The ESO Key-Programme ``A Homogeneous Bright QSO Survey'' - I The Methods and the ``Deep'' Fields

This is the first paper in a series aimed at defining a statistically significant sample of QSOs in the range $15 < B < 18.75$ and $0.3 < z < 2.2$. The selection is carried out using direct plates obtained at the ESO and UK Schmidt Telescopes, scanned with the COSMOS facility and searched for objects with an ultraviolet excess. Follow-up spectroscopy, carried out at ESO La Silla, is used to classify each candidate. In this initial paper, we describe the scientific objectives of the survey; the selection and observing techniques used. We present the first sample of 285 QSOs ($M_B < -23$) in a 153 deg$^2$ area, covered by the six ``deep'' fields, intended to obtain significant statistics down $B \simeq 18.75$ with unprecedented photometric accuracy. From this database, QSO counts are determined in the magnitude range $17 < B < 18.75$.Comment: 21 pages uuencoded compressed postscript, to appear in Astronomy and Astrophysics Supplements, 199

Can the Pioneer anomaly be of gravitational origin? A phenomenological answer

In order to satisfy the equivalence principle, any non-conventional mechanism proposed to gravitationally explain the Pioneer anomaly, in the form in which it is presently known from the so-far analyzed Pioneer 10/11 data, cannot leave out of consideration its impact on the motion of the planets of the Solar System as well, especially those orbiting in the regions in which the anomalous behavior of the Pioneer probes manifested itself. In this paper we, first, discuss the residuals of the right ascension \alpha and declination \delta of Uranus, Neptune and Pluto obtained by processing various data sets with different, well established dynamical theories (JPL DE, IAA EPM, VSOP). Second, we use the latest determinations of the perihelion secular advances of some planets in order to put on the test two gravitational mechanisms recently proposed to accommodate the Pioneer anomaly based on two models of modified gravity. Finally, we adopt the ranging data to Voyager 2 when it encountered Uranus and Neptune to perform a further, independent test of the hypothesis that a Pioneer-like acceleration can also affect the motion of the outer planets of the Solar System. The obtained answers are negative.Comment: Latex2e, 26 pages, 6 tables, 2 figure, 47 references. It is the merging of gr-qc/0608127, gr-qc/0608068, gr-qc/0608101 and gr-qc/0611081. Final version to appear in Foundations of Physic

Marcosian Atrocities: Historical Revisionism and the Legal Constraints on Forgetting

The Philippines resoundingly cried ‘never again’ to the horrors of the Marcos dictatorship through the People Power revolution of 1986. Thirty years later, the Filipino people have come to realise that success is indeed fleeting. On 18 November 2016, the remains of Philippine dictator Ferdinand E. Marcos were buried in the Libingan ng mga Bayani—the Heroes’ Cemetery. While the Philippine Supreme Court insists that the hero’s burial conferred to the author of the nation’s darkest chapter is a political question, from established doctrines here and abroad, the authors seek to derive the political answer. This article will look at the legitimacy of memory laws within the Philippine Constitutional framework. Finding guidance from the Auschiwtz lie case of the German Constitutional Court, the article seeks to combat historical revisionism and prohibit the Marcosian lie. Our research begins by looking at the resurgence of authoritarianism as seen through the populist presidency of Rodrigo Roa Duterte. We will then proceed to address the threshold issue of state-sanctioned narratives. Recognising that the duty to establish the truth involves the power to determine the narrative, the authors will reconcile the conflicting demands of the freedom of thought and the right to the truth. We will then proceed by utilising the fact-opinion distinction to demonstrate how the Marcosian lie may be the valid subject of regulation. The last phase of the research looks into the approaches adopted by the United Nations (un) Human Rights Committee and the European Court of Human Rights in dealing with negationism and historical revisionism

Surface plasmon resonance based analysis of the binding of LYAR protein to the rs368698783 (G>A) polymorphic Aγ-globin gene sequences mutated in β-thalassemia

Recent studies have identified and characterized a novel putative transcriptional repressor site in a 5' untranslated region of the Aγ-globin gene that interacts with the&nbsp;Ly-1 antibody reactive clone (LYAR) protein. LYAR binds the 5'-GGTTAT-3' site of the Aγ-globin gene, and this molecular interaction causes repression of gene transcription. In β-thalassemia patients, a polymorphism has been demonstrated (the rs368698783 G&gt;A polymorphism) within the 5'-GGTTAT-3' LYAR-binding site of the Aγ-globin gene. The major results gathered from surface plasmon resonance based biospecific interaction analysis (SPR-BIA) studies (using crude nuclear extracts, LYAR-enriched lysates, and recombinant LYAR) support the concept that the rs368698783 G&gt;A polymorphism of the Aγ-globin gene attenuates the efficiency of LYAR binding to the LYAR-binding site. This conclusion was fully confirmed by a molecular docking analysis. This might lead to a very important difference in erythroid cells from β-thalassemia patients in respect to basal and induced levels of production of fetal hemoglobin. The novelty of the reported SPR-BIA method is that it allows the characterization and validation of the altered binding of a key nuclear factor (LYAR) to mutated LYAR-binding sites. These results, in addition to theoretical implications, should be considered of interest in applied pharmacology studies as a basis for the screening of drugs able to inhibit LYAR-DNA interactions. This might lead to the identification of molecules facilitating induced increase of γ-globin gene expression and fetal hemoglobin production in erythroid cells, which is associated with possible reduction of the clinical severity of the β-thalassemia phenotype. Graphical abstract

