Novel economy and carbon emissions prediction model of different countries or regions in the world for energy optimization using improved residual neural network.

Nowadays, the world has achieved tremendous economic development at the expense of the long-term habitability of the planet. With the rapid economic development, the global greenhouse effect caused by excessive carbon dioxide (CO2) emissions is also accumulating, which generates the negative impact of global warming on nature and human beings. Meanwhile, economy and CO2 emissions prediction methods based on traditional neural networks lead to gradient disappearance or gradient explosion, making the economy and CO2 emissions prediction inaccurate. Therefore, this paper proposes a novel economy and CO2 emissions prediction model based on a residual neural network (RESNET) to optimize and analyze energy structures of different countries or regions in the world. The skip links are used in the inner residual block of the RESNET to alleviate vanishing gradients due to increasing depth in deep neural networks. Consequently, the proposed RESNET can optimize this problem and protect the integrity of information by directly bypassing the input information to the output, which can increase the precision of the prediction model. The needs for natural gas, hydroelectricity, oil, coal, nuclear energy, and renewable energy in 24 different countries or regions from 2009 to 2020 are used as inputs, the CO2 emissions and the gross domestic product (GDP) per capita are respectively used as the undesired output and the desired output of the RESNET to build an economy and CO2 emissions prediction model. The experimental results show that the RESNET has higher correctness and functionality than the traditional convolutional neural network (CNN), the radial basis function (RBF), the extreme learning machine (ELM) and the back propagation (BP). Furthermore, the proposed model provides guidance and development plans for countries or regions with low energy efficiency, which can improve energy efficiency, economic development and reasonably control CO2 emissions.

Molecular Subsets in Renal Cancer Determine Outcome to Checkpoint and Angiogenesis Blockade.

Integrated multi-omics evaluation of 823 tumors from advanced renal cell carcinoma (RCC) patients identifies molecular subsets associated with differential clinical outcomes to angiogenesis blockade alone or with a checkpoint inhibitor. Unsupervised transcriptomic analysis reveals seven molecular subsets with distinct angiogenesis, immune, cell-cycle, metabolism, and stromal programs. While sunitinib and atezolizumab + bevacizumab are effective in subsets with high angiogenesis, atezolizumab + bevacizumab improves clinical benefit in tumors with high T-effector and/or cell-cycle transcription. Somatic mutations in PBRM1 and KDM5C associate with high angiogenesis and AMPK/fatty acid oxidation gene expression, while CDKN2A/B and TP53 alterations associate with increased cell-cycle and anabolic metabolism. Sarcomatoid tumors exhibit lower prevalence of PBRM1 mutations and angiogenesis markers, frequent CDKN2A/B alterations, and increased PD-L1 expression. These findings can be applied to molecularly stratify patients, explain improved outcomes of sarcomatoid tumors to checkpoint blockade versus antiangiogenics alone, and develop personalized therapies in RCC and other indications.

Microfluidic Pneumatic Printed Sandwiched Microdroplet Array for High-Throughput Enzymatic Reaction and Screening.

High-throughput enzyme screening for desired functionality is highly demanded. This paper utilizes a newly developed microfluidic pneumatic printing platform for high-throughput enzyme screening applications. The novel printing platform can achieve distinct features including a disposable cartridge, which avoids crosstalk; a flexible cartridge design, allowing for integration of multiple channels; and fast printing speed with submicroliter spot size. Moreover, a polydimethylsiloxane (PDMS)-based sandwich structure has been proposed and used during the printing and imaging, which can lead to better results, including reduced evaporation as well as a uniform light path during imaging. Using this microfluidic pneumatic printed PDMS sandwiched microdroplet array platform, we have demonstrated the capability of high-throughput generation of a combinatorial droplet array with concentration and volume gradients. Furthermore, the potential for enzymatic study has been validated by quantified cellulose reaction implemented with the printing platform.

Dotette: Programmable, high-precision, plug-and-play droplet pipetting.

Manual micropipettes are the most heavily used liquid handling devices in biological and chemical laboratories; however, they suffer from low precision for volumes under 1 µl and inevitable human errors. For a manual device, the human errors introduced pose potential risks of failed experiments, inaccurate results, and financial costs. Meanwhile, low precision under 1 µl can cause severe quantification errors and high heterogeneity of outcomes, becoming a bottleneck of reaction miniaturization for quantitative research in biochemical labs. Here, we report Dotette, a programmable, plug-and-play microfluidic pipetting device based on nanoliter liquid printing. With automated control, protocols designed on computers can be directly downloaded into Dotette, enabling programmable operation processes. Utilizing continuous nanoliter droplet dispensing, the precision of the volume control has been successfully improved from traditional 20%-50% to less than 5% in the range of 100 nl to 1000 nl. Such a highly automated, plug-and-play add-on to existing pipetting devices not only improves precise quantification in low-volume liquid handling and reduces chemical consumptions but also facilitates and automates a variety of biochemical and biological operations.

Microfluidic Print-to-Synthesis Platform for Efficient Preparation and Screening of Combinatorial Peptide Microarrays.

