H

This paper studies the infinite horizon H∞ control problem for a general class of nonlinear stochastic systems with time-delay and multiplicative noise. The exponential/asymptotic mean square H∞ control design of delayed nonlinear stochastic systems is presented by solving Hamilton-Jacobi inequalities. Two numerical examples are provided to show the effectiveness of the proposed design method

RETRACTED: NEAT1 Overexpression Indicates a Poor Prognosis and Induces Chemotherapy Resistance via the miR-491-5p/SOX3 Signaling Pathway in Ovarian Cancer

BackgroundAccumulated studies have reported that dysregulated long non-coding RNAs (lncRNAs) are crucial in ovarian cancer (OC) initiation and development. However, detailed biological functions of lncRNA NEAT1 during the progression of OC remains to be uncovered.PurposeOur aim was to identify the role of NEAT1 in cisplatin resistance of ovarian cancer and the underlying mechanisms.MethodsThe expression patterns of NEAT1 in OC cell lines and tissue samples were identified by qRT-PCR. The cisplatin (DDP) sensitivity of OC cells was detected by MTT and CCK8 assay, while OC cell apoptosis and cell cycle were detected using flow cytometer assays. In addition, effects of NEAT1 on tumor growth were determined by xenograft tumor model. Luciferase reporter assay was conducted to prove the regulatory relation of miR-491-5p, NEAT1, and SOX3. Importantly, the expression of NEAT1 in exosomes from cisplatin-resistant patients was also determined by using qRT-PCR.ResultsIn this study, upregulated NEAT1 was detected in OC cell lines and tissues. Meanwhile, NEAT1 was also increased in cisplatin-resistant OC cell lines and tissues. Upregulation of NEAT1 inhibited cisplatin-induced OC cell apoptosis and promoted cell proliferation, while knockdown of NEAT1 played the opposite role. These effects were also observed in vivo. Furthermore, direct interaction was observed between NEAT1 and miR-491-5p. NEAT1 led to the upregulation of miR-491-5p-targeted SOX3 mRNA. Importantly, this study also showed upregulated NEAT1 expression in serum exosomes derived from cisplatin-resistant patients.ConclusionNEAT1 is vital in the chemoresistance of ovarian cancer through regulating miR-491-5p/SOX3 pathway, showing that NEAT1 might be a potential target for OC resistance treatment

Learning World Models with Identifiable Factorization

Extracting a stable and compact representation of the environment is crucial for efficient reinforcement learning in high-dimensional, noisy, and non-stationary environments. Different categories of information coexist in such environments -- how to effectively extract and disentangle these information remains a challenging problem. In this paper, we propose IFactor, a general framework to model four distinct categories of latent state variables that capture various aspects of information within the RL system, based on their interactions with actions and rewards. Our analysis establishes block-wise identifiability of these latent variables, which not only provides a stable and compact representation but also discloses that all reward-relevant factors are significant for policy learning. We further present a practical approach to learning the world model with identifiable blocks, ensuring the removal of redundants but retaining minimal and sufficient information for policy optimization. Experiments in synthetic worlds demonstrate that our method accurately identifies the ground-truth latent variables, substantiating our theoretical findings. Moreover, experiments in variants of the DeepMind Control Suite and RoboDesk showcase the superior performance of our approach over baselines

ASPEN: High-Throughput LoRA Fine-Tuning of Large Language Models with a Single GPU

Transformer-based large language models (LLMs) have demonstrated outstanding performance across diverse domains, particularly when fine-turned for specific domains. Recent studies suggest that the resources required for fine-tuning LLMs can be economized through parameter-efficient methods such as Low-Rank Adaptation (LoRA). While LoRA effectively reduces computational burdens and resource demands, it currently supports only a single-job fine-tuning setup. In this paper, we present ASPEN, a high-throughput framework for fine-tuning LLMs. ASPEN efficiently trains multiple jobs on a single GPU using the LoRA method, leveraging shared pre-trained model and adaptive scheduling. ASPEN is compatible with transformer-based language models like LLaMA and ChatGLM, etc. Experiments show that ASPEN saves 53% of GPU memory when training multiple LLaMA-7B models on NVIDIA A100 80GB GPU and boosts training throughput by about 17% compared to existing methods when training with various pre-trained models on different GPUs. The adaptive scheduling algorithm reduces turnaround time by 24%, end-to-end training latency by 12%, prioritizing jobs and preventing out-of-memory issues.Comment: 14 pages, 14 figure

Total contact casts versus removable offloading interventions for the treatment of diabetic foot ulcers: a systematic review and meta-analysis