The optical variability of QSOs

The long-term variability of a sample of 180 optically selected QSOs in the field of the Selected Area 94 has been studied. The relations between variability and luminosity and between variability and redshift have been investigated by means of statistical estimators that are ''robust'' and allow at the same time to eliminate the influence of the measurement errors. A comparison is carried out with the results of two other samples of QSOs, in the fields of the South Galactic Pole (Hook et al. 1994) and of the Selected Area 57 (Trevese et al. 1994). Merging the three samples provides a total of 486 QSOs. The analysis in the QSOs rest frame of both the ensemble structure function (SF) and the individual variability indices show that: 1) a negative correlation between variability and luminosity is clearly present, in the sense that more luminous QSOs show less variability; 2) a significant positive correlation exists between variability and redshift; 3) such correlations may be equally well parameterized either with a model in which the timescale of the variability is fixed for all the QSOs (tau similar to 2.4 yr), while the amplitude linearly increases with the absolute magnitude and redshift, or with a model in which the timescale of the variability linearly depends on the absolute magnitude and the amplitude is only a function of the redshift. The same analysis carried out in the observer's frame provides the following results: 1) there is a negative correlation between variability and luminosity; 2) the timescale of variability does not depend significantly either on the absolute magnitude or on the redshift; 3) the ensemble structure function is well represented by a parameterization in which, with a fixed timescale of about 5.5 yr, the amplitude linearly increases with the absolute magnitude; 4) although the general behaviour of the SF does not show a systematic variation of the timescale and/or amplitude with redshift, if we examine the average variability index for objects with -25 > M(B) > -27, we find that below redshift 1 quasars are significantly less variable than at higher redshift. The implications in terms of the black-hole, starburst and microlensing models are briefly discussed

Peptide nucleic acids targeting β-globin mRNAs selectively inhibit hemoglobin production in murine erythroleukemia cells.

In the treatment of hemoglobinopathies, amending altered hemoglobins and/or globins produced in excess is an important part of therapeutic strategies and the selective inhibition of globin production may be clinically beneficial. Therefore the development of drug-based methods for the selective inhibition of globin accumulation is required. In this study, we employed peptide nucleic acids (PNAs) to alter globin gene expression. The main conclusion of the present study was that PNAs designed to target adult murine β-globin mRNA inhibit hemoglobin accumulation and erythroid differentiation of murine erythroleukemia (MEL) cells with high efficiency and fair selectivity. No major effects were observed on cell proliferation. Our study supports the concept that PNAs may be used to target mRNAs that, similar to globin mRNAs, are expressed at very high levels in differentiating erythroid cells. Our data suggest that PNAs inhibit the excess production of globins involved in the pathophysiology of hemoglobinopathies

Peptide nucleic acids targeting the murine beta-globin mRNAs selectively inhibit hemoglobin production in Murine Erythroleukemia (MEL) cells.

In sickle-cell anemia (SCA), HbS appears to be an important therapeutic target, since its polymerization is responsible for sickling of SCA red- blood cells and important adverse clinical parameters. Inhibition of beta- globin might be beneficial, allowing further reduction of sickling properties. Therefore drugs-based methods enabling efficient inhibition of accumulation of this defective globin can be of great interest. In this field of investigation peptide nucleic acids (PNAs) might be of great interest as potent antisense molecules targeting mRNAs. Murine Erythroleukemia (MEL) cells were chosen as experimental model system, in consideration of the fact that they express, under treatment with different inducers, almost adult hemoglobins, being therefore an excellent and reliable cellular “biosensor” for alteration of beta-globin gene expression using, as red-out assay, the simple benzidine-test for Hb accumulation. We designed (R8-GAGGCAGAGGATAGGTCT) an anti-M-βglob-PNA able to hybridize to a region of both mouse βmajor- and βminor-globin mRNAs exhibiting similar predicted secondary structure. This PNA was linked to a polyarginine tail (R8) in order to improve uptake. We found that the Anti-M-βglob-PNA inhibits the erythroid differentiation and Hb production induced in MEL cells by DMSO and HMBA. No effects on cell growth was observed. In addition, the same PNA failed to inhibit the expression of globin genes when administered to control human K562 cells. Our study allow to propose PNAs to down- regulate pathological hemoglobins involved in the onset of several clinical problems, such as the sickle-hemoglobin (HbS) which is responsible for polymerization and the sickling feature of the SCA red- blood cells

Sirolimus-mediated induction of fetal hemoglobin in beta-thalassemia: impact of the XmnI rs74482144 polymophism

The in vivo effects of sirolimus on the induction of fetal hemoglobin (HbF) is of key importance for therapeutic protocols in a variety of hemoglobinopathies, including β-thalassemia and sickle-cell disease (SCD)