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Cell proliferation and differentiation require signalling pathways that enforce appropriate and timely gene expression. We find that Tor2, the catalytic subunit of the TORC1 complex in fission yeast, targets a conserved nuclear RNA elimination network, particularly the serine and proline-rich protein Pir1, to control gene expression through RNA decay and facultative heterochromatin assembly. Phosphorylation by Tor2 protects Pir1 from degradation by the ubiquitin-proteasome system involving the polyubiquitin Ubi4 stress-response protein and the Cul4–Ddb1 E3 ligase. This pathway suppresses widespread and untimely gene expression and is critical for sustaining cell proliferation. Moreover, we find that the dynamic nature of Tor2-mediated control of RNA elimination machinery defines gene expression patterns that coordinate fundamental chromosomal events during gametogenesis, such as meiotic double-strand-break formation and chromosome segregation. These findings have important implications for understanding how the TOR signalling pathway reprogrammes gene expression patterns and contributes to diseases such as cancer.

ABSTRACTMacroautophagy (autophagy) is driven by the coordinated actions of core autophagy-related (Atg) proteins. Atg8, the core Atg protein generally considered acting most downstream, has recently been shown to interact with other core Atg proteins via their Atg8-family-interacting motifs (AIMs). However, the extent, functional consequence, and evolutionary conservation of such interactions remain inadequately understood. Here, we show that, in the fission yeast Schizosaccharomyces pombe, Atg38, a subunit of the phosphatidylinositol 3-kinase (PtdIns3K) complex I, interacts with Atg8 via an AIM, which is highly conserved in Atg38 proteins of fission yeast species, but not conserved in Atg38 proteins of other species. This interaction recruits Atg38 to Atg8 on the phagophore assembly site (PAS) and consequently enhances PAS accumulation of the PtdIns3K complex I and Atg proteins acting downstream of the PtdIns3K complex I, including Atg8. The disruption of the Atg38-Atg8 interaction leads to the reduction of autophagosome size and autophagic flux. Remarkably, the loss of this interaction can be compensated by an artificial Atg14-Atg8 interaction. Our findings demonstrate that the Atg38-Atg8 interaction in fission yeast establishes a positive feedback loop between Atg8 and the PtdIns3K complex I to promote efficient autophagosome formation, underscore the prevalence and diversity of AIM-mediated connections within the autophagic machinery, and reveal unforeseen flexibility of such connections.Abbreviations: AIM: Atg8-family-interacting motif; AP-MS: affinity purification coupled with mass spectrometry; Atg: autophagy-related; FLIP: fluorescence loss in photobleaching; PAS: phagophore assembly site; PB: piggyBac; PE: phosphatidylethanolamine; PtdIns3K: phosphatidylinositol 3-kinase; PtdIns3P: phosphatidylinositol 3-phosphate.

Metastatic castration-resistant prostate cancer (PC) is the final stage of PC that acquires resistance to androgen deprivation therapies (ADT). Despite progresses in understanding of disease mechanisms, the specific contribution of the metastatic microenvironment to ADT resistance remains largely unknown. The current study identified that the macrophage is the major microenvironmental component of bone-metastatic PC in patients. Using a novel in vivo model, we demonstrated that macrophages were critical for enzalutamide resistance through induction of a wound-healing–like response of ECM–receptor gene expression. Mechanistically, macrophages drove resistance through cytokine activin A that induced fibronectin (FN1)-integrin alpha 5 (ITGA5)–tyrosine kinase Src (SRC) signaling cascade in PC cells. This novel mechanism was strongly supported by bioinformatics analysis of patient transcriptomics datasets. Furthermore, macrophage depletion or SRC inhibition using a novel specific inhibitor significantly inhibited resistant growth. Together, our findings elucidated a novel mechanism of macrophage-induced anti-androgen resistance of metastatic PC and a promising therapeutic approach to treat this deadly disease.

Melt electrospinning is a novel technology in the field of 1D micro/nanostructure fabrication. Decreasing the diameter and promoting surface morphology of melt fiber are the key for the application of melt electrospinning technology. Heated sheath gas is introduced to build up melt electrospinning direct-write technology, and then orderly micro/nanofibers can be direct-written. The heated sheath gas provided a good way to increase the temperature of melt jet, by which solidification can be slowed. With the help of heated sheath gas, the diameter of melt fiber can be decreased. The affects of process parameters on the diameter of melt electrospinning fiber was investigated, the diameter of melt electrospinning fiber increased with the increasing of temperature of spinneret and feed rate, but decreased with the increasing of voltage and distance between spinneret and collector. Heated sheath gas is an excellent method to promote the application of melt electrospinning.

