Miracle-dz/UniFAR-FTUs huggingface dataset:
Phase I Trial of Antigen-Specific Gene Therapy Using a Recombinant Vaccinia Virus Encoding MUC-1 and IL-2 in MUC-1-Positive Patients With Advanced Prostate Cancer

Abstract: MUC-1 is overexpressed on many tumor cells. In addition, aberrant glycosylation of MUC-1 on human tumors leads to exposure of cryptic peptide epitopes that play a role in tumor immunity. As such, it has been identified as a potential target for immunotherapy. The purpose of this phase 1 clinical trial was to determine the maximum tolerated dose, safety of a multiple-dose regimen, and the immunologic effect of vaccinia virus expressing MUC-1 and IL-2 genes (VV/MUC-1/IL-2) in patients with advanced prostate cancer. Five × 105, 5 × 106, and 5 × 107 plaque-forming units (pfu) of vaccinia viruses were used in the dose-escalating study. Viruses were given via intramuscular injection, and clinical response and immune function modulation were analyzed. No grade 3 or 4 toxicity was observed. Objective clinical response was observed after the fourth injection (0.3 ng/mL) in only one patient who received an intermediate dose of virus. Systemic immune modulation in this patient included (1) up-regulation of IL-2 (CD25) and T cell (TcR &agr;β) receptors, (2) increase in the CD4/CD8 ratio (2.5-fold) (3) augmentation of T-helper type 1 cell (TH1) (interferon-γ and tumor necrosis factor-&agr; ) but not TH2 (IL-4) cytokine mRNA expression, (4) induction of natural killer cell activity and MHC independent MUC-1 specific cytotoxic T-cell activity, and (5) normalization of mRNA expression of T-cell–associated signal transduction molecules TcR-ζ and p56lck. These results suggest that VV/MUC-1/IL-2 gene therapy with a maximum tolerated dose of 5 × 107 pfu is safe and well tolerated.
Efficient Antennas for Terahertz and Optical Frequencies.

ii To God To my father Siyoung Choi, and my mother Jaenam Jeon To my fiancé Saebom Jung iii ACKNOWLEDGEMENTS First and foremost, I would like to deeply thank and dedicate all my success to God, my parents, sister, and fiancé. Without their love and care, I would not be able to accomplish my ph.D work. I want to express my sincere gratitude and appreciation to my advisors Prof. Kamal Sarabandi for his continuous support, encouragement and guidance throughout my studies. I would like to extend my sincere gratitude to my other committee members, Prof. for devoting their time to review this thesis and advising me with valuable suggestions. I would like to thank my colleagues and friends at the Radiation Laboratory and EECS for constructive and insightful discussions. Figure 1.1: (a) 160 nm-length gold dipole antenna with diameter of 10 nm and the gap size of 3 nm filled by vacuum, (b) and (c) field magnitude (complex electric field) along a cut plane across the center of the antenna of the antenna consists of PEC (at f = 1,150 THz) and Drude model gold
Genre effects on automatic sentence segmentation of speech: A comparison of broadcast news and broadcast conversations

We investigate genre effects on the task of automatic sentence segmentation, focusing on two important domains - broadcast news (BN) and broadcast conversation (BC). We employ an HMM model based on textual and prosodic information and analyze differences in segmentation accuracy and feature usage between the two genres using both manual and automatic speech transcripts. Experiments are evaluated using Czech broadcast corpora annotated for sentence-like units (SUs). Prosodic features capture information about pause, duration, pitch, and energy patterns. Textual knowledge sources include words, part-of-speech, and automatically induced classes. We also analyze effects of using additional textual data that is not annotated for SUs. Feature analysis reveals significant differences in both textual and prosodic feature usage patterns between the two genres. The analysis is important for building automatic understanding systems when limited matched-genre data are available, or for designing eventual genre-independent systems.
Comparison of exhalation time methods (6 sec vs. 10 sec) of a hand‐held exhaled nitric oxide analyzer

