Delayed hippocampal neuronal death in young gerbil following transient global cerebral ischemia is related to higher and longer-term expression of p63 in the ischemic hippocampus

The tumor suppressor p63 is one of p53 family members and plays a vital role as a regulator of neuronal apoptosis in the development of the nervous system. However, the role of p63 in mature neuronal death has not been addressed yet. In this study, we first compared ischemia-induced effects on p63 expression in the hippocampal regions （CA1-3） between the young and adult gerbils subjected to 5 minutes of transient global cerebral ischemia. Neuronal death in the hippocampal CA1 region of young gerbils was significantly slow compared with that in the adult gerbils after transient global cerebral ischemia, p63 immunoreactivity in the hippocampal CA1 pyramidal neurons in the sham-operated young group was significantly low compared with that in the sham-operated adult group, p63 immunoreactivity was apparently changed in ischemic hippocampal CA1 pyramidal neurons in both ischemia-operated young and adult groups. In the ischemia-operated adult groups, p63 immunoreactivity in the hippocampal CA1 pyramidal neurons was significantly decreased at 4 days post-ischemia; however, p63 immunoreactivity in the ischemia-operated young group was significantly higher than that in the ischemia-operated adult group. At 7 days post-ischemia, p63 immunoreactivity was decreased in the hippocampal CA1 pyramidal neurons in both ischemia-operated young and adult groups. Change patterns of p63 level in the hippocampal CA1 region of adult and young gerbils after ischemic damage were similar to those observed in the immunohistochemical results. These findings indicate that higher and longer-term expression of p63 in the hippocampal CA1 region of the young gerbils after ischemia/reperfusion may be related to more delayed neuronal death compared to that in the adults.

A Study of Radiation-Induced Instability for the Gene Locus Associated with Intellectual Disorders or Developmental Delays

Multiplex Ligation-Dependent Probe Amplification (MLPA) was used to study the integrity of the chromosomes for two WIL2-derived lymphoblastoid cell lines (TK6 and WTK1) in the presence and absence of ionizing radiation. WTK1 cells contain a p53 mutation, whereas the TK6 cell line has the native p53 tumor-suppressor gene. Each cell line was isolated pre- and post-irradiation (2 and 3 Gy) and analyzed by MLPA. Using probes that target specific regions on chromosomes associated with a distinct subset of microdeletions and microduplications either established or thought to be responsible for intellectual disability or developmental delay, we have demonstrated that WTK1 and TK6 are not impacted in the same way by irradiation. Instead, each cell line presents its own unique MLPA profile. The most notable differences are the appearance of nine unique probe signals only seen in WTK1 cells. These results are important in the study of how different cell lines can be affected in significantly different ways depending on the presence or absence of wild type p53.

A novel mathematical model on Peer-to-Peer botnet

Peer-to-Peer （P2P） botnet has emerged as one of the most serious threats to lnternet security. To effectively elimi- nate P2P botnet, a delayed SEIR model is proposed,which can portray the formation process of P2P botnet. Then, the local stability at equilibria is carefully analyzed by considering the eigenvalues＇ distributed ranges of characteristic equations. Both mathematical analysis and numerical simulations show that the dynamical features of the proposed model rely on the basic re- production number and time delay r. The results can help us to better understand the propagation behaviors of P2P botnet and design effective counter-botnet methods.

A mathematical model of a P53 oscillation network triggered by DNA damage

Taking the interaction between a DNA damage repair module, an ATM module, and a P53--MDM2 oscillation module into account, this paper presents a mathematical model of a P53 oscillation network triggered by a DNA damage signal in individual cells. The effects of the DNA damage signal and the delay time of P53-induced MDM2 expression on the behaviours of the P53 oscillation network are studied. In the oscillatory state of the P53--MDM2 oscillator, it is found that the pulse number of P53--P oscillation increases with the increase of the initial DNA damage signal, whereas the amplitude and the period of P53--P oscillation are fixed for different initial DNA damage signals, and the period numbers of P53--P oscillations decrease with the increase of time delay of MDM2 expression induced by P53. These theoretical predictions are consistent with previous experimental results. The combined negative feedback of P53--MDM2 with the time delay of P53-induced MDM2 expression causes oscillation behaviour in the P53 network.

GPSA:A Greedy Pull-based Scheduling Approach for P2P Live Streaming under Heterogeneous Environments

Pull-based P2P live streaming is a promising solution for the large scale streaming systems, like PPStream, PPlive, due to its high scalability, low cost and high resilience. However, they usually suffer from bad delay performance. In this paper, we seek to improve the delay performance under ensuring video display quality stemming from chunk scheduling. And so we model Pull-based chunk scheduling problem as a multi-objective optimization problem to minimize the video delay and maximize video display quality in the environment of heterogeneous upload bandwidths, heterogeneous and dynamic propagation delays. Finally we put up with a greedy Pull-based scheduling approach(GPSA) to solve the optimization problem. The evaluation shows GPSA can outperform two classical chunk scheduling approaches and adapt to dynamic variance of propagation delays.