In this paper, we introduce a novel microfluidic combinatorial synthesis platform, referred to as Microfluidic Print-to-Synthesis (MPS), for custom high-throughput and automated synthesis of a large number of unique peptides in a microarray format. The MPS method utilizes standard Fmoc chemistry to link amino acids on a polyethylene glycol (PEG)-functionalized microdisc array. The resulting peptide microarrays permit rapid screening for interactions with molecular targets or live cells, with low nonspecific binding. Such combinatorial peptide microarrays can be reliably prepared at a spot size of 200 µm with 1 mm center-to-center distance, dimensions that require only minimal reagent consumption (less than 30 nL per spot per coupling reaction). The MPS platform has a scalable design for extended multiplexibility, allowing for 12 different building blocks and coupling reagents to be dispensed in one microfluidic cartridge in the current format, and could be further scaled up. As proof of concept for the MPS platform, we designed and constructed a focused tetrapeptide library featuring 2560 synthetic peptide sequences, capped at the N-terminus with 4-[( N'-2-methylphenyl)ureido]phenylacetic acid. We then used live human T lymphocyte Jurkat cells as a probe to screen the peptide microarrays for their interaction with α4ß1 integrin overexpressed and activated on these cells. Unlike the one-bead-one-compound approach that requires subsequent decoding of positive beads, each spot in the MPS array is spatially addressable. Therefore, this platform is an ideal tool for rapid optimization of lead compounds found in nature or discovered from diverse combinatorial libraries, using either biochemical or cell-based assays.

Synthetic microbial consortia enable rapid assembly of pure translation machinery.

Assembly of recombinant multiprotein systems requires multiple culturing and purification steps that scale linearly with the number of constituent proteins. This problem is particularly pronounced in the preparation of the 34 proteins involved in transcription and translation systems, which are fundamental biochemistry tools for reconstitution of cellular pathways ex vivo. Here, we engineer synthetic microbial consortia consisting of between 15 and 34 Escherichia coli strains to assemble the 34 proteins in a single culturing, lysis, and purification procedure. The expression of these proteins is controlled by synthetic genetic modules to produce the proteins at the correct ratios. We show that the pure multiprotein system is functional and reproducible, and has low protein contaminants. We also demonstrate its application in the screening of synthetic promoters and protease inhibitors. Our work establishes a novel strategy for producing pure translation machinery, which may be extended to the production of other multiprotein systems.

Multi-dimensional studies of synthetic genetic promoters enabled by microfluidic impact printing.

Natural genetic promoters are regulated by multiple cis and trans regulatory factors. For quantitative studies of these promoters, the concentration of only a single factor is typically varied to obtain the dose response or transfer function of the promoters with respect to the factor. Such design of experiments has limited our ability to understand quantitative, combinatorial interactions between multiple regulatory factors at promoters. This limitation is primarily due to the intractable number of experimental combinations that arise from multifactorial design of experiments. To overcome this major limitation, we integrate impact printing and cell-free systems to enable multi-dimensional studies of genetic promoters. We first present a gradient printing system which comprises parallel piezoelectric cantilever beams as a scalable actuator array to generate droplets with tunable volumes in the range of 100 pL-10 nL, which facilitates highly accurate direct dilutions in the range of 1-10 000-fold in a 1 µL drop. Next, we apply this technology to study interactions between three regulatory factors at a synthetic genetic promoter. Finally, a mathematical model of gene regulatory modules is established using the multi-parametric and multi-dimensional data. Our work creates a new frontier in the use of cell-free systems and droplet printing for multi-dimensional studies of synthetic genetic constructs.

Piezoelectric-driven droplet impact printing with an interchangeable microfluidic cartridge.

Microfluidic impact printing has been recently introduced, utilizing its nature of simple device architecture, low cost, non-contamination, and scalable multiplexability and high throughput. In this paper, we have introduced an impact-based droplet printing platform utilizing a simple plug-and-play microfluidic cartridge driven by piezoelectric actuators. Such a customizable printing system allows for ultrafine control of droplet volume from picoliters (∼23 pl) to nanoliters (∼10 nl), a 500 fold variation. The high flexibility of droplet generation can be simply achieved by controlling the magnitude of actuation (e.g., driving voltage) and the waveform shape of actuation pulses, in addition to nozzle size restrictions. Detailed printing characterizations on these parameters have been conducted consecutively. A multiplexed impact printing system has been prototyped and demonstrated to provide the functions of single-droplet jetting and droplet multiplexing as well as concentration gradient generation. Moreover, a generic biological assay has also been tested and validated on this printing platform. Therefore, the microfluidic droplet printing system could be of potential value to establish multiplexed micro reactors for high-throughput life science applications.

Reconfigurable microfluidic dilution for high-throughput quantitative assays.

This paper reports a reconfigurable microfluidic dilution device for high-throughput quantitative assays, which can easily produce discrete logarithmic/binary concentration profiles ranging from 1 to 100-fold dilution in parallel from a fixed sample volume (e.g., 10 µL) without any assistance of continuous fluidic pump or robotic automation. The integrated dilution generation chip consists of switchable distribution and collection channels, metering reservoirs, reaction chambers, and pressure-activatable Laplace valves. Following the sequential loading of a sample, a diluent, and a detection reagent into their individual metering chambers, the top microfluidic layer can be reconfigured to collect the metered chemicals into the reaction chambers in parallel, where detection will be conducted. To facilitate mixing and reaction in the microchambers, two acoustic microstreaming actuation mechanisms have been investigated for easy integrability and accessibility. Furthermore, the microfluidic dilution generator has been characterized by both colorimetric and fluorescent means. A further demonstration of the generic usage of the quantitative dilution chip has utilized the commonly available bicinchoninic acid (BCA) assay to analyse the protein concentrations of human tissue extracts. In brief, the microfluidic dilution generator offers a high-throughput high-efficiency quantitative analytical alternative to conventional quantitative assay platforms, by simple manipulation of a minute amount of chemicals in a compact microfluidic device with minimal equipment requirement, which can serve as a facile tool for biochemical and biological analyses in regular laboratories, point-of-care settings and low-resource environments.