Single Molecule Michaelis-Menten Equation beyond Quasi-Static Disorder

The classic Michaelis-Menten equation describes the catalytic activities for ensembles of enzyme molecules very well. But recent single-molecule experiment showed that the waiting time distribution and other properties of single enzyme molecule are not consistent with the prediction based on the viewpoint of ensemble. It has been contributed to the slow inner conformational changes of single enzyme in the catalytic processes. In this work we study the general dynamics of single enzyme in the presence of dynamic disorder. We find that at two limiting cases, the slow reaction and nondiffusion limits, Michaelis-Menten equation exactly holds although the waiting time distribution has a multiexponential decay behaviors in the nondiffusion limit.Particularly, the classic Michaelis-Menten equation still is an excellent approximation other than the two limits.Comment: 10 pages, 1 figur

Modifiers of Hearing Impairment in Humans and Mice

Lack of penetrance and variability of expression are common findings in nonsyndromic hearing loss with autosomal dominant mode of inheritance, but are also seen with recessive inheritance. Now we know that genotype cannot necessarily predict phenotype due to the complexity of the genome, the proteome interacting with the transcriptome, and the dynamically coupled systems that are involved. The contribution of genetic background to phenotypic diversity reflects the additive and interactive (epistasis) effects of multiple genes. Because, individual genes do not act alone but rather in concert with many other genes, it is not surprising that, modifier genes are common source of phenotypic variation in human populations. They can affect the phenotypic outcome of a given genotype by interacting in the same or in a parallel biological pathway as the disease gene. These modifier genes modulate penetrance, dominance, pleiotropy or expressivity in individuals with Mendelian traits and can also be exerted by influencing the severity, the penetrance, the age of onset and the progression of a disease. In this review, we focus on modifier genes that specifically affect hearing loss phenotypes in humans as well as those described in mice. We also include examples of digenic inheritance of deafness, because additive or interactive effects can also result from interaction between two mutant genes

Generate to Understand for Representation

In recent years, a significant number of high-quality pretrained models have emerged, greatly impacting Natural Language Understanding (NLU), Natural Language Generation (NLG), and Text Representation tasks. Traditionally, these models are pretrained on custom domain corpora and finetuned for specific tasks, resulting in high costs related to GPU usage and labor. Unfortunately, recent trends in language modeling have shifted towards enhancing performance through scaling, further exacerbating the associated costs. Introducing GUR: a pretraining framework that combines language modeling and contrastive learning objectives in a single training step. We select similar text pairs based on their Longest Common Substring (LCS) from raw unlabeled documents and train the model using masked language modeling and unsupervised contrastive learning. The resulting model, GUR, achieves impressive results without any labeled training data, outperforming all other pretrained baselines as a retriever at the recall benchmark in a zero-shot setting. Additionally, GUR maintains its language modeling ability, as demonstrated in our ablation experiment. Our code is available at \url{https://github.com/laohur/GUR}

Time To Live: Temporal Management of Large-Scale RFID Applications

In coming years, there will be billions of RFID tags living in the world tagging almost everything for tracking and identification purposes. This phenomenon will impose a new challenge not only to the network capacity but also to the scalability of event processing of RFID applications. Since most RFID applications are time sensitive, we propose a notion of Time To Live (TTL), representing the period of time that an RFID event can legally live in an RFID data management system, to manage various temporal event patterns. TTL is critical in the "Internet of Things" for handling a tremendous amount of partial event-tracking results. Also, TTL can be used to provide prompt responses to time-critical events so that the RFID data streams can be handled timely. We divide TTL into four categories according to the general event-handling patterns. Moreover, to extract event sequence from an unordered event stream correctly and handle TTL constrained event sequence effectively, we design a new data structure, namely Double Level Sequence Instance List (DLSIList), to record intermediate stages of event sequences. On the basis of this, an RFID data management system, namely Temporal Management System over RFID data streams (TMS-RFID), has been developed. This system can be constructed as a stand-alone middleware component to manage temporal event patterns. We demonstrate the effectiveness of TMS-RFID on extracting complex temporal event patterns through a detailed performance study using a range of high-speed data streams and various queries. The results show that TMS-RFID has a very high throughout, namely 170,000 - 870,000 events per second for different highly complex continuous queries. Moreover, the experiments also show that the main structure to record the intermediate stages in TMS-RFID does not increase exponentially with the number of events. These illustrate that TMS-RFID not only has a high processing speed, but also has a good scalability

