Absolute stability of lurie systems with impulsive effects

AbstractThis paper studies absolute stability of Lurie systems with impulsive effects. Using the method of Lyapunov functions and the variation of parameters technique, we establish sufficient conditions for absolute stability

Histone deacetylases (HDACs) in XPC gene silencing and bladder cancer

Bladder cancer is one of the most common malignancies and causes hundreds of thousands of deaths worldwide each year. Bladder cancer is strongly associated with exposure to environmental carcinogens. It is believed that DNA damage generated by environmental carcinogens and their metabolites causes development of bladder cancer. Nucleotide excision repair (NER) is the major DNA repair pathway for repairing bulk DNA damage generated by most environmental carcinogens, and XPC is a DNA damage recognition protein required for initiation of the NER process. Recent studies demonstrate reduced levels of XPC protein in tumors for a majority of bladder cancer patients. In this work we investigated the role of histone deacetylases (HDACs) in XPC gene silencing and bladder cancer development. The results of our HDAC inhibition study revealed that the treatment of HTB4 and HTB9 bladder cancer cells with the HDAC inhibitor valproic acid (VPA) caused an increase in transcription of the XPC gene in these cells. The results of our chromatin immunoprecipitation (ChIP) studies indicated that the VPA treatment caused increased binding of both CREB1 and Sp1 transcription factors at the promoter region of the XPC gene for both HTB4 and HTB9 cells. The results of our immunohistochemistry (IHC) staining studies further revealed a strong correlation between the over-expression of HDAC4 and increased bladder cancer occurrence (p < 0.001) as well as a marginal significance of increasing incidence of HDAC4 positivity seen with an increase in severity of bladder cancer (p = 0.08). In addition, the results of our caspase 3 activation studies demonstrated that prior treatment with VPA increased the anticancer drug cisplatin-induced activation of caspase 3 in both HTB4 and HTB9 cells. All of these results suggest that the HDACs negatively regulate transcription of the XPC gene in bladder cancer cells and contribute to the severity of bladder tumors

The effect of caffeine on cisplatin-induced apoptosis of lung cancer cells

Background: Cisplatin is an important DNA-damaging anticancer drug that has been used to treat many cancer types. However, the effectiveness of cisplatin treatment diminishes quickly as cancer cells develop resistance to the drug, which eventually results in treatment failure. Caffeine is an ingredient contained in many food sources. Caffeine can inhibit activities of both ATM and ATR, two important protein kinases involved in DNA damage-induced cell cycle arrest and apoptosis. The effect of caffeine on cisplatin-based cancer treatment is not well known. Methods: Caspase-3 activation and cell growth inhibition assays were used to determine the effect of caffeine on cisplatin-induced apoptosis and cell growth in lung cancer cells. Real time PCR, immunoblotting, and flow cytometry assays were used determine a mechanism through which the presence of caffeine increased cisplatin-induced apoptosis of the lung cancer cells. Results: Our caspase-3 activation studies demonstrated that the presence of caffeine increased the cisplatin-induced apoptosis in both HTB182 and CRL5985 lung cancer cells. Our cell growth inhibition studies indicated that the presence of caffeine caused a more increase for cisplatin-induced cell growth inhibition. The results obtained from our real time PCR and western blot studies revealed that the presence of caffeine increased cisplatin-induced expression of the PUMA pro-apoptotic protein in these lung cancer cells. The results of our protein phosphorylation studies indicated that the presence of caffeine caused a decrease in CHK1 phosphorylation at Ser317/Ser345but an increase in ATM phosphorylation at Ser1981 in the lung cancer cells treated with cisplatin. In addition, our flow cytometry studies also revealed that the presence of caffeine caused an increase in G1 cell population but a decrease for cisplatin-induced cell cycle arrests at the S and the G2 checkpoints in HTB182 and CRL5985 cells respectively. Conclusion: Our results suggest that the presence of caffeine increases the cisplatin-induced lung cancer cell killings by inhibiting ATR but inducing ATM activation, resulting in an increase in expression of PUMA protein and an increase in apoptosis

Cell–Cell Adhesion Prevents Mutant Cells Lacking Myosin II from Penetrating Aggregation Streams ofDictyostelium

