Miracle-dz/UniFAR-FTUs huggingface dataset:
Materials and Methods Figs. S1 to S4 Tables S1 to S5 References and Notes Micrornas Regulate Brain Morphogenesis in Zebrafish

for lively discussion and critical comments on the manuscript. We thank D. J. Grau for assistance with Rab5 expression constructs. We also thank members of the Drosophila RNAi Screening Center (DRSC) and Institute of Chemistry and Cell Biology (ICCB) for their assistance. We thank G. Weidinger for assistance with zebrafish experiments and J. Tee for assistance with construction of siRNA and cDNA expression constructs. R.D. MicroRNAs (miRNAs) are small RNAs that regulate gene expression posttranscriptionally. To block all miRNA formation in zebrafish, we generated maternal-zygotic dicer (MZdicer) mutants that disrupt the Dicer ribonuclease III and double-stranded RNA–binding domains. Mutant embryos do not process precursor miRNAs into mature miRNAs, but injection of preprocessed miRNAs restores gene silencing, indicating that the disrupted domains are dispensable for later steps in silencing. MZdicer mutants undergo axis formation and differentiate multiple cell types but display abnormal morphogenesis during gastrulation, brain formation, somito-genesis, and heart development. Injection of miR-430 miRNAs rescues the brain defects in MZdicer mutants, revealing essential roles for miRNAs during morphogenesis. MicroRNAs are evolutionarily conserved small non–protein-coding RNA gene products that regulate gene expression at the posttran-scriptional level (1–3). In animals, mature miRNAs are È22 nucleotides (nt) long and are generated from a primary transcript (termed pri-miRNA) through sequential processing by nucleases belonging to the ribo-nuclease III (RNaseIII) family. Initially, Drosha cleaves the pri-miRNA and excises a stem-loop precursor of È70 nt (termed pre-miRNA), which is then cleaved by Dicer (4–7). One strand of the processed duplex is incorporated into a silencing complex and guides it to target sequences (1, 3). This results in the cleavage of target mRNAs and/or the inhibition of their productive translation (1–3). Several hundred vertebrate miRNAs and several thousand miRNA targets have been predicted or identified, but little is known about miRNA function during development (1, 2, 8, 9). Clues to vertebrate miRNA function have come from several approaches, These studies have led to the suggestions that vertebrate miRNAs might be involved in processes such as stem cell maintenance (12, 19) or cell fate determination (17, 18, 20); however , no loss-of-function analysis has assigned a role for a particular miRNA or miRNA family in vivo, and it has been unclear how widespread the role of miRNAs is during vertebrate embryogenesis. One approach to reveal the global role of vertebrate miRNAs is to abolish the generation of mature miRNAs with the use of dicer mutants. For example, dicer …
CT and US Findings of Multilocular Cystic Renal Cell Carcinoma

Objective Multilocular cystic renal cell carcinoma (MCRCC) is a recently described variety of renal cell carcinoma with characteristic pathologic and clinical features. The purpose of this study was to analyze the imaging findings of MCRCCs. Materials and Methods Ten adult patients with pathologically proven unilateral MCRCC who underwent renal US and CT were included in this study. The radiologic findings were retrospectively evaluated for cystic content, wall, septum, nodularity, calcification and solid portion by three radiologists who established a consensus. Imaging and postnephrectomy pathologic findings were compared. Results All patients were adults (six males and four females) and their ages ranged from 33 to 68 years (mean, 46). On US and CT images, all tumors appeared as well-defined multilocular cystic masses composed of serous or complicated fluid. In all patients, unenhanced CT scans revealed hypodense cystic portions, and in four tumors, due to the presence of hemorrhage or gelatinous fluid, some hyperdense areas were also noted. In no tumor was an expansile solid nodule seen in the thin septa, and in only one was there dystrophic calcification in a septum. Small areas of solid portion constituting less than 10% of the entire lesion were found in six of the ten tumors, and these areas were slightly enhanced on enhanced CT scans. In all patients, imaging and pathologic findings correlated closely. Conclusion On US and CT images, MCRCC appeared as a well-defined multilocular cystic mass with serous, proteinaceous or hemorrhagic fluid, with no expansile solid nodules in the thin septa, and sometimes with small slightly enhanced solid areas. Where radiologic examinations demonstrate a cystic renal mass of this kind in adult males, MCRCC should be included in the differential diagnosis.
Invasive cancers are not necessarily from preformed in situ tumours — an alternative way of carcinogenesis from misplaced stem cells

