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Van der Waals (vdW) tunnel junctions are attractive due to their atomically sharp interface, gate tunablity, and robustness against lattice mismatch between the successive layers. However, the negative differential resistance (NDR) demonstrated in this class of tunnel diodes often exhibits noisy behaviour with low peak current density, and lacks robustness and repeatability, limiting their practical circuit applications. Here we propose a strategy of using a 1L-WS$_2$ as an optimum tunnel barrier sandwiched in a broken gap tunnel junction of highly doped black phosphorus (BP) and SnSe$_2$. We achieve high yield tunnel diodes exhibiting highly repeatable, ultra-clean, and gate tunable NDR characteristics with a signature of intrinsic oscillation, and a large peak-to-valley current ratio (PVCR) of 3.6 at 300 K (4.6 at 7 K), making them suitable for practical applications. We show that the thermodynamic stability of the vdW tunnel diode circuit can be tuned from astability to bistability by altering the constraint through choosing a voltage or a current bias, respectively. In the astable mode under voltage bias, we demonstrate a compact, voltage controlled oscillator without the need for an external tank circuit. In the bistable mode under current bias, we demonstrate a highly scalable, single element one-bit memory cell that is promising for dense random access memory applications in memory intensive computation architectures.

Introduction: Pyruvate(Pyr) metabolism is a keystone in cancer metabolism, as well as normal cells, and has two major metabolic fluxes; Glycolysis and Oxidative Phosphorylation (OXPHOS). Especially in cancer cells, increased Pyr metabolism meets the demand of higher energy consumption during rapid cell growing state. Therefore, monitoring tumor Pyr metabolic flux in vitro and in vivo should be necessary to develop a therapeutic strategy using small molecules which can inhibit the fluxes.Aim: We performed in vitro metabolic analysis on pancreatic cancer cells (MiaPaCa2) and applied a novel in vivo imaging technology “hyperpolarized 13C-pyruvate magnetic resonance spectroscopic imaging (HP-MRSI)” to dynamic monitoring of the impact of Glycolysis and OXPHOS inhibitors on the MiaPaCa2 xenografts. Methods: We used a novel LDH inhibitor “NCI-006” for Glycolysis inhibition and Mitochondrial Complex 1(MC1) Inhibitor "Metformin(Met)", which is already clinically available, and “IACS-010759(IACS)” for OXPHOS inhibition, in vitro and in vivo. Extracellular flux (EXF) analysis and HP-MRSI were performed before and after administration of each or both to assess inhibitor impact on metabolic flux in vitro and in vivo, respectively. Results: HP-MRSI confirmed that LDH activity in the tumor was suppressed by NCI-006 (83.3±4.4% decrease) and accelerated by Met (69.9±6.6% increase) and IACS (88.6±25.1% increase). We confirmed these in vivo observations are fully consistent with the effect of those inhibitors in vitro on the energy profile of MiaPaCa2, and also the close correlation of these data with the results of the ex vivo LDH activity assay, suggesting HP-MRSI can reliably monitor in vivo on target effects of the inhibitors without need for tissue sampling. In addition, combined treatment with the NCI-006 and MC1 inhibitor significantly suppressed in vitro cell growth and tumor growth in an efficacy study of MiaPaCa2 xenografts, compared to each single administration. Apoptosis assay showed the combined treatment induced apoptosis in MIA Paca2 cells. Conclusion: Using EXF analyzer and HP-MRSI revealed that Glycolysis inhibition redirects tumor Pyr toward OXPHOS and also MC1 inhibition redirects tumor Pyr toward Glycolysis. Combination therapy suppresses metabolic plasticity, causing metabolic quiescence in vitro and tumor growth inhibition in vivo. HP-MRSI is thought to be useful for pancreatic cancer patients to establish the current treatment model because of no need to obtain clinical samples, such as patients-derived cancer cells or spheroid from the patients. The current proof of concept can be of great value in developing new therapeutic strategies using metabolic inhibitors to treat cancers. Citation Format: Nobu Oshima, Yuki Aisu, Shigeo Hisamori, Shigeru Tsunoda, Hiroki Hashida, Kenji Uryuhara, Hiroyuki Kobayashi, Masato Kondo, koji Kitamura, Satoshi Kaihara, Kazutaka Obama, Krishna Murali, Len Neckers. Comprehensive monitoring of pyruvate metabolism in cancer cells and tumors reveals vulnerability to metabolic inhibition therapy with small molecules [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6222.

