A Nick-sensing DNA 3′-Repair Enzyme fromArabidopsis

DNA single-strand breaks, a major cause of genome instability, often produce unconventional end groups that must be processed to restore terminal moieties suitable for reparative DNA gap filling or ligation. Here, we describe a bifunctional repair enzyme from Arabidopsis (named AtZDP) that recognizes DNA strand breaks and catalyzes the removal of 3'-end-blocking lesions. The isolated C-terminal domain of AtZDP is by itself competent for 3'-end processing, but not for strand break recognition. The N-terminal domain instead contains three Cys(3)-His zinc fingers and recognizes various kinds of damaged double-stranded DNA. Gapped DNA molecules are preferential targets of AtZDP, which bends them by approximately 73 degrees upon binding, as measured by atomic force microscopy. Potential partners of AtZDP were identified in the Arabidopsis genome using the human single-strand break repairosome as a reference. These data identify a novel pathway for single-strand break repair in which a DNA-binding 3'-phosphoesterase acts as a "nick sensor" for damage recognition, as the catalyst of one repair step, and possibly as a nucleation center for the assembly of a fully competent repair complex

A 28-nm CMOS pixel read-out ASIC for real-time tracking with time resolution below 20 ps

We present the development of a test ASIC, named Timespot1, designed in CMOS 28-nm technology, featuring a 32x32 pixel matrix and a pitch of 55 μm, The ASIC is conceived as the first prototype in a series, capable to read-out pixels with timing capabilities in the range of 30 ps and below. Each pixel is endowed with a charge amplifier, a discriminator and a Time-to-Digital-Converter, capable of time resolutions below 20 ps and read-out rates (per pixel) around 3 MHz. The timing performance are obtained respecting a power budget of about 50 μW per pixel, corresponding to a power density of approximately 2 W/cm 2 · This feature makes the Timespot1 approach an interesting solution for vertex detectors of the next generation of colliders, where high space and time resolutions will be mandatory requirements to cope with the huge amount of tracks per event to be detected and processed

Timespot1: A 28nm CMOS Pixel Read-Out ASIC for 4D Tracking at High Rates

We present the first characterization results of Timespot1, an ASIC designed in CMOS 28 nm technology, featuring a $32 \times 32$ pixel matrix with a pitch of $55 ~ \mu m$. Timespot1 is the first small-size prototype, conceived to readout fine-pitch pixels with single-hit time resolution below $50 ~ ps_\text{rms}$ and input rates of several hundreds of kilohertz per pixel. Such experimental conditions will be typical of the next generation of high-luminosity collider experiments, from the LHC run5 and beyond. Each pixel of the ASIC includes a charge amplifier, a discriminator, and a Time-to-Digital Converter with time resolution indicatively of $22.6 ~ ps_\text{rms}$ and maximum readout rates (per pixel) of $3 ~ MHz$. To respect system-level constraints, the timing performance has been obtained keeping the power budget per pixel below $40 ~ \mu W$. The ASIC has been tested and characterised in the laboratory concerning its performance in terms of time resolution, power budget and sustainable rates. The ASIC will be hybridized on a matched $32 \times 32$ pixel sensor matrix and will be tested under laser beam and Minimum Ionizing Particles in the laboratory and at test beams. In this paper we present a description of the ASIC operation and the first results obtained from characterization tests concerning its performance

A Configurable 64-Channel ASIC for Cherenkov Radiation Detection from Space

This work presents the development of a 64-channel application-specific integrated circuit (ASIC), implemented to detect the optical Cherenkov light from sub-orbital and orbital altitudes. These kinds of signals are generated by ultra-high energy cosmic rays (UHECRs) and cosmic neutrinos (CNs). The purpose of this front-end electronics is to provide a readout unit for a matrix of silicon photo-multipliers (SiPMs) to identify extensive air showers (EASs). Each event can be stored into a configurable array of 256 cells where the on-board digitization can take place with a programmable 12-bits Wilkinson analog-to-digital converter (ADC). The sampling, the conversion process, and the main digital logic of the ASIC run at 200 MHz, while the readout is managed by dedicated serializers operating at 400 MHz in double data rate (DDR). The chip is designed in a commercial 65 nm CMOS technology, ensuring a high configurability by selecting the partition of the channels, the resolution in the interval 8–12 bits, and the source of its trigger. The production and testing of the ASIC is planned for the forthcoming months

The first ASIC prototype of a 28 nm time-space front-end electronics for real-time tracking

