Effective Rheology of Bubbles Moving in a Capillary Tube

We calculate the average volumetric flux versus pressure drop of bubbles moving in a single capillary tube with varying diameter, finding a square-root relation from mapping the flow equations onto that of a driven overdamped pendulum. The calculation is based on a derivation of the equation of motion of a bubble train from considering the capillary forces and the entropy production associated with the viscous flow. We also calculate the configurational probability of the positions of the bubbles.Comment: 4 pages, 1 figur

The added value of quantitative multi-voxel MR spectroscopy in breast magnetic resonance imaging

To determine whether quantitative multivoxel MRS improves the accuracy of MRI in the assessment of breast lesions. Twenty-five consecutive patients with 26 breast lesions a parts per thousand yen1 cm assessed as BI-RADS 3 or 4 with mammography underwent quantitative multivoxel MRS and contrast-enhanced MRI. The choline (Cho) concentration was calculated using the unsuppressed water signal as a concentration reference. ROC analysis established the diagnostic accuracy of MRI and MRS in the assessment of breast lesions. Respective Cho concentrations in 26 breast lesions re-classified by MRI as BI-RADS 2 (n = 5), 3 (n = 8), 4 (n = 5) and 5 (n = 8) were 1.16 +/- 0.43 (mean +/- SD), 1.43 +/- 0.47, 2.98 +/- 2.15 and 4.94 +/- 3.10 mM. Two BI-RADS 3 lesions and all BI-RADS 4 and 5 lesions were malignant on histopathology and had Cho concentrations between 1.7 and 11.8 mM (4.03 +/- 2.72 SD), which were significantly higher (P = 0.01) than that in the 11 benign lesions (0.4-1.5 mM; 1.19 +/- 0.33 SD). Furthermore, Cho concentrations in the benign and malignant breast lesions in BI-RADS 3 category differed (P = 0.01). The accuracy of combined multivoxel MRS/breast MRI BI-RADS re-classification (AUC = 1.00) exceeded that of MRI alone (AUC = 0.96 +/- 0.03). These preliminary data indicate that multivoxel MRS improves the accuracy of MRI when using a Cho concentration cut-off a parts per thousand currency sign1.5 mM for benign lesions. Key Points aEuro cent Quantitative multivoxel MR spectroscopy can improve the accuracy of contrast-enhanced breast MRI. aEuro cent Multivoxel-MRS can differentiate breast lesions by using the highest Cho-concentration. aEuro cent Multivoxel-MRS can exclude patients with benign breast lesions from further invasive diagnostic procedures

Bisphosphonates-related osteonecrosis of the jaw in Korea: a preliminary report

Objectives: Bisphosphonates (BP) are widely used in medicine for inhibiting bone resorption; however bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a major side effect of BP. To date, there have been no specific reports on the incidence of BRONJ among Koreans. This study investigated the preliminary results from a nationwide survey of BRONJ in the Departments of Oral and Maxillofacial Surgery (OMFS) at individual training hospitals. Materials and Methods: A total of 15 OMFS departments (10 from dental schools, 4 from medical schools, and 1 from a dental hospital) participated in a multi-centric survey. This study assessed every BRONJ case diagnosed between January 2010 and December 2010. The patient age and BP type were evaluated. Results: A total of 254 BRONJ cases were collected. The majority of BRONJ cases were associated with oral BP therapy, while 21.8% of the cases were associated with intravenous administration. Alendronate was the drug most frequently related to BRONJ (59.2% of cases), followed by risedronate (14.3%) and zolendronate (17.0%). The average age of BRONJ patients was 70.0±10.1 years, with a range of 38-88 years of age. With the number of BP patients in Korea reported to be around 600,000 in 2008, the estimated incidence of BRONJ is at least 0.04% or 1 per 2,300 BP patients. Conclusion: The results suggest that the estimated incidence of BRONJ in Korea is higher than the incidence of other countries. Future prospective studies should be carried out to investigate the exact epidemiological characteristics of BRONJ in Korea

