ROLE OF THE HISTONE DEMETHYLASE LSD1 IN THE REGULATION OF DIFFERENTIATION OF ACUTE PROMYELOCYTIC LEUKEMIA CELLS

Acute promyelocytic leukemia (APL) is characterized by the appearance of blasts, insensitive to physiological retinoic acid (RA)-dependent differentiation and in the majority of the cases, expressing PML-RAR fusion protein. PML-RAR works as a dominant negative counterpart of retinoic acid receptor (RAR) and represses its target genes by cooperating with many epigenetic regulators. Some of the known epigenetic enzymes involved in the APL pathogenesis also interact with LSD1 in other systems. LSD1 is a demethylase involved in transcriptional regulation, mainly acting on dimethylated lysine 4 of Histone H3 (H3K4me2). We showed that LSD1 inhibition sensitizes an APL cell line to physiological RA concentration. Here we characterize for the first time mechanistic insights of LSD1 activity in PML-RAR expressing APL cells. We determined the genomic distribution of LSD1, in particular LSD1 binds both promoters and candidate enhancer regions. We found that LSD1 works as finetuners of genes involved in differentiation and cell growth control as assessed by gene ontology analysis. Moreover, LSD1 modulates H3K4me2 levels at regions enriched in binding sites of master regulators of the myeloid/monocytic lineage, suggesting their regulatory potential. We also described a previously unknown large fraction of genomic loci bound by LSD1 and PR. Commonly bound regions show a peculiar H3K4me2 enrichment and a subset of them resulted dynamically regulated upon differentiation, suggesting a functional interplay between the two proteins in reshaping the local chromatin environment. Overall, our findings contribute to the mechanistic understanding of the role of LSD1 in the sensitization of APL cells to differentiation

Electrochemical properties and electrochemical impedance spectroscopy of polypyrrole-coated platinum electrodes

Polypyrrole (PPy) films of different thickness were characterized by electrochemical impedance spectroscopy (EIS) measurements in acetonitrile and aqueous solutions, containing 0.1 M NaClO4 or sodium dodecylsulfate as the dopant. The PPy films were electrochemically deposited on Pt, and their electrochemical properties studied by cyclic voltammetry. Impedance spectra were obtained at potentials ranging from 0 to 0.8 V/SCE. The EIS data were fitted using two different equivalent electrical circuits (depending on the nature of the dopant). They involve a diffusive capacitance, which increased with the passing charge during electrosynthesis (i.e. film thickness) for ClO4--doped PPy, but was practically unaffected by the film thickness in the case of SDS-doped PPy. Also, a double-layer capacitance was found only in the circuit of ClO4--doped PPy. It increased with the film thickness, and showed a minimum near the open-circuit potential. Finally the charge-transfer resistance (Rct) obtained with SDS is nearly 200-fold higher than that obtained with ClO4- in the same solvent (H2O). With the same dopant (ClO4-), Rct is about five times higher in acetonitrile relative to water. All these EIS results of the different types of PPy suggest a relation with the wettability of the polymer.KEY WORDS: Conducting polymers, Polypyrrole, Electrochemical impedance spectroscopy, Equivalent-electrical circuit, Micellar mediaBull. Chem. Soc. Ethiop. 2006, 20(2), 279-293

Stability and collisions of moving semi-gap solitons in Bragg cross-gratings

We report results of a systematic study of one-dimensional four-wave moving solitons in a recently proposed model of the Bragg cross-grating in planar optical waveguides with the Kerr nonlinearity; the same model applies to a fiber Bragg grating (BG) carrying two polarizations of light. We concentrate on the case when the system's spectrum contains no true bandgap, but only semi-gaps (which are gaps only with respect to one branch of the dispersion relation), that nevertheless support soliton families. Solely zero-velocity solitons were previously studied in this system, while current experiments cannot generate solitons with the velocity smaller than half the maximum group velocity. We find the semi-gaps for the moving solitons in an analytical form, and demonstrated that they are completely filled with (numerically found) solitons. Stability of the moving solitons is identified in direct simulations. The stability region strongly depends on the frustration parameter, which controls the difference of the present system from the usual model for the single BG. A completely new situation is possible, when the velocity interval for stable solitons is limited not only from above, but also from below. Collisions between stable solitons may be both elastic and strongly inelastic. Close to their instability border, the solitons collide elastically only if their velocities c1 and c2 are small; however, collisions between more robust solitons are elastic in a strip around c1=-c2.Comment: 16 pages, 7 figures, Physics Letters A, in pres

