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Abstract The authors report a novel structure to improve the high‐frequency performance of nitrogen‐polar GaN deep‐recess high electron mobility transistors (HEMTs) wherein a timed plasma etch was used to tailor the profile of the gate dielectric. A favourable trade‐off between gate fringing capacitance and transconductance was established, resulting in an improved current gain cutoff frequency times gate length (ft·LG) figure of merit compared to standard Schottky‐gate and metal‐insulator‐semiconductor (MIS) HEMTs. The etched gate dielectric MISHEMT demonstrated a maximum ft·LG of 15.0 GHz·µm for an LG of 100 nm.

A wet-etching technique based on a mixture of hydrochloric (HCl) and nitric (HNO3) acids is introduced, demonstrating exceptional 42:1 selectivity for etching N-polar GaN over Al0.24Ga0.76N. In the absence of an AlGaN etch stop layer, the etchant primarily targets N-polar unintentionally doped (UID) GaN, indicating its potential as a suitable replacement for selective dry etches in the fabrication of GaN high-electron-mobility transistors (HEMTs). The efficacy and selectivity of this etchant were confirmed through its application to a gate recess module of a deep-recess HEMT, where, despite a 228% over-etch, the 2.6 nm AlGaN etch stop layer remained intact. We also evaluated the proposed method for the selective etching of the GaN cap in the n+ regrowth process, achieving a contact resistance matching that of a BCl3/SF6 ICP process. These findings underscore the applicability and versatility of the etchant in both the electronic and photonic domains and are particularly applicable to the development of N-polar deep-recess HEMTs.

The role of creativity in teaching gifted children is essential for gifted students to develop their high abilities and creative potential. Teaching and fostering creativity and creative thinking within other academic domains can provide opportunities for excellence and achievement within students' talent development and interests. This manuscript aims to highlight research participants' perceptions of teaching strategies and the importance of creativity in the development of gifted students. These perceptions were captured utlizing a qualitative, case-study design approach whereby the data was collected through semi-structured interviews and observations, and these data were analyzed through an exploratory analysis approach. Findings revealed that the perceptions of the selected participants (three gifted students, two mothers, five teachers, two principals, and one educator) are in line with the recommendations of experts in the field of creativity and giftedness. Implications for educators are discussed, including creating an environment that is responsive to the needs of gifted students and their creativity and cultivating a psychologically safe school space, that promotes the development of creative potential.

The electrical properties of InN give it potential for applications in III-nitride electronic devices, and the use of lower-dimensional epitaxial structures could mitigate issues with the high lattice mismatch of InN to GaN (10%). N-polar MOCVD growth of InN was performed to explore the growth parameter space of the horizontal one-dimensional InN quantum wire-like structures on miscut substrates. The InN growth temperature, InN thickness, and NH3 flow during growth were varied to determine optimal quantum wire segment growth conditions. Quantum wire segment formation was observed through AFM images for N-polar InN samples with a low growth temperature of 540 °C and 1–2 nm of InN. Below 1 nm of InN, quantum dashes formed, and 2-D layers were formed above 2 nm of InN. One-dimensional anisotropy of the electrical conduction of N-polar InN wire-like samples was observed through TLM measurements. The sheet resistances of wire-like samples varied from 10–26 kΩ/□ in the longitudinal direction of the wire segments. The high sheet resistances were attributed to the close proximity of the treading dislocations at the InN/GaN interface and might be lowered by reducing the lattice mismatch of InN wire-like structures with the substrate using high lattice constant base layers such as relaxed InGaN.

