Fine Needle Aspiration Cytology of Metastatic Plasmacytoid Urothelial Carcinoma- Report of Four Cases Including a Case of Mixed Plasmacytoid and Micropapillary Morphology

Objectives: The aim of this study was to report a small series of fine-needle aspiration (FNA) cytology of the plasmacytoid variant of urothelial carcinoma (PVUC). Study Design: A computerized search of our laboratory information system was performed for the 5-year period between January 2008 and January 2013 to identify all FNA cases in which the corresponding surgical pathology cases were diagnosed as PVUC. Results: The 4 cases identified were from 2 men (aged 56 and 64 years) and 2 women (aged 72 and 46 years). The FNA smears demonstrated low-to-moderate cellularity and consisted predominantly of single and dyshesive, medium-sized tumor cells with eccentrically located nuclei and a moderate-to-abundant dense cytoplasm. The nuclei were oval with slightly irregular nuclear membranes and contained coarse granular chromatin with inconspicuous or small nucleoli. There was moderate nuclear variation in size. The nuclear-to-cytoplasmic ratio ranged from <1 to 3. Binucleation, cytoplasmic vacuoles, and perinuclear hof were occasionally seen. Conclusions: FNA cytology of PVUC shares features with plasma cell neoplasms, lobular carcinoma of the breast, and signet ring cell carcinoma of the stomach. Being aware of the patient's clinical history and the potential diagnostic pitfall of this rare variant of urothelial carcinoma is important for an accurate diagnosis on FNA biopsy

Development of genomic SSR and potential EST-SSR markers in Bupleurum chinense DC.

Nineteen genomic SSR markers were developed using inter-simple sequence repeat (ISSR)- suppression PCR technique in Bupleurum chinense DC., a widely used Chinese medicinal plant. A total of 126 alleles were detected across 22 individual plants of B. chinense DC. f. octoradiatum (Bunge) Shan et Sheh, with an average of 3 - 13 alleles per locus. The observed heterozygosity (HO) and the expected heterozygosity (HE) values ranged from 0.23 to 1.00 and from 0.29 to 0.92, respectively. Nine loci deviated from Hardy-Weinberg equilibrium (HWE) (P < 0.05) and eight pairs of loci showed significant linkage disequilibrium (LD) (Fisher’s exact test, P < 0.01). The species transferability of these genomic SSR markers was also detected in seven other Bupleurum species. Eight SSR markers were successfully amplified in all tested species. In addition, forty four EST-SSRs which can be amplified with expected sizes were identified from a B. chinense root cDNA library. The genomic SSR markers and potential EST-SSR markers developed in the present study should be useful for genetic diversity and molecular marker assistant selection breeding research in Bupleurum species

Predicting Gonadal Germ Cell Cancer in People with Disorders of Sex Development; Insights from Developmental Biology

The risk of gonadal germ cell cancer (GGCC) is increased in selective subgroups, amongst others, defined patients with disorders of sex development (DSD). The increased risk is due to the presence of part of the Y chromosome, i.e., GonadoBlastoma on Y chromosome GBY region, as well as anatomical localization and degree of testicularization and maturation of the gonad. The latter specifically relates to the germ cells present being at risk when blocked in an embryonic stage of development. GGCC originates from either germ cell neoplasia in situ (testicular environment) or gonadoblastoma (ovarian-like environment). These precursors are characterized by presence of the markers OCT3/4 (POU5F1), SOX17, NANOG, as well as TSPY, and cKIT and its ligand KITLG. One of the aims is to stratify individuals with an increased risk based on other parameters than histological investigation of a gonadal biopsy. These might include evaluation of defined susceptibility alleles, as identified by Genome Wide Association Studies, and detailed evaluation of the molecular mechanism underlying the DSD in the individual patient, combined with DNA, mRNA, and microRNA profiling of liquid biopsies. This review will discuss the current opportunities as well as limitations of available knowledge in the context of predicting the risk of GGCC in individual patients

