Eigenvalue problem for p-Laplacian three-point boundary value problems on time scales

AbstractLet T be a time scale such that 0,T∈T, β,γ⩾0 and 0<η<ρ(T). We consider the following p-Laplacian three-point boundary problem on time scales(φp(uΔ(t)))∇+λh(t)f(u(t))=0,t∈(0,T),u(0)−βuΔ(0)=γuΔ(η),uΔ(T)=0, where p>1, λ>0, h∈Cld((0,T),[0,∞)) and f∈C([0,∞),(0,∞)). Some sufficient conditions for the nonexistence and existence of at least one or two positive solutions for the boundary value problem are established. In doing so the usual restriction that f0=limu→0+f(u)φp(u) and f∞=limu→∞f(u)φp(u) exist is removed. An example is also given to illustrate the main results

Upregulation of Endogenous HMOX1 Expression by a Computer-Designed Artificial Transcription Factor

Heme oxygenase-1 (HO-1) is well known as a cytoprotective factor. Research has revealed that it is a promising therapeutic target for cardiovascular diseases. In the current study, an HMOX1 (HO-1 gene) enhancer-specific artificial zinc-finger protein (AZP) was designed using bioinformatical methods. Then, an artificial transcription factor (ATF) was constructed based on the AZP. In the ATF, the p65 functional domain was used as the effector domain (ED), and a nuclear localization sequence (NLS) was also included. We next analyzed the affinity of the ATF to the HMOX1 enhancer and the effect of the ATF on endogenous HMOX1 expression. The results suggest that the ATF could effectively upregulate endogenous HMOX1 expression in ECV304 cells. With further research, the ATF could be developed as a potential drug for cardiovascular diseases

Upregulation of Endogenous HMOX1 Expression by a Computer-Designed Artificial Transcription Factor

Heme oxygenase-1 (HO-1) is well known as a cytoprotective factor. Research has revealed that it is a promising therapeutic target for cardiovascular diseases. In the current study, an HMOX1 (HO-1 gene) enhancer-specific artificial zinc-finger protein (AZP) was designed using bioinformatical methods. Then, an artificial transcription factor (ATF) was constructed based on the AZP. In the ATF, the p65 functional domain was used as the effector domain (ED), and a nuclear localization sequence (NLS) was also included. We next analyzed the affinity of the ATF to the HMOX1 enhancer and the effect of the ATF on endogenous HMOX1 expression. The results suggest that the ATF could effectively upregulate endogenous HMOX1 expression in ECV304 cells. With further research, the ATF could be developed as a potential drug for cardiovascular diseases

In situ epicatechin-loaded hydrogel implants for local drug delivery to spinal column for effective management of post-traumatic spinal injuries

Purpose: To prepare hydrogels loaded with epicatechin, a strong antioxidant,  anti-inflammatory, and neuroprotective tea flavonoid, and characterise them in situ as a vehicle for prolonged and safer drug delivery in patients with post-traumatic spinal cord injury.Methods: Five in situ gel formulations were prepared using chitosan and evaluated in terms of their visual appearance, clarity, pH, viscosity, and in vitro drug release. In vivo anti-inflammatory activity was determined and compared with 2 % piroxicam gel as standard. Motor function activity in a rat model of spinal injury was examined comparatively with i.v. methylprednisolone as standard.Results: The N-methyl pyrrolidone solution (containing 1 % w/w epicatechin with 2 to 10 % w/w chitosan) of the in situ gel formulation had a uniform pH in the range of 4.01 ± 0.12 to 4.27 ± 0.02. High and uniform drug loading, ranging from 94.48 ± 1.28 to 98.08 ± 1.24 %, and good in vitro drug release (79.48 ± 2.84 to 96.48 ± 1.02 % after 7 days) were achieved. The in situ gel prepared from 1 % epicatechin and 2 % chitosan (E5) showed the greatest in vivo anti-inflammatory activity  (60.58 % inhibition of paw oedema in standard carrageenan-induced hind rat paw oedema model, compared with 48.08 % for the standard). The gels showed  significant therapeutic effectiveness against post-traumainduced spinal injury in rats. E5 elicited maximum motor activity (horizontal bar test) in the spinal injuryrat model; the rats that received E5 treatment produced an activity score of 3.62 ± 0.02 at the end of 7 days, compared with 5.0 ± 0.20 following treatment with the standard.Conclusion: In situ epicatechin-loaded gel exhibits significant neuroprotective and anti-inflammatory effects, and therefore can potentially be used for prolonged and safe drug delivery in patients with traumatic spinal cord injury.Keywords: Epicatechin, In situ gel, Chitosan, Spinal injury, Post-traumatic, Motor activity, Antiinflammator

