Miracle-dz/UniFAR-FTUs huggingface dataset:
p 38-Mediated Inactivation of Cyclin D 1 / Cyclin-Dependent Kinase 4 Stimulates Nucleolar Translocation of RelA and Apoptosis in Colorectal Cancer Cells

Aberrant nuclear factor-KB (NF-KB) signaling plays a role in cancer initiation and progression; thus, it represents a potential therapeutic target. We previously identified a mechanism of repression of NF-KB transcriptional activity and induction of apoptosis in colon cancer cells involving nuclear/nucleolar translocation of the RelA (p65) component of NF-KB. This response was stimulated by cellular stress-inducing agents, including aspirin, but not by tumor necrosis factor. Here, we investigate the upstream molecular mechanisms responsible for nucleolar targeting of RelA and show that aspirin activates the p38 mitogen-activated protein kinase (MAPK) pathway in colorectal cancer cells. We also show that aspirin causes rapid, ubiquitin-dependent degradation of cyclin D1, a known p38 target. Aspirin-induced p38 activation preceded cyclin D1 degradation, which was then followed by activation of the NF-KB pathway, suggesting a causative link. Indeed, chemical p38 inhibition (PD169316) and small interfering RNA directed against p38 blocked aspirin-induced cyclin D1 degradation, nucleolar translocation of RelA, and apoptosis. Furthermore, chemical inhibition of the cyclin D1/cyclindependent kinase 4 (CDK4) kinase complex, used as a surrogate for cyclin D1 degradation, caused nucleolar translocation of RelA, repression of KB-driven transcription, and apoptosis, thereby reproducing the effects of aspirin. In addition, we found that aspirin and the CDK4 inhibitor induced nucleolar translocation of RelA and apoptosis through a common mechanism involving the NH2-terminal nucleolar localization signal. Collectively, these data suggest that aspirin causes inhibition of cyclin D1/CDK4 through the p38 MAPK pathway. This inhibition stimulates the NF-KB pathway to induce nucleolar translocation of RelA and apoptosis. These novel findings have considerable relevance to the rational design of novel chemotherapeutic and chemopreventative strategies. [Cancer Res 2007;67(4):1660–9]
Microwave-Assisted Solution-Phase Synthesis and DART-Mass Spectrometric Monitoring of a Combinatorial Library of Indolin-2,3-dione Schiff Bases with Potential Antimycobacterial Activity

A combinatorial library composed of eleven hydrazides A-K and eleven indolin-1,2-dione derivatives 1-11 has been designed to formally generate sublibraries of 22 mixtures, M1-M22 comprising of 121 Schiff bases, A-K(1-11). The designed library has been synthesized by the solution-phase method and microwave-assisted synthetic techniques. The formation of individual compounds of each mixture was confirmed by Direct Analysis in Real Time (DART) as ionization technique connected to an Ion Trap as a mass detector. The synthesized mixtures were evaluated for their antimycobacterial activity against four Mycobacterium strains; M. intercellulari, M. xenopi, M. cheleneoi and M. smegmatis. Variable antimycobacterial activity was revealed with the investigated mixtures and maximum activity was shown by M8, M10, M11, and M15 with MIC values of 1.5, 3.1, 6.2 and 0.09 μg/mL, respectively. Application of the indexed method of analysis on these active mixtures revealed that compounds D8, D10 and D11 may contribute to the activity of the tested mixtures.
First-in-Human Molecular Imaging of HER2 Expression in Breast Cancer Metastases Using the 111In-ABY-025 Affibody Molecule

