m6A mRNA demethylase FTO regulates melanoma tumorigenicity and response to anti-PD-1 blockade

Melanoma is one of the most deadly and therapy-resistant cancers. Here we show that N6-methyladenosine (m6A) mRNA demethylation by fat mass and obesity-associated protein (FTO) increases melanoma growth and decreases response to anti-PD-1 blockade immunotherapy. FTO level is increased in human melanoma and enhances melanoma tumorigenesis in mice. FTO is induced by metabolic starvation stress through the autophagy and NF-κB pathway. Knockdown of FTO increases m6A methylation in the critical protumorigenic melanoma cell-intrinsic genes including PD-1 (PDCD1), CXCR4, and SOX10, leading to increased RNA decay through the m6A reader YTHDF2. Knockdown of FTO sensitizes melanoma cells to interferon gamma (IFNγ) and sensitizes melanoma to anti-PD-1 treatment in mice, depending on adaptive immunity. Our findings demonstrate a crucial role of FTO as an m6A demethylase in promoting melanoma tumorigenesis and anti-PD-1 resistance, and suggest that the combination of FTO inhibition with anti-PD-1 blockade may reduce the resistance to immunotherapy in melanoma. © 2019, The Author(s)

Case report: Unusual cause of refractory hypoxemia after pacemaker lead extraction

A 59-year-old woman with a history of a pacemaker implanted for III-degree atrioventricular block was admitted due to pocket infection. The atrial and ventricular leads were removed via the right femoral vein using a needle's eye snare. Hypoxemia was observed immediately after the removal of the lead. It was refractory to oxygen therapy. The pulse oxygen saturation (SpO2) showed 89% in the supine position and 77% in the upright position. However, the CTPA and pulmonary perfusion SPECT/CT imaging did not reveal any signs of pulmonary embolism. Pulmonary function tests and chest CT showed normal results. Transthoracic contrast echocardiography revealed a patent foramen ovale (PFO) and a right-to-left intracardiac shunt, no significant tricuspid regurgitation, without any signs of elevated right heart pressure or pulmonary hypertension. Hypoxemia was considered to be associated with the right-to-left shunt through PFO. The condition was relieved by percutaneous closure of the PFO. Refractory hypoxemia resulting from an intracardiac right-to-left shunt following pacemaker lead extraction is a rare but serious complication. Transthoracic contrast echocardiography helps in diagnosis. If the right-to-left intracardiac shunt through PFO persists irreversibly and the associated hypoxemic symptoms are significant, closure of the PFO is necessary. Transesophageal echocardiography also revealed the presence of a left-to-right shunt through PFO during cardiac systole. The closure of the PFO is also necessary to avoid long-term complications, such as chronic pulmonary hypertension and right heart failure

Reliability of Microelectromechanical Systems Devices

Microelectromechanical systems (MEMS) reliability issues, apart from traditional failure mechanisms like fatigue, wear, creep, and contamination, often involve many other specific mechanisms which do not damage the system’s function but may degrade the performance of MEMS devices. This chapter focuses on the underlying mechanisms of specific reliability issues, storage long-term drift and thermal drift. The comb finger capacitive micro-accelerometers are selected as the case for this study. The material viscoelasticity of packaging adhesive and thermal effects induced by structure layout are considered so as to explain the physical phenomenon of output change over time and temperature. Each section showcases the corresponding experiments and analysis of reliability

Gate-tunable negative differential conductance in hybrid semiconductor-superconductor devices

Negative differential conductance (NDC) manifests as a significant characteristic of various underlying physics and transport processes in hybrid superconducting devices. In this work, we report the observation of gate-tunable NDC outside the superconducting energy gap on two types of hybrid semiconductor-superconductor devices, i.e., normal metal-superconducting nanowire-normal metal and normal metal-superconducting nanowire-superconductor devices. Specifically, we study the dependence of the NDCs on back-gate voltage and magnetic field. When the back-gate voltage decreases, these NDCs weaken and evolve into positive differential conductance dips; and meanwhile they move away from the superconducting gap towards high bias voltage, and disappear eventually. In addition, with the increase of magnetic field, the NDCs/dips follow the evolution of the superconducting gap, and disappear when the gap closes. We interpret these observations and reach a good agreement by combining the Blonder-Tinkham-Klapwijk (BTK) model and the critical supercurrent effect in the nanowire, which we call the BTK-supercurrent model. Our results provide an in-depth understanding of the tunneling transport in hybrid semiconductor-superconductor devices.Comment: 15+6 pages, 4+6 figure

Soliton, kink and antikink solutions of a 2-component of the Degasperis-Procesi equation

In this paper, we employ the bifurcation theory of planar dynamical systems to investigate the traveling wave solutions of a 2-component of the Degasperis-Procesi equation. The expressions for smooth soliton, kink and antikink solutions are obtained.Comment: 16 pages, 18 figure

New horizons of regulatory RNA

Genetic information flows from DNA to protein through RNA in the central dogma. Different RNA species are known to accomplish essential tasks of protein encoding (mRNAs), amino acid loading (tRNAs), and translation machinery assembly (rRNAs). However, on top of these well-known roles, RNAs are central to various cellular regulatory pathways. Here we summarize newly emerging regulatory functions of RNA, specifically focusing on regulations through RNA modifications, RNP granules, and chromatin-associated regulatory RNA. In addition to being an essential building block of the central dogma, RNA can be critical to the regulation of many cellular processes

Structural Designing of a MEMS Capacitive Accelerometer for Low Temperature Coefficient and High Linearity

The low temperature coefficient and high linearity of the input-output characteristics are both required for high-performance microelectromechanical systems (MEMS) capacitive accelerometers. In this work, a structural designing of a bulk MEMS capacitive accelerometer is developed for both low temperature coefficient and high linearity. Firstly, the contrary effect of the wide-narrow gaps ratio (WNGR) on the temperature coefficient of the scale factor (TCSF) and linearity error is discussed. Secondly, the ability of an improved structure that can avoid the contrary effect is illustrated. The improved structure is proposed in our previous work for reducing the temperature coefficient of bias (TCB) and TCSF. Within the improved structure, both the TCSF and linearity error decrease with increasing WNGR. Then, the precise designing of the improved structure is developed for achieving lower TCB, TCSF, and linearity error. Finally, the precise structural designing is experimentally verified