Miracle-dz/UniFAR-FTUs huggingface dataset:
Retinoid‐related molecule AGN193198 potently induces G2M arrest and apoptosis in bladder cancer cells

The novel synthetic retinoid‐related molecule 4‐[3‐(1‐heptyl‐4,4‐dimethyl‐2‐oxo‐1,2,3,4‐tetrahydroquinolin‐6‐yl)‐3‐oxo‐propenyl]benzoic acid (AGN193198) neither binds effectively to retinoic acid receptors (RARs) and retinoid X receptors (RXRs) nor transactivates in RAR‐ and RXR‐mediated reporter assays. Even so, AGN193198 is potent in inducing apoptosis in human prostate and breast carcinoma cells (Keedwell et al., Cancer Res 2004;64:3302–12). Here, we extend these findings to show that AGN193198 potently and rapidly induces apoptosis in bladder carcinoma cell lines. One micromolar of AGN193198 completely abolished the growth of the transitional cell carcinoma lines UM‐UC‐3 and J82, and the squamous cell carcinoma line SCaBER; the transitional cell papilloma line RT‐4 was slightly less sensitive to the growth inhibitory effect of AGN193198. Treated cells accumulated in the G2M phase of the cell cycle. This was accompanied by apoptosis, as revealed by staining cells for exposure of phosphatidylserine at their surface (binding of Annexin V) and FACS analysis of propidium iodide labeled cells. As reported for prostate cancer cells, AGN193198 provoked rapid activation of caspases‐3 (by 6 hr), ‐8 (by 16 hr) and ‐9 (by 6 hr) in bladder cancer cells. These findings suggest that AGN193198 and related compounds, whose mechanism of action does not appear to involve RARs and RXRs, may be useful in the treatment of bladder cancer. © 2005 Wiley‐Liss, Inc.
A comparison of the PWC170 and 20-MST tests of aerobic fitness in adolescent schoolchildren.

The aim of this study was to compare the validity of two field tests of aerobic fitness for predicting maximal oxygen uptake (VO2max) in a group of adolescent schoolchildren. Twenty four schoolboys (means age = 15.6 +/- 0.6 yr) and twenty four schoolgirls (means age = 15.4 +/- 0.7 yr) underwent three different tests of aerobic capacity, with one week separating each assessment. The test were: (a) VO2max, using a continuous, progressive treadmill protocol, (b) a physical work capacity test at a heart rate of 170 beats per minute (PWC170), and (c) a 20-metre endurance shuttle run (20-MST), using a modified lapscoring protocol. Heart rates were monitored continuously in all tests. Results (means +/- SD) for boys n = 23) and girls (n = 18) respectively were: VO2max, 53.3 +/- 5.9 and 42.6 +/- 5.8 ml.kg-1.min-1; PWC170, 2.84 +/- 0.47 and 1.86 +/- 0.39 w.kg-1; 20-MST, 81.7 +/- 15.9 and 50.4 +/- 12.5 laps. Linear regression of PWC170 and 20-MST on VO2max scores (n = 41), revealed similarly high powers of prediction for both field tests (PWC170 vs VO2max, r = 0.84; 20-MST vs VO2max, r = 0.87), with an indication that the shuttle run test may be preferable for use with girls. In conclusion, the PWC170 and 20-MST field tests both appear to be valid predictors of VO2max in adolescent schoolchildren. However constraints of time and tester expertise favour the 20-MST for the assessment of aerobic capacity in the field.
LOCAL ADAPTATION AND COGRADIENT SELECTION IN THE ALPINE PLANT, POA HIEMATA, ALONG A NARROW ALTITUDINAL GRADIENT

Abstract Alpine environments are particularly susceptible to environmental changes associated with global warming but there is potential for alpine plants to adapt to warming if local adaptation occurs and gene flow allows genotypes adapted to low altitudes to colonize higher altitude sites. Here we examine the adaptive potential of a common alpine grass, Poa hiemata, within the restricted alpine habitat of Australian mountains, across a narrow altitudinal gradient replicated in three areas. Grasses at high altitude sites had shorter leaf lengths and larger circumferences than those at lower sites. Transplant experiments with clonal material and plants grown from seed indicated that these differences were partly genetic, with environmental and genetic factors both contributing to the differences between altitudes. Differences in altitudinal forms were also evident in a common garden experiment. Plants showed a home-site advantage in terms of survival. A fitness analysis indicated that at high altitude sites, selection favored plants with short leaves and larger circumferences, whereas these traits were selected in the opposite direction at the low altitude sites. These findings indicate cogradient selection and potential for both plastic and genotypic shifts in response to climate change in P. hiemata.
Critical Role Played by Cyclin D3 in the MyoD-Mediated Arrest of Cell Cycle during Myoblast Differentiation