The expression status of human epidermal growth factor receptor type 2 (HER2) predicts the response of HER2-targeted therapy in breast cancer. ABY-025 is a small reengineered Affibody molecule targeting a unique epitope of the HER2 receptor, not occupied by current therapeutic agents. This study evaluated the distribution, safety, dosimetry, and efficacy of 111In-ABY-025 for determining the HER2 status in metastatic breast cancer. Methods: Seven patients with metastatic breast cancer and HER2-positive (n = 5) or -negative (n = 2) primary tumors received an intravenous injection of approximately 100 μg (∼140 MBq) of 111In-ABY-025. Planar γ-camera imaging was performed after 30 min, followed by SPECT/CT after 4, 24, and 48 h. Blood levels of radioactivity, antibodies, shed serum HER2, and toxicity markers were evaluated. Lesional HER2 status was verified by biopsies. The metastases were located by 18F-FDG PET/CT 5 d before 111In-ABY-025 imaging. Results: Injection of 111In-ABY-025 yielded a mean effective dose of 0.15 mSv/MBq and was safe, well tolerated, and without drug-related adverse events. Fast blood clearance allowed high-contrast HER2 images within 4–24 h. No anti–ABY-025 antibodies were observed. When metastatic uptake at 24 h was normalized to uptake at 4 h, the ratio increased in HER2-positive metastases and decreased in negative ones (P < 0.05), with no overlap and confirmation by biopsies. In 1 patient, with HER2-positive primary tumor, 111In-ABY-025 imaging correctly suggested a HER2-negative status of the metastases. The highest normal-tissue uptake was in the kidneys, followed by the liver and spleen. Conclusion: 111In-ABY-025 appears safe for use in humans and is a promising noninvasive tool for discriminating HER2 status in metastatic breast cancer, regardless of ongoing HER2-targeted antibody treatment.
Ising field parameter estimation from incomplete and noisy data

The present paper deals with the estimation problem of the Ising field parameter and extends a previous one [1]. It proposes an estimate from indirect observation (incomplete and noisy), whereas the previous paper proposed an estimate from direct observation (complete and noiseless). Both of them are based on an explicit expression for the partition function, known for a long time [2] but, to the best of our knowledge, never used for parameter estimation (except in our previous paper [1]). Both of them are developed in a Bayesian framework. In our previous study (direct observation), the posterior law is explicit but in the present case (indirect observation) the posterior law is not explicit due to the hidden structure. The proposed approach relies on a full Bayesian strategy and a stochastic sampling algorithm (Gibbs sampler including a Metropolis-Hastings step) for posterior exploration. The paper proposes a numerical evaluation of the proposed method.
Uveitis in Children and Adolescents

ISSN: 0927-3948 (Print) 1744-5078 (Online) Journal homepage: https://www.tandfonline. com/loi/ioii20 Uveitis in Children and Adolescents Emmett T. Cunningham Jr., Justine R. Smith, Ilknur Tugal-Tutkun, Aniki Rothova & Manfred Zierhut To cite this article: Emmett T. Cunningham Jr., Justine R. Smith, Ilknur Tugal-Tutkun, Aniki Rothova & Manfred Zierhut (2016) Uveitis in Children and Adolescents, Ocular Immunology and Inflammation, 24:4, 365-371, DOI: 10.1080/09273948.2016. 1204777 To link to this article: https://doi.org/10.1080/09273948.2016. 1204777
Oral Clonidine Premedication Reduces Postoperative Pain in Children

Clonidine is an effective preanesthetic medication in children, providing a preoperative sedative effect.The analgesic properties of the drug have been well documented in adults. The current study was designed to investigate the effect of oral clonidine given preoperatively on postoperative pain in children undergoing minor surgery. In a prospective, randomized, controlled clinical trial, 90 children aged 5-12 yr undergoing elective ophthalmic, urologic, and otologic surgery received placebo (control), clonidine 2 micro gram/kg, or clonidine 4 micro gram/kg. These drugs were administered 105 min before the estimated time of induction of anesthesia and followed by treatment with oral atropine 0.03 mg/kg 60 min before anesthesia. Anesthesia was induced and maintained with halothane and nitrous oxide in oxygen. Postoperative pain was assessed by a blinded observer using an objective pain scale (OPS). Clonidine 4 micro gram/kg provided lower OPS (highest) scores during 12 h after surgery and reduced requirement for postoperative supplementary analgesic (diclofenac suppository) compared with the other two regimens. These data suggest that oral clonidine premedication (4 micro gram/kg) is a possible approach to facilitating postoperative analgesia in children undergoing minor surgery. (Anesth Analg 1996;82:225-30)
Speech errors across the lifespan

Dell, Burger, and Svec (1997) proposed that the proportion of speech errors classified as anticipations (e.g., “moot and mouth”) can be predicted solely from the overall error rate, such that the greater the error rate, the lower the anticipatory proportion (AP) of errors. We report a study examining whether this effect applies to changes in error rates that occur developmentally and as a result of ageing. Speech errors were elicited from 8- and 11-year-old children, young adults, and older adults. The error rate decreased and the AP increased from children to young adults, but neither error rate nor AP differed significantly between young and older adults. In cases where fast speech resulted in a higher error rate than slow speech, the AP was lower. Thus, there was overall support for Dell et al.'s prediction from speech error data across the lifespan.
Factors associated with differences in Canadian perinatal nurses' attitudes toward birth practices.