Standard exhalation time for measuring fractional exhaled nitric oxide (FeNO) is 10 sec, but this is not easy for younger children. We aimed to investigate the agreement between FeNO values during 10‐sec (FeNO‐10) and 6‐sec (FeNO‐6) exhalation and the feasibility of measuring FeNO‐6, using a hand‐held analyzer, NIOX‐MINO®. FeNO values measured during 10‐ and 6‐sec (random order) were compared. Success rates of the two different time modes were also evaluated. In 119 asthmatic children (median age 8 years [range 4–15]) who had been already accustomed to NIOX‐MINO®, median FeNO‐10 (29 ppb [IQR 15.2–42.0]) and FeNO‐6 (27 ppb [IQR 16.0–43.5]) did not differ significantly (P = 0.90), and there was a good correlation between both values (r = 0.984, P < 0.001). Mean difference (FeNO‐10–FeNO‐6) was −0.151 ppb (95% CI: −0.95 to 0.65, limits of agreement: −8.8 to 8.5). In 46 asthmatic children (median age 7 years [range 4–15]) who had never used any FeNO analyzers, all the children aged 8 years and more (n = 21) succeeded in measuring FeNO on both time modes, whereas for children aged younger than 8 years (n = 25) success rates of the 10‐ and 6‐sec mode were 60.0% and 92.0%, respectively. In conclusion, we showed good agreement between FeNO‐10 and FeNO‐6, and the 6‐sec mode of NIOX‐MINO® is more feasible than 10‐sec mode for measuring FeNO in younger children. Pediatr Pulmonol. 2010; 45:1005–1008. © 2010 Wiley‐Liss, Inc.
SKP2 inactivation suppresses prostate tumorigenesis by mediating JARID1B ubiquitination

Aberrant elevation of JARID1B and histone H3 lysine 4 trimethylation (H3K4me3) is frequently observed in many diseases including prostate cancer (PCa), yet the mechanisms on the regulation of JARID1B and H3K4me3 through epigenetic alterations still remain poorly understood. Here we report that Skp2 modulates JARID1B and H3K4me3 levels in vitro in cultured cells and in vivo in mouse models. We demonstrated that Skp2 inactivation decreased H3K4me3 levels, along with a reduction of cell growth, cell migration and malignant transformation of Pten/Trp53 double null MEFs, and further restrained prostate tumorigenesis of Pten/Trp53 mutant mice. Mechanistically, Skp2 decreased the K63-linked ubiquitination of JARID1B by E3 ubiquitin ligase TRAF6, thus decreasing JARID1B demethylase activity and in turn increasing H3K4me3. In agreement, Skp2 deficiency resulted in an increase of JARID1B ubiquitination and in turn a reduction of H3K4me3, and induced senescence through JARID1B accumulation in nucleoli of PCa cells and prostate tumors of mice. Furthermore, we showed that the elevations of Skp2 and H3K4me3 contributed to castration-resistant prostate cancer (CRPC) in mice, and were positively correlated in human PCa specimens. Taken together, our findings reveal a novel network of SKP2- JARID1B, and targeting SKP2 and JARID1B may be a potential strategy for PCa control.
Functional imaging of multidrug-resistant P-glycoprotein with an organotechnetium complex.

The multidrug-resistant P-glycoprotein (Pgp), a M(r) 170,000 plasma membrane protein encoded by the mammalian multidrug resistance gene (MDR1), appears to function as an energy-dependent efflux pump. Many of the drugs that interact with Pgp are lipophilic and cationic at physiological pH. We tested the hypothesis that the synthetic gamma-emitting organotechnetium complex, hexakis(2-methoxyisobutylisonitrile)technetium(I) ([99mTc]SESTAMIBI), a lipophilic cationic radiopharmaceutical, could be a suitable Pgp transport substrate capable of functional imaging of the MDR phenotype. The cellular pharmacological profile of [99mTc]SESTAMIBI transport was examined in Chinese hamster V79 lung fibroblasts and the 77A and LZ derivative cell lines which express modestly low, intermediate, and very high levels of Pgp, respectively. Steady-state contents of [99mTc]SESTAMIBI in V79, 77A, and LZ cells were 10.0 +/- 0.5 (SEM) (n = 9), 3.6 +/- 0.5 (n = 8), and 0.4 +/- 0.02 (n = 9) fmol. (mg protein)-1 (nMo)-1, respectively, consistent with enhanced extrusion of the imaging agent by Pgp-enriched cells. Maximal doses (> 100 microM) of the multidrug-resistant reversal agents verapamil and cyclosporin A enhanced [99mTc]SESTAMIBI accumulation in V79, 77A, and LZ cells by approximately 10-, 25-, and 200-fold, respectively. The median effective concentration values for tracer accumulation in the presence of verapamil in V79, 77A, and LZ cells were 4, 100, and 200 microM, and those for cyclosporin A were 0.9, 3, and > 25 microM, respectively. Pgp-mediated [99mTc]SESTAMIBI transport occurred against its electrochemical gradient and was found to be ATP dependent displaying an apparent Km of 50 microM. Carrier-added [99Tc]SESTAMIBI was 11- to 13-fold less toxic in multidrug-resistant cells, and inhibited photolabeling of Pgp by [125I]iodoaryl azidoprazosin in a concentration-dependent manner; half-maximal displacement was observed at approximately 100- to 1000-fold molar excess [99Tc]SESTAMIBI. Exploiting the favorable gamma emission properties of 99mTc, functional expression of Pgp was successfully imaged in human tumor xenographs in nude mice with pharmacologically inert tracer quantities of [99mTc]SESTAMIBI. Functional imaging with these organotechnetium complexes may provide a novel mechanism to rapidly characterize Pgp expression in human tumors in vivo, target reversal agents in vivo, and ultimately provide a means to direct patients to specific cancer therapies.
Citation for Published Item: Use Policy Emotional Modulation of Body-selective Visual Areas

