\u3csup\u3e99m\u3c/sup\u3eTc-Labeled C2A Domain of Synaptotagmin I as a Target-Specific Molecular Probe for Noninvasive Imaging of Acute Myocardial Infarction

Abstract: The exposure of phosphatidylserine (PtdS) is a common molecular marker for both apoptosis and necrosis and enables the simultaneous detection of these distinct modes of cell death. Our aim was to develop a radiotracer based on the PtdS-binding activity of the C2A domain of synaptotagmin I and assess 99mTc-C2A-GST (GST is glutathione S-transferase) using a reperfused acute myocardial infarction (AMI) rat model. Methods: The binding of C2A-GST toward apoptosis and necrosis was validated in vitro. After labeling with 99mTc via 2-iminothiolane thiolation, radiochemical purity and radiostability were tested. Pharmacokinetics and biodistribution were studied in healthy rats. The uptake of 99mTc-C2A-GST within the area at risk was quantified by direct γ-counting, whereas nonspecific accumulation was estimated using inactivated 99mTc-C2A-GST. In vivo planar imaging of AMI in rats was performed on a γ-camera using a parallel-hole collimator. Radioactivity uptake was investigated by region-of-interest analysis, and postmortem tetrazolium staining versus autoradiography. Results: Fluorescently labeled and radiolabeled C2A-GST bound both apoptotic and necrotic cells. 99mTc-C2A-GST had a radiochemical purity of \u3e98% and remained stable. After intravenous injection, the uptake in the liver and kidneys was significant. For 99mTc-C2A-GST, radioactivity uptake in the area at risk reached between 2.40 and 2.63 %ID/g (%ID/g is percentage injected dose per gram) within 30 min and remained plateaued for at least 3 h. In comparison, with the inactivated tracer the radioactivity reached 1.06 ± 0.49 %ID/g at 30 min, followed by washout to 0.52 ± 0.23 %ID/g. In 7 of 7 rats, the infarct was clearly identifiable as focal uptake in planar images. At 3 h after injection, the infarct-to-lung ratios were 2.48 ± 0.27, 1.29 ± 0.09, and 1.46 ± 0.04 for acute-infarct rats with 99mTc-C2A-GST, sham-operated rats with 99mTc-C2A-GST, and acute-infarct rats with 99mTc-C2A-GST-NHS (NHS is N-hydroxy succinimide), respectively. The distribution of radioactivity was confirmed by autoradiography and histology. Conclusion: The C2A domain of synaptotagmin I labeled with fluorochromes or a radioisotope binds to both apoptotic and necrotic cells. Ex vivo and in vivo data indicate that, because of elevated vascular permeability, both specific binding and passive leakage contribute to the accumulation of the radiotracer in the area at risk. However, the latter component alone is insufficient to achieve detectable target-to-background ratios with in vivo planar imaging

Sex-related difference in food-anticipatory activity of mice

The expression of food-anticipatory activity (FAA) is induced by restricted feeding (RF), and its entrainment requires food-entrainable oscillators, the neuroanatomical basis of which is currently unclear. Although RF impacts various hormones, sex-related differences in FAA are unclear. 'Here, we report significantly more food-anticipatory wheel-running activity in male than in female mice during RF. In parallel with the sex-related difference in FAA, male and female mice display different food intake and body weight in response to RF. Since gonadal hormones could be involved in the sex-specific difference in FAA, we compared sham and gonadectomized male and female wild-type mice. In gonadectomized mice, the sex difference in FAA was abolished, indicating a role for gonadal hormones in FAA. Further, plasma concentrations of the hormone ghrelin were higher in female than in male mice during ad libitum (AL) feeding, and RF induced a temporal advance in its peak in both sexes. RF also shifted the expression peak of the circadian gene mPer1 in the hippocampus and liver, although no sex difference was found in either the level or the cyclic phase of its expression. Per1(Brdm1) mutant mice were still sexually dimorphic for FAA, but diminished FAA was noted in both male and female Per2(Brdm1) mutant mice. In summary, our results imply that gonadal hormones contribute to the sex difference in FAA, possibly through modulating ghrelin activity. (C) 2015 Published by Elsevier Inc

Clinical study on the feasibility of new thrombus markers in predicting massive cerebral infarction

ObjectiveThis study investigated the diagnostic performance of the thrombin-antithrombin complex (TAT), plasmin-α2 plasmin inhibitor complex (PIC), tissue plasminogen activator-plasminogen activator inhibitor complex (t-PAIC), and thrombomodulin (TM) in the early identification of massive cerebral infarction.MethodA total of 423 patients with cerebral infarction confirmed by imaging examination were divided into the massive cerebral infarction (MCI) group and the non-massive cerebral infarction (NMCI) group. TAT, PIC, t-PAIC, and TM were measured immediately after admission. The diagnostic performance was analyzed by the receiver characteristic operating curve (ROC).ResultThe median plasma concentrations of TAT, PIC, and t-PAIC in patients with MCI at early onset were 5.10 ng/ml, 1.11 μg/ml, and 8.80 ng/ml, respectively, which were higher than those in patients with NMCI (2.20 ng/ml, 0.59 μg/ml, and 7.35 ng/ml), and the difference was statistically significant (P < 0.001). TAT was shown to be an independent risk factor for the development of massive cerebral infarction by a multivariate logistic regression analysis (OR = 1.138). A ROC curve analysis showed that PIC had the best performance in identifying MCI at an early stage (AUC = 82.8%), with a sensitivity of 80.7% and a specificity of 76.2% when the PIC concentration was ≥0.8 μg/ml; TAT had the highest specificity in identifying MCI, with a specificity of 80.6% when the TAT concentration was ≥3.97 ng/ml.ConclusionThe detection of PIC, TAT, t-PAIC, and TM is a comprehensive assessment of vascular endothelial damage and activation of the coagulation and fibrinolytic systems and has diagnostic value for early identification of patients with MCI, which, together with its ease of detection, can be used as a plasma marker for early identification of large vessel occlusion

