Distinct promoter elements mediate the co-operative effect of Brn-3a and p53 on the p21 promoter and their antagonism on the Bax promoter

Although the promoters of both the Bax and p21 genes are activated by p53, they differ in the effect on this activation of the POU family transcription factor Brn-3a. Thus, Brn-3a inhibits activation of the Bax promoter by p53 but enhances the ability of p53 to activate the p21 promoter. We demonstrate that repression of p53-mediated activation of the Bax promoter involves a complex upstream sequence in which two Brn-3a response elements flank the p53 response element. In contrast, a minimal p21 promoter is activated by Brn-3a and such activation cannot be abolished without abolishing basal promoter activity. Moreover, synergistic activation by Brn-3a and p53 continues to be observed when the p53-binding sites in the p21 promoter are substituted by the Bax p53 site or by the region of the Bax promoter essential for Brn-3a-mediated repression, indicating that the p21 core promoter plays a central role in this response. The significance of these effects is discussed in terms of the different responses of the Bax and p21 promoters and the overlapping but distinct roles of Brn-3a and p53 in neuronal growth arrest and apoptosis

1.5V fully programmable CMOS Membership Function Generator Circuit with proportional DC-voltage control

A Membership Function Generator Circuit (MFGC) with bias supply of 1.5 Volts and independent DC-voltage programmable functionalities is presented. The realization is based on a programmable differential current mirror and three compact voltage-to-current converters, allowing continuous and quasi-linear adjustment of the center position, height, width and slopes of the triangular/trapezoidal output waveforms. HSPICE simulation results of the proposed circuit using the parameters of a double-poly, three metal layers, 0.5 μm CMOS technology validate the functionality of the proposed architecture, which exhibits a maximum deviation of the linearity in the programmability of 7 %

High Gain Amplifier with Enhanced Cascoded Compensation

A two-stage CMOS operational amplifier with both, gain-boosting and indirect current feedback frequency compensation performed by means of regulated cascode amplifiers, is presented. By using quasi-floating-gate transistors (QFGT) the supply requirements, the number of capacitors and the size of the compensation capacitors respect to other Miller schemes are reduced. A prototype was fabricated using a 0.5 μm technology, resulting, for a load of 45 pF and supply voltage of 1.65 V, in open-loop-gain of 129 dB, 23 MHz of gain-bandwidth product, 60o phase margin, 675 μW power consumption and 1% settling time of 28 ns

Discovery of a wide companion near the deuterium burning mass limit in the Upper Scorpius association

We present the discovery of a companion near the deuterium burning mass limit located at a very wide distance, at an angular separation of 4.6+/-0.1 arcsec (projected distance of ~ 670 AU) from UScoCTIO108, a brown dwarf of the very young Upper Scorpius association. Optical and near-infrared photometry and spectroscopy confirm the cool nature of both objects, with spectral types of M7 and M9.5, respectively, and that they are bona fide members of the association, showing low gravity and features of youth. Their masses, estimated from the comparison of their bolometric luminosities and theoretical models for the age range of the association, are 60+/-20 and 14^{+2}_{-8} MJup, respectively. The existence of this object around a brown dwarf at this wide orbit suggests that the companion is unlikely to have formed in a disk based on current planet formation models. Because this system is rather weakly bound, they did not probably form through dynamical ejection of stellar embryos.Comment: 10 pages, including 4 figures and 2 table

Identification of a novel sequence motif recognised by the ankyrin-repeat domain of zDHHC17/13 S-acyl-transferases

S-acylation is a major post-translational modification affecting several cellular processes and being particularly important for neuronal functions. This modification is catalysed by a family of transmembrane S-acyl-transferases that contain a conserved zinc-finger DHHC (zDHHC) domain. Typically, eukaryote genomes encode for 7-24 distinct zDHHC enzymes, with 2 members also harbouring an ankyrin-repeat (AR) domain at their cytosolic N-terminus. The AR domain of zDHHC enzymes is predicted to engage in numerous interactions, and facilitates both substrate recruitment and S-acylation-independent functions; however, the sequence/structural features recognised by this module remain unknown. The two mammalian AR-containing S-acyltransferases are the Golgi-localised zDHHC17 and zDHHC13, also known as Huntingtin-interacting proteins 14 and 14-like, respectively; these are highly expressed in brain, and their loss in mice leads to neuropathological deficits that are reminiscent of Huntington disease. Here, we report that zDHHC17 and zDHHC13 recognise via their AR domain, evolutionary conserved and closely related sequences of a [VIAP][VIT]xxQP consensus in SNAP25, SNAP23, Cysteine-String Protein, Huntingtin, Cytoplasmic Linker Protein 3 and Microtubule Associated Protein 6. This novel AR-binding sequence motif is found in regions predicted to be unstructured, and is present in a number of zDHHC17 substrates and zDHHC17/13-interacting S-acylated proteins. This is the first study to identify a motif recognised by AR-containing zDHHCs

Efficiency enhancement by reconfigurable matching networks in LINC transmitters

This paper proposes the use of a transmitter based on a linear amplification with nonlinear components (LINC) architecture, in which the reconfigurable matching networks (RMNs) are included. By varying the RMN active cell number, it is possible to change the load impedance at the power amplifier (PA) output, improving the amplifier drain efficiency and therefore the efficiency of the whole system. A long-term evolution (LTE) downlink signal with a bandwidth of 1.4 MHz and a peak-to-average power ratio (PAPR) of 11.48 dB is applied in order to carry out the experiments. Results show that the use of the RMNs in a LINC architecture improves the efficiency at all tested frequencies, especially at 927 MHz reaching an enhancement of 36.50%. Regarding the distortion, the adjacent channel leakage ratio (ACLR) values increase in all cases, with an improvement of 3.5 dB at 958 MHz. Finally, in terms of error vector magnitude (EVM), the proposed architecture offers a value of 1.96% at 927 MHz