Miracle-dz/UniFAR-FTUs huggingface dataset:
Targeting of Runx 2 by miR-135 and miR-203 Impairs Progression of Breast Cancer and Metastatic Bone Disease

Progressionofbreast cancer tometastatic bonedisease is linked to deregulated expression of the transcription factor Runx2. Therefore, our goal was to evaluate the potential for clinical use of Runx2-targeting miRNAs to reduce tumor growth and bone metastatic burden. Expression analysis of a panel of miRNAs regulating Runx2 revealed a reciprocal relationship between the abundance of Runx2 protein and two miRNAs, miR-135 and miR-203. These miRNAs are highly expressed in normal breast epithelial cells where Runx2 is not detected, and absent in metastatic breast cancer cells and tissue biopsies that express Runx2. Reconstituting metastatic MDA-MB-231-luc cells with miR-135 and miR-203 reduced the abundance of Runx2 and expression of the metastasis-promoting Runx2 target genes IL11, MMP-13, and PTHrP. In addition, tumor cell viability was decreased and migration suppressed in vitro. Orthotopic implantation of MDA-MB-231-luc cells delivered with miR-135 or miR-203, followed by an intratumoral administration of the synthetic miRNAs, reduced the tumor growth and spontaneous metastasis to bone. Furthermore, intratibial injection of these miRNA-delivered cells impaired tumor growth in the bone environment and inhibitedbone resorption. Importantly, reconstitution of Runx2 in MDA-MB-231-luc cells delivered with miR-135 and miR-203 reversed the inhibitory effect of the miRNAs on tumor growth and metastasis. Thus, we have identified that aberrant expression of Runx2 in aggressive tumor cells is related to the loss of specific Runx2-targeting miRNAs and that a clinically relevant replacement strategy by delivery of synthetic miRNAs is a candidate for a therapeutic approach topreventmetastatic bonedisease by this route. Cancer Res; 75(7); 1433–44. 2015 AACR.
Demographic and Life Styles Determinants of Somatic Complaints’ Structures: A Cross-sectional Study on a Large Sample of Iranian Adults Using Factor Mixture Model

Background: To identify somatic complaints dimensions, classify studied population and study the association of demographic and lifestyle factors with somatic complaints dimensions. Methods: In a cross-sectional study conducted on 4763 Iranian adults, somatic complaints were assessed using a comprehensive 30-item questionnaire. Self-administered standard questionnaires were used to assess demographic and lifestyle factors. Factor mixture modeling (FMM) was used to identify somatic complaints dimensions and classify studied population. Results: The mean age of participants was 36.58 ± 0.13 years, 55.8% were females, 81.2% were married, and 57.2% had college education. About 9.4% of individuals were obese, and 34.8% of participants had regular physical activity. Four domains of somatic complaints were extracted, including “psychological,” “gastrointestinal,” “neuro-skeletal,” and “pharyngeal-respiratory. ” Females, obese and inactive participants, and those in low educations had significantly greater scores in terms of four domains than the others (P < 0.05). A two-class, four-factor structure fitted to the somatic complaints based on FMM. Two classes were labeled “high psychological complaints” (519 individuals (11%) and “low psychological complaints” (4243 individuals (89%). There were no significant differences between two classes in terms of demographic and lifestyle factors, except in educational level. Conclusions: This study suggested that somatic complaints had a dimensional-categorical structure within studied population so that it could be useful for dealing with diagnostic and therapeutic approaches. The results did not show any association between somatic complaints dimensions and demographic, lifestyle factors, except in educational level.
Interference Signal Effects on a High-Frequency Monolithic Voltage-Controlled Oscillator: Experiments and Simulations

This paper reflects a part of electromagnetic susceptibility studies conducted on active circuits. An electromagnetic interference (EMI) is injected on a 5 GHz monolithic voltage-controlled oscillator (VCO). This circuit is implemented on a 0.35 μm BiCMOS SiGe process. Injection locking and pulling are put in evidence when the circuit is subject to a high frequency interference with possible frequency band widened with respect to the oscillation frequency band of the VCO. A simulation process based on envelope-transient method is presented. Its main goal is to predict the behavior of the VCO under injection with interference signal power ranging from low to high level.
The dynamics of yeast telomeres and silencing proteins through the cell cycle.

