Gallium-nitride power transistor (GaN HEMT) and integrated circuit technologies have matured dramatically over the last few years, and many hundreds of thousands of devices have been manufactured and ...fielded in applications ranging from pulsed radars and counter-IED jammers to CATV modules and fourth-generation infrastructure base-stations. GaN HEMT devices, exhibiting high power densities coupled with high breakdown voltages, have opened up the possibilities for highly efficient power amplifiers (PAs) exploiting the principles of waveform engineered designs. This paper summarizes the unique advantages of GaN HEMTs compared to other power transistor technologies, with examples of where such features have been exploited. Since RF power densities of GaN HEMTs are many times higher than other technologies, much attention has also been given to thermal management-examples of both commercial "off-the-shelf" packaging as well as custom heat-sinks are described. The very desirable feature of having accurate large-signal models for both discrete transistors and monolithic microwave integrated circuit foundry are emphasized with a number of circuit design examples. GaN HEMT technology has been a major enabler for both very broadband high-PAs and very high-efficiency designs. This paper describes examples of broadband amplifiers, as well as several of the main areas of high-efficiency amplifier design-notably Class-D, Class-E, Class-F, and Class-J approaches, Doherty PAs, envelope-tracking techniques, and Chireix outphasing.
A three-way Doherty 100-W GaN base-station power amplifier at 2.14 GHz is presented. Simple, but accurate design equations for the output power combiner of the amplifier are introduced. Mixed-signal ...techniques are utilized for uncompromised control of the amplifier stages to optimize efficiency, as well as linearity. The combination of the above techniques resulted in an unprecedented high efficiency over a 12-dB power backoff range, facilitating a record high power-added efficiency for a wideband code division multiple access test signal with high crest factor, while meeting all the spectral requirements for Universal Mobile Telecommunications System base stations.
Crop yields need to nearly double over the next 35 years to keep pace with projected population growth. Improving photosynthesis, via a range of genetic engineering strategies, has been identified as ...a promising target for crop improvement with regard to increased photosynthetic yield and better water-use efficiency (WUE). One approach is based on integrating components of the highly efficient CO2-concentrating mechanism (CCM) present in cyanobacteria (blue-green algae) into the chloroplasts of key C3 crop plants, particularly wheat and rice. Four progressive phases towards engineering components of the cyanobacterial CCM into C3 species can be envisaged. The first phase (1a), and simplest, is to consider the transplantation of cyanobacterial bicarbonate transporters to C3 chloroplasts, by host genomic expression and chloroplast targeting, to raise CO2 levels in the chloroplast and provide a significant improvement in photosynthetic performance. Mathematical modelling indicates that improvements in photosynthesis as high as 28% could be achieved by introducing both of the single-gene, cyanobacterial bicarbonate transporters, known as BicA and SbtA, into C3 plant chloroplasts. Part of the first phase (1b) includes the more challenging integration of a functional cyanobacterial carboxysome into the chloroplast by chloroplast genome transformation. The later three phases would be progressively more elaborate, taking longer to engineer other functional components of the cyanobacterial CCM into the chloroplast, and targeting photosynthetic and WUE efficiencies typical of C4 photosynthesis. These later stages would include the addition of NDH-1-type CO2 pumps and suppression of carbonic anhydrase and C3 Rubisco in the chloroplast stroma. We include a score card for assessing the success of physiological modifications gained in phase 1a.
In C₄ plants, acclimation to growth at low irradiance by means of anatomical and biochemical changes to leaf tissue is considered to be limited by the need for a close interaction and coordination ...between bundle sheath and mesophyll cells. Here differences in relative growth rate (RGR), gas exchange, carbon isotope discrimination, photosynthetic enzyme activity, and leaf anatomy in the C₄ dicot Flaveria bidentis grown at a low (LI; 150 μmol quanta m² s⁻¹) and medium (MI; 500 μmol quanta m² s⁻¹) irradiance and with a 12 h photoperiod over 36 d were examined. RGRs measured using a 3D non-destructive imaging technique were consistently higher in MI plants. Rates of CO₂ assimilation per leaf area measured at 1500 μmmol quanta m² s⁻¹ were higher for MI than LI plants but did not differ on a mass basis. LI plants had lower Rubisco and phosphoenolpyruvate carboxylase activities and chlorophyll content on a leaf area basis. Bundle sheath leakiness of CO₂ ({phi}) calculated from real-time carbon isotope discrimination was similar for MI and LI plants at high irradiance. {phi} increased at lower irradiances, but more so in MI plants, reflecting acclimation to low growth irradiance. Leaf thickness and vein density were greater in MI plants, and mesophyll surface area exposed to intercellular airspace (Sm) and bundle sheath surface area per unit leaf area (Sb) measured from leaf cross-sections were also both significantly greater in MI compared with LI leaves. Both mesophyll and bundle sheath conductance to CO₂ diffusion were greater in MI compared with LI plants. Despite being a C₄ species, F. bidentis is very plastic with respect to growth irradiance.
Human phenotype ontology terms assigned across the 27 participants of primary immunodeficiency cohort.
