Generative complex networks within a dynamic memristor with intrinsic variability.

Artificial neural networks (ANNs) have gained considerable momentum in the past decade. Although at first the main task of the ANN paradigm was to tune the connection weights in fixed-architecture networks, there has recently been growing interest in evolving network architectures toward the goal of creating artificial general intelligence. Lagging behind this trend, current ANN hardware struggles for a balance between flexibility and efficiency but cannot achieve both.

LiNbO dynamic memristors for reservoir computing.

Information in conventional digital computing platforms is encoded in the steady states of transistors and processed in a quasi-static way. Memristors are a class of emerging devices that naturally embody dynamics through their internal electrophyiscal processes, enabling nonconventional computing paradigms with enhanced capability and energy efficiency, such as reservoir computing. Here, we report on a dynamic memristor based on LiNbO.

Intelligent Microsystem for Sound Event Recognition in Edge Computing Using End-to-End Mesh Networking.

Wireless acoustic sensor networks (WASNs) and intelligent microsystems are crucial components of the Internet of Things (IoT) ecosystem. In various IoT applications, small, lightweight, and low-power microsystems are essential to enable autonomous edge computing and networked cooperative work. This study presents an innovative intelligent microsystem with wireless networking capabilities, sound sensing, and sound event recognition.

Self-Powered Long-Life Microsystem for Vibration Sensing and Target Recognition.

Microsystems play an important role in the Internet of Things (IoT). In many unattended IoT applications, microsystems with small size, lightweight, and long life are urgently needed to achieve covert, large-scale, and long-term distribution for target detection and recognition. This paper presents for the first time a low-power, long-life microsystem that integrates self-power supply, event wake-up, continuous vibration sensing, and target recognition.

ERK inactivation enhances stemness of NSCLC cells via promoting Slug-mediated epithelial-to-mesenchymal transition.

The mitogen-activated protein kinase pathway (MAPK) is one of the major cancer-driving pathways found in non-small cell lung cancer (NSCLC) patients. ERK inhibitors (ERKi) have been shown to be effective in NSCLC patients with MAPK pathway mutations. However, like other MAPK inhibitors, ERKi rarely confers complete and durable responses.

Pembrolizumab activity in patients with Fanconi anemia repair pathway competent and deficient tumors.

Background: Given the observed antitumor activity of immune-checkpoint-inhibitors in patients with mismatch-repair deficient (MSI-H) tumors, we hypothesized that deficiency in homologous-recombination-repair (HRR) can also influence susceptibility.

Methods: Patients with disease progression on standard of care and for whom pembrolizumab had no FDA approved indication received pembrolizumab. Patients with MSI-H tumors were excluded.

Ammonia stimulates SCAP/Insig dissociation and SREBP-1 activation to promote lipogenesis and tumour growth.

Tumorigenesis is associated with elevated glucose and glutamine consumption, but how cancer cells can sense their levels to activate lipid synthesis is unknown. Here, we reveal that ammonia, released from glutamine, promotes lipogenesis via activation of sterol regulatory element-binding proteins (SREBPs), endoplasmic reticulum-bound transcription factors that play a central role in lipid metabolism. Ammonia activates the dissociation of glucose-regulated, N-glycosylated SREBP-cleavage-activating protein (SCAP) from insulin-inducible gene protein (Insig), an endoplasmic reticulum-retention protein, leading to SREBP translocation and lipogenic gene expression.

A phase 1 and pharmacodynamic study of chronically-dosed, single-agent veliparib (ABT-888) in patients with BRCA1- or BRCA2-mutated cancer or platinum-refractory ovarian or triple-negative breast cancer.

Purpose: BRCA1 or BRCA2 mutated cancers (BRCAmut) have intrinsic sensitivity to PARP inhibitors due to deficiency in homologous recombination-mediated DNA repair. There are similarities between BRCAmut and BRCAwt ovarian and basal-like breast cancers. This phase I study determined the recommended phase II dose (RP2D) and preliminary efficacy of the PARP inhibitor, veliparib (ABT-888), in these patients.

