Characterization of a renoprotective AATF peptide in models of diabetic nephropathy

Inflammation and cell death play central roles in diabetic kidney complications. Identification of novel renoprotective molecules is essential for developing new therapies. We have identified an unconventional extrinsic renoprotective pathway mediated by a 12-amino acid peptide (SAP-12) derived from extracellularly secreted AATF (apoptosis antagonizing transcription factor) in blocking renal damage in models of diabetic nephropathy (DN). SAP-12 (secreted AATF peptide of 12 amino acids, SALKNSHKALKA) is conserved among human, mouse, and rat AATF proteins, and confers potent renoprotective properties at femtomolar concentrations with a broad effective range in renal tubular epithelial cells (RTECs) following exposure to high levels of glucose. We reported previously that AATF was a highly effective in protecting against renal damage and it rescues renal tubular epithelial cells from both apoptotic and necrotic death. The rationale for the current study was based on our recent observation that the renoprotective actions of AATF seemed to be accomplished in a highly unusual manner in diabetic kidneys. As a transcription factor, AATF often functions as an intracellular protein located in cytoplasmic and/or nuclear compartments. However, we have unexpectedly noted that a significant amount of intracellular AATF protein was secreted extracellularly by RTECs under diabetic conditions. Furthermore, secreted AATF (sAATF) functions, at least in part, as a specific ligand and antagonist of the cell surface receptor TLR4 (Toll-like receptor-4). Of importance, TLR4-mediated signaling has been shown to be critically involved in the inflammation and cell death in DN. A region corresponding to the amino acid sequence between AATF179 and AATF279 was responsible for interacting with TLR-4. Based on these observations, several small AATF core peptides derived from this region of AATF were synthesized and tested for their renoprotective properties and their ability to interact with TLR4. One of these peptides, SAP-12, was identified at the interface of AATF/TLR4 interaction. Surprisingly, SAP-12 had a much greater potency and broader effective dose range than the full length sAATF in protecting RTECs in models of diabetic nephropathy. The extrinsic pathway mediated by sAATF and SAP-12 provides strong support for the existence of non-classical secretory pathways where cytoplasmic and nuclear proteins can be secreted extracellularly without a classical N-terminal signal peptide. The region(s) in the extracellular ectodomain of TLR4 involved in interacting with SAP-12 and the potential therapeutic applications of SAP-12 in DN will be discussed. By studying the structure-activity relationships of SAP-12, it may also be possible to develop additional novel versatile peptides with even greater renoprotective capacity and specificity. This study is therefore highly innovative and significant. This work supported in part by an award from Harold Hamm Diabetes Center at the University of Oklahoma. # To whom correspondence should be addressed: Dept. of Physiology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104. Tel.: 405-271-2226; Fax: 405-271-3181; E-mail: [email protected]

Remote information concentration and multipartite entanglement in multilevel systems

Remote information concentration (RIC) in $d$-level systems (qudits) is studied. It is shown that the quantum information initially distributed in three spatially separated qudits can be remotely and deterministically concentrated to a single qudit via an entangled channel without performing any global operations. The entangled channel can be different types of genuine multipartite pure entangled states which are inequivalent under local operations and classical communication. The entangled channel can also be a mixed entangled state, even a bound entangled state which has a similar form to the Smolin state, but has different features from the Smolin state. A common feature of all these pure and mixed entangled states is found, i.e., they have $d^2$ common commuting stabilizers. The differences of qudit-RIC and qubit-RIC ($d=2$) are also analyzed.Comment: 10 pages, 3 figure

