Thermal shock fracture behavior of wave-transparent brittle materials in hypersonic vehicles under high thermal flux by digital image correlation.

During diving, high orbit maneuver, or target detection and positioning, a hypersonic vehicle will experience high thermal flux. Aerodynamic heating will cause intense thermal shock to the antenna window and radar dome, which are usually made of brittle materials that are transparent to electromagnetic waves and are critical to the mission of target positioning and hitting. Therefore, determination of the time to fracture of the brittle materials under high thermal flux is of great significance. In this study, thermal shock tests were performed on two brittle materials, i.e., SiO2 and Al2O3, using a quartz lamp radiator test system with a maximum thermal flux of 1.5MW/m2. The difference between the pre-set and actual thermal fluxes for the tests was smaller than 1.0%. The time to fracture was determined for the two brittle materials by employing the digital image correlation method to capture and analyze changes in speckle images of the specimen's surface. The speckle image analysis also revealed variations in the surface strain values (εx and εy) prior to fracture. The test results provide important input for the safety and reliability design of radar domes and other electromagnetic wave-transparent signal detection and positioning components of hypersonic vehicles when subjected to high thermal fluxes.

Accurate ex situ deformation measurement using an ultra-stable two-dimensional digital image correlation system.

In situ planar deformation measurement using two-dimensional digital image correlation (2D-DIC) and a fixed camera has been fully investigated in many published works and widely used for various applications. However, in certain special cases (e.g., long-term deformation monitoring of engineering structures, or deformation measurement of a specimen subjected to uncommon loading), it is very difficult or impossible to carry out in situ deformation measurement using 2D-DIC, and necessitates ex situ 2D-DIC measurements for a repositioned specimen or using a relocated camera. To achieve accurate measurements, the error sources of ex situ 2D-DIC measurements should be identified and minimized, and the strain accuracy of ex situ 2D-DIC measurements should be quantified. In this work, the potential error sources of ex situ 2D-DIC measurements are first discussed in detail. Then, to mitigate the errors associated with these issues, an ultra-stable 2D-DIC system combining the idea of active imaging and a well-designed bilateral telecentric lens is established, which is invariant to the potential variations in ambient lighting and the possible small out-of-plane motions in object surface and/or image plane. The established ultra-stable 2D-DIC system is first compared with the regular 2D-DIC setup in determining the surface strains of an unstrained sample. Then, ex situ residual stress measurement using the hole-drilling technique and the established 2D-DIC system was conducted and compared with the applied ones. The results of this work confirm that the accuracy of ex situ 2D-DIC deformation measurements using the proposed system is of high fidelity, and can be used for accurate deformation measurement in practical ex situ tests.

Analysis of Characteristics and Driving Mechanisms of Non-Grain Production of Cropland in Mountainous Areas at the Plot Scale-A Case Study of Lechang City.

With the continuous advancement of urbanization and industrialization, non-grain production on cropland (NGPCL) is gradually becoming more widespread. This phenomenon will compress the space for grain production and trigger a global food crisis. How to scientifically understand and effectively control NGPCL has become a scientific issue. This study, conducted at the plot scale, establishes a measurement index for NGPCL and further explores the characteristics and driving mechanisms of NGPCL in mountainous areas. The results indicate the following: (1) Compared to plots for food-growing, plots for non-grain production tend to be more dispersed, with terraces showing the most significant dispersion, while plains exhibit the highest degree of aggregation. (2) In terms of irrigation conditions, irrigated land and dry land are more likely to undergo NGPCL. In terms of topography, slope croplands have the highest probability of being used for NGPCL. (3) Regions with steeper slopes, higher elevations, greater differences in altitude from the settlement, farther distances from settlements and roads, yet closer proximity to forests, are more likely to engage in NGPCL. (4) Different plot characteristics have varying impacts on NGPCL. Plot characteristics primarily affect the costs and returns of grain production, driving farmers to change their production patterns and triggering NGPCL.

Lower serum branched-chain amino acid catabolic intermediates are predictive signatures specific to patients with diabetic foot.

