Large-size Substrates Research Articles

Getting Drugs through Small Pores: Exploiting the Porins Pathway in Pseudomonas aeruginosa.

Understanding molecular properties of outer membrane channels of Gram-negative bacteria is of fundamental significance as they are the entry point of polar antibiotics into bacteria. Outer membrane proteomics revealed OccK8 (OprE) to be among the five most expressed substrate specific channels of the clinically important Pseudomonas aeruginosa. The high-resolution X-ray structure and electrophysiology highlighted a very narrow pore. However, experimental in vitro methods showed the transport of natural amino acids and antibiotics, among them ceftazidime. We used molecular dynamics simulations to reveal the importance of the physicochemical properties of ceftazidime in modulating the translocation through OccK8, proposing a structure-function relationship. As in general porins, the internal electric field favors the translocation of polar molecules by gainful energy compensation in the central constriction region. Importantly, the comparatively narrow OccK8 pore can undergo a substrate-induced expansion to accommodate relatively large-sized substrates.

Seasonal patterns of stream macroinvertebrate communities in response to anthropogenic stressors in monsoonal Taiwan

Freshwater ecosystems are affected by a variety of anthropogenic stressors. Temporal variability of biotic communities in these ecosystems makes it difficult to accurately assess the impacts of specific stressors, which has seldom been considered in understudied regions of Asia. We studied the seasonal effects of anthropogenic stressors on stream macroinvertebrates based on sampling every three months over two years at five stream sites in central Taiwan. Several macroinvertebrate metrics (taxon richness, Shannon diversity index, and relative abundance of Trichoptera) were lower during the wet season than the dry season. The presence of dams caused changes in the structure of macroinvertebrate communities, decreased the seasonal variability in relative abundances of Trichoptera, as well as resulted in lower dissolved inorganic nitrogen concentrations and larger substrate size. The presence of urban areas had less or no influence on environmental factors and structural changes. However, significantly lower total abundance, taxon richness, and relative abundance of Trichoptera occurred in the presence of either dams and/or urban areas. One key management implication from the present study is that bioassessment utilizing macroinvertebrates should be facilitated by awareness of the potential role of temporal factors on the effects of anthropogenic stressors, especially in monsoonal Asia.

A New Approach for Product Acceptance Determination for Multiple Manufacturing Lines

Plasma-enhanced chemical vapor deposition is a process used to deposit SiNx film in thin film transistor array fabrication. It can prepare various nonstoichiometric films with tailored properties and be effective in developing high-quality film at low temperature; it also can deposit uniform films on a large-size substrate. In this paper, we present two variables sampling plans for product acceptance determination for multiple manufacturing lines. The first plan is based on a resubmitted scheme, and the second plan is based on an exponentially weighted moving average model with yield index. A new approach is developed to obtain the sample size and the acceptance value for various producer’s risks and consumer’s risks and various number of manufacturing lines. The proposed plans provide more economical sample size than the existing sampling plan and maintain the same protection for both producer and customer risks. The applications of proposed plans are given with the help of two industrial examples.

Ultrathin-Barrier AlGaN/GaN Heterostructure: A Recess-Free Technology for Manufacturing High-Performance GaN-on-Si Power Devices

(Al)GaN recess-free normally OFF technology is developed for fabrication of high-yield lateral GaN-based power devices. The recess-free process is achieved by an ultrathin-barrier (UTB) AlGaN/GaN heterostructure that features a natural pinched-off 2-D electron gas channel. The top–down manufacturing technique overcomes the challenges in etching of AlGaN barrier with well-controlled depth and uniformity, which is especially attractive for fabrication of normally OFF GaN-based high-electron-mobility transistors (HEMTs) and metal–insulator–semiconductor HEMTs (MIS-HEMTs) on large-size Si substrate. With SiNx passivation grown by low-pressure chemical-vapor deposition, on-resistance of the UTB-AlGaN/GaN-based power devices can be significantly reduced. High-uniformity low-hysteresis normally OFF HEMTs and Al2O3/AlGaN/GaN MIS-HEMTs are successfully demonstrated on the UTB AlGaN/GaN-on-Si platform. It is also a compelling technology platform for manufacturing high-performance GaN-based lateral power diodes, and normally OFF p-(Al)GaN heterojunction field-effect transistors.