Expression of p53 and p21 proteins in rat brain tissue after reperfusion following forebrain ischemia

Objective: To investigate the relationship between p53, p21 proteins and delayed neuronal death (DND) after reperfusion following forebrain ischemia in rats. Methods With four-vessel occlusion model of rats, the expression of p53, p21 proteins in brain tissue using labeled streptavindin-biotin immunohistochemical (LAAB) suming were observed. Re sults: The expression of p53, p21 proteins in brain was upregulated after reperfusion following 15 min forebrain ischemia and their distribution was similar. p53 and p21 proteins in brian sections was detected earlier in the white matter of hippocampal formation, thalamus, hypothalamus (6 h following reperfusion) than in the neuronal nuclei in cerebral cortex and CA1 region (24h), and the maximal induction was observed at 72 h following reperfusion. CA1 region suffered the most serious injury, where the positive expression of p53 and off proteins was most. Conclusion: Reperfusion following forebrain ischemia could upregulate the expression of p53 and p21 proteins in the brain region, suggesting that p53 and p21 proteins participate in and possibly promote the apoptosis of ’DND.

Kinetic analysis of p53 gene network with time delays and PIDD

p53 kinetics plays a key role in regulating cell fate.Based on the p53 gene regulatory network composed by the core regulatory factors ATM,Mdm2,Wipl,and PIDD,the effect of the delays in the process of transcription and translation of Mdm2 and Wipl on the dynamics of p53 is studied theoretically and numerically.The results show that these two time delays can affect the stability of the positive equilibrium.With the increase of delays,the dynamics of p53 presents an oscillating state.Further,we also study the effects of PIDD and chemotherapeutic drug etoposide on the kinetics of p53.The model indicates that(i)PIDD low-level expression does not significantly affect p53 oscillatory behavior,but high-level expression could induce two-phase kinetics of p53;(ii)Too high and too low concentration of etoposide is not conducive to p53 oscillation.These results are in good agreement with experimental findings.Finally,we consider the infuence of internal noise on the system through Binomial r-leap algorithm.Stochastic simulations reveal that high-intensity noise completely destroys p53 dynamics in the deterministic model,whereas low-intensity noise does not alter p53 dynamics.Interestingly,for the stable focus,the internal noise with appropriate intensity can induce quasi-limit cycle oscillations of the system.Our work may provide the useful insights for the development of anticancer therapy.

New β-delayed proton precursor^(121)Ce near the proton drip-line

Unknown β delayed proton precursor 121 Ce was produced via the reaction of 92 Mo( 32 S, 3n), and identified by an He jet fast tape transport system with "P γ" coincidence measurements. The half life of 121 Ce decay was determined to be (1.1±0.1)s. Its energy spectrum of β delayed protons was measured and the β delayed proton branching ratio for 121 Ce decay was roughly estimated to be ～1%. After β delayed proton decay of the precursors \{ 119 Ba,\} \{ 121 Ba\} and 122 La, some of γ transitions from low lying states to the ground states in their "daughters" were observed for the first time.

八路抢先电路和双路延时器的设计

本文介绍一种八路抢先电路和双路延时器的设计与制作,特点是采用可控硅元件作为抢先电路的关键元件,可以无限制地增加抢先电路的分组数目,同时解决了抢先电路和555延时电路的抗扰性问题。

Oscillatory behavior of p53-Mdm2 system driven by transcriptional and translational time delays

Biological experiments clarify that p53-Mdm2 module is the core of tumor network and p53 oscillation plays an important role in determining the tumor cell fate.In this paper,we investigate the effect of time delay on the oscillatory behavior induced by Hopf bifurcation in p53-Mdm2 system.First,the stability of the unique positive equilibriurm point and the existence of Hopf bifurcation are investigated by using the time delay as the bifurcation parameter and by applying the bifurcation theory.Second,the explicit criteria determining the direction of Hopf bifurcation and the stability of bifurcating periodic solutions are developed based on the normal form theory and the center manifold theorem.In addition,the combination of numerical simulation results and theoretical calculation results indicates that time delays in p53-Mdm2 system are critical for p53 oscillations.The results may help us to better understand the biological functions of p53 pathway and provide clues for treatment of cancer.

Age- and gender-dependent obesity in individuals with 16pl1.2 deletion

Recurrent genomic imbalances at 16p 11.2 are genetic risk factors of variable penetrance for developmental delay and autism.Recently, 16pl 1.2（chr16：29.5 Mb-30.1 Mb） deletion has also been detected in individuals with early-onset severe obesity.The penetrance of 16p11.2 deletion as a genetic risk factor for obesity is unknown.We evaluated the growth and body mass characteristics of 28 individuals with 16p11.2 （chr16：29.5 Mb-30.1 Mb） deletion originally ascertained for their developmental disorders by reviewing their medical records.We found that nine individuals could be classified as obese and six as overweight.These individuals generally had early feeding and growth difficulties,and started to gain excessive weight around 5-6 years of age.Thirteen out of the 18 deletion carriers aged 5 years and older（72%） were overweight or obese,whereas only two of 10 deletion carriers（20%） younger than five were overweight or obese.Males exhibited more severe obesity than females.Thus,the obesity phenotype of 16p11.2 deletion carriers is of juvenile onset,exhibited an age- and gender-dependent penetrance. 16p11.2 deletion appears to predispose individuals to juvenile onset obesity and in this case are similar to the well-described Prader-Willi syndrome（PWS）.Early detection of this deletion will provide opportunity to prevent obesity.