Towards a single-photon energy-sensitive pixel readout chip: pixel level ADCs and digital readout circuitry

Unlike conventional CMOS imaging, a single\ud photon imager detects each individual photon impinging on\ud a detector, accumulating the number of photons during a\ud certain time window and not the charge generated by the all\ud the photons hitting the detector during said time window.\ud The latest developments in the semiconductor industry\ud are allowing faster and more complex chips to be designed\ud and manufactured. With these developments in mind we are\ud working towards the next step in single photon X-ray imaging:\ud energy sensitive pixel readout chips. The goal is not only\ud to detect and count individual photons, but also to measure\ud the charge deposited in the detector by each photon, and\ud consequently determine its energy. Basically, we are aiming\ud at a spectrometer-in-a-pixel, or a “color X-ray camera”.\ud The approach we have followed towards this goal is the\ud design of small analog-to-digital-converters at the pixel level,\ud together with a very fast digital readout from the pixels to\ud the periphery of the chip, where the data will be transmitted\ud off-chip.\ud We will present here the design and measurement on prototype\ud chips of two different 4-bit pixel level ADCs. The\ud ADCs are optimized for very small area and low power, with\ud a resolution of 4-bits and a sample rate of 1 Msample/s. The\ud readout architecture is based around current-mode sense\ud amplifiers and asynchronous token-passing between the pixels.\ud This is done in order to achieve event-by-event readout\ud and, consequently, on-line imaging. We need to read eventby-\ud event (photon-by-photon), because we cannot have memory\ud on the pixels due to obvious size constraints. We use\ud current-mode sense amplifiers because they perform very\ud well in similar applications as very fast static-RAM readout

Speech into Sign Language Statistical Translation System for Deaf People

This paper presents a set of experiments used to develop a statistical system from translating speech to sign language for deaf people. This system is composed of an Automatic Speech Recognition (ASR) system, followed by a statistical translation module and an animated agent that represents the different signs. Two different approaches have been used to perform the translations: a phrase-based system and a finite state transducer. For the evaluation, the followings figures have been considered: WER (Word Error Rate), BLEU and NIST. The paper presents translation results of reference sentences and sentences from the automatic speech recognizer. Also three different configurations have been evaluated for the speech recognizer. The best results were obtained with the finite state transducer, with a word error rate of 28.21% for the reference text, and 29.27% using the ASR output

Transgenic mice expressing bovine PrP with a four extra repeat octapeptide insert mutation show a spontaneous, non-transmissible, neurodegenerative disease and an expedited course of BSE infection

AbstractTransgenic (Tg) mice carrying four extra octapeptide repeats (OR) in the bovine PrP gene (10OR instead of 6) have been generated. In these mice, neuropathological changes were observed depending upon the level of transgene expression. These changes primarily involved a slowly advancing neurological disorder, characterized clinically by ataxia, and neuropathologically, by vacuolization in different brain areas, gliosis, and loss of cerebellar granule cells. Accumulation of insoluble bovine 10OR-PrP (bo10OR-PrP) was observed depending on the level of expression but no infectivity was found associated with this insoluble form. We also compared the behavior of bo6OR-PrP and bo10OR-PrP Tg mouse lines in response to BSE infection. BSE-inoculated bo10ORTg mice showed an altered course of BSE infection, reflected by reduced incubation times when compared to bo6ORTg mice expressing similar levels of the wild type 6OR-PrP. In BSE-inoculated mice, it was possible to detect PrPres in 100% of the animals. While insoluble bo10OR-PrP from non-inoculated bo10ORTg mice was non-infectious, brain homogenates from BSE-inoculated bo10ORTg mice were highly infectious in all the Tg mouse lines tested. This Tg mouse model constitutes a new way of understanding the pathobiology of bovine transmissible spongiform encephalopathy. Its potential applications include the assessment of new therapies against prion diseases

Synergistic DNA-damaging effect in multiple myeloma with the combination of zalypsis, bor tezomib and dexamethasone