Diabetic foot (DF) is one of the serious chronic complications of diabetes. Accurate prediction of the risk of DF may take timely intervention measures to prevent its occurrence. The understanding of metabolomic changes in the progression of diabetes to DF may reveal new targets for interventions. We hypothesized that changes in metabolic pathways during DF would lead to changes in the metabolic profile, which could be predictive signature specific to it. In the present study, 43 participants with type 2 diabetes mellitus (T2DM), 32 T2DM participants with DF (T2DM-F), and 36 healthy subjects were enrolled and their serum samples were used for targeted and nonpolar metabolic analysis with liquid chromatography-tandem mass spectrometry. Differential metabolites related to T2DM-F were discovered in metabolomic analysis. Lasso machine learning regression model, random forest algorithm, causal mediation analysis, disease risk assessment, and clinical decision model were carried out. T2DM and T2DM-F groups could be distinguished with the healthy control group. The differential metabolites were all enriched in alpha-linolenic acid and linoleic acid metabolic pathways including arachidonic acid, docosapentaenoic-acid 22N-6, and docosahexaenoic-acid, which were significantly lower in the T2DM and T2DM-F groups compared with the healthy control group. The differential metabolites in T2DM-F vs T2DM groups were enriched to branched-chain amino acid (BCAA) catabolic pathways involving in methylmalonic acid, succinic acid, 3-methyl-2-oxovaleric acid, and ketoleucine, which were the BCAA catabolic intermediates and significantly lower in the T2DM-F compared with the T2DM group except for succinic acid. We reveal a new set of predictive signatures and associate the lower BCAA catabolic intermediates with the progression from T2DM to T2DM-F.

Evaluation of popular science tourism in Guangzhou HEMC based on PLS-SEM.

Science popularization is not only a prerequisite for national development, but also an effective means of enhancing citizens' personal quality. All sectors of society, represented by colleges and universities, bear the responsibility of promoting popular science. The integration of popular science and tourism in popular science tourism serves to advance both the field of popular science and the tourism industry simultaneously. The Guangzhou Higher Education Mega Center (HEMC) possesses abundant resources for science popularization and has the potential to develop popular science tourism, yet its current development in this area remains insufficient. This study utilizes Guangzhou HEMC as a case study and modifies the American Customer Satisfaction Index model by incorporating relevant questions pertaining to popular science tourism. A total of 280 valid questionnaires were collected through surveying, which were then analyzed to measure tourist satisfaction using the Tourist Satisfaction Index. The partial least squares structural equation model was employed for analysis, and on the basis of calculation results, the IPA map was constructed. The research revealed that tourists' satisfaction with popular science tourism at Guangzhou HEMC was suboptimal. Among the factors correlating to satisfaction, expectations, quality, and price are all important factors to consider when making a purchase decision; however, prioritizing expectations and quality can lead to greater satisfaction in the long run. Therefore, there is still ample room for improvement in the popular science tourism of HEMC Guangzhou. This can be achieved by intensifying publicity efforts, enhancing infrastructure, improving the quality and safety of catering services, strengthening the introduction and construction of popular science content, as well as appropriately reducing the price of popular science products and services.

Optimization of a three-dimensional digital image correlation system for deformation measurements in extreme environments.

An optimized 3D digital image correlation (3D-DIC) system using active optical imaging is developed for accurate shape and 3D deformation measurements in nonlaboratory conditions or extreme high-temperature environments. In contrast to a conventional 3D-DIC system using white or natural light illumination, the proposed active imaging 3D-DIC system is based on a combination of monochromatic lighting and bandpass filter imaging. Because the bandpass filter attached before the imaging lenses allows only the actively illuminated monochromatic light to pass through and blocks all light outside of its bandpass range, the active imaging 3D-DIC system is therefore insensitive to serious variations in ambient light in nonlaboratory environments and to the thermal radiation of hot objects in extreme high-temperature environments. Two challenging experiments that cannot be performed by a conventional 3D-DIC system were carried out to verify the robustness and accuracy of the developed active imaging 3D-DIC system. Because a much wider application range can be achieved with relatively simple and easy-to-implement improvements, the proposed active imaging 3D-DIC system is highly recommended for practical use instead of the conventional 3D-DIC system.

Evolution and Simulation of Terrestrial Ecosystem Carbon Storage and Sustainability Assessment in Karst Areas: A Case Study of Guizhou Province.