Genes integrated near the telomeres of budding yeast have a variegated pattern of gene repression that is mediated by the silent information regulatory proteins Sir2p, Sir3p, and Sir4p. Immunolocalization and fluorescence in situ hybridization (FISH) reveal 6-10 perinuclear foci in which silencing proteins and subtelomeric sequences colocalize, suggesting that these are sites of Sir-mediated repression. Telomeres lacking subtelomeric repeat elements and the silent mating locus, HML, also localize to the periphery of the nucleus. Conditions that disrupt telomere proximal repression disrupt the focal staining pattern of Sir proteins, but not necessarily the localization of telomeric DNA. To monitor the telomere-associated pools of heterochromatin-binding proteins (Sir and Rap1 proteins) during mitotic cell division, we have performed immunofluorescence and telomeric FISH on populations of yeast cells synchronously traversing the cell cycle. We observe a partial release of Rap1p from telomeres in late G2/M, although telomeres appear to stay clustered during G2-phase and throughout mitosis. A partial release of Sir3p and Sir4p during mitosis also occurs. This is not observed upon HU arrest, although other types of DNA damage cause a dramatic relocalization of Sir and Rap1 proteins. The observed cell cycle dynamics were confirmed by direct epifluorescence of a GFP-Rap1p fusion. Using live GFP fluorescence we show that the diffuse mitotic distribution of GFP-Rap1p is restored to the interphase pattern of foci in early G1-phase.
A hybrid framework for assessing socioeconomic drought: Linking climate variability, local resilience, and demand

Socioeconomic drought broadly refers to conditions whereby the water supply cannot satisfy the demand. Most previous studies describe droughts based on large‐scale meteorological/hydrologic conditions, ignoring the demand and local resilience to cope with climate variability. Reservoirs provide resilience against climatic extremes and play a key role in water supply and demand management. Here we outline a unique multivariate approach as a measure of socioeconomic drought, termed Multivariate Standardized Reliability and Resilience Index (MSRRI). The model combines information on the inflow and reservoir storage relative to the demand. MSRRI combines (I) a “top‐down” approach that focuses on processes/phenomena that cannot be simply controlled or altered by decision makers, such as climate change and variability, and (II) a “bottom‐up” methodology that represents the local resilience and societal capacity to respond or adapt to droughts. MSRRI is based on a nonparametric multivariate distribution function that links inflow‐demand reliability indicator to water storage resilience indicator. These indicators are used to assess socioeconomic drought during the Australian Millennium drought (1998–2010) and the 2011–2014 California drought. The results show that MSRRI is superior to univariate indices because it captures both early onset and persistence of water stress over time. The suggested framework can be applied to both individual reservoirs and a group of reservoirs in a region, and it is consistent with the currently available standardized drought indicators. MSRRI provides complementary information on socioeconomic drought development and recovery based on reservoir storage and demand that cannot be achieved from the commonly used drought indicators.
GENETICS OF RELATIVE TOE LENGTHS.

Twin and pedigree data are presented which indicate that relative length of hallux and adjacent second toe is based on simple Mendelian genetic factors. The normal anatomical trait involves two alleles and a single autosomal locus. The factor for relatively long hallux is recessive to the one for relatively long second toe. There is no evidence of sex influence. Penetrance is 100%. Expressivity is variable, and bilateral discordance is observed in a minority of heterozygous subjects. In every such case, the dominant genotype is expressed in the right foot. The recessive and dominant phenotypes occur, respectively, in 76% and 24% of the greater Cleveland area Caucasian population. Gene frequencies in this population are 87% and 13%, respectively, for the recessive and dominant allele.
Positive regulation of amidase synthesis in Pseudomonas aeruginosa

