Predictive temperature control design for reaction calorimeter based on mechanism parameter model.

Isothermal control is the most basic and crucial function in the principle of a reaction calorimeter system and affects the speed and validity of the calorimetric experiment. However, the complex and uncertain working conditions in different reaction processes pose a challenge to the adaptability of temperature control algorithms. Aiming at the problem, a heat transfer model of the system is first established for temperature control design. From the simulation results, a prediction model based on equivalent mechanism parameters is determined for the control. Then, an integrated model predictive control (MPC) strategy is presented. To reduce the influence on the temperature control caused by the mismatch of the prediction model, a set of online parameter identification and adjustment methods is proposed. Simulations of the MPC control were implemented to analyze the control's performance. Experiments were also carried out to verify the advantages of the proposed strategy over the proportional-integral-derivative algorithm and demonstrate the role and efficiency of online identification. This control strategy can be applied to other laboratory-scale instruments with tank reactors.

A millikelvin precision temperature control system designed for a low cost, portable and variable temperature blackbody from 298.15 to 693.15 K.

Millikelvin precision portable variable temperature blackbody from 298.15 to 693.15 K is very important in the on-site calibration of infrared measuring instruments. The stability of the blackbody temperature directly affects the calibration quality. However, the temperature measurement and control system is the key component to guarantee the stability of the blackbody temperature. In this article, a measurement and control system of the low-cost and portable blackbody was designed and verified. A Pt100 platinum resistance thermometer was employed to measure the temperature of the blackbody radiation source. Based on the round-robin structure and current reversing technology, the precision of the temperature measurement achieved a sub-millikelvin level. To overcome the drawbacks that traditional proportional integral derivative (PID) controller would lead to large overshoot and long adjustment time during the temperature control of the large thermal inertia blackbody, a feedforward and segmented PID controller was introduced to improve the dynamic performance of the blackbody radiation source. The experimental results showed that the precision of the temperature measurement at 0.5 Hz was better than 0.5 mK and the temperature stability within 10 min was better than 3 mK in the temperature range from 298.15 to 693.15 K. Hence, the millikelvin precision measurement and control system has a strong prospect for practical application in high-performance blackbody development.

Correction of nonlinearities in series structure-based resistance thermometry readouts.

Series structure-based resistance thermometry readouts offer several advantages for multi-point temperature measurements. However, because of the diversity of nonlinear error sources and differences among channels in such readouts, existing nonlinear error correction methods are ineffective. In view of this situation, a nonlinear error correction method based on error source analysis is proposed. The proposed method first determines the impacts of error sources by analyzing the circuit architecture. The contributions of the common-mode rejection ratio and the mismatch between positive and opposite exciting currents are then eliminated using resistance bridge calibrators. Finally, the residuals are fitted to various polynomial functions. The results of experiments show that correction based on the proposed method results in a maximum nonlinear readout error of 1.87 × 10-5, compared with 4.01 × 10-5 using the classical method. Thus, the proposed method of nonlinear error correction is effective for series structure-based resistance thermometry readout.

Effects of Commemorations and Postdonation Services on Public Willingness to Donate Bodies in China.

Multiple body donation programs have been established throughout China over the last 20 years, but these programs remain challenged by an insufficient supply of cadavers for medical education. The commemoration of body donors is a feature of many successful programs, and adopting this practice throughout the country could be an important element of raising public awareness and encouraging body donation among the public. The present study aimed to investigate public views on the commemoration of whole-body donors and postdonation services in China by analyzing the factors that influence participants' willingness to donate. A survey was conducted using convenience sampling with a non-probability sampling method, and data were analyzed using chi-square and post hoc multiple comparisons tests. A total of 1,800 questionnaires were distributed, 1,717 were returned, and 1,605 were considered valid. Of the respondents, 20.87% were willing to donate, and 64.80% thought that it is necessary to commemorate donors. The results of multiple comparisons demonstrated that the elderly and those with a higher educational level were more willing to donate than participants in other groups. Education was also found to influence views on donation memorial activities, and the chi-square test revealed that conducting commemorations and improving postdonation services can promote the establishment of successful donor programs in China and improve the social acceptance of body donation.

Fibroblast growth factors stimulate hair growth through ß-catenin and Shh expression in C57BL/6 mice.