Against the background of "carbon neutrality" and sustainable development goals, it is of great significance to assess the carbon storage changes and sustainability of terrestrial ecosystems in order to maintain the coordinated sustainable development of regional ecological economies and the balance of terrestrial ecosystems. In this study, the terrestrial ecosystem carbon storage in Guizhou from 2010 to 2020 was assessed with the InVEST model. Using the PLUS model, the distribution of terrestrial ecosystem carbon storage by 2030 and 2050 was predicted. The current sustainable development level of the terrestrial ecosystem of Guizhou was evaluated after establishing an index system based on SDGs. The results showed the following: (1) From 2010 to 2020, the terrestrial ecosystem carbon storage decreased by 1106.68 × 104 Mg. The area and carbon storage of the forest and farmland ecosystems decreased while the area and carbon storage of the grassland and settlement ecosystems increased. (2) Compared with 2020, the terrestrial ecosystem carbon storage will be reduced by 4091.43 × 104 Mg by 2030. Compared with 2030, the terrestrial ecosystem carbon storage will continue to decrease by 3833.25 × 104 Mg by 2050. (3) In 2020, the average score of the sustainable development of the terrestrial ecosystem was 0.4300. Zunyi City had the highest sustainable development score of 0.6255, and Anshun had the lowest sustainable development score of 0.3236. Overall, the sustainable development of the terrestrial ecosystem of Guizhou was found to be high in the north, low in the south, high in the east, and low in the west. The sustainable regional development of the terrestrial ecosystem of Guizhou was found to be unbalanced, and the carbon storage of the terrestrial ecosystem will keep decreasing in the future. In order to improve the sustainable development capacity of the terrestrial ecosystem, the government needs to take certain measures, such as returning farmland to forests and grasslands, curbing soil erosion, and actively supervising.

Land suitability assessment for supporting transport planning based on carrying capacity and construction demand.

With the rapid global urbanization, the unlimited increasing transportation infrastructure has met the needs of urban expansion, but it has caused a series of ecological problems lacking consideration of ecological conservation. The land suitability assessment for supporting transport planning based on carrying capacity and demand for construction is an effective way to promote urban socioeconomic development and ecological conservation. Therefore, we constructed a logical framework of resources and environment supporting, traffic construction demand driving, and ecological protection red line and basic farmland constraining, and applied the analytic hierarchy process (AHP), GIS, three-dimensional magic cube method, and gravity model to evaluate the suitability of expressway development in Sichuan Province, China. The results showed that the spatial difference in the carrying capacity of resources and environment and the demand for expressway construction was relatively high in Sichuan, and those in eastern cities were even higher. The land suitability for supporting transport planning was relatively high, and the suitable areas with a grade from 8 to 10, accounted for 20.77% of the total study area, which could almost meet the demand for transportation infrastructure construction. The land suitability performed a circle structure with Chengdu as the core and gradually decreasing to the periphery. Overall, this study adds new insights to transport planning reform in other similar regions around the world and can provide important references for regional development planning and environmental protection.

[Clinical manifestations and neuroimaging characteristics of children with moyamoya disease].

OBJECTIVE: To study the clinical manifestations and neuroimaging characteristics of pediatric moyamoya disease. METHODS: The clinical data of 17 children with moyamoya disease were retrospectively studied. RESULTS: The onset age was between 3 and 14 years. The main clinical manifestations included motor weakness of extremities or hemiplegia, sensory disturbance and headache. Cranial CT or/and MRI examinations predominately showed cerebral infarct. Magnetic resonance angiography (MRA) and digital subtraction angiography (DSA) showed stenosis or occlusion at the terminus of the siphon portions of internal carotid arteries and proximal portions of anterior or middle cerebral arteries, and abnormal vascular networks at the base of brain. CONCLUSIONS: Cerebral ischemia is main clinical manifestations in children with moyamoya disease, presenting motor weakness of extremities or hemiplegia, sensory disturbance and headache. DSA is essential to the diagnosis of the disease.

Paraneoplastic ocular sarcoidosis in the setting of recurrent rectal carcinoid tumor diagnosed by F18-fluorodeoxyglucose PET CT.