AbstractWhen a small number of fluorescently labeled myosin II mutant cells (mhcA−) are mixed with wild-type cells and development of the chimeras is observed by confocal microscopy, the mutant cells are localized to the edges of aggregation streams and mounds. Moreover, the mutant cells stick to wild-type cells and become distorted (Shelden and Knecht, 1995). Two independent adhesion mechanisms, Contact Sites A and Contact Sites B, function during the aggregation stage and either one or both might be responsible for excluding the myosin II null cells. We have mixedmhcA−cells with cells in which the appearance of Contact Sites B is delayed (strain TL72) as well as cells which lack Contact Sites A (strain GT10) and double mutants in which both adhesion mechanisms are affected (strain TL73). In all chimeras, themhcA−cells were distorted by interactions with the adhesion mutant cells, indicating that it does not require significant adhesive interaction to distort the flaccid cortex ofmhcA−cells.mhcA−cells were excluded from streams composed of cells lacking either Contact Sites A or Contact Sites B but mixed randomly with cells lacking both adhesion systems. By 10 hr of development, cells of strain TL73 acquire Contact Sites B adhesion. If cells of this strain were mixed with labeledmhcA−cells, allowed to develop for 9 hr, and then dissociated before replating, the myosin II null cells were seen to be distorted and excluded from the reaggregates. Thus the exclusion ofmhcA−cells from streams can be accomplished by either Contact Sites A or B. When chimeras of labeled TL73 and wild-type cells were made, the TL73 cells were found to be randomly mixed into aggregation streams. This result indicates that adhesive sorting does not function during aggregation and so cannot account for the exclusion ofmhcA−cells from streams. We hypothesize that the flaccid cortex ofmhcA−cells cannot generate sufficient protrusive force to break the contacts between adhered cells in aggregation streams but can enter streams where the cells are weakly adherent

DPL: Decoupled Prompt Learning for Vision-Language Models

Prompt learning has emerged as an efficient and effective approach for transferring foundational Vision-Language Models (e.g., CLIP) to downstream tasks. However, current methods tend to overfit to seen categories, thereby limiting their generalization ability for unseen classes. In this paper, we propose a new method, Decoupled Prompt Learning (DPL), which reformulates the attention in prompt learning to alleviate this problem. Specifically, we theoretically investigate the collaborative process between prompts and instances (i.e., image patches/text tokens) by reformulating the original self-attention into four separate sub-processes. Through detailed analysis, we observe that certain sub-processes can be strengthened to bolster robustness and generalizability by some approximation techniques. Furthermore, we introduce language-conditioned textual prompting based on decoupled attention to naturally preserve the generalization of text input. Our approach is flexible for both visual and textual modalities, making it easily extendable to multi-modal prompt learning. By combining the proposed techniques, our approach achieves state-of-the-art performance on three representative benchmarks encompassing 15 image recognition datasets, while maintaining parameter-efficient. Moreover, our DPL does not rely on any auxiliary regularization task or extra training data, further demonstrating its remarkable generalization ability.Comment: 11 pages, 5 figures, 8 table

Expression of Robo4 in the fibrovascular membranes from patients with proliferative diabetic retinopathy and its role in RF/6A and RPE cells

Purpose: Robo4, a member of the roundabout (Robo) family, acts as a neuronal guidance receptor and plays some role in vasculogenesis and angiogenesis. This study investigated the effect of Robo4 on the formation of fibrovascular membranes (FVMs) from patients with proliferative diabetic retinopathy and its roles in choroid-retina endothelial (RF/6A) and human retinal pigment epithelial (RPE) cells. Methods: RT-PCR and immunohistochemistry were used to determine the levels of mRNA and the presence and distribution of Robo4 in FVMs. Small interfering RNA (siRNA) technology was used to knock down Robo4 expression and to study its effects on RF/6A and RPE cells in vitro. Cell proliferation, migration, spreading, cycling, and apoptosis were assessed with MTT assay, Boyden chamber assay, immunocytochemistry, and flow cytometry. Tube formation by RF/6A on Matrigel was also analyzed. Results: The level of Robo4 mRNA was high in FVMs. Robo4 was expressed in the vessels and fibrous-like tissue co-immunostained for CD31 and GFAP, respectively. Robo4 siRNA knockdown inhibited cell proliferation and migration. Tube formation by RF/6A cells was also disturbed. Under hypoxic conditions, more apoptotic cells were evident among the knockdown cells than among the control cells (p &lt; 0.01). Conclusions: Robo4 may play a role in the formation of FVMs. Silencing the expression of Robo4 in RF/6A and RPE cells inhibited their proliferation and reduced their tolerance of hypoxic conditions, suggesting physiologic functions of Robo4 in the cells of the retina.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000267136400001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Biochemistry &amp; Molecular BiologyOphthalmologySCI(E)PubMed15ARTICLE112-131057-10691

Transplantation of Ciliary Neurotrophic Factor-Expressing Adult Oligodendrocyte Precursor Cells Promotes Remyelination and Functional Recovery after SpinalCord Injury