OBJECTIVE To test whether demographic characteristics predict registered nurses' attitudes toward birth practices. DESIGN A secondary analysis of a cross-sectional survey, the National Maternity Care Attitudes Survey. SETTING A national survey conducted with health care providers providing maternity care in Canada. PARTICIPANTS A convenience sample of 545 registered nurses. METHODS Hierarchical regression analysis was used to examine three hypotheses about nurses' demographic differences in relationship to their attitudes toward birth practices. Attitude scales included acceptability of doulas, effects of routine electronic fetal monitoring, factors decreasing cesarean birth rates, the importance of vaginal birth for women, safety of birth, episiotomy, and epidural analgesia. RESULTS Tertiary hospital-level of employment was associated with more positive attitudes toward epidural analgesia and less positive attitudes toward the importance of vaginal birth. Nurses working at a tertiary hospital were more likely to select an obstetrician for their own maternity care. Those who worked at a community hospital were more likely to select a family physician. Nurses' selection of an obstetrician was associated with less positive attitudes toward the safety of birth and importance of vaginal birth and more positive attitudes toward electronic fetal monitoring, episiotomy, and epidural analgesia. CONCLUSION Nurses' attitudes may be influenced by exposure in their workplaces to predominant care providers' birth practices. Research examining the relationships between nurses' workplace exposures, attitudes, and practice behaviors is needed to develop understanding about how nurses contribute to rates of intervention in maternity care.
Maximising the Quality of Influence

In percolation theory, vertices within a graph have a binary state: either active or inactive. Furthermore, a percolation process decides how activation spreads within the graph. Firstly, we propose and analyse a simple data-driven percolation process in which percolations are preliminarily learnt from a graph with observed percolations. Secondly, we study a problem related to the one solved by Kempe et al. in [1]: given a percolation process, which k vertices should one choose in order to maximise the number of active vertices at the end of process? This question is important in many areas, ranging from viral marketing to the study of epidemic spread. We generalise the problem by considering activations in [0, 1], measuring the “quality” of percolation, and percolation decays along edges in the percolation graph. For a varying cost of activating each vertex, we maximise the total activation whilst keeping within a budget L. The problem can be solved with a greedy algorithm with a guaranteed approximation quality, and furthermore we show its connection to the maximal coverage problem. The resulting algorithm is analysed empirically over predicted percolation graphs on a synthetic dataset and on a real dataset modelling information diffusion within a social network.
A randomized, controlled trial to test the effectiveness of a glaucoma patient navigator to improve appointment adherence

Purpose Patients with glaucoma who do not keep their follow-up eye care appointments are at risk for developing more severe ocular disease. The primary aim of the current study was to evaluate whether the use of a patient navigator altered adherence to follow-up eye care appointments in community-versus office-based settings. Patients and methods Patients diagnosed with a glaucoma-related condition following a comprehensive eye examination at 43 community sites in Philadelphia, PA, USA, were enrolled in this prospective, randomized, controlled trial. Patients were randomized into three groups for a 1-year period: Group 1 (G1) received follow-up eye care in a community-based setting with assistance from a patient navigator; Group 2 (G2) received follow-up eye care in an office-based setting with assistance from a patient navigator; and Group 3 (G3) received follow-up eye care in an office-based setting without a patient navigator (usual care). Adherence rates were compared among these three groups using a chi-squared test at a significance level of 0.05. Results A total of 155 patients with glaucoma-related diagnoses were enrolled. The mean age (±standard deviation) was 71.2 (±10.0) years. Patients were predominantly female (65.8%, n=102/155) and African-American (71.6%, n=111/155). The mean (±standard deviation) number of follow-up visits during the 1-year study period was 1.3 (±1.3) for G1, 1.6 (±1.3) for G2, and 1.3 (±1.1) for G3 (P=0.48). Appointment adherence, defined as attendance of ≥1 follow-up visit, was 69.8% (n=37/53) for G1, 82.5% (n=47/57) for G2, and 73.3% (n=33/45) for G3, (P=0.28). Sub-analysis of adherence rates for patients who attended ≥2 follow-up visits were 91.3% (n=21/23) for G1, 74.3% (n=26/35) for G2, and 66.7% (n=18/27) for G3, (P=0.11). Conclusion Help from a patient navigator did not increase the likelihood of keeping ≥1 follow-up appointment in an office-based setting. Adherence rates for follow-up appointments reached close to 70% or above in a self-selected patient population.
Anaerobic Oxidation of Arsenite Linked to Chlorate Reduction

