Internal tissue displacement measurement based on ultrasonic wave Doppler signal digital detection and its application to fetal movement monitoring

We have developed a fetal movement monitoring system based on small displacement measurement of internal tissues. When ultrasonic pulses are transmitted to the fetus, the reflected ultrasonic waves which have a Doppler frequency shift due to the fetal movements are detected by using an ultrasonic pulsed Doppler technique. In this paper, we propose a displacement measurement method for internal tissues which is based on the Doppler signal digital detection technique. In the method, the received ultrasonic RF signals are sampled with a sampling frequency of four times higher than the centre frequency of the ultrasonic waves; the Doppler frequency shift signals are derived using digital signal processing. From the detected signals, the internal displacements are estimated using the arc-tangent method. The basic algorithm of the detection method has already been used in the area of blood flow sensing, however, we apply the algorithm to the displacement measurement of internal tissues. The comparison between the proposed method and the conventional method is presented. The fetal movement quantitative monitoring system based on the method which has been constructed is shown.     

Physical and chemical aspects of a new porous hydroxyapatite

The new engineered porous hydroxyapatite (EP-HA) described in this paper seems to be suitable as a bone substitute. Its physico-chemical characteristics and morphology are similar to those of natural bone. Study of its histological behaviour in humans revealed bone formation within and around the porous hydroxyapatite that is markedly resorbed.     

考虑更新延长两阶段保修的二手产品维修策略优化

针对二手产品的维修问题,给出了二手产品生命周期的定义,提出了考虑更新延长两阶段保修的维修策略模型。该策略综合考虑了产品的年龄变化、延保折扣、小修和生产损失费用等因素,从顾客的角度出发,建立以顾客期望总费用率最小化为目标的免费更换保修和按比例更换保修两种策略模型,并给出模型最优化的相关理论证明。算例研究验证了模型的有效性,并对参数的灵敏度进行了分析,文中结论可为顾客进行产品维修计划提供决策依据。     

MSE-MRI sequence optimisation for measurement of bi- and tri-exponential T2 relaxation in a phantom and fruit

The transverse relaxation signal from vegetal cells can be described by multi-exponential behaviour, reflecting different water compartments. This multi-exponential relaxation is rarely measured by conventional MRI imaging protocols; mono-exponential relaxation times are measured instead, thus limiting information about of the microstructure and water status in vegetal cells. In this study, an optimised multiple spin echo (MSE) MRI sequence was evaluated for assessment of multi-exponential transverse relaxation in fruit tissues. The sequence was designed for the acquisition of a maximum of 512 echoes. Non-selective refocusing RF pulses were used in combination with balanced crusher gradients for elimination of spurious echoes. The study was performed on a bi-compartmental phantom with known T₂ values and on apple and tomato fruit. T₂ decays measured in the phantom and fruit were analysed using bi- and tri-exponential fits, respectively. The MRI results were compared with low field non-spatially resolved NMR measurements performed on the same samples.     

Fluorescence Correlation Spectroscopy of the Binding of Nucleotide Excision Repair Protein XPC-hHr23B with DNA Substrates

The interaction of the nucleotide excision repair (NER) protein dimeric complex XPC-hHR23B, which is implicated in the DNA damage recognition step, with three Cy3.5 labeled 90-bp double-stranded DNA substrates (unmodified, with a central unpaired region, and cholesterol modified) and a 90-mer single-strand DNA was investigated in solution by fluorescence correlation spectroscopy. Autocorrelation functions obtained in the presence of an excess of protein show larger diffusion times (tau (d)) than for free DNA, indicating the presence of DNA-protein bound complexes. The fraction of DNA bound (theta), as a way to describe the percentage of protein bound to DNA, was directly estimated from FCS data. A significantly stronger binding capability for the cholesterol modified substrate (78% DNA bound) than for other double-stranded DNA substrates was observed, while the lowest affinity was found for the single-stranded DNA (27%). This is in accordance with a damage recognition role of the XPC protein. The similar affinity of XPC for undamaged and 'bubble' DNA substrates (58% and 55%, respectively) indicates that XPC does not specifically bind to this type of DNA substrate comprising a large (30-nt) central unpaired region.     

