Thermal rectification in defect-engineered graphene with asymmetric hole arrangements is assessed via molecular dynamics simulations. Asymmetry in two different configurations (triangular and ...rectangular hole arrangements) is controlled by manipulating geometrical parameters, such as hole size; effects of geometry on the resultant rectification are investigated. Filtering of phonon propagation directions by geometrical confinement, and asymmetric relaxation distance induce a difference in heat transfer depending on transport direction, or thermal rectification. Increase in porosity, which results in additional confinement and larger difference in relaxation, produces more significant thermal rectification. While a rectangular arrangement of holes results in 70% of the maximum thermal rectification, up to 78% of rectification was achieved using a triangular arrangement within 47.5 nm of graphene, which can be attributed to more effective phonon-hole boundary scattering with a triangular arrangement. This study suggests a feasible approach to create thermal rectification and enables its fine control, contributing to the development of phononic devices and enhancement of thermal system design for electronics.
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Knowledge regarding the frequency of ocular abnormalities and abnormal visual function in children exposed to Zika virus (ZIKV) in utero but born without congenital Zika syndrome (CZS) is limited. We ...hypothesized that children exposed to ZIKV in utero born without CZS may have visual impairments in early childhood. We performed ophthalmic examination between 16 and 21 months of age and neurodevelopment assessment at 24 months of age with the Mullen Scales of Early Learning test (MSEL) on children enrolled in a cohort born to women pregnant during and shortly after the ZIKV epidemic in Nicaragua (2016-2017). ZIKV exposure status was defined based on maternal and infant serological testing. Visual impairment was defined as abnormal if the child had an abnormal ophthalmic exam and/or low visual reception score in the MSEL assessment. Of 124 children included in the analysis, 24 (19.4%) were classified as ZIKV-exposed and 100 (80.6%) unexposed according to maternal or cord blood serology. Ophthalmic examination showed that visual acuity did not differ significantly between groups, thus, 17.4% of ZIKV-exposed and 5.2% of unexposed had abnormal visual function (p = 0.07) and 12.5% of the ZIKV-exposed and 2% of the unexposed had abnormal contrast testing (p = 0.05). Low MSEL visual reception score was 3.2-fold higher in ZIKV-exposed than unexposed children, but not statistically significant (OR 3.2, CI: 0.8-14.0; p = 0.10). Visual impairment (a composite measure of visual function or low MESL visual reception score) was present in more ZIKV-exposed than in unexposed children (OR 3.7, CI: 1.2, 11.0; p = 0.02). However, the limited sample size warrants future investigations to fully assess the impact of in utero ZIKV exposure on ocular structures and visual function in early childhood, even in apparently healthy children.
To understand the dynamics of Zika virus (ZIKV)-specific antibody immunity in children born to mothers in a flavivirus-endemic region during and after the emergence of ZIKV in the Americas.
We ...performed serologic testing for ZIKV cross-reactive and type-specific IgG in two longitudinal cohorts, which enrolled pregnant women and their children (PW1 and PW2) after the beginning of the ZIKV epidemic in Nicaragua. Quarterly samples from children over their first two years of life and maternal blood samples at birth and at the end of the two-year follow-up period were studied.
Most mothers in this dengue-endemic area were flavivirus-immune at enrollment. ZIKV-specific IgG (anti-ZIKV EDIII IgG) was detected in 82 of 102 (80.4%) mothers in cohort PW1 and 89 of 134 (66.4%) mothers in cohort PW2, consistent with extensive transmission observed in Nicaragua during 2016. ZIKV-reactive IgG decayed to undetectable levels by 6-9 months in infants, whereas these antibodies were maintained in mothers at the year two time point. Interestingly, a greater contribution to ZIKV immunity by IgG3 was observed in babies born soon after ZIKV transmission. Finally, 43 of 343 (13%) children exhibited persistent or increasing ZIKV-reactive IgG at ≥9 months, with 10 of 30 (33%) tested demonstrating serologic evidence of incident dengue infection.
These data inform our understanding of protective and pathogenic immunity to potential flavivirus infections in early life in areas where multiple flaviviruses co-circulate, particularly considering the immune interactions between ZIKV and dengue and the future possibility of ZIKV vaccination in women of childbearing potential. This study also shows the benefits of cord blood sampling for serologic surveillance of infectious diseases in resource-limited settings.