(2007) 'Emotional modulation of body-selective visual areas. ', Social cognitive and aective neuroscience. , 2 (4). pp. 274-283. in any medium, provided the original work is properly cited. For commercial re-use, please contact The full-text may be used and/or reproduced, and given to third parties in any format or medium, without prior permission or charge, for personal research or study, educational, or not-for-prot purposes provided that: • a full bibliographic reference is made to the original source • a link is made to the metadata record in DRO • the full-text is not changed in any way The full-text must not be sold in any format or medium without the formal permission of the copyright holders. Please consult the full DRO policy for further details. Emotionally expressive faces have been shown to modulate activation in visual cortex, including face-selective regions in ventral temporal lobe. Here, we tested whether emotionally expressive bodies similarly modulate activation in body-selective regions. We show that dynamic displays of bodies with various emotional expressions vs neutral bodies, produce significant activation in two distinct body-selective visual areas, the extrastriate body area and the fusiform body area. Multi-voxel pattern analysis showed that the strength of this emotional modulation was related, on a voxel-by-voxel basis, to the degree of body selectivity, while there was no relation with the degree of selectivity for faces. Across subjects, amygdala responses to emotional bodies positively correlated with the modulation of body-selective areas. Together, these results suggest that emotional cues from body movements produce topographically selective influences on category-specific populations of neurons in visual cortex, and these increases may implicate discrete modulatory projections from the amygdala. INTRODUCTION The ability to perceive and accurately interpret other people's emotions is central to social interaction. We gain information about others' emotional states from multimodal cues, including postures and movements of the face and body. One of the consistent findings from research on emotional face perception is an enhanced activation of face-selective visual areas such as the fusiform face area (FFA; Kanwisher et al., 1997) in response to faces expressing emotions, relative to emotionally neutral faces (Vuilleumier et al., 2001; Pessoa et al., 2002; Winston et al., 2003). This enhanced activation in FFA in response to emotional faces has been shown to correlate with activity in amygdala (Morris et al., 1998), and has been attributed to feedback modulatory influences from the amygdala, serving to prioritize visual processing of emotionally salient …
Privacy and Statistical Risk: Formalisms and Minimax Bounds

We explore and compare a variety of definitions for privacy and disclosure limitation in statistical estimation and data analysis, including (approximate) differential privacy, testing-based definitions of privacy, and posterior guarantees on disclosure risk. We give equivalence results between the definitions, shedding light on the relationships between different formalisms for privacy. We also take an inferential perspective, where---building off of these definitions---we provide minimax risk bounds for several estimation problems, including mean estimation, estimation of the support of a distribution, and nonparametric density estimation. These bounds highlight the statistical consequences of different definitions of privacy and provide a second lens for evaluating the advantages and disadvantages of different techniques for disclosure limitation.
Comparing performance of classical methods for service restoration in MV networks with a new method based on sensitivity parameters