Mutants of Pseudomonas aeruginosa were isolated that were acetamide-negative in growth phenotype at 41 degrees C and constitutive for amidase synthesis at 28 degrees C. Two mutants were derived from the magno-constitutive amidase mutant PAC111 (C11), and a third from a mutant that had enhanced inducibility by formamide, PAC153 (F6). The three temperature-sensitive mutants produced amidases with the same thermal stabilities as the wild-type enzyme. Cultures growing exponentially at 28 degrees C, synthesizing amidase constitutively, ceased amidase synthesis almost immediately on transfer to 41 degrees C. Cultures growing at 41 degrees C were transferred to 28 degrees C and had a lag of about 0.5 of a generation before amidase synthesis became detectable. Pulse-heating for 10 min at 45 degrees C of a culture growing exponentially at 28 degrees C resulted in a lag of about 0.5 of a generation before amidase synthesis recommenced after returning to 28 degrees C. Acetamide-negative mutants that were unable to synthesize amidase at any growth temperature were isolated from an inducible strain producing the mutant B amidase PAC398 (IB10). Two mutants were examined that gave revertants producing B amidase but with novel regulatory phenotypes. It is suggested that amidase synthesis is regulated by positive control exerted by gene amiR.
Interlaboratory variation of plasma total homocysteine measurements: results of three successive homocysteine proficiency testing surveys.

BACKGROUND Numerous studies have demonstrated that increased plasma total homocysteine (tHcy), whether measured after fasting or after a methionine load, is associated with increased risk for cardiovascular and thromboembolic diseases. However, little information is available regarding interlaboratory variation of tHcy measurements, especially at the increased tHcy concentrations observed after loading. METHODS We conducted three Homocysteine Proficiency Testing Surveys at 6-month intervals. Sets of five plasma pools with endogenous tHcy concentrations ranging from 5 to 48 micromol/L were sent to participants. We received 11, 23, and 17 responses in the first, second, and third surveys, respectively. The following methods were used by participating laboratories: fluorescence polarization immunoassay (FPIA); HPLC with fluorescent detection (HPLC-FD), further subdivided by type of reduction/derivatization; HPLC with electrochemical detection (HPLC-ED); amino acid analyzer with ninhydrin detection; and liquid chromatography-electrospray tandem mass spectrometry (LC-MS/MS). RESULTS In surveys 1 and 2, no notable differences among the mean tHcy values obtained by the different methods performed were observed. In survey 3, tHcy values obtained by the FPIA method were significantly lower (P <0.05) at increased tHcy concentrations (34 micromol/L) compared with values obtained by HPLC-FD regardless of reduction/derivatization agents used. Our laboratory confirmed the observation that tHcy values obtained by the FPIA method differed from those obtained by HPLC-FD at increased tHcy concentrations by reanalyzing each pool 10 times by FPIA and HPLC-FD using tributylphosphine-ammonium 7-fluoro-2,1,3-benzoxadiazole-4-sulfonate (P <0.001 for tHcy >19 micro mol/L). The mean among-method variations in surveys 1, 2, and 3 were 19%, 12%, and 9.6%, respectively. When results of the three surveys were combined, the mean among-method variation on 170 samples was 13%. Within-method variation was lowest for the FPIA method (4.4%), and ranged from 11-20% for HPLC methods. CONCLUSIONS Various degrees of imprecision and lack of correlation among tHcy methods indicate that there is a need to improve analytical precision, decrease analytical difference, and standardize tHcy measurements among laboratories.
Application of Principal Component Analysis in Evaluating Influence Factors of Evaporation in Northern Cold Area

There are many meteorological factors affecting evaporation, which are not only considered comprehensively, but also their influence degree respectively. The contribution of each factor to principle component can be reflected by the coefficient of each factor in principal component equation, and then the main factor can be determined. Taking Chahayang irrigation area in Heilongjiang province for example, the data of influence factors from May to September in 2007 such as temperature, relative humidity, wind speed, vapor pressure and sunshine is analyzed with Principal Component Analysis (PCA for short). The results show that the change of evaporation is the result of the combined effect of numerous metrological factors which interact with each other, but when the temperature is kept unchanged, the average sunshine turns out to be the main factor.
(Bio)ethicists and (Bio)ethical Expertise in National Ethical Advisory Bodies: Roles, Functions and Perceptions