Zika virus, an arthropod-borne flavivirus pathogen in humans, is unusual because it can be sexually transmitted and can be shed for prolonged periods in semen. We report viral shedding in vaginal ...secretions for up to 6 months, indicating the potential for sexual and vertical transmission by infected women.
JAK1 is a critical effector of pro-inflammatory cytokine signaling and plays important roles in immune function, while abnormal JAK1 activity has been linked to immunological and neoplastic diseases. ...Specific functions of JAK1 in the context of hematopoiesis, and specifically within hematopoietic stem cells (HSCs), have not clearly been delineated. Here, we show that conditional Jak1 loss in HSCs reduces their self-renewal and markedly alters lymphoid/myeloid differentiation in vivo. Jak1-deficient HSCs exhibit decreased competitiveness in vivo and are unable to rescue hematopoiesis in the setting of myelosuppression. They exhibit increased quiescence, an inability to enter the cell cycle in response to hematopoietic stress, and a marked reduction in cytokine sensing, including in response to type I interferons and IL-3. Moreover, Jak1 loss is not fully rescued by expression of a constitutively active Jak2 allele. Together, these data highlight an essential role for Jak1 in HSC homeostasis and stress responses.
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•Conditional deletion of Jak1 in HSCs alters hematopoietic differentiation•Jak1 and Jak2 have non-redundant signaling functions in HSC stress response•Jak1 is a critical mediator of interferon and IL-3 signaling in HSCs•MPN-like phenotypes induced by Jak2 activation are depending on Jak1 signaling
Selective JAK1 inhibition has emerged as a potential strategy for treating autoimmune and hematological diseases. Levine and colleagues show that Jak1 integrates multiple cytokine signals in normal and malignant HSCs to regulate their self-renewal and quiescence, highlighting further potential therapeutic benefits and risks of Jak1 inhibition.
Zika virus (ZIKV) RNA has been found to remain in human semen for up to one year after infection, but the presence of Flavivirus antigens in the different compartments of semen has been largely ...unexplored. Following the introduction of ZIKV in Nicaragua (2016), a prospective study of patients with clinical symptoms consistent with ZIKV was conducted in León to investigate virus shedding in different fluids. ZIKV infection was confirmed in 16 male subjects (≥18 years of age) by RT-qPCR in either blood, saliva or urine. Of these, three provided semen samples at 7, 14, 21, 28, 60 and 180 days postsymptom onset (DPSO) for Flavivirus antigens and RNA studies. These cases were compared with 19 asymptomatic controls. Flavivirus antigens were examined by immunofluorescence (IF) using the 4G2 Mabs, and confocal microscopy was used to explore fluorescence patterns. The three (100%) symptomatic subjects and 3 (16%) of the 19 asymptomatic subjects had Flavivirus antigens and viral RNA in the spermatozoa fraction. The percentage of IF Flavivirus-positive spermatozoa cells ranged from 1.9% to 25% in specimens from symptomatic subjects, as compared with 0.8% to 3.8% in specimens from asymptomatic controls. A marked IF-pattern in the cytoplasmic droplets and tail of the spermatozoa was observed. The sperm concentrations (45 × 10
/mL vs. 63.5 × 10
/mL,
= 0.041) and the total motility percentage (54% vs. 75%,
= 0.009) were significantly lower in specimens from ZIKV-positive than in those of ZIKV-negative. In conclusion, this study demonstrated the presence of Flavivirus antigens and RNA within a time frame of 28 DPSO in sperm cells of symptomatic and asymptomatic subjects during the ZIKV epidemic. These findings have implications for public health, in terms of nonarthropod-born, silent transmission facilitated by sperm cells and potential transmission from asymptomatic males to pregnant women, with consequences to the fetus.
The American Zika virus (ZIKV) epidemic has highlighted the need to gain a better understanding of this emerging virus. The goal of this study was to describe the clinical symptoms, laboratory ...findings, and risk factors for symptomatic ZIKV infection in an area with ongoing transmission of other arboviral infections. We recruited patients at least 2 years of age seeking care at public health centers in León, Nicaragua, between January 2016 and August 2017, for fever, maculopapular rash, and/or nonsuppurative conjunctivitis with a duration of less than 1 week. A laboratory diagnosis of ZIKV was established using a combination of molecular and serological tests. Clinical and laboratory findings and potential risk factors were compared between participants with and without acute ZIKV infection. Fifty-eight (26%) of the 225 participants included in the analysis were found to have acute ZIKV infection. Pregnancy and reports of previous arboviral infection were associated with a higher risk of ZIKV infection. Rash, conjunctivitis, sore throat, and lower absolute neutrophil counts were associated with acute ZIKV infection. The clinical characteristics and risk factors identified were consistent with those identified by previous studies; however, we found sore throat to be a feature of ZIKV infection. We also found that neutrophil counts were lower in ZIKV-infected subjects. These clinical symptoms and laboratory data may help clinicians suspect ZIKV infection during future outbreaks.
