Reservoir Computing Based on Oxygen-Vacancy-Mediated X-ray Optical Synaptic Device for Medical CT Bone Diagnosis.

Recognition and judgment of X-ray computed tomography (CT) images play a crucial role in medical diagnosis and disease prevention. However, the storage and calculation of the X-ray imaging system applied in the traditional CT diagnosis is separate, and the pathological judgment is based on doctors' experience, which will affect the timeliness and accuracy of decision-making. In this paper, a simple-structured reservoir computing network (RC) is proposed based on Ga2O3 X-ray optical synaptic devices to recognize medical skeletal CT images with high accuracy. Through oxygen vacancy engineering, Ga2O3 X-ray optical synaptic devices with adjustable photocurrent gain and a persistent photoconductivity effect were obtained. By using the Ga2O3 X-ray optical synaptic device as a reservoir, we constructed an RC network for medical skeletal CT diagnosis and verified its image recognition capability using the MNIST data set with an accuracy of 78.08%. In the elbow skeletal CT image recognition task, the recognition rate is as high as 100%. This work constructs a simple-structured RC network for X-ray image recognition, which is of great significance in applications in medical fields.

Pyroelectric Photoconductive Diode for Highly Sensitive and Fast DUV Detection.

Detecting high-energy photons from the deep ultraviolet (DUV) to X-rays is vital in security, medicine, industry, and science. Wide bandgap (WBG) semiconductors exhibit great potential for detecting high-energy photons. However, the implementation of highly sensitive and high-speed detectors based on WBG semiconductors has been a huge challenge due to the inevitable deep level traps and the lack of appropriate device structure engineering. Here, a sensitive and fast pyroelectric photoconductive diode (PPD), which couples the interface pyroelectric effect with the photoconductive effect based on tailored polycrystal Ga-rich GaOx (PGR-GaOx) Schottky photodiode, is first proposed. The PPD device exhibits ultrahigh detection performance for DUV and X-ray light. The responsivity for DUV light and sensitivity for X-ray are up to 104 A W-1 and 105 µC Gyair -1 cm-2, respectively. Especially, the interface pyroelectric effect induced by polar symmetry in the depletion region of the PGR-GaOx can significantly improve the response speed of the device by 105 times. Furthermore, the potential of the device is demonstrated for imaging enhancement systems with low power consumption and high sensitivity. This work fully excavates the potential of the pyroelectric effect for detectors and provides a novel design strategy to achieve sensitive and high-speed detectors.

Effect of Strain Rate on Nano-Scale Mechanical Behavior of A-Plane (112¯0) ZnO Single Crystal by Nanoindentation.

In this study, nanoindentation tests at three different strain rates within 100 nm indentation depth were conducted on an a-plane (112¯0) ZnO single crystal to investigate the effect of strain rate on its nano-scale mechanical behavior. The load-indentation-depth curves, pop-in events, hardness and Young's moduli of an a-plane (112¯0) ZnO single crystal at different strain rates were investigated at the nano-scale level. The results indicated that, with the indentation depth increasing, the load increased gradually at each maximum indentation depth, hma, during the loading process. A distinct pop-in event occurred on each loading curve except that corresponding to the hmax of 10 nm. The applied load at the same indentation depth increased with the increasing strain rate during the nanoindentation of the a-plane (112¯0) ZnO single crystal. The higher strain rate deferred the pop-in event to a higher load and deeper indentation depth, and made the pop-in extension width larger. The hardness showed reverse indentation size effect (ISE) before the pop-in, and exhibited normal ISE after the pop-in. Both the hardness and the Young's modulus of the a-plane (112¯0) ZnO single crystal increased with the increasing strain rate, exhibiting the positive strain-rate sensitivity.

Optimization Effect of Metakaolin on Macro- and Micro-Mechanical Properties of Composite Cementitious Materials under Different Curing Conditions.