Over the past decades, (bio)ethical expertise has been gaining considerable influence in decision-making processes on various levels, but the nature and role of bioethical expertise and experts has only rarely been subject to empirical investigation in institutional contexts. One of the characteristics of modern (bio)ethics is its “empirical” and “policy” turn, which has led to the formation of institutions that were given the remit to provide political decision-makers with ethical advice on dealing with contentious developments in new and emerging sciences and technologies. In Europe, such national Ethical Advisory Bodies (EABs) have become a key mechanism in the legitimization of contested sociopolitical decisions. (Bio)ethicists can be seen as important experts in the workings of such institutions, but the role and function of (bio)ethical expertise and (bio)ethicists have so far not been systematically investigated in European national EABs. The present article thus tackles some of the theoretical and practical questions concerning ethicists and ethics in the context of EABs by combining theoretical reflection with empirical investigation. The first part provides a brief sketch of the development of modern (bio)ethics and its institutionalization in various expert bodies, especially EABs at the national level in Europe. The second part explores theoretical questions relating to the notion of ethical and moral expertise, as well as the attributes that ethicists should possess in order to be able to perform the role of experts in ethics within EABs. The third part compares theory to practice by examining the results of a survey conducted among European national EABs on how ethicists and ethical expertise are actually perceived by EABs and what functions they perform in such institutions.
Association Analysis of Peroxisome Proliferator-Activated Receptor Gamma Polymorphisms and Late Onset Alzheimer’s Disease in the Finnish Population

Alzheimer’s disease (AD), especially late-onset AD (LOAD), is a complex disease. To date, the only established genetic risk factor for LOAD is apolipoprotein E (APOE) Ε4, which explains partially the risk of the disease and modifies the age of onset. Peroxisome proliferator-activated receptor γ (PPARγ) regulates the transcription of BACE1 as well as inflammatory responses in the brain and atherosclerotic risk factors known to be involved also in AD. Based on these findings, the gene encoding PPARγ can be viewed as an interesting candidate in AD. We examined the effect of the two previously reported variants of PPARγ polymorphisms, the Pro12Ala and exon 6 C478T, on the risk of LOAD and age of onset in a population-based follow-up sample of aged subjects (125 LOAD patients and 462 non-demented controls). The genetic risk of AD was not significantly associated with the studied polymorphisms, but the PPARγ Ala12-478T genotype carriers were significantly younger at the onset of dementia than the non-carriers (p = 0.026). These results suggest that the PPARγ gene may modify the age of onset in LOAD.
Measuring Adherence to a Women’s Walking Program

The purpose of this study is to demonstrate the use of a self-report exercise log and a heart-rate monitor in the measurement of adherence to the dimensions of an exercise prescription and to propose an alternative way to define adherence to a 24-week home-based women’s walking program, which reflects the dynamic process of behavior change. Adherence was measured with exercise logs, Polar Vantage XL Heart-Rate Monitors, and pre-to postintervention change in VO2 max. Of the dimensions of the exercise prescription, frequency of walks documented by both the heart-rate monitor and the exercise log had a higher correlation than duration and intensity of walking, with change in VO2 max suggesting that frequency was potentially the most predictive adherence measure. Examination of the total number of walks and the number and sequence of weeks without walks over the 24-week intervention revealed dynamic patterns of adherence suggesting variation in the degree of behavioral change.
Contribution of serotonin to liver injury following canine small-intestinal ischemia and reperfusion.

