Significance and positive predictive values of mammographic findings in the Asia-Pacific region: a single-centre study in Taiwan.

AIM: To report positive predictive values (PPVs) of mammographic findings (MFs) of a screening cohort in Taiwan with a view to providing radiologists around the world with adequate information for assessing MFs before recommending biopsy for Asian women. MATERIALS AND METHODS: Between January 2014 and June 2017, 18,449 women received screening mammography at Tri-Service General Hospital (TSGH). Of these women, 1,622 exhibited specific MFs, namely mass (n=518), microcalcification (n=668), focal asymmetry (FA; n=462), and architectural distortion (AD; n=117). The distribution and PPVs of each MF were calculated after stratification based on cancer type, age, and breast density. RESULTS: The age group with the highest proportion of women was 50-59 years (48.1%), and most women presented with dense breasts (68.6%). The most common MF in the recalled women was microcalcification (41.2%) and the least common was AD (7.2%). AD was the most predictive MF for overall breast cancers, invasive carcinomas, and carcinomas in situ. Microcalcification was the second most predictive MF among recalled women for predicting overall breast cancers; however, it was less predictive than mass and FA in women who received a biopsy recommendation or underwent biopsy. CONCLUSION: AD can indicate the likelihood of breast cancer development in Asian women with abnormal screening results. Benign breast diseases are more likely to occur in women recommended for or receiving breast biopsy owing to microcalcification than to mass or FA.

Germline expression of the hunchback orthologues in the asexual viviparous aphids: a conserved feature within the Aphididae.

In animals, differentiation of germline from soma usually takes place during embryogenesis. Genes and their products that are preferentially expressed in the embryonic germ cells are regarded as candidates for maintaining germline fate or promoting germline identity. In Drosophila, for example, the protein encoded by the germline gene vasa is specifically restricted to the germ cells, while products of the gap gene hunchback (hb), a somatic gene, are preferentially expressed in the neuroblasts. In this study, we report the expression of both messenger RNA and protein encoded by Aphb, an hb orthologue in the asexual viviparous pea aphid Acyrthosiphon pisum, in germ cells as well as in neuroblasts. We infer that expression of Aphb messenger RNA in the germ cells during the formation of germaria is required for the anterior localization of Aphb in the protruding oocytes. Germarial expression and anterior localization of ApKrüppel was also identified but, unlike Aphb, its expression was not detected in the migrating germ cells. Very similar patterns of hb expression were also identified in the green peach aphid Myzus persicae, suggesting that germline expression of hb is conserved within the Aphididae. To date, this pattern of hb germline expression has not been reported in other insects.

Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) promotes EGF receptor signaling of oral squamous cell carcinoma metastasis via the complex N-glycosylation.

Aberrant protein glycosylation could be a distinct surface-marker of cancer cells that influences cancer progression and metastasis because glycosylation can regulate membrane protein folding which alters receptor activation and changes epitope exposure for antibody (Ab) recognition. Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6), a glycophosphoinositol-anchored protein, is a heavily glycosylated tumor antigen. However, the clinical significance and biological effect of CEACAM6 glycosylation has not been addressed in cancers. We recently developed an anti-CEACAM6 Ab (TMU) from an immune llama library which can be engineered to a single-domain (sd)Ab or a heavy-chain (HC)Ab. The TMU HCAb specifically recognized glycosylated CEACAM6 compared to the conventional antibodies. Using the TMU HCAb, we found that glycosylated CEACAM6 was a tumor marker associated with recurrence in early-stage OSCC (oral squamous cell carcinoma) patients. CEACAM6 promoted OSCC cell invasion, migration, cytoskeletal rearrangement, and metastasis via interaction with epidermal growth factor (EGF) receptor (EGFR) and enhancing EGFR activation, clustering and intracellular signaling cascades. These functions were modulated by N-acetylglucosaminyltransferase 5 (MGAT5) which mediated N-glycosylation at Asn256 (N256) of CEACAM6. Finally, the TMU sdAb and HCAb treatment inhibited the migration, invasion and EGF-induced signaling in CEACAM6-overexpressing cells. In conclusion, the complex N-glycosylation of CEACAM6 is critical for EGFR signaling of OSCC invasion and metastasis. Targeting glycosylated CEACAM6 with the TMU sdAb or TMU HCAb could be a feasible therapy for OSCC.

Induction of Salivary Gland-Like Cells from Dental Follicle Epithelial Cells.