Prognostic Value of Axillary Nodal Ratio after Neoadjuvant Chemotherapy of Doxorubicin/Cyclophosphamide Followed by Docetaxel in Breast Cancer: A Multicenter Retrospective Cohort Study

PURPOSE: The purpose of this study is to investigate the prognostic value of lymph node (LN) ratio (LNR) in patients with breast cancer after neoadjuvant chemotherapy. MATERIALS AND METHODS: This retrospective analysis is based on the data of 814 patientswith stage II/III breast cancer treated with four cycles of doxorubicin/cyclophosphamide followed by four cycles of docetaxel before surgery. We evaluated the clinical significance of LNR (3 categories: low 0-0.20 vs. intermediate 0.21-0.65 vs. high 0.66-1.00) using a Cox proportional regression model. RESULTS: A total of 799 patients underwent breast surgery. Pathologic complete response (pCR, ypT0/isN0) was achieved in 129 patients (16.1%) (hormone receptor [HR] +/human epidermal growth factor receptor 2 [HER2] -, 34/373 [9.1%]: HER2+, 45/210 [21.4%]: triple negative breast cancer, 50/216 [23.1%]). The mean numbers of involved LN and retrieved LN were 2.70 (range, 0 to 42) and 13.98 (range, 1 to 64), respectively. The mean LNR was 0.17 (low, 574 [71.8%]: intermediate, 170 [21.3%]: high, 55 [6.9%]). In univariate analysis, LNR showed significant association with a worse relapse-free survival (3-year relapse-free survival rate 84.8% in low vs. 66.2% in intermediate vs. 54.3% in high: p < 0.001, log-rank test). In multivariate analysis, LNR did not show significant association with recurrence after adjusting for other clinical factors (age, histologic grade, subtype, ypT stage, ypN stage, lymphatic or vascular invasion, and pCR). In subgroup analysis, the LNR system had good prognostic value in HR+/HER2-subtype. CONCLUSION: LNR is not superior to ypN stage in predicting clinical outcome of breast cancer after neoadjuvant chemotherapy. However, the prognostic value of the LNR system in HR+/HER2-patients is notable and worthy of further investigation

Quantum nanomagnets and nuclear spins: an overview

This mini-review presents a simple and accessible summary on the fascinating physics of quantum nanomagnets coupled to a nuclear spin bath. These chemically synthesized systems are an ideal test ground for the theories of decoherence in mesoscopic quantum degrees of freedom, when the coupling to the environment is local and not small. We shall focus here on the most striking quantum phenomenon that occurs in such nanomagnets, namely the tunneling of their giant spin through a high anisotropy barrier. It will be shown that perturbative treatments must be discarded, and replaced by a more sophisticated formalism where the dynamics of the nanomagnet and the nuclei that couple to it are treated together from the beginning. After a critical review of the theoretical predictions and their experimental verification, we continue with a set of experimental results that challenge our present understanding, and outline the importance of filling also this last gap in the theory.Comment: 14 pages, 3 figures. Chapter in the Proceedings of the 2006 Les Houches summer school "Quantum Magnetism", ed. B. Barbara & Y. Imry, Springer (2007

Comparative study of unsupervised dimension reduction techniques for the visualization of microarray gene expression data