ABSTRACT Microorganisms play a significant role in the speciation and mobility of arsenic in the environment. In this study, the oxidation of arsenite [As(III)] to arsenate [As(V)] linked to chlorate (ClO3−) reduction was shown to be catalyzed by sludge samples, enrichment cultures (ECs), and pure cultures incubated under anaerobic conditions. No activity was observed in treatments lacking inoculum or with heat-killed sludge, or in controls lacking ClO3−. The As(III) oxidation was linked to the complete reduction of ClO3− to Cl−, and the molar ratio of As(V) formed to ClO3− consumed approached the theoretical value of 3:1 assuming the e− equivalents from As(III) were used to completely reduce ClO3−. In keeping with O2 as a putative intermediate of ClO3− reduction, the ECs could also oxidize As(III) to As(V) with O2 at low concentrations. Low levels of organic carbon were essential in heterotrophic ECs but not in autotrophic ECs. 16S rRNA gene clone libraries indicated that the ECs were dominated by clones of Rhodocyclaceae (including Dechloromonas, Azospira, and Azonexus phylotypes) and Stenotrophomonas under autotrophic conditions. Additional phylotypes (Alicycliphilus, Agrobacterium, and Pseudoxanthomonas) were identified in heterotrophic ECs. Two isolated autotrophic pure cultures, Dechloromonas sp. strain ECC1-pb1 and Azospira sp. strain ECC1-pb2, were able to grow by linking the oxidation of As(III) to As(V) with the reduction of ClO3−. The presence of the arsenite oxidase subunit A (aroA) gene was demonstrated with PCR in the ECs and pure cultures. This study demonstrates that ClO3− is an alternative electron acceptor to support the microbial oxidation of As(III).
Takashi Iyanagi: UGT1 gene complex: from Gunn rat to human

UDP-glucuronosyltransferases (UGT) comprise a large gene superfamily that can be classified, based on the degree of amino-acid similarity between isoforms, into several gene families. Among these gene families, the UDP-glucuronosyltransferase family 1 (UGT1) gene is a unique gene complex organized to generate enzymes that share a common carboxyl terminal portion and are unique in the variable amino terminal region. Each variable exon I is preceded by a regulatory 5’-region and, in response to a specific signal, transcription processing splices mRNA from each unique exon 1 to the four common exons ( 2, 3, 4, and 5) to provide a template for synthesis of the individual isoforms. A novel clue to elucidate the gene structure of mammalian UGT1 was cDNA cloning of rat UGT1A6 from the hyperbilirubinemic Gunn rat by Professor Takashi Iyanagi Ph.D. The elucidation of the structure of the rat UGT1 gene complex has led to a greater understanding of the genetic basis of Crigler-Najjar and Gilbert’s syndromes. Now, examination of the UGT1 gene structure in hyperbilirubinemic patients has revealed more than 100 different genetic defects in Crigler-Najjar syndromes and one genetic alternation that accounts for the majority of Gilbert’s syndrome cases. This review of a chapter in UGT history will focus on the extensive research of Iyanagi and coworkers with the rat UGT1 gene complex and advancing to the study of the human gene.
Intelligent Bearing Fault Diagnosis Method Combining Compressed Data Acquisition and Deep Learning