Cancers are thought to be the result of accumulated gene mutations in cells. Carcinomas, which are cancers arising from epithelial tissues usually go through several stages of development: atypical hyperplasia, carcinoma in situ and then invasive carcinoma, which might further metastasize. However, we think that the present pathological data are enough to prove that there might be an alternative way of carcinogenesis. We propose that majority of invasive cancers arise in the connective tissue stroma de novo, from the misplaced epithelial stem cells which come to the wrong land of connective tissue stroma by accident. The in situ carcinomas, which are mostly curable, should not be considered genuine cancer, but rather as quasi‐cancer. We design this new theory of carcinogenesis as the stem cell misplacement theory (SCMT). Our SCMT theory chains together other carcinogenesis theories such as the inflammation‐cancer chain, the stem cell theory and the tissue organization field theory. However, we deny the pathway of somatic mutation theory as the major pathway of carcinogenesis.
Higher intratumor than peritumor expression of DUSP6/MKP‐3 is associated with recurrence after curative resection of hepatocellular carcinoma

Background The MAPK phosphatases (MKPs) are a family of dual‐specificity phosphatases (DUSPs) that can dephosphorylate both phosphothreonine and phosphotyrosine residues, thus inactivating MAPK signaling. DUSP6 is a cytoplasmic MKP that can inactivate ERK. DUSP6 has been implicated in the development of some tumors. The aim of this research was to investigate the expression of DUSP6 in hepatocellular carcinoma (HCC) and the correlation of DUSP6 with mitogen‐activated protein kinases (MAPKs), clinicopathological characteristics, and prognosis. Methods Tissues from 305 patients who had undergone hepatectomy for HCC was used in this study. The expression of DUSP6, p‐ERK, p‐JNK, and p‐p38&agr; was determined using tissue microarrays for immunohistochemical analysis. The prognostic value of DUSP6 and other clinicopathological factors were evaluated. Results The expression of DUSP6 was significantly higher in the tumor tissue when compared to the peritumor or normal liver tissue (P <0.001). Tumor DUSP6 expression was significantly associated with disease‐free survival (DFS) (P=0.013). Tumor DUSP6 expression was an independent prognostic factor for DFS (Hazard ratio = 1.635, P=0.006). Conclusions DUSP6 is over expressed in tumor tissue compared to peritumor or normal liver tissue. Higher expression of DUSP6 in tumor tissue, than in peritumor tissue, is associated with the recurrence after curative resection of HCC, and the relative tumor DUSP6 expression has good power to predict the recurrence of HCC.
A Reformer Model for Fuel Cell Power Systems

This paper concerns the modeling of a natural gas steam reformer intended for hydrogen production in a fuel cell power systems. The system issues are discussed and a steam reformer model is described. The reformer model will be included in a previously developed library to be used as a tool for the simulation of hybrid energy systems. The paper describes also an analysis of steady state and dynamical operation of a PEM-Reformer system, performed through the simulation tool.
Impartial comparative analysis of measurement of leukocyte telomere length/DNA content by Southern blots and qPCR

Telomere length/DNA content has been measured in epidemiological/clinical settings with the goal of testing a host of hypotheses related to the biology of human aging, but often the conclusions of these studies have been inconsistent. These inconsistencies may stem from various reasons, including the use of different telomere length measurement techniques. Here, we report the first impartial evaluation of measurements of leukocyte telomere length by Southern blot of the terminal restriction fragments and quantitative PCR (qPCR) of telomere DNA content, expressed as the ratio of telomeric product (T)/single copy gene (S) product. Blind measurements on the same samples from 50 donors were performed in two independent laboratories on two different occasions. Both the qPCR and Southern blots displayed highly reproducible results as shown by r values > 0.9 for the correlations between results obtained by either method on two occasions. The inter-assay CV measurement for the qPCR was 6.45%, while that of the Southern blots was 1.74%. The relation between the results generated by Southern blots versus those generated by qPCR deviated from linearity. We discuss the ramifications of these findings with regard to measurements of telomere length/DNA content in epidemiological/clinical circumstances.
Suppression of Reserve MCM Complexes Chemosensitizes to Gemcitabine and 5-Fluorouracil

