Design and evaluation of additive manufactured highly efficient inclined-wing type continuous mixer.

We develop a novel milli-scale mixer (tilted-wings mixing unit, TWM unit) based on the design for additive manufacturing (DfAM). The proposed tilted-wings mixer has basically designed to have three separate wings that split and combine fluids in order to mix together effectively. Its structure is simple for easy fabrication: two major design parameters of angle among three wings and connecting angle between tilted-unit, which are optimized using the computational fluid dynamics (CFD) analysis. From the CFD analysis, we obtain the best-combined mixing module from analyses of various combinations of TWM units for a highly effective mixing ratio. The mixing ratio of three combined units reaches near 100%, which is validated by the experiment and analysis. We believe that the proposed milli-scale mixer can be utilized in diverse chemical continuous mixers and reactors for minimizing of use of chemicals that can pollute the environment.

The unprecedented catalytic activity of alkanolamine CO2 scrubbers in the cycloaddition of CO2 and oxiranes: a DFT endorsed study.

A novel application of alkanolamines, widely employed as CO2 scrubbers in catalyzing the insertion of CO2 into epoxides generating cyclic carbonates in excellent yield and selectivity via the synergistic activity of hydroxyl and amine groups, is unravelled along with computational studies.

Protection from UV-induced skin carcinogenesis by genetic inhibition of the ataxia telangiectasia and Rad3-related (ATR) kinase.

Multiple human epidemiologic studies link caffeinated (but not decaffeinated) beverage intake with significant decreases in several types of cancer, including highly prevalent UV-associated skin carcinomas. The mechanism by which caffeine protects against skin cancer is unknown. Ataxia telangiectasia and Rad3-related (ATR) is a replication checkpoint kinase activated by DNA stresses and is one of several targets of caffeine. Suppression of ATR, or its downstream target checkpoint kinase 1 (Chk1), selectively sensitizes DNA-damaged and malignant cells to apoptosis. Agents that target this pathway are currently in clinical trials. Conversely, inhibition of other DNA damage response pathways, such as ataxia telangiectasia mutated (ATM) and BRCA1, promotes cancer. To determine the effect of replication checkpoint inhibition on carcinogenesis, we generated transgenic mice with diminished ATR function in skin and crossed them into a UV-sensitive background, Xpc(-/-). Unlike caffeine, this genetic approach was selective and had no effect on ATM activation. These transgenic mice were viable and showed no histological abnormalities in skin. Primary keratinocytes from these mice had diminished UV-induced Chk1 phosphorylation and twofold augmentation of apoptosis after UV exposure (P = 0.006). With chronic UV treatment, transgenic mice remained tumor-free for significantly longer (P = 0.003) and had 69% fewer tumors at the end of observation of the full cohort (P = 0.019), compared with littermate controls with the same genetic background. This study suggests that inhibition of replication checkpoint function can suppress skin carcinogenesis and supports ATR inhibition as the relevant mechanism for the protective effect of caffeinated beverage intake in human epidemiologic studies.

The persistent thrombus: complications, diagnosis, and novel treatment intervention.

OBJECTIVE: To review the findings and discuss the implications of the topic of pharmacomechanical thrombolysis in pediatric patients with persistent thrombus. DESIGN: A pediatric case presentation with a brief literature review on treatment of venous thrombosis and pharmacomechanical thrombolysis. INTERVENTIONS: None. MAIN RESULTS: Thrombotic events refractory to standard medical and surgical care remain a life-threatening clinical challenge in the pediatric population. Research on persistent deep venous thrombosis and treatment modalities is limited. We present a pediatric patient with a history of malignant osteosarcoma who was diagnosed with deep venous thrombosis. Despite appropriate anticoagulation therapy, the thrombus remained persistent. Pharmacomechanical thrombolysis was utilized and proved to be an effective method in providing diagnosis and treatment. CONCLUSION: Pharmacomechanical thrombolysis is a valuable and effective method in providing diagnosis and treatment of persistent thrombus.

Decreased endothelial progenitor cells in umbilical cord blood in severe preeclampsia.

