Enhancing LED spectral output with perylene dye-based remote phosphor.

LEDs offer a wide range of spectral output with high efficiencies. However, the efficiencies of solid-state LEDs with green and yellow wavelengths are rather low due to the lack of suitable direct bandgap materials. Here, we introduce and develop perylene-enhanced green LEDs that produce a higher wall-plug efficiency of 48% compared to 38% for a solid-state green LED. While the wall-plug efficiency of the perylene-enhanced red LED is still lower than that of a solid-state red LED, we demonstrate that remote phosphor colour converters are effective solutions for targeted spectral tuning across the visible spectrum for horticultural lighting. In this work, we retrofit existing white LEDs and augment photosynthesis via spectral output tuning to achieve a higher red-to-blue ratio. Our results show a significant improvement in plant growth by up to 39%, after a 4-month growth cycle. We observe no visible degradation of the colour converter even under continuous illumination with a current of 400 mA. This opens up new opportunities for using perylene-based colour converters for tuneable illumination with high brightness.

Efficient recall of SARS-CoV-2 variant-reactive B cells and T responses in the elderly upon heterologous mRNA vaccines as boosters.

Waning antibody levels against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the emergence of variants of concern highlight the need for booster vaccinations. This is particularly important for the elderly population, who are at a higher risk of developing severe coronavirus disease 2019 (COVID-19) disease. While studies have shown increased antibody responses following booster vaccination, understanding the changes in T and B cell compartments induced by a third vaccine dose remains limited. We analyzed the humoral and cellular responses in subjects who received either a homologous messenger RNA(mRNA) booster vaccine (BNT162b2 + BNT162b2 + BNT162b2; ''BBB") or a heterologous mRNA booster vaccine (BNT162b2 + BNT162b2 + mRNA-1273; ''BBM") at Day 0 (prebooster), Day 7, and Day 28 (postbooster). Compared with BBB, elderly individuals (≥60 years old) who received the BBM vaccination regimen display higher levels of neutralizing antibodies against the Wuhan and Delta strains along with a higher boost in immunoglobulin G memory B cells, particularly against the Omicron variant. Circulating T helper type 1(Th1), Th2, Th17, and T follicular helper responses were also increased in elderly individuals given the BBM regimen. While mRNA vaccines increase antibody, T cell, and B cell responses against SARS-CoV-2 1 month after receiving the third dose booster, the efficacy of the booster vaccine strategies may vary depending on age group and regimen combination.

Evaluation of the safety and immunogenicity of different COVID-19 vaccine combinations in healthy individuals: study protocol for a randomized, subject-blinded, controlled phase 3 trial [PRIBIVAC].

BACKGROUND: Over 2021, COVID-19 vaccination programs worldwide focused on raising population immunity through the primary COVID-19 vaccine series. In Singapore, two mRNA vaccines (BNT162b2 and mRNA-1273) and the inactivated vaccine CoronaVac are currently authorized under the National Vaccination Programme for use as the primary vaccination series. More than 90% of the Singapore population has received at least one dose of a COVID-19 vaccine as of December 2021. With the demonstration that vaccine effectiveness wanes in the months after vaccination, and the emergence of Omicron which evades host immunity from prior infection and/or vaccination, attention in many countries has shifted to how best to maintain immunity through booster vaccinations. METHODS: The objectives of this phase 3, randomized, subject-blinded, controlled clinical trial are to assess the safety and immunogenicity of heterologous boost COVID-19 vaccine regimens (intervention groups 1-4) compared with a homologous boost regimen (control arm) in up to 600 adult volunteers. As non-mRNA vaccine candidates may enter the study at different time points depending on vaccine availability and local regulatory approval, participants will be randomized at equal probability to the available intervention arms at the time of randomization. Eligible participants will have received two doses of a homologous mRNA vaccine series with BNT162b2 or mRNA-1273 at least 6 months prior to enrolment. Participants will be excluded if they have a history of confirmed SARS or SARS-CoV-2 infection, are immunocompromised, or are pregnant. Participants will be monitored for adverse events and serious adverse events by physical examinations, laboratory tests and self-reporting. Blood samples will be collected at serial time points [pre-vaccination/screening (day - 14 to day 0), day 7, day 28, day 180, day 360 post-vaccination] for assessment of antibody and cellular immune parameters. Primary endpoint is the level of anti-SARS-CoV-2 spike immunoglobulins at day 28 post-booster and will be measured against wildtype SARS-CoV-2 and variants of concern. Comprehensive immune profiling of the humoral and cellular immune response to vaccination will be performed. DISCUSSION: This study will provide necessary data to understand the quantity, quality, and persistence of the immune response to a homologous and heterologous third booster dose of COVID-19 vaccines. This is an important step in developing COVID-19 vaccination programs beyond the primary series. TRIAL REGISTRATION: ClinicalTrials.gov NCT05142319 . Registered on 2 Dec 2021.

