Algal proliferation risk assessment using Vine Copula-based coupling methods in the South-to-North Water Diversion Project of China

The Middle Route of the South-to-North Water Diversion Project of China (MRSNWDPC), i.e., the longest inter-basin water diversion project (1,432 km) in the world, has delivered more than 60 billion m3 of water resources to North China and benefiting more than 100 million people since December 2014. However, the abnormal algal proliferation in the main canal under low nutrient background has seriously threatened the water quality safety of this mega project. In this research, 3 years of monitoring data matrix, including water temperature (WT), flow discharge (Q), flow velocity (V), dissolved oxygen (DO), and the algal cell density (ACD), from the main canal of the MRSNWDPC were analyzed. The nonlinear relationships were determined based on multiple regression models, and a composite risk analysis model was constructed by Latin hypercube sampling (LHS) method coupled with Vine Copula function. The impacts of different hydrological and environmental factors on algal proliferation were comprehensively analyzed by Bayesian theory. The results showed that the WT gradually decreased from upstream to downstream, with a narrow range of 16.6–17.4°C, and the annual average concentrations of DO showed a gradual increase from upstream to downstream. The flow velocity of MRSNWDPC had a tendency to increase year by year, and the maximum flow velocity exceeds 0.8 m/s upstream, midstream and downstream by 2018. The ACD accumulated along the main canal, and the annual average ACDs of downstream were the highest, ranging from 366.17 to 462.95 × 104 cells/L. The joint early-warning method considering both water temperature and flow velocity conditions is an effective way for algal proliferation risk warning management. When water temperatures of the upstream, midstream, and downstream were below 26, 26, and 23°C, respectively, the algal proliferation risk can be controlled under 50% by the flow velocity at 0.3 m/s; otherwise, the flow velocity needs to be regulated higher than 0.8 m/s. In order to keep the midstream and downstream avoid abnormal algal proliferation events (ACD ≥ 500 × 104 cells/L), the corresponding ACDs of the upstream and midstream need to be controlled lower than 319 × 104 cells/L and 470 × 104 cells/L, respectively. This study provides a scientific reference for the long-distance water diversion project’s algal control and environmental protection. The proposed coupling Vine Copula models can also be widely applied to multivariate risk analysis fields

Algal proliferation risk assessment using Vine Copula-based coupling methods in the South-to-North Water Diversion Project of China

The Middle Route of the South-to-North Water Diversion Project of China (MRSNWDPC), i.e., the longest inter-basin water diversion project (1,432 km) in the world, has delivered more than 60 billion m3 of water resources to North China and benefiting more than 100 million people since December 2014. However, the abnormal algal proliferation in the main canal under low nutrient background has seriously threatened the water quality safety of this mega project. In this research, 3 years of monitoring data matrix, including water temperature (WT), flow discharge (Q), flow velocity (V), dissolved oxygen (DO), and the algal cell density (ACD), from the main canal of the MRSNWDPC were analyzed. The nonlinear relationships were determined based on multiple regression models, and a composite risk analysis model was constructed by Latin hypercube sampling (LHS) method coupled with Vine Copula function. The impacts of different hydrological and environmental factors on algal proliferation were comprehensively analyzed by Bayesian theory. The results showed that the WT gradually decreased from upstream to downstream, with a narrow range of 16.6–17.4°C, and the annual average concentrations of DO showed a gradual increase from upstream to downstream. The flow velocity of MRSNWDPC had a tendency to increase year by year, and the maximum flow velocity exceeds 0.8 m/s upstream, midstream and downstream by 2018. The ACD accumulated along the main canal, and the annual average ACDs of downstream were the highest, ranging from 366.17 to 462.95 × 104 cells/L. The joint early-warning method considering both water temperature and flow velocity conditions is an effective way for algal proliferation risk warning management. When water temperatures of the upstream, midstream, and downstream were below 26, 26, and 23°C, respectively, the algal proliferation risk can be controlled under 50% by the flow velocity at 0.3 m/s; otherwise, the flow velocity needs to be regulated higher than 0.8 m/s. In order to keep the midstream and downstream avoid abnormal algal proliferation events (ACD ≥ 500 × 104 cells/L), the corresponding ACDs of the upstream and midstream need to be controlled lower than 319 × 104 cells/L and 470 × 104 cells/L, respectively. This study provides a scientific reference for the long-distance water diversion project’s algal control and environmental protection. The proposed coupling Vine Copula models can also be widely applied to multivariate risk analysis fields

Visual acuity and foveal thickness after vitrectomy for macular edema associated with branch retinal vein occlusion: a case series

Abstract Background The mechanism by which vitrectomy improves macular edema in patients with branch retinal vein occlusion remains unclear, although intraocular levels of vascular endothelial growth factor have been suggested to influence the visual prognosis and macular edema. Methods A series of 54 consecutive patients (54 eyes) with branch retinal vein occlusion was studied prospectively. All patients underwent pars plana vitrectomy for treatment of macular edema. Best corrected visual acuity and retinal thickness (examined by optical coherence tomography) were assessed before and after surgery. The level of vascular endothelial growth factor in vitreous fluid harvested at operation was determined. Patients were followed for at least 6 months postoperatively. Results Both the visual acuity and the retinal thickness showed significant improvement at 6 months postoperatively (P = 0.0002 and P Conclusions These results suggest that the vitreous level of vascular endothelial growth factor might influence the visual prognosis and the response of macular edema to vitrectomy in patients with branch retinal vein occlusion.</p

Suppression of uPA and uPAR Attenuates Angiogenin Mediated Angiogenesis in Endothelial and Glioblastoma Cell Lines