Growth factors are involved in the regulation of hair morphogenesis and cycle hair growth. The present study sought to investigate the hair growth promoting activities of three approved growth factor drugs, fibroblast growth factor 10 (FGF-10), acidic fibroblast growth factor (FGF-1), and basic fibroblast growth factor (FGF-2), and the mechanism of action. We observed that FGFs promoted hair growth by inducing the anagen phase in telogenic C57BL/6 mice. Specifically, the histomorphometric analysis data indicates that topical application of FGFs induced an earlier anagen phase and prolonged the mature anagen phase, in contrast to the control group. Moreover, the immunohistochemical analysis reveals earlier induction of ß-catenin and Sonic hedgehog (Shh) in hair follicles of the FGFs-treated group. These results suggest that FGFs promote hair growth by inducing the anagen phase in resting hair follicles and might be a potential hair growth-promoting agent.

Administration of exogenous 1,25(OH)2D3 normalizes overactivation of the central renin-angiotensin system in 1α(OH)ase knockout mice.

Previously, we reported that active vitamin D deficiency in mice causes secondary hypertension and cardiac dysfunction, but the underlying mechanism remains largely unknown. To clarify whether exogenous active vitamin D rescues hypertension by normalizing the altered central renin-angiotensin system (RAS) via an antioxidative stress mechanism, 1-alpha-hydroxylase [1α(OH)ase] knockout mice [1α(OH)ase(-/-)] and their wild-type littermates were fed a normal diet alone or with 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], or a high-calcium, high-phosphorus "rescue" diet with or without antioxidant N-acetyl-l-cysteine (NAC) supplementation for 4 weeks. Compared with their wild-type littermates, 1α(OH)ase(-/-)mice had high mean arterial pressure, increased levels of renin, angiotensin II (Ang II), and Ang II type 1 receptor, and increased malondialdehyde levels, but decreased anti-peroxiredoxin I and IV proteins and the antioxidative genes glutathione reductase (Gsr) and glutathione peroxidase 4 (Gpx4) in the brain samples. Except Ang II type 1 receptor, these pathophysiological changes were rescued by exogenous 1,25(OH)2D3 or NAC plus rescue diet, but not by rescue diet alone. We conclude that 1,25(OH)2D3 normalizes the altered central RAS in 1α(OH)ase(-/-)mice, at least partially, through a central antioxidative mechanism.

Recombinant keratinocyte growth factor 1 in tobacco potentially promotes wound healing in diabetic rats.

Keratinocyte growth factor 1 (KGF1) is a growth factor that promotes epidermal cell proliferation, migration, differentiation, and wound repair. It is expressed at low levels in a form of inclusion body in E. coli. In order to increase its expression and activity, we produced tobacco plants expressing KGF1 via Agrobacterium-mediated transformation using a potato virus X (PVX)-based vector (pgR107). The vector contained the sequence encoding the KGF1 gene fused with a green florescence protein. The recombinant plasmid was introduced into leaf cells of Nicotiana benthamiana (a wild Australian tobacco) via Agrobacterium-mediated agroinfiltration. As determined by fluorescence and Western blot of leaf extracts, the KGF1 gene was correctly translated into the tobacco plants. The recombinant KGF1 was purified from plant tissues by heparin affinity chromatography, and cell proliferation in NIH/3T3 cells was stimulated by the purified KGF1. The purified KGF1 was also applied to the wounds of type-II diabetic rats. KGF1 had accumulated to levels as high as 530 µ g/g fresh weight in the leaves of agroinfected plants. We show that plant-derived KGF1 can promote the proliferation of NIH/3T3 cells and have significant effects on the type-II diabetic rat. The present findings indicated that KGF1 from tobacco maintains its biological activity, implying prospective industrial production in a plant bioreactor.

Heterozygous knockout of the Bmi-1 gene causes an early onset of phenotypes associated with brain aging.

Previous studies reported that the polycomb group gene Bmi-1 is downregulated in the aging brain. The aim of this study was to investigate whether decreased Bmi-1 expression accelerates brain aging by analyzing the brain phenotype of adult Bmi-1 heterozygous knockout (Bmi-1(+/-)) mice. An 8-month-old Bmi-1(+/-) brains demonstrated mild oxidative stress, revealed by significant increases in hydroxy radical and nitrotyrosine, and nonsignificant increases in reactive oxygen species and malonaldehyde compared with the wild-type littermates. Bmi-1(+/-) hippocampus had high apoptotic percentage and lipofuscin deposition in pyramidal neurons associated with upregulation of cyclin-dependent kinase inhibitors p19, p27, and p53 and downregulation of anti-apoptotic protein Bcl-2. Mild activation of astrocytes was also observed in Bmi-1(+/-) hippocampus. Furthermore, Bmi-1(+/-) mice showed mild spatial memory impairment in the Morris Water Maze test. These results demonstrate that heterozygous Bmi-1 gene knockout causes an early onset of age-related brain changes, suggesting that Bmi-1 has a role in regulating brain aging.