ABSTRACT During the terminal differentiation of skeletal myoblasts, the activities of myogenic factors regulate not only tissue-specific gene expressions but also the exit from the cell cycle. The induction of cell cycle inhibitors such as p21 and pRb has been shown to play a prominent role in the growth arrest of differentiating myoblasts. Here we report that, at the onset of differentiation, activation by MyoD of the Rb, p21, and cyclin D3 genes occurs in the absence of new protein synthesis and with the requirement of the p300 transcriptional coactivator. In differentiated myocytes, cyclin D3 also becomes stabilized and is found nearly totally complexed with unphosphorylated pRb. The detection of complexes containing cyclin D3, cdk4, p21, and PCNA suggests that cdk4, along with PCNA, may get sequestered into high-order structures held together by pRb and cyclin D3. Cyclin D3 up-regulation and stabilization is inhibited by adenovirus E1A, and this correlates with the ability of E1A to promote pRb phosphorylation; conversely, the overexpression of cyclin D3 in differentiated myotubes counteracts the E1A-mediated reactivation of DNA synthesis. These results indicate that cyclin D3 critically contributes to the irreversible exit of differentiating myoblasts from the cell cycle.
Privacy Preservation in Social Network Based on Anonymization Techniques

Social network data can be released for various purposes, such as statistical analysis, cluster queries, data mining and so on. However, when social network data are released, the privacy of some individuals and organizations may be disclosed. Serious concerns on privacy preservation in social networks have been raised in recent years. In this paper, in order to reduce the privacy disclosure, we propose a privacy preservation model and algorithm based on anonymization techniques for social network data, that is (
A cytometric dual-bead array for analyzing PML-raralpha fusion protein

This study investigated a cytometric dual-bead array used to analyze PML-RARalpha fusion protein. The carboxylated and aminated polystyrene beads were prepared and barcoded with either high or low brightness using a fluorescein isothiocyanate (FITC) penetration method. Using anti-RARalpha antibody, homotype control antibody, barcoded beads and phycoerythrin (PE)-labeled antibody, the analytical capability of the cytometric dual-bead array was tested with two cell models containing a NB4 cell line. Fusion protein levels were normalized using a PE mean fluorescence intensity (MFI) ratio (PE MFI of high brightness beads/PE MFI of low brightness beads). In flow cytometry, the cytometric dual-bead array could analyze PML(L)-RARalpha protein with high specificity, and this assay possessed analytical sensitivity of at least 0.6%. A dilution experiment also demonstrated a concordant result between the logarithm of the PE MFI ratio and the logarithm of the NB4 cell concentration (R2 = 0.9936). When compared with a cytometric single-bead assay, this array exhibited a lower relative standard deviation (R.S.D.) and a lower relative error (R.E.). In conclusion, using the MFI ratio can attenuate data error in fusion protein cytometric analysis, and the cytometric dual-bead array presented here may be of use in the quantification of PML-RARalpha fusion protein.
Enhanced PI3K p110α Signaling Confers Acquired Lapatinib Resistance That Can Be Effectively Reversed by a p110α-Selective PI3K Inhibitor