Abstract 5217: Mechanism of polyspecificity of P-glycoprotein: Substitution of fifteen residues in the drug-binding pocket with tyrosine reveals a negative correlation between substrate size and transport

Abstract P-glycoprotein (P-gp) belongs to the superfamily of ATP-binding cassette (ABC) transporters. This energy-dependent cell surface transporter can pump various chemically dissimilar amphipathic or hydrophobic compounds out of cells. In cancer cells, the expression of P-gp is often linked to the development of multidrug resistance (MDR). Several studies have demonstrated that P-gp can recognize and transport various chemotherapeutic drugs and limit their bioavailability and effectiveness. The drug-substrate binding sites, translocation mechanism, and the signal transduction between drug-binding sites and ATP-hydrolysis at nucleotide-binding domains of this clinically important transporter are not yet well defined. Utilizing molecular modeling and mutagenesis, we previously identified key amino acid residues that interact with the most potent inhibitors of P-gp (zosuquidar, tariquidar, and elacridar). We found that replacing key interacting amino acids (Y307, Y953, and Q725) with alanine in the drug-binding pocket switches inhibition by these modulators of ATPase activity to stimulation. The data demonstrated that hydrogen bond interactions are critical for inhibition of ATP hydrolysis of P-gp by modulators. As tyrosine and glutamine residues can function as both hydrogen bond donors and acceptors, we hypothesized that increasing the potential for hydrogen bond interactions by introducing more tyrosine residues into the drug-binding pocket would increase the affinity of substrates for P-gp. To investigate this, we first identified residues in the transmembrane domains that interact with a number of substrates by employing a molecular modeling technique. Then we substituted fifteen conserved residues (11 Phe, 2 Leu, 2 Ilu and 1 Met) with tyrosine, creating a mutant we named 15Y. Compared to WT, for the majority of tested substrates, we observed normal transport of thirteen fluorescent substrates by the 15Y P-gp mutant demonstrating that fifteen mutations in the transmembrane domains is well tolerated in P-gp. Additionally, these changes have no effect on the cell surface expression or total level of the mutant protein and normal conformational changes occur during transport, further confirming flexible nature of transmembrane domains of P-gp. Interestingly, transport of three large-size substrates was significantly decreased. Physiochemical characterization of the substrates revealed a negative correlation between drug transport and molecular size for the tyrosine-enriched P-gp mutant, possibly due to increased hydrogen bond interactions. These data also demonstrate that hydrogen bond interactions are substrate- or modulator-specific. Citation Format: Shahrooz Vahedi, Eduardo Chufan, Suresh V. Ambudkar. Mechanism of polyspecificity of P-glycoprotein: Substitution of fifteen residues in the drug-binding pocket with tyrosine reveals a negative correlation between substrate size and transport [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5217. doi:10.1158/1538-7445.AM2017-5217

Simulation of thin film thickness distribution for thermal evaporation process using a scanning linear source

Thermal evaporation process is the main process involved in the production of OLED displays and with the trends toward larger substrate size and display resolution, film thickness uniformity must be carefully controlled in order to implement exact pixel data. To secure stable film thickness uniformity on the substrate area, thin films are deposited on large-area glass substrates via thermal evaporation process using a linear source. We designed a linear source and mathematical model was developed to describe the system with a focus on the linear source. Then, system parameters were determined to guarantee uniform thickness using computer-based simulation, replacing wasteful actual experiments, followed by carrying out experiments based on the determined parameters. After the deposition process, data from the mathematical model and experiments was compared and the resulting agreement was good, verifying the validity of the proposed method. Consequently, by applying the proposed method, display manufacturing process related to thermal evaporation can be controlled within a tight tolerance in order to maximize the production yield rate.

Cyber-physical Modeling of Rotation Vibration Compensation of MOCVD Substrate Bearing Disk

MOCVD large size substrate bearing disk, working in high temperature, high speed rotating and complex gas phase environment, in the high-speed rotation of the material is easy to deformation, vibration or flutter, to its rotation compensation control vibration will become very complicated. This article is based on fuzzy neural network study of bearing plate of high speed vibration, through optimal controller is designed to make the whole system performance index.