PURPOSE: Nuclear medicine imaging can provide a noninvasive means of distinguishing inflammatory mass lesions from oncologic intraocular tumors. OBSERVATION: We report a case of paraneoplastic ocular sarcoidosis with choroidal mass lesions that was initially concerning for choroidal metastasis of a primary carcinoid tumor. PET CT was utilized with two different tracers to characterize the choroidal mass as being FDG-avid, consistent with a sarcoid-like lesion, and lacking the Gallium (Ga-68) DOTATAE uptake of carcinoid tumor metastases. CONCLUSIONS AND IMPORTANCE: Functional imaging is valuable to distinguish clinically similar inflammatory verses oncologic intraocular pathology.

Granulomatous disease: is it a nuisance or an asset during PET/computed tomography evaluation of lung cancers?

OBJECTIVES: To evaluate combined PET-computed tomography (CT) criteria for differentiating between granulomatous disease (GD) and malignancy (CA) in oncologic PET-CT studies. METHODS: Sixty-two patients who were referred for fluoro-2-deoxyglucose (FDG) PET-CT evaluation of pulmonary lesion(s) without a history of concurrent infection were studied. PET-CT was performed 1.5 h after intravenous administration of 555 MBq 18F-FDG in the fasting state with oral contrast. Combined PET-CT criteria including (i) calcifications (Ca2+) within lymph nodes, (ii) Ca2+ in lung nodules, (iii) liver and/or spleen Ca2+, (iv) locations of lung lesion(s), (v) hilar FDG uptake, (vi) comparison of lung versus maximum mediastinal FDG uptake, (vii) lymph node uptake not in the most probable lymphatic drainage pathway from a particular lung lesion, and (viii) extra pulmonary abnormal FDG uptake were each assigned a numerical score (0-3) with progressively higher score and sum of scores toward the increasing likelihood of GD. These patients either had pathological confirmation by biopsy/resection or were followed radiographically for a period of 2 years (CA=13; GD=49). Discriminant analysis was performed on all the above criteria with this gold standard. Simple t-test and box plot analysis were also performed on the summation of the scores (from 0 in CA to 13 in GD). RESULTS: When all eight criteria were entered into discriminant analysis, the combined PET-CT criteria classified correctly 71% of patients with a sensitivity of 65% and specificity of 92% for GD. The most significant discriminating criterion was FDG uptake in the lung lesion(s) less than maximum mediastinal uptake (P=0.01). The sum scores in GD and CA were significantly different (4.9+/-2.4 vs. 3.2+/-1.5, respectively, P=0.014). Box plots showed a clear separation at a cut-off value of around 3.5. CONCLUSION: Results show that the set of combined PET-CT criteria are highly specific for GD, which is not necessarily a nuisance during oncologic evaluation. Knowledge of these criteria may attribute some of the abnormal PET findings to GD, which is a useful asset for quick recognition and clinical interpretation.

Assessment of progression and treatment response of optic pathway glioma with positron emission tomography using alpha-[(11)C]methyl-L-tryptophan.

PURPOSE: To report the utility of positron emission tomography (PET) with alpha-[(11)C]methyl-L-tryptophan (AMT) for monitoring progression and response to treatment of an isolated optic pathway glioma (OPG) in a 16-year-old girl. PROCEDURES: Positron emission tomography scanning of the brain was performed 20 minutes after intravenous administration of AMT. The AMT-PET images were reconstructed and examined for tumor uptake of the tracer in correlation with coregistered magnetic resonance images. RESULTS: The PET scan demonstrated increased uptake of AMT by OPG in a clinically symptomatic child whose magnetic resonance imaging (MRI) was inconclusive for morphological changes of the tumor. The tracer uptake was dramatically decreased on the images obtained after chemotherapy. Subsequently, AMT-PET revealed a new tumor lesion of increased AMT uptake when the patient developed vision problems and MRI showed no significant interval morphological changes. Significant vision improvement was observed after external beam radiotherapy for the newly identified tumor lesion. CONCLUSIONS: Positron emission tomography with alpha-[(11)C]methyl-L-tryptophan may be useful for monitoring progression and response to treatment of OPGs, which needs to be further investigated in a prospective study of more patients, including those with neurofibromatosis.