Although the HER2-targeting agents trastuzumab and lapatinib have improved the survival of patients with HER2-positive breast cancer, resistance to these targeted therapies is a major challenge. To investigate mechanisms of acquired lapatinib resistance, we generated acquired lapatinib resistance cell models by extended exposure of two HER2-positive breast cancer cell lines to lapatinib. Genomic and proteomic analyses revealed that lapatinib-resistant breast cancer cells gained additional phosphoinositide 3-kinase (PI3K) activation through activating mutation in PI3K p110α and/or increasing protein expression of existing mutant p110α. p110α protein upregulation in lapatinib-resistant cells occurred through gene amplification or posttranscriptional upregulation. Knockdown of p110α, but not p110β, the other PI3K catalytic subunit present in epithelial cells, inhibited proliferation of lapatinib-resistant cells, especially when combined with lapatinib. Lapatinib-resistant xenograft growth was inhibited persistently by combination treatment with the p110α-selective PI3K inhibitor BYL719 and lapatinib; the drug combination was also well tolerated in mice. Mechanistically, the combination of lapatinib plus BYL719 more effectively inhibited Akt phosphorylation and, surprisingly, Erk phosphorylation, than either drug alone in the resistance model. These findings indicate that lapatinib resistance can occur through p110α protein upregulation-mediated, and/or mutation-induced, PI3K activation. Moreover, a combinatorial targeted therapy, lapatinib plus BYL719, effectively overcame lapatinib resistance in vivo and could be further tested in clinical trials. Finally, our findings indicate that p110β may be dispensable for lapatinib resistance in some cases. This allows the usage of p110α-specific PI3K inhibitors and thus may spare patients the toxicities of pan-PI3K inhibition to allow maximal dosage and efficacy. Mol Cancer Ther; 13(1); 60–70. ©2013 AACR.
Policy learning over a decade or more and the role of interests therein: The European liberalization policy process of Belgian network industries

When individual actors are involved in a policy process, do they assess and revise their policy preferences according to their interests or are they open to other forms of arguments over time? This study examines the effect of policy actors' interests on policy learning. It is based on a survey conducted in 2012 among 376 Belgian actors (from 38 organizations) involved in the European liberalization policy process of two network industries: the rail and electricity sectors. Borrowing from organizational research and behavioral economics, several hypotheses are drawn from a model of the individual shared by various policy approaches, such as the advocacy coalition framework. A “simple gain scores” approach to the measurement of policy learning is introduced. Regression analyses show that policy actors align their policy preferences with the impacts of policies on their own material well-being (personal interests) and the material prosperity of their organization (organizational interests). This tendency is independent of the importance that policy actors give to their interests in their everyday lives. This suggests that policy actors experience a sort of “interest shift” when they assess their policy preferences over time. This shift, however, exerts a limited influence on policy learning. The theoretical and practical implications are discussed.
Volume regulation of spermatozoa by quinine‐sensitive channels

Bovine spermatozoa were shown to exhibit rapid regulatory volume decrease (RVD) when exposed to hypotonic saline media. This quinine‐ and quinidine‐sensitive regulatory volume decrease was coincident with K+ release due to stretch‐activation of inhibitor‐specific presumptive K+ channels. The regulatory volume decrease response was much faster than a similar phenomenon observed in human peripheral blood lymphocytes. Studies on volume changes in different electrolyte and nonelectrolyte media suggested that: (1) this inhibitor‐specific channel could also be a nonspecific pore in the spermatozoal membrane for nonelectrolytes below 150 daltons; (2) subpopulations (of nearly equal size) of the spermatozoa differ in the expression of the pore; (3) capacitation abolishes this distinction between subpopulations of spermatozoa; and (4) the general case of RVD for other mammalian spermatozoa was also established. Mol. Reprod. Dev. 46:535–550, 1997. © 1997 Wiley‐Liss, Inc.
Variations of perioperative baroreflex sensitivity in hypertensive and normotensive patients

ABSTRACT Background: Impaired baroreflex sensitivity (BRS) is a marker of autonomous dysfunction, which may play an important role in the long-term development of hypertension. Perioperative patients with hypertension are rapidly increasing in all populations worldwide. Objective: To estimate the value of BRS for hypertension in a surgery cohort. Methods: An observational and cross-sectional study was performed, involving 96 patients who underwent video-assisted thoracoscopic pulmonary lobectomy or segmentectomy. Invasive blood pressure and heart rate before and after giving nitroglycerin were measured in 48 normotensive patients and 48 hypertensive patients (25 and 23 undergoing regular treatment hypertensive [HR] and irregular treatment hypertensive [HI], respectively) while entering the operation room, 30 minutes after skin incision, and 10 minutes after skin suture. Results: BRSpreoperative of hypertensive group (Group H) was lower than normotensive group (Group N) (3.49 ± 1.55 vs. 5.75 ± 4.15 ms/mmHg; P < 0.05). BRSintraoperative of Group H was lower than Group N (1.70 ± 1.18 vs. 2.84 ± 1.11 ms/mmHg; P < 0.05). BRSpreoperative of patients in irregular-treated group (Group HI) was lower than regular-treated group (Group HR) (2.92 ± 1.36 vs. 4.31 ± 1.87 ms/mmHg; P < 0.05). BRSintraoperative of Group HI was lower than Group HR (1.45 ± 0.90 vs. 2.08 ± 1.82 ms/mmHg; P < 0.05). BRSintraoperative and BRSpostoperative were lower than BRSpreoperative in each group (P < 0.01). Conclusion: The perioperative autonomic nerve function was significantly impaired in hypertensive patients. This effect was less pronounced for those who were on regular antihypertensive treatment. Attention should be paid to maintain the stability of cardiovascular function, to ensure patients can go through perioperative period safely.
Mapping of the 45M1 epitope to the C‐terminal cysteine‐rich part of the human MUC5AC mucin