Antibody Response of Heterologous vs Homologous Messenger RNA Vaccine Boosters Against the Severe Acute Respiratory Syndrome Coronavirus 2 Omicron Variant: Interim Results from the PRIBIVAC Study, a Randomized Clinical Trial.

BACKGROUND: Waning antibody levels post-vaccination and the emergence of variants of concern (VOCs) capable of evading protective immunity have raised the need for booster vaccinations. However, which combination of coronavirus disease 2019 (COVID-19) vaccines offers the strongest immune response against the Omicron variant is unknown. METHODS: This randomized, participant-blinded, controlled trial assessed the reactogenicity and immunogenicity of different COVID-19 vaccine booster combinations. A total of 100 BNT162b2-vaccinated individuals were enrolled and randomized 1:1 to either homologous (BNT162b2 + BNT162b2 + BNT162b2; "BBB") or heterologous messenger RNA (mRNA) (BNT162b2 + BNT162b2 + mRNA-1273; "BBM") booster vaccine. The primary end point was the level of neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) wild-type and VOCs at day 28. RESULTS: A total of 51 participants were allocated to BBB and 49 to BBM; 50 and 48, respectively, were analyzed for safety and immunogenicity outcomes. At day 28 post-boost, mean SARS-CoV-2 spike antibody titers were lower with BBB (22 382 IU/mL; 95% confidence interval [CI], 18 210 to 27 517) vs BBM (29 751 IU/mL; 95% CI, 25 281 to 35 011; P = .034) as was the median level of neutralizing antibodies: BBB 99.0% (interquartile range [IQR], 97.9% to 99.3%) vs BBM 99.3% (IQR, 98.8% to 99.5%; P = .021). On subgroup analysis, significant higher mean spike antibody titer, median surrogate neutralizing antibody level against all VOCs, and live Omicron neutralization titer were observed only in older adults receiving BBM. Both vaccines were well tolerated. CONCLUSIONS: Heterologous mRNA-1273 booster vaccination compared with homologous BNT123b2 induced a stronger neutralizing response against the Omicron variant in older individuals. CLINICAL TRIALS REGISTRATION: NCT05142319.

Structural color three-dimensional printing by shrinking photonic crystals.

The coloration of some butterflies, Pachyrhynchus weevils, and many chameleons are notable examples of natural organisms employing photonic crystals to produce colorful patterns. Despite advances in nanotechnology, we still lack the ability to print arbitrary colors and shapes in all three dimensions at this microscopic length scale. Here, we introduce a heat-shrinking method to produce 3D-printed photonic crystals with a 5x reduction in lattice constants, achieving sub-100-nm features with a full range of colors. With these lattice structures as 3D color volumetric elements, we printed 3D microscopic scale objects, including the first multi-color microscopic model of the Eiffel Tower measuring only 39 µm tall with a color pixel size of 1.45 µm. The technology to print 3D structures in color at the microscopic scale promises the direct patterning and integration of spectrally selective devices, such as photonic crystal-based color filters, onto free-form optical elements and curved surfaces.

