Hit and run versus long-term activation of PARP-1 by its different domains fine-tunes nuclear processes.

Poly(ADP-ribose) polymerase 1 (PARP-1) is a multidomain multifunctional nuclear enzyme involved in the regulation of the chromatin structure and transcription. PARP-1 consists of three functional domains: the N-terminal DNA-binding domain (DBD) containing three zinc fingers, the automodification domain (A), and the C-terminal domain, which includes the protein interacting WGR domain (W) and the catalytic (Cat) subdomain responsible for the poly(ADP ribosyl)ating reaction. The mechanisms coordinating the functions of these domains and determining the positioning of PARP-1 in chromatin remain unknown. Using multiple deletional isoforms of PARP-1, lacking one or another of its three domains, as well as consisting of only one of those domains, we demonstrate that different functions of PARP-1 are coordinated by interactions among these domains and their targets. Interaction between the DBD and damaged DNA leads to a short-term binding and activation of PARP-1. This hit and run activation of PARP-1 initiates the DNA repair pathway at a specific point. The long-term chromatin loosening required to sustain transcription takes place when the C-terminal domain of PARP-1 binds to chromatin by interacting with histone H4 in the nucleosome. This long-term activation of PARP-1 results in a continuous accumulation of pADPr, which maintains chromatin in the loosened state around a certain locus so that the transcription machinery has continuous access to DNA. Cooperation between the DBD and C-terminal domain occurs in response to heat shock (HS), allowing PARP-1 to scan chromatin for specific binding sites

A Student-Initiated Elective in Medical Ethics: Innovations in Design and Institutionalization

Introduction: This study addresses how to best approach the instruction and evaluation of clinical ethics with preclinical medical students. [See PDF for complete abstract

A CMOS compatible ultracompact silicon photonic optical add-drop multiplexer with misaligned Sidewall Bragg gratings

We experimentally and via simulations demonstrate ultracompact single-stage and cascaded optical add-drop multiplexers using misaligned sidewall Bragg grating in a Mach-Zehnder interferometer for the silicon-on-insulator platform. The single-stage configuration has a device footprint of 400 μm × 90 μm, and the cascaded configuration has a footprint of 400 μm × 125 μm. The proposed designs have 3-dB bandwidths of 6 nm and extinction ratios of 25 dB and 51 dB, respectively, and have been fabricated for the transverse electric mode. A minimum lithographic feature size of 80 nm is used in our design, which is within the limitation of 193 nm deep ultraviolet lithography

200 Gb/s transmission using a dual-polarization O-Band silicon photonic intensity modulator for Stokes vector direct detection applications

We present a dual-polarization O-band silicon photonic (SiP) transmitter for intra-datacenter optical interconnects. The transmitter is built using two identical O-band traveling wave Mach-Zehnder modulators with an average VπL and a bandwidth at 1.5 V bias voltage of 2.88 V.cm and 24.5 GHz, respectively. We experimentally demonstrate the transmitter in a Stokes vector direct-detection (SV-DD) system for dual-polarization intensity modulated signals with 2-level and 4-level pulse amplitude modulation (DP-PAM2 and DP-PAM4) formats. The direct-detection Stokes vector receiver (DD-SVR) followed by offline digital signal processing (DSP) is implemented for SOP de-rotation. We characterize the performance of the SV-DD system versus number of taps, received signal power, state of polarization (SOP), reach, and bit rate. Results reveal that 112 Gb/s DP-PAM2 can be transmitted over 10 km of single mode fiber (SMF) at a bit error rate (BER) below 10−5 at −1 dBm received signal power irrespective of the SOP. Moreover, a 168 Gb/s (42 Gbaud) DP-PAM4 signal can be transmitted over 2 km and 10 km at a BER below the 7% hard-decision forward error correction (HD-FEC) threshold (i.e., 3.8 × 10−3) at 0 dBm and 2 dBm, respectively. Furthermore, 224 Gb/s and 200 Gb/s DP-PAM4 are successfully received at a BER below the HD-FEC in the back-to-back and 2 km cases, respectively. Finally, we compare the performance of the 6 × 2 multiple-input multiple-output (MIMO) equalization to a simpler 4 × 2 MIMO equalization and explain the superior performance of the 6 × 2 in the presence of SVR imperfections