Quelques propriétés physico-chimiques des verres CdGe1-xSb xAs2

Glassy compounds of the system CdGe1-xSbxAs 2 with x varying from 0 to 0.5 have been investigated by means of differential thermal analysis and microhardness measurements. The density and the electrical conductivity have been measured for different compounds. The thermograms show a progressive decrease of the glass transition and crystallization temperatures as the Sb content increases. The microhardness decreases linearly in the composition range 0 ≤ x ≤ 0.3 and tends to be stabilized for higher composition. It is found that the heat capacity measured for two compounds (x = 0, x = 0.5) increases abruptly near the glass transition ; the increase is of less magnitude for compound containing Sb. The crystallization process in different compounds is found to obey approximatively first-order kinetics. The partial substitution of Sb for Ge leads to a strong decrease of the crystallization rate. The enthalpy of crystallization is found to decrease slightly with the increase of Sb content. Optical microscope observations and microhardness measurements on crystallized compounds show the appearance of several phases for samples containing Sb. The chemical composition of these phases has been determined by means of scanning electron microscopy.Des échantillons de verres du système CdGe1-xSbxAs 2 avec 0 ≤ x ≤ 0,5 ont été caractérisés par l'analyse thermique différentielle (A. T. D.) et les mesures de microdureté. La masse spécifique et la conductivité électrique ont été également mesurées pour différentes compositions. Les thermogrammes A. T. D. révèlent une diminution progressive des températures de transition vitreuse et de cristallisation. La microdureté décroît linéairement pour 0 ≤ x ≤ 0,3 et tend à se stabiliser pour des compositions x ≽ 0,3. La chaleur spécifique mesurée pour deux compositions x = 0 et x = 0,5 montre un accroissement brusque au voisinage de la température de transition vitreuse ; l'accroissement est moins élevé pour le composé contenant Sb. Le processus de cristallisation dans les différents composés obéit approximativement à une cinétique du premier ordre. Le remplacement d'une concentration atomique de Ge par une même quantité de Sb conduit à une forte décroissance de la vitesse de cristallisation. L'enthalpie de cristallisation diminue légèrement quand la teneur en Sb augmente. Les observations au microscope optique et les mesures de microdureté sur les échantillons cristallisés révèlent l'apparition de plusieurs phases dans des composés contenant Sb. La composition chimique de ces phases a été déterminée à l'aide de la microscopie électronique à balayage

Electron transport and kinetics of transformations in the amorphous alloy Ni66B34

The amorphous alloy Ni66B34 prepared by chemical methods at 20 °C appears to be formed of a large number of clusters of about 8 Å, surrounded by a disordered matrix, the former giving to the latter local order similar to that of the boride Ni3B. The kinetics of transformations which accompany all thermal treatments of the material at a temperature above 20 °C are deduced from study of the resulting isotherm of decreasing electrical resistivity. Two regions of linear increase in apparent activation energy Ea are defined versus annealing temperature : the first in the temperature domain where the alloy maintains its amorphous character; the second beyond 350 °C, corresponding to precipitation of the crystallized phases.L'alliage amorphe Ni66B34 préparé par voie chimique à 20° C apparait comme constitué d'un grand nombre d'agrégats de 8 Å environ, noyés dans une matrice désordonnée, et qui lui confère un ordre local voisin de celui du borure Ni3B. La cinétique des transformations qui accompagnent tout traitement thermique du matériau à une température supérieure à 20 °C est déduite de l'étude des isothermes de décroissance de la résistivité électrique qui en résulte. Deux domaines d'accroissement linéaire de l'énergie d'activation apparente Ea sont définis en fonction de la température de recuit : le premier dans le domaine de températures où l'alliage conserve son caractère amorphe, le deuxième au-delà de 350 °C qui correspond à la précipitation des phases cristallines

Noncanonical function of AGO2 augments T-cell receptor signaling in T-cell prolymphocytic leukemia

T-cell prolymphocytic leukemia (T-PLL) is a chemotherapy-refractory T-cell malignancy with limited therapeutic options and a poor prognosis. Current disease concepts implicate TCL1A oncogene-mediated enhanced T-cell receptor (TCR) signaling and aberrant DNA repair as central perturbed pathways. We discovered that recurrent gains on chromosome 8q more frequently involve the AGO2 gene than the adjacent MYC locus as the affected minimally amplified genomic region. AGO2 has been understood as a pro-tumorigenic key regulator of microRNA (miR) processing. In primary tumor material and cell line models, AGO2 overrepresentation associated (i) with higher disease burden, (ii) with enhanced in vitro viability and growth of leukemic T-cells, and (iii) with miR-omes and transcriptomes that highlight altered survival signaling, abrogated cell cycle control, and defective DNA damage responses. Moreover, AGO2 elicited immediate, rather than non-RNA mediated, effects in leukemic T-cells. Systems of genetically modulated AGO2 revealed that it enhances TCR signaling, particularly at the level of ZAP70, PLCγ1, and LAT kinase phospho-activation. In global mass-spectrometric analyses, AGO2 interacted with a unique set of partners in a TCR-stimulated context, including the TCR kinases LCK and ZAP70, forming membranous protein complexes. Models of their three-dimensional structure also suggested that AGO2 undergoes post-transcriptional modi-fications by LCK. This novel TCR-associated non-canonical function of AGO2 represents, in addition to TCL1A-mediated TCR signal augmentation, another enhancer mechanism of this important deregulated growth pathway in T-PLL. These findings further emphasize TCR signaling intermediates as candidates for therapeutic targeting

Small molecule inhibition of phosphatidylinositol-3,4,5-triphosphate (PIP3) binding to pleckstrin homology domains

The PI3-kinase (PI3K) pathway regulates many cellular processes, especially cell metabolism, cell survival, and apoptosis. Phosphatidylinositol-3,4,5-trisphosphate (PIP3), the product of PI3K activity and a key signaling molecule, acts by recruiting pleckstrin-homology (PH) domain-containing proteins to cell membranes. Here, we describe a new structural class of nonphosphoinositide small molecule antagonists (PITenins, PITs) of PIP3–PH domain interactions (IC50 ranges from 13.4 to 31 μM in PIP3/Akt PH domain binding assay). PITs inhibit interactions of a number of PIP3-binding PH domains, including those of Akt and PDK1, without affecting several PIP2-selective PH domains. As a result, PITs suppress the PI3K-PDK1-Akt pathway and trigger metabolic stress and apoptosis. A PIT-1 analog displayed significant antitumor activity in vivo, including inhibition of tumor growth and induction of apoptosis. Overall, our studies demonstrate the feasibility of developing specific small molecule antagonists of PIP3 signaling