Stacking of colors in exfoliable plasmonic superlattices.

Color printing with plasmonic resonators can overcome limitations in pigment-based printing approaches. While layering in pigment-based prints results in familiar color mixing effects, the color effects of stacking plasmonic resonator structures have not been investigated. Here, we demonstrate an experimental strategy to fabricate a 3-tiered complex superlattice of nanostructures with multiple sets of building blocks. Laser interference lithography was used to fabricate the nanostructures and a thin-layer of aluminum was deposited to introduce plasmonic colors. Interestingly, the structures exhibited drastic color changes when the layers of structures were sequentially exfoliated. Our theoretical analysis shows that the colors of the superlattice nanostructure were predominantly determined by the plasmonic properties of the two topmost layers. These results suggest the feasibility of the sub-wavelength vertical stacking of multiple plasmonic colors for applications in sensitive tamper-evident seals, dense 3D barcoding, and substrates for plasmonic color laser printing.

All-metal nanostructured substrates as subtractive color reflectors with near-perfect absorptance.

All-metal structures consisting of nanoprotrusions on a bulk silver layer are theoretically investigated and shown to have narrow near-perfect absorption peaks (>95%). Within the constraints of constant nanostructure height (50 nm) and pitch (250 nm), these peaks are tunable across the visible spectrum by adjusting the width and shape of the protrusion. The peaks are caused by localized surface plasmon resonances leading to dissipation on the surface of the protrusions. As the peaks occur in the visible range, they produce subtractive colors with high saturation, in accordance with Schrödinger's rule for maximum pigment purity.

Inherited duplication Xq27-qter at Xp22.3 in severely affected males: molecular cytogenetic evaluation and clinical description in three unrelated families.

We describe the clinical phenotype in four males from three families with duplication (X)(qter-->q27::p22.3-->qter). This is an unusual duplication of the distal long arm segment, Xq27-qter, onto the distal short arm of the X chromosome at Xp22.3, as shown by fluorescent in situ hybridization analysis with multiple X-specific probes. The patients are young male offspring of three unrelated, phenotypically normal carrier women. The affected males have similar clinical manifestations including severe growth retardation and developmental delay, severe axial hypotonia, and minor anomalies. Such clinical similarity in three unrelated families demonstrates that this chromosome abnormality results in a new and distinct clinical phenotype. Replication studies, performed on two of the mothers, provided evidence that inactivation of the abnormal X chromosome permitted the structural abnormality to persist in these families for a generation or more in females without phenotypic expression.

Postnatal confirmation of prenatally diagnosed trisomy 16 mosaicism in two phenotypically abnormal liveborns.

Two phenotypically abnormal liveborns in whom trisomy 16 mosaicism was diagnosed prenatally by amniocentesis are described. Analysis of a percutaneous umbilical blood sample in one case revealed a normal chromosomal complement. Ultrasound examinations performed at the time of amniocentesis were normal. Serial sonography during the late second and third trimesters demonstrated progressive intrauterine growth retardation (IUGR) in both fetuses and a cardiac defect in one. At birth, both infants had dysmorphic features and multiple congenital anomalies. Trisomy 16 mosaicism was confirmed postnatally in both infants in skin fibroblasts; however, peripheral blood samples contained only chromosomally normal cells. The two mosaic trisomy 16 cases described in this report, together with the five confirmed cases reported previously, demonstrate the need for caution in the counselling of patients when trisomy 16 mosaicism is diagnosed prenatally in amniotic fluid samples. Such cases potentially can result in the birth of dysmorphic infants with significant birth defects, growth retardation, and possible developmental disabilities.

Distribution of diploidy, polyploidy, and endoreduplication in fra(X) positive and negative lymphocytes, amniocytes, and chorionic villi.

