85 research outputs found
Physics and Applications of Laser Diode Chaos
An overview of chaos in laser diodes is provided which surveys experimental
achievements in the area and explains the theory behind the phenomenon. The
fundamental physics underpinning this behaviour and also the opportunities for
harnessing laser diode chaos for potential applications are discussed. The
availability and ease of operation of laser diodes, in a wide range of
configurations, make them a convenient test-bed for exploring basic aspects of
nonlinear and chaotic dynamics. It also makes them attractive for practical
tasks, such as chaos-based secure communications and random number generation.
Avenues for future research and development of chaotic laser diodes are also
identified.Comment: Published in Nature Photonic
Transient acceleration events in LISA Pathfinder data: Properties and possible physical origin
We present an in depth analysis of the transient events, or glitches, detected at a rate of about one per day in the differential acceleration data of LISA Pathfinder. We show that these glitches fall in two rather distinct categories: fast transients in the interferometric motion readout on one side, and true force transient events on the other. The former are fast and rare in ordinary conditions. The second may last from seconds to hours and constitute the majority of the glitches. We present an analysis of the physical and statistical properties of both categories, including a cross-analysis with other time series like magnetic fields, temperature, and other dynamical variables. Based on these analyses we discuss the possible sources of the force glitches and identify the most likely, among which the outgassing environment surrounding the test-masses stands out. We discuss the impact of these findings on the LISA design and operation, and some risk mitigation measures, including experimental studies that may be conducted on the ground, aimed at clarifying some of the questions left open by our analysis
Comparative expression of Cbf genes in the Triticeae under different acclimation induction temperatures
In plants, the C-repeat binding factors (Cbfs) are believed to regulate low-temperature (LT) tolerance. However, most functional studies of Cbfs have focused on characterizing expression after an LT shock and have not quantified differences associated with variable temperature induction or the rate of response to LT treatment. In the Triticeae, rye (Secale cereale L.) is one of the most LT-tolerant species, and is an excellent model to study and compare Cbf LT induction and expression profiles. Here, we report the isolation of rye Cbf genes (ScCbfs) and compare their expression levels in spring- and winter-habit rye cultivars and their orthologs in two winter-habit wheat (Triticum aestivum L.) and barley (Hordeum vulgare L.) cultivars. Eleven ScCbfs were isolated spanning all four major phylogenetic groups. Nine of the ScCbfs mapped to 5RL and one to chromosome 2R. Cbf expression levels were variable, with stronger expression in winter- versus spring-habit rye cultivars but no clear relationship with cultivar differences in LT, down-stream cold-regulated gene expression and Cbf expression were detected. Some Cbfs were expressed only at warmer acclimation temperatures in all three species and their expression was repressed at the end of an 8-h dark period at warmer temperatures, which may reflect a temperature-dependent, light-regulated diurnal response. Our work indicates that Cbf expression is regulated by complex genotype by time by inductionâtemperature interactions, emphasizing that sample timing, inductionâtemperature and light-related factors must receive greater consideration in future studies involving functional characterization of LT-induced genes in cereals
Impaired immunogenicity to COVID-19 vaccines in autoimmune systemic diseases. High prevalence of non-response in different patientsâ subgroups