Primary immunodeficiencies (PIDs) are rare monogenic inborn errors of immunity that result in ...impairment of functions of the human immune system. PIDs have a broad phenotype with increased morbidity and mortality, and treatment choices are often complex. With increased accessibility of next‐generation sequencing (NGS), the rate of discovery of genetic causes for PID has increased exponentially. Identification of an underlying monogenic diagnosis provides important clinical benefits for patients with the potential to alter treatments, facilitate genetic counselling, and pre‐implantation diagnostics. We investigated a NGS PID panel of 242 genes within clinical care across a range of PID phenotypes. We also evaluated Phenomizer to predict causal genes from human phenotype ontology (HPO) terms. Twenty‐seven participants were recruited, and a total of 15 reportable variants were identified in 48% (13/27) of the participants. The panel results had implications for treatment in 37% (10/27) of participants. Phenomizer identified the genes harbouring variants from HPO terms in 33% (9/27) of participants. This study shows the clinical efficacy that genetic testing has in the care of PID. However, it also highlights some of the disadvantages of gene panels in the rapidly moving field of PID genomics and current challenges in HPO term assignment for PID.
Improving global yields of agricultural crops is a complex challenge with evidence indicating benefits in productivity are achieved by enhancing photosynthetic carbon assimilation. Towards improving ...rates of CO2 capture within leaf chloroplasts, this study shows the versatility of plastome transformation for expressing the Synechococcus PCC7002 BicA bicarbonate transporter within tobacco plastids. Fractionation of chloroplast membranes from transplastomic tobBicA lines showed that ~75% of the BicA localized to the thylakoid membranes and ~25% to the chloroplast envelope. BicA levels were highest in young emerging tobBicA leaves (0.12 μmol m–2, ≈7mg m–2) accounting for ~0.1% (w/w) of the leaf protein. In these leaves, the molar amount of BicA was 16-fold lower than the abundant thylakoid photosystem II D1 protein (~1.9 μmol m–2) which was comparable to the 9:1 molar ratio of D1:BicA measured in air-grown Synechococcus PCC7002 cells. The BicA produced had no discernible effect on chloroplast ultrastructure, photosynthetic CO2-assimilation rates, carbon isotope discrimination, or growth of the tobBicA plants, implying that the bicarbonate transporter had little or no activity. These findings demonstrate the utility of plastome transformation for targeting bicarbonate transporter proteins into the chloroplast membranes without impeding growth or plastid ultrastructure. This study establishes the span of experimental measurements required to verify heterologous bicarbonate transporter function and location in chloroplasts and underscores the need for more detailed understanding of BicA structure and function to identify solutions for enabling its activation and operation in leaf chloroplasts.
Individuals from three families ascertained in Bogota, Colombia, showing syndromic phenotypes, including cleft lip and/or palate, were exome‐sequenced. In each case, sequencing revealed the ...underlying causal variation confirming or establishing diagnoses. The findings include very rare and novel variants providing insights into genotype and phenotype relationships. These include the molecular diagnosis of an individual with Nager syndrome and a family exhibiting an atypical incontinentia pigmenti phenotype with a missense mutation in IKBKG. IKBKG mutations are typically associated with preterm male death, but this variant is associated with survival for 8–15 days. The third family exhibits unusual phenotypic features and the proband received a provisional diagnosis of Pierre Robin sequence (PRS). Affected individuals share a novel deleterious mutation in IRF6. Mutations in IRF6 cause Van der Woude and popliteal pterygium syndrome and contribute to nonsyndromic cleft lip phenotypes but have not previously been associated with a PRS phenotype. Exome sequencing followed by in silico screening to identify candidate causal variant(s), and functional assay in some cases offers a powerful route to establishing molecular diagnoses. This approach is invaluable for conditions showing phenotypic and/or genetic heterogeneity including cleft lip and/or palate phenotypes where many underlying causal genes have not been identified.
The husk surrounding the ear of corn/maize (Zea mays) has widely spaced veins with a number of interveinal mesophyll (M) cells and has been described as operating a partial C₃ photosynthetic pathway, ...in contrast to its leaves, which use the C₄ photosynthetic pathway. Here, we characterized photosynthesis in maize husk and leaf by measuring combined gas exchange and carbon isotope discrimination, the oxygen dependence of the CO₂ compensation point, and photosynthetic enzyme activity and localization together with anatomy. The CO₂ assimilation rate in the husk was less than that in the leaves and did not saturate at high CO₂, indicating CO₂ diffusion limitations. However, maximal photosynthetic rates were similar between the leaf and husk when expressed on a chlorophyll basis. The CO₂ compensation points of the husk were high compared with the leaf but did not vary with oxygen concentration. This and the low carbon isotope discrimination measured concurrently with gas exchange in the husk and leaf suggested C₄-like photosynthesis in the husk. However, both Rubisco activity and the ratio of phosphoeno/pyruvate carboxylase to Rubisco activity were reduced in the husk. Immunolocalization studies showed that phosphoeno/pyruvate carboxylase is specifically localized in the layer of M cells surrounding the bundle sheath cells, while Rubisco and glycine decarboxylase were enriched in bundle sheath cells but also present in M cells. We conclude that maize husk operates C₄ photosynthesis dispersed around the widely spaced veins (analogous to leaves) in a diffusion-limited manner due to low M surface area exposed to intercellular air space, with the functional role of Rubisco and glycine decarboxylase in distant M yet to be explained.