In our earlier reports, we showed that downregulation of uPA and uPAR inhibited glioma tumor angiogenesis in SNB19 cells, and intraperitoneal injection of a hairpin shRNA expressing plasmid targeting uPA and uPAR inhibited angiogenesis in nude mice. The exact mechanism by which inhibition of angiogenesis takes place is not clearly understood.In the present study, we have attempted to investigate the mechanism by which uPA/uPAR downregulation by shRNA inhibits angiogenesis in endothelial and glioblastoma cell lines. uPA/uPAR downregulation by shRNA in U87 MG and U87 SPARC co-cultures with endothelial cells inhibited angiogenesis as assessed by in vitro angiogenesis assay and in vivo dorsal skin-fold chamber model in nude mice. Protein antibody array analysis of co-cultures of U87 and U87 SPARC cells with endothelial cells treated with pU2 (shRNA against uPA and uPAR) showed decreased angiogenin secretion and angiopoietin-1 as well as several other pro-angiogenic molecules. Therefore, we investigated the role of angiogenin and found that nuclear translocation, ribonucleolytic and 45S rRNA synthesis, which are all critical for angiogenic function of angiogenin, were significantly inhibited in endothelial cells transfected with uPA, uPAR and uPA/uPAR when compared with controls. Moreover, uPA and uPAR downregulation significantly inhibited the phosphorylation of Tie-2 receptor and also down regulated FKHR activation in the nucleus of endothelial cells via the GRB2/AKT/BAD pathway. Treatment of endothelial cells with ruPA increased angiogenin secretion and angiogenin expression as determined by ELISA and western blotting in a dose-dependent manner. The amino terminal fragment of uPA down regulated ruPA-induced angiogenin in endothelial cells, thereby suggesting that uPA plays a critical role in positively regulating angiogenin in glioblastoma cells.Taken together, our results suggest that uPA/uPAR downregulation suppresses angiogenesis in endothelial cells induced by glioblastoma cell lines partially by downregulation of angiogenin and by inhibition of the angiopoietin-1/AKT/FKHR pathway

Theories of schizophrenia: a genetic-inflammatory-vascular synthesis

BACKGROUND: Schizophrenia, a relatively common psychiatric syndrome, affects virtually all brain functions yet has eluded explanation for more than 100 years. Whether by developmental and/or degenerative processes, abnormalities of neurons and their synaptic connections have been the recent focus of attention. However, our inability to fathom the pathophysiology of schizophrenia forces us to challenge our theoretical models and beliefs. A search for a more satisfying model to explain aspects of schizophrenia uncovers clues pointing to genetically mediated CNS microvascular inflammatory disease. DISCUSSION: A vascular component to a theory of schizophrenia posits that the physiologic abnormalities leading to illness involve disruption of the exquisitely precise regulation of the delivery of energy and oxygen required for normal brain function. The theory further proposes that abnormalities of CNS metabolism arise because genetically modulated inflammatory reactions damage the microvascular system of the brain in reaction to environmental agents, including infections, hypoxia, and physical trauma. Damage may accumulate with repeated exposure to triggering agents resulting in exacerbation and deterioration, or healing with their removal. There are clear examples of genetic polymorphisms in inflammatory regulators leading to exaggerated inflammatory responses. There is also ample evidence that inflammatory vascular disease of the brain can lead to psychosis, often waxing and waning, and exhibiting a fluctuating course, as seen in schizophrenia. Disturbances of CNS blood flow have repeatedly been observed in people with schizophrenia using old and new technologies. To account for the myriad of behavioral and other curious findings in schizophrenia such as minor physical anomalies, or reported decreased rates of rheumatoid arthritis and highly visible nail fold capillaries, we would have to evoke a process that is systemic such as the vascular and immune/inflammatory systems. SUMMARY: A vascular-inflammatory theory of schizophrenia brings together environmental and genetic factors in a way that can explain the diversity of symptoms and outcomes observed. If these ideas are confirmed, they would lead in new directions for treatments or preventions by avoiding inducers of inflammation or by way of inflammatory modulating agents, thus preventing exaggerated inflammation and consequent triggering of a psychotic episode in genetically predisposed persons

Vitamin A derivatives in the prevention and treatment of human cancer.

Vitamin A is essential for normal cellular growth and differentiation. A vast amount of laboratory data have clearly demonstrated the potent antiproliferative and differentiation-inducing effects of vitamin A and the synthetic analogues (retinoids). Recent in-vitro work has led to the exciting proposal that protein kinase-C may be centrally involved in many of retinoids' anticancer actions including the effects on ornithine decarboxylase induction, intracellular polyamine levels, and epidermal growth factor receptor number. Several intervention trials have clearly indicated that natural vitamin A at clinically tolerable doses has only limited activity against human neoplastic processes. Therefore, clinical work has focused on the synthetic derivatives with higher therapeutic indexes. In human cancer prevention, retinoids have been most effective for skin diseases, including actinic keratosis, keratoacanthoma, epidermodysplasia verruciformis, dysplastic nevus syndrome, and basal cell carcinoma. Several noncutaneous premaligancies, however, are currently receiving more attention in retinoid trials. Definite retinoid activity has been documented in oral leukoplakia, laryngeal papillomatosis, superficial bladder carcinoma, cervical dysplasia, bronchial metaplasia, and preleukemia. Significant therapeutic advances are also occurring with this class of drugs in some drug-resistant malignancies and several others that have become refractory, including advanced basal cell cancer, mycosis fungoides, melanoma, acute promyelocytic leukemia, and squamous cell carcinoma of the skin and of the head and neck. This report comprehensively presents the clinical data using retinoids as anticancer agents in human premalignant disorders and outlines the ongoing and planned studies with retinoids in combination and adjuvant therapy