Mucins are large glycoproteins protecting mucosal surfaces throughout the body. Their expressions are tissue‐specific, but in disease states such as cystic fibrosis, inflammation and cancer, this specificity can be disturbed. MUC5AC is normally expressed in the mucous cells of the epithelia lining the stomach and the trachea, where it constitutes a major component of the gastric and respiratory mucus. A number of mAbs have been raised against the gastric M1 antigen, an early marker for colonic carcinogenesis. Several of these mAbs recognize epitopes present on MUC5AC, suggesting that MUC5AC is the antigen. However, some of the mAbs raised against the gastric M1 antigen are widely used as antibodies against MUC5AC, despite the fact that their specificity for MUC5AC has not been clearly shown. In this study, we have tested the reactivity of the latter antibodies against a recombinantly expressed C‐terminal cysteine‐rich part of human MUC5AC. We demonstrate for the first time that the widely used mAb 45M1, as well as 2‐12M1 and 166M1, are true antibodies against MUC5AC, with epitopes located in the C‐terminal cysteine‐rich part of the mucin.
Postcards from Another's Home: Visual Dialogues for Cultural Tolerance

P ostcards are a familiar genre-s-they offer stories of anoth er place. and are accessible to many people. 'Ihcy are pr ima ry source artifacts that serve to document moments and cu ltural values of a particu lar time period. hell thou gh they may 110t be intended as "art:' postcards influence our perception s and are thu s part of ou r visual cultu re. Postcards as part of a museum exhibi tion, assum e a differen t status from thos e received in a mailbox. 'Ihey move from private to public nnd test the bound ar ies between "fine" and "popula r" art. An exhibition of everyday objects such as postcards can be a cata lyst for tilt' developm ent of innovative ar t cur ric ula that ask stude nts ! O interact with place. histor y, and language development [Vallance. 1995) and to partici pate in the interrogation , the sociopo litical pe rspective, and the construc tion of new reactive rcp rescntauo ns (Freed man, 2(03 ).
Long-Term Deterioration of Lung Function in Asthmatic Outpatients

Background: Although the long-term deterioration of lung function in asthmatic patients has been described, the exact mechanism remains to be determined. Objectives: The aim of this study was to find correlations between age, sex, atopic status, duration of asthma, asthma severity and the decline in pulmonary function. Method: The medical histories of 1,006 randomly chosen asthmatic outpatients were studied and retrospective data on asthma duration, spirometry results, treatment and symptomatology were gathered. A screening spirometry was performed. Results: 598 women and 408 men (age: 44.59, range 12–95 years) participated in the study. Intermittent asthma was diagnosed in 35.4%, chronic mild asthma in 33.4%, moderate asthma in 23.8% and severe asthma in 7.45% of the patients. Statistically significant correlations between patient age, asthma duration and lung function measurements were found. Linear regression revealed the following differences in lung functions per year of asthma duration: FEV1: –0.882% of predicted; FVC: –0.509% of predicted; FEV1/FVC: –0.324% of predicted. The unadjusted annual decline was 80.1 ml/year (p = 0.00003) in FEV1 and 20.5 ml/year (p = 0.036) in FVC. A multiple regression model revealed that asthma severity appears to be the strongest factor influencing pulmonary function (β = –0.55, p < 0.001 for FEV1). Also, significant associations between pulmonary function measurements, patient age, atopic status and male sex were noted. Conclusions: The results of this large cohort study show that asthmatic patients develop a progressive decline in pulmonary function correlated with age, sex, duration of asthma and asthma severity. Early diagnosis and intervention is necessary to ameliorate any potential negative impact of asthma on lung function.
Costimulation Requirements of Induced Murine Systemic Autoimmune Disease1