A front-end ASIC for 4D tracking is presented. The prototype includes the block necessary to build a pixel front-end chain for timing measurement, as independent circuits. The architecture includes a charge-sensitive amplifier, a discriminator with programmable threshold, and a time- to-digital converter. The blocks were designed with target specifications in mind including: an area occupation of 55 μm × 55 μm, a power consumption tens of micro ampere per channel and timing a resolution of at least 100 ps. The prototype has been designed and integrated in 28 nm CMOS technology. The presented design is part of the TimeSpOT project which aims to reach a high-resolution particle tracking both in space and in time, in order to provide front-end circuitry suitable for next generation colliders

Laboratory and beam test results of TOFFEE ASIC and ultra fast silicon detectors

In this report we present measurements performed on the full custom ASIC TOFFEE, designed to pre-amplify and discriminate signals of Ultra Fast Silicon Detectors. The ASIC has been characterized in laboratory with custom test boards, and with infrared laser light hitting the sensor emulating a minimum ionizing particle signal. Laser measurements show that a jitter term better than 50 (40) ps is achievable with a 10 (12) fC input charge.We also present some preliminary results on the TOFFEE performances, as obtained during recent beam tests with a 180 GeV/c pion beam, on the SPS-H8 beam line at CERN.Peer Reviewe

TOFPET ASIC for PET applications

A 64-channel ASIC for Time-of-Flight Positron Emission Tomography (TOF PET) imaging has been designed and simulated. The circuit is optimized for the readout of signals pro- duced by the scintillation of a L(Y)SO crystal optically coupled to a silicon photomultiplier (SiPM). Developed in the framework of the EndoTOFPET-US collaboration (1), the ASIC is integrated in the external PET plate and performs timing, digitization and data transmission for 511 keV and lower-energy events due to Compton scattering. Multi-event buffering capability allows event rates up to 100 kHz per channel. The channel cell includes a low input impedance low-noise current conveyor and two trans-impedance amplifier branches separately optimized for energy and time resolution. Two voltage mode discriminators generate respectively a fast trigger for accurate timing and a signal for time-over-threshold calcu- lation, used for charge measurement. The digitization of these signals is done by two low-power TDCs, providing coarse and fine time stamps that are saved into a local register and later managed by a global controller, which builds-up the 40-bit event data and runs the interface with the data acquisition back-end. Running at 160 MHz the chip yields a 50 ps time binning and dissipates u 7 mW per channel (simulated for 40 kHz event rate p/channel) for high capacitance photodetectors (9 mm 2 active area Silicon Photomultiplier with 320 pF terminal capacitance). The minimum SNR of 23.5 dB expected with this capacitance should allow triggering on the first photoelectron to achieve the envisaged timing performance for a TOF-PET system

Design and characterization of the readout ASIC for the BESIII CGEM detector

TIGER (Turin Integrated Gem Electronics for Readout) is a mixed-mode ASIC for the readout of signals from CGEM (Cylindrical Gas Electron Multiplier) detector in the upgraded inner tracker of the BESIII experiment, carried out at BEPCII in Beijing. The ASIC includes 64 channels, each of which features a dual-branch architecture optimized for timing and energy measurement. The input signal time-of-arrival and charge measurement is provided by low-power TDCs, based on analogue interpolation techniques, and Wilkinson ADCs, with a fully-digital output. The silicon results of TIGER first prototype are presented showing its full functionality.Peer Reviewe

Conformation-sensitive Antibodies against Alzheimer Amyloid-β by Immunization with a Thioredoxin-constrained B-cell Epitope Peptide

Immunotherapy against the amyloid-beta (Abeta) peptide is a valuable potential treatment for Alzheimer disease (AD). An ideal antigen should be soluble and nontoxic, avoid the C-terminally located T-cell epitope of Abeta, and yet be capable of eliciting antibodies that recognize Abeta fibrils and neurotoxic Abeta oligomers but not the physiological monomeric species of Abeta. We have described here the construction and immunological characterization of a recombinant antigen with these features obtained by tandem multimerization of the immunodominant B-cell epitope peptide Abeta1-15 (Abeta15) within the active site loop of bacterial thioredoxin (Trx). Chimeric Trx(Abeta15)n polypeptides bearing one, four, or eight copies of Abeta15 were constructed and injected into mice in combination with alum, an adjuvant approved for human use. All three polypeptides were found to be immunogenic, yet eliciting antibodies with distinct recognition specificities. The anti-Trx(Abeta15)4 antibody, in particular, recognized Abeta42 fibrils and oligomers but not monomers and exhibited the same kind of conformational selectivity against transthyretin, an amyloidogenic protein unrelated in sequence to Abeta. We have also demonstrated that anti-Trx(Abeta15)4, which binds to human AD plaques, markedly reduces Abeta pathology in transgenic AD mice. The data indicate that a conformational epitope shared by oligomers and fibrils can be mimicked by a thioredoxin-constrained Abeta fragment repeat and identify Trx(Abeta15)4 as a promising new tool for AD immunotherapy