Twist-angle-controlled neutral exciton annihilation in WS homostructures.

Exciton-exciton annihilation (EEA), as typical nonradiative recombination, plays an unpopular role in semiconductors. The nonradiative process significantly reduces the quantum yield of photoluminescence, which substantially inhibits the maximum efficiency of optoelectronic devices. Recently, laser irradiation, introducing defects and applying strain have become effective means to restrain EEA in two-dimensional (2D) transition metal dichalcogenides (TMDCs).

Deregulation of AKT-mTOR Signaling Contributes to Chemoradiation Resistance in Lung Squamous Cell Carcinoma.

Unlabelled: Lung squamous cell carcinoma (LUSC) accounts for one of three of non-small cell lung carcinoma (NSCLC) and 30% of LUSC patients present with locally advanced, unresectable/medically inoperable disease, who are commonly treated with definitive chemoradiation. However, disease relapse in the radiation fields occurs in one of three cases. We aim to explore the underlying molecular mechanisms of chemoradiation resistance of LUSC.

A new opportunity for the emerging tellurium semiconductor: making resistive switching devices.

The development of the resistive switching cross-point array as the next-generation platform for high-density storage, in-memory computing and neuromorphic computing heavily relies on the improvement of the two component devices, volatile selector and nonvolatile memory, which have distinct operating current requirements. The perennial current-volatility dilemma that has been widely faced in various device implementations remains a major bottleneck. Here, we show that the device based on electrochemically active, low-thermal conductivity and low-melting temperature semiconducting tellurium filament can solve this dilemma, being able to function as either selector or memory in respective desired current ranges.

MiRNA-200C expression in Fanconi anemia pathway functionally deficient lung cancers.

The Fanconi Anemia (FA) pathway is essential for human cells to maintain genomic integrity following DNA damage. This pathway is involved in repairing damaged DNA through homologous recombination. Cancers with a defective FA pathway are expected to be more sensitive to cross-link based therapy or PARP inhibitors.

Computational identification of biomarker genes for lung cancer considering treatment and non-treatment studies.

Background: Lung cancer is the number one cancer killer in the world with more than 142,670 deaths estimated in the United States alone in the year 2019. Consequently, there is an overreaching need to identify the key biomarkers for lung cancer. The aim of this study is to computationally identify biomarker genes for lung cancer that can aid in its diagnosis and treatment.

The oncogenic potential of a mutant TP53 gene explored in two spontaneous lung cancer mice models.

Background: Lung cancer is the number one cancer killer worldwide. A major drawback in the lung cancer treatment field is the lack of realistic mouse models that replicate the complexity of human malignancy and immune contexture within the tumor microenvironment. Such models are urgently needed.

Phase I Study of Veliparib on an Intermittent and Continuous Schedule in Combination with Carboplatin in Metastatic Breast Cancer: A Safety and [18F]-Fluorothymidine Positron Emission Tomography Biomarker Study.

Background: Poly(ADP-ribose) polymerase inhibitors (PARPis) are U.S. Food and Drug Administration (FDA) approved for treatment of BRCA-mutated metastatic breast cancer.

Type of TP53 mutation influences oncogenic potential and spectrum of associated K-ras mutations in lung-specific transgenic mice.

TP53 and K-ras mutations are two of the major genetic alterations in human nonsmall cell lung cancers. The association between these two genes during lung tumorigenesis is unknown. We evaluated the potential of two common Type I (273H, contact) and Type II (175H, conformational) TP53 mutations to induce lung tumors in transgenic mice, as well as K-ras status, and other driver mutations in these tumors.

Notch3-dependent β-catenin signaling mediates EGFR TKI drug persistence in EGFR mutant NSCLC.