The Dynamic Organization of the Perinucleolar Compartment in the Cell Nucleus

The perinucleolar compartment (PNC) is a unique nuclear structure preferentially localized at the periphery of the nucleolus. Several small RNAs transcribed by RNA polymerase III (e.g., the Y RNAs, MRP RNA, and RNase P H1 RNA) and the polypyrimidine tract binding protein (PTB; hnRNP I) have thus far been identified in the PNC (Ghetti, A., S. PinolRoma, W.M. Michael, C. Morandi, and G. Dreyfuss. 1992. Nucleic Acids Res. 20:3671–3678; Matera, A.G., M.R. Frey, K. Margelot, and S.L. Wolin. 1995. J. Cell Biol. 129:1181–1193; Lee, B., A.G. Matera, D.C. Ward, and J. Craft. 1996. Proc. Natl. Acad. Sci. USA. 93: 11471–11476). In this report, we have further characterized this structure in both fixed and living cells. Detection of the PNC in a large number of human cancer and normal cells showed that PNCs are much more prevalent in cancer cells. Analysis through the cell cycle using immunolabeling with a monoclonal antibody, SH54, specifically recognizing PTB, demonstrated that the PNC dissociates at the beginning of mitosis and reforms at late telophase in the daughter nuclei. To visualize the PNC in living cells, a fusion protein between PTB and green fluorescent protein (GFP) was generated. Time lapse studies revealed that the size and shape of the PNC is dynamic over time. In addition, electron microscopic examination in optimally fixed cells revealed that the PNC is composed of multiple strands, each measuring ∼80–180 nm diam. Some of the strands are in direct contact with the surface of the nucleolus. Furthermore, analysis of the sequence requirement for targeting PTB to the PNC using a series of deletion mutants of the GFP–PTB fusion protein showed that at least three RRMs at either the COOH or NH2 terminus are required for the fusion protein to be targeted to the PNC. This finding suggests that RNA binding may be necessary for PTB to be localized in the PNC

Anatomical changes in the East Asian midface skeleton with aging

Background: Understanding the aging process of the midface skeleton is considered crucial for correct facial rejuvenation. However, the canine fossa, an important morphological feature of the midface skeleton, has not yet been observed in connection with aging, despite the fact that it is the most main part of the maxillary bone. Here, the authors focus on the depression of the canine fossa to evaluate the Asian midface skeleton. Materials and methods: Computed tomography (CT) scans of the facial skeleton of 114 Koreans (59 males and 55 females) were reconstructed to three-dimensional (3D) images using a 3D analysis software programme. The study subjects included 27 young males, 32 old males, 28 young females and 27 old females. The angular measurements of three bony regions were measured for each 3D model: the canine fossa angle (assessing depth of the canine fossa), the maxillary angle (assessing orientation of the lateral maxilla) and the piriform angle (assessing orientation of the medial maxilla). Results: The canine fossa angle showed a statistically significant decrease with aging in both sexes, indicating the canine fossa actually becomes more concave with age. In contrast, the maxillary and piriform angle showed statistically insignificant changes with aging in female subjects. Conclusions: These results suggest that the canine fossa may be one of the effective markers to evaluate the anatomical changes to the facial skeleton with midface aging. (

Multi-scale structural and mechanical characterisation in bioinspired polyurethane-based pancreatic cancer model

In this work, novel bioinspired polyurethane (PU) scaffolds were fabricated via freeze casting for PU-based Pancreatic Ductal Adenocarcinoma (PDAC) model. In order to reproduce the tumour micro-environment that facilitates cellular kinetics, the PU scaffolds were surface modified with extracellular matrix (ECM) proteins including collagen and fibronectin (Col and FN). Synchrotron-based small- and wide-angle X-ray scattering (SAXS/WAXS) techniques were applied to probe structural evolution during in situ mechanical testing. Strains at macroscopic, nano-, and lattice scales were obtained to investigate the effects of ECM proteins and pancreatic cell activities to PU scaffolds. Significant mechanical strengthening across length scales of PU scaffolds was observed in specimens surface modified by FN. A model of stiffness modulation via enhanced interlamellar recruitment is proposed to explain the multi-scale strengthening mechanisms. Understanding multi-scale deformation mechanisms of a series of PU scaffolds opens an opportunity in developing a novel pancreatic cancer model for studying cancer evolution and predicting outcomes of drug/treatments