DNA依赖的蛋白激酶抑制剂STL127705的合成工艺研究

DNA依赖的蛋白激酶（DNA-PK）是肿瘤治疗的一个潜在靶点,其抑制剂具有增强放化疗敏感性的作用。STL127705是一种有效的DNA-PK抑制剂,本文采用逆合成分析,以2-甲硫醚-4-氯嘧啶-5-基甲酸乙酯为起始原料,先后经过氨化、水解、酰胺缩合、合环、氧化、取代等6步反应制备得到目标化合物,总收率为36.8%,纯度达到95.5%,产物结构通过1H-NMR、13C-NMR、MS等表征。     

Structure based pharmacophore study to identify possible natural selective PARP-1 trapper as anti-cancer agent

Inhibition of poly(ADP-ribose) polymerase-1 (PARP-1) has turned out an innovative approach for cancer therapy due to its involvement in DNA repair pathways. Although several potent PARP-1 inhibitors have been identified, they exhibit high toxicity, resistivity and diverse pharmacological profile in clinical trials, which necessitate for extensive investigation and development of selective inhibitors. Therefore, the study aimed to identify selective natural PARP-1 inhibitors to reduce toxicity and resistivity with high potency. Accordingly, the combined approach of structure-based pharmacophore and molecular docking study was performed. Hence, the two hits (SN00167272 and STOCK1N-92279) were identified to have all the pharmacophoric features that showed interaction with key residues (Gly863, Ser904, Tyr896, and Tyr907) and least conserved residues (Tyr889 and Asp766). Additionally, these inhibitors represented interactions with unique selective residues (Asp756, Val762, Glu763 and Val886) and exhibited strong interaction with PARP-1 through binding free energy and molecular dynamics study. Hence, the identified hits could further considered for experimental investigations as they may reduce off-target and resistivity of currently available inhibitors and developed as potential anti-cancer agents in the future. Also, the study provides a specific structural insight which could further help to design selective and potent PARP-1 inhibitors.     

Ultrasound enhanced thrombolysis in acute arterial ischemia

In vitro and animal studies have shown that thrombolysis with intravenous tissue plasminogen activator (tPA) can be enhanced with ultrasound. Ultrasound delivers mechanical pressure waves to the clot, thus exposing more thrombus surface to circulating drug. Moreover, intravenous gaseous microspheres with ultrasound have been shown to be a potential alternative to fibrinolytic agents to recanalize discrete peripheral thrombotic arterial occlusions or acute arteriovenous graft thromboses. Small phase I-II randomized and non-randomized clinical trials have shown promising results concerning the potential applications of ultrasound-enhanced thrombolysis in the setting of acute cerebral ischemia. CLOTBUST was an international four-center phase II trial, which demonstrated that, in patients with acute ischemic stroke, transcranial Doppler (TCD) monitoring augments tPA-induced arterial recanalization (sustained complete recanalization rates: 38% vs. 13%) with a non-significant trend toward an increased rate of clinical recovery from stroke, as compared with placebo. The rates of symptomatic intracerebral hemorrhage (sICH) were similar in the active and placebo group (4.8% vs. 4.8%). Smaller single-center clinical trials using transcranial color-coded sonography (TCCD) reported recanalization rates ranging from 27% to 64% and sICH rates of 0-18%. A separate clinical trial evaluating the safety and efficacy of therapeutic low-frequency ultrasound was discontinued because of a concerning sICH rate of 36% in the active group. To further enhance the ability of tPA to break up thrombi, current ongoing clinical trials include phase II studies of a single beam 2 MHz TCD with perflutren-lipid microspheres. Moreover, potential enhancement of intra-arterial tPA delivery is being clinically tested with 1.7-2.1 MHz pulsed wave ultrasound (EKOS catheter) in ongoing phase II-III clinical trials. Intravenous platelet-targeted microbubbles with low-frequency ultrasound are currently investigated as a rapid noninvasive technique to identify thrombosed intracranial and peripheral vessels. Multi-national dose escalation studies of microspheres and the development of an operator independent ultrasound device are underway.