<p>Abstract</p> <p>Background</p> <p>Visualization of DNA microarray data in two or three dimensional spaces is an important exploratory analysis step in order to detect quality issues or to generate new hypotheses. Principal Component Analysis (PCA) is a widely used linear method to define the mapping between the high-dimensional data and its low-dimensional representation. During the last decade, many new nonlinear methods for dimension reduction have been proposed, but it is still unclear how well these methods capture the underlying structure of microarray gene expression data. In this study, we assessed the performance of the PCA approach and of six nonlinear dimension reduction methods, namely Kernel PCA, Locally Linear Embedding, Isomap, Diffusion Maps, Laplacian Eigenmaps and Maximum Variance Unfolding, in terms of visualization of microarray data.</p> <p>Results</p> <p>A systematic benchmark, consisting of Support Vector Machine classification, cluster validation and noise evaluations was applied to ten microarray and several simulated datasets. Significant differences between PCA and most of the nonlinear methods were observed in two and three dimensional target spaces. With an increasing number of dimensions and an increasing number of differentially expressed genes, all methods showed similar performance. PCA and Diffusion Maps responded less sensitive to noise than the other nonlinear methods.</p> <p>Conclusions</p> <p>Locally Linear Embedding and Isomap showed a superior performance on all datasets. In very low-dimensional representations and with few differentially expressed genes, these two methods preserve more of the underlying structure of the data than PCA, and thus are favorable alternatives for the visualization of microarray data.</p

Biology and biotechnology of Trichoderma

Fungi of the genus Trichoderma are soilborne, green-spored ascomycetes that can be found all over the world. They have been studied with respect to various characteristics and applications and are known as successful colonizers of their habitats, efficiently fighting their competitors. Once established, they launch their potent degradative machinery for decomposition of the often heterogeneous substrate at hand. Therefore, distribution and phylogeny, defense mechanisms, beneficial as well as deleterious interaction with hosts, enzyme production and secretion, sexual development, and response to environmental conditions such as nutrients and light have been studied in great detail with many species of this genus, thus rendering Trichoderma one of the best studied fungi with the genome of three species currently available. Efficient biocontrol strains of the genus are being developed as promising biological fungicides, and their weaponry for this function also includes secondary metabolites with potential applications as novel antibiotics. The cellulases produced by Trichoderma reesei, the biotechnological workhorse of the genus, are important industrial products, especially with respect to production of second generation biofuels from cellulosic waste. Genetic engineering not only led to significant improvements in industrial processes but also to intriguing insights into the biology of these fungi and is now complemented by the availability of a sexual cycle in T. reesei/Hypocrea jecorina, which significantly facilitates both industrial and basic research. This review aims to give a broad overview on the qualities and versatility of the best studied Trichoderma species and to highlight intriguing findings as well as promising applications

Discovery of Porcine microRNAs in Multiple Tissues by a Solexa Deep Sequencing Approach

The domestic pig (Sus scrofa) is an important economic animal for meat production and as a suitable model organism for comparative genomics and biomedical studies. In an effort to gain further identification of miRNAs in the pig, we have applied the Illumina Solexa sequencing technology to carry out an in-depth analysis of the miRNA transcriptome in a pool of equal amounts of RNA from 16 different porcine tissues. From this data set, we identified 437 conserved and 86 candidate novel miRNA/miRNA* in the pig, corresponding to 329 miRNA genes. Compared with all the reported porcine miRNAs, the result showed that 112 conserved and 61 candidate novel porcine miRNA were first reported in this study. Further analysis revealed extensive sequence variations (isomiRs) of porcine miRNAs, including terminal isomiRs at both the 5′ and 3′ ends and nucleotide variants. Read counts of individual porcine miRNA spanned from a few reads to approximately 405541 reads, confirming the different level of expression of porcine miRNAs. Subsequently, the tissue expression patterns of 8 miRNAs were characterized by Northern blotting. The results showed that miR-145, miR-423-5p, miR-320, miR-26a, and miR-191 are ubiquitously expressed in diverse tissues, while miR-92, miR-200a, and miR-375 were selectively enriched and expressed in special tissues. Meanwhile, the expression of 8 novel porcine-specific miRNAs was validated by stem-loop RT-PCR, and one of these was detected by Northern blotting. Using the porcine miRNA array designed according to our Solexa results, 123 miRNAs were detected expression in porcine liver tissues. A total of 58 miRNAs showed differential expression between the Tongcheng (a Chinese indigenous fatty breed) and Large White pig breeds (a lean type pig). Taken together, our results add new information to existing data on porcine miRNAs and should be useful for investigating the biological functions of miRNAs in pig and other species

