Improved drug target deconvolution with PISA-DIA using an extended, overlapping temperature gradient.

Thermal proteome profiling (TPP) is a powerful tool for drug target deconvolution. Recently, data-independent acquisition mass spectrometry (DIA-MS) approaches have demonstrated significant improvements to depth and missingness in proteome data, but traditional TPP (a.k.a. CEllular Thermal Shift Assay "CETSA") workflows typically employ multiplexing reagents reliant on data-dependent acquisition (DDA). Herein, we introduce a new experimental design for the Proteome Integral Solubility Alteration via label-free DIA approach (PISA-DIA). We highlight the proteome coverage and sensitivity achieved by using multiple overlapping thermal gradients alongside DIA-MS, which maximizes efficiencies in PISA sample concatenation and safeguards against missing protein targets that exist at high melting temperatures. We demonstrate our extended PISA-DIA design has superior proteome coverage as compared to using tandem-mass tags (TMT) necessitating DDA-MS analysis. Importantly, we demonstrate our PISA-DIA approach has the quantitative and statistical rigor using A-1331852, a specific inhibitor of BCL-xL. Due to the high melt temperature of this protein target, we utilized our extended multiple gradient PISA-DIA workflow to identify BCL-xL. We assert our novel overlapping gradient PISA-DIA-MS approach is ideal for unbiased drug target deconvolution, spanning a large temperature range whilst minimizing target dropout between gradients, increasing the likelihood of resolving the protein targets of novel compounds.

Higher-order nonequilibrium term: Effective power density quantifying evolution towards or away from local thermodynamic equilibrium.

A common approach to assess the nature of energy conversion in a classical fluid or plasma is to compare power densities of the various possible energy conversion mechanisms. A leading research area is quantifying energy conversion for systems that are not in local thermodynamic equilibrium (LTE), as is common in a number of fluid and plasma systems. Here we introduce the "higher-order nonequilibrium term" (HORNET) effective power density, which quantifies the rate of change of departure of a phase space density from LTE. It has dimensions of power density, which allows for quantitative comparisons with standard power densities. We employ particle-in-cell simulations to calculate HORNET during two processes, magnetic reconnection and decaying kinetic turbulence in collisionless magnetized plasmas, that inherently produce non-LTE effects. We investigate the spatial variation of HORNET and the time evolution of its spatial average. By comparing HORNET with power densities describing changes to the internal energy (pressure dilatation, Pi-D, and divergence of the vector heat flux density), we find that HORNET can be a significant fraction of these other measures (8% and 35% for electrons and ions, respectively, for reconnection; up to 67% for both electrons and ions for turbulence), meaning evolution of the system towards or away from LTE can be dynamically important. Applications to numerous plasma phenomena are discussed.

Using Direct Laboratory Measurements of Electron Temperature Anisotropy to Identify the Heating Mechanism in Electron-Only Guide Field Magnetic Reconnection.

Anisotropic electron heating during electron-only magnetic reconnection with a large guide magnetic field is directly measured in a laboratory plasma through in situ measurements of electron velocity distribution functions. Electron heating preferentially parallel to the magnetic field is localized to one separatrix, and anisotropies of 1.5 are measured. The mechanism for electron energization is identified as the parallel reconnection electric field because of the anisotropic nature of the heating and spatial localization. These characteristics are reproduced in a 2D particle-in-cell simulation and are also consistent with numerous magnetosheath observations. A measured increase in the perpendicular temperature along both separatrices is not reproduced by our 2D simulations. This work has implications for energy partition studies in magnetosheath and laboratory reconnection.

First report on the bacterial community composition, diversity, and functions in Ramsar site of Central Himalayas, Nepal.