In vivo uptake and metabolism of alpha-[11C]methyl-L-tryptophan in human brain tumors.

Abnormal metabolism of tryptophan has been implicated in modulation of tumor cell proliferation and immunoresistance. alpha-[(11)C]Methyl-L-tryptophan (AMT) is a PET tracer to measure cerebral tryptophan metabolism in vivo. In the present study, we have measured tumor tryptophan uptake in 40 patients with primary brain tumors using AMT PET and standard uptake values (SUV). Tryptophan metabolism was further quantified in 23 patients using blood input data. Estimates of the volume of distribution (VD') and the metabolic rate constant (k(3)') were calculated and related to magnetic resonance imaging (MRI) and histology findings. All grade II to IV gliomas and glioneuronal tumors showed increased AMT SUV, including all recurrent/residual tumors. Gadolinium enhancement on MRI was associated with high VD' values, suggesting impaired blood-brain barrier, while k(3)' values were not related to contrast enhancement. Low-grade astrocytic gliomas showed increased tryptophan metabolism, as measured by k(3)'. In contrast, oligodendrogliomas showed high VD' values but lower k(3)' as compared with normal cortex. In astrocytic tumors, low grade was associated with high k(3)' and lower VD', while high-grade tumors showed the reverse pattern. The findings show high AMT uptake in primary and residual/recurrent gliomas and glioneuronal tumors. Increased AMT uptake can be due to increased metabolism of tryptophan and/or high volume of distribution, depending on tumor type and grade. High tryptophan metabolic rates in low-grade tumors may indicate activation of the kynurenine pathway, a mechanism regulating tumor cell growth. AMT PET might be a useful molecular imaging method to guide therapeutic approaches aimed at controlling tumor cell proliferation by acting on tryptophan metabolism.

Ultrasound microbubble-carried PNA targeting to c-myc mRNA inhibits the proliferation of rabbit iliac arterious smooth muscle cells and intimal hyperplasia.

OBJECTIVE: To elucidate the transfected effect of albumin ultrasound microbubbles carrying peptide nucleic acids (PNAs) against c-myc gene to the vascular walls and their effect on the intimal proliferation induced by vascular denudation. METHODS: A rabbit iliac artery intimal proliferation model was constructed and PNA against c-myc mRNA was designed and synthesized and was added to albumin solution before ultrasound microbubbles were prepared and encapsulated in matrix of albumin. The ultrasound microbubbles carrying PNA were transfected to intima under ultrasound exposure. The transfected effect was identified by a histochemical method and the expression of c-myc was detected by in situ hybridization. The proliferation of intimal smooth muscle cells was estimated by the expression of proliferative cell nuclear antigen (PCNA) of them. The intimal area and thickness were judged morphologically for intimal hyperplasia. RESULTS: The ultrasound microbubbles with PNA were successfully prepared and c-myc PNA was transfected to vascular intimal cells. The expression of c-myc and PCNA by intimal vascular smooth muscle cells (vSMCs) was inhibited significantly and the intimal thickness and area were reduced remarkably. CONCLUSION: Transfection of c-myc PNA could inhibit proliferartion of vSMCs and intima in the rabbit iliac artery intimal proliferation model and the targeted transfection of albumin ultrasound microbubbles carrying PNA offers a feasible way to facilitate its access to specific cells in vivo and produce bioavailability.

Detection of Aberrant Right Subclavian Artery by PET/CT.

An aberrant right subclavian artery can be diagnosed by PET/CT, as demonstrated in this case of a 70-y-old man undergoing PET/CT for staging of squamous cell carcinoma of the right lung. It is important to report this finding during the evaluation of oncologic patients, to prevent severe complications that may arise from various oncologic interventions.

The association of (18)F-FDG PET and glucose metabolism biomarkers GLUT1 and HK2 in p16 positive and negative head and neck squamous cell carcinomas.