The dental follicle (DF), most often associated with unerupted teeth, is a condensation of ectomesenchymal cells that surrounds the tooth germ in early stages of tooth development. In the present study, we aim to isolate epithelial stem-like cells from the human DF and explore their potential differentiation into salivary gland (SG) cells. We demonstrated the expression of stem cell-related genes in the epithelial components of human DF tissues, and these epithelial progenitor cells could be isolated and ex vivo expanded in a reproducible manner. The human DF-derived epithelial cells possessed clonogenic and sphere-forming capabilities, as well as expressed a panel of epithelial stem cell-related genes, thus conferring stem cell properties (hDF-EpiSCs). When cultured under in vitro 3-dimensional induction conditions, hDF-EpiSCs were capable to differentiate into SG acinar and duct cells. Furthermore, transplantation of hDF-EpiSC-loaded native de-cellularized rat parotid gland scaffolds into the renal capsule of nude mice led to the differentiation of transplanted hDF-EpiSCs into salivary gland-like cells. These findings suggest that hDF-EpiSCs might be a promising source of epithelial stem cells for the development of stem cell-based therapy or bioengineering SG tissues to repair/regenerate SG dysfunction.

Modal analysis and efficient coupling of TE01 mode in small-core THz Bragg fibers.

We report a design of low-loss THz Bragg fibers with a core size on the order of wavelength that operates near the cutoff frequency of its TE01 mode. We also propose a broadband Y-type mode converter based on branched rectangular metallic waveguides to facilitate coupling between the TE01 mode of the Bragg fiber and the TEM mode in free space with 60% efficiency. Our fiber holds strong promise to facilitate beam-wave interaction in gyrotron for high-efficiency THz generation.

COL11A1 promotes tumor progression and predicts poor clinical outcome in ovarian cancer.

Biomarkers that predict disease progression might assist the development of better therapeutic strategies for aggressive cancers, such as ovarian cancer. Here, we investigated the role of collagen type XI alpha 1 (COL11A1) in cell invasiveness and tumor formation and the prognostic impact of COL11A1 expression in ovarian cancer. Microarray analysis suggested that COL11A1 is a disease progression-associated gene that is linked to ovarian cancer recurrence and poor survival. Small interference RNA-mediated specific reduction in COL11A1 protein levels suppressed the invasive ability and oncogenic potential of ovarian cancer cells and decreased tumor formation and lung colonization in mouse xenografts. A combination of experimental approaches, including real-time RT-PCR, casein zymography and chromatin immunoprecipitation (ChIP) assays, showed that COL11A1 knockdown attenuated MMP3 expression and suppressed binding of Ets-1 to its putative MMP3 promoter-binding site, suggesting that the Ets-1-MMP3 axis is upregulated by COL11A1. Transforming growth factor (TGF)-beta (TGF-ß1) treatment triggers the activation of smad2 signaling cascades, leading to activation of COL11A1 and MMP3. Pharmacological inhibition of MMP3 abrogated the TGF-ß1-triggered, COL11A1-dependent cell invasiveness. Furthermore, the NF-YA-binding site on the COL11A1 promoter was identified as the major determinant of TGF-ß1-dependent COL11A1 activation. Analysis of 88 ovarian cancer patients indicated that high COL11A1 mRNA levels are associated with advanced disease stage. The 5-year recurrence-free and overall survival rates were significantly lower (P=0.006 and P=0.018, respectively) among patients with high expression levels of tissue COL11A1 mRNA compared with those with low expression. We conclude that COL11A1 may promote tumor aggressiveness via the TGF-ß1-MMP3 axis and that COL11A1 expression can predict clinical outcome in ovarian cancer patients.

WWOX suppresses autophagy for inducing apoptosis in methotrexate-treated human squamous cell carcinoma.

Squamous cell carcinoma (SCC) cells refractory to initial chemotherapy frequently develop disease relapse and distant metastasis. We show here that tumor suppressor WW domain-containing oxidoreductase (WWOX) (also named FOR or WOX1) regulates the susceptibility of SCC to methotrexate (MTX) in vitro and cure of SCC in MTX therapy. MTX increased WWOX expression, accompanied by caspase activation and apoptosis, in MTX-sensitive SCC cell lines and tumor biopsies. Suppression by a dominant-negative or small interfering RNA targeting WWOX blocked MTX-mediated cell death in sensitive SCC-15 cells that highly expressed WWOX. In stark contrast, SCC-9 cells expressed minimum amount of WWOX protein and resisted MTX-induced apoptosis. Transiently overexpressed WWOX sensitized SCC-9 cells to apoptosis by MTX. MTX significantly downregulated autophagy-related Beclin-1, Atg12-Atg5 and LC3-II protein expression and autophagosome formation in the sensitive SCC-15, whereas autophagy remained robust in the resistant SCC-9. Mechanistically, WWOX physically interacted with mammalian target of rapamycin (mTOR), which potentiated MTX-increased phosphorylation of mTOR and its downstream substrate p70 S6 kinase, along with dramatic downregulation of the aforementioned proteins in autophagy, in SCC-15. When WWOX was knocked down in SCC-15, MTX-induced mTOR signaling and autophagy inhibition were blocked. Thus, WWOX renders SCC cells susceptible to MTX-induced apoptosis by dampening autophagy, and the failure in inducing WWOX expression leads to chemotherapeutic drug resistance.