To provide the theoretical basis for the engineering application of metakaolin as aluminum-rich pozzolanic ash materials, the promoting effect of metakaolin on the macro- and micro-mechanical properties of composite cement-based composite materials was explored under high-temperature steam and standard curing conditions. Analysis techniques, which involved thermogravimetric and nanoindentation coupled with scanning electron microscopy-energy dispersive X-ray spectroscopy, were used. To analyze the experimental data, the ACI empirical formula and the copula function were used. The correlation among the hydration degree of the MK-cement cementation system, the Al/Si of the C-(A)-S-H phase, and the nanomechanical properties of the C-(A)-S-H gel phase was investigated. According to prior research, the macroscopic mechanical properties and the substitution rate of the MK-cement composite cementitious system can be improved under high-temperature curing conditions in a short period, in which the optimum substitution rate of metakaolin is 20%. The ACI empirical formula was used to demonstrate the functional relationship between the metakaolin replacement rate, curing time, and compressive strength. The MK-cement cementation system can eliminate the defect phase, reduce the CH phase content, and then increase the C-(A)-S-H gel phase content and bulk density. The micro-mechanical properties of the C-(A)-S-H gel phase rises due to its phase content and Al/Si ratio. Furthermore, the copula function verifies the dependence of the nanomechanical properties of C-(A)-S-H gel and Al/Si.

In-sensor reservoir computing system for latent fingerprint recognition with deep ultraviolet photo-synapses and memristor array.

Detection and recognition of latent fingerprints play crucial roles in identification and security. However, the separation of sensor, memory, and processor in conventional ex-situ fingerprint recognition system seriously deteriorates the latency of decision-making and inevitably increases the overall computing power. In this work, a photoelectronic reservoir computing (RC) system, consisting of DUV photo-synapses and nonvolatile memristor array, is developed to detect and recognize the latent fingerprint with in-sensor and parallel in-memory computing. Through the Ga-rich design, we achieve amorphous GaOx (a-GaOx) photo-synapses with an enhanced persistent photoconductivity (PPC) effect. The PPC effect, which induces nonlinearly tunable conductivity, renders the a-GaOx photo-synapses an ideal deep ultraviolet (DUV) photoelectronic reservoir, thus mapping the complex input vector into a dimensionality-reduced output vector. Connecting the reservoirs and a memristor array, we further construct an in-sensor RC system for latent fingerprint identification. The system maintains over 90% recognition accuracy for latent fingerprint within 15% stochastic noise level via the proposed dual-feature strategy. This work provides a subversive prototype system of DUV in-sensor RC for highly efficient recognition of latent fingerprints.

Mechanical Property Evaluation and Prediction of Cementing Composites Blended with MK and UFA under High-Temperature Steam Curing.

In this paper, the influence of the substitution rate of metakaolin (MK) and ultrafine fly ash (UFA) on the hydration degree, the micromechanical properties, the pore size distribution, and the corresponding fractal dimension of composite cement-based material was investigated under high-temperature steam curing. Furthermore, Thermogravimetric, Nanoindentation, and low-field nuclear magnetic resonance tests were used to explore the influencing factors of pore size distribution and its corresponding multi-fractal dimension. Finally, the correlations among the pore size distribution, related fractal dimensions, and compression strength were analyzed. Results indicate that the MK-UFA cement ternary cementation system (TCS) can improve the compressive strength and fluidity of samples and enhance the hydration degree and micromechanical properties of the cementitious system. TCS effectively refines the pore size and increases microporosity. In addition, micropore and its fractal dimension have a stronger correlation with the compressive strength of composite cement-based materials. Furthermore, the micro-fractal dimensions can better reflect the essential characteristics of the composite cementitious system. The higher the degree of hydration of the cementitious system and the nanomechanical properties of the C-(A)-S-H gel, the lower the micro-fractal dimension. Finally, the GM (1,3) prediction model of compressive strength, micro-fractal dimension, and microporosity are established based on the grey relational theory.

Anticancer effects of a single intramuscular dose of a minicircle DNA vector expressing anti-CD3/CD20 in a xenograft mouse model.