EGFR tyrosine kinase inhibitors cause dramatic responses in EGFR-mutant lung cancer, but resistance universally develops. The involvement of β-catenin in EGFR TKI resistance has been previously reported, however, the precise mechanism by which β-catenin activation contributes to EGFR TKI resistance is not clear. Here, we show that EGFR inhibition results in the activation of β-catenin signaling in a Notch3-dependent manner, which facilitates the survival of a subset of cells that we call "adaptive persisters".

Complete Tri-Axis Magnetometer Calibration with a Gyro Auxiliary.

Magnetometers combined with inertial sensors are widely used for orientation estimation, and calibrations are necessary to achieve high accuracy. This paper presents a complete tri-axis magnetometer calibration algorithm with a gyro auxiliary. The magnetic distortions and sensor errors, including the misalignment error between the magnetometer and assembled platform, are compensated after calibration.

Rad51C-ATXN7 fusion gene expression in colorectal tumors.

Background: Fusion proteins have unique oncogenic properties and their identification can be useful either as diagnostic or therapeutic targets. Next generation sequencing data have previously shown a fusion gene formed between Rad51C and ATXN7 genes in the MCF7 breast cancer cell line. However, the existence of this fusion gene in colorectal patient tumor tissues is largely still unknown.

Veliparib Alone or in Combination with Mitomycin C in Patients with Solid Tumors With Functional Deficiency in Homologous Recombination Repair.

Background: BRCA germline mutations are being targeted for development of PARP inhibitors. BRCA genes collaborate with several others in the Fanconi Anemia (FA) pathway. We screened cancer patients' tumors for FA functional defects then aimed to establish the safety/feasibility of administering PARP inhibitors as monotherapy and combined with a DNA-breaking agent.

XPC inhibits NSCLC cell proliferation and migration by enhancing E-Cadherin expression.

Xeroderma pigmentosum complementation group C (XPC) protein is an important DNA damage recognition factor in nucleotide excision repair. Deletion of XPC is associated with early stages of human lung carcinogenesis, and reduced XPC mRNA levels predict poor patient outcome for non-small cell lung cancer (NSCLC). However, the mechanisms linking loss of XPC expression and poor prognosis in lung cancer are still unclear.

Overexpression of Rad51C splice variants in colorectal tumors.

Functional alterations in Rad51C are the cause of the Fanconi anemia complementation group O (FANCO) gene disorder. We have identified novel splice variants of Rad51C mRNA in colorectal tumors and cells. The alternatively spliced transcript variants are formed either without exon-7 (variant 1), without exon 6 and 7 (variant 2) or without exon 7 and 8 (variant 3).

Fanconi anemia repair pathway dysfunction, a potential therapeutic target in lung cancer.

The Fanconi anemia (FA) pathway is a major mechanism of homologous recombination DNA repair. The functional readout of the pathway is activation through mono-ubiquitination of FANCD2 leading to nuclear foci of repair. We have recently developed an FA triple-staining immunofluorescence based method (FATSI) to evaluate FANCD2 foci formation in formalin fixed paraffin-embedded (FFPE) tumor samples.

FANCD2 is a potential therapeutic target and biomarker in alveolar rhabdomyosarcoma harboring the PAX3-FOXO1 fusion gene.

Purpose: Alveolar rhabdomyosarcoma that harbors the PAX3-FOXO1 fusion gene (t-ARMS) is a common and lethal subtype of this childhood malignancy. Improvement in clinical outcomes in this disease is predicated upon the identification of novel therapeutic targets.

Experimental Design: Robust mouse models were used for in vivo analysis, and molecular studies were performed on xenografts treated in parallel.

NRAS isoforms differentially affect downstream pathways, cell growth, and cell transformation.

Neuroblastoma rat sarcoma (RAS) viral oncogene homolog (NRAS), a small GTPase, is one of the most thoroughly studied oncogenes that controls cell growth, differentiation, and survival by facilitating signal transduction. Here, we identify four novel naturally occurring NRAS isoforms (isoforms 2-5) in addition to the canonical isoform (isoform 1). Expression analyses performed on a panel of several different human malignancies and matching normal tissue revealed distinct isoform expression patterns.