ObjectiveThis study aimed to evaluate the effectiveness of total contact casts (TCCs) versus removable offloading interventions among patients with diabetic foot ulcers (DFUs).MethodsA comprehensive search was done in databases Embase, Cochrane Library, and, PubMed. The references of retrieved articles were reviewed, up until February 2023. Controlled trials comparing the effects of TCCs with removable offloading interventions (removable walking casts and footwear) in patients with DFUs were eligible for review.ResultsTwelve studies were included in the meta-analysis, involving 591 patients with DFUs. Among them, 269 patients were in the intervention group (TCC), and 322 in the control group (removable walking casts/footwear). The analysis revealed that the TCC group had higher healing rates (Risk Ratio(RR)=1.22; 95% confidence interval(CI):1.11 to 1.34, p<0.001), shorter healing time (Standard Mean Difference(SMD)=-0.57; 95%CI: -1.01 to -0.13, P=0.010), and elevated occurrence of device-related complications (RR=1.70; 95%CI:1.01 to 2.88, P=0.047), compared with the control group. Subgroup analysis illustrated patients using TCCs had higher healing rates than those using removable walking casts (RR=1.20; 95%CI:1.08 to 1.34, p=0.001) and footwear (RR=1.25; 95%CI:1.04 to 1.51, p=0.019), but they required comparable time for ulcer healing compared with those using removable walking casts (SMD=-0.60; 95%CI: -1.22 to 0.02, P=0.058) or footwear group (SMD=-0.52; 95%CI: -1.17 to 0.12, P=0.110). Although patients using TCCs had significantly higher incidence of device-related complications than those using footwear (RR=4.81; 95%CI:1.30 to 17.74, p=0.018), they had similar one compared with those using the removable walking casts (RR=1.27; 95%CI:0.70 to 2.29, p=0.438).ConclusionThe use of TCCs in patients with DFUs resulted in improved rates of ulcer healing and shorter healing time compared to removable walking casts and footwear. However, it is important to note that TCCs were found to be associated with increased prevalence of complications

Development and Molecular Cytogenetic Identification of a New Wheat–Psathyrostachys huashanica Keng Translocation Line Resistant to Powdery Mildew

Psathyrostachys huashanica Keng, a wild relative of common wheat with many desirable traits, is an invaluable source of genetic material for wheat improvement. Few wheat–P. huashanica translocation lines resistant to powdery mildew have been reported. In this study, a wheat–P. huashanica line, E24-3-1-6-2-1, was generated via distant hybridization, ethyl methanesulfonate (EMS) mutagenesis, and backcross breeding. A chromosome karyotype of 2n = 44 was observed at the mitotic stage in E24-3-1-6-2-1. Genomic in situ hybridization (GISH) analysis revealed four translocated chromosomes in E24-3-1-6-2-1, and P. huashanica chromosome-specific marker analysis showed that the alien chromosome fragment was from the P. huashanica 4Ns chromosome. Moreover, fluorescence in situ hybridization (FISH) analysis demonstrated that reciprocal translocation had occurred between the P. huashanica 4Ns chromosome and the wheat 3D chromosome; thus, E24-3-1-6-2-1 carried two translocations: T3DS·3DL-4NsL and T3DL-4NsS. Translocation also occurred between wheat chromosomes 2A and 4A. At the adult stage, E24-3-1-6-2-1 was highly resistant to powdery mildew, caused by prevalent pathotypes in China. Further, the spike length, numbers of fertile spikelets, kernels per spike, thousand-kernel weight, and grain yield of E24-3-1-6-2-1 were significantly higher than those of its wheat parent 7182 and addition line 24-6-3-1. Thus, this translocation line that is highly resistant to powdery mildew and has excellent agronomic traits can be used as a novel promising germplasm for breeding resistant and high-yielding cultivars

Identification of <em>CHIP</em> as a novel causative gene for autosomal recessive cerebellar ataxia

Autosomal recessive cerebellar ataxias are a group of neurodegenerative disorders that are characterized by complex clinical and genetic heterogeneity. Although more than 20 disease-causing genes have been identified, many patients are still currently without a molecular diagnosis. In a two-generation autosomal recessive cerebellar ataxia family, we mapped a linkage to a minimal candidate region on chromosome 16p13.3 flanked by single-nucleotide polymorphism markers rs11248850 and rs1218762. By combining the defined linkage region with the whole-exome sequencing results, we identified a homozygous mutation (c.493CT) in CHIP (NM_005861) in this family. Using Sanger sequencing, we also identified two compound heterozygous mutations (c.389AT/c.441GT; c.621C>G/c.707GC) in CHIP gene in two additional kindreds. These mutations co-segregated exactly with the disease in these families and were not observed in 500 control subjects with matched ancestry. CHIP colocalized with NR2A, a subunit of the N-methyl-D-aspartate receptor, in the cerebellum, pons, medulla oblongata, hippocampus and cerebral cortex. Wild-type, but not disease-associated mutant CHIPs promoted the degradation of NR2A, which may underlie the pathogenesis of ataxia. In conclusion, using a combination of whole-exome sequencing and linkage analysis, we identified CHIP, encoding a U-box containing ubiquitin E3 ligase, as a novel causative gene for autosomal recessive cerebellar ataxia