Despite new advances in multiple myeloma treatment and the consequent improvement in overall survival, most patients relapse or become refractory to treatment. This suggests that new molecules and combinations that may further inhibit important survival pathways for these tumor cells are needed. In this context, zalypsis is a novel compound, derived from marine organisms, with a powerful preclinical anti-myeloma effect based on the sensitivity of malignant plasma cells to DNA-damage induction; and it has already been tested in a phase I/II clinical trial in multiple myeloma. We hypothesized that the addition of this compound to the combination of bortezomib plus dexamethasone may improve efficacy with acceptable toxicity. The triple combination demonstrated strong synergy and higher efficacy compared with double combinations; not only in vitro, but also ex vivo and, especially, in in vivo experiments. The triple combination triggers cell death, mainly through a synergistic induction of DNA damage and a decrease in the nuclear localization of nuclear factor kappa B. Our findings support the clinical evaluation of this combination for relapsed and refractory myeloma patients.This work was in part funded by the Spanish ISCIII-FIS (PI 15/0067 and PI15/02156) and FEDER, the Spanish RTICC (RD12/0036/0058), "Asociación Española Contra el Cancer" (AECC, GCB120981SAN), the regional Council from “Castilla y León” (GRS 1175/A/15 and FIC335U14) and a research grant from Pharmamar SAU. MMS were also supported by the Network of Centers for Regenerative Medicine and Cellular Therapy from Castilla y León, Spain. A-A López-Iglesias was supported by a grant from the Spanish Society of Hematology and Hemotherapy.Peer Reviewe

A ‘higher order' of telomere regulation: telomere heterochromatin and telomeric RNAs

Protection of chromosome ends from DNA repair and degradation activities is mediated by specialized protein complexes bound to telomere repeats. Recently, it has become apparent that epigenetic regulation of the telomric chromatin template critically impacts on telomere function and telomere-length homeostasis from yeast to man. Across all species, telomeric repeats as well as the adjacent subtelomeric regions carry features of repressive chromatin. Disruption of this silent chromatin environment results in loss of telomere-length control and increased telomere recombination. In turn, progressive telomere loss reduces chromatin compaction at telomeric and subtelomeric domains. The recent discoveries of telomere chromatin regulation during early mammalian development, as well as during nuclear reprogramming, further highlights a central role of telomere chromatin changes in ontogenesis. In addition, telomeres were recently shown to generate long, non-coding RNAs that remain associated to telomeric chromatin and will provide new insights into the regulation of telomere length and telomere chromatin. In this review, we will discuss the epigenetic regulation of telomeres across species, with special emphasis on mammalian telomeres. We will also discuss the links between epigenetic alterations at mammalian telomeres and telomere-associated diseases

Marker-assisted introgression of the salinity tolerance locus Saltol in temperate japonica rice

Background Rice is one of the most salt sensitive crops at seedling, early vegetative and reproductive stages. Varieties with salinity tolerance at seedling stage promote an efficient growth at early stages in salt affected soils, leading to healthy vegetative growth that protects crop yield. Saltol major QTL confers capacity to young rice plants growing under salt condition by maintaining a low Na+/ K+ molar ratio in the shoots. Results Marker-assisted backcross (MABC) procedure was adopted to transfer Saltol locus conferring salt tolerance at seedling stage from donor indica IR64-Saltol to two temperate japonica varieties, Vialone Nano and Onice. Forward and background selections were accomplished using polymorphic KASP markers and a final evaluation of genetic background recovery of the selected lines was conducted using 15,580 SNP markers obtained from Genotyping by Sequencing. Three MABC generations followed by two selfing, allowed the identification of introgression lines achieving a recovery of the recurrent parent (RP) genome up to 100% (based on KASP markers) or 98.97% (based on GBS). Lines with highest RP genome recovery (RPGR) were evaluated for agronomical-phenological traits in field under nonsalinized conditions. VN1, VN4, O1 lines were selected considering the agronomic evaluations and the RPGR% results as the most interesting for commercial exploitation. A physiological characterization was conducted by evaluating salt tolerance under hydroponic conditions. The selected lines showed lower standard evaluation system (SES) scores: 62% of VN4, and 57% of O1 plants reaching SES 3 or SES 5 respectively, while only 40% of Vialone Nano and 25% of Onice plants recorded scores from 3 to 5, respectively. VN1, VN4 and O1 showed a reduced electrolyte leakage values, and limited negative effects on relative water content and shoot/root fresh weight ratio. Conclusion The Saltol locus was successfully transferred to two elite varieties by MABC in a time frame of three years. The application of background selection until BC3F3 allowed the selection of lines with a RPGR up to 98.97%. Physiological evaluations for the selected lines indicate an improved salinity tolerance at seedling stage. The results supported the effectiveness of the Saltol locus in temperate japonica and of the MABC procedure for recovering of the RP favorable traits