Autosomal dominant tubulointerstitial kidney disease (ADTKD) caused by mutations in the UMOD gene (ADTKD-UMOD) is considered rare and often remains unrecognised. We aimed to establish the prevalence ...of genetic kidney diseases, ADTKD and ADTKD-UMOD in adult chronic kidney disease (CKD) patients, and to investigate characteristic features.
We sent questionnaires on family history to all patients with CKD stages 3-5 in our tertiary renal centre to identify patients with inherited renal disease. Details on clinical and family history were obtained from patient interviews and clinical records. Sanger sequencing of the UMOD gene was performed from blood or saliva samples.
2027 of 3770 sent questionnaires were returned. 459 patients reported a family history, which was consistent with inherited kidney disease in 217 patients. 182 non-responders with inherited kidney diseases were identified through a database search. Of these 399 individuals, 252 had autosomal dominant polycystic kidney disease (ADPKD), 28 had ADTKD, 25 had Alports, and 44 were unknown, resulting in 11% of CKD 3-5 patients and 19% of end-stage renal disease patients with genetic kidney diseases. Of the unknown, 40 were genotyped, of whom 31 had findings consistent with ADTKD. 30% of unknowns and 39% of unknowns with ADTKD had UMOD mutations. Altogether, 35 individuals from 18 families were found to have ten distinct UMOD mutations (three novel), making up 1% of patients with CKD 3-5, 2% of patients with end-stage renal disease, 9% of inherited kidney diseases and 56% with ADTKD. ADTKD-UMOD was the most common genetic kidney disease after ADPKD with a population prevalence of 9 per million. Less proteinuria and haematuria, but not hyperuricaemia or gout were predictive of ADTKD-UMOD. The main limitations of the study are the single-centre design and a predominantly Caucasian population.
The prevalence of genetic kidney diseases and ADTKD-UMOD is significantly higher than previously described. Clinical features poorly predicted ADTKD-UMOD, highlighting the need for genetic testing guided by family history alone.
Fifteen years ago subterranean clover (
Trifolium subterraneum) and annual medics (
Medicago spp.) dominated annual pasture legume sowings in southern Australia, while limited pasture legume options ...existed for cropping areas of subtropical Australia. Since then a number of sustainability and economic challenges to existing farming systems have emerged, exposing shortcomings in these species and the lack of legume biodiversity. Public breeding institutions have responded to these challenges by developing 58 new annual and short-lived perennial pasture legumes with adaptation to both existing and new farming systems. This has involved commercialisation of new species and overcoming deficiencies in traditional species. Traits incorporated in legumes of Mediterranean Basin origin for the Mediterranean, temperate and southern subtropical climates of Australia include deeper root systems, protection from false breaks (germination-inducing rainfall events followed by death from drought), a range of hardseed levels, acid-soil tolerant root nodule symbioses, tolerance to pests and diseases and provision of lower cost seed through ease of seed harvesting and processing. Ten new species, French serradella (
Ornithopus sativus), biserrula (
Biserrula pelecinus), sulla (
Hedysarum coronarium), gland (
Trifolium glanduliferum), arrowleaf (
Trifolium vesiculosum), eastern star (
Trifolium dasyurum) and crimson (
Trifolium incarnatum) clovers and sphere (
Medicago sphaerocarpos), button (
Medicago orbicularis) and hybrid disc (
Medicago tornata
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Medicago littoralis) medics have been commercialised. Improved cultivars have also been developed of subterranean (
T. subterraneum), balansa (
Trifolium michelianum), rose (
Trifolium hirtum), Persian (
Trifolium resupinatum) and purple (
Trifolium purpureum) clovers, burr (
Medicago polymorpha), strand (
M. littoralis), snail (
Medicago scutellata) and barrel (
Medicago truncatula) medics and yellow serradella (
Ornithopus compressus). New tropical legumes for pasture phases in subtropical cropping areas include butterfly pea (
Clitoria ternatea), burgundy bean (
Macroptilium bracteatum) and perennial lablab (
Lablab purpureus). Other species and cultivars of Mediterranean species are likely to be released soon. The contributions of genetic resources, rhizobiology, pasture ecology and agronomy, plant pathology, entomology, plant chemistry and animal science have been paramount to this success. A farmer survey in Western Australia has shown widespread adoption of the new pasture legumes, while adoption of new tropical legumes has also been high in cropping areas of the subtropics. This trend is likely to increase due to the increasing cost of inorganic nitrogen, the need to combat herbicide-resistant crop weeds and improved livestock prices. Mixtures of these legumes allows for more robust pastures buffered against variable seasons, soils, pests, diseases and management decisions. This paper discusses development of the new pasture legumes, their potential use and deficiencies in the current suite.
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