With the rapid advancement in multiplex tissue staining, computer hardware, and machine learning, computationally-based tools are becoming indispensable for the evaluation of digital histopathology. Historically, standard histochemical staining methods such as hematoxylin and eosin, periodic acid- Schiff, and trichrome have been the gold standard for microscopic tissue evaluation by pathologists, and therefore brightfield microscopy images derived from such stains are primarily used for developing computational pathology tools. However, these histochemical stains are nonspecific in terms of highlighting structures and cell types. In contrast, immunohistochemical stains use antibodies to specifically detect and quantify proteins, which can be used to specifically highlight structures and cell types of interest. Traditionally, such immunofluorescence-based methods are only able to simultaneously stain a limited number of target proteins/antigens, typically up to three channels. Fluorescence-based multiplex immunohistochemistry (mIHC) is a new technology that enables simultaneous localization and quantification of numerous proteins/antigens, allowing for the possibility to detect a wide range of histologic structures and cell types within tissue. However, this method is limited by cost, specialized equipment, technical expertise, and time. In this study, we implemented a deep learning-based pipeline to synthetically generate in silico mIHC images from brightfield images of tissue slides-stained with routinely used histochemical stains, in particular PAS. Our tool was trained using fluorescence-based mIHC images as the ground-truth. The proposed pipeline offers high contrast detection of structures in brightfield imaged tissue sections stained with standard histochemical stains. We demonstrate the performance of our pipeline by computationally detecting multiple compartments in kidney biopsies, including cell nuclei, collagen/fibrosis, distal tubules, proximal tubules, endothelial cells, and leukocytes, from PAS-stained tissue sections. Our work can be extended for other histologic structures and tissue types and can be used as a basis for future automated annotation of histologic structures and cell types without the added cost of actually generating mIHC slides.

PurposeWith the initiation of human hyperpolarized 13 C (HP-13 C) trials at multiple sites and the development of improved acquisition methods, there is an imminent need to maximally extract diagnostic information to facilitate clinical interpretation. This study aims to improve human HP-13 C MR spectroscopic imaging through means of Tensor Rank truncation-Image enhancement (TRI) and optimal receiver combination (ORC).MethodsA data-driven processing framework for dynamic HP 13 C MR spectroscopic imaging (MRSI) was developed. Using patient data sets acquired with both multichannel arrays and single-element receivers from the brain, abdomen, and pelvis, we examined the theory and application of TRI, as well as 2 ORC techniques: whitened singular value decomposition (WSVD) and first-point phasing. Optimal conditions for TRI were derived based on bias-variance trade-off.ResultsTRI and ORC techniques together provided a 63-fold mean apparent signal-to-noise ratio (aSNR) gain for receiver arrays and a 31-fold gain for single-element configurations, which particularly improved quantification of the lower-SNR-[13 C]bicarbonate and [1-13 C]alanine signals that were otherwise not detectable in many cases. Substantial SNR enhancements were observed for data sets that were acquired even with suboptimal experimental conditions, including delayed (114 s) injection (8× aSNR gain solely by TRI), or from challenging anatomy or geometry, as in the case of a pediatric patient with brainstem tumor (597× using combined TRI and WSVD). Improved correlation between elevated pyruvate-to-lactate conversion, biopsy-confirmed cancer, and mp-MRI lesions demonstrated that TRI recovered quantitative diagnostic information.ConclusionOverall, this combined approach was effective across imaging targets and receiver configurations and could greatly benefit ongoing and future HP 13 C MRI research through major aSNR improvements.

van der Waals (vdW) tunnel junctions are attractive because of their atomically sharp interface, gate tunability, and robustness against lattice mismatch between the successive layers. However, the negative differential resistance (NDR) demonstrated in this class of tunnel diodes often exhibits noisy behavior with low peak current density and lacks robustness and repeatability, limiting their practical circuit applications. Here, we propose a strategy of using a 1L-WS

Generative adversarial networks (GANs) have received immense attention in the field of machine learning for their potential to learn high-dimensional and real data distribution. These methods do not rely on any assumptions about the data distribution of the input sample and can generate real-like samples from latent vector space based on unsupervised learning. In the medical field, particularly, in digital pathology expert annotation and availability of a large set of training data is costly and the study of manifestations of various diseases is based on visual examination of stained slides. In clinical practice, various staining information is required to improve the pathological diagnosis process. But when the sampled tissue to be examined is limited, the final diagnosis made by the pathologist is based on limited stain styles. These limitations can be overcome by studying the usability and reliability of generative models in the field of digital pathology. To understand the usability of the generative models, we synthesize in an unsupervised manner, high resolution renal microanatomical structures like renal glomerulus in thin tissue histology images using state-of-art architectures like Deep Convolutional Generative Adversarial Network (DCGAN) and Enhanced Super-Resolution Generative Adversarial Network (ESRGAN). Successful generation of such structures will lead to obtaining a large set of labeled data for further developing supervised algorithms for disease classification and understanding progression. Our study suggests while GAN is able to attain formalin fixed and paraffin embedded tissue image quality, GAN requires further prior knowledge as input to model intrinsic micro-anatomical details, such as capillary wall, urinary pole, nuclei placement, suggesting developing semi-supervised architectures by using these above details as prior information. Also, the generative models can be used to create an artificial effect of staining without physically tampering the histopathological slide. To demonstrate this, we use a CycleGAN network to transform Hematoxylin and eosin (H&E) stain to Periodic acid-Schiff (PAS) stain and Jones methenamine silver (JMS) stain to PAS stain. In this way GAN can be employed to translate different renal pathology stain styles when the relevant staining information is not available in the clinical settings.

