Voter conformism and inefficient policies

A reelection-seeking politician makes a policy decision that can reveal her private information on whether her political orientation and capabilities will be a good fit to future circumstances. We study how she may choose inappropriate policies to hide her information, even in the absence of specific conflicts of interests, and how voters’ conformism affects her incentives to do so. Conformism is independent from policies and from voters’ perceptions; yet we identify a ‘conformism advantage’ for the incumbent that exists only when there is also an incumbency advantage. Conformism changes the incentives of the incumbent and favors the emergence of an efficient, separating equilibrium. It may even eliminate the pooling equi-librium (that can consist in inefficient persistence). Conformism has a mixed impact on social welfare however: it improves policy choices and the information available to independent vot-ers, but fosters inefficient reelection in the face of a stronger opponent. When the incumbent is ‘altruistic’ and values social welfare even when not in power, she partly internalizes this latter effect. The impact of conformism is then non monotonous

Voter Conformism and Inefficient Policies

We study the efficiency of policies when some voters are conformists who like being on the winner's side and when policies signal information. A reelection-seeking incumbent has private and fully informative information on both her ability and the quality of her policy. Repealing a policy signals a mistake, which downgrades her perceived ability and may thus cause inefficient policy persistence. Conformism is independent from policies and from voters' perceptions, yet we identify a `conformism advantage' for the incumbent that exists only when there is also an incumbency advantage. We contrast an efficient equilibrium with an inefficient, pooling, one . Strong conformism makes pandering less likely, and may even eliminate it. Nonzero weak conformism can however deteriorate welfare and increase pandering, but paradoxically only when the incumbent is `altruistic' and values social welfare even when not in power

Case report: SAF-189s is a potent inhibitor in a lorlatinib-resistant NSCLC patient with acquired compound mutations ALK L1196M and D1203N

Acquired anaplastic lymphoma kinase (ALK) mutation is the major resistant mechanism to ALK tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC) patients. At present, treatment options after acquiring secondary ALK mutations are still limited. Here, we report on a patient with metastatic ALK-rearranged NSCLC who was sequentially treated with ALK TKIs, from crizotinib to lorlatinib, and developed rare acquired compound ALK mutations (L1196M and D1203N) that confer resistance to lorlatinib. Moreover, our report describes the clinical response of an NSCLC patient with these compound mutations to multiple anti-tumor therapies. Among them, the patient was treated with SAF-189s 120 mg daily and had a stable disease lasting 3 months. Chemotherapy (pemetrexed-carboplatin) combined with bevacizumab was then administered. She achieved a partial response, which was maintained for 7 months as the best response. Since both SAF-189s and chemotherapy have shown a clear antitumor effect, they may be viable therapeutic options for these patients. Thus, our study can provide some reference in the treatment of NSCLC patients with ALK L1196M/D1203N compound mutations

SpikingJelly: An open-source machine learning infrastructure platform for spike-based intelligence

Spiking neural networks (SNNs) aim to realize brain-inspired intelligence on neuromorphic chips with high energy efficiency by introducing neural dynamics and spike properties. As the emerging spiking deep learning paradigm attracts increasing interest, traditional programming frameworks cannot meet the demands of the automatic differentiation, parallel computation acceleration, and high integration of processing neuromorphic datasets and deployment. In this work, we present the SpikingJelly framework to address the aforementioned dilemma. We contribute a full-stack toolkit for pre-processing neuromorphic datasets, building deep SNNs, optimizing their parameters, and deploying SNNs on neuromorphic chips. Compared to existing methods, the training of deep SNNs can be accelerated $11\times$, and the superior extensibility and flexibility of SpikingJelly enable users to accelerate custom models at low costs through multilevel inheritance and semiautomatic code generation. SpikingJelly paves the way for synthesizing truly energy-efficient SNN-based machine intelligence systems, which will enrich the ecology of neuromorphic computing.Comment: Accepted in Science Advances (https://www.science.org/doi/10.1126/sciadv.adi1480

Simulating the effect of climate change on soil microbial community in an Abies georgei var. smithii forest

Qinghai–Tibet Plateau is considered a region vulnerable to the effects of climate change. Studying the effects of climate change on the structure and function of soil microbial communities will provide insight into the carbon cycle under climate change. However, to date, changes in the successional dynamics and stability of microbial communities under the combined effects of climate change (warming or cooling) remain unknown, which limits our ability to predict the consequences of future climate change. In this study, in situ soil columns of an Abies georgei var. smithii forest at 4,300 and 3,500 m elevation in the Sygera Mountains were incubated in pairs for 1 year using the PVC tube method to simulate climate warming and cooling, corresponding to a temperature change of ±4.7°C. Illumina HiSeq sequencing was applied to study alterations in soil bacterial and fungal communities of different soil layers. Results showed that warming did not significantly affect the fungal and bacterial diversity of the 0–10 cm soil layer, but the fungal and bacterial diversity of the 20–30 cm soil layer increased significantly after warming. Warming changed the structure of fungal and bacterial communities in all soil layers (0–10 cm, 10–20 cm, and 20–30 cm), and the effect increased with the increase of soil layers. Cooling had almost no significant effect on fungal and bacterial diversity in all soil layers. Cooling changed the structure of fungal communities in all soil layers, but it showed no significant effect on the structure of bacterial communities in all soil layers because fungi are more adapted than bacteria to environments with high soil water content (SWC) and low temperatures. Redundancy analysis (RDA) and hierarchical analysis showed that changes in soil bacterial community structure were primarily related to soil physical and chemical properties, whereas changes in soil fungal community structure primarily affected SWC and soil temperature (Soil Temp). The specialization ratio of fungi and bacteria increased with soil depth, and fungi were significantly higher than bacteria, indicating that climate change has a greater impact on microorganisms in deeper soil layers, and fungi are more sensitive to climate change. Furthermore, a warmer climate could create more ecological niches for microbial species to coexist and increase the strength of microbial interactions, whereas a cooler climate could have the opposite effect. However, we found differences in the intensity of microbial interactions in response to climate change in different soil layers. This study provides new insights to understand and predict future effects of climate change on soil microbes in alpine forest ecosystems

