Vulnerability of CMOS image sensors in megajoule class laser harsh environment

CMOS image sensors (CIS) are promising candidates as part of optical imagers for the plasma diagnostics devoted to the study of fusion by inertial confinement. However, the harsh radiative environment of Megajoule Class Lasers threatens the performances of these optical sensors. In this paper, the vulnerability of CIS to the transient and mixed pulsed radiation environment associated with such facilities is investigated during an experiment at the OMEGA facility at the Laboratory for Laser Energetics (LLE), Rochester, NY, USA. The transient and permanent effects of the 14 MeV neutron pulse on CIS are presented. The behavior of the tested CIS shows that active pixel sensors (APS) exhibit a better hardness to this harsh environment than a CCD. A first order extrapolation of the reported results to the higher level of radiation expected for Megajoule Class Laser facilities (Laser Megajoule in France or National Ignition Facility in the USA) shows that temporarily saturated pixels due to transient neutron-induced single event effects will be the major issue for the development of radiation-tolerant plasma diagnostic instruments whereas the permanent degradation of the CIS related to displacement damage or total ionizing dose effects could be reduced by applying well known mitigation techniques

Hardening approach to use CMOS image sensors for fusion by inertial confinement diagnostics

A hardening method is proposed to enable the use of CMOS image sensors for Fusion by Inertial Confinement Diagnostics. The mitigation technique improves their radiation tolerance using a reset mode implemented in the device. The results obtained evidence a reduction of more than 70% in the number of transient white pixels induced in the pixel array by the mixed neutron and γ-ray pulsed radiation environment

Decoding the Epigenetic Language of Plant Development

Epigenetics refers to the study of heritable changes in gene expression or cellular phenotype without changes in DNA sequence. Epigenetic regulation of gene expression is accomplished by DNA methylation, histone modifications, histone variants, chromatin remodeling, and may involve small RNAs. DNA methylation at cytosine is carried out by enzymes called DNA Methyltransferases and is involved in many cellular processes, such as silencing of transposable elements and pericentromeric repeats, X-chromosome inactivation and genomic imprinting, etc. Histone modifications refer to posttranslational covalent attachment of chemical groups onto histones such as phosphorylation, acetylation, and methylation, etc. Histone variants, the non-canonical histones with amino acid sequences divergent from canonical histones, can have different epigenetic impacts on the genome from canonical histones. Higher-order chromatin structures maintained or modified by chromatin remodeling proteins also play important roles in regulating gene expression. Small non-coding RNAs play various roles in the regulation of gene expression at pre- as well as posttranscriptional levels. A special issue of Molecular Plant on ‘Epigenetics and Plant Development’ (Volume 4, Number 2, 2009) published a variety of articles covering many aspects of epigenetic regulation of plant development. We have tried here to present a bird's-eye view of these credible efforts towards understanding the mysterious world of epigenetics. The majority of the articles are about the chromatin modifying proteins, including histone modifiers, histone variants, and chromatin remodeling proteins that regulate various developmental processes, such as flowering time, vernalization, stem cell maintenance, and response to hormonal and environmental stresses, etc. Regulation of expression of seed transcriptome, involvement of direct tandem repeat elements in the PHE1 imprinting in addition to PcG proteins activity, paramutation, and epigenetic barriers in species hybridization are described well. The last two papers are about the Pol V-mediated heterochromatin formation independent of the 24nt-siRNA and the effect of genome position and tissue type on epigenetic regulation of gene expression. These findings not only further our current understanding of epigenetic mechanisms involved in many biological phenomena, but also pave the path for the future work, by raising many new questions that are discussed in the following lines