Bispecific antibodies (BsAbs) are a class of promising anticancer immunotherapies. Among them, the US Food and Drug Administration (FDA)-approved blinatumomab (BLI) is very effective in eliminating the minimum residual disease (MRD) of acute lymphoblastic leukemia (ALL), resulting in long-term remission in many individuals. However, the need for months-long intravenous delivery and high cost limit its clinical acceptance. Here we demonstrate that these problems can be solved by a BsAb expressed by one intramuscular (i.m.) dose of a minicircle DNA vector (MC). In a human B lymphoma xenograft mouse model, when microcancers became detectable in bone marrow, the mice received an i.m. dose of the MC encoding the BsAb anti-CD3/CD20 (BsAb.CD20), followed by 8 subsequent intravenous (i.v.) doses, one every other day (q2d), of human T cells to serve as effectors. The treatment resulted in persistent expression of a therapeutic level of serum BsAb.CD20 and complete regression or growth retardation of the cancers in the mice. These results suggest that the i.m. MC technology can eliminate the physical and financial burdens of i.v. delivered BLI without compromising anticancer efficacy and that cancer can be treated as easily as injecting a vaccine. This, together with other superior MC features, such as safety and affordability, suggests that the i.m. MC BsAb technology has great clinical application potential.

High-Performance Harsh-Environment-Resistant GaOX Solar-Blind Photodetectors via Defect and Doping Engineering.

Gallium oxide (Ga2 O3 ), with an ultrawide bandgap, is currently regarded as one of the most promising materials for solar-blind photodetectors (SBPDs), which are greatly demanded in harsh environment, such as space exploration and flame prewarning. However, realization of high-performance SBPDs with high tolerance toward harsh environments based on low-cost Ga2 O3 material faces great challenges. Here, defect and doping (DD) engineering towards amorphous GaOX (a-GaOX ) has been proposed to obtain ultrasensitive SBPDs for harsh condition application. Serious oxygen deficiency and doping compensation of the engineered a-GaOX film ensure the high response currents and low dark currents, respectively. Annealing item in nitrogen of DD engineering also incurs the recrystallization of material, formation of nanopores by oxygen escape, and suppression of sub-bandgap defect states. As a result, the tailored GaOX SBPD based on DD engineering not only harvests a record-high responsivity rejection ratio (R254 nm /R365 nm ) of 1.8 × 107 , 102 times higher detectivity, and 2 × 102 times faster decay speed than the control device, but also keeps a high responsivity, high photo-to-dark current ratio, and sharp imaging capability even at high temperature (280 °C) or high bias (100 V). The proposed DD engineering provides an effective strategy towards highly harsh-environment-resistant GaOX SBPDs.

Calcium phosphate nanoneedle based gene delivery system for cancer genetic immunotherapy.

Ovarian cancer has become one of the most common gynecological cancers with a high mortality. However, conventional surgery together with combination chemotherapy is difficult to achieve ideal therapeutic effect. Although genetic immunotherapy is applied to active immune responses against cancer, the absence of efficient in vivo gene delivery technique is still an obstacle in clinical application. To overcome these problems, a minicircle DNA vector encoding humanized anti-EpCAM/CD3 bispecific antibody (BsAbEPH) has been constructed. Moreover, different shapes of calcium phosphate (CaPO) biomaterials were prepared. Specifically, the CaPO-nanoneedle-mediated "cell perforation" transfection technology achieves high levels of gene expression in peritoneal cavity. In an intraperitoneal xenograft model with human ovarian cancer cell line SKOV3, the CaPO-nanoneedle/minicircle DNA system expressed BsAbEPH resulted in significant retardation of cancer growth and extension of mouse life-span with limited toxicity. And this system can be made as off-the-shelf and easy-to-use products. Therefore, CaPO-nanoneedle based non-viral gene delivery technology will have great potential in clinical application.

Effect of the Solution Temperature on the Precipitates and Grain Evolution of IN718 Fabricated by Laser Additive Manufacturing.