Costimulation between T cells and APC is required for productive immune responses. A number of receptor/ligand pairs have been shown to mediate costimulation, including CD28/B7 molecules (CD80 and CD86), CD40/CD40 ligand (CD40L, CD154), and LFA-1 (CD18)/ICAM-1 (CD54). T-B cell costimulation also plays a significant role in autoimmune diseases such as systemic lupus erythematosus. Murine HgCl2-induced autoimmunity (mHgIA) is a T cell-dependent systemic autoimmune disease that shares a number of common pathogenic mechanisms with idiopathic lupus. In this report, the significance of costimulation in mHgIA is examined by attempting to induce disease in mice deficient in either CD40L, CD28, or ICAM-1. Unlike absence of ICAM-1, homozygous deficiencies in either CD40L or CD28 significantly reduced the development of mHgIA. CD40L displayed a gene dosage effect as heterozygous mice also showed reduction of autoantibody responses and immunopathology. Markers of T cell activation such as CD44 and CTLA-4 were associated with disease expression in wild-type and ICAM-1-deficient mice but not in CD40L- or CD28-deficient mice. Absence of CTLA-4 expression in CD40L−/− mice suggests that signaling via both CD28 and CD40L is important for T cell activation and subsequent autoimmunity in mHgIA. Attempts to circumvent the absence of CD40L by increasing CD28 signaling via agonistic Ab failed to elicit CTLA-4 expression. These findings indicate that breaking of self-tolerance in mHgIA requires signaling via both the CD28/B7 and CD40/CD40L pathways.
A Novel Time-Based Readout Scheme for a Combined PET-CT Detector Using APDs

This paper summarizes CERN R&D work done in the framework of the European Commission's FP6 BioCare Project. The objective was to develop a novel "time-based" signal processing technique to read out LSO-APD photodetectors for medical imaging. An important aspect was to employ the technique in a combined scenario for both computer tomography (CT) and positron emission tomography (PET) with effectively no tradeoffs in efficiency and resolution compared to traditional single mode machines. This made the use of low noise and yet very high-speed monolithic front-end electronics essential so as to assure the required timing characteristics together with a high signal-to-noise ratio. Using APDs for photon detection, two chips, traditionally employed for particle physics, could be identified to meet the above criteria. Although both were not optimized for their intended new medical application, excellent performance in conjunction with LSO-APD sensors could be derived. Whereas a measured energy resolution of 16% (FWHM) at the 511 keV photo peak competes favorably with that of 'classical' PMTs, the coincidence time resolution of 1.6 ns FWHM with dual APD readout is typically lower. This is attributed to the stochastic photon production mechanism in LSO and the photon conversion characteristic of the photo diode, as well as to the fluctuations in photon conversion, albeit the APD's superior quantum efficiency. Also in terms of CT counting speed, the chosen readout principle is limited by the intrinsic light decay in LSO (40 ns) for each impinging X-ray.
Real Exchange Rate Misalignment and Economic Growth in Nigeria

This paper investigates the impact of Naira real exchange rate misalignment on Nigeria's economic growth using quarterly data spanning the period 2000-2014. We derive estimates of Real Exchange Rate Misalignment (RERMIS) by computing deviations of the actual real exchange rate from a sustainable equilibrium path that is determined using the Behavioural Equilibrium Exchange Rate (BEER) approach of Edwards (1989). Our modelling approach accounts for the possible effects of endogeneity and structural breaks in the estimated relationships. In terms of the extent of RERMIS, results show that the Naira was on the average overvalued by 0.17 per cent during the study period. The Gregory and Hansen procedure provides evidence of co-integration between output and its determinants with a structural break in 2003Q2. Furthermore, we found empirical support for a negative impact of RERMIS on economic growth. In view of these findings, the study recommends the continued use of market-based exchange rate arrangements as a way of ensuring that the Naira real exchange rate follows its path of sustainable equilibrium. This would complement other government policies aimed at promoting economic growth in the country.