Autoimmune systemic diseases (ASD) may show impaired immunogenicity to COVID-19 vaccines. Our prospective observational multicenter study aimed to evaluate the seroconversion after the vaccination cycle and at 6-12-month follow-up, as well the safety and efficacy of vaccines in preventing COVID-19. The study included 478 unselected ASD patients (mean age 59 ± 15 years), namely 101 rheumatoid arthritis (RA), 38 systemic lupus erythematosus (SLE), 265 systemic sclerosis (SSc), 61 cryoglobulinemic vasculitis (CV), and a miscellanea of 13 systemic vasculitis. The control group included 502 individuals from the general population (mean age 59 ± 14SD years). The immunogenicity of mRNA COVID-19 vaccines (BNT162b2 and mRNA-1273) was evaluated by measuring serum IgG-neutralizing antibody (NAb) (SARS-CoV-2 IgG II Quant antibody test kit; Abbott Laboratories, Chicago, IL) on samples obtained within 3 weeks after vaccination cycle. The short-term results of our prospective study revealed significantly lower NAb levels in ASD series compared to controls [286 (53â1203) vs 825 (451â1542) BAU/mL, p < 0.0001], as well as between single ASD subgroups and controls. More interestingly, higher percentage of non-responders to vaccine was recorded in ASD patients compared to controls [13.2% (63/478), vs 2.8% (14/502); p < 0.0001]. Increased prevalence of non-response to vaccine was also observed in different ASD subgroups, in patients with ASD-related interstitial lung disease (p = 0.009), and in those treated with glucocorticoids (p = 0.002), mycophenolate-mofetil (p < 0.0001), or rituximab (p < 0.0001). Comparable percentages of vaccine-related adverse effects were recorded among responder and non-responder ASD patients. Patients with weak/absent seroconversion, believed to be immune to SARS-CoV-2 infection, are at high risk to develop COVID-19. Early determination of serum NAb after vaccination cycle may allow to identify three main groups of ASD patients: responders, subjects with suboptimal response, non-responders. Patients with suboptimal response should be prioritized for a booster-dose of vaccine, while a different type of vaccine could be administered to non-responder individuals
Misfolded SOD1 Associated with Motor Neuron Mitochondria Alters Mitochondrial Shape and Distribution Prior to Clinical Onset
Mutations in superoxide dismutase (SOD1) are causative for inherited amyotrophic lateral sclerosis. A proportion of SOD1 mutant protein is misfolded onto the cytoplasmic face of mitochondria in one or more spinal cord cell types. By construction of mice in which mitochondrially targeted enhanced green fluorescent protein is selectively expressed in motor neurons, we demonstrate that axonal mitochondria of motor neurons are primary in vivo targets for misfolded SOD1. Mutant SOD1 alters axonal mitochondrial morphology and distribution, with dismutase active SOD1 causing mitochondrial clustering at the proximal side of Schmidt-Lanterman incisures within motor axons and dismutase inactive SOD1 producing aberrantly elongated axonal mitochondria beginning pre-symptomatically and increasing in severity as disease progresses. Somal mitochondria are altered by mutant SOD1, with loss of the characteristic cylindrical, networked morphology and its replacement by a less elongated, more spherical shape. These data indicate that mutant SOD1 binding to mitochondria disrupts normal mitochondrial distribution and size homeostasis as early pathogenic features of SOD1 mutant-mediated ALS
Hv-CBF2A overexpression in barley accelerates COR gene transcript accumulation and acquisition of freezing tolerance during cold acclimation
Abstract C-Repeat Binding Factors (CBFs) are DNAbinding
transcriptional activators of gene pathways imparting
freezing tolerance. Poaceae contain three CBF subfamilies,
two of which, HvCBF3/CBFIII and HvCBF4/CBFIV,
are unique to this taxon. To gain mechanistic insight into
HvCBF4/CBFIV CBFs we overexpressed Hv-CBF2A in
spring barley (Hordeum vulgare) cultivar âGolden Promiseâ.
The Hv-CBF2A overexpressing lines exhibited stunted
growth, poor yield, and greater freezing tolerance compared
to non-transformed âGolden Promiseâ. Differences in
freezing tolerance were apparent only upon cold acclimation.