Mechanism of formate-nitrite transporters by dielectric shift of substrate acidity.

Bacterial formate-nitrite transporters (FNTs) regulate the metabolic flow of small, weak mono-acids. Recently, the eukaryotic PfFNT was identified as the malaria parasite's lactate transporter and novel drug target. Despite crystal data, central mechanisms of FNT gating and transport remained unclear. Here, we show elucidation of the FNT transport mechanism by single-step substrate protonation involving an invariant lysine in the periplasmic vestibule. Opposing earlier gating hypotheses and electrophysiology reports, quantification of total uptake by radiolabeled substrate indicates a permanently open conformation of the bacterial formate transporter, FocA, irrespective of the pH Site-directed mutagenesis, heavy water effects, mathematical modeling, and simulations of solvation imply a general, proton motive force-driven FNT transport mechanism: Electrostatic attraction of the acid anion into a hydrophobic vestibule decreases substrate acidity and facilitates protonation by the bulk solvent. We define substrate neutralization by proton transfer for transport via a hydrophobic transport path as a general theme of the Amt/Mep/Rh ammonium and formate-nitrite transporters.

Influence of substrate depth and particle size on phosphorus removal in a surface flow constructed wetland.

Substrate adsorption is one of the main processes by which redundant phosphorus is removed from wastewater in surface flow constructed wetlands (SFCWs). The physical properties of the substrate, such as depth and particle size, will influence the amount of phosphorus adsorption. This study was carried out in a long-running intermittent inflow constructed wetland that covered a total area of 940.4 m2 in the Shunyi District of Beijing, China. We investigated how the concentrations of four phosphorus fractions, namely calcium phosphate (CaP), iron phosphate (FeP), adsorbed phosphorus (AdsP), and organic phosphorus (OP), varied between the surface (0-10 cm) and subsurface (10-20 cm) substrate and among the different substrate particle sizes. The total phosphorus concentrations in the substrate ranged from 154.97 to 194.69 mg/kg; CaP accounted for more than 80% of the total phosphorus content. The concentrations of OP were significantly higher in the surface layer than in the subsurface layer, but the concentrations of inorganic phosphorus were not significantly different between the two layers. The CaP, AdsP, and OP adsorption capacities were greater for small-sized substrate particles than for large-sized substrate particles. The results from this study provide a theoretical basis for the construction of constructed wetlands.

Highly stable 2D material (2DM) field-effect transistors (FETs) with wafer-scale multidyad encapsulation

Field-effect transistors (FETs) composed of 2D materials (2DMs) such as transition-metal dichalcogenide (TMD) materials show unstable electrical characteristics in ambient air due to the high sensitivity of 2DMs to water adsorbates. In this work, in order to demonstrate the long-term retention of electrical characteristics of a TMD FET, a multidyad encapsulation method was applied to a MoS2 FET and thereby its durability was warranted for one month. It was well known that the multidyad encapsulation method was effective to mitigate high sensitivity to ambient air in light-emitting diodes (LEDs) composed of organic materials. However, there was no attempt to check the feasibility of such a multidyad encapsulation method for 2DM FETs. It is timely to investigate the water vapor transmission ratio (WVTR) required for long-term stability of 2DM FETs. The 2DM FETs were fabricated with MoS2 flakes by both an exfoliation method, that is desirable to attain high quality film, and a chemical vapor deposition (CVD) method, that is applicable to fabrication for a large-sized substrate. In order to eliminate other unwanted variables, the MoS2 FETs composed of exfoliated flakes were primarily investigated to assure the effectiveness of the encapsulation method. The encapsulation method uses multiple dyads comprised of a polymer layer by spin coating and an Al2O3 layer deposited by atomic layer deposition (ALD). The proposed method shows wafer-scale uniformity, high transparency, and protective barrier properties against adsorbates (WVTR of 8 × 10−6 g m−2 day−1) over one month.

Identification of Surface-Exposed Protein Radicals and A Substrate Oxidation Site in A-Class Dye-Decolorizing Peroxidase from Thermomonospora curvata.