OBJECTIVES: To investigate the relationship between FDG-PET maximum standard uptake value (SUVmax), p16, EGFR, GLUT1 and HK2 expression in head and neck squamous cell carcinomas (HNSCC). MATERIALS AND METHODS: Immunohistochemical staining of p16, EGFR, GLUT1 and HK2 was performed on primary tumor tissue from 97 locally advanced HNSCC patients treated with definitive chemoradiation. SUVmax along with p16, EGFR, GLUT1 and HK2 expression were analyzed for associations including local control, locoregional control and disease free survival. RESULTS: Pretreatment SUVmax in primary tumors did not differ when stratified by p16, EGFR or GLUT1 expression but SUVmax was significantly higher in HK2 expressing tumors (p=0.021) and in tumors with higher T-stage (p=0.022). GLUT1 expression was significantly higher in p16 negative (p<0.001) and EGFR positive tumors (p<0.01). HK2 expressing tumors were associated with EGFR positive tumors (p=0.022) but not with p16 or GLUT1 expression. EGFR positive, p16 negative and high GLUT1 expressing tumors were associated with worse local control and disease free survival on univariate analyses. After adjusting for patient and treatment characteristics p16 status was the only factor that predicted for outcome on multivariate analysis. CONCLUSIONS: High GLUT1 expression was associated with EGFR positive and p16 negative HNSCC tumors. GLUT1 maybe an important biomarker in HNSCC but its expression appears dependent on p16 status.

Imaging endogenous gene expression in brain cancer in vivo with 111In-peptide nucleic acid antisense radiopharmaceuticals and brain drug-targeting technology.

UNLABELLED: Imaging endogenous gene expression with sequence-specific antisense radiopharmaceuticals is possible if the antisense agent is enabled to traverse the biologic membrane barriers that separate the blood compartment from messenger RNA (mRNA) molecules in the cytoplasm of the target cell. The present studies were designed to image endogenous gene expression in brain cancer using peptide nucleic acid (PNA) antisense agents that were modified to allow for (a) chelation of the 111In radionuclide and (b) attachment to a brain targeting system, which delivers the PNA across both the blood-brain barrier (BBB) and the tumor cell membrane. METHODS: PNAs were designed that were antisense to either the rat glial fibrillary acidic protein (GFAP) mRNA or the rat caveolin-1alpha (CAV) mRNA. The PNA contained an amino-terminal diethylenetriaminepentaacetic acid moiety to chelate 111In and a carboxyl-terminal epsilon-biotinyl lysine residue, which enabled attachment to the delivery system. The latter comprised streptavidin (SA) and the murine OX26 monoclonal antibody to the rat transferrin receptor (TfR), which were joined by a thiol-ether linker. Control PNAs were not conjugated to SA-OX26. Brain tumors developed after the intracerebral injection of rat RG2 glial cells in adult Fischer CD344 rats. GFAP and CAV gene expression in the tumor in vivo was monitored by confocal microscopy and Northern blotting with GFAP and CAV complementary DNAs. RESULTS: If the PNA was not targeted to the TfR, then no imaging of any brain structures was possible, owing to the absence of PNA transport across the BBB. Conjugation of the 111In-GFAP-PNA to the SA-OX26 delivery system did not image brain cancer, owing to the downregulation of the GFAP mRNA in brain glial tumors. In contrast, brain cancer was selectively imaged with the 111In-CAV-PNA conjugated to SA-OX26 owing to upregulation of CAV gene expression in brain cancer. CONCLUSION: Imaging endogenous gene expression in vivo with PNA antisense radiopharmaceuticals is possible if drug-targeting technology is used. Attachment of the PNA antisense agent to the targeting ligand enables the antisense radiopharmaceutical to traverse biologic membrane barriers and access intracellular target mRNA molecules.

Hypoxia and reoxygenation of brain microvascular smooth muscle cells in vitro: cellular responses and expression of cerebral amyloid angiopathy-associated proteins.