The objective of this paper is to demonstrate the validity of the use of sensibility parameters as a low computational cost tool to implement service restoration in medium voltage distribution networks. A linearization of the relationship between accumulated powers - active and reactive - in a node and the voltages of all nodes can be carried out by means of sensitivity parameters, in order to determine the influence in voltages, caused by variations in powers in the network nodes as intending supply restoration of loads. The validity of this analysis tool is made comparing it with the restoration/reconfiguration classical methods that uses either a constructive process or an opening process of mesh. It was observed that the service restoration by the use of sensitivity parameters normally presents a very small number of complete calculations of load flow when compared with the classical methods, in addition to a significant reduction in the switching operations, with obvious advantages in the time of restoration, and in the rates of network reliability.
Oncotargets and Therapy Dovepress Dovepress Expression Profiles of Pivotal Micrornas and Targets in Thyroid Papillary Carcinoma: an Analysis of the Cancer Genome Atlas

In the present study, we analyzed microRNA (miRNA) and gene expression profiles using 499 papillary thyroid carcinoma (PTC) samples and 58 normal thyroid tissues obtained from The Cancer Genome Atlas database. A pivotal regulatory network of 18 miRNA and 16 targets was identified. Upregulated miRNAs (miR-222, miR-221, miR-146b, miR-181a/b/d, miR-34a, and miR-424) and downregulated miRNAs (miR-9-1, miR-138, miR-363, miR-20b, miR-195, and miR-152) were identified. Among them, the upregulation of miR-424 and downregulation of miR-363, miR-195, and miR-152 were not previously identified. The genes HSP90B1 were newly identified. Based on receiver operating characteristic curves, several miRNAs (miR-222, miR-221, and miR-34a) and genes (CCND1 and MET) were ideal diagnostic indicators, with sensitivities and specificities greater than 90%. The combination of inversely expressed miRNAs and targets improved diagnostic accuracy. In a clinical feature analysis, several miRNAs (miR-34a, miR-424, miR-20b, and miR-152) and genes (CCNE2, COL4A1, TRAF6, and HSP90B1) were associated with aggressive clinical features, which have not previously been reported. Our study not only identified a pivotal miRNA regulatory network associated with PTC but also provided evidence that miRNAs and target genes can be used as biomarkers in PTC diagnosis and clinical risk evaluation.
Flightin, a novel myofibrillar protein of Drosophila stretch-activated muscles

The indirect flight muscles of Drosophila are adapted for rapid oscillatory movements which depend on properties of the contractile apparatus itself. Flight muscles are stretch activated and the frequency of contraction in these muscles is independent of the rate of nerve impulses. Little is known about the molecular basis of these adaptations. We now report a novel protein that is found only in flight muscles and has, therefore, been named flightin. Although we detect only one gene (in polytene region 76D) for flightin, this protein has several isoforms (relative gel mobilities, 27-30 kD; pIs, 4.6-6.0). These isoforms appear to be created by posttranslational modifications. A subset of these isoforms is absent in newly emerged adults but appears when the adult develops the ability to fly. In intact muscles flightin is associated with the A band of the sarcomere, where evidence suggests it interacts with the myosin filaments. Computer database searches do not reveal extensive similarity to any known protein. However, the NH2-terminal 12 residues show similarity to the NH2- terminal sequence of actin, a region that interacts with myosin. These features suggest a role for flightin in the regulation of contraction, possibly by modulating actin-myosin interaction.
Role of XPC, XPD, XRCC1, GSTP genetic polymorphisms and Barrett’s esophagus in a cohort of Italian subjects. A neural network analysis