Intestinal ischemia and reperfusion (I/R) has been shown to be associated with multiple organ damages. Serotonin (5-hydroxytriptamine; 5-HT), which is synthesized in the enterochromaffin cells in the intestine and stored in platelets, is known to play an important role in platelet aggregation and vasoconstriction and may ultimately enhance such organ injuries. The purpose of this study was to investigate the association between liver damage and 5-HT levels in the liver after intestinal I/R. The entire canine small intestine, isolated on a vascular pedicle that consisted of the proximal superior mesenteric artery and superior mesenteric vein, was subjected to 4-h ischemia by clamping these vessels and the marginal arteries supplying the proximal and distal ends of the small intestine. Hepatic blood flow, liver tissue blood flow, bile flow rate, and hepatic venous ketone body ratio (HVKBR) were measured before and at the end of intestinal ischemia and at 5, 15, and 30 min, and 1 and 2 h after reperfusion. 5-HT levels in plasma of the portal vein and hepatic vein were assayed at the same intervals. Time-matched, sham-operated animals served as controls. Intestinal I/R significantly decreased the liver tissue flow, bile flow rate, and HVKBR. Compared to those in controls, 5-HT levels in the portal vein and hepatic vein were markedly increased after reperfusion. Furthermore, intravenous administration of 5-HT receptor antagonists attenuated the liver dysfunction after intestinal reperfusion. These results suggest that intestinal I/R induces continuous disturbance of hepatic microcirculation, leading to liver dysfunction, and that 5-HT may be implicated as one of the mediators of liver dysfunction after intestinal I/R.
Involvement of topoisomerases in replication, transcription, and packaging of the linear adenovirus genome

The role of topoisomerases in the replication of human adenovirus type 5 was investigated with topoisomerase inhibitors. Both topoisomerase I and topoisomerase II inhibitors blocked adenovirus replication when added at the time of infection. Both types of inhibitors induced strand cleavages at specific sites in the adenovirus early templates. The cleavage sites were mapped near the 5' and 3' ends of the genes transcribed early during infection. At late times after infection, camptothecin, a topoisomerase I inhibitor, inhibited adenovirus DNA replication and induced the formation of single- and double-stranded fragments with breakpoints located at defined regions of the viral genome. The topoisomerase II inhibitors, VP-16 (etoposide) and ellipticine, did not block adenovirus DNA replication and did not induce an appreciable amount of double-strand cleavages in the newly synthesized DNA. On the other hand, VP-16 promoted double-strand cleavages at specific sites of nonreplicating adenovirus DNA. The packaging of adenovirus DNA into virus particles, which contain supercoiled adenovirus DNA (M.-L. Wong and M.-T. Hsu, Nucleic Acids Res. 17:3535-3550, 1989), was inhibited by the topoisomerase II inhibitors. Transcription of adenovirus major late genes was inhibited by both topoisomerase I and topoisomerase II inhibitors. In addition, camptothecin caused a premature termination of major late transcription. Electron microscopic analysis showed that adenovirus templates late after infection were arranged in topologically constrained loop domains. Together, these data provide evidence for the requirement of topoisomerase activities in the replication, transcription, and packaging of the linear adenovirus genome.
Assessing Relationships between Forest Spatial Patterns and Fire History with Fusion of Optical and Microwave Remote Sensing

Abstract In this paper, we tested the use of active and passive sensor fusion for relating forest fire history to landscape spatial patterns. Principal Components Analysis (PCA) was implemented to combine Landsat Thematic Mapper (TM) and Shuttle Imaging Radar (SIR-C) data from October 1994. Resulting PCs were converted to landscape patch maps. Plots with known fire history were delineated using a fire atlas of the study area. These plots came from four fire history categories: unburned (nine plots), once burned (three plots), twice burned (three plots), and multiple burned (three plots). Landscape metrics were calculated for each plot, including a shape index, mean patch size, Shannon's Diversity Index, and Shannon's Evenness Index. Spearman's Rank Correlation Analysis was used to compare the patch map‐derived landscape metrics to fire history characteristics, such as average fire‐free interval and number of fire‐free years in different time periods. Results showed that landscape patterns derived from fused data were significantly (p < 0.05) related to fire history and typically performed better than SIR-C data (a greater number of significant correlations), but not as well as TM data.