E6-type specific polymerase chain reaction (PCR) had fair to good agreement for detecting HPV DNA across all grades of CIN (kappa coefficient, 0.37-0.73). Among 44 samples of negative FISH and positive E6 type-specific PCR in HPV 16, 18, 31, 33, 52 and 58, 82% (36/44) of E6 mRNA were not detected, in contrast to 41% (48/118) of positive FISH and positive E6 type-specific PCR (p <0.0001). Among HR-HPV DNA positive cases tested by the FISH assay, the specificity of predicting CIN3 using the punctuate pattern is higher than that using E6 mRNA (96.3% vs. 44.8%). The punctate pattern was 0% in patients with

Surface geometric and electronic structures of BaFe2As2(001).

BaFe2As2 exhibits properties that are characteristic of the parent compounds of the newly discovered iron (Fe)-based high-T(C) superconductors. By combining real-space imaging of scanning tunneling microscopy and spectroscopy (STM+STS) with momentum-space quantitative low-energy electron diffraction (LEED), we have identified the surface plane of cleaved BaFe2As2 crystals as the As terminated Fe-As layer-the plane where superconductivity occurs. LEED and STM+STS data on the BaFe2As2(001) surface indicate an ordered arsenic (As) terminated metallic surface without reconstruction or lattice distortion. It is surprising that STM images the different Fe-As orbitals associated with the orthorhombic structure, but not the As atoms in the surface plane.

Spatially localized self-injection of electrons in a self-modulated laser-wakefield accelerator by using a laser-induced transient density ramp.

By using a laser-induced transient density ramp, we demonstrate self-injection of electrons in a self-modulated laser-wakefield accelerator with spatial localization. The number of injected electrons reaches 1.7 x 10(8). The transient density ramp is produced by a prepulse propagating transversely to drill a density depression channel via ionization and expansion. The same mechanism of injection with comparable efficiency is also demonstrated with a transverse plasma waveguide driven by Coulomb explosion.

Optically controlled seeding of Raman forward scattering and injection of electrons in a self-modulated laser-wakefield accelerator.

Optical seeding of plasma waves and the injection of electrons are key issues in self-modulated laser-wakefield accelerators. By implementing a copropagating laser prepulse with proper timing, we are able to control the growth of Raman forward scattering and the production of accelerated electrons. The dependence of the Raman intensity on prepulse timing indicates that the seeding of Raman forward scattering is dominated by the ionization-induced wakefield, and the dependence of the divergence and number of accelerated electrons further reveals that the stimulated Raman backward scattering of the prepulse plays the essential role of injecting hot electrons into the fast plasma wave driven by the main pulse.

Malignant mixed müllerian tumors of the ovary.

Malignant mixed Müllerian tumor (MMMT) of the ovary is very rare, and to the best of our knowledge, only a few cases have been reported in the literature from Taiwan. We report two recent cases of ovarian MMMT at our hospital. Case 1 was a 59-year-old female with stage IIIC MMMT of the ovary, with a tumor having carcinomatous and sarcomatous elements. The carcinomatous component was composed of a high-grade epithelial malignancy including serous, endometrioid, clear cell and undifferentiated carcinoma elements. The sarcomatous component was composed of a homologous malignant mesenchymal element with conspicuous hyaline globules. The patient died of the disease six months after debulking surgery. Case 2 was a 42-year-old female with ovarian stage IIC MMMT. The carcinomatous component was composed of grade II-III clear cell carcinoma and the sarcomatous component was composed of high-grade non-specific spindle cell sarcoma, which was positive for vimentin, but negative for cytokeratin, desmin and S-100 protein on immunostaining. The patient died of the disease four months after debulking surgery. These two patients both underwent hysterectomy, bilateral salpingo-oophorectomy and omentectomy and both received platinum-based chemotherapy after debulking surgery.

Staging of cervical cancer: comparison between magnetic resonance imaging, computed tomography and pelvic examination under anesthesia.

A prospective study was undertaken to compare magnetic resonance imaging (MRI) with computed tomography (CT) and examination under anesthesia (EUA) in staging cervical carcinoma, with special emphasis on parametrial status. Twenty patients with carcinoma of the cervix, in whom the extent of the disease was surgically confirmed, were analyzed by MRI, CT and EUA. The tumor size estimated by MRI correlated well (r = 0.79, p < 0.001) with those obtained by histopathologic measurement of the surgical specimen. Neither clinical examination nor CT could precisely estimate tumor size. The overall accuracy rate of MRI in staging carcinoma of the cervix was 75%, compared with 32% for CT staging and 55% for clinical staging. The accuracy rate of these modalities for parametrial status was 90% for MRI, 55% for CT and 82.5% for EUA. MRI accurately excluded all 20 patients with pelvic side wall, bladder and rectal involvement. In conclusion, MRI is superior to CT and EUA in assessment of the parametrium (90% vs 55% vs 82.5%, p < 0.005). From MRI, tumor size can be estimated precisely. Although a larger scale study comparing MRI and CT is needed to determine their roles, both should help in the diagnosis and selection of proper treatment for cervical carcinoma. Our preliminary report agrees with previous reports that MRI is promising and indispensable. MRI should be routinely used in conjunction with clinical staging to determine appropriate therapy in patients with cervical carcinoma.

Transdermal dual-controlled delivery of contraceptive drugs: formulation development, in vitro and in vivo evaluations, and clinical performance.

Several transdermal contraceptive device (TCD) formulations were developed to provide a dual-controlled transdermal delivery of levonorgestrel (LN), a potent progestin, and 17 beta-estradiol (E2), a natural estrogen. Using a sensitive HPLC method, the in vitro release and skin permeation profiles of LN and E2 from various TCD formulations were simultaneously characterized in the hydrodynamically well-calibrated Valia-Chien skin permeation cells and both were found to follow zero-order kinetics. The rates of drug release and skin permeation were observed to vary significantly depending upon some formulation parameters. Six-month stability studies were performed on seven formulations at room and elevated temperatures (37 and 45 degrees C), and two (Formulations 4 and 5) were found to be acceptable, based on drug recovery, release rate, and skin permeation rate data. Judging from the 6-month accelerated stability studies, it is projected these two formulations will have shelf-life of at least 2 years. As a result of development of an efficient manufacturing process, Formulation 4 was selected for further evaluation. One-week primary skin irritation evaluation in 6 rabbits indicated that Formulation 4 is nonirritating, and it was thus selected for Phase I clinical bioavailability/dose proportionality studies in 12 healthy female volunteers of child-bearing age. Results of pharmacokinetic and pharmacodynamic analyses demonstrated that it is capable of achieving and maintaining a steady-state serum level of LN throughout the 3-week treatment period by weekly applications of one or two TCD patches (10 or 20 cm2). A dose proportionality was obtained in the serum drug levels, daily dose delivered, and contraception efficacy. An excellent correlation was obtained for the rates of transdermal delivery determined by the in vitro studies using human cadaver skin, the in vivo studies in rabbits, and the clinical studies in living subjects.