An overview of the roles and responsibilities of Chinese medical colleges in body donation programs.

The use of human tissue is critical for gross anatomy education in the health professions. Chinese medical colleges have faced a shortage of anatomical specimens over the past decade. While body donation plays an important role in overcoming this gap, this practice has only recently been introduced in China, and the donation rate is relatively low and fraught with a number of difficulties. In the past, traditional Chinese culture focused on preserving the human body intact, which often limited body donation. In recent years, the public has become more open toward body donation. At Nanjing Medical University, only 20 bodies were donated in 2001. After the university became involved in an organized body donation program, this number increased to 70 donated bodies per year (2007 to 2012). This article describes and reviews Chinese medical colleges as a special case study among body donation programs, particularly in terms of the multiple responsibilities and roles that such institutions must assume in the course of adopting these programs. Medical colleges in China must serve as advocates, coordinators, builders, managers, educators, and beneficiaries in undertaking body donation programs. It is important for medical colleges to recognize these pluripotent roles and educate the public in order to promote body donation programs. This case study may also effectively guide and encourage Chinese medical colleges in refining their own body donation programs in the future.

Aerobic exercise combined with antioxidative treatment does not counteract moderate- or mid-stage Alzheimer-like pathophysiology of APP/PS1 mice.

AIMS: The present study evaluated the combined treatment effects of aerobic exercise and antioxidative stress on moderate-stage Alzheimer's disease (AD). METHODS: Ten-month-old APP/PS1 mice were given antioxidative treatment with acetylcysteine, along with aerobic exercise for 6 weeks. Spatial learning and memory were tested using the Morris water maze, and ß-amyloid (Aß) plaque deposits in the forebrain were quantified by Thioflavin-S staining. Levels of soluble Aß1-42, ß-secretase enzyme, Ò¯-secretase enzyme, oxidative and antioxidant stress markers nitrotyrosine and peroxiredoxin-1, glial markers glial fibrillary acidic protein and ionized calcium-binding adaptor molecule 1, and synaptic protein synaptophysin in the hippocampus were all measured by western blotting and/or immunohistochemistry. RESULTS: APP/PS1 mice showed severe declines in spatial learning and memory compared with their wild-type littermates, which were not attenuated by aerobic exercise combined with antioxidative treatment. The pathologic analysis revealed that Aß deposition and production, oxidative stress, glial inflammation, and synaptic loss were not mitigated in the brain of exercised APP/PS1 mice, compared with the sedentary APP/PS1 animals. CONCLUSION: This study reveals that a combined treatment of aerobic exercise plus antioxidative stress does not counteract pathophysiology in the moderate- or mid-stages of AD.

Calcium sensing receptor absence delays postnatal brain development via direct and indirect mechanisms.

Calcium sensing receptor (CaSR) is implicated in the establishment of neural connections and myelin formation. However, its contribution to brain development remains unclear. We addressed this issue by analyzing brain phenotype in postnatal CaSR null mice, a model of human neonatal severe hyperparathyroidism. One- and 2-week-old CaSR null mice exhibited decreased brain weight and size with a developmental delay in expression of proliferating cell nuclear antigen. Neuronal and glial differentiation markers, neuronal specific nuclear protein, glial fibrillary acidic protein, and myelin basic protein, were also decreased compared with age-matched wild-type littermates. Moreover, deletion of the parathyroid hormone gene that corrects hyperparathyroidism, hypercalcemia, hypophosphatemia, and whole-body growth retardation normalized brain cell proliferation, but not differentiation, in CaSR null mice. Cultured neural stem cells (NSCs) derived from the subventricular zones of CaSR null neonatal mice exhibited normal proliferation capacity but decreased differentiation capacity, compared with wild-type controls. These results demonstrate that direct effects of CaSR absence impair NSC differentiation, while secondary effects of parathyroid hormone-related endocrine abnormalities impair NSC proliferation, both of which contribute to delayed brain development in CaSR null newborn mice.

Aquaporin-4 expression contributes to decreases in brain water content during mouse postnatal development.