Wetland bacterial communities are highly sensitive to altered hydrology and the associated change in water physicochemical and biological properties leading to shifts in community composition and diversity, hence affecting the ecological roles. However, relevant studies are lacking in the wetlands of central Himalayas Nepal. Thus, we aimed to explore the variation of bacterial communities, diversity, and ecologic functions in the wet and dry periods of a wetland (designed as Ramsar site, Ramsar no 2257) by using 16S rRNA gene-based Illumina MiSeq sequencing. We reported a pronounced variation in water physicochemical and biological properties (temperature, pH, Chla, DOC, and TN), bacterial diversity, and community composition. Bacterial communities in the dry season harbored significantly higher alpha diversity, while significantly higher richness and abundance were reflected in the wet season. Our results uncovered the effect of nutrients on bacterial abundance, richness, and community composition. Fourteen percent of the total OTUs were shared in two hydrological periods, and the largest portion of unique OTUs (58%) was observed in the dry season. Planctomycetes and Bacteroidetes dominated the wet season exclusive OTUs; meanwhile, Actinobacteria dominated the dry season exclusive OTUs. Bacteria in these wetlands exhibited divergent ecological functions during the dry and wet seasons. By disclosing the variation of water bacterial communities in different hydrologic periods and their relationship with environmental factors, this first-hand work in the Ramsar site of Nepal will develop a baseline dataset for the scientific community that will assist in understanding the wetland's microbial ecology and biogeography.

Deciphering the Kidney Matrisome: Identification and Quantification of Renal Extracellular Matrix Proteins in Healthy Mice.

Precise characterization of a tissue's extracellular matrix (ECM) protein composition (matrisome) is essential for biomedicine. However, ECM protein extraction that requires organ-specific optimization is still a major limiting factor in matrisome studies. In particular, the matrisome of mouse kidneys is still understudied, despite mouse models being crucial for renal research. Here, we comprehensively characterized the matrisome of kidneys in healthy C57BL/6 mice using two ECM extraction methods in combination with liquid chromatography tandem mass spectrometry (LC-MS/MS), protein identification, and label-free quantification (LFQ) using MaxQuant. We identified 113 matrisome proteins, including 22 proteins that have not been previously listed in the Matrisome Database. Depending on the extraction approach, the core matrisome (structural proteins) comprised 45% or 73% of kidney ECM proteins, and was dominated by glycoproteins, followed by collagens and proteoglycans. Among matrisome-associated proteins, ECM regulators had the highest LFQ intensities, followed by ECM-affiliated proteins and secreted factors. The identified kidney ECM proteins were primarily involved in cellular, developmental and metabolic processes, as well as in molecular binding and regulation of catalytic and structural molecules' activity. We also performed in silico comparative analysis of the kidney matrisome composition in humans and mice based on publicly available data. These results contribute to the first reference database for the mouse renal matrisome.

Atmospheric wet deposition of trace elements in Bangladesh: A new insight into spatiotemporal variability and source apportionment.

The interaction between water vapor and natural/anthropogenic airborne particles deposits a massive amount of trace elements in the ecosystem. As the principal source region of the Indian monsoon originated from the Bay of Bengal, atmospheric trace elements in Bangladesh have impacted atmospheric wet deposition along the pathway, even reaching the headwaters in the Asian water tower. However, no study reports the atmospheric wet deposition of trace elements at the spatiotemporal scale. Thus, this study investigated the concentration, sources, and deposition of eighteen trace elements (Al, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Rb, Sr, Mo, Cd, Sn, Sb, Ba, and Pb) from 232 precipitation samples at four sites in Bangladesh. Results showed that the VWM concentrations of the eighteen measured trace elements ranged from 0.03 to 535.6 µg L-1. Zn, Fe, and Al were the principal elements of the atmosphere at four sites with mean values of 207.9 ± 227.8, 18.2 ± 9.3, and 16.3 ± 6.8 µg L-1, respectively. Besides, the eighteen trace elements showed significant variation in spatial scale with distinct seasonality. Enrichment factors of Zn, Sb, and Cd indicated serious anthropogenic influences. The major sources of trace elements were fossil fuel combustion, brick kilns, crustal dust, fugitive Pb, metal smelters, and battery recycling. Both the concentration and precipitation amount played a pivotal role in the deposition. Most of the air masses during the monsoon season came from marine sources passing over southern India and Sri Lanka. Meanwhile, the air masses during the non-monsoon season were from West Asia and the northwestern Indian subcontinent. The air masses are transported over a long range and deposit massive amounts of particulate matter in the Third Pole Himalayan region. This first-hand work on spatiotemporal variation provides a reference dataset for future targeting of the scientific community and policymakers for the development of strategies and action plans.

