Phosphorylation of proteins on tyrosine (Tyr) residues evolved in metazoan organisms as a mechanism of coordinating tissue growth
. Multicellular eukaryotes typically have more than 50 distinct ...protein Tyr kinases that catalyse the phosphorylation of thousands of Tyr residues throughout the proteome
. How a given Tyr kinase can phosphorylate a specific subset of proteins at unique Tyr sites is only partially understood
. Here we used combinatorial peptide arrays to profile the substrate sequence specificity of all human Tyr kinases. Globally, the Tyr kinases demonstrate considerable diversity in optimal patterns of residues surrounding the site of phosphorylation, revealing the functional organization of the human Tyr kinome by substrate motif preference. Using this information, Tyr kinases that are most compatible with phosphorylating any Tyr site can be identified. Analysis of mass spectrometry phosphoproteomic datasets using this compendium of kinase specificities accurately identifies specific Tyr kinases that are dysregulated in cells after stimulation with growth factors, treatment with anti-cancer drugs or expression of oncogenic variants. Furthermore, the topology of known Tyr signalling networks naturally emerged from a comparison of the sequence specificities of the Tyr kinases and the SH2 phosphotyrosine (pTyr)-binding domains. Finally we show that the intrinsic substrate specificity of Tyr kinases has remained fundamentally unchanged from worms to humans, suggesting that the fidelity between Tyr kinases and their protein substrate sequences has been maintained across hundreds of millions of years of evolution.
Flexible integrated circuits with complex functionalities are the missing link for the active development of wearable electronic devices. Here, we report a scalable approach to fabricate self-aligned ...graphene microwave transistors for the implementation of flexible low-noise amplifiers and frequency mixers, two fundamental building blocks of a wireless communication receiver. A devised AlO x T-gate structure is used to achieve an appreciable increase of device transconductance and a commensurate reduction of the associated parasitic resistance, thus yielding a remarkable extrinsic cutoff frequency of 32 GHz and a maximum oscillation frequency of 20 GHz; in both cases the operation frequency is an order of magnitude higher than previously reported. The two frequencies work at 22 and 13 GHz even when subjected to a strain of 2.5%. The gigahertz microwave integrated circuits demonstrated here pave the way for applications which require high flexibility and radio frequency operations.
High-quality graphene grown on metal-free substrates represents a vital milestone that provides an atomic clean interface and a complementary metal-oxide-semiconductor-compatible manufacturing ...process for electronic applications. We report a scalable approach to fabricate radio frequency field-effect transistors with a graphene channel grown directly on the sapphire substrate using the technique of remote-catalyzed chemical vapor deposition (CVD). A mushroom-shaped AlO x top gate is used to allow the self-aligned drain/source contacts, yielding remarkable increase of device transconductance and reduction of the associated parasitic resistance. The quality of thus-grown graphene is reflected in the high extrinsic cutoff frequency and maximum oscillation frequency of 10.1 and 5.6 GHz for the graphene channel of length 200 nm and width 80 μm, respectively, potentially comparable with those of transferred CVD graphene at the same channel length and holding promise for applications in high-speed wireless communications.
This paper presents CMOS distributed amplifiers (DAs) using the proposed gate-drain transformer feedback technique. The feedback allows reuse of the traveling signal to achieve a high gain-bandwidth ...product while maintaining low power consumption of DAs. With the folded transmission lines and patterned ground shield, the miniaturized transformer has high quality factors and a well-controlled feedback coupling coefficient. Two DAs are realized using the proposed technique in both 0.18-μm and 90-nm CMOS technologies, respectively. The 0.18-μm CMOS DA achieves a gain of 9.5 dB with a 3-dB bandwidth of 32 GHz, and the noise figure (NF) ranges from 4.1 to 7.6 dB under a power consumption of 71 mW. Under a power consumption of 60 mW, the 90-nm DA demonstrates a gain of 7 dB, a bandwidth of 61.3 GHz, and an NF below 6.2 dB up to 40 GHz. The core areas of the 0.18-μm and 90-nm designs are only 0.58 and 0.41 mm 2 , respectively.