Adult skeletal muscle has robust regenerative capabilities due to the presence of a resident stem cell population called satellite cells. Muscle injury leads to these normally quiescent cells becoming molecularly and metabolically activated and embarking on a program of proliferation, migration, differentiation, and fusion culminating in the repair of damaged tissue. These processes are highly coordinated by paracrine signaling events that drive cytoskeletal rearrangement and cell-cell communication. Pannexins are a family of transmembrane channel proteins that mediate paracrine signaling by ATP release. It is known that Pannexin1 (Panx1) is expressed in skeletal muscle, however, the role of Panx1 during skeletal muscle development and regeneration remains poorly understood. Here we show that Panx1 is expressed on the surface of myoblasts and its expression is rapidly increased upon induction of differentiation and that Panx1–/– mice exhibit impaired muscle regeneration after injury. Panx1–/– myoblasts activate the myogenic differentiation program normally, but display marked deficits in migration and fusion. Mechanistically, we show that Panx1 activates P2 class purinergic receptors, which in turn mediate a lipid signaling cascade in myoblasts. This signaling induces bleb-driven amoeboid movement that in turn supports myoblast migration and fusion. Finally, we show that Panx1 is involved in the regulation of cell-matrix interaction through the induction of ADAMTS (Disintegrin-like and Metalloprotease domain with Thrombospondin-type 5) proteins that help remodel the extracellular matrix. These studies reveal a novel role for lipid-based signaling pathways activated by Panx1 in the coordination of myoblast activities essential for skeletal muscle regeneration.

Abstract Background One of the principles underpinning our understanding of ageing is that DNA damage induces a stress response that shifts cellular resources from growth towards maintenance. A contrasting and seemingly irreconcilable view is that prompting growth of, for example, skeletal muscle confers systemic benefit. Methods To investigate the robustness of these axioms, we induced muscle growth in a murine progeroid model through the use of activin receptor IIB ligand trap that dampens myostatin/activin signalling. Progeric mice were then investigated for neurological and muscle function as well as cellular profiling of the muscle, kidney, liver, and bone. Results We show that muscle of Ercc1Δ/− progeroid mice undergoes severe wasting (decreases in hind limb muscle mass of 40–60% compared with normal mass), which is largely protected by attenuating myostatin/activin signalling using soluble activin receptor type IIB (sActRIIB) (increase of 30–62% compared with untreated progeric). sActRIIB‐treated progeroid mice maintained muscle activity (distance travel per hour: 5.6 m in untreated mice vs. 13.7 m in treated) and increased specific force (19.3 mN/mg in untreated vs. 24.0 mN/mg in treated). sActRIIb treatment of progeroid mice also improved satellite cell function especially their ability to proliferate on their native substrate (2.5 cells per fibre in untreated progeroids vs. 5.4 in sActRIIB‐treated progeroids after 72 h in culture). Besides direct protective effects on muscle, we show systemic improvements to other organs including the structure and function of the kidneys; there was a major decrease in the protein content in urine (albumin/creatinine of 4.9 sActRIIB treated vs. 15.7 in untreated), which is likely to be a result in the normalization of podocyte foot processes, which constitute the filtration apparatus (glomerular basement membrane thickness reduced from 224 to 177 nm following sActRIIB treatment). Treatment of the progeric mice with the activin ligand trap protected against the development of liver abnormalities including polyploidy (18.3% untreated vs. 8.1% treated) and osteoporosis (trabecular bone volume; 0.30 mm3 in treated progeroid mice vs. 0.14 mm3 in untreated mice, cortical bone volume; 0.30 mm3 in treated progeroid mice vs. 0.22 mm3 in untreated mice). The onset of neurological abnormalities was delayed (by ~5 weeks) and their severity reduced, overall sustaining health without affecting lifespan. Conclusions This study questions the notion that tissue growth and maintaining tissue function during ageing are incompatible mechanisms. It highlights the need for future investigations to assess the potential of therapies based on myostatin/activin blockade to compress morbidity and promote healthy ageing.

Fully relaxed, crack free, smooth AlxGa1−xN layers with up to 50% Al composition were demonstrated on pseudo-substrates composed of dense arrays of 10 × 10 µm2 compliant porous GaN-on-porous-GaN tiles. The AlGaN layers were grown in steps for a total of 1.3 µm. The growth conditions necessary to demonstrate high quality films at higher Al compositions also suppressed any sidewall growth.

Duchenne Muscular Dystrophy is a devastating disease caused by the absence of a functional rod-shaped cytoplasmic protein called dystrophin. Several avenues are being developed aimed to restore dystrophin expression in boys affected by this X-linked disease. However, its complete cure is likely to need combinational approaches which may include regimes aimed at restoring muscle mass. Augmenting muscle growth through the manipulation of the Myostatin/Activin signalling axis has received much attention. However, we have recently shown that while manipulation of this axis in wild type mice using the sActRIIB ligand trap indeed results in muscle growth, it also had a detrimental impact on the testis. Here we examined the impact of administering a powerful Myostatin/Activin antagonist in two mouse models of Duchenne Muscular Dystrophy. We report that whilst the impact on muscle growth was not always positive, both models showed attenuated testis development. Sperm number, motility and ultrastructure were significantly affected by the sActRIIB treatment. Our report suggests that interventions based on Myostatin/Activin should investigate off-target effects on tissues as well as muscle.