Background Barrett’s esophagus (BE), a metaplastic premalignant disorder, represents the primary risk factor for the development of esophageal adenocarcinoma. Chronic gastroesophageal reflux disease and central obesity have been associated with BE and esophageal adenocarcinoma, but relatively little is known about the specific genes that confer susceptibility to BE carcinogenesis. Methods A total of 74 patients with BE and 67 controls coming from six gastrointestinal Italian units were evaluated for six polymorphisms in four genes: XPC, XPD nucleotide excision repair (NER) genes, XRCC1 (BER gene), and glutathione S-transferase P1. Smoking status was analyzed together with the genetic data. Statistical analysis was performed through Artificial Neural Networks. Results Distributions of sex, smoking history, and polymorphisms among BE cases and controls did not show statistically significant differences. The r-value from linear correlation allowed us to identify possible protective factors as well as possible risk factors. The application of advanced intelligent systems allowed for the selection of a subgroup of nine variables. Artificial Neural Networks applied on the final data set reached mean global accuracy of 60%, reaching as high as 65.88%. Conclusion We report here results from an exploratory study. Results from this study failed to find an association among the tested single nucleotide polymorphisms and BE phenotype through classical statistical methods. On the contrary, advanced intelligent systems are really able to handle the disease complexity, not treating the data with reductionist approaches unable to detect multiple genes of smaller effect in predisposing to the disease. Impact To detect multiple genes of smaller effects in predisposing individuals to Barrett’s esophagus.
Comparison of immunogenicity and safety of an influenza vaccine administered concomitantly with a 13-valent pneumococcal conjugate vaccine or 23-valent polysaccharide pneumococcal vaccine in the elderly

Purpose Previous studies have demonstrated the immunogenicity and safety of the co-administration of the trivalent inactivated influenza vaccine (IIV3) with the polysaccharide pneumococcal vaccine (PPV) or pneumococcal conjugate vaccine (PCV). However, there is no direct comparison study that evaluates the immunogenicity and safety of IIV3 given concomitantly with PCV13 or PPV23 in the elderly. Materials and Methods During the 2012-2013 influenza vaccination period, 224 healthy elderly volunteers aged 65 years and older randomly received IIV3 given concomitantly with either PCV13 (PCV13+IIV3) or PPV23 (PPV23+IIV3) in a 1:1 ratio. Serum hemagglutination-inhibiting antibodies for IIV3 were measured at the time of vaccination and 1 month after vaccination. Adverse events were recorded prospectively in a clinical diary during a 7-day period. Results A total of 220 participants blood samples for analysis of immunogenicity and kept a clinical diary for safety analysis (PCV13+IIV3, n=110; PPV23+IIV3, n=110). One month after vaccination, both groups satisfied the Committee for Medical Products for Human Use criteria for A/H1N1, A/H3N2 and B strains, showing comparable seroprotection rates, seroconversion rates and geometric mean titer fold. The assessments of immunogenicity were similar in both groups. The most common local and systemic reactions were pain at the injection site and generalized myalgia. They were generally mild or moderate in intensity. The adverse events were not statistically different between the two groups. Conclusion PCV13+IIV3 and PPV23+IIV3 demonstrated similar immunogenicity and safety in the elderly.
A Variational Inequality Sufficient Condition for Optimal Stopping with Application to an Optimal Stock Selling Problem

We give a variational inequality sufficient condition for optimal stopping problems. This result is illustrated by computing solutions to an optimal stock selling problem. The stock selling problem has a model for the stock price, which initially has a "hot" growth rate and then "tanks. " Solution of the conditions allows for computation of both the value function and the optimal stopping times. Optimal stock selling times are computed for two utility functions and a variety of realistic parameter values.
Archiving Data Objects using Web Feeds

Web feeds, either in RSS or Atom XML-based formats, are evolving descriptive documents that characterize a dynamic hub of a Web site and help subscribers keep up with what is the most recent Web content of interest. In this paper, we show how Web feeds can be useful instruments for information extraction and Web page change detection. Web pages referenced by feed items are usually blog posts or news articles, data with a dynamic (then ephemeral) nature and which is clustered topically in a feed channel. We monitor Web channels and extract from the associated Web pages the text and references corresponding to Web articles. The result is enriched with the timestamp and additional metadata mined from the feed, and encapsulated in a 'data object'. The data object will be in particular information devoided of all the template elements or advertisements. These irrelevant elements, generically called boileplate, are not only consuming time and space from the crawler's point of view, but also hinder the data analysis process. We first make some statistics on a set of Web feeds, by crawling them for a period of time and observing their temporal aspects. Then we present the algorithm used for article extraction, algorithm that uses the feed semantics (more specifically the description and title of feed items) in order to identify the DOM node in the HTML page that contains the article. The data objects constructed in this way can be used as a semantic overlay collection for an archive or in the context of an incremental crawl, making it more efficient by detecting change at data object level. Experiments on the extraction technique are done in order to validate our approach, with good results even in cases when other techniques fail. We finally discuss useful applications based on the extraction and change detection of Web objects.