Ppm1b negatively regulates necroptosis through dephosphorylating ​Rip3

该研究论文发现蛋白磷酸酶Ppm1b 通过去磷酸化RIP3负调控程序性细胞坏死（necroptosis），阐明了RIP3磷酸化状态的精确调控对于细胞和机体在生理和病理状态下的存活至关重要。The auto-phosphorylation of murine ​receptor-interacting protein 3 (​Rip3) on Thr 231 and Ser 232 in the necrosome is required to trigger necroptosis. However, how ​Rip3 phosphorylation is regulated is still largely unknown. Here we identified ​protein phosphatase 1B (​Ppm1b) as a ​Rip3 phosphatase and found that ​Ppm1b restricts necroptosis in two settings: spontaneous necroptosis caused by ​Rip3 auto-phosphorylation in resting cells, and ​tumour necrosis factor-α (​TNF)-induced necroptosis in cultured cells. We revealed that ​Ppm1b selectively suppresses necroptosis through the dephosphorylation of ​Rip3, which then prevents the recruitment of ​mixed lineage kinase domain-like protein (​Mlkl) to the necrosome. We further showed that ​Ppm1b deficiency (​Ppm1bd/d) in mice enhanced ​TNF-induced death in a ​Rip3-dependent manner, and the role of ​Ppm1b in inhibiting necroptosis was evidenced by elevated ​Rip3 phosphorylation and tissue damage in the caecum of ​TNF-treated ​Ppm1bd/d mice. These data indicate that ​Ppm1b negatively regulates necroptosis through dephosphorylating ​Rip3 in vitro and in vivo

The innate immune sensor NLRC3 attenuates Toll-like receptor signaling via modification of the signaling adaptor TRAF6 and transcription factor NF-κB

Several members of the NLR family of sensors activate innate immunity. In contrast, we found here that NLRC3 inhibited Toll-like receptor (TLR)-dependent activation of the transcription factor NF-κB by interacting with the TLR signaling adaptor TRAF6 to attenuate Lys63 (K63)-linked ubiquitination of TRAF6 and activation of NF-κB. We used bioinformatics to predict interactions between NLR and TRAF proteins, including interactions of TRAF with NLRC3. In vivo, macrophage expression of Nlrc3 mRNA was diminished by the administration of lipopolysaccharide (LPS) but was restored when cellular activation subsided. To assess biologic relevance, we generated Nlrc3−/− mice. LPS-treated Nlrc3−/− macrophages had more K63-ubiquitinated TRAF6, nuclear NF-κB and proinflammatory cytokines. Finally, LPS-treated Nlrc3−/− mice had more signs of inflammation. Thus, signaling via NLRC3 and TLR constitutes a negative feedback loop. Furthermore, prevalent NLR-TRAF interactions suggest the formation of a ‘TRAFasome’ complex

Determination of relevance between surface free energy and adsorption capacity of cement particles

ABSTRACT The compatibility between superplasticizer and cement was influenced by the adsorption capacity of cement particles. This study investigated the relevance between the adsorption capability and surface free energy. Adsorption capacity and surface free energy of both sulphoaluminate cement and portland cement were measured. The adsorption capacity of cement particles was measured by ultraviolet spectrophotometry. The test showed that particles of sulphoaluminate cement adsorbed more molecules of superplasticizer than portland cement particles. The weight of superplasticizer adsorbed by 2g of sulphoaluminate cement and portland cement were 0.28mg and 0.159mg respectively. Surface free energy of cement particles was calculated by contact angle and the contact angles were determined by the thin-layer wicking technique and washburn equation which is theoretical basis of thin-layer wiching technique presented by Chibowski E. The sulphoaluminate cement, portland cement's surface free energy were 51.46 mJ·m-2 and 49.36 mJ·m-2 respectively. The results showed that the higher adsorption capacity of particles was usual accompanied by higher surface free energy. The fluidity of cement paste was influenced by the adsorption capacity of cement particles because the more molecules of superplasticizer was adsorbed by cement particles there were lacking superplasticizer in the paste. The macro-behaviour of higher adsorption capacity is that the cement paste need more superplasticizer to reach the needed fluidity