Numerous approaches are being developed to promote post-natal muscle growth based on attenuating Myostatin/Activin signalling for clinical uses such as the treatment neuromuscular diseases, cancer cachexia and sarcopenia. However there have been concerns about the effects of inhibiting Activin on tissues other than skeletal muscle. We intraperitoneally injected mice with the Activin ligand trap, sActRIIB, in young, adult and a progeric mouse model. Treatment at any stage in the life of the mouse rapidly increased muscle mass. However at all stages of life the treatment decreased the weights of the testis. Not only were the testis smaller, but they contained fewer sperm compared to untreated mice. We found that the hypertrophic muscle phenotype was lost after the cessation of sActRIIB treatment but abnormal testis phenotype persisted. In summary, attenuation of Myostatin/Activin signalling inhibited testis development. Future use of molecules based on a similar mode of action to promote muscle growth should be carefully profiled for adverse side-effects on the testis. However the effectiveness of sActRIIB as a modulator of Activin function provides a possible therapeutic strategy to alleviate testicular seminoma development.

Abstract Pathological conditions affecting skeletal muscle function may lead to irreversible volumetric muscle loss (VML). Therapeutic approaches involving acellular matrices represent an emerging and promising strategy to promote regeneration of skeletal muscle following injury. Here we investigated the ability of three different decellularised skeletal muscle scaffolds to support muscle regeneration in a xenogeneic immune-competent model of VML, in which the EDL muscle was surgically resected. All implanted acellular matrices, used to replace the resected muscles, were able to generate functional artificial muscles by promoting host myogenic cell migration and differentiation, as well as nervous fibres, vascular networks, and satellite cell (SC) homing. However, acellular tissue mainly composed of extracellular matrix (ECM) allowed better myofibre three-dimensional (3D) organization and the restoration of SC pool, when compared to scaffolds which also preserved muscular cytoskeletal structures. Finally, we showed that fibroblasts are indispensable to promote efficient migration and myogenesis by muscle stem cells across the scaffolds in vitro. This data strongly support the use of xenogeneic acellular muscles as device to treat VML conditions in absence of donor cell implementation, as well as in vitro model for studying cell interplay during myogenesis.

Snakebite is a major neglected tropical health issue that affects over 5 million people worldwide resulting in around 1.8 million envenomations and 100,000 deaths each year. Snakebite envenomation also causes innumerable morbidities, specifically loss of limbs as a result of excessive tissue/muscle damage. Snake venom metalloproteases (SVMPs) are a predominant component of viper venoms, and are involved in the degradation of basement membrane proteins (particularly collagen) surrounding the tissues around the bite site. Although their collagenolytic properties have been established, the molecular mechanisms through which SVMPs induce permanent muscle damage are poorly understood. Here, we demonstrate the purification and characterisation of an SVMP from a viper (Crotalus atrox) venom. Mass spectrometry analysis confirmed that this protein is most likely to be a group III metalloprotease (showing high similarity to VAP2A) and has been referred to as CAMP (Crotalus atrox metalloprotease). CAMP displays both collagenolytic and fibrinogenolytic activities and inhibits CRP-XL-induced platelet aggregation. To determine its effects on muscle damage, CAMP was administered into the tibialis anterior muscle of mice and its actions were compared with cardiotoxin I (a three-finger toxin) from an elapid snake (Naja pallida) venom. Extensive immunohistochemistry analyses revealed that CAMP significantly damages skeletal muscles by attacking the collagen scaffold and other important basement membrane proteins, and prevents their regeneration through disrupting the functions of satellite cells. In contrast, cardiotoxin I destroys skeletal muscle by damaging the plasma membrane, but does not impact regeneration due to its inability to affect the extracellular matrix. Overall, this study provides novel insights into the mechanisms through which SVMPs induce permanent muscle damage.