Dust Devil Tracks

Dust devils that leave dark- or light-toned tracks are common on Mars and they can also be found on the Earth’s surface. Dust devil tracks (hereinafter DDTs) are ephemeral surface features with mostly sub-annual lifetimes. Regarding their size, DDT widths can range between ∼1 m and ∼1 km, depending on the diameter of dust devil that created the track, and DDT lengths range from a few tens of meters to several kilometers, limited by the duration and horizontal ground speed of dust devils. DDTs can be classified into three main types based on their morphology and albedo in contrast to their surroundings; all are found on both planets: (a) dark continuous DDTs, (b) dark cycloidal DDTs, and (c) bright DDTs. Dark continuous DDTs are the most common type on Mars. They are characterized by their relatively homogenous and continuous low albedo surface tracks. Based on terrestrial and martian in situ studies, these DDTs most likely form when surficial dust layers are removed to expose larger-grained substrate material (coarse sands of ≥500 μm in diameter). The exposure of larger-grained materials changes the photometric properties of the surface; hence leading to lower albedo tracks because grain size is photometrically inversely proportional to the surface reflectance. However, although not observed so far, compositional differences (i.e., color differences) might also lead to albedo contrasts when dust is removed to expose substrate materials with mineralogical differences. For dark continuous DDTs, albedo drop measurements are around 2.5 % in the wavelength range of 550–850 nm on Mars and around 0.5 % in the wavelength range from 300–1100 nm on Earth. The removal of an equivalent layer thickness around 1 μm is sufficient for the formation of visible dark continuous DDTs on Mars and Earth. The next type of DDTs, dark cycloidal DDTs, are characterized by their low albedo pattern of overlapping scallops. Terrestrial in situ studies imply that they are formed when sand-sized material that is eroded from the outer vortex area of a dust devil is redeposited in annular patterns in the central vortex region. This type of DDT can also be found in on Mars in orbital image data, and although in situ studies are lacking, terrestrial analog studies, laboratory work, and numerical modeling suggest they have the same formation mechanism as those on Earth. Finally, bright DDTs are characterized by their continuous track pattern and high albedo compared to their undisturbed surroundings. They are found on both planets, but to date they have only been analyzed in situ on Earth. Here, the destruction of aggregates of dust, silt and sand by dust devils leads to smooth surfaces in contrast to the undisturbed rough surfaces surrounding the track. The resulting change in photometric properties occurs because the smoother surfaces have a higher reflectance compared to the surrounding rough surface, leading to bright DDTs. On Mars, the destruction of surficial dust-aggregates may also lead to bright DDTs. However, higher reflective surfaces may be produced by other formation mechanisms, such as dust compaction by passing dust devils, as this may also cause changes in photometric properties. On Mars, DDTs in general are found at all elevations and on a global scale, except on the permanent polar caps. DDT maximum areal densities occur during spring and summer in both hemispheres produced by an increase in dust devil activity caused by maximum insolation. Regionally, dust devil densities vary spatially likely controlled by changes in dust cover thicknesses and substrate materials. This variability makes it difficult to infer dust devil activity from DDT frequencies. Furthermore, only a fraction of dust devils leave tracks. However, DDTs can be used as proxies for dust devil lifetimes and wind directions and speeds, and they can also be used to predict lander or rover solar panel clearing events. Overall, the high DDT frequency in many areas on Mars leads to drastic albedo changes that affect large-scale weather patterns

Differential cross section and recoil polarization measurements for the gamma p to K+ Lambda reaction using CLAS at Jefferson Lab

We present measurements of the differential cross section and Lambda recoil polarization for the gamma p to K+ Lambda reaction made using the CLAS detector at Jefferson Lab. These measurements cover the center-of-mass energy range from 1.62 to 2.84 GeV and a wide range of center-of-mass K+ production angles. Independent analyses were performed using the K+ p pi- and K+ p (missing pi -) final-state topologies; results from these analyses were found to exhibit good agreement. These differential cross section measurements show excellent agreement with previous CLAS and LEPS results and offer increased precision and a 300 MeV increase in energy coverage. The recoil polarization data agree well with previous results and offer a large increase in precision and a 500 MeV extension in energy range. The increased center-of-mass energy range that these data represent will allow for independent study of non-resonant K+ Lambda photoproduction mechanisms at all production angles.Comment: 22 pages, 16 figure