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest forms of cancer and is very difficult to treat with conventional chemotherapeutic regimens. Gemcitabine and 5-fluorouracil are used in the management of PDAC and act by indirectly blocking replicative forks. However, these drugs are not highly effective at suppressing disease progression, indicating a need for the development of innovative therapeutic approaches. Recent studies indicate that suppression of the MCM helicase may provide a novel means to sensitize cancer cells to chemotherapeutic agents that inhibit replicative fork progression. Mammalian cells assemble more MCM complexes on DNA than are required to start S-phase. The excess MCM complexes function as backup initiation sites under conditions of replicative stress. The current study provides definitive evidence that cosuppression of the excess/backup MCM complexes sensitizes PDAC tumor lines to both gemcitabine and 5-FU, leading to increased loss of proliferative capacity compared with drugs alone. This occurs because reduced MCM levels prevent efficient recovery of DNA replication in tumor cells exposed to drug. PDAC tumor cells are more sensitive to MCM loss in the presence of gemcitabine than are nontumor, immortalized epithelial cells. Similarly, colon tumor cells are rendered less viable when cosuppression of MCM complexes occurs during exposure to the crosslinking agent oxaliplatin or topoisomerase inhibitor etoposide. Implications: These studies demonstrate that suppressing the backup complement of MCM complexes provides an effective sensitizing approach with the potential to increase the therapeutic index of drugs used in the clinical management of PDAC and other cancers. Mol Cancer Res; 13(9); 1296–305. ©2015 AACR.
Endoglin is required for hemangioblast and early hematopoietic development

Endoglin (ENG), an ancillary receptor for several members of the transforming growth factor (TGF)-beta superfamily, has a well-studied role in endothelial function. Here, we report that endoglin also plays an important role early in development at the level of the hemangioblast, an embryonic progenitor of the hematopoietic and endothelial lineages. Eng-/-, Eng+/- and Eng+/+ mouse embryonic stem (ES) cells were differentiated as embryoid bodies (EBs) and assayed for blast colony-forming cells (BL-CFCs). Our results showed a profound reduction in hemangioblast frequency in the absence of endoglin. Furthermore, cell-sorting experiments revealed that endoglin marks the hemangioblast on day 3 of EB differentiation. When analyzed for hematopoietic and endothelial activity, replated Eng-/- BL-CFCs presented limited hematopoietic potential, whereas endothelial differentiation was unaltered. Analysis of hematopoietic colony formation of EBs, at different time points, further supports a function for endoglin in early hematopoiesis. Taken together, these findings point to a role for endoglin in both hemangioblast specification and hematopoietic commitment.
Epithelial–Mesenchymal Transitioned Circulating Tumor Cells Capture for Detecting Tumor Progression