Expression of fragile X [fra(X)] (q27.3) and endoreduplicated metaphases have been reported in methotrexate-treated (MTX) fra(X) cultures (Kerem B, Biotein R, Schaap T [1988]: Chromosoma 97: 6-10). Further, new data (Kimchi-Sarfaty C, Goitein R, Kerem B, Werner M, Medan B, Schaap T [1991]: Am J Med Genet, this issue) indicate that MTX may specifically induce polyploidy and endoreduplication in cells with the fra(X) mutation. To confirm and extend these results, we have studied short-term lymphocyte cultures incubated in M199, a folate deficient system, and RPMI-1640 in the presence and absence of 5-fluorodeoxyuridine (FUdR) exposure during the last day of a 4 day culture. No endoreduplicated cells were seen under these conditions and there was no change in the level of polyploidy. We also studied the distribution of polyploid and endoreduplicated cells in amniotic fluid and chorionic villus sample cultures from one fra(X) positive and 4 at-risk specimens. No increase in the incidence of polyploidy or endoreduplication was observed in cultures exposed to MTX for both 24 and 48 hours from a fra(X) positive amniotic fluid case. Cytogenetic results were fra(X) negative for the remaining 4 cases tested. There was significant discordance between our findings and those expected based on MTX-induced increased frequencies of polyploidy and endoreduplication. Thus, our studies do not confirm the reported correlation between the presence of FRAXA and increased frequencies of polyploidy and endoreduplication in MTX-exposed amniocyte cultures and there was no evidence for increased levels of polyploidy and endoreduplication in short-term fra(X) lymphocyte cultures exposed to non-MTX fra(X) induction.

A test for Fanconi's anemia.

A simple and reliable cytogenetic test for Fanconi's anemia (FA) that is based on the hypersensitivity of FA cells to mitomycin C (MC) is described. Equal volumes of whole blood from a patient in whom the diagnosis of FA is suspected and from a normal person of the opposite sex are co-cultured in phytohemagglutinin-containing medium in the presence and absence of MC. After five days' co-cultivation, 100 quinacrine-stained metaphases from both the MC-containing and the MC-free cultures are examined for the presence of a Y chromosome using fluorescence microscopy. In all bona fide FA patients in whom testing was successful, hypersensitivity to MC was readily demonstrated by the striking deficiency of FA metaphases (0.9% to 14.9%) in the MC-containing co-cultures. In contrast, none of the three patients with Diamond-Blackfan anemia and none of the five with undiagnosed conditions reminiscent of FA exhibited hypersensitivity to MC; cells from them, from parents of FA patients, and from several normal laboratory personnel constituted approximately half of the metaphases (40.4% to 71.2%) of MC-containing co-cultures, as would be expected in the absence of hypersensitivity to MC.

Different mutations are responsible for the elevated sister-chromatid exchange frequencies characteristic of Bloom's syndrome and hamster EM9 cells.

Experimental hybridization of cultured cells was employed to determine whether the strikingly elevated rates of sister-chromatid exchange (SCE) exhibited by Bloom's syndrome (BS) and hamster cell line EM9 have the same or different bases. Seventeen cell lines were developed from polyethylene glycol-treated mixtures of BS and EM9 cells. Cytogenetic analysis proved the hybrid nature of 12 of the lines; 9 of those 12 exhibited low (normal) numbers of SCEs, signifying complementation. The parental BS and EM9 cells, although resembling each other in exhibiting very high SCE frequencies in BrdUrd-containing medium, differ from one another with respect to their proliferative abilities in such medium, the EM9 cells but not the BS cells being exquisitely hypersensitive to BrdUrd. In the low-SCE hybrid lines, hypersensitivity to growth in BrdUrd-containing medium was restored to normal whereas the hypersensitivity was retained by the high-SCE hybrids. It is concluded, first, that the mutations in BS and EM9 cells are different and, second, that both the elevated SCE frequency and the excessive BrdUrd hypersensitivity of EM9 cells are due to the same mutation.

Altered DNA ligase I activity in Bloom's syndrome cells.