Polycomb Repressive Complex 2 Controls the Embryo-to-Seedling Phase Transition

Polycomb repressive complex 2 (PRC2) is a key regulator of epigenetic states catalyzing histone H3 lysine 27 trimethylation (H3K27me3), a repressive chromatin mark. PRC2 composition is conserved from humans to plants, but the function of PRC2 during the early stage of plant life is unclear beyond the fact that it is required for the development of endosperm, a nutritive tissue that supports embryo growth. Circumventing the requirement of PRC2 in endosperm allowed us to generate viable homozygous null mutants for FERTILIZATION INDEPENDENT ENDOSPERM (FIE), which is the single Arabidopsis homolog of Extra Sex Combs, an indispensable component of Drosophila and mammalian PRC2. Here we show that H3K27me3 deposition is abolished genome-wide in fie mutants demonstrating the essential function of PRC2 in placing this mark in plants as in animals. In contrast to animals, we find that PRC2 function is not required for initial body plan formation in Arabidopsis. Rather, our results show that fie mutant seeds exhibit enhanced dormancy and germination defects, indicating a deficiency in terminating the embryonic phase. After germination, fie mutant seedlings switch to generative development that is not sustained, giving rise to neoplastic, callus-like structures. Further genome-wide studies showed that only a fraction of PRC2 targets are transcriptionally activated in fie seedlings and that this activation is accompanied in only a few cases with deposition of H3K4me3, a mark associated with gene activity and considered to act antagonistically to H3K27me3. Up-regulated PRC2 target genes were found to act at different hierarchical levels from transcriptional master regulators to a wide range of downstream targets. Collectively, our findings demonstrate that PRC2-mediated regulation represents a robust system controlling developmental phase transitions, not only from vegetative phase to flowering but also especially from embryonic phase to the seedling stage

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Evaluation of drug-induced sleep endoscopy as a tool for selecting patients with obstructive sleep apnea for maxillomandibular advancement

Study Objectives: (1) To investigate if drug-induced sleep endoscopy (DISE) findings are predictive of surgical response for patients undergoing maxillomandibular advancement (MMA) for obstructive sleep apnea (OSA) and (2) to investigate the predictive value of the jaw thrust maneuver during DISE in terms of surgical response to MMA. Methods: A retrospective cohort study was conducted in patients with OSA who underwent a baseline polysomnography (PSG) and DISE followed by MMA and a 3- to 6-month follow-up PSG between September 1, 2011, and September 30, 2020. Results: Sixty-four patients with OSA (50 males [78.1%]; mean ± SD age = 51.7 ± 9.5 years; mean ± SD apnea-hypopnea index = 49.0 ± 20.8 events/h) were included. Thirty-nine patients were responders, and 25 were nonresponders. Adjusting for baseline characteristics and surgical characteristics (eg, age, baseline apnea-hypopnea index, degree of maxillary advancement), patients with complete anteroposterior epiglottic collapse had 0.239 times lower odds for response to MMA (95% confidence interval, 0.059–0.979; P = .047). No significant relationship was found between complete concentric velum collapse and MMA response. There was no statistically significant association between effect of jaw thrust maneuver during DISE on upper airway patency and treatment outcome of MMA. Conclusions: This study indicates that DISE is a promising tool to identify patients who will or will not respond to MMA for treating OSA. Patients with complete anteroposterior epiglottic collapse may be less suitable candidates for MMA

Evaluation of drug-induced sleep endoscopy as a tool for selecting patients with obstructive sleep apnea for maxillomandibular advancement

STUDY OBJECTIVES: (1) To investigate if drug-induced sleep endoscopy (DISE) findings are predictive of surgical response for patients undergoing maxillomandibular advancement (MMA) for obstructive sleep apnea (OSA) and (2) to investigate the predictive value of the jaw thrust maneuver during DISE in terms of surgical response to MMA. METHODS: A retrospective cohort study was conducted in patients with OSA who underwent a baseline polysomnography (PSG) and DISE followed by MMA and a 3- to 6-month follow-up PSG between September 1, 2011, and September 30, 2020. RESULTS: Sixty-four patients with OSA (50 males [78.1%]; mean ± SD age = 51.7 ± 9.5 years; mean ± SD apnea-hypopnea index = 49.0 ± 20.8 events/h) were included. Thirty-nine patients were responders, and 25 were nonresponders. Adjusting for baseline characteristics and surgical characteristics (eg, age, baseline apnea-hypopnea index, degree of maxillary advancement), patients with complete anteroposterior epiglottic collapse had 0.239 times lower odds for response to MMA (95% confidence interval, 0.059-0.979; P = .047). No significant relationship was found between complete concentric velum collapse and MMA response. There was no statistically significant association between effect of jaw thrust maneuver during DISE on upper airway patency and treatment outcome of MMA. CONCLUSIONS: This study indicates that DISE is a promising tool to identify patients who will or will not respond to MMA for treating OSA. Patients with complete anteroposterior epiglottic collapse may be less suitable candidates for MMA. CITATION: Zhou N, Ho J-PTF, de Vries N, Bosschieter PFN, Ravesloot MJL, de Lange J. Evaluation of drug-induced sleep endoscopy as a tool for selecting patients with obstructive sleep apnea for maxillomandibular advancement. J Clin Sleep Med. 2022;18(4):1073-1081