Hydrochemical characterization and irrigation suitability of the Ganges Brahmaputra River System: review and assessment.

The hydrochemical characterization and irrigation suitability assessment of the Ganges-Brahmaputra River System (GBRS) has immense importance for the livelihoods of people and ecosystem sustainability in the region. This study aims to assess the hydrochemical characteristics and evaluate the irrigation suitability of water in the GBRS by reviewing published literature of the major tributaries. The studied rivers were categorized into two groups namely Group-1 and Group-2 considering the similarities of climatic patterns, hydrochemical attributes, and drainage characteristics. The hydrochemistry of the river water was characterized by the Piper diagram, Gibbs plot, mixing plots, and ionic ratios. Furthermore, irrigation water qualities were evaluated by electrical conductivity (EC), sodium percentage (Na%), sodium adsorption ratio (SAR), magnesium hazard (MH), and Wilcox diagram. The results indicated that the hydrochemistry of the GBRS was slightly alkaline to alkaline (7.42-8.78) in nature. The average concentrations of most of the chemical attributes showed higher in Group-1, whereas the average concentrations of K+ and NO3 - were found higher in Group-2. The average concentration of the major ions followed the dominancy order Ca2+ > Mg2+ > Na+ > K+ for cations and HCO3 - >SO4 2- > Cl- > NO3 - for anions in both groups. Gibbs plot and mixing plot indicated that carbonate rock weathering dominates the hydrochemical process, which was further confirmed by the Piper diagram and the ionic ratios. From the analyses of irrigational water quality, almost all the rivers (except Gomti River in terms of MH and Rangit River in terms of Na%) in the GBRS were found to be suitable based on EC, SAR, Na%, MH, and Wilcox diagram. Finally, the majority of river systems in the GBRS were characterized by carbonate dominated lithology and irrigational water quality is mostly suitable for utilization. This study could be useful for water quality management in the glacial-fed Himalayan river under the context of global climate change.

Hydrochemical appraisal and solute acquisitions in Seti River Basin, Central Himalaya, Nepal.

The chemical characterization and assessment of the water quality in the headwater areas of the Himalaya are necessary for securing the water in the future. This study aims to assess the hydrochemistry and water quality concerning drinking and irrigational uses in the Seti River Basin (SRB), Nepal. A total of 45 water samples were collected in 2016 from the SRB during pre-monsoon, monsoon, and post-monsoon seasons, and pH, EC, TDS, and DO were measured on-site, whereas Ca2+, Mg2+, K+, Na+, Cl-, SO42-, NO3-, and dissolved Si were analyzed in the laboratory. The results revealed mildly alkaline pH (8.40 ± 0.43) with the pattern of average ionic dominancy: Ca2+ > Mg2+ > Na+ > K+ and HCO3- > SO42- > Cl- > NO3- for cations and anions, respectively. Gibbs diagram implied that the lithogenic weathering mainly controlled the solute acquisition process, which was further confirmed by the Piper diagram, exhibiting Ca-HCO3 as the governing hydrochemical facies (91%). The average molar ratios were 0.88, 8.33, and 6.86 of (Ca2+ + Mg2+)/TZ+, (Ca2+ + Mg2+)/(Na+ + K+), and HCO3-/(Na+ + K+), respectively, which specified that the carbonate weathering largely controlled the solute acquisition processes with a minor contribution of silicates. The mass budget calculation also confirmed the dominance of carbonate weathering (72.0%, 78.9%, and 62.0% in Pre-Monsoon, Monsoon, and Post-Monsoon, respectively) and the high monsoon rainfall's dilution effect to anthropogenic input of cations. Principal component analysis and correlation matrix exhibited that the major sources of ions in the basin were geogenic with minor anthropic signatures. Furthermore, water quality in connection to drinking and irrigation uses revealed that the basin has mostly retained its natural water quality. This investigation suggests that regular monitoring and assessment are essential for maintaining the water quality and ecological integrity in the Himalayan river basins.

