Studies of the effects of pancreatic beta cell antioxidant transgenes on experimental models of diabetes.

Pancreatic beta cells are extremely vulnerable to the destruction of Reactive Oxygen Species (ROS). In both type 1 and type 2 diabetes ROS are involved in the loss of U+000DF-cells. We hypothesized that the deficiency in ROS detoxifying system of U+000DF-cells resulted in U+000DF-cell vulnerability and enhanced ROS protection would protect from diabetes. To test this hypothesis, transgenic mice with overexpression of U+000DF-cell antioxidant protein metallothionein (MT), manganese superoxide dismutase (MnSOD) and catalase were produced on an FVB background. Initial studies demonstrated that these transgenes did not affect U+000DF-cell normal function and morphology. But those transgenes significantly protected pancreatic islets or mice from ROS induced U+000DF-cell damage and diabetes. The transgenic islet cells had high efficacy in scavenging most forms of ROS, and generally survived and functioned better than control cells when exposed to various ROS insults. The transgenic mice were highly resistant to STZ induced diabetes. However, inconsistent with studies on insulin secreting tumor cell lines in which antioxidants were shown to be protective, all these antioxidant transgenes failed to prevent cytokine toxicities in the cultured islets. We employed a speed congenic strategy to produce two lines of congenic NOD mice containing U+000DF-cell specific expression of MT and catalase. NOD mice spontaneously develop type 1 diabetes, and cyclophosphamide (CYP) injection accelerates NOD diabetes onset. But very unexpectedly, either transgene MT or catalase dramatically hastened diabetes onset in NOD mice. In addition, no antioxidant transgene was found to be able to protect from type 2 diabetes in an Agouti obese diabetic model. But the MT transgene also unexpectedly caused severe diabetes on a normal C57BL/KsJ mouse which can be made to develop type 2 diabetes by producing obesity and insulin resistance. The data from this project indicate that the overexpression of antioxidant transgenes protects U+000DF-cells from ROS damaging stimuli but sensitizes U+000DF-cells to some other insults. Some of these data are at odds with the long term favored concept that antioxidant treatment is always beneficial for treatment of diabetes. These results imply that oxidative stress may not only be harmful, but it may also be necessary to activate self-protective mechanisms in the U+000DF-cells

Deep Reinforcement Learning for Flipper Control of Tracked Robots

The autonomous control of flippers plays an important role in enhancing the intelligent operation of tracked robots within complex environments. While existing methods mainly rely on hand-crafted control models, in this paper, we introduce a novel approach that leverages deep reinforcement learning (DRL) techniques for autonomous flipper control in complex terrains. Specifically, we propose a new DRL network named AT-D3QN, which ensures safe and smooth flipper control for tracked robots. It comprises two modules, a feature extraction and fusion module for extracting and integrating robot and environment state features, and a deep Q-Learning control generation module for incorporating expert knowledge to obtain a smooth and efficient control strategy. To train the network, a novel reward function is proposed, considering both learning efficiency and passing smoothness. A simulation environment is constructed using the Pymunk physics engine for training. We then directly apply the trained model to a more realistic Gazebo simulation for quantitative analysis. The consistently high performance of the proposed approach validates its superiority over manual teleoperation

Probing Product Description Generation via Posterior Distillation

In product description generation (PDG), the user-cared aspect is critical for the recommendation system, which can not only improve user's experiences but also obtain more clicks. High-quality customer reviews can be considered as an ideal source to mine user-cared aspects. However, in reality, a large number of new products (known as long-tailed commodities) cannot gather sufficient amount of customer reviews, which brings a big challenge in the product description generation task. Existing works tend to generate the product description solely based on item information, i.e., product attributes or title words, which leads to tedious contents and cannot attract customers effectively. To tackle this problem, we propose an adaptive posterior network based on Transformer architecture that can utilize user-cared information from customer reviews. Specifically, we first extend the self-attentive Transformer encoder to encode product titles and attributes. Then, we apply an adaptive posterior distillation module to utilize useful review information, which integrates user-cared aspects to the generation process. Finally, we apply a Transformer-based decoding phase with copy mechanism to automatically generate the product description. Besides, we also collect a large-scare Chinese product description dataset to support our work and further research in this field. Experimental results show that our model is superior to traditional generative models in both automatic indicators and human evaluation

Case report: Desquamating dermatitis, bilateral cerebellar lesions in a late-onset methylmalonic acidemia patient

IntroductionCobalamin C (cblC) deficiency is a rare hereditary disorder affecting intracellular cobalamin metabolism, primarily caused by mutations in MMACHC. This condition is characterized by combined methylmalonic acidemia and hyperhomocysteinemia, displaying a wide range of clinical manifestations involving multiple organs. Owing to its uncommon occurrence and diverse clinical phenotypes, diagnosing cblC deficiency is challenging and often leads to delayed or missed diagnoses.Case descriptionIn this report, we present a case of late-onset cblC deficiency with brown desquamating dermatitis on the buttocks. Magnetic resonance imaging (MRI) of the brain revealed bilateral cerebellar abnormalities. The suspicion of an inherited metabolic disorder was raised by abnormal serum amino acid and acylcarnitine levels, along with increased urine methylmalonic acid and serum homocysteine levels. Whole-exome sequencing helped identify a homozygous variant (c.482G>A) in MMACHC, confirming the diagnosis of cblC deficiency. However, despite receiving treatment with hydroxocobalamin and betaine, the patient did not experience clinical improvement, which may be attributed to the delayed diagnosis as indicated by the declining homocysteine and methylmalonic acid levels.ConclusionCollectively, we emphasize the significance of recognizing the skin lesions and observing serial MRI changes in patients with cblC deficiency. Our case underscores the importance of early diagnosis and timely therapeutic intervention for this severe yet frequently manageable condition

The Chinese automobile industry’s research and development capability and innovative performance

The Report of China’s Automobile Industry Development 2016 points out that China’s automobile industry faces increasingly fierce competition from global peers, and domestic automobile manufacturers shall continuously improve independent innovation and industry innovative performance. Automobile manufacturers’ participation in distributed innovation and their research & development (R&D) capability play a key role in the growth of innovative performances of China’s automobile industry. With development of China’s automobile industry as the background, this study presents a theoretical framework of correlation of distributed innovation embedment, R&D capability and innovative performances of China’s automobile industry from the microscopic perspective of single industry. Several hypotheses were proposed and then verified by empirical method. Specifically, 117 effective questionnaires were collected through non-probability sampling and analyzed quantitatively, followed by hypothesis test. The results clarify the working principles of the three dimensions of distributed innovation embedment influencing innovative performances of China’s automobile industry and improvement of R&D capability of enterprises by distributed innovation. This study provides references to improvements of innovative performances of China’s automobile industry