The effects of the solution heat treatment temperature on the precipitates, grain boundary evolution and response of the microhardness of Inconel 718 (IN718) superalloy fabricated by selective laser melting (SLM) were investigated. It was found that: (1) The long-chained Laves phases formed in the as-deposited condition dissolved into the matrix when the solution temperature rises above 980 °C. (2) The width-to-length ratio was maintained at approximately 1.6 when the solution was heated from 980 °C to 1080 °C, and dropped down to 1.03 when heated to 1130 °C. (3) Low-angle grain boundaries kept the same number fraction of 65% from 980 to 1080 °C as the as-deposited condition, and decreased dramatically from 1090 to 1130 °C to 4%. (4) Annealing twin boundaries occurred at 1090 °C with a number fraction of 3%, and quickly increased to 65% when heated to 1130 °C. It is concluded that the static recrystallization of IN718 fabricated by selective laser melting (SLM) occurred at 1090 °C and fast proceeded to full recrystallization at 1130 °C. The forming of annealing twins accompanies the recrystallization process and is an effective way to refine the recrystallized grain size.

Coherent strain of Guinier-Preston II zone in an Al-Zn-Mg-Cu alloy.

The Guinier-Preston (GP) II zone in an Al-Zn-Mg-Cu alloy was investigated by using a high-resolution electron microscopy (HREM). We used Geometric Phase Analysis (GPA) technique to measure the experimental HREM image and the simulated HREM image to obtain the strain distribution maps. The results show converging strain fields in the GP II zone, and the maximum compressive strain can reach -7.2% and -6.7%, respectively. The distribution of the experimental strain field was in consistence with that of the simulation result. The average strain of the alloy measured using XRD is 0.191%.

The synthesis of amphiphilic polyethyleneimine/calcium phosphate composites for bispecific T-cell engager based immunogene therapy.

Bispecific T-cell engagers (BiTEs) are single chain variable fragments with specific structures, which could connect the surface antigen on cancer cells and CD3 ligands on T cells, and then engage the T cells for cancer immunotherapy. In this report, a novel organic-inorganic hybrid gene delivery system composed of stearic acid modified polyethyleneimine (stPEI) and calcium phosphate (CaP) was used to deliver MC.DNA into cells to express BiTE antibodies. This gene delivery system exhibits high transfection efficiency, long-term effects and low cytotoxicity in vitro. Furthermore, the gene production, anti-IGF1R/CD3 bispecific T-cell engager, exhibited a rapid redirection activity in T cells to induce cancer cell apoptosis. In summary, the results confirmed that stPEI-CaP could be an efficient gene delivery system for BiTE encoding MC.DNA based gene immunotherapy.

Treatment of Human B-Cell Lymphomas Using Minicircle DNA Vector Expressing Anti-CD3/CD20 in a Mouse Model.

Bispecific antibodies (BsAbs), capable of directing T cells to kill specific cancer cells by transiently binding the two cell types, have emerged as one class of promising cancer immunotherapies. However, their wide clinical application might be hampered by two deficiencies: high cost and inconvenience in drug administration. This study presents concept-proving data that these problems could be bypassed by using an enhanced nonviral DNA vector minicircle (MC) to produce BsAb in vivo. It was found that the anti-CD3/CD20 produced from the minicircle (MC.CD20) could effectively mediate the T-cell killing of multiple CD20-positive human B-cell lymphoma cell lines in vitro. More importantly, it was demonstrated that delivery of 5 µg of MC.CD20 to mouse liver via hydrodynamic injection resulted in both the expression of a therapeutic level of anti-CD3/CD20 throughout the 32-day experiment and effective anticancer activity in a B-cell lymphoma xenograft mouse model. The data suggest that MC encoding the BsAbs may become an attractive cancer immunotherapy modality based on its excellent features of safety, efficacy, and convenience in both preparation and use, and its affordability once the delivery technology matures.

Erythrocyte membrane based cationic polymer-mcDNA complexes as an efficient gene delivery system.