Purpose: This study aimed to detect cell-surface vimentin (CSV) on the surface of epithelial–mesenchymal transitioned (EMT) circulating tumor cells (CTC) from blood of patients with epithelial cancers. Experimental Design: In this study, 101 patients undergoing postsurgery adjuvant chemotherapy for metastatic colon cancer were recruited. EMT CTCs were detected from blood of patients using the 84-1 monoclonal antibody against CSV as a marker. EMT CTCs isolated were characterized further using EMT-specific markers, fluorescent in situ hybridization, and single-cell mutation analysis. Results: Using the 84-1 antibody, we detected CSV exclusively on EMT CTCs from a variety of tumor types but not in the surrounding normal cells in the blood. The antibody exhibited very high specificity and sensitivity toward different epithelial cancer cells. With this antibody, we detected and enumerated EMT CTCs from patients. From our observations, we defined a cutoff of <5 or ≥5 EMT CTCs as the optimal threshold with respect to therapeutic response using ROC curves. Using this defined threshold, the presence of ≥5 EMT CTCs was associated with progressive disease, whereas patients with <5 EMT CTCs showed therapeutic response. Conclusion: Taken together, the number of EMT CTCs detected correlated with the therapeutic outcome of the disease. These results establish CSV as a universal marker for EMT CTCs from a wide variety of tumor types and thus provide the foundation for emerging CTC detection technologies and for studying the molecular regulation of these EMT CTCs. Clin Cancer Res; 21(4); 899–906. ©2014 AACR.
Electrocardiographic Changes Mimicking Acute Coronary Syndrome in a Metastatic Cardiactumor: A Case Report

Electrocardiographic abnormalities are commonly seenin cases with metastatic invasion of the heart. However, most of these changes are nonspecific; certain findings may be highly suggestive of myocardial tumor invasion. We report a patient with lung cancer who presented with ST-segment elevation on electrocardiogram (ECG), myocardial invasion of lung cancer on echocardiogram (ECHO) and with mass invasion of pericardium and epicardiumon computed tomography (CT) chest.
Inhibitive effect of purple sweet potato leaf extract and its components on cell adhesion and inflammatory response in human aortic endothelial cells

This study investigated the effects of purple sweet potato leaf extract (PSPLE) and its components, cyanidin and quercetin, on human aortic endothelial cells (HAECs) during the inflammatory process. HAECs were pretreated with 100 μg/mL PSPLE or 10 μM quercetin, cyanidin or aspirin for 18 h followed by TNF-α (2 ng/mL) for 6 h, and U937 cell adhesion was determined. Adhesion molecule expression and CD40 were evaluated; NFκB p65 protein localization and DNA binding were assessed. PSPLE, aspirin, cyanidin and quercetin significantly inhibited TNF-α-induced monocyte-endothelial cell adhesion (p < 0.05). Cyanidin, quercetin and PSPLE also significantly attenuated VCAM-1, IL-8 and CD40 expression, and quercetin significantly attenuated ICAM-1 and E-selectin expression (p < 0.05). Significant reductions in NFκB expression and DNA binding by aspirin, cyanidin and quercetin were also observed in addition to decreased expression of ERK1, ERK2 and p38 MAPK (p < 0.05). Thus, PSPLE and its components, cyanidin and quercetin, have anti-inflammatory effects through modulation of NFκB and MAPK signaling. Further in vivo studies are necessary to explore the possible therapeutic effects of PSPLE on atherosclerosis.
Alcoholic marriage: later start, sooner end.

BACKGROUND Although associations between drinking behavior and marital status are well documented, timing of marital transitions as a function of alcohol use or disorder has received limited empirical attention. METHODS We examine the relationship between lifetime history of alcohol dependence (AD) and timing and survival of first marriages in a sample of 3,575 female and 1,845 male adult Australian twins born mostly between 1940 and 1964. Survival analyses were conducted using Cox proportional hazards regression models. RESULTS Results indicate moderate delays in marriage associated with AD for both women and men. Among ever-married respondents, AD was strongly predictive of early separation, with similar effects observed for women and men. Heritable sources of covariation were also documented. For women, genetic influences shared between early-onset AD and marital timing were found. Genetic influences shared between AD and marital survival were observed for women without regard to onset and for men with later-onset AD. CONCLUSIONS Results confirm the importance of AD as a predictor of both timing and survival of first marriages, with genetic influences contributing to observed associations.
Extracting person names from diverse and noisy OCR text