J/ψ→ppˉϕJ/\psi \rightarrow p\bar{p}\phi decay in the isobar resonance model

Based on the effective Lagrangian approach, the $J/\psi \to p \bar{p} \phi$ decay is studied in an isobar resonance model with the assumption that the $\phi$-meson is produced from intermediate nucleon resonances. The contributions from the $N^*_{1/2^-}(1535)$, $N^*_{3/2^+}(1900)$, $N^*_{1/2^-}(2090)$ and $N^*_{1/2^+}(2100)$ states are considered. In terms of the coupling constants $g^{2}_{\phi N N^{*}}$ and $g^{2}_{\phi N N^{*}}$ extracted from the data of the partial decay widths of the $N^*$s to the $N\pi$ channel, the reaction cross section of the $\pi^{-}p\rightarrow n\phi$ process and the partial decay widths of the $J/\psi\rightarrow p\bar{p}\eta$ and $J/\psi\rightarrow p\bar{n}\pi^{-}$ processes, respectively, the invariant mass spectrum and the Dalitz plot for $J/\psi \to p \bar{p} \phi$ are predicted. It is shown that there are two types of results. In the type I case, a large peak structure around 2.09GeV implies that a considerable mount of $N\phi$ or $qqqs\bar s$ component may exist in the narrow-width $N^*_{1/2^-}(2090)$ state, but for the wide-width $N^*_{1/2^+}(2100)$ state, it has little $qqqs\bar s$ component. In the type II case, a small peak around 2.11GeV may only indicate the existence of a certain mount of $p\phi$ or $qqqs\bar s$ component in the narrow-width $N^*_{1/2^+}(2100)$ state, but no information for the wide-width $N^*_{1/2^-}(2090)$ state. Further BESIII data with high statistics would help us to distinguish the strange structures of these $N^*$s

Multiple Model Rao-Blackwellized Particle Filter for Manoeuvring Target Tracking

Particle filters can become quite inefficient when applied to a high-dimensional state space since a prohibitively large number of samples may be required to approximate the underlying density functions with desired accuracy. In this paper, a novel multiple model Rao-Blackwellized particle filter (MMRBPF)-based algorithm has been proposed for manoeuvring target tracking in a cluttered environment. The advantage of the proposed approach is that the Rao-Blackwellization allows the algorithm to be partitioned into target tracking and model selection sub-problems, where the target tracking can be solved by the probabilistic data association filter, and the model selection by sequential importance sampling. The analytical relationship between target state and model is exploited to improve the efficiency and accuracy of the proposed algorithm. Moreover, to reduce the particle-degeneracy problem, the resampling approach is selectively carried out. Finally, experiment results, show that the proposed algorithm, has advantages over the conventional IMM-PDAF algorithm in terms of robust and  efficiency.Defence Science Journal, 2009, 59(3), pp.197-204, DOI:http://dx.doi.org/10.14429/dsj.59.151

Renalase Deficiency in Heart Failure Model of Rats—A Potential Mechanism Underlying Circulating Norepinephrine Accumulation

BACKGROUND: Sympathetic overactivity and catecholamine accumulation are important characteristic findings in heart failure, which contribute to its pathophysiology. Here, we identify a potential mechanism underlying norepinephrine accumulation in a rat model of heart failure. METHODOLOGY/PRINCIPAL FINDINGS: Initially, we constructed a rat model of unilateral renal artery stenosis (n = 16) and found that the expression of renalase, a previously identified secreted amine oxidase, was markedly reduced in the ischemic compared to the non-ischemic kidney (protein: 0.295±0.085 versus 0.765±0.171, p<0.05). Subsequently, we utilized an isolated perfused rat kidney model to demonstrate that the clearance rate of norepinephrine decreased with reduction of perfusion flow. On the basis of these findings, we hypothesized the reduced renal blood supply which occurs in heart failure would result in impaired synthesis of renalase by the kidney and consequently reduced degradation of circulating norepinephrine. To verify this, we used a rat model of infarction-induced heart failure (n = 12 per group). In these rats, the flow velocity of renal artery, when measured at four weeks, is obviously lower in the operation group. Renal expression of renalase was reduced (protein: 0.476±0.043 for control, 0.248±0.029 for operation versus 0.636±0.151 for sham-operation) and this was associated with an increase in circulating norepinephrine (0.168±0.016 ng/mL for control, 0.203±0.019 ng/mL for operation versus 0.138±0.008 ng/mL for sham-operation). CONCLUSIONS/SIGNIFICANCE: Renalase expression is influenced by renal blood flow and impaired synthesis of renalase by the kidney may represent a potential mechanism underlying circulating norepinephrine accumulation in heart failure

Influence of bushenhuoxue on primary visual cortex' BDNF damage in rat model of chronic elevated intraocular pressure