Dye-decolorizing peroxidases (DyPs) are a family of heme peroxidases, in which a catalytic distal aspartate is involved in H2O2 activation to catalyze oxidations in acidic conditions. They have received much attention due to their potential applications in lignin compound degradation and biofuel production from biomass. However, the mode of oxidation in bacterial DyPs remains unknown. We have recently reported that the bacterial TcDyP from Thermomonospora curvata is among the most active DyPs and shows activity toward phenolic lignin model compounds (J. Biol. Chem.2015, 290, 23447). Based on the X-ray crystal structure solved at 1.75 Å, sigmoidal steady-state kinetics with Reactive Blue 19 (RB19), and formation of compound II-like product in the absence of reducing substrates observed with stopped-flow spectroscopy and electron paramagnetic resonance (EPR), we hypothesized that the TcDyP catalyzes oxidation of large-size substrates via multiple surface-exposed protein radicals. Among 7 tryptophans and 3 tyrosines in TcDyP consisting of 376 residues for the matured protein, W263, W376, and Y332 were identified as surface-exposed protein radicals. Only the W263 was also characterized as one of surface-exposed oxidation sites. SDS-PAGE and size-exclusion chromatography demonstrated that W376 represents an off-pathway destination for electron transfer, resulting in the crosslinking of proteins in the absence of substrates. Mutation of W376 improved compound I stability and overall catalytic efficiency toward RB19. While Y332 is highly conserved across all four classes of DyPs, its catalytic function in A-class TcDyP is minimal possibly due to its extremely small solvent accessible areas. Identification of surface-exposed protein radicals and substrate oxidation sites is important for understanding DyP mechanism and modulating its catalytic functions for improved activity on phenolic lignin.

Direct write lithography approach for Panel Level Package

Abstract Fan-out processing a is booming technology at wafer level packaging. However, chip last process in fan-out gives great difficulty to lithography. At the same time, the industry is looking for increasing substrate size in order to reduce production cost. Direct write technology shall be the key lithography process having both flexibility and compatibility for large size substrate.

Wafer scale fabrication of carbon nanotube thin film transistors with high yield

Carbon nanotube thin film transistors (CNT-TFTs) are promising candidates for future high performance and low cost macro-electronics. However, most of the reported CNT-TFTs are fabricated in small quantities on a relatively small size substrate. The yield of large scale fabrication and the performance uniformity of devices on large size substrates should be improved before the CNT-TFTs reach real products. In this paper, 25 200 devices, with various geometries (channel width and channel length), were fabricated on 4-in. size ridged and flexible substrates. Almost 100% device yield were obtained on a rigid substrate with high out-put current (>8 μA/μm), high on/off current ratio (>105), and high mobility (>30 cm2/V·s). More importantly, uniform performance in 4-in. area was achieved, and the fabrication process can be scaled up. The results give us more confidence for the real application of the CNT-TFT technology in the near future.

Millimeter Wave E-Plane Transition From Waveguide to Microstrip Line With Large Substrate Size Related to MMIC Integration

This letter demonstrates a packaging concept where a waveguide-to-microstrip transition can be assimilated on a mm-wave MMIC of an arbitrary size and thus avoid the use of bond wires at the high frequency ports of the MMIC circuit. The advantage of the proposed concept is that- it does not require an extra substrate with sub-critical dimensions for the waveguide-to-microstrip transition. The transition can be integrated onto the MMIC, and thus the MMIC can be coupled directly to the waveguide. A Perfect Magnetic Conductor (PMC) surface is used to suppress the unwanted waveguide mode coupling to the oversized circuit cavity. The measured back-to-back transition works over the frequency band 66–98 GHz (relative BW of 38%) with minimum return loss of 12.7 dB. The total insertion loss of the manufactured prototype is found to be 3.26 dB, which also includes a 14.8 mm long microstrip line on an Alumina substrate. The losses in a single transition vary between 0.25 and 0.42 dB.