During cold acclimation freezing tolerance of the
Hv-CBF2A overexpressing lines increased more rapidly
than that of âGolden Promiseâ and paralleled the freezing
tolerance of the winter hardy barley âDicktooâ. Transcript
levels of candidate CBF target genes, COR14B and DHN5
were increased in the overexpressor lines at warm temperatures,
and at cold temperatures they accumulated to much
higher levels in the Hv-CBF2A overexpressors than in
âGolden Promiseâ. Hv-CBF2A overexpression also
increased transcript levels of other CBF genes at FROST
RESISTANCE-H2-H2 (FR-H2) possessing CRT/DRE sites
in their upstream regions, the most notable of which was
CBF12. CBF12 transcript levels exhibited a relatively constant
incremental increase above levels in âGolden Promiseâ
both at warm and cold. These data indicate that Hv-CBF2A
activates target genes at warm temperatures and that transcript
accumulation for some of these targets is greatly
enhanced by cold temperatures
Long-Term Retention Rate of Tofacitinib in Rheumatoid Arthritis: An Italian Multicenter Retrospective Cohort Study
Background: Tofacitinib (TOFA) was the first Janus kinase inhibitor (JAKi) to be approved for the treatment of rheumatoid arthritis (RA). However, data on the retention rate of TOFA therapy are still far from definitive. Objective: The goal of this study is to add new real-world data on the TOFA retention rate in a cohort of RA patients followed for a long period of time. Methods: A multicenter retrospective study of RA subjects treated with TOFA as monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) was conducted in 23 Italian tertiary rheumatology centers. The study considered a treatment period of up to 48 months for all included patients. The TOFA retention rate was assessed with the KaplanâMeier method. Hazard ratios (HRs) for TOFA discontinuation were obtained using Cox regression analysis. Results: We enrolled a total of 213 patients. Data analysis revealed that the TOFA retention rate was 86.5% (95% CI: 81.8â91.5%) at month 12, 78.8% (95% CI: 78.8â85.2%) at month 24, 63.8% (95% CI: 55.1â73.8%) at month 36, and 59.9% (95% CI: 55.1â73.8%) at month 48 after starting treatment. None of the factors analyzed, including the number of previous treatments received, disease activity or duration, presence of rheumatoid factor and/or anti-citrullinated protein antibody, and presence of comorbidities, were predictive of the TOFA retention rate. Safety data were comparable to those reported in the registration studies. Conclusions: TOFA demonstrated a long retention rate in RA in a real-world setting. This result, together with the safety data obtained, underscores that TOFA is a viable alternative for patients who have failed treatment with csDMARD and/or biologic DMARDs (bDMARDs). Further large, long-term observational studies are urgently needed to confirm these results
Different Human Copper-Zinc Superoxide Dismutase Mutants, SOD1G93A and SOD1H46R, Exert Distinct Harmful Effects on Gross Phenotype in Mice
Amyotrophic lateral sclerosis (ALS) is a heterogeneous group of fatal neurodegenerative diseases characterized by a selective loss of motor neurons in the brain and spinal cord. Creation of transgenic mice expressing mutant Cu/Zn superoxide dismutase (SOD1), as ALS models, has made an enormous impact on progress of the ALS studies. Recently, it has been recognized that genetic background and gender affect many physiological and pathological phenotypes. However, no systematic studies focusing on such effects using ALS models other than SOD1G93A mice have been conducted. To clarify the effects of genetic background and gender on gross phenotypes among different ALS models, we here conducted a comparative analysis of growth curves and lifespans using congenic lines of SOD1G93A and SOD1H46R mice on two different genetic backgrounds; C57BL/6N (B6) and FVB/N (FVB). Copy number of the transgene and their expression between SOD1G93A and SOD1H46R lines were comparable. B6 congenic mutant SOD1 transgenic lines irrespective of their mutation and gender differences lived longer than corresponding FVB lines. Notably, the G93A mutation caused severer disease phenotypes than did the H46R mutation, where SOD1G93A mice, particularly on a FVB background, showed more extensive body weight loss and earlier death. Gender effect on survival also solely emerged in FVB congenic SOD1G93A mice. Conversely, consistent with our previous study using B6 lines, lack of Als2, a murine homolog for the recessive juvenile ALS causative gene, in FVB congenic SOD1H46R, but not SOD1G93A, mice resulted in an earlier death, implying a genetic background-independent but mutation-dependent phenotypic modification. These results indicate that SOD1G93A- and SOD1H46R-mediated toxicity and their associated pathogenic pathways are not identical. Further, distinctive injurious effects resulted from different SOD1 mutations, which are associated with genetic background and/or gender, suggests the presence of several genetic modifiers of disease expression in the mouse genome
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