The composition of the extracellular matrix (ECM) of skeletal muscle fibers is a unique environment that supports the regenerative capacity of satellite cells; the resident stem cell population. The impact of environment has great bearing on key properties permitting satellite cells to carry out tissue repair. In this study, we have investigated the influence of the ECM and glycolytic metabolism on satellite cell emergence and migration—two early processes required for muscle repair. Our results show that both influence the rate at which satellite cells emerge from the sub-basal lamina position and their rate of migration. These studies highlight the necessity of performing analysis of satellite behavior on their native substrate and will inform on the production of artificial scaffolds intended for medical uses.

A central tenet of skeletal muscle biology is the existence of an inverse relationship between the oxidative fibre capacity and its size. However, robustness of this relationship is unknown. We show that superimposition of Estrogen-related receptor gamma (Errγ) on the myostatin (Mtn) mouse null background (Mtn-/-/ErrγTg/+) results in hypertrophic muscle with a high oxidative capacity thus violating the inverse relationship between fibre size and oxidative capacity. We also examined the canonical view that oxidative muscle phenotype positively correlate with Satellite cell number, the resident stem cells of skeletal muscle. Surprisingly, hypertrophic fibres from Mtn-/-/ErrγTg/+ mouse showed satellite cell deficit which unexpectedly did not affect muscle regeneration. These observations 1) challenge the concept of a constraint between fibre size and oxidative capacity and 2) indicate the important role of the microcirculation in the regenerative capacity of a muscle even when satellite cell numbers are reduced.

Animals are imbued with adaptive mechanisms spanning from the tissue/organ to the cellular scale which insure that processes of homeostasis are preserved in the landscape of size change. However we and others have postulated that the degree of adaptation is limited and that once outside the normal levels of size fluctuations, cells and tissues function in an aberant manner. In this study we examine the function of muscle in the myostatin null mouse which is an excellent model for hypertrophy beyond levels of normal growth and consequeces of acute starvation to restore mass. We show that muscle growth is sustained through protein synthesis driven by Serum/Glucocorticoid Kinase 1 (SGK1) rather than Akt1. Furthermore our metabonomic profiling of hypertrophic muscle shows that carbon from nutrient sources is being channelled for the production of biomass rather than ATP production. However the muscle displays elevated levels of autophagy and decreased levels of muscle tension. We demonstrate the myostatin null muscle is acutely sensitive to changes in diet and activates both the proteolytic and autophagy programmes and shutting down protein synthesis more extensively than is the case for wild-types. Poignantly we show that acute starvation which is detrimental to wild-type animals is beneficial in terms of metabolism and muscle function in the myostatin null mice by normalising tension production.

Skeletal muscle fibres are unique cells in large animals, often composed of thousands of post-mitotic nuclei. Following skeletal muscle damage, resident stem cells, called satellite cells, commit to myogenic differentiation and migrate to carry out repair. Satellite stem cells migrate on muscle fibres through amoeboid movement, which relies on dynamic cell membrane extension and retraction (blebbing). It is not known whether blebbing is due to the intrinsic properties of satellite cells, or induced by features of the myofibre surface. Here, we determined the influence of the muscle fibre matrix on two important features of muscle regeneration: the ability to migrate and to differentiate down a myogenic lineage. We show that the muscle fibre is able to induce amoeboid movement in non-muscle stem cells and non-stem cells. Secondly, we show that prolonged co-culture on myofibres caused amniotic fluid stem cells and breast cancer cells to express MyoD, a key myogenic determinant. Finally, we show that amniotic fluid stem cells co-cultured on myofibres are able to fuse and make myotubes that express Myosin Heavy Chain.

It can be thrilling when parents receive a letter notifying them their child is eligible for the school's gifted program. However the academic and talent development that a child receives at school should also be complemented by social and emotional support at home. There are many books that can help provide the information a parent needs to support a child at home. A book study with other parents is a one way to learn more about supporting their gifted children. It is informal, yet comprehensive, allowing for networking, parent-to-parent support, and resource development. It can serve as a collaborative model to help parents explore the social-emotional aspects of giftedness and foster a child's talents in the context of home and community. The purpose of this article is to examine the various formats and strategies of book studies and provides a list of book recommendations that parents can explore.