Short channel carbon nanotube thin film transistors with high on/off ratio fabricated by two-step fringing field dielectrophoresis

A two-step fringing field dielectrophoretic assembly method for carbon nanotube thin film transistors (CNT-TFTs) fabrication was demonstrated. Densely aligned CNT arrays were assembled at the source and drain electrodes sequentially which form a cascade structure of the aligned CNT arrays. The cascade structure reduces the possibility of percolating metallic pathways in the channel, which is beneficial to device performance. In this way, both high on/off current ratio Ion/Ioff (up to 107) and high out-put current density (8.5μA/μm) were obtained in short channel length (1–2.5μm) CNT-TFTs. The reported CNT assembling strategy is site selective and highly efficient, which can be scaled up to large size substrates and leads to high throughput of CNT-TFTs fabrication.

Stress engineering with AlN/GaN superlattices for epitaxial GaN on 200 mm silicon substrates using a single wafer rotating disk MOCVD reactor

Abstract

Fabrication of disposable flexible SERS substrates by nanoimprint

In this work, we report on the fabrication of disposable flexible substrates dedicated to the Surface-Enhanced Raman Scattering (SERS) technique. The transfer of pyramidal features elaborated on silicon wafers towards flexible plastic foil is performed via a two-steps nanoimprint process. Gold coated normal and inverted square pyramids patterned on the master silicon molds are reproduced with fidelity into a double-layer flexible plastic foil. SERS spectroscopy characterization was performed on the master SERS devices as well as on the final polymeric duplicated structures. Both, masters and replica, were shown to exhibit a good Raman signal enhancement. Moreover, this fabrication procedure was shown to be compatible with the use of large size substrates and well-mastered collective fabrication techniques. As a consequence, the developed SERS-active polymeric devices combine cost effectiveness and a high application potential in various detection and process control domains.

Wideband 60 GHz circularly polarised stacked patch antenna array in low‐temperature co‐fired ceramic technology

A wideband circularly polarised (CP) cross-aperture-coupled stacked feed antenna array with the top-metal strip via fence based on multilayer low-temperature co-fired ceramic technology is designed and measured for 60 GHz wireless communication applications. The influence of the large substrate and ground size on the radiation patterns of the proposed CP antenna array is investigated. Considering the 10 dB impedance bandwidth, 3 dB axial ratio bandwidth and 3 dB gain bandwidth, the measured results reveal that a wide operating bandwidth more than 17% at the centre frequency of 61.75 GHz from 56.5 to 67 GHz of the presented CP antenna array is achieved.

A study of improving overlay accuracy by applying a new outlier handling method in FPD manufacturing

As the pixel size of display devices has been reduced, overlay accuracy between layers needs to be more improved in flat panel display (FPD) manufacturing. However, because of large substrate size and non-uniform processes in FPD manufacturing, an improvement of overlay accuracy has been a challenging work. As an effort to improve overlay accuracy, overlay error correction, which is a kind of feedback control similar to one in semiconductor manufacturing, has also been applied in the photo lithography processes for FPD. However, its characteristics and problems were not technically well investigated as much as in semiconductor manufacturing. This paper investigates one of the problems encountered in the practice of the overlay error correction: outliers in the measurement of overlay errors. Such outliers can cause undesirable effects on overlay accuracy, if used for the overlay error correction. In order to systematically cope with such outliers, a new framework is proposed for detecting and handling outliers as well as for verifying the result. In the consideration of the proposed framework, a new outlier detecting and handling method is also proposed. This method is based on a robust regression technique and is compared with others through simulation to confirm its better performance.

Design and development of an in-line sputtering system and process development of thin film multilayer neutron supermirrors.

Neutron supermirrors and supermirror polarizers are thin film multilayer based devices which are used for reflecting and polarizing neutrons in various neutron based experiments. In the present communication, the in-house development of a 9 m long in-line dc sputtering system has been described which is suitable for deposition of neutron supermirrors on large size (1500 mm × 150 mm) substrates and in large numbers. The optimisation process of deposition of Co and Ti thin film, Co/Ti periodic multilayers, and a-periodic supermirrors have also been described. The system has been used to deposit thin film multilayer supermirror polarizers which show high reflectivity up to a reasonably large critical wavevector transfer of ∼0.06 Å(-1) (corresponding to m = 2.5, i.e., 2.5 times critical wavevector transfer of natural Ni). The computer code for designing these supermirrors has also been developed in-house.