Noncanonical expression of caudal during early embryogenesis in the pea aphid Acyrthosiphon pisum: maternal cad-driven posterior development is not conserved.

Previously we identified anterior localization of hunchback (Aphb) mRNA in oocytes and early embryos of the parthenogenetic and viviparous pea aphid Acyrthosiphon pisum, suggesting that the breaking of anterior asymmetry in the oocytes leads to the formation of the anterior axis in embryos. In order to study posterior development in the asexual pea aphid, we cloned and analysed the developmental expression of caudal (Apcad), a posterior gene highly conserved in many animal phyla. We found that transcripts of Apcad were not detected in germaria, oocytes and embryos prior to the formation of the blastoderm in the asexual (viviparous) pea aphid. This unusual expression pattern differs from that of the existing insect models, including long- and short-germ insects, where maternal cad mRNA is passed to the early embryos and forms a posterior-anterior gradient. The first detectable Apcad expression occurred in the newly formed primordial germ cells and their adjacent blastodermal cells during late blastulation. From gastrulation onward, and as in other insects, Apcad mRNA is restricted to the posteriormost region of the germ band. Similarly, in the sexual (oviparous) oocytes we were able to identify anterior localization of Aphb mRNA but posterior localization of Apcad was not detected. This suggests that cad-driven posterior development is not conserved during early embryogenesis in asexual and sexual pea aphids.

Efficient heating with a controlled microwave field.

To uncover the intriguing non-thermal microwave effect, an experiment was conducted using an amplifier rather than an oscillator as the radiation source, which was injected into an applicator with strong electromagnetic field enhancement. The characteristics of the applicator are discussed and the enhancement of the microwave field is illustrated and explained. Thermal distribution is simulated based on the calculated microwave field profile. It was demonstrated that the proposed system heated a SiC susceptor to a temperature of 637 °C with the input power of 60 W. The reasons for such an efficient heating are discussed.

X-ray microfabrication and measurement of a terahertz mode converter.

Mode converters are critical for frequency-tunable terahertz gyrotrons. This study reports the development of a broadband TE(02) mode converter centered at 0.2 THz. An octafeed sidewall coupling structure was employed and the mode purity was analyzed. The converter was built using the technique of x-ray microfabrication. The x rays irradiated on the SU-8 resist and generated a template of very high thickness of 1.295 mm. Pulse electroplating technique was used to deposit copper on the structure along the template. The parts then went through precise machining and the residual resist was removed via high-flux radical etching. A computer-aided diagnostic system was introduced to measure the performance of the converter. Results suggest that the frequency response of resistivity should be taken into consideration for the devices in terahertz region.

Comparison of photodegradative efficiencies and mechanisms of Victoria Blue R assisted by Nafion-coated and fluorinated TiO2 photocatalysts.

The purposes of this research were to study the effects of two modified photocatalysts, Nafion-coated TiO(2) and fluorinated TiO(2), and photocatalytic degradation of Victoria Blue R in aqueous solution. Photocatalytic degradation of Victoria Blue R was accelerated by the modified photocatalysts. Bulk and surface characterizations of the resulting powders were carried out. Attachment of the anions to the TiO(2) surface using the Nafion-coated-TiO(2) possibly results in increased adsorption of the cationic dye, and the degradation rate is larger for the cationic dye. It was found that Victoria Blue R on the two illuminated TiO(2) surfaces underwent very different changes. To obtain a better understanding on the mechanistic details of this modified-TiO(2)-assisted photodegradation of the Victoria Blue R dye with UV irradiation, a large number of intermediates of the process were separated, identified, and characterized by a high-performance liquid chromatography-mass spectrometry technique. Several probable photodegradation pathways were proposed and discussed.

Measurement of angular distributions of Drell-Yan dimuons in p+p interactions at 800 GeV/c.

We report a measurement of the angular distributions of Drell-Yan dimuons produced using an 800 GeV/c proton beam on a hydrogen target. The polar and azimuthal angular distribution parameters have been extracted over the kinematic range 4.5

Examination for double-stranded RNA viruses in Trichomonas gallinae and identification of a novel sequence of a Trichomonas vaginalis virus.