Investigation of the Effect of Dimple Bionic Nonsmooth Surface on Tire Antihydroplaning

Inspired by the idea that bionic nonsmooth surfaces (BNSS) reduce fluid adhesion and resistance, the effect of dimple bionic nonsmooth structure arranged in tire circumferential grooves surface on antihydroplaning performance was investigated by using Computational Fluid Dynamics (CFD). The physical model of the object (model of dimple bionic nonsmooth surface distribution, hydroplaning model) and SST k-ω turbulence model are established for numerical analysis of tire hydroplaning. By virtue of the orthogonal table L16(45), the parameters of dimple bionic nonsmooth structure design compared to the smooth structure were analyzed, and the priority level of the experimental factors as well as the best combination within the scope of the experiment was obtained. The simulation results show that dimple bionic nonsmooth structure can reduce water flow resistance by disturbing the eddy movement in boundary layers. Then, optimal type of dimple bionic nonsmooth structure is arranged on the bottom of tire circumferential grooves for hydroplaning performance analysis. The results show that the dimple bionic nonsmooth structure effectively decreases the tread hydrodynamic pressure when driving on water film and increases the tire hydroplaning velocity, thus improving tire antihydroplaning performance

Arginine Relieves the Inflammatory Response and Enhances the Casein Expression in Bovine Mammary Epithelial Cells Induced by Lipopolysaccharide

As one of functional active amino acids, L-arginine holds a key position in immunity. However, the mechanism that arginine modulates cow mammary inflammatory response in ruminant is unclear. Therefore, this study was conducted to investigate the effects of L-arginine on inflammatory response and casein expression after challenging the bovine mammary epithelial cells (BMECs) with lipopolysaccharide (LPS). The cells were divided into four groups, stimulated with or without LPS (10 g/mL) and treated with or without arginine (100 g/mL) for 12 h. The concentration of proinflammatory cytokines, inducible nitric oxide synthase (iNOS), mammalian target of rapamycin (mTOR), and Toll-like receptor 4 (TLR4) signaling pathways as well as the casein was determined. The results showed that arginine reduced the LPS-induced production like IL-1 , IL-6, TNF-, and iNOS. Though the expression of NF-B was attenuated and the mTOR signaling pathway was upregulated, arginine had no effect on TLR4 expression. In addition, our results show that the content of -casein and the total casein were enhanced after arginine was supplemented in LPS-induced BMECs. In conclusion, arginine could relieve the inflammatory reaction induced by LPS and enhance the concentration of -casein and the total casein in bovine mammary epithelial cells

Multifunctional magnetic Fe3O4 nanoparticles combined with chemotherapy and hyperthermia to overcome multidrug resistance

Yanyan Ren1,2,*, Haijun Zhang1,2,*, Baoan Chen1, Jian Cheng1, Xiaohui Cai1, Ran Liu1, Guohua Xia1, Weiwei Wu1, Shuai Wang1, Jiahua Ding1, Chong Gao1, Jun Wang1, Wen Bao1, Lei Wang1, Liang Tian1, Huihui Song1, Xuemei Wang1,2 1Department of Hematology and Oncology, Key Medical Discipline, Jiangsu Province, Zhongda Hospital, and Faculty of Oncology, Medical School, Nanjing, 2State Key Laboratory of Bioelectronics, Southeast University, Nanjing, People's Republic of China*These authors contributed equally to this workBackground: Multidrug resistance in cancer is a major obstacle for clinical therapeutics, and is the reason for 90% of treatment failures. This study investigated the efficiency of novel multifunctional Fe3O4 magnetic nanoparticles (Fe3O4-MNP) combined with chemotherapy and hyperthermia for overcoming multidrug resistance in an in vivo model of leukemia.Methods: Nude mice with tumor xenografts were randomly divided into a control group, and the treatment groups were allocated to receive daunorubicin, 5-bromotetrandrine (5-BrTet) and daunorubicin, Fe3O4-MNP, and Fe3O4-MNP coloaded with daunorubicin and 5-bromotetrandrine (Fe3O4-MNP-DNR-5-BrTet), with hyperthermia in an alternating magnetic field. We investigated tumor volume and pathology, as well as P-glycoprotein, Bcl-2, Bax, and caspase-3 protein expression to elucidate the effect of multimodal treatment on overcoming multidrug resistance.Results: Fe3O4-MNP played a role in increasing tumor temperature during hyperthermia. Tumors became significantly smaller, and apoptosis of cells was observed in both the Fe3O4-MNP and Fe3O4-MNP-DNR-5-BrTet groups, especially in the Fe3O4-MNP-DNR-5-BrTet group, while tumor volumes in the other groups had increased after treatment for 12 days. Furthermore, Fe3O4-MNP-DNR-5-BrTet with hyperthermia noticeably decreased P-glycoprotein and Bcl-2 expression, and markedly increased Bax and caspase-3 expression.Conclusion: Fe3O4-MNP-DNR-5-BrTet with hyperthermia may be a potential approach for reversal of multidrug resistance in the treatment of leukemia.Keywords: magnetic nanoparticles, daunorubicin, 5-bromotetrandrine, multidrug resistance, hyperthermi