Analysis of remarkable bolides observed between June and July 2022 in the framework of the Southwestern EuropeMeteor Network

Some of the bright bolides spotted in the framework of the Southwestern Europe Meteor Network from June to July 2022 are discussed here. These were observed from Spain. Their absolute magnitude ranges from –6 to –11. Fireballs included in this work were generated by different sources: the sporadic background, major meteoroid streams, and poorly known streams.Spanish Ministry of Science and Innovation (project PID2019-105797GB-I00). State Agency for Research of the Spanish MCIU through the “Center of Excellence Severo Ochoa” award to the Instituto de Astrofísica de Andalucía (SEV-2017-0709). Spanish grant AYA - RTI2018 – 098657 – J - I00 “LEO-SBNAF” (MCIU / AEI / FEDER, UE)

Analysis of bright bolides recorded between October and November 2022 by the Southwestern Europe Meteor Network

We present in this work the analysis of some of the bright fireballs spotted in the framework of the Southwestern Europe Meteor Network (SWEMN) between October and November 2022. They have been observed from the Iberian Peninsula and had a maximum brightness ranging from mag. –7 to mag. –15. Most meteors included in this report were linked to the sporadic background and also to the Southern Taurids.Spanish Ministry of Science and Innovation (project PID2019-105797GB-I00). State Agency for Research of the Spanish MCIU through the “Center of Excellence Severo Ochoa” award to the Instituto de Astrofísica de Andalucía (SEV-2017-0709). Spanish grant AYA -RTI2018–098657–J-I00 “LEO-SBNAF” (MCIU / AEI / FEDER, UE)

Remarkable fireballs spotted in the framework of the Southwestern Europe Meteor Network along August and September 2022

Some of the bright bolides observed in the framework of the Southwestern Europe Meteor Network between August and September 2022 are described in this work. These have been spotted from the Iberian Peninsula. Their maximum luminosity ranges from mag. –7 to mag. –12. One of these bolides gave rise to a meteorite.Spanish Ministry of Science and Innovation (project PID2019-105797GB-I00). Spanish MCIU through the “Center of Excellence Severo Ochoa” award to the Instituto de Astrofísica de Andalucía (SEV-2017-0709).Spanish grant AYA - RTI2018 – 098657 -J- I00 “LEO-SBNAF” (MCIU / AEI / FEDER, UE)

The Southwestern Europe Meteor Network: notable meteors spotted between December 2022 and January 2023

We present in this report the analysis of some of the notable meteors registered in the framework of the Southwestern Europe Meteor Network between December 2022 and January 2023. These were recorded from Spain. Their peak brightness ranges from mag. –7 to mag. –10. The emission spectrum of one of them is also presented. Bright meteors included here were produced by different sources: the sporadic background, major meteoroid streams, and poorly-known streams.Spanish Ministry of Science and Innovation (project PID2019-105797GB-I00). State Agency for Research of the Spanish MCIU through the “Center of Excellence Severo Ochoa” award to the Instituto de Astrofísica de Andalucía (SEV-2017-0709). Spanish grant AYA - RTI2018 – 098657 – J - I00 “LEO – SBNAF” (MCIU / AEI / FEDER, UE)