Gene therapy has great promise for the treatment of obtained and inherited serious diseases. However, the lack of safe and efficient gene delivery systems remains a barrier for their clinical application. Here, we reported a potential gene delivery vehicle composed of the erythrocyte membrane and cationic polymers, for example the XtremeGENE from Roche and the ε-caprolactone modified polyethylenimine. In addition to high efficiency, this system showed negligible cytotoxicity compared to the two cationic polymers alone in various cell lines, including human embryonic kidney cells (293T), human liver cancer cells (Huh7 and HepG2), murine dendritic cells (DC2.4) and human umbilical cord mesenchymal stem cells (Hu-MSCs). Moreover, the results of confocal laser scanning microscopy and flow cytometry suggested that the cell uptake of this gene vector was improved and might be introduced by the fusion interaction between the erythrocyte membrane and targeted cells.Thus, all the results revealed that the erythrocyte membrane based gene delivery system might be able to serve as an excellent gene delivery system.

Synthesis of Amphiphilic Poly(ß-amino ester) for Efficiently Minicircle DNA Delivery in Vivo.

Minicircle DNA (mcDNA) is a kind of enhanced nonviral DNA vector with excellent profiles in biosafety and transgene expression. Herein, we reported a novel amphiphilic polymer comprising polyethylenimine(PEI) modified Poly(ß-amino ester) PEI-PBAE(C16) for efficient mcDNA delivery in vivo. The synthesized polymer could condense mcDNA into nanoscaled structure and exhibited efficient gene transfection ability without detectable cytotoxicity. Importantly, when injected into mouse intraperitoneally, these PEI-PBAE(C16) nanocomplexes were able to result in high level of trangene expression which lasted at least 72 h. Overall, these results demonstrated the PEI-PBAE(C16) can mediate effective and safe gene delivery in vivo with clinical application potential.

The recombined cccDNA produced using minicircle technology mimicked HBV genome in structure and function closely.

HBV covalently closed circular DNA (cccDNA) is drug-resistant and responsible for viral persistence. To facilitate the development of anti-cccDNA drugs, we developed a minicircle DNA vector (MC)-based technology to produce large quantity of recombined cccDNA (rcccDNA) resembling closely to its wild-type counterpart both in structure and function. The rcccDNA differed to the wild-type cccDNA (wtcccDNA) only in that it carried an extra 36-bp DNA recombinant product attR upstream of the preC/C gene. Using a procedure similar to standard plasmid production, milligrams of rcccDNA can be generated in common laboratories conveniently. The rcccDNA demonstrated many essential biological features of wtcccDNA, including: (1) undergoing nucleation upon nucleus entry; (2) serving as template for production of all HBV RNAs and proteins; (3) deriving virions capable of infecting tree shrew, and subsequently producing viral mRNAs, proteins, rcccDNA and infectious virions. As an example to develop anti-cccDNA drugs, we used the Crispr/Cas9 system to provide clear-cut evidence that rcccDNA was cleaved by this DNA editing tool in vitro. In summary, we have developed a convenient technology to produce large quantity of rcccDNA as a surrogate of wtcccDNA for investigating HBV biology and developing treatment to eradicate this most wide-spreading virus.

Increasing the minicircle DNA purity using an enhanced triplex DNA technology to eliminate DNA contaminants.

DNA vectors for human gene therapy have to meet the efficacy and safety requirements. Minicircles (MCs), a class of optimized DNA vectors free of plasmid backbone (PB) DNAs, have emerged as promising candidates because of their superior transgene expression profiles. However, the existence of impure DNAs, including the unrecombined MC producing plasmid (PP) and PB circle, in the MC products made using the current technologies exceed the safety limit. Here, we report the development of an enhanced triplex DNA (TriD) technology to eliminate almost all the impure DNAs from the MC products. To do this, a pair of optimized TriD forming sequences was placed to flank the kanamycin resistance gene in the PP. The MC products were incubated with a biotinylated TriD forming DNA oligonucleotide (olig), and the resulted TriDs were removed by binding to streptovidin-coated magnetic beads. Consequently, the residual impure DNAs were 0.03% or less in the final MC products. The reproducibility of this technique was confirmed with MCs of various transgene expression cassettes, sizes, and quantities, suggesting its great potential in making high quality MC for human gene therapy.

Engineering Clostridium acetobutylicum for alcohol production.