Static detection of control-flow-related vulnerabilities using graph embedding

© 2019 IEEE. Static vulnerability detection has shown its effectiveness in detecting well-defined low-level memory errors. However, high-level control-flow related (CFR) vulnerabilities, such as insufficient control flow management (CWE-691), business logic errors (CWE-840), and program behavioral problems (CWE-438), which are often caused by a wide variety of bad programming practices, posing a great challenge for existing general static analysis solutions. This paper presents a new deep-learning-based graph embedding approach to accurate detection of CFR vulnerabilities. Our approach makes a new attempt by applying a recent graph convolutional network to embed code fragments in a compact and low-dimensional representation that preserves high-level control-flow information of a vulnerable program. We have conducted our experiments using 8,368 real-world vulnerable programs by comparing our approach with several traditional static vulnerability detectors and state-of-the-art machine-learning-based approaches. The experimental results show the effectiveness of our approach in terms of both accuracy and recall. Our research has shed light on the promising direction of combining program analysis with deep learning techniques to address the general static analysis challenges

Production Research in China

(First paragraph) China is the world’s largest emerging economy. In recent years, China has moved to an increasingly market-oriented economy that opens to international trade and investment. At the same time, the popularity of China as a manufacturing base, assembling goods for sale worldwide is growing. In addition to global manufacturers who have built their own plants in China, many manufacturing companies are outsourcing production to Chinese subcontractors and branding the products with their own logos. In today’s China, production research is becoming more and more important; advanced production research becomes an important enabler to make its manufacturing industry competitive. Although China has different financial, legal, and physical infrastructure, production researchers in China have successfully proven that production research can help to manage global manufacturing competition

Self-bias and the emotionality of foreign languages

Article first published online: June 13, 2018Foreign language contexts impose a relative psychological and emotional distance in bilinguals. In our previous studies, we demonstrated that the use of a foreign language changes the strength of the seemingly automatic emotional responses in the self-paradigm, showing a robust asymmetry in the self-bias effect in a native and a foreign language context. Namely, larger effects were found in the native language, suggesting an emotional blunting in the foreign language context. In the present study, we investigated the source of these effects by directly comparing whether they stem from a language’s foreignness versus its non-nativeness. We employed the same self-paradigm (a simple perceptual matching task of associating simple geometric shapes with the labels “you,” “friend,” and “other”), testing unbalanced Spanish–Basque–English trilinguals. We applied the paradigm to three language contexts: native, non-native but contextually present (i.e., non-native local), and non-native foreign. Results showed a smaller self-bias only in the foreign language pointing to the foreign-language-induced psychological/emotional distance as the necessary prerequisite for foreign language effects. Furthermore, we explored whether perceived emotional distance towards foreign languages in Spanish–English bilinguals modulates foreign language effects. Results suggest that none of the different indices of emotional distance towards the foreign language obtained via questionnaires modulated the self-biases in the foreign language contexts. Our results further elucidate the deeply rooted and automatic nature of foreign-language-driven differential emotional processing.This research has been partially funded by grants PSI2015-65689-P and SEV-2015-0490 from the Spanish Government, AThEME-613465 from the European Union, and a 2016 BBVA Foundation Grant for Researchers and Cultural Creators awarded to the last author (J.A.D.)

A modified protocol for the detection of three different mRNAs with a new-generation in situ hybridization chain reaction on frozen sections

A new multiple fluorescence in situ hybridization method based on hybridization chain reaction was recently reported, enabling simultaneous mapping of multiple target mRNAs within intact zebrafish and mouse embryos. With this approach, DNA probes complementary to target mRNAs trigger chain reactions in which metastable fluorophore-labeled DNA hairpins self-assemble into fluorescent amplification polymers. The formation of the specific polymers enhances greatly the sensitivity of multiple fluorescence in situ hybridization. In this study we describe the optimal parameters (hybridization chain reaction time and temperature, hairpin and salt concentration) for multiple fluorescence in situ hybridization via amplification of hybridization chain reaction for frozen tissue sections. The combined use of fluorescence in situ hybridization and immunofluorescence, together with other control experiments (sense probe, neutralization and competition, RNase treatment, and anti-sense probe without initiator) confirmed the high specificity of the fluorescence in situ hybridization used in this study. Two sets of three different mRNAs for oxytocin, vasopressin and somatostatin or oxytocin, vasopressin and thyrotropin releasing hormone were successfully visualized via this new method. We believe that this modified protocol for multiple fluorescence in situ hybridization via hybridization chain reaction would allow researchers to visualize multiple target nucleic acids in the future