The water channel protein aquaporin-4 (AQP4) is implicated to facilitate water efflux from the brain parenchyma into the blood and CSF, playing a critical role in maintaining brain water homeostasis. Nevertheless, its contribution to decreases in brain water content during postnatal development remains unknown. A quantitative Western blot analysis was performed to investigate developmental expression of AQP4 in the whole mouse brain and showed that AQP4 expression level in 1 week-old brain was only 21.3% of that in the adult brain, but significantly increased to 67.4% of the adult level by 2 weeks after birth. Statistical analysis demonstrated that increased AQP4 expression partially relates to decreased brain water content in postnatal mice (r(2)=0.92 and P=0.002). Moreover, AQP4 null mice had greater brain water content than littermate controls from 2 weeks up to adult age. Consistently, mature pattern of AQP4 localization at the brain-blood and brain-CSF interfaces were completed at approximately at 2 weeks after birth. In addition, AQP4 expression in the brain stem and hypothalamus was earlier than that in the cerebral cortex and cerebellum, suggesting a brain regional variation in developmental expression of AQP4. These results characterize the developmental feature of AQP4 expression in the postnatal brain and provide direct evidence for a role of AQP4 in postnatal brain water uptake.

Prenatal ethanol exposure does not cause neurological alterations in adult CD1 mice.

Genetic factors are involved in variation in fetal alcohol spectrum disorders (FASD), which is also observed among various inbred mouse strains. The CD1 mouse strain is often used in toxicological and genetic experiments. However, there is little literature using this strain to study long-term neurologic abnormalities of FASD. In the present study, we addressed the effect of prenatal ethanol exposure on neurological alterations in adult CD1 mice. The female CD1 mice received exposure to ethanol solution (10 vol%) starting from 2 weeks before mating up to pups born (postnatal day 1). At 24 weeks after the birth, the prenatal ethanol-exposed mice and control mice showed no difference in spatial learning and memory performance in a Morris water maze. Consistently, pathological changes, such as increased neuronal apoptosis, decreased synaptic protein synaptophysin expression, synaptic loss and reactive astrogliosis, were not observed in the hippocampus of mice prenatally exposed to ethanol. These results suggest that CD1 mice are highly resistant to prenatal alcohol exposure and may serve as genetic modification models of FASD.

Cellular localization of aquaporin-1 in the human and mouse trigeminal systems.

Previous studies reported that a subpopulation of mouse and rat trigeminal neurons express water channel aquaporin-1 (AQP1). In this study we make a comparative investigation of AQP1 localization in the human and mouse trigeminal systems. Immunohistochemistry and immunofluorescence results showed that AQP1 was localized to the cytoplasm and cell membrane of some medium and small-sized trigeminal neurons. Additionally, AQP1 was found in numerous peripheral trigeminal axons of humans and mice. In the central trigeminal root and brain stem, AQP1 was specifically expressed in astrocytes of humans, but was restricted to nerve fibers within the central trigeminal root and spinal trigeminal tract and nucleus in mice. Furthermore, AQP1 positive nerve fibers were present in the mucosal and submucosal layers of human and mouse oral tissues, but not in the muscular and subcutaneous layers. Fluorogold retrograde tracing demonstrated that AQP1 positive trigeminal neurons innervate the mucosa but not skin of cheek. These results reveal there are similarities and differences in the cellular localization of AQP1 between the human and mouse trigeminal systems. Selective expression of AQP1 in the trigeminal neurons innervating the oral mucosa indicates an involvement of AQP1 in oral sensory transduction.

Aquaporin-4 mediates astrocyte response to ß-amyloid.

It has been demonstrated that the water channel protein aquaporin-4 (AQP4) plays an important role in astrocyte plasticity in response to a variety of injuries or stimuli. However, the potential role of AQP4 in astrocyte response to ß-amyloid (Aß) has not been studied. The purpose of this study was to investigate this issue. Compared to media control, the lower concentrations of Aß(1-42) (0.1-1 µM) increased AQP4 expression in cultured mouse cortical astrocytes, while the higher concentrations of Aß(1-42) (10 µM) decreased AQP4 expression. AQP4 gene knockout reduced Aß(1-42)-induced astrocyte activation and apoptosis, which was associated with a reduction in the uptake of Aß via decreased upregulation of low-density lipoprotein receptor related protein-1. Moreover, time-course and levels of Aß(1-42)-induced mitogen-activated protein kinase phosphorylation were altered in AQP4 null astrocytes compared with wild-type controls. Our data reveal a novel role of AQP4 in the uptake of Aß by astrocytes, indicating that AQP4 is a molecular target for Alzheimer's disease.

Bmi-1 absence causes premature brain degeneration.

Bmi-1, a polycomb transcriptional repressor, is implicated in cell cycle regulation and cell senescence. Its absence results in generalized astrogliosis and epilepsy during the postnatal development, but the underlying mechanisms are poorly understood. Here, we demonstrate the occurrence of oxidative stress in the brain of four-week-old Bmi-1 null mice. The mice showed various hallmarks of neurodegeneration including synaptic loss, axonal demyelination, reactive gliosis and brain mitochondrial damage. Moreover, astroglial glutamate transporters and glutamine synthetase decreased in the Bmi-1 null hippocampus, which might contribute to the sporadic epileptic-like seizures in these mice. These results indicate that Bmi-1 is required for maintaining endogenous antioxidant defenses in the brain, and its absence subsequently causes premature brain degeneration.