Use of a Recombinant Biomarker Protein DDA Library Increases DIA Coverage of Low Abundance Plasma Proteins.

Credible detection and quantification of low abundance proteins from human blood plasma is a major challenge in precision medicine biomarker discovery when using mass spectrometry (MS). In this proof-of-concept study, we employed a mixture of selected recombinant proteins in DDA libraries to subsequently identify (not quantify) cancer-associated low abundance plasma proteins using SWATH/DIA. The exemplar DDA recombinant protein spectral library (rPSL) was derived from tryptic digestion of 36 recombinant human proteins that had been previously implicated as possible cancer biomarkers from both our own and other studies. The rPSL was then used to identify proteins from nondepleted colorectal cancer (CRC) EDTA plasmas by SWATH-MS. Most (32/36) of the proteins used in the rPSL were reliably identified from CRC plasma samples, including 8 proteins (i.e., BTC, CXCL10, IL1B, IL6, ITGB6, TGFα, TNF, TP53) not previously detected using high-stringency protein inference MS according to PeptideAtlas. The rPSL SWATH-MS protocol was compared to DDA-MS using MARS-depleted and postdigestion peptide fractionated plasmas (here referred to as a human plasma DDA library). Of the 32 proteins identified using rPSL SWATH, only 12 could be identified using DDA-MS. The 20 additional proteins exclusively identified using the rPSL SWATH approach were almost exclusively lower abundance (i.e., <10 ng/mL) proteins. To mitigate justified FDR concerns, and to replicate a more typical library creation approach, the DDA rPSL library was merged with a human plasma DDA library and SWATH identification repeated using such a merged library. The majority (33/36) of the low abundance plasma proteins added from the rPSL were still able to be identified using such a merged library when high-stringency HPP Guidelines v3.0 protein inference criteria were applied to our data set. The MS data set has been deposited to ProteomeXchange Consortium via the PRIDE partner repository (PXD022361).

A high-stringency blueprint of the human proteome.

The Human Proteome Organization (HUPO) launched the Human Proteome Project (HPP) in 2010, creating an international framework for global collaboration, data sharing, quality assurance and enhancing accurate annotation of the genome-encoded proteome. During the subsequent decade, the HPP established collaborations, developed guidelines and metrics, and undertook reanalysis of previously deposited community data, continuously increasing the coverage of the human proteome. On the occasion of the HPP's tenth anniversary, we here report a 90.4% complete high-stringency human proteome blueprint. This knowledge is essential for discerning molecular processes in health and disease, as we demonstrate by highlighting potential roles the human proteome plays in our understanding, diagnosis and treatment of cancers, cardiovascular and infectious diseases.

Decelerated Hot Carrier Cooling in Graphene via Nondissipative Carrier Injection from MoS2.

One key to improve the performance of advanced optoelectronic devices and energy harvesting in graphene is to understand the predominant carrier scattering via optical phonons. Nevertheless, low light absorbance in graphene yields a limited photoexcited carrier density, hampering the hot carrier effect, which is strongly correlated to the hot optical phonon bottleneck effect as the energy-loss channel. Here, by integrating graphene with monolayer MoS2 possessing stronger light absorbance, we demonstrate an efficient interfacial hot carrier transfer between graphene and MoS2 in their heterostructure with a prolonged relaxation time using broadband transient differential transmittance spectroscopy. We observe that the carrier relaxation time of graphene in the heterostructure is 4 times slower than that of bare graphene. This is explained by nondissipative interlayer transfer from MoS2 to graphene, which is attributed to the enhanced hot optical phonon bottleneck effect of graphene in the heterostructure by an increased photoexcited carrier population. A significant reduction of both amplitude and relaxation time in A- and B-excitons is another evidence of the interlayer transfer from MoS2 to graphene. The nondissipative interlayer charge transfer from MoS2 to graphene is confirmed by density functional calculations. This provides a different platform to further study the photoinduced hot carrier effect in graphene heterostructures for photothermoelectric detectors or hot carrier solar cells.