Electrohydrodynamic Direct-Writing (EDW) provides a simple and rapid way to print micro/nanostructures from viscoelastic solution, which meets the demand in the development of all-printed organic electronics. Overlapped printing of different functional materials to build up multi-layer devices displays excellent advantages in the flexible electron. The 3D multi-layer devices as well as flat interconnection can be fabricated on the flexible substrate directly via EDW technology. The technology of EDW utilized stable charged jet to print orderly conductive and insulator micro/nanostructure. Silver ink is used to print conductor connection, and polyvinylpyrrolidone (PVP) solution is used to fabricate insulator layer. Multi-layer interconnection can be printed layer by layer on the polyimide (PI) flexible insulator substrate. The resistance of top and bottom conductor connection was 6.1Ω and 5.9Ω, respectively. The insulator layer demonstrated excellent insulation characteristics between the bottom and top silver interconnection.

As a novel and simple non-contact fabrication method, electrohydrodynamic direct-write (EDW) has been regarded as one of the most potential technologies for large scale manufacturing of flexible and organic electronics. An inducing tip was introduced into the EDW apparatus. The enhanced electrical field between spinneret and inducing tip provided an excellent way to restrict the motion of charged jet, by which the stabilization of EDW jet can be promoted and the disturbances can also be overcome. Charged jet is deposited layer by layer to construct three dimension structure between spinneret and collector. The three dimension structure grows directly to the spinneret by the guidance and restriction of focused electric field. With the help of X-Y motion stage, the motion track of collector can be controlled by the host computer to fabricate designed pattern. The inducing tip provides a good way to increase the stability and deposition accurate of EDW charged jet.

This paper proposes an efficient PSP-based model for cross-coupled metal-oxide-semiconductor field-effect transistors (MOSFETs) with optimized layout in the voltage controlled oscillator (VCO). The model employs a PSP charge model to characterize the bias-dependent extrinsic capacitance instead of numerical functions with strong non-linearity. The simulation convergence is greatly improved by this method. An original scheme is developed to extract the parameters of the PSP charge model based on S-parameters measurement. The interconnection parasitics of the cross-coupled MOSFETs are modeled based on vector fitting. The model is verified with an LC VCO design, and exhibits excellent convergence during simulation. The results show improvements as high as 60.5% and 61.8% in simulation efficiency and accuracy, respectively, indicating that the proposed model better characterizes optimized cross-coupled MOSFETs in advanced radio frequency (RF) circuit design.

The effect of the addition of stearic acid on properties of wheat, mung bean and potato starches were studied. Soluble amylose content in three kinds of starches was significantly reduced. Both λmax values and the 630/520 nm ratio were decreased. Stearic acid added starches showed a significantly higher pasting temperature, breakdown and setback compared to the native starches as measured by RVA. Texture properties analysis showed that hardness of wheat and mung bean starches significantly decreased, while that of potato starch significantly increased after the addition of stearic acid. Diffraction peaks of wheat, mung bean and potato starches appeared at 22° which indicated that complex formation by X-ray diffraction

A literal circuit with a three-track-output structure is presented based on resonant tunneling diodes (RTDs). It can be transformed conveniently into a single-track-output structure according to the definition and properties of the literal operation. A ternary resonant tunneling JK flip-flop is created based on the RTD literal circuit and the module-3 operation, and the JK flip-flop also has two optional types of output structure. The design of the ternary RTD JK flip-flop is verified by simulation. The RTD literal circuit is the key design component for achieving various types of multi-valued logic (MVL) flip-flops. It can be converted into ternary D and JK flip-flops, and the ternary JK flip-flop can also be converted simply and conveniently into ternary D and ternary T flip-flops when the input signals satisfy certain logical relationships. All these types of flip-flops can be realized using the traditional Karnaugh maps combined with the literal and module-3 operations. This approach offers a novel design method for MVL resonant tunneling flip-flop circuits.

This paper discusses the finite element approximation for a Steklov eigenvalue problem. Based on the work of Armentano and Padra ( Appl Numer Math 58 (2008) 593-601), an a posteriori error estimator is provided and its validity and reliability are proved theoretically. Finally, numerical experiments with Matlab program are carried out to confirm the theoretical analysis.

This paper deals with the problem of adaptive control for a class of nonlinear systems. The system considered in the paper contains non-parameterized uncertainties and periodic disturbances. A semi-global adaptive control method is proposed using the barrier Lyapunov functions. The method does not need to assume that the solution of the closed loop system remains in the domain of approximation by neural networks and guarantees that the solution of the system converges to zero.