Evaluation of drug-induced sleep endoscopy as a tool for selecting patients with obstructive sleep apnea for maxillomandibular advancement

Study Objectives: (1) To investigate if drug-induced sleep endoscopy (DISE) findings are predictive of surgical response for patients undergoing maxillomandibular advancement (MMA) for obstructive sleep apnea (OSA) and (2) to investigate the predictive value of the jaw thrust maneuver during DISE in terms of surgical response to MMA. Methods: A retrospective cohort study was conducted in patients with OSA who underwent a baseline polysomnography (PSG) and DISE followed by MMA and a 3- to 6-month follow-up PSG between September 1, 2011, and September 30, 2020. Results: Sixty-four patients with OSA (50 males [78.1%]; mean ± SD age = 51.7 ± 9.5 years; mean ± SD apnea-hypopnea index = 49.0 ± 20.8 events/h) were included. Thirty-nine patients were responders, and 25 were nonresponders. Adjusting for baseline characteristics and surgical characteristics (eg, age, baseline apnea-hypopnea index, degree of maxillary advancement), patients with complete anteroposterior epiglottic collapse had 0.239 times lower odds for response to MMA (95% confidence interval, 0.059–0.979; P = .047). No significant relationship was found between complete concentric velum collapse and MMA response. There was no statistically significant association between effect of jaw thrust maneuver during DISE on upper airway patency and treatment outcome of MMA. Conclusions: This study indicates that DISE is a promising tool to identify patients who will or will not respond to MMA for treating OSA. Patients with complete anteroposterior epiglottic collapse may be less suitable candidates for MMA

Short Integuments1/suspensor1/carpel Factory, a Dicer Homolog, Is a Maternal Effect Gene Required for Embryo Development in Arabidopsis

The importance of maternal cells in controlling early embryogenesis is well understood in animal development, yet in plants the precise role of maternal cells in embryogenesis is unclear. We demonstrated previously that maternal activity of the SIN1 (SHORT INTEGUMENTS1) gene of Arabidopsis is essential for embryo pattern formation and viability, and that its postembryonic activity is required for several processes in reproductive development, including flowering time control and ovule morphogenesis. Here, we report the cloning of SIN1, and demonstrate its identity to the CAF (CARPEL FACTORY) gene important for normal flower morphogenesis and to the SUS1 (SUSPENSOR1) gene essential for embryogenesis. SIN1/SUS1/CAF has sequence similarity to the Drosophila melanogaster gene Dicer, which encodes a multidomain ribonuclease specific for double-stranded RNA, first identified by its role in RNA silencing. The Dicer protein is essential for temporal control of development in animals, through the processing of small RNA hairpins that in turn inhibit the translation of target mRNAs. Structural modeling of the wild-type and sin1 mutant proteins indicates that the RNA helicase domain of SIN1/SUS1/CAF is important for function. The mRNA was detected in floral meristems, ovules, and early embryos, consistent with the mutant phenotypes. A 3.3-kb region 5′ of the SIN1/SUS1/CAF gene shows asymmetric parent-of-origin activity in the embryo: It confers transcriptional activation of a reporter gene in early embryos only when transmitted through the maternal gamete. These results suggest that maternal SIN1/SUS1/CAF functions early in Arabidopsis development, presumably through posttranscriptional regulation of specific mRNA molecules