AIM: To observe the effect of traditional Chinese medicine(TCM)of bushenhuoxue on primary visual cortex(PVC)brain-derived neurotrophic factor(BDNF)in rat model of chronic elevated intraocular pressure(EIOP), and explore the mechanism of it initially. METHODS: The rat model of chronic EIOP was established by unilaterally cauterizing 3 episcleral veins, then 30 rats were divided into 3 groups randomly: control group, model group, and treatment group. After given drugs or normal saline for 8 weeks, the rats were put to death. The effect of intraocular pressure(IOP), expression of BDNF and ultrastructure of neuron cell in the PVC was observed. RESULTS: Unilaterally cauterizing episcleral veins increased IOP of the rat model obviously, there was significant difference compared with pre-operation(P<0.01). Semi-quantitative pathological analysis on PVC showed that BDNF of total area in the model group was(82438±2597.39)S/μm2,mean optical density was(1155.9±123.14), integrated optical density was(12915±673.28), compared with the control group {total area was(132370±7588.47)S/μm2, mean optical density was(5365±379.65), integrated optical density was(35102±2648.5)}, there were statistical differences(all P<0.05),there was statistical difference in BDNF of total area between model group and treatment group{(108980±9126.77)S/μm2, P<0.05}, significant difference in mean optical density between the model group and treatment group(3220.4±413.67, P<0.05), statistical difference in integrated optical density between the model group and treatment group(23821±3431.68, P<0.05). CONCLUSION: TCM of bushenhuoxue can repair the PVC damage in the rat model of chronic EIOP by enhancing expression of BDNF, improving ultrastructure of neuron cell

JefiGPU: Jefimenko's Equations on GPU

We have implemented a GPU version of the Jefimenko's equations -- JefiGPU. Given the proper distributions of the source terms $\rho$ (charge density) and $\mathbf{J}$ (current density) in the source volume, the algorithm gives the electromagnetic fields in the observational region (not necessarily overlaps the vicinity of the sources). To verify the accuracy of the GPU implementation, we have compared the obtained results with that of the theoretical ones. Our results show that the deviations of the GPU results from the theoretical ones are around 5\%. Meanwhile, we have also compared the performance of the GPU implementation with a CPU version. The simulation results indicate that the GPU code is significantly faster than the CPU version. Finally, we have studied the parameter dependence of the execution time and memory consumption on one NVIDIA Tesla V100 card. Our code can be consistently coupled to RBG (Relativistic Boltzmann equations on GPUs) and many other GPU-based algorithms in physics.Comment: 21 pages, 8 figures, 4 table

A saúde mental é o fator mais importante que influencia a qualidade de vida de idosos deixados para trás quando as famílias emigram da China rural

OBJECTIVES: to investigate the quality of life and the associated factors on left behind elderly in rural China. METHOD: the research was conducted cluster sampling to select 456 elderly left behind when family members migrated out of rural China to participate in a cross-sectional study by completing a general data questionnaire and Quality of Life questionnaire. RESULTS: 91.5% of the elderly requested psychological counseling and education. For the elderly, scores for mental health (39.56±13.73) were significantly lower compared with Chinese standard data (61.6±13.7) (POBJETIVOS: investigar la calidad de vida y los factores asociados a los adultos mayores que se quedan en las zonas rurales de China. MÉTODO: la investigación se realizó por medio de muestreo por conglomerados para seleccionar 456 adultos mayores que se quedaron cuando los miembros de la familia emigraron de zonas rurales de China, para participar en un estudio de corte transversal, completando un cuestionario de datos generales y cuestionario de calidad de vida. RESULTADOS: el 91.5% de los adultos mayores solicitó asistencia psicológica y educación. Para los adultos mayores, las puntuaciones de salud mental (39.56±13.73) fueron significativamente más bajos en comparación con los datos estándar de China (61.6±13.7) (pOBJETIVOS: investigar a qualidade de vida e fatores associados de idosos deixados para trás na China rural. MÉTODO: foi realizada amostragem por conglomerado para selecionar 456 idosos deixados para trás quando os membros da família emigram da China rural. Este é um estudo transversal com preenchimento de um questionário de dados gerais e de qualidade de vida. RESULTADOS: 91,5% dos idosos convidados solicitaram aconselhamento e educação psicológicos. Para os idosos, os escores de saúde mental (39,56±13,73) foram significativamente menores em comparação aos dados padrões chineses (61,6±13,7) (