Effective intelligent fault diagnosis has long been a research focus on the condition monitoring of rotary machinery systems. Traditionally, time-domain vibration-based fault diagnosis has some deficiencies, such as complex computation of feature vectors, excessive dependence on prior knowledge and diagnostic expertise, and limited capacity for learning complex relationships in fault signals. Furthermore, following the increase in condition data, how to promptly process the massive fault data and automatically provide accurate diagnosis has become an urgent need to solve. Inspired by the idea of compressed sensing and deep learning, a novel intelligent diagnosis method is proposed for fault identification of rotating machines. In this paper, a nonlinear projection is applied to achieve the compressed acquisition, which not only reduces the amount of measured data that contained all the information of faults but also realizes the automatic feature extraction in transform domain. For exploring the discrimination hidden in the acquired data, a stacked sparse autoencoders-based deep neural network is established and performed with an unsupervised learning procedure followed by a supervised fine-tuning process. We studied the significance of compressed acquisition and provided the effects of key factors and comparison with traditional methods. The effectiveness of the proposed method is validated using data sets from rolling element bearings and the analysis shows that it is able to obtain high diagnotic accuracies and is superior to the existing methods. The proposed method reduces the need of human labor and expertise and provides new strategy to handle the massive data more easily.
The 1.3-Angstrom-Resolution Crystal Structure of β-Ketoacyl-Acyl Carrier Protein Synthase II from Streptococcus pneumoniae

ABSTRACT The β-ketoacyl-acyl carrier protein synthases are members of the thiolase superfamily and are key regulators of bacterial fatty acid synthesis. As essential components of the bacterial lipid metabolic pathway, they are an attractive target for antibacterial drug discovery. We have determined the 1.3 Å resolution crystal structure of the β-ketoacyl-acyl carrier protein synthase II (FabF) from the pathogenic organism Streptococcus pneumoniae. The protein adopts a duplicated βαβαβαββ fold, which is characteristic of the thiolase superfamily. The two-fold pseudosymmetry is broken by the presence of distinct insertions in the two halves of the protein. These insertions have evolved to bind the specific substrates of this particular member of the thiolase superfamily. Docking of the pantetheine moiety of the substrate identifies the loop regions involved in substrate binding and indicates roles for specific, conserved residues in the substrate binding tunnel. The active site triad of this superfamily is present in spFabF as His 303, His 337, and Cys 164. Near the active site is an ion pair, Glu 346 and Lys 332, that is conserved in the condensing enzymes but is unusual in our structure in being stabilized by an Mg2+ ion which interacts with Glu 346. The active site histidines interact asymmetrically with Lys 332, whose positive charge is closer to His 303, and we propose a specific role for the lysine in polarizing the imidazole ring of this histidine. This asymmetry suggests that the two histidines have unequal roles in catalysis and provides new insights into the catalytic mechanisms of these enzymes.
Diagnostic Utility of the Germinal Center–associated Markers GCET1, HGAL, and LMO2 in Hematolymphoid Neoplasms

Implementation of new phenotypic markers in routine diagnostics of hematolymphoid neoplasms is a challenging task with a plethora of potentially relevant proteins. We investigated 3 recently discovered proteins expressed in the germinal centers of lymph nodes (LMO2, GCET1, and HGAL) in a compilation of leukemia, lymphoma, and thymic tumor entities. Altogether, 1590 cases (1519 on tissue microarrays, 71 on conventional slides) were included. Expressions of LMO2, GCET1, and HGAL were investigated by immunohistochemistry, evaluated for their differential diagnostic relevance, and correlated with the clinical outcome of patients. In Hodgkin lymphoma (HL), the expression of LMO2, GCET1, and HGAL could be largely seen in tumor cells of nodular lymphocyte predominant HL (NLPHL) but only occasionally in classic HL. The majority of B-cell lymphoma cases was positive for LMO2 [except for Burkitt lymphoma (BL)] and HGAL with weaker to moderate staining intensity, compared with the intensely staining follicular lymphomas (FL). Except for FL (60% of cases) and diffuse large B-cell lymphomas (DLBCL, 36% of cases), all other B-cell lymphomas expressed little or no GCET1. In thymomas, the non-neoplastic immature T-cells were LMO2-negative, whereas the neoplastic lymphoblasts were LMO2-positive in more than half of the lymphoblastic lymphomas (LBL). Our findings provide new potential assistance in the differential diagnosis of FL to marginal zone lymphoma, classic HL to NLPHL and primary mediastinal B-cell lymphoma, DLBCL to BL, and thymoma to LBL. Finally, HGAL proved to be a prognostic marker for classic HL regarding the background population and in DLBCL regarding the tumor cells.