Carrier multiplication in van der Waals layered transition metal dichalcogenides.

Carrier multiplication (CM) is a process in which high-energy free carriers relax by generation of additional electron-hole pairs rather than by heat dissipation. CM is promising disruptive improvements in photovoltaic energy conversion and light detection technologies. Current state-of-the-art nanomaterials including quantum dots and carbon nanotubes have demonstrated CM, but are not satisfactory owing to high-energy-loss and inherent difficulties with carrier extraction. Here, we report CM in van der Waals (vdW) MoTe2 and WSe2 films, and find characteristics, commencing close to the energy conservation limit and reaching up to 99% CM conversion efficiency with the standard model. This is demonstrated by ultrafast optical spectroscopy with independent approaches, photo-induced absorption, photo-induced bleach, and carrier population dynamics. Combined with a high lateral conductivity and an optimal bandgap below 1 eV, these superior CM characteristics identify vdW materials as an attractive candidate material for highly efficient and mechanically flexible solar cells in the future.

Potential early clinical stage colorectal cancer diagnosis using a proteomics blood test panel.

BACKGROUND: One of the most significant challenges in colorectal cancer (CRC) management is the use of compliant early stage population-based diagnostic tests as adjuncts to confirmatory colonoscopy. Despite the near curative nature of early clinical stage surgical resection, mortality remains unacceptably high-as the majority of patients diagnosed by faecal haemoglobin followed by colonoscopy occur at latter stages. Additionally, current population-based screens reliant on fecal occult blood test (FOBT) have low compliance (~ 40%) and tests suffer low sensitivities. Therefore, blood-based diagnostic tests offer survival benefits from their higher compliance (≥ 97%), if they can at least match the sensitivity and specificity of FOBTs. However, discovery of low abundance plasma biomarkers is difficult due to occupancy of a high percentage of proteomic discovery space by many high abundance plasma proteins (e.g., human serum albumin). METHODS: A combination of high abundance protein ultradepletion (e.g., MARS-14 and an in-house IgY depletion columns) strategies, extensive peptide fractionation methods (SCX, SAX, High pH and SEC) and SWATH-MS were utilized to uncover protein biomarkers from a cohort of 100 plasma samples (i.e., pools of 20 healthy and 20 stages I-IV CRC plasmas). The differentially expressed proteins were analyzed using ANOVA and pairwise t-tests (p < 0.05; fold-change > 1.5), and further examined with a neural network classification method using in silico augmented 5000 patient datasets. RESULTS: Ultradepletion combined with peptide fractionation allowed for the identification of a total of 513 plasma proteins, 8 of which had not been previously reported in human plasma (based on PeptideAtlas database). SWATH-MS analysis revealed 37 protein biomarker candidates that exhibited differential expression across CRC stages compared to healthy controls. Of those, 7 candidates (CST3, GPX3, CFD, MRC1, COMP, PON1 and ADAMDEC1) were validated using Western blotting and/or ELISA. The neural network classification narrowed down candidate biomarkers to 5 proteins (SAA2, APCS, APOA4, F2 and AMBP) that had maintained accuracy which could discern early (I/II) from late (III/IV) stage CRC. CONCLUSION: MS-based proteomics in combination with ultradepletion strategies have an immense potential of identifying diagnostic protein biosignature.

Proteomics Reveals Cell-Surface Urokinase Plasminogen Activator Receptor Expression Impacts Most Hallmarks of Cancer.