Clinical observation of treatment of fungal corneal ulcer with application of iodine tincture and fluconazole

AIM: To explore the effect of 30g/L iodine rubbed and debridement of wound together with 2g/L fluconazole in the treatment of fungal corneal ulcers. <p>METHODS: Fifty fungal keratitis cases(50 eyes)diagnosed by corneal smear examination were cleaned locally, iodine blanch. All patients were given 2g/L fluconazole for systemic treatment, treated eye with 2g/L fluconazole eye-drops and loxacin eye-drops, and 30g/L atropine eye ointment dilate the pupils.<p>RESULTS:Fifty cases(50 eyes)were selected, of which, 40 cases were healed, 8 cases were improved and 2 cases were aggravated with operation being given.<p>CONCLUSION:After early and timely diagnosis of fungal keratitis, local debridement, 30g/L iodine rubbed the wound and joint with systemic and local treatment of fluconazole can achieve good effect

Unknown Sniffer for Object Detection: Don't Turn a Blind Eye to Unknown Objects

The recently proposed open-world object and open-set detection achieve a breakthrough in finding never-seen-before objects and distinguishing them from class-known ones. However, their studies on knowledge transfer from known classes to unknown ones need to be deeper, leading to the scanty capability for detecting unknowns hidden in the background. In this paper, we propose the unknown sniffer (UnSniffer) to find both unknown and known objects. Firstly, the generalized object confidence (GOC) score is introduced, which only uses class-known samples for supervision and avoids improper suppression of unknowns in the background. Significantly, such confidence score learned from class-known objects can be generalized to unknown ones. Additionally, we propose a negative energy suppression loss to further limit the non-object samples in the background. Next, the best box of each unknown is hard to obtain during inference due to lacking their semantic information in training. To solve this issue, we introduce a graph-based determination scheme to replace hand-designed non-maximum suppression (NMS) post-processing. Finally, we present the Unknown Object Detection Benchmark, the first publicly benchmark that encompasses precision evaluation for unknown object detection to our knowledge. Experiments show that our method is far better than the existing state-of-the-art methods. Code is available at: https://github.com/Went-Liang/UnSniffer.Comment: CVPR 2023 camera-read

The protective effect of resveratrol on human lens epithelial cells against ultraviolet-induced apoptosis

AIM: To investigate the protective effect of resveratrol on human lens epithelial cells against ultraviolet-induced apoptosis. METHODS:Subcultured human lens epithelial cell line, ultraviolet induced cell apoptosis, 20μmol/L resveratrol pretreated cell, the indicators change was observed: rate of apoptosis was detected by flow cytometry and apoptosis-related factors of caspses-3 and caspase-9 were detected by colorimetric detection, ultrastructure changes were observed under transmission electron microscope. RESULTS: Flow cytometry instrument testing found that resveratrol can suppress the apoptosis induced by ultraviolet irradiation, caspses-3 and caspase-9 content in positive control group were significantly higher than that of the negative control group at the same time period, the difference was statistically significant(P<0.05); caspses-3 and caspase-9 content in experimental group were lower than that in the positive control group at the same time, the difference was statistically significant(P<0.05). In addition, the damage of human lens epithelial cells was alleviated with the incubation time of resveratrol elongated. CONCLUSION:Resveratrol may inhibit ultraviolet-induced apoptosis of human lens epithelial cells, it has preventive function against radioactive cataract, and it can provide reliable evidence for pursuing effective medicine to prevent and treat cataract

3-Benzyl­amino-2-cyano-N-[N-(2-fluoro­phenyl)­carbamo­yl]-3-(methyl­sulfanyl)acryl­amide

In the crystal structure of the title compound, C19H17FN4O2S, mol­ecules are linked via pairs of N—H⋯N inter­actions, forming centrosymmetric dimers. Two intra­molecular N—H⋯O hydrogen bonds stabilize the mol­ecular conformation