In 1H monolayer transition metal dichalcogenide, the inversion symmetry is broken, while the reflection symmetry is maintained. On the contrary, in the bilayer, the inversion symmetry is restored, but the reflection symmetry is broken. As a consequence of these contrasting symmetries, here we show that bilayer WS$_2$ exhibits a quantum confined Stark effect (QCSE) that is linear with the applied out-of-plane electric field, in contrary to a quadratic one for a monolayer. The interplay between the unique layer degree of freedom in the bilayer and the field driven partial inter-conversion between intra-layer and inter-layer excitons generates a giant tunability of the exciton oscillator strength. This makes bilayer WS$_2$ a promising candidate for an atomically thin, tunable electro-absorption modulator at the exciton resonance, particularly when stacked on top of a graphene layer that provides an ultra-fast non-radiative relaxation channel. By tweaking the biasing configuration, we further show that the excitonic response can be largely tuned through electrostatic doping, by efficiently transferring the oscillator strength from neutral to charged exciton. The findings are prospective towards highly tunable, atomically thin, compact and light, on chip, reconfigurable components for next generation optoelectronics., Comment: Accepted in ACS Photonics

This article proposes a novel discrete event simulation model for predicting cyber maintenance costs under multiple scenarios. In this study, our model of the evolution of computer hosts is similar to the Susceptible-Infected-Removed (S-I-R) epidemiological model. A double or "nested birth and death" construction is used for the hosts and the vulnerabilities on the hosts. The objectives of the model are to study the benefits and drawbacks of current scanning policy and maintenance policy, evaluate cost-effective alternatives, and investigate the significance of celebrity vulnerabilities.

Graphene, owing to its zero-band-gap electronic structure, is promising as an absorption material for ultra-wideband photodetection applications. However, graphene-absorption-based detectors inherently suffer from poor responsivity because of weak absorption and fast photocarrier recombination, limiting their viability for low-intensity light detection. Here, we use a graphene/WS

1T-TaS2 is a layered material that exhibits charge density wave (CDW) -induced distinct electrical resistivity phases and has attracted a lot of attention for interesting device applications. However, such resistivity switching effects are often weak, and cannot be modulated by an external gate voltage - limiting their widespread usage. Using a back-gated 1T-TaS2/2H-MoS2 heterojunction, we show that the usual resistivity switching in TaS2 due to different phase transitions is accompanied with a surprisingly strong modulation in the Schottky barrier height (SBH) at the TaS2/MoS2 interface - providing an additional knob to control the degree of the phase-transition-driven resistivity switching by an external gate voltage. In particular, the commensurate (C) to triclinic (T) phase transition results in an increase in the SBH owing to a collapse of the Mott gap in TaS2. The change in SBH allows us to estimate an electrical Mott-gap opening of approximately 71 +/- 7 meV in the C phase of TaS2. On the other hand, the nearly commensurate (NC) to incommensurate (IC) phase transition results in a suppression in the SBH, and the heterojunction shows a gate-controlled resistivity switching ratio up to 17.3, which is approximately 14.5 times higher than that of stand-alone TaS2. The findings mark an important step forward showing a promising pathway to externally control as well as amplify the CDW-induced resistivity switching. This will boost device applications that exploit these phase transitions, such as ultra-broadband photodetection, negative differential conductance, fast oscillator and threshold switching in neuromorphic circuits.