Hypoxia is known to cause complex cascades of physiological, biochemical, and morphological changes in the brain. Cerebral microvascular smooth muscle cell (MV-SMC) damage may occur following hypoxic conditions and lead to SMC dysfunction. However, little is known about the exact cellular and molecular responses of these cells to hypoxia. To partly address these questions, MV-SMC were isolated from human brain, cultured and placed in conditions of ambient hypoxia (H) and hypoxia followed by reoxygenation (H/R). Cell morphology, proliferation, and the expression of amyloid precursor protein (APP) and cystatin C peptide were investigated and compared (after induction of hypoxia) between cerebral MV- and human aortic SMC. Our results show that MV-SMC proliferation was inhibited after 48 h of hypoxia and H/R, whereas aortic SMC proliferation was stimulated after 48 h of hypoxia and H/R. Hypoxia and H/R induced an increase of intracellular APP and cystatin C expression in both types of SMC, though the effect of H and H/R on APP upregulation was quantitatively more robust in MV-SMC than aortic SMC. Patterns of hypoxia-induced APP upregulation in SMC differed significantly from those found in cultured neuronal cells (PC12, NT2). These results suggest that hypoxia and H/R-induced APP and cystatin C upregulation appear to occur independently of the inhibition of cerebral MV-SMC proliferation. Overexpression of APP and cystatin C in response to hypoxia may thus represent an initiating event in the pathogenesis of amyloid angiopathy, or mediate progression of this microvascular lesion.

Positron emission tomography in diagnosis and management of invasive breast cancer: current status and future perspectives.

[18F]fluorodeoxyglucose positron emission tomography (FDG-PET) is a metabolic imaging modality that has increasing applications in oncology, neurology, and cardiology. Among the oncology applications, breast cancer is one of the most extensively studied diseases. FDG-PET has been performed for diagnosis, staging, and restaging of invasive breast cancer and for monitoring responsiveness to therapies. At the present time, the results of FDG-PET in detection of primary breast cancer and axillary staging are mixed and inconclusive. However, results demonstrating the superiority of FDG-PET over anatomic imaging modalities in detection of distant metastasis, recurrence, and monitoring therapies are relatively well documented. These applications have been accepted by medical professionals and the public, as evidenced by a recent decision by the Centers for Medicare and Medicaid Services (formerly Health Care Financing Agency) to provide coverage for the procedure. Future trends in this exciting area include development of novel breast cancer-specific PET radiopharmaceuticals and use of dedicated breast PET technologies for scans of breast/axillary lesions. PET/computed tomography technology, which combines anatomic and molecular/biochemical information, is also rapidly proliferating and should help to further improve the management of patients with breast cancer. The role of FDG-PET in breast cancer is increasing and evolving, and this metabolic imaging modality, in conjunction with newer tracers and other anatomic imaging methods, should improve diagnosis and management of patients with breast cancer

Pharmacokinetics and brain uptake of biotinylated basic fibroblast growth factor conjugated to a blood-brain barrier drug delivery system.

Human basic fibroblast growth factor (bFGF) is a potent neuroprotective agent. The clinical efficacy of this neurotrophin, however, is restricted by poor permeability across the blood-brain barrier (BBB). This study was designed to test the hypotheses that bFGF will retain its biological activity and have an enhanced BBB transport after re-formulation and conjugation to a BBB peptide drug delivery vector. The BBB delivery vector is comprised of a conjugate of streptavidin (SA) and the murine OX26 monoclonal antibody against the rat transferrin receptor, and the conjugate of biotinylated bFGF (bio-bFGF) bound to a vector is designated bio-bFGF/OX26-SA. A radioreceptor binding assay shows that the native bFGF, bio-bFGF, and bio-bFGF/OX26-SA conjugate have IC50 values of 0.12, 0.40, and 0.56 nM, respectively. After an IV bolus injection to the rat, [125I]-bio-bFGF is avidly taken up by peripheral organs, with low brain uptake at 60 min, 0.010+/-0.004% of injected dose (ID)/g brain. By contrast, the brain uptake of the [125I]-bio-bFGF/OX26-SA is increased 5-fold to 0.050+/-0.011%ID/g, although the uptake of the conjugate by peripheral tissues was decreased relative to the unconjugated bio-bFGF. In conclusion, conjugation of bio-bFGF to a BBB drug delivery vector (a) causes only a minor decrease in affinity for the bFGF receptor, (b) decreases the peripheral organ uptake of the bFGF, and (c) increases the brain uptake of the neurotrophin. The re-formulation of bFGF to enable receptor-mediated transcytosis across the BBB may improve the therapeutic index of this neurotrophin as a neuroprotective agent.