Robust factorization machine: A doubly capped norms minimization

National Research Foundation (NRF) Singapor

Research on Minimization of Data Set for State of Charge Prediction

The quick estimation and prediction of lithium-ion batteries’ (LIBs) state of charge (SoC) are attracting growing attention, since the LIB has become one of the most essential power sources for daily consumer electronics. Most deep learning methods require plenty of data and more than two LIB parameters to train the model for predicting SoC. In this paper, a single-parameter SoC prediction based on deep learning is realized by cleaning the data for lithium-ion battery parameters and constructing the feature matrix based on the cleaned data. Then, by analyzing the feature matrix’s periodicity and principal component to obtain two kinds of the original eigenmatrix’s substitution matrices, the two substitutions are fused to obtain an excellent prediction effect. In the end, the minimization method is verified with newly measured lithium battery data, and the results show that the MAPE of the SoC prediction reaches 0.96%, the input data are reduced by 93.33%, and the training time is reduced by 96.68%. Fast and accurate prediction of the SoC is achieved by using only a minimum amount of voltage data

The inheritance of acquired trait and epigenetic mechanism

Environmental cues during early development can exert transgenerational effects on brain function and behavior through epigenetic regulation.However,the function of histone modifications in mammalian phenotypic inheritance remains largely unknown.Here,we report that gestational choline supplementation(GCS)in maternal mice exerted anxiolytic effects on male offspring across two generations.</p

Design optimization of PVDF-based piezoelectric energy harvesters

Energy harvesting is a promising technology that powers the electronic devices via scavenging the ambient energy. Piezoelectric energy harvesters have attracted considerable interest for their high conversion efficiency and easy fabrication in minimized sensors and transducers. To improve the output capability of energy harvesters, properties of piezoelectric materials is an influential factor, but the potential of the material is less likely to be fully exploited without an optimized configuration. In this paper, an optimization strategy for PVDF-based cantilever-type energy harvesters is proposed to achieve the highest output power density with the given frequency and acceleration of the vibration source. It is shown that the maximum power output density only depends on the maximum allowable stress of the beam and the working frequency of the device, and these two factors can be obtained by adjusting the geometry of piezoelectric layers. The strategy is validated by coupled finite-element-circuit simulation and a practical device. The fabricated device within a volume of 13.1 mm3 shows an output power of 112.8 μW which is comparable to that of the best-performing piezoceramic-based energy harvesters within the similar volume reported so far

Modeling of Ship DC Power Grid and Research on Secondary Control Strategy

Compared to alternating current (AC) grids, direct current (DC) grids are becoming more and more popular. A power distribution approach is suggested in order to solve the issue of uneven power distribution of distributed generation (DG) in a ship DC microgrid. Power control is carried out using a tracking differentiator (TD), while the output power change rate is not greater than the maximum power ramp rate permitted by the battery, and state-of-charge balance is attained quickly. The proposed strategy also reduces the communication pressure on the power grid. A distributed hierarchical control model of a DC microgrid based on a consensus algorithm is created in order to validate the suggested methodology. The simulation results demonstrate that the established model is capable of simulating the DC microgrid accurately, that the states of charge values of the five batteries gradually converge under the adjustment of the secondary strategy, and that the suggested strategy is reasonable and efficient

Robust Model-Free Fault-Tolerant Predictive Control for PMSM Drive System

The parameter mismatch caused by the parameter uncertainties and unknown disturbances degrades the performance of finite-control-set model predictive control (FCS-MPC). This paper presents a model-free fault-tolerant predictive control (MFFTPC) method based on an extended sliding mode observer (ESMO) for the surface-mounted permanent magnet synchronous motor (SPMSM) drive system. First, considering parameter uncertainties and unknown disturbances, a novel ultra-local model (ULM) is established for the PMSM drive system. Next, a finite-control-set model-free fault-tolerant predictive current controller (FCS-MFFTPCC) is designed in the current loop, and the model-free deadbeat fault-tolerant predictive speed controller (MFDFTPSC) is designed in the speed loop. Then, unknown parts of the novel ULM are estimated by the designed ESMO and compensated for the errors caused by the parameter mismatches. Thus, the presented method reduces the dependence on the precise model and eliminates the effect caused by parameter mismatches on the MPC control performance of the SPMSM drive system