Functional Diversity of Human Basic Helix-Loop-Helix Transcription Factor TCF4 Isoforms Generated by Alternative 5′ Exon Usage and Splicing

BACKGROUND: Transcription factor 4 (TCF4 alias ITF2, E2-2, ME2 or SEF2) is a ubiquitous class A basic helix-loop-helix protein that binds to E-box DNA sequences (CANNTG). While involved in the development and functioning of many different cell types, recent studies point to important roles for TCF4 in the nervous system. Specifically, human TCF4 gene is implicated in susceptibility to schizophrenia and TCF4 haploinsufficiency is the cause of the Pitt-Hopkins mental retardation syndrome. However, the structure, expression and coding potential of the human TCF4 gene have not been described in detail. PRINCIPAL FINDINGS: In the present study we used human tissue samples to characterize human TCF4 gene structure and TCF4 expression at mRNA and protein level. We report that although widely expressed, human TCF4 mRNA expression is particularly high in the brain. We demonstrate that usage of numerous 5' exons of the human TCF4 gene potentially yields in TCF4 protein isoforms with 18 different N-termini. In addition, the diversity of isoforms is increased by alternative splicing of several internal exons. For functional characterization of TCF4 isoforms, we overexpressed individual isoforms in cultured human cells. Our analysis revealed that subcellular distribution of TCF4 isoforms is differentially regulated: Some isoforms contain a bipartite nuclear localization signal and are exclusively nuclear, whereas distribution of other isoforms relies on heterodimerization partners. Furthermore, the ability of different TCF4 isoforms to regulate E-box controlled reporter gene transcription is varied depending on whether one or both of the two TCF4 transcription activation domains are present in the protein. Both TCF4 activation domains are able to activate transcription independently, but act synergistically in combination. CONCLUSIONS: Altogether, in this study we have described the inter-tissue variability of TCF4 expression in human and provided evidence about the functional diversity of the alternative TCF4 protein isoforms

Oxaliplatin (3 months v 6 months) with 6 Months of Fluoropyrimidine as Adjuvant Therapy in Patients with Stage II/III Colon Cancer: KCSG CO09-07

PURPOSE: The combination of oxaliplatin and fluoropyrimidine for 6 months is one of the standard options for adjuvant therapy for high-risk stage II and III colorectal cancers (CRCs). The optimal duration of oxaliplatin to diminish neurotoxicity without compromising efficacy needs to be clarified. PATIENTS AND METHODS: This open-label, randomized, phase III, noninferiority trial randomly assigned patients with high-risk stage II and III CRC to 3 and 6 months of oxaliplatin with 6 months of fluoropyrimidine groups (3- and 6-month arms, respectively). The primary end point was disease-free survival (DFS), and the noninferiority margin was a hazard ratio (HR) of 1.25. RESULTS: In total, 1,788 patients were randomly assigned to the 6-month (n = 895) and 3-month (n = 893) arms, and 83.6% in the 6-month arm and 85.7% in the 3-month arm completed the treatment. The neuropathy rates with any grade were higher in the 6-month arm than in the 3-month arm (69.5% v 58.3%; P &lt; .0001). The 3-year DFS rates were 83.7% and 84.7% in the 6-month and 3-month arms, respectively, with an HR of 0.953 (95% CI, 0.769 to 1.180; test for noninferiority, P = .0065) within the noninferiority margin. Among patients with stage III CRC treated by capecitabine plus oxaliplatin, the 3-year DFS of the 3-month arm was noninferior as compared with that of the 6-month arm with an HR of 0.713 (95% CI, 0.530 to 0.959; P = .0009). However, among patients with high-risk stage II and stage III CRC treated by infusional fluorouracil, leucovorin, and oxaliplatin, the noninferiority of the 3-month arm compared with the 6-month arm was not proven. CONCLUSION: This study suggests that adding 3 months of oxaliplatin to 6 months of capecitabine could be considered an alternative adjuvant treatment for stage III CRC (ClinicalTrials.gov identifier: NCT01092481)