While Clostridium acetobutylicum has been used for large-scale butanol production (ABE fermentation), its by-product acetone cannot be used as a biofuel. In this study, C. acetobutylicum was engineered for alcohol titers (butanol plus ethanol). The adc gene was inactivated to eliminate acetone production, and glutathione biosynthetic capability was introduced into C. acetobutylicum to improve the strain's robustness by expressing Escherichia coli's gshAB genes in the adc locus. Acetone production was reduced from 2.64±0.22 g/L to 0.15±0.08 g/L in the engineered strain 824adc::gsh, whereas butanol production was increased from 5.17±0.26 g/L to 8.27±0.27 g/L. To further improve the alcohol titers, the metabolic flux in the alcohol biosynthesis pathways was enhanced. Overlapping PCR was used to generate expression cassette EC, which expresses the hbd, thl, crt, and bcd genes, and the Sol operon was amplified to express the adhE and ctfAB genes. Butanol and alcohol production reached 14.86±0.26 g/L and 18.11±0.66 g/L, respectively, in 824adc::gsh Sol-EC. Furthermore, the butanol and alcohol yields were 0.336 g/g and 0.409 g/g, respectively, in 824adc::gsh Sol-EC. This study provided a combined strategy for enhancing alcohol production in C. acetobutylicum.

(L)-Valine production with minimization of by-products' synthesis in Corynebacterium glutamicum and Brevibacterium flavum.

Corynebacterium glutamicum ATCC13032 and Brevibacterium flavum JV16 were engineered for L-valine production by over-expressing ilvEBN ( r ) C genes at 31 °C in 72 h fermentation. Different strategies were carried out to reduce the by-products' accumulation in L-valine fermentation and also to increase the availability of precursor for L-valine biosynthesis. The native promoter of ilvA of C. glutamicum was replaced with a weak promoter MPilvA (P-ilvAM1CG) to reduce the biosynthetic rate of L-isoleucine. Effect of different relative dissolved oxygen on L-valine production and by-products' formation was recorded, indicating that 15 % saturation may be the most appropriate relative dissolved oxygen for L-valine fermentation with almost no L-lactic acid and L-glutamate formed. To minimize L-alanine accumulation, alaT and/or avtA was inactivated in C. glutamicum and B. flavum, respectively. Compared to high concentration of L-alanine accumulated by alaT inactivated strains harboring ilvEBN ( r ) C genes, L-alanine concentration was reduced to 0.18 g/L by C. glutamicum ATCC13032MPilvA△avtA pDXW-8-ilvEBN ( r ) C, and 0.22 g/L by B. flavum JV16avtA::Cm pDXW-8-ilvEBN ( r ) C. Meanwhile, L-valine production and conversion efficiency were enhanced to 31.15 g/L and 0.173 g/g by C. glutamicum ATCC13032MPilvA△avtA pDXW-8-ilvEBN ( r ) C, 38.82 g/L and 0.252 g/g by B. flavum JV16avtA::Cm pDXW-8-ilvEBN ( r ) C. This study provides combined strategies to improve L-valine yield by minimization of by-products' production.

Improvement of L-valine production at high temperature in Brevibacterium flavum by overexpressing ilvEBNrC genes.

Brevibacterium flavum ATCC14067 was engineered for L: -valine production by overexpression of different ilv genes; the ilvEBN(r)C genes from B. flavum NV128 provided the best candidate for L: -valine production. In traditional fermentation, L: -valine production reached 30.08 ± 0.92 g/L at 31°C in 72 h with a low conversion efficiency of 0.129 g/g. To further improve the L: -valine production and conversion efficiency based on the optimum temperatures of L: -valine biosynthesis enzymes (above 35°C) and the thermotolerance of B. flavum, the fermentation temperature was increased to 34, 37, and 40°C. As a result, higher metabolic rate and L: -valine biosynthesis enzymes activity were obtained at high temperature, and the maximum L: -valine production, conversion efficiency, and specific L: -valine production rate reached 38.08 ± 1.32 g/L, 0.241 g/g, and 0.133 g g(-1) h(-1), respectively, at 37°C in 48 h fermentation. The strategy for enhancing L: -valine production by overexpression of key enzymes in thermotolerant strains may provide an alternative approach to enhance branched-chain amino acids production with other strains.