To determine if double-stranded RNA (dsRNA) viruses exist and are potential virulence factors in Trichomonas gallinae, virus purification via ultracentrifugation was attempted for 12 T. gallinae isolates recovered from wild birds. Following purification, virus-like particles were not observed by transmission electron microscopy, nor were dsRNA segments visualized in agarose gels after electrophoresis of extracted RNA from any of the 12 T. gallinae isolates. However, virus particles and dsRNA segments were detected from a previously determined virus-infected T. vaginalis isolate as a control using identical purification procedures. Subsequent reverse transcription-polymerase chain reaction analysis of the dsRNA of the virus in this isolate revealed a novel sequence of the RNA-dependent RNA polymerase gene of T. vaginalis viruses.

High-power millimeter-wave rotary joint.

The rotary joint is a useful microwave component that connects a fixed part to a rotatable part. This study systematically analyzes the effect of the discontinuity on the interface of a rotary joint for several waveguide modes. Simulation results indicate that the transmission of the TE(01) mode is independent of the geometry of the joint, and thus is ideal for such application. A rotary joint consisting of two identical TE(01) mode converters, clasped each other by a bearing, is designed, fabricated, and tested. Back-to-back transmission measurements exhibit an excellent agreement to the results of computer simulations. The measured optimum transmission is 97% with a 3 dB bandwidth of 8.5 GHz, centered at 35.0 GHz. The cold measurement shows that the results are independent of the angle of rotation. In addition, a high-power experiment is conducted. The just developed rotary joint can operate up to a peak input power of 210 W with a duty of 18%. The working principle, although demonstrated in the millimeter-wave region, can be applied up to the terahertz region where the joint gap is generally critical except for the operating TE(01) mode.

Measurement of Upsilon production for p + p and p + d interactions at 800 GeV/c.

We report a high statistics measurement of Upsilon production with an 800 GeV/c proton beam on hydrogen and deuterium targets. The dominance of the gluon-gluon fusion process for Upsilon production at this energy implies that the cross section ratio, sigma(p+d-->Upsilon)/2sigma(p+p-->Upsilon), is sensitive to the gluon content in the neutron relative to that in the proton. Over the kinematic region 0

Prognostic factors affecting the outcome of early cervical cancer treated with radical hysterectomy and post-operative adjuvant therapy.

The purpose of this study is to investigate the clinical and histological features that may affect the survival of the patients and to evaluate the impact of post-operative adjuvant therapy on the outcomes of patients with stage IB and IIA carcinoma of the cervix. From August 1998 to January 2005, 140 patients with International Federation of Gynecology and Obstetrics stage IB and IIA cervical cancer were treated with radical hysterectomy and post-operative pelvic radiation therapy with or without chemotherapy. The median age was 55 years (range, 29-86 years). Seventy-six patients had stage IB and 64 patients had stage IIA disease. Tumour size was <4 cm in 96 patients and > or = 4 cm in 44 patients. One hundred and eleven patients had histology of squamous cell carcinoma, 12 patients has adenocarcinoma and 17 patients had other histologic types. Depth of stromal invasion was <2/3 in 20 patients and > or = 2/3 in 120 patients. Twenty-three patients had parametrial invasion and 117 patients had no parametrial invasion. Thirteen patients had lymphovascular space invasion and 127 had no lymphovascular space invasion. Nine patients had positive surgical margin and 131 patients had negative margin. Twenty-seven patients had pelvic lymph node metastasis and 113 patients had no pelvic lymph node metastasis. Seventy-five patients received concurrent chemoradiotherapy and 65 patients received radiotherapy alone. The 5-year overall survival (OAS) and disease-free survival were 83% and 72% respectively. In the log rank test, tumour size (P = 0.0235), pararmetrial invasion (P = 0.0121), pelvic lymph node metastasis (P < 0.0001) and adjuvant chemotherapy + radiotherapy (P = 0.0119) were significant prognostic factors for OAS, favouring tumour size <4 cm, absence of parametrial invasion and pelvic lymph node metastasis, and those who received adjuvant chemoradiotherapy. The patients who received radiation with concomitant chemotherapy had a 5-year OAS rate of 90% versus those who received radiotherapy alone, with a rate of 76%. For patients with high-risk early stage cervical cancer who underwent a radical hysterectomy and pelvic lymphadenectomy, adjuvant chemoradiotherapy resulted in better survival than radiotherapy alone. The addition of weekly cisplatin to radiotherapy is recommended. The treatment-related morbidity is tolerable.

Measurement of angular distributions of Drell-Yan dimuons in p+d interactions at 800 GeV/c.

We report a measurement of the angular distributions of Drell-Yan dimuons produced using an 800 GeV/c proton beam on a deuterium target. The muon angular distributions in the dilepton rest frame have been measured over the kinematic range 4.5