Demyelination contributes to the dysfunction after traumatic spinal cord injury (SCI). We explored whether the combination of neurotrophic factors and transplantation of adult rat spinal cord oligodendrocyte precursor cells (OPCs) could enhance remyelination and functional recovery after SCI. Ciliary neurotrophic factor (CNTF) was the most effective neurotrophic factor to promote oligodendrocyte (OL) differentiation and survival of OPCs in vitro. OPCs were infected with retroviruses expressing enhanced green fluorescent protein (EGFP) or CNTF and transplanted into the contused adult thoracic spinal cord 9 d after injury. Seven weeks after transplantation, the grafted OPCs survived and integrated into the injured spinal cord. The survival of grafted CNTF-OPCs increased fourfold compared with EGFP-OPCs. The grafted OPCs differentiated into adenomatus polyposis coli (APC+) OLs, and CNTF significantly increased the percentage of APC+ OLs from grafted OPCs. Immunofluorescent and immunoelectron microscopic analyses showed that the grafted OPCs formed central myelin sheaths around the axons in the injured spinal cord. The number of OL-remyelinated axons in ventrolateral funiculus (VLF) or lateral funiculus (LF) at the injured epicenter was significantly increased in animals that received CNTF-OPC grafts compared with all other groups. Importantly, 75% of rats receiving CNTF-OPC grafts recovered transcranial magnetic motor-evoked potential and magnetic interenlargement reflex responses, indicating that conduction through the demyelinated axons in VLF or LF, respectively, was partially restored. More importantly, recovery of hindlimb locomotor function was significantly enhanced in animals receiving grafts of CNTF-OPCs. Thus, combined treatment with OPC grafts expressing CNTF can enhance remyelination and facilitate functional recovery after traumatic SCI

Parameter design oriented analysis of the current control stability of the weak-grid-tied VSC

This paper studies the dynamic behaviors of weak-grid-tied VSCs with simplified transfer functions, which provides an accurate stability analysis and useful indications for tuning system parameters. A reduced-order multi-input multi-output (MIMO) transfer function that contains four single-input single-output (SISO) transfer functions for the weak-grid-tied VSC is first presented. It is found that the four SISO transfer functions share the same equivalent open-loop transfer function, i.e., the same stability conclusion. The Bode plots of the equivalent open-loop transfer function show that the inner current loop behaves as a band-pass filter whose maximum gain is approximately at the frequency of the PLL's bandwidth. By stability criterion, the harmonic amplification and instability occur when its maximum gain exceeds 0dB caused by high PLL's bandwidth, large grid impedance or high active power. It is also found that the target system is less stable when it works as an inverter than as a rectifier, due to the risk of the local positive feedback in the inverter mode. An effective criterion is further proposed to guide the selection of a proper PLL's bandwidth to ensure the stability of the VSC system. Simulation results validate the correctness of the analysis and the efficacy of the criterion

Protective effect of paeoniflorin against oxidative stress in human retinal pigment epithelium in vitro

Purpose: This study was conducted to determine whether paeoniflorin (PF) could prevent H(2)O(2)-induced oxidative stress in ARPE-19 cells and to elucidate the molecular pathways involved in this protection. Methods: Cultured ARPE-19 cells were subjected to oxidative stress with H(2)O(2) in the presence and absence of PF. The preventive effective of PF on reactive oxygen species (ROS) production and retinal pigment epithelium (RPE) cell death induced by H(2)O(2) was determined by 2&apos;, 7&apos;-dichlorodihydrofluorescein diacetate (H(2)DCFDA) fluorescence and 3-(4, 5dimethylthiazol-2-yl)-2, 5 diphenyl tetrazolium bromide (MTT) assay. The ability of PF to protect RPE cells against ROS-mediated apoptosis was assessed by caspase-3 activity and 4&apos;, 6-diamidino-2-phenylindole (DAPI) staining. Furthermore, the protective effect of PF via the mitogen-activated protein kinase (MAPK) pathway was determined by western blot analysis. Results: PF protected ARPE-19 cells from H(2)O(2)-induced cell death with low toxicity. H(2)O(2)-induced oxidative stress increased ROS production and caspase-3 activity, which was significantly inhibited by PF in a dose-dependent manner. Pretreatment with PF attenuated H(2)O(2)-induced p38MAPK and extracellular signal regulated kinase (ERK) phosphorylation in human RPE cells, which contributed to cell viability in ARPE-19 cells. Conclusions: This is the first report to show that PF can protect ARPE-19 cells from the cellular apoptosis induced by oxidative stress. The results of this study open new avenues for the use of PF in treatment of ocular diseases, such as age-related macular degeneration (AMD), where oxidative stress plays a major role in disease pathogenesis.Biochemistry &amp; Molecular BiologyOphthalmologySCI(E)PubMed1ARTICLE373-783512-35221