In this letter, a selective Si diffusion approach is proposed to improve both the forward and reverse characteristics of AlGaN/GaN Schottky barrier diodes on Si substrates. The Si diffusion layer ...forms a dual Schottky barrier anode structure, which results in a low Schottky barrier portion to reduce the onset voltage V ON from 1.3 to 1.0 V (23%). In the same process step, the selectively diffused Si is adopted in the cathode to reduce the ohmic contact resistance R C and improve the breakdown voltage V BK . A low R C of 0.21 Ω·mm and enhanced V BK up to 20% (from 1250 to 1500 V) are demonstrated, which can be attributed to the alleviated electric-field peaks around the alloy spikes beneath the ohmic contact.
Microsomal prostaglandin E synthase 1 (mPGES-1) is an α-helical homotrimeric integral membrane inducible enzyme that catalyzes the formation of prostaglandin E2 (PGE2) from prostaglandin H2 (PGH2). ...Inhibition of mPGES-1 has been proposed as a therapeutic strategy for the treatment of pain, inflammation, and some cancers. Interest in mPGES-1 inhibition can, in part, be attributed to the potential circumvention of cardiovascular risks associated with anti-inflammatory cyclooxygenase 2 inhibitors (coxibs) by targeting the prostaglandin pathway downstream of PGH2 synthesis and avoiding suppression of antithrombotic prostacyclin production. We determined the crystal structure of mPGES-1 bound to four potent inhibitors in order to understand their structure–activity relationships and provide a framework for the rational design of improved molecules. In addition, we developed a light-scattering-based thermal stability assay to identify molecules for crystallographic studies.
Both temporomandibular disorders (TMDs) and sleep bruxism (SB) are known to be destructive to the masticatory system. However, the association between the 2 conditions is poorly understood. The aim ...of our study was to assess the relationship between TMD and SB through the signs and symptoms in 2 patient groups: TMD only and TMD with SB.
A retrospective chart review was conducted from November 1, 2015, to April 1, 2018, on patients with completed International Network for Orofacial Pain and Related Disorders Methodology history questionnaires and Diagnostic Criteria for Temporomandibular Disorder clinical examinations. Fifty-two patients, including 12 with TMD only and 40 with TMD with SB, met the study criteria. Subjective descriptions and objective measurements of patient symptoms were investigated. The χ2 test and Fisher's exact test were used for statistical analysis.
The TMD with SB group exhibited increased oral behaviors compared with the TMD-only group (P = .0004). The TMD with SB group also experienced more headaches compared with the TMD-only group (P = .045).
Our results revealed that patients with jaw pain who self-report increased oral behaviors and/or exhibit temporal headaches should be evaluated for sleep bruxism.
In this letter, we propose using an oxide-filled isolation structure followed by N 2 /H 2 postgate annealing to reduce the leakage current in AlGaN/GaN HEMTs. An off-state drain leakage current that ...is smaller than 10 -9 A/mm (minimum 5.1 × 10 -10 A/mm) can be achieved, and a gate leakage current in the range of 7.8 ×10 -10 to 9.2 × 10 -11 A/mm ( V GS from -10 to 0 V and V DS = 10 V) is obtained. The substantially reduced leakage current results in an excellent on/off current ratio that is up to 1.5 × 10 8 . An improved flicker noise characteristic is also observed in the oxide-filled devices compared with that in the traditional mesa-isolated GaN HEMTs.
An ultra-low-power 60 GHz low-noise amplifier (LNA) with a 12.5 dB peak gain and a 5.4 dB minimum NF is demonstrated in a 90 nm CMOS technology. The LNA is composed of four cascaded common-source ...stages with the gate-source transformer feedback applied to the input stage for simultaneous noise and input matching. Also, the drain-source transformer feedback is used in the following stages for gain enhancement and interstage/output matching. This LNA consumes only 4.4 mW from a 1 V supply with a compact core area of 0.047 .
The proposed hybrid Schottky-ohmic drain structure is analyzed in detail for AlGaN/GaN power high-electron mobility transistors on the Si substrate. Without any additional photomasks and process ...steps, the hybrid drain design can alter the electric field distribution to improve the breakdown voltage V BK . In addition, it provides an additional current path to achieve zero onset voltage and reduce the ON-resistance. It was found that the Schottky extension L ext is critical to V BK , R ON , and also the current collapse phenomena of the transistors. The extended Schottky electrodes for optimized transistor characteristics are investigated, and the physics behind are discussed. With an L ext ~ 2-3 μm, V BK can be improved up to 60% with an R ON degradation below 3%.
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