BACKGROUND/AIMS: We compared the numbers of endothelial progenitor cells (EPCs) in umbilical cord blood in severe preeclampsia and normal pregnancy, along with the cord blood plasma levels of free VEGF and sVEGFR-1. METHODS: Umbilical cord blood EPC counts in severe preeclampsia (n = 15) and gestationally matched normal pregnant women (n = 30) were retrospectively analyzed. Cord plasma free VEGF and sVEGFR-1 levels were measured by enzyme immunoassay. RESULTS: Significantly higher systolic blood pressure, lower birth weight, and higher rate of small for gestational age were noted in the severe preeclampsia group. Circulating EPCs in cord blood and umbilical cord plasma free VEGF were significantly decreased in severe preeclampsia compared to the control group (p = 0.009 and 0.04, respectively). CONCLUSION: In severe preeclampsia, cord blood EPCs were reduced markedly and this was accompanied by a significant decrease in cord plasma free VEGF which is known to play a role in EPC mobilization.

Difference in the expression of alpha 7 nicotinic receptors in the placenta in normal versus severe preeclampsia pregnancies.

OBJECTIVE: The prevalence of preeclampsia is low in smokers, suggesting a possible role of nicotinic receptor in the pathophysiology of the disease. Alpha 7 nicotinic acetylcholine receptor (alpha7 nAChR) was recently found in non-neuronal tissue with various mediating functions. Therefore, we investigated the difference in the placental expression of the alpha7 nAChR in normal versus severe preeclampsia placentas. STUDY DESIGN: Central portions of placenta were obtained from 9 severe preeclampsia women and 11 gestational-age-matched normal pregnant women delivered between the gestational ages of 33 and 40 weeks following elective or emergency cesarean section. RT-PCR, western blotting, and immunohistochemical staining were performed to evaluate the alpha7 nAChR expression difference. RESULTS: In all the placentas, the alpha7 nAChR was expressed in endothelial cells, vascular smooth muscle cells, and stromal cells, but not in trophoblasts. The vascular staining was more intense in the severe preeclampsia placenta (p=0.02). Although the gene expression did not differ between the two groups, protein expression was greater in 7 of 9 placenta samples from the severe preeclampsia group. CONCLUSION: Placental expression of alpha7 nAChR differs between normal and severe preeclampsia placentas, suggesting that it may be involved in the pathogenesis of preeclampsia.

ATR is not required for p53 activation but synergizes with p53 in the replication checkpoint.

ATR (ataxia telangiectasia and Rad-3-related) is a protein kinase required for survival after DNA damage. A critical role for ATR has been hypothesized to be the regulation of p53 and other cell cycle checkpoints. ATR has been shown to phosphorylate p53 at Ser(15), and this damage-induced phosphorylation is diminished by expression of a catalytically inactive (ATR-kd) mutant. p53 function could not be examined directly in prior studies of ATR, however, because p53 was mutant or because cells expressed the SV40 large T antigen that blocks p53 function. To test the interactions of ATR and p53 directly we generated human U2OS cell lines inducible for either wild-type or kinase-dead ATR that also have an intact p53 pathway. Indeed, ATR-kd expression sensitized these cells to DNA damage and caused a transient decrease in damage-induced serine 15 phosphorylation of p53. However, we found that the effects of ATR-kd expression do not result in blocking the response of p53 to DNA damage. Specifically, prior ATR-kd expression had no effect on DNA damage-induced p53 protein up-regulation, p53-DNA binding, p21 mRNA up-regulation, or G(1) arrest. Instead of promoting survival via p53 regulation, we found that ATR protects cells by delaying the generation of mitotic phosphoproteins and inhibiting premature chromatin condensation after DNA damage or hydroxyurea. Although p53 inhibition (by E6 or MDM2 expression) had little effect on premature chromatin condensation, when combined with ATR-kd expression there was a marked loss of the replication checkpoint. We conclude that ATR and p53 can function independently but that loss of both leads to synergistic disruption of the replication checkpoint.