Due to Fermi level pinning (FLP), metal-semiconductor contact interfaces result in a Schottky barrier height (SBH), which is usually difficult to tune. This makes it challenging to efficiently inject both electrons and holes using the same metal - an essential requirement for several applications, including light-emitting devices and complementary logic. Interestingly, modulating the SBH in the Schottky-Mott limit of de-pinned van der Waals (vdW) contacts becomes possible. However, accurate extraction of the SBH is essential to exploit such contacts to their full potential. In this work, we propose a simple technique to accurately estimate the SBH at the vdW contact interfaces by circumventing several ambiguities associated with SBH extraction. Using this technique on several vdW contacts, including metallic 2H-TaSe$_2$, semi-metallic graphene, and degenerately doped semiconducting SnSe$_2$, we demonstrate that vdW contacts exhibit a universal de-pinned nature. Superior ambipolar carrier injection properties of vdW contacts are demonstrated (with Au contact as a reference) in two applications, namely, (a) pulsed electroluminescence from monolayer WS$_2$ using few-layer graphene (FLG) contact, and (b) efficient carrier injection to WS$_2$ and WSe$_2$ channels in both nFET and pFET modes using 2H-TaSe$_2$ contact.

Backward diodes conduct more efficiently in the reverse bias than in the forward bias, providing superior high-frequency response, temperature stability, radiation hardness, and 1/f noise performance than a conventional diode conducting in the forward direction. Here, we demonstrate a van der Waals material-based backward diode by exploiting the giant staggered band offsets of WSe

Background: Tephrosia is a large tropical and sub-tropical genus belonging to the family Fabaceae. Tephrosia maxima is reported to be rich in phenols and flavonoid. The folklore of Andhra Pradesh use the plant for inflammatory conditions, in diabetes, as anti ulcer and anti cancer agents. Objective: The present work focuses on the o Pharmacognostical standardization on the root of the plant which will help in setting a suitable plant profile. Materials and Methods: The morphological, microscopical, proximate analysis, fluorescence analysis, preliminary chemical screenings followed by thin layer chromatographic analysis was performed. Quercetin was used as the standard in the tlc analysis. Results: A thin transverse section of the root showed the presence of mucilaginous vessels which was considered as tissue of diagnostic importance. Abundant vessels with lateral wall pits and perforation plates were seen throughout the powdered microscopy. The fluorescence analyses showed a range of fluorescent colours which help in the identification of chemical nature of constituents present. The physico chemical parameters like ash values extractive values, crude fibre content and loss on drying were conducted, the values of which will help in the detection of impurities. The thin layer chromatographic finger printings revealed the presence of quercetin or its derivatives as similar Rf values were observed. Conclusion: the results obtained in this research investigation will help in the development of a suitable monograph which will help in the proper identification and authentication of the plant from its related species.

Pressure-actuated reed valves play an important role in the compression process of a refrigerator compressor. The material properties and geometrical parameters of the valve and geometrical properties of valve port determine the flow coefficient which in turn impacts the compressor efficiency. Also, the moving mass of the valve and its stiffness governs the transient response (valve flutter) which impacts life and reliability of the valve in operation. Therefore, it is imperative to carefully design the reed valves to maximize compressor performance while meeting the above requirements. The design of reed valves involves determining the geometrical parameters (length, width and thickness) and material properties (type of steel etc.). These properties are chosen such that they correspond to the desired mass and stiffness of the valve. This work mainly focuses on determining the basic valve topology (geometrical parameters) with the desired mass and stiffness of the reed valve as design constraints. In order to obtain the optimum reed valve mass and stiffness values, an in-house system level performance simulation model is used. An analytical finite element based model has been built that searches for geometrical parameters which meets both target valve parameters and material limitations for reliability and life. This provides multiple valve designs with different geometrical parameters and gives the designer the flexibility to choose the most suitable valve design for a targeted application. Additionally, the basic valve topology will facilitate a more detailed performance analyses, viz. flow-thermal simulations and flow-structure interaction.

We investigated the antidiabetic activity of 50% ethanolic extract of roots of Ricinus communis (RCRE) along with its bioassay-guided purification. Five-hundred milligram per kilogram body weight appeared to be the effective dose as it caused the maximum lowering of the fasting blood glucose, both in normal as well as type 1 diabetic animals. The maximum hypoglycemic effect was always observed at the 8th h up to which the study has been conducted. Administration of the effective dose of RCRE to the diabetic rats for 20 days showed favorable effects not only on fasting blood glucose, but also on total lipid profile and liver and kidney functions on 10th and 20th day. RCRE was purified using silica gel column chromatography. Out of several different fractions tested, only one fraction (R-18) showed significant antihyperglycemic activity. RCRE seemed to have a high margin of safety as no mortality and no statistically significant difference in alkaline phosphatase, serum bilirubin, creatinine, serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase and total protein was observed even after the administration of the extract at a dose of 10 g/kg b.wt. Thus R. communis seems to have a promising value for the development of a potent phytomedicine for diabetes.