Cisplatin Resistance in Ovarian Cancer: Classical Outlook and Newer Perspectives

Ovarian cancer is one of the most common gynecological cancers. Recently, there is increase in incidence of ovarian cancer not only India but also worldwide. Ovarian cancer patients exhibit nonspecific symptoms during early course of disease. As a consequence, 70% of these patients are diagnosed in advanced stages. Ovarian cancer treatment includes cytoreductive surgery followed by platinum-based chemotherapy. However, these patients develop fatal recurrence due to development of platinum resistance. Cisplatin, (platinum analog) resistance is multifactorial and complex. Earlier, resistance was mainly attributed to conventional molecular mechanisms like decreased intracellular accumulation of cisplatin, enhanced DNA repair and increased cisplatin detoxification. Nevertheless, emergence of knowledge of tumor biology have lead to discovery of other contributing mechanisms. These tumor microenvironment related factors include physical blockade, hypoxia, cancer stem cells, cancer associated fibroblasts and many others. Understanding these mechanisms of cisplatin resistance is crucial for development of novel strategy to combat the same. Hence, this review summarizes all the mechanisms of resistance of cisplatin in ovarian cancer.

Multi-Level Control of Resistive RAM (RRAM) Using a Write Termination to Achieve 4 Bits/Cell in High Resistance State

RRAM density enhancement is essential not only to gain market share in the highly competitive emerging memory sector but also to enable future high-capacity and power-efficient brain-inspired systems, beyond the capabilities of today’s hardware. In this paper, a novel design scheme is proposed to realize reliable and uniform multi-level cell (MLC) RRAM operation without the need of any read verification. RRAM quad-level cell (QLC) capability with 4 bits/cell is demonstrated for the first time. QLC is implemented based on a strict control of the cell programming current of 1T-1R HfO2-based RRAM cells. From a design standpoint, a self-adaptive write termination circuit is proposed to control the RESET operation and provide an accurate tuning of the analog resistance value of each cell of a memory array. The different resistance levels are obtained by varying the compliance current in the RESET direction. Impact of variability on resistance margins is simulated and analyzed quantitatively at the circuit level to guarantee the robustness of the proposed MLC scheme. The minimal resistance margin reported between two consecutive states is 2.1 kΩ along with an average energy consumption and latency of 25 pJ/cell and 1.65 μs, respectively.

Memristive Switching Characteristics in Biomaterial Chitosan-Based Solid Polymer Electrolyte for Artificial Synapse

This study evaluated the memristive switching characteristics of a biomaterial solid polymer electrolyte (SPE) chitosan-based memristor and confirmed its artificial synaptic behavior with analog switching. Despite the potential advantages of organic memristors for high-end electronics, the unstable multilevel states and poor reliability of organic devices must be overcome. The fabricated Ti/SPE-chitosan/Pt-structured memristor has stable bipolar resistive switching (BRS) behavior due to a cation-based electrochemical reaction between a polymeric electrolyte and metal ions and exhibits excellent endurance in 5 × 102 DC cycles. In addition, we achieved multilevel per cell (MLC) BRS I-V characteristics by adjusting the set compliance current (Icc) for analog switching. The multilevel states demonstrated uniform resistance distributions and nonvolatile retention characteristics over 104 s. These stable MLC properties are explained by the laterally intensified conductive filaments in SPE-chitosan, based on the linear relationship between operating voltage margin (ΔVswitching) and Icc. In addition, the multilevel resistance dependence on Icc suggests the capability of continuous analog resistance switching. Chitosan-based SPE artificial synapses ensure the emulation of short- and long-term plasticity of biological synapses, including excitatory postsynaptic current, inhibitory postsynaptic current, paired-pulse facilitation, and paired-pulse depression. Furthermore, the gradual conductance modulations upon repeated stimulation by 104 electric pulses were evaluated in high stability.

Carrier localization in perovskite nickelates from oxygen vacancies

Point defects, such as oxygen vacancies, control the physical properties of complex oxides, relevant in active areas of research from superconductivity to resistive memory to catalysis. In most oxide semiconductors, electrons that are associated with oxygen vacancies occupy the conduction band, leading to an increase in the electrical conductivity. Here we demonstrate, in contrast, that in the correlated-electron perovskite rare-earth nickelates, RNiO3 (R is a rare-earth element such as Sm or Nd), electrons associated with oxygen vacancies strongly localize, leading to a dramatic decrease in the electrical conductivity by several orders of magnitude. This unusual behavior is found to stem from the combination of crystal field splitting and filling-controlled Mott–Hubbard electron–electron correlations in the Ni 3d orbitals. Furthermore, we show the distribution of oxygen vacancies in NdNiO3 can be controlled via an electric field, leading to analog resistance switching behavior. This study demonstrates the potential of nickelates as testbeds to better understand emergent physics in oxide heterostructures as well as candidate systems in the emerging fields of artificial intelligence.