Measurement of the nuclear multiplicity ratio for Ks0K^0_s hadronization at CLAS

The influence of cold nuclear matter on lepto-production of hadrons in semi-inclusive deep inelastic scattering is measured using the CLAS detector in Hall B at Jefferson Lab and a 5.014 GeV electron beam. We report the $K_s^0$ multiplicity ratios for targets of C, Fe, and Pb relative to deuterium as a function of the fractional virtual photon energy $z$ transferred to the $K_s^0$ and the transverse momentum squared $p_{T}^2$ of the $K_s^0$. We find that the multiplicity ratios for $K^0_s$ are reduced in the nuclear medium at high $z$ and low $p_{T}^2$, with a trend for the $K^0_s$ transverse momentum to be broadened in the nucleus for large $p_{T}^2$.Comment: Submitted to Phys. Lett.

Coherent Photoproduction of pi^+ from 3^He

We have measured the differential cross section for the $\gamma$$^3$He$\rightarrow \pi^+ t$ reaction. This reaction was studied using the CEBAF Large Acceptance Spectrometer (CLAS) at Jefferson Lab. Real photons produced with the Hall-B bremsstrahlung tagging system in the energy range from 0.50 to 1.55 GeV were incident on a cryogenic liquid $^3$He target. The differential cross sections for the $\gamma$$^3$He$\rightarrow \pi^+ t$ reaction were measured as a function of photon-beam energy and pion-scattering angle. Theoretical predictions to date cannot explain the large cross sections except at backward angles, showing that additional components must be added to the model.Comment: 11 pages, 16 figure

Demonstration of a novel technique to measure two-photon exchange effects in elastic e±pe^\pm p scattering

The discrepancy between proton electromagnetic form factors extracted using unpolarized and polarized scattering data is believed to be a consequence of two-photon exchange (TPE) effects. However, the calculations of TPE corrections have significant model dependence, and there is limited direct experimental evidence for such corrections. We present the results of a new experimental technique for making direct $e^\pm p$ comparisons, which has the potential to make precise measurements over a broad range in $Q^2$ and scattering angles. We use the Jefferson Lab electron beam and the Hall B photon tagger to generate a clean but untagged photon beam. The photon beam impinges on a converter foil to generate a mixed beam of electrons, positrons, and photons. A chicane is used to separate and recombine the electron and positron beams while the photon beam is stopped by a photon blocker. This provides a combined electron and positron beam, with energies from 0.5 to 3.2 GeV, which impinges on a liquid hydrogen target. The large acceptance CLAS detector is used to identify and reconstruct elastic scattering events, determining both the initial lepton energy and the sign of the scattered lepton. The data were collected in two days with a primary electron beam energy of only 3.3 GeV, limiting the data from this run to smaller values of $Q^2$ and scattering angle. Nonetheless, this measurement yields a data sample for $e^\pm p$ with statistics comparable to those of the best previous measurements. We have shown that we can cleanly identify elastic scattering events and correct for the difference in acceptance for electron and positron scattering. The final ratio of positron to electron scattering: $R=1.027\pm0.005\pm0.05$ for $=0.206$ GeV$^2$ and $0.830\leq \epsilon\leq 0.943$

Measurement of the Nucleon Structure Function F2 in the Nuclear Medium and Evaluation of its Moments

We report on the measurement of inclusive electron scattering off a carbon target performed with CLAS at Jefferson Laboratory. A combination of three different beam energies 1.161, 2.261 and 4.461 GeV allowed us to reach an invariant mass of the final-state hadronic system W~2.4 GeV with four-momentum transfers Q2 ranging from 0.2 to 5 GeV2. These data, together with previous measurements of the inclusive electron scattering off proton and deuteron, which cover a similar continuous two-dimensional region of Q2 and Bjorken variable x, permit the study of nuclear modifications of the nucleon structure. By using these, as well as other world data, we evaluated the F2 structure function and its moments. Using an OPE-based twist expansion, we studied the Q2-evolution of the moments, obtaining a separation of the leading-twist and the total higher-twist terms. The carbon-to-deuteron ratio of the leading-twist contributions to the F2 moments exhibits the well known EMC effect, compatible with that discovered previously in x-space. The total higher-twist term in the carbon nucleus appears, although with large systematic uncertainites, to be smaller with respect to the deuteron case for n<7, suggesting partial parton deconfinement in nuclear matter. We speculate that the spatial extension of the nucleon is changed when it is immersed in the nuclear medium.Comment: 37 pages, 15 figure