A high cholesterol diet ameliorates hippocampus-related cognitive and pathological deficits in ovariectomized mice.

Both sex hormone deficiency and hypercholesterolemia are related to cognitive decline or Alzheimer's disease. However, their interactive influence on the neurodegenerative progress is not clear. This study was designed to assess the effects of ovarian hormone depletion and high cholesterol diet alone or in combination on hippocampus-related cognitive and pathological deficits in adult female ICR mice. Depletion of ovarian hormones by ovariectomy for 9 weeks resulted in significant spatial learning and memory deficits as revealed by the water maze testing. Such cognitive alteration was accompanied with increases in neuron death and decreases in choline acetyltransferase activity and synaptopysin expression in the hippocampus. On the other hand, the high cholesterol diet (3% cholesterol plus normal chow) did not exacerbate, but slightly alleviated cognitive decline and significantly attenuated hippocampal pathological changes in ovariectomized mice. Moreover, ovariectomized mice fed high cholesterol had increased serum estrogen levels compared with those fed a normal chow. These results indicate that high cholesterol intake increases the sex hormone synthesis and in turn partially attenuates hippocampus-related cognitive and pathological deficits caused by ovariectomy.

Aquaporin-4 deficiency exacerbates brain oxidative damage and memory deficits induced by long-term ovarian hormone deprivation and D-galactose injection.

Astrocyte dysfunction is implicated in pathogenesis of certain neurological disorders including Alzheimer's disease (AD). A growing body of evidence indicates that water channel aquaporin-4 (AQP4) is a potential molecular target for the regulation astrocyte function. Recently, we reported that AQP4 expression was increased in the hippocampus of an AD mouse model established by long-term ovarian hormone deprivation combined with D-galactose (D-gal) exposure. However, pathophysiological roles and mechanisms of AQP4 up-regulation remain unclear. To address this issue, age-matched female wild-type and AQP4 null mice underwent ovariectomy, followed by D-gal administration for 8 wk. AQP4 null mice showed more severe brain oxidative stress, spatial learning and memory deficits, and basal forebrain cholinergic impairment than the wild-type controls. Notably, AQP4 null hippocampus contained more prominent amyloid-ß production and loss of synapse-related proteins. These results suggested that ovariectomy and D-gal injection induced oxidative damage results in compensatory increases of AQP4 expression, and deficiency of AQP4 exacerbates brain oxidative stress and memory deficits. Therefore, regulation of astrocyte function by AQP4 may attenuate oxidative damage, offering a promising therapeutic strategy for AD.

Astrocyte activation but not neuronal impairment occurs in the hippocampus of mice after 2 weeks of d-galactose exposure.

AIMS: The objective of this study is to prove that activation of astrocytes precedes neuron cell death in the neurodegenerative process induced by d-galactose (d-gal) exposure. MAIN METHODS: Male adult mice were given intraperitoneal injection of d-gal (200 mg/kg per day) for 2 weeks. The whole brain homogenate and hippocampal sections were then prepared for biochemical analyses, immunohistochemistry and electron microscopy, respectively. KEY FINDINGS: There were no statistically significant differences in brain oxidative and antioxidative parameters between d-gal-treated mice and saline controls. There was also lack of morphological impairment in hippocampal neuronal soma, dendrites and synapses in the model mice. In contrast, hippocampal astrocytes were dramatically activated, and perisynaptic processes of astrocytes were swelling as revealed by ultrastructural analysis. Moreover, d-gal-treated group showed increases in immunostaining levels of glutamate transporter-1 and aquaporin-4 in the hippocampus, which might increase uptake of glutamate from the synaptic cleft into astrocytes. SIGNIFICANCE: These results reveal that astrocytes undergo structural and biochemical changes while no impairment of neuronal elements occurs after 2 weeks of d-gal exposure. Thus, targeting astrocytes may be a promising strategy for the treatment of neurodegenerative diseases at the early stages.

Pretraining affects Morris water maze performance with different patterns between control and ovariectomized plus D-galactose-injected mice.

There is little literature addressing the influences of the repeated Morris water maze (MWM) test on behavioral performance under physiological and neurodegenerative conditions. The results revealed that pretraining had distinctively different effects on MWM performances of vehicle control mice and Alzheimer's disease model mice induced by ovariectomy plus injection of D-galactose after an 8-w interval. This interference effect should be considered during analyzing behavioral outcomes using repeated MWM tests.