The ability of the pathogenic fungus Candida albicans to switch cellular morphologies is important for infection and virulence. Recent studies have revealed that C. albicans yeast cells can switch to filamentous growth under genotoxic stress in a manner dependent on the DNA replication/damage checkpoint. Here, we have investigated the functions of Pph3 (orf19.4378) and Psy2 (orf19.3685), whose orthologues in Saccharomyces cerevisiae mediate the dephosphorylation of the DNA damage checkpoint kinase Rad53 and the histone variant H2AX during recovery from DNA damage. Deleting PPH3 or PSY2 causes hypersensitivity to DNA-damaging agents, including cisplatin, methylmethane sulfonate (MMS), and UV light. In addition, pph3Δ and psy2Δ cells exhibit strong filamentous growth under genotoxic stress. Flow cytometry analysis shows that the mutant cells have lost the ability to adapt to genotoxic stress and remain arrested even after the stress is withdrawn. Furthermore, we show that Pph3 and Psy2 are required for the dephosphorylation of Rad53, but not H2AX, during DNA damage recovery. Taken together, these results show that C. albicans Pph3 and Psy2 have important roles in mediating genotoxin-induced filamentous growth and regulating Rad53 dephosphorylation.

ABSTRACTThe ability of the pathogenic fungus Candida albicansto switch cellular morphologies is important for infection and virulence. Recent studies have revealed that C. albicansyeast cells can switch to filamentous growth under genotoxic stress in a manner dependent on the DNA replication/damage checkpoint. Here, we have investigated the functions of Pph3 (orf19.4378) and Psy2 (orf19.3685), whose orthologues in Saccharomyces cerevisiaemediate the dephosphorylation of the DNA damage checkpoint kinase Rad53 and the histone variant H2AX during recovery from DNA damage. Deleting PPH3or PSY2causes hypersensitivity to DNA-damaging agents, including cisplatin, methylmethane sulfonate (MMS), and UV light. In addition, pph3? and psy2? cells exhibit strong filamentous growth under genotoxic stress. Flow cytometry analysis shows that the mutant cells have lost the ability to adapt to genotoxic stress and remain arrested even after the stress is withdrawn. Furthermore, we show that Pph3 and Psy2 are required for the dephosphorylation of Rad53, but not H2AX, during DNA damage recovery. Taken together, these results show that C. albicansPph3 and Psy2 have important roles in mediating genotoxin-induced filamentous growth and regulating Rad53 dephosphorylation.

Abstract: The problems existing in the binary logic system and the advantages of multiple-valued logic (MVL) are introduced. A literal circuit with three-track-output structure is created based on resonant tunneling diodes (RTDs) and it has the most basic memory function. A ternary RTD D flip-flop with pre-set and pre-reset functions is also designed, the key module of which is the RTD literal circuit. Two types of output structure of the ternary RTD D flip-flop are optional: one is three-track and the other is single-track; these two structures can be transformed conveniently by merely adding tri-valued RTD NAND, NOR, and inverter units after the three-track output. The design is verified by simulation. Ternary flip-flop consists of an RTD literal circuit and it not only is easy to understand and implement but also provides a solution for the algebraic interface between the multiple-valued logic and the binary logic. The method can also be used for design of other types of multiple-valued RTD flip-flop circuits.

Micropumps represent one of the major components in microfluidic technology. This paper describes the fabrication and performance testing of a simple, compact, inexpensive and disposable micropump suitable for microfluidic applications. The micropump was fabricated with polydimethylsiloxane (PDMS) which was bonded permanently on glass substrate. Piezoelectric-discs were used to actuate the micropumps. As a flow-rectifying element, the diffusers were used instead of passive check valves. The performances of the micropump, such as pump rate, were characterized. The flow rate of micropump increases with enhancing the applied voltage to piezoelectric-disc due to the increase of diaphragm deflection. The flow rate of the micropump with diffusers were about 9 μl/min when applying a 20 V square wave driving voltage at 300 Hz. This prototype can be used as a platform to develop an inexpensive micropump which is suitable to be part of a disposable microfluidic system.

UHF RFID system has been mainly used in logistics,production and supply chain management. The implementation of UHF RFID reader with excellent performance is still challenging. This paper presents a UHF RFID reader implementation for EPC C1G2 protocol. EPC C1G2 physical layer architecture and some critical modules like encoder ,decoder, modulator and demodulator are described in details. All modules are verified in FPGA and the experiments demonstrate that the designed RFID reader baseband system could perform well.

Neurons with complex-valued weights have stronger capability because of their multi-valued threshold logic. Neurons with such features may be suitable for solution of different kinds of problems including associative memory, image recognition and digital logical mapping. In this paper, robustness or tolerance is introduced and newly defined for this kind of neuron according to both their mathematical model and the perceptron neuron’s definition of robustness. Also, the most robust design for basic digital logics of multiple variables is proposed based on these robust neurons. Our proof procedure shows that, in robust design each weight only takes the value of i or -i, while the value of threshold is with respect to the number of variables. The results demonstrate the validity and simplicity of using robust neurons for realizing arbitrary digital logical functions.