Cells from patients with Bloom's syndrome, a rare disease associated with increased cancer frequency, exhibit cytological abnormalities. These include increased numbers of homologous chromatid interchange figures and sister-chromatid exchanges, together with abnormally slow replicon-fork progression and retarded rate of DNA-chain maturation, and suggest that the primary defect in this recessive disorder affects S-phase DNA replication. DNA ligases and DNA polymerases have long been prime candidates for abnormality in Bloom's syndrome, but various studies of DNA polymerases in Bloom's syndrome cells have disclosed no abnormalities. Evidence is presented here, as in the accompanying paper from a different laboratory, for the existence in Bloom's syndrome of an abnormality of the DNA ligase involved in semi-conservative DNA replication.

Hybridization with human cells corrects the elevated SCE frequency and BrdU hypersensitivity of hamster cell line EM9.

Cells of the Chinese hamster line EM9 exhibit an elevated SCE frequency and a decreased proliferative response in bromodeoxyuridine (BrdU)-containing medium. Here, these phenotypic features were examined experimentally using polyethylene glycol fusion of EM9 and normal human cells. EM9/human hybrids exhibited both normal SCE frequencies and normal proliferative responses in BrdU-containing medium, suggesting that SCE elevation and BrdU hypersensitivity in EM9 have a common molecular basis.

Sister-chromatid exchange induction by sodium selenite: reduced glutathione converts Na2SeO3 to its SCE-inducing form.

Sodium selenite (Na2SeO3) is an anticarcinogenic/antimutagenic agent that exhibits carcinogenic/mutagenic properties in some short-term test systems used for the detection of DNA-damaging agents. One such test system is sister-chromatid exchange (SCE) induction. Na2SeO3 induces SCEs only if red blood cells (RBCs) are present to 'activate' it to its SCE-inducing form. Here, the ability of reduced glutathione, a major component of RBCs, to serve as an RBC substitute in the activation of Na2SeO3 was determined. Reduced glutathione (10(-4) and 10(-3) M) was shown to be as capable as RBCs in activating Na2SeO3 (7.95 X 10(-6) M) to its SCE-inducing form. These data suggest strongly that the pathway normally utilized by RBCs in the metabolism of Na2SeO3 is the same as that in which Na2SeO3 is converted to its SCE-inducing form.

Bloom's syndrome and EM9 cells in BrdU-containing medium exhibit similarly elevated frequencies of sister chromatid exchange but dissimilar amounts of cellular proliferation and chromosome disruption.

Bloom's syndrome (BS) and EM9 cells both display elevated frequencies of sister chromatid exchange (SCE) following growth for two rounds of DNA replication in bromodeoxyuridine (BrdU)-containing medium. To learn whether hyperresponsiveness to BrdU itself might play a role in causing the SCE elevation, the effects of BrdU on two other parameters, cellular proliferation and chromosome disruption, were examined, comparing the responses of BS and normal lymphoblastoid cells and of EM9 and CHO cells. BS and normal cells responded similarly with respect to growth for 4 days in BrdU-containing medium (0, 1, 3, and 5 micrograms/ml). Chromosome aberrations were increased only slightly in the BS and normal cells after 2 days in BrdU. CHO cells responded to growth in BrdU-containing medium like BS and normal cells; however, little growth of EM9 was detected at any of the BrdU concentrations employed. CHO and EM9 cells also exhibited strikingly different amounts of chromosome damage following growth in BrdU. After 2 days in 1, 3, and 5 micrograms/ml BrdU 21%, 46%, and 50%, respectively, of the CHO cells had chromosome aberrations in contrast to 92%, 96%, and 98% of the EM9 cells. Most of the aberrations in the BrdU-treated CHO cells consisted of what appeared to be polycentric and ring chromosomes or chromosomes exhibiting telemere association. Acentric fragments were absent from most cells with polycentric and ring chromosomes, indicating either that the abnormal chromosomes were formed during an earlier cell cycle or that the abnormal chromosomes represent a form of association in which the telomeres are apposed so tightly that the juncture between chromosomes cannot be identified microscopically.(ABSTRACT TRUNCATED AT 250 WORDS)

Bloom's syndrome: evidence for an increased mutation frequency in vivo.