Y-STR Haplotypic Polymorphisms for the Hakka Population in West China and Its Phylogenic Comparison with Other Chinese Populations

The Hakkas, undergone a series of great migrations, are usually identified with people who speak the Hakka language or share at least same Hakka ancestry. As the largest Hakka dialect island in West China, the Dongshan region was closely linked with the great migration wave of Hakka. However, the paternal genetic profiles of Dongshan Hakka have never been revealed. In the present study, 41 Y-chromosomal short tandem repeat (Y-STR) loci included in the SureID® PathFinder Plus Kit were analyzed in 353 unrelated male individuals (171 Hakka and 182 Han) of Sichuan Province, China. By analyzing 166 different haplotypes among Dongshan Hakkas and 176 different haplotypes among Sichuan Han males, haplotype diversity (HD) of the Hakka population was calculated as 0.9997 with a discrimination capacity (DC) of 0.9708. HD and DC were 0.9996 and 0.9670 for the Sichuan Han population, respectively. Most of the Y-STR loci were highly informative in both populations except DYS645. The genetic relationships were evaluated by comparing the Hakka population with 11 other groups that are relevant to the migration routes of Hakkas. The results of the MDS plot and phylogenetic tree indicate that the Dongshan Hakka population was closely related to Han nationalities from Anhui, Jiangxi, and Fujian Provinces

Bidirectional End-to-End Learning of Retriever-Reader Paradigm for Entity Linking

Entity Linking (EL) is a fundamental task for Information Extraction and Knowledge Graphs. The general form of EL (i.e., end-to-end EL) aims to first find mentions in the given input document and then link the mentions to corresponding entities in a specific knowledge base. Recently, the paradigm of retriever-reader promotes the progress of end-to-end EL, benefiting from the advantages of dense entity retrieval and machine reading comprehension. However, the existing study only trains the retriever and the reader separately in a pipeline manner, which ignores the benefit that the interaction between the retriever and the reader can bring to the task. To advance the retriever-reader paradigm to perform more perfectly on end-to-end EL, we propose BEER$^2$, a Bidirectional End-to-End training framework for Retriever and Reader. Through our designed bidirectional end-to-end training, BEER$^2$ guides the retriever and the reader to learn from each other, make progress together, and ultimately improve EL performance. Extensive experiments on benchmarks of multiple domains demonstrate the effectiveness of our proposed BEER$^2$.Comment: This work has been submitted to the IEEE for possible publication. Copyright may be transferred without notice, after which this version may no longer be accessibl

HORMETIC EFFECTS OF ACUTE METHYLMERCURY EXPOSURE ON GRP78 EXPRESSION IN RAT BRAIN CORTEX

This study aims to explore the expression of GRP78, a marker of endoplasmic reticulum (ER) stress, in the cortex of rat brains acutely exposed to methylmercury (MeHg). Thirty Sprague-Dawley (SD) rats were randomly divided into six groups, and decapitated 6 hours (h) after intraperitoneal (i.p.) injection of MeHg (2, 4, 6, 8 or 10 mg/kg body weight) or normal saline. Protein and mRNA expression of Grp78 were detected by western blotting and real-time PCR, respectively. The results showed that a gradual increase in GRP78 protein expression was observed in the cortex of rats acutely exposed to MeHg (2, 4 or 6 mg/kg). Protein levels peaked in the 6 mg/kg group (p \u3c 0.05 vs. controls), decreased in the 8 mg/kg group, and bottomed below the control level in the 10 mg/kg group. Parallel changes were noted for Grp78 mRNA expression. It may be implied that acute exposure to MeHg induced hormetic dose-dependent changes in Grp78 mRNA and protein expression, suggesting that activation of ER stress is involved in MeHg-induced neurotoxicity. Low level MeHg exposure may induce GRP78 protein expression to stimulate endogenous cytoprotective mechanisms