Named entity recognition applied to scanned and OCRed historical documents can contribute to the discoverability of historical information. However, entity recognition from some historical corpora is much more difficult than from natively digital text because of the marked presence of word errors and absence of page layout information. How difficult can it be and what level of quality can be expected? We apply three typical extraction algorithms to the task of extracting person names from multiple types of noisy OCR documents found in the collection of a major genealogy content provider and compare their performance using a number of quality metrics. We also show an improvement in extraction quality using a majority-vote ensemble of the three extractors. We evaluate the extraction quality with respect to two references: what a human can manually extract from OCR output and from the original document images. We illustrate the challenges and opportunities at hand for extracting names from OCRed data and identify directions for further improvement.
Asynchronous information consensus in distributed control of irrigation canals

In distributed model predictive control, accounting for the interactions of subsystems requires exchanging information between controllers. However, challenges arise when controllers may lose the synchronization and when shared information may encounter the divergence due to the switching topology and the imperfection in communication. Managing divergent (or outdated) information is considered in this paper as a consensus problem and solved by an asynchronous consensus protocol. This approach based on multi-agent system paradigm to distributed control requires each controller to agree on some data values needed during action computation with its neighbors. Under certain assumptions, the convergence of consensus protocol is analytically obtained with various communication patterns (for example, directed and delayed communication). As a result, the performance of control system is improved in comparison with the decentralized strategy, and approached to the distributed strategy with sequential timing. Some simulation examples are given to illustrate the efficiency of this approach for the control of irrigation canals modeled by the Lattice Boltzmann method.
Some perspectives on Scale-up of Flow and Transport in Heterogeneous Media

Performance predictions of reactive processes such as those that occur when injected fluids interact with subsurface rocks require accurate models for the processes. Frequently, these processes are studied at laboratory scale and modeling them at the field scale entails scaling-up laboratory observations taking into account the spatial variability of parameters. The current practice is to perform spatial averaging of attributes measured at fine scale and account for residual variability by calibration and history matching. This results in poor predictions of future reservoir performance. In this paper we scale-up such reactive transport processes for two different applications using a numerical procedure that accounts for both the spatial and temporal characteristics of these processes.
Comparison of (+)-(11)C-McN5652 and (11)C-DASB as serotonin transporter radioligands under various experimental conditions.

UNLABELLED There has been considerable interest in the development of a PET radioligand selective for the serotonin (5-hydroxytryptamine [5-HT]) transporter (SERT) that can be used to image 5-HT neurons in the living human brain. The most widely used SERT radiotracer to date, trans-1,2,3,5,6,10-beta-hexahydro-6-[4-(methylthio)phenyl[pyrrolo-[2,1-a]isoquinoline ((+)-(11)C-McN5652), has been successful in this regard but may have some limitations. Recently, another promising SERT radiotracer, 3-(11)C-amino-4-(2-dimethylaminomethylphenylsulfanyl)benzonitrile ((11)C-DASB), has been described. The purpose of this study was to compare and contrast (+)-(11)C-McN5652 and (11)C-DASB under various experimental conditions. METHODS Radioligand comparisons were performed in a control baboon, a baboon with reduced SERT density ((+/-)-3,4-methylenedioxymethamphetamine [MDMA] lesion), and a baboon with reduced SERT availability (paroxetine pretreatment). Under each of these experimental conditions, repeated (triplicate) PET studies were performed with each ligand. RESULTS Both radiotracers bound preferentially in brain regions known to contain high SERT density. For both ligands, there was a high correlation between the amount of regional brain ligand binding and the known regional brain concentration of SERT. Binding of both ligands was decreased after MDMA neurotoxicity (reduced SERT density), and (+)-(11)C-McN5652 and (11)C-DASB were comparably effective in detecting reduced SERT density after MDMA-induced 5-HT neurotoxicity. Pretreatment with paroxetine dramatically altered the metabolism and kinetics of both tracers and appeared to displace both ligands primarily from regions with high SERT density. Compared with (+)-(11)C-McN5652, (11)C-DASB had higher brain activity and a faster washout rate and provided greater contrast between subcortical and cortical brain regions. CONCLUSION (11)C-DASB and (+)-(11)C-McN5652 are suitable as PET ligands of the SERT and for detecting MDMA-induced 5-HT neurotoxicity. (11)C-DASB may offer some advantages. Additional studies are needed to further characterize the properties and capabilities of both ligands in health and disease.