The incidence of lymphocytes resistant to the purine analog 6-thioguanine was studied in seven patients with Bloom's syndrome. The mean frequency was 17.3 X 10(-4). The mean incidence in age- and sex-matched controls was 2.1 X 10(-4), so approximately eight times the normal number of 6-thioguanine-resistant lymphocytes were detected in Bloom's syndrome blood. The basis for this increase is unknown, but the inherent genomic instability demonstrated in the form of chromosomal aberrations is one possible explanation.

Sister-chromatid exchange induction by sodium selenite: plasma protein-bound selenium is not the active SCE-inducing metabolite of Na2SeO3.

Sodium selenite (Na2SeO3) is an anticarcinogenic/antimutagenic/anticlastogenic agent that under certain incubation conditions induces sister-chromatid exchanges (SCEs), unscheduled DNA synthesis, and chromosome aberrations. Previous work has shown that SCE induction by Na2SeO3 depends on the presence of red blood cells (RBCs). Therefore, Na2SeO3 uptake and release by RBCs was studied in the present report as was the effect of plasma protein-bound selenium, the end product of Na2SeO3 metabolism by RBCs, on the SCE frequency of purified lymphocyte cultures. Na2SeO3 uptake by human whole blood, RBCs in plasma, RBCs in fetal calf serum, and RBCs in Hanks' balanced salt solution occurs rapidly, reaching a maximum after 2 min (37 degrees C). Release of Na2SeO3 from RBCs depends on the presence of plasma proteins to which the metabolized selenium becomes bound. In spite of the fact that plasma protein-bound selenium is the major product of Na2SeO3 metabolism by RBCs, the SCE frequency of purified lymphocyte cultures was unchanged when plasma protein-bound selenium (7.90 X 10(-6) and 1.19 X 10(-5) M) was added to the medium for the final 19 h of incubation. Further study showed that Na2SeO3 could induce SCEs in blood cultures that had been washed to remove plasma proteins and incubated in medium 199, a maintenance medium lacking fetal calf serum. These findings indicate that a Na2SeO3 metabolite other than plasma protein-bound selenium is responsible for Na2SeO3's SCE-inducing ability in human whole-blood cultures.

Dependence of the sister-chromatid exchange-inducing abilities of inorganic selenium compounds on the valence state of selenium.

Inorganic selenium (Se) compounds having Se of different valence states were tested for their abilities to induce sister-chromatid exchanges (SCEs) in human whole blood cultures. The Se compounds tested (and their Se valence states) were: sodium selenide (Se(2-)), selenium dioxide (Se(4+)), selenium (Se(0)), sodium selenate (Se(6+)), and sodium selenite (Se(4+)). Human whole blood cultures were exposed to concentrations of these compounds ranging from 1.12 X 10(-6)-8.00 X 10(-5) M for the final 18 h of the 96-h incubation period. Only sodium selenate failed to induce SCEs at high concentrations. Of the 4 SCE-inducing Se compounds studied selenium was the most potent inducer of SCEs, and sodium selenite was the least effective SCE-inducing agent. The SCE-inducing abilities of the Se compounds in decreasing order of their effectiveness were: selenium > selenium dioxide > solium selenide > sodium selenite > sodium selenate.

Rubber solvent: a clastogenic agent that fails to induce sister-chromatid exchanges.

Rubber solvent was tested for its ability to induce chromosome aberrations and sister-chromatid exchanges in human whole blood cultures. Following exposure to relatively low rubber solvent concentrations (0.0125% and greater) significant increases in the frequencies of chromatid gaps and breaks were observed. At higher rubber-solvent concentrations (0.05% and greater) there were also significant increases in the frequency of chromosome breaks. In contrast to the increase in chromosome aberrations following rubber-solvent exposure, rubber-solvent concentrations up to the toxic level failed to produce increases in the sister-chromatid exchange frequency.