Data on long-term neurodevelopmental outcomes of normocephalic children (born with normal head circumference) exposed to Zika virus in utero are scarce. We aimed to compare neurodevelopmental ...outcomes in normocephalic children up to age 48 months with and without Zika virus exposure in utero.
In this prospective cohort study, we included infants from two cohorts of normocephalic children born in León and Managua, Nicaragua during the 2016 Zika epidemic. In León, all women pregnant during the two enrolment periods were eligible. In Managua, mother–child pairs were included from three districts in the municipality of Managua: all women who became pregnant before June 15, 2016, and had a due date of Sept 15, 2016 or later were eligible. Infants were serologically classified as Zika virus-exposed or Zika virus-unexposed in utero and were followed up prospectively until age 48 months. At 36 months and 48 months of age, the Mullen Scales of Early Learning (MSEL) assessment was administered. Primary outcomes were MSEL early learning composite (ELC) scores at 30–48 months in León and 36–48 months in Managua. We used an inverse probability weighting generalised estimating equations model to assess the effect of Zika virus exposure on individual MSEL cognitive domain scores and ELC scores, adjusted for maternal education and age, poverty status, and infant sex.
The initial enrolment period for the León cohort was between Jan 31 and April 5, 2017 and the second was between Aug 30, 2017, and Feb 22, 2018. The enrolment period for the Managua cohort was between Oct 24, 2019, and May 5, 2020. 478 mothers (482 infants) from the León cohort and 615 mothers (609 infants) from the Managua cohort were enrolled, of whom 622 children (303 from the León cohort; 319 from the Managua cohort) were included in the final analysis; four children had microcephaly at birth and thus were excluded from analyses, two from each cohort. 33 (11%) of 303 children enrolled in León and 219 (69%) of 319 children enrolled in Managua were exposed to Zika virus in utero. In both cohorts, no significant differences were identified in adjusted mean ELC scores between Zika virus-exposed and unexposed infants at 36 months (between-group difference 1·2 points 95% CI –4·2 to 6·5 in the León cohort; 2·8 –2·4 to 8·1 in the Managua cohort) or at 48 months (–0·9 –10·8 to 8·8 in the León cohort; 0·1 –5·1 to 5·2 in the Managua cohort). No differences in ELC scores between Zika virus-exposed and unexposed infants exceeded 6 points at any time between 30 months and 48 months in León or between 36 months and 48 months in Managua, which was considered clinically significant in other settings.
We found no significant differences in neurodevelopmental scores between normocephalic children with in-utero Zika virus exposure and Zika virus-unexposed children at age 36 months or 48 months. These findings are promising, supporting typical neurodevelopment in Zika virus-exposed normocephalic children, although additional follow-up and research is warranted.
National Institute of Child Health and Development, National Institute of Allergy and Infectious Diseases, and Fogarty International Center.
For the Spanish translation of the abstract see Supplementary Materials section.
Summary
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Measurements of CO2 efflux from stems and branches, sap velocity, and respiratory activity of excised wood cores were conducted in Dacrydium cupressinum trees that differed in diameter, ...age, and canopy emergence. The objective of this study was to determine if consistent linkages exist among respiratory production of CO2 within stems, xylem transport of CO2, and the rate of CO2 diffusing from stem surfaces.
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Stem CO2 efflux was depressed during periods of sap flow compared with the efflux rate expected for a given stem temperature and was positively correlated with sapwood density. By contrast, no significant relationships were observed between CO2 efflux and the respiratory activity of wood tissues.
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Between 86 and 91% of woody tissue respiration diffused to the atmosphere over a 24‐h period. However, at certain times of the day, xylem transport and internal storage of CO2 may account for up to 13–38% and 12–18%, respectively, of woody tissue respiration.
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These results demonstrate that differences in sap flow rates and xylem anatomy are critically important for explaining within‐ and between‐tree variation in CO2 efflux from stems.
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