While metastasis is the primary cause of colorectal cancer (CRC) mortality, the molecular mechanisms underpinning it remains elusive. Metastasis is propagated through driver oncogene/suppressor gene mutations, accompanied by passenger mutations and underlying genomic instability. To understand cancer biology, a unifying framework called the "hallmarks of cancer" (HoCs) has been developed, which organizes cell biological alterations under ten key hallmarks. Underlying these HoCs, genome instability generates mutational diversity that is amplified by inflammation. Recognizing how critical cancer cell-surface proteins influence, these HoCs have been proposed to accelerate precision medicine therapeutic development. A moderate decrease (43%↓) in HCT116 cell surface urokinase plasminogen activator receptor (uPAR) expression mitigates against many HoCs driven by these cell's KRAS and PIK3CA mutational signature. Comprehensive proteomics (whole cell lysis with two membrane protein enrichments) coupled with ingenuity pathway analysis (IPA) demonstrates that uPAR negates essential pathways across the HoC spectrum, particularly those associated with metastasis, resisting cell death, and sustaining proliferation, and parallels Cancer Hallmarks Analytics Tool analysis. Decreasing uPAR predominantly alters metastasis-related and uPAR-interactome protein expression (e.g., EGFR, caveolin, vitronectin, integrin ß4). Collectively, it is demonstrated that uPAR is a lynchpin protein capable of regulating several HoC pathways in a classical CRC mutational background.

In Silico Peptide Repertoire of Human Olfactory Receptor Proteomes on High-Stringency Mass Spectrometry.

Human olfactory receptors (ORs) are seven-pass transmembrane G-protein coupled receptors (GPCR) involved in smell perception and many other signaling pathways. They are primarily expressed in the olfactory epithelium and ectopically expressed in several other organs and tissues. neXtProt contains 4 PE1 (protein existence 1, evidenced at the protein level) ORs, determined on the basis of either protein interaction data (i.e., OR1D4 and OR2AG1) or convincing genetic, haplotype, or biochemical data (i.e., OR1D2 and OR2J3). Not a single OR currently qualifies for neXtProt PE1 status based on mass spectrometry (MS) evidence. Many reasons for this absence of MS-based identification have been proposed, including (i) confined or spatiotemporal or developmental expression, (ii) low copy number, (iii) OR repertoire gene silencing, and (iv) limited tissue availability. OR transmembrane domains (TMDs) inherently limit MS identification because the hydrophobic nature restricts the access of trypsin to potential cleavage sites. Equally, the extremely low frequency or lack of accessible arginine and lysine residues in TMDs renders trypsin cleavage ineffective. Here, we demonstrate an analytical approach specifically focused on the hydrophilic (trypsin-accessible) domains of ORs [i.e., with all transmembrane segments and anchored peptides excluded). We predicted the ability of OR soluble (hydrophilic) domains to yield 2 or more >9 amino acids (aa) length unique mapping (unique to a protein only), non-nested (peptides with varying length at the N or C terminal but containing the same core sequence), leucine/isoleucine (I/L) switch examined (I and L have same mass and cannot be distinguished by MS) tryptic peptides. Our analysis showed that ∼58% of the human OR proteome could potentially generate tryptic peptides that satisfy current the Human Proteome Project data interpretation guidelines (version 2.1) when no missed cleavages are allowed and increases to ∼78% when one missed cleavage is allowed. The utilization of current biological data (adjuvant genomics, expression profile, transcriptomics, epigenome silencing data, etc.) and the adoption of a non-conventional proteomics approach (e.g., Confetti multiprotease digestion, CNBr cleavage of TMDs, and more-extreme chromatographic and MS methods) could aid in the detection of the remaining ORs.

Minimizing Trap Charge Density towards an Ideal Diode in Graphene-Silicon Schottky Solar Cell.

Photovoltaic device performance of graphene/n-Si Schottky diodes is largely affected by inhomogeneous oxide formation at the interface that suppresses the tunneling current of injected and photoexcited charges. The accumulated trap charges at low current induce charge recombination at the interface and degrade the ideality factor of the diode and the fill factor (FF) of the solar cell. This consequently gives rise to a nonlinear current-voltage ( I- V) feature in solar cells, commonly known as an S-shaped kink, which can be engineered by optimizing the interface barrier thickness or by increasing the carrier mobility. Here, we present chemical and electrochemical doping methods to increase the conductivity of graphene that transforms nonlinear kink photodiodes with a low FF and solar cell efficiency towards trap-free linear photovoltaic I- V. Space-charge-limited-current manifested Ohmic I- V diode behavior with enhanced conductance in graphene by injecting homogeneous ionic liquid; confirming the significant reduction of trap charge density. This was further congruent with the disappearance of the nonlinear kink in photodiodes with a high FF and nearly ideal diodes. The solar cell efficiency obtained with our strategy is around 13.6% and suggests possibilities to reach the theoretical limit of 19% by tailoring parameters such as conductance of graphene, carrier density of Si, and oxidation of the interfaces.

Mitotane-induced dyspnoea: an unusual side effect.

Mitotane is a cytostatic antineoplastic agent that is used in the treatment of adrenocortical carcinoma and Cushing's syndrome. The commonly reported side effects associated with mitotane are anorexia, nausea, vomiting, diarrhoea, decreased memory, rash, gynaecomastia, arthralgias and leucopenia. We present a case of a 68-year-old female who developed gradual dyspnoea concurrent with the use of mitotane for the treatment of adrenocortical carcinoma. To the best of our knowledge and literate review, this is the first reported case of dyspnoea associated with the use of this medication. The purpose of this case report is to raise awareness about this uncommon adverse effect of mitotane that may have gone unrecognised on postmarketing surveillance because of under-reporting, lack of case follow-up or other comorbidities masking shortness of breath.

A High-On/Off-Ratio Floating-Gate Memristor Array on a Flexible Substrate via CVD-Grown Large-Area 2D Layer Stacking.

Memristors such as phase-change memory and resistive memory have been proposed to emulate the synaptic activities in neuromorphic systems. However, the low reliability of these types of memories is their biggest challenge for commercialization. Here, a highly reliable memristor array using floating-gate memory operated by two terminals (source and drain) using van der Waals layered materials is demonstrated. Centimeter-scale samples (1.5 cm × 1.5 cm) of MoS2 as a channel and graphene as a trap layer grown by chemical vapor deposition (CVD) are used for array fabrication with Al2 O3 as the tunneling barrier. With regard to the memory characteristics, 93% of the devices exhibit an on/off ratio of over 103 with an average ratio of 104 . The high on/off ratio and reliable endurance in the devices allow stable 6-level memory applications. The devices also exhibit excellent memory durability over 8000 cycles with a negligible shift in the threshold voltage and on-current, which is a significant improvement over other types of memristors. In addition, the devices can be strained up to 1% by fabricating on a flexible substrate. This demonstration opens a practical route for next-generation electronics with CVD-grown van der Waals layered materials.

Proteomic Analysis of Secreted Proteins from Cell Microenvironment.

Cell microenvironment consists of various types of cells which communicate with each other by vast number of secreted proteins. An unbiased profiling of these secreted proteins on a global scale is often critical for understanding the intercellular signaling in an autocrine or paracrine manner. Mass spectrometry-based proteomics has become one of the most popular technology for characterization of the secreted proteins. In this chapter, we discuss the standard workflow for secreted proteins characterization, including harvesting secreted proteins from conditioned media, digesting the obtained proteins, liquid chromatography-mass spectrometry analysis, and downstream data analysis.

Charge Transport in MoS2/WSe2 van der Waals Heterostructure with Tunable Inversion Layer.

Despite numerous studies on two-dimensional van der Waals heterostructures, a full understanding of the charge transport and photoinduced current mechanisms in these structures, in particular, associated with charge depletion/inversion layers at the interface remains elusive. Here, we investigate transport properties of a prototype multilayer MoS2/WSe2 heterojunction via a tunable charge inversion/depletion layer. A charge inversion layer was constructed at the surface of WSe2 due to its relatively low doping concentration compared to that of MoS2, which can be tuned by the back-gate bias. The depletion region was limited within a few nanometers in the MoS2 side, while charges are fully depleted on the whole WSe2 side, which are determined by Raman spectroscopy and transport measurements. Charge transport through the heterojunction was influenced by the presence of the inversion layer and involves two regimes of tunneling and recombination. Furthermore, photocurrent measurements clearly revealed recombination and space-charge-limited behaviors, similar to those of the heterostructures built from organic semiconductors